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Based on historical documents, population data, published results, remote sensing data products, statistical data, and survey data, this study reconstructed the cropland area and the spatial pattern changes at 28 time points from 1000 to 2020 in Northeast China. The period from 1000 to 1600 corresponds to historical provincial-level administrative districts, while the period from 1700 to 2020 corresponds to modern county-level administrative districts. The main findings are as follows: (1) the cropland in Northeast China exhibited phase changes of expansion–reduction–expansion over the past millennium. (2) The cropland area in Northeast China increased from 0.55×104 km2 in 1000 to 37.90×104 km2 in 2020, and the average cropland fraction increased from 0.37 % to 26.27 %; (3) from 1000 to 1200, the cropland area exhibited an increasing trend, which peaked in 1200. The scope of land reclamation was comparable to modern times, but the overall cropland fraction remained low. The cropland area significantly decreased between 1300 and 1600, with the main land reclamation area being reduced southward into Liaoning province. From 1700 to 1850, the cropland area increased slowly and the agricultural reclamation gradually expanded northward. After 1850, there was almost exponential growth, with the cropland area continuously expanding to the whole study area, and this growth trend persists until 2020; (4) the dataset of changes in the cropland of administrative districts in Northeast China, reconstructed based on multiple data sources and improved historical cropland reconstruction methods, significantly enhances time resolution and reliability. Additionally, the dataset shows relatively better credibility assessment results, which can provide a refined database for historical land use and land cover change (LUCC) dataset reconstruction, carbon emission estimation, climate data construction, etc. The dataset can be downloaded from https://doi.org/10.6084/m9.figshare.25450468.v2 (Jia et al., 2024).

The lunar south pole, particularly its permanently shadowed regions (PSRs), has been the focus of future lunar exploration. The solar altitude angle at the lunar south pole is less than ∼ 2°, resulting in the PSRs not being directly illuminated and the possible existence of water ice in the PSRs due to the low temperatures. High-resolution digital elevation models (DEMs) in PSRs are crucial for future exploration missions and scientific research. However, existing image datasets (e.g., LROC NAC images) cannot penetrate the PSRs. Laser altimetry (e.g., LOLA) can measure the PSRs, but the DEMs derived from LOLA suffer from noises and interpolation defects. ShadowCam is a newly deployed camera onboard the Korea Pathfinder Lunar Orbiter, with a high imaging sensitivity. ShadowCam can capture the faint secondary illumination within PSRs, revealing previously indistinguishable topographic features in persistent darkness. Based on our existing Shape-from-Shading (SfS) pipeline for generating high-resolution DEMs from monocular images, we introduce a novel SfS approach that utilizes secondary illumination and reflectance to reconstruct pixel-wise high-resolution DEMs from ShadowCam images in PSRs. The approach consists of three steps: (1) modeling the secondary illumination on the target surfaces in PSRs based on the view factor; (2) optimizing a low-resolution LOLA DEM using the secondary illumination model; (3) refining the DEM to pixel-wise resolution based on SfS using the ShadowCam images. A test area (approximately 1 km × 1 km) within the PSR in the Shackleton crater near the lunar south pole is used for experimental evaluation. The results show that the DEM generated by the proposed approach is highly consistent with the direct LOLA measurements, particularly in small-scale topographic features such as crater floors and rims that are absent from the LOLA DEM. A first look at the results indicates that the proposed approach has great potential for generating high-resolution DEMs from ShadowCam images in PSRs, which can aid future exploration missions targeting the PSRs at the lunar south pole and support related scientific research on the water ice in the PSRs.

It is common knowledge that R2R3-MYB transcription factors play significant roles in plant biological and physiological processes, especially in the phenylpropanoid metabolism pathway. The cultivated strawberry (Fragaria × ananassa Duch.) is an octoploid (2n = 8x = 56) species from the Rosaceae family and it is also an important fruit crop species. However, the function of R2R3-MYB genes in strawberry remains largely unknown. Here, based on the genome of the cultivated strawberry cv. Reikou, 66 FanMYB genes were found and systematically analyzed. RNA-seq analysis revealed that some FanMYBs exhibited tissue-specific expressions and were methyl jasmonate (MeJA)-responsive. Phylogenetic relationships and protein-protein interaction analysis suggested that 13 FanMYBs were likely associated with phenylpropanoid metabolism. Out of these genes, FanMYB22, FanMYB36, FanMYB47, FanMYB49, and FanMYB63 were post-transcriptionally regulated by miR858 according to the degradome data analysis, suggesting the conservation and complex regulation network in F. × ananassa. Current findings provide a useful resource for future research on the function of FanMYBs and the regulatory mechanism of the phenylpropanoid pathway in strawberry.

We present a deep-learning approach based on the physics-informed neural networks (PINNs) for estimating thermal evolution of the crust during tectonic uplift with a changing landscape. The approach approximates the temperature field of the crust with a deep neural network, which is trained by optimizing the heat advection–diffusion equation, assuming initial and boundary temperature conditions that follow a prescribed topographic history. From the trained neural network of temperature field and the prescribed velocity field, one can predict the temperature history of a given rock particle that can be used to compute the cooling ages of thermochronology. For the inverse problem, the forward model can be combined with a global optimization algorithm that minimizes the misfit between predicted and observed thermochronological data, in order to constrain unknown parameters in the rock uplift history or boundary conditions. We demonstrate the approach with solutions of one- and three-dimensional forward and inverse models of the crustal thermal evolution, which are consistent with results of the finite-element method. As an example, the three-dimensional model simulates the exhumation and post-orogenic topographic decay of the Dabie Shan, eastern China, whose post-orogenic evolution has been constrained by previous thermochronological data and models. This approach takes advantage of the computational power of machine learning algorithms, offering a valuable alternative to existing analytical and numerical methods, with great adaptability to diverse boundary conditions and easy integration with various optimization schemes.

A lightning location system consisting of multiple ground-based stations is an effective means of lightning observation. The dataset from CNLDN (China National Lightning Detection Network) in 2016–2022 is employed to analyze the temporal and spatial lightning distributions and the differences between +CG (positive cloud-to-ground lightning) and −CG (negative cloud-to-ground lightning) strokes in China. On the annual scale, lightning activity is most prevalent during the summer months (June, July, and August), accounting for 72.6 % of the year. Spring sees more lightning than autumn, and winter has only a small amount in southeastern coastal areas. During the day, the frequency of lightning peaks at 15:00–17:00 CST (China standard time) and is lowest at 8:00–10:00 CST. For the period with high CG stroke frequency (summer of a year or afternoon of a day), the proportion of +CG strokes and the discharge peak current are relatively small. Winter in a year and morning or midnight in a day correspond to a greater +CG stroke proportion and discharge current. Spatially, low latitudes, undulating terrain, the seaside, and humid surfaces are favorable factors for lightning occurrence. Thus, the southeast coastland has the largest lightning stroke density, while the northwest deserts and basins and the western and northern Tibetan Plateau, with altitudes over 6000 m, have almost no lightning. The proportion of +CG strokes and the peak current are low in the southern region with high density but diverse in other regions. The Tibetan Plateau causes the diversity of lightning activity in China and lays the foundation for studying the impact of surface elevation on lightning. Results indicate that the +CG stroke proportion on the eastern and southern Tibetan Plateau is up to 15 %, larger than the plain regions. The peak current of −CG strokes is positively correlated with altitude, but +CG strokes show a negative correlation, resulting in a large difference in peak current between +CG and −CG on the plain and a small difference on the plateau.

The big events cause substantial deviations in the city traffic, especially railway transportation which happens to be the dominant mode of transportation for most of the major cities. Analysis of big events’ impact on railway transportation, therefore, is of great importance to urban planning and transport management, yet is quite challenging because of the lack of readily available data about railway passengers’ citywide flow and event participants’ choice of transportation mode. Previous works have mainly relied on precise but limited data like sensors, AFC (Automated Fare Collection), or smart-card get-on get-off data to estimate the railway passengers, and did not take a holistic multi-dimensional approach to analyze railway traffic congestion caused by the events. To tackle these challenges, we propose a novel interactive Dashboard system that utilizes millions of smartphone GPS records across Japan. The dashboard can estimate and visualize railway passengers for the stations nearby the event venue as well as other relevant event participants’ information. We also introduce a Congestion Index to measure the increase in congestion of stations during events. The dashboard can be highly useful for event organizers, railway administrators, and city planners to assess and compare the impact of big events on railway traffic.

Stratospheric ozone transported to the troposphere is estimated to account for 5 %–15 % of the tropospheric ozone sources. However, the chances of intruded stratospheric ozone reaching the surface are low. Here, we report an event of a strong surface ozone surge of stratospheric origin in the North China Plain (NCP, 34–40∘ N, 114–121∘ E) during the night of 31 July 2021. The hourly measurements reveal surface ozone concentrations of up to 80–90 ppbv at several cities over the NCP from 23:00 LST (Local Standard time, = UTC +8 h) on 31 July to 06:00 LST on 1 August 2021. The ozone enhancement was 40–50 ppbv higher than the corresponding monthly mean. A high-frequency surface measurement indicates that this ozone surge occurred abruptly, with an increase reaching 40–50 ppbv within 10 min. A concurrent decline in surface carbon monoxide (CO) concentrations suggests that this surface ozone surge might have resulted from the downward transport of a stratospheric ozone-rich and CO-poor air mass. This is further confirmed by the vertical evolutions of humidity and ozone profiles based on radiosonde and satellite data respectively. Such an event of stratospheric impact on surface ozone is rarely documented in view of its magnitude, coverage, and duration. We find that this surface ozone surge was induced by a combined effect of dying Typhoon In-fa and shallow local mesoscale convective systems (MCSs) that facilitated transport of stratospheric ozone to the surface. This finding is based on analysis of meteorological reanalysis and radiosonde data, combined with high-resolution Weather Research and Forecasting (WRF) simulation and backward trajectory analysis using the FLEXible PARTicle (FLEXPART) particle dispersion model. Although Typhoon In-fa on the synoptic scale was at its dissipation stage when it passed through the NCP, it could still bring down a stratospheric dry and ozone-rich air mass. As a result, the stratospheric air mass descended to the middle-to-low troposphere over the NCP before the MCSs formed. With the pre-existing stratospheric air mass, the convective downdrafts of the MCSs facilitated the final descent of stratospheric air mass to the surface. Significant surface ozone enhancement occurred in the convective downdraft regions during the development and propagation of the MCSs. This study underscores the substantial roles of weak convection in transporting stratospheric ozone to the lower troposphere and even to the surface, which has important implications for air quality and climate change.

The effort for combating the COVID-19 pandemic around the world has resulted in a huge amount of data, e.g., from testing, contact tracing, modelling, treatment, vaccine trials, and more. In addition to numerous challenges in epidemiology, healthcare, biosciences, and social sciences, there has been an urgent need to develop and provide visualisation and visual analytics (VIS) capacities to support emergency responses under difficult operational conditions. In this paper, we report the experience of a group of VIS volunteers who have been working in a large research and development consortium and providing VIS support to various observational, analytical, model-developmental, and disseminative tasks. In particular, we describe our approaches to the challenges that we have encountered in requirements analysis, data acquisition, visual design, software design, system development, team organisation, and resource planning. By reflecting on our experience, we propose a set of recommendations as the first step towards a methodology for developing and providing rapid VIS capacities to support emergency responses.

Xinghua Bay is one of the largest wintering sites of the black-faced spoonbill Platalea minor in mainland China. The ecosystem of Xinghua Bay has shown a deteriorating trend with the increasing pressure of economic development in recent decades. To understand the current conservation status of the wintering spoonbills in Xinghua Bay, we collected water samples along the coast of Xinghua Bay and important spoonbill habitats during the wintering period to analyze the pollution degree of 7 target heavy metals and organics. The Nemerow pollution index (NPI), heavy metal pollution index (HPI) and contamination degree (CD) were used to assess the heavy metal pollution levels. The ecological risk index of a target heavy metal (Efi) and potential ecological risk index of all target heavy metals (RI) were used to assess the ecological risk of heavy metals levels in Xinghua Bay. Positive matrix factorization (PMF) was used to determine the sources of heavy metals in coastal waters with the EPA PMF5.0 model. The results showed that there was moderate to very heavy pollution by heavy metals and moderate associated ecological risks in Xinghua Bay, in which Hg and Cd were the major heavy metal pollution sources, and the level of organic pollution was of serious concern. The use of fertilizers for cultured shellfish and aquaculture in and around the bay were the major cause of the excessive nitrogen and phosphorus levels, and factories surrounding Xinghua Bay were the major sources of heavy metals and organic pollution. We propose conservation measures to increase black-faced spoonbill population and enhance its habitats.

Prior studies have investigated the immediate impacts of substances on temporal perception, the impact of temporal outlook, and the consequences of modified temporal perception on addictive behaviors. These inquiries have provided valuable perspectives on the intricate associations between addiction and time perception, enriching the groundwork for forthcoming research and therapeutic strategies. This comprehensive review aims to further explore intricate correlation among diverse addictive substances-namely alcohol, cannabis, nicotine, opioids-and non-substance addictions such as internet gaming, elucidating their influence on temporal perception. Adhering to the PICOS method and adhering to PRISMA guidelines, we systematically reviewed and critically evaluated all existing research concerning temporal perception in individuals with substance and non-substance use disorders. Specifically, our analyses involved 31 pertinent articles encompassing six unique groups-alcohol, nicotine, cannabis, stimulants, opioids, and internet-related addictions-sourced from a pool of 551 papers. The findings revealed differences in time perception between addicts and control groups, as indicated by medium to large effect sizes (Hedge's g = 0.8, p < 0.001). However, the nature of these differences-whether they predominantly involve time overestimation or underestimation-is not yet definitively clear. This variability underscores the complexity of the relationship between addiction and temporal perception, paving the way for further research to unravel these intricate dynamics., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Waveguide interconnect coupling control is essential for enhancing the chip density of photonic integrated circuits to incorporate a growing number of components. However, a critical engineering challenge is to achieve both strong waveguide isolation and efficient long-range coupling on a single chip. Here, a novel photonic supercoupling phenomenon is demonstrated for waveguide coupling over separation distances from a quarter to five wavelengths (λ), leveraging the tunable mode tails and the vortex energy flow in topological valley Hall system. A supercoupled integrated chip is developed, realizing a 91% coupling ratio and a -30 dB isolation over 2.8λ waveguide separations simultaneously. Supercoupled devices are further showcased including a waveguide-cavity system with 3.2λ excitation distance, and a waveguide directional supercoupler with a compact coupling area of nearly λ 2 /4, which outperform conventional devices. Supercoupling provides new degrees of freedom for optimizing coupling and isolation between photonic integrated components, facilitating new applications in on-chip sensing, lasing, and telecommunications., (© 2024 Wiley‐VCH GmbH.)

In this study, ovalbumin (OV) and sodium alginate (SA), two macromolecular complexes, were coagulated into the emulsifier (OV/SA), which stabilized soybean oil by electrostatic interaction, hydrophobic interactions, and hydrogen bonding. The structure of OV/SA and properties of OV/SA Pickering emulsion were investigated. Additionally, the effect of emulsions on the gel and protein properties of hairtail surimi was studied. The results revealed that with the increasing concentration of OV/SA, the particle size and zeta potential value (negative value) of the emulsion initially decreased and then increased, while the rheological properties gradually improved. Compared with the surimi gel directly supplemented with soybean oil, the addition of emulsion enhanced gel strength, whiteness, water holding capacity, and hydrophobic interactions, resulting in a more stable gel network structure. In summary, incorporating emulsion into surimi at the same lipid content not only maintained its gel properties but also improved its color and compensated for lipid loss., Competing Interests: Declaration of competing interest The authors declared no conflicts of interest in connection with the research, authorship, and/or publication of this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The migration behavior of microplastics in water is affected by many factors; in particular, the migration mechanism of microplastics in the terrestrial freshwater environment is more complicated than that in the marine environment. In order to understand the migration behavior of microplastics in the freshwater environment, the hydraulic parameter thresholds of different types of microplastics in water were identified based on hydraulic experiments and force analysis methods. The results show that the motion state of microplastics is affected by their own internal factors and external environmental factors, and the flow rate is the key external factor affecting the change of their motion state. In the vertical direction, the higher the density, the rougher the environment, and the closer the shape to the flake, the greater the critical starting flow velocity and the critical resuspension flow velocity. The settling velocities, critical initiation velocities, and critical resuspension velocities of microplastics range from 0.05 to 0.17 m s -1 , 0.03 to 0.44 m s -1 , and 0.251 to 0.83 m s -1 , respectively. Horizontally, the bottom rolling velocities of microplastics vary significantly. These velocities are positively correlated with water flow velocity but are inversely proportional to the density of the microplastics and the roughness of the substrate. By combining experimental data, mathematical expressions for the critical hydraulic parameters of microplastics were derived, showing improved accuracy compared to traditional methods. This paper explores the trajectory of different types of microplastics after entering the water body and analyzes their migration mechanism in the river. The research results have certain theoretical guiding significance for revealing the migration law of microplastics in the freshwater environment.

Exploring ionogels with superior conductivity, mechanical properties, and long-lasting room temperature phosphorescence (RTP) offers considerable potential for new-generation optoelectronics. However, reports on ionogels remain limited owing to the contradiction between the flexibility required for stretching and the rigidity necessary for RTP and load-bearing within the same ionogels. Here, a facile strategy is reported to enhance the toughness and extend the RTP of ionogels by salting-out-induced microphase separation, which results in the formation of an IL-rich phase (soft) for stretching and ionic conduction and a polymer-rich phase (stiff) for energy dissipation and clustering-triggered phosphorescence. The obtained ionogels exhibit high stretchability (≈400% strain), toughness (≈∼20 MJ m -3 ), ionic conductivity (8.4 mS cm -1 ), and ultralong afterglow lifetime (112.4 ms). This strategy is applicable to chromophores with color-tunable phosphorescence. By leveraging observable full-color RTP and real-time electrical signals in response to diverse stimuli (i.e., stretching and pressing), an intelligent grasping strategy is developed for robust hand pose reconstruction. In addition, a tactile-visual fusion recognition keyboard is created with dual functionality of information encryption and signal transmission. The ease of fabrication, wide tunability, and multifunctionality will help expand the scope of ionogels for smart devices., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The functional properties of starch-polyphenol complexes closely related to the digestion process. Here, dynamic in vitro digestion properties and prebiotic activities of lotus seed starch-chlorogenic acid complexes under autoclaving treatment (A-LS-CA) were investigated. The results showed that the ordered structure, thermal stability and molecular weight of the A-LS-CA complexes significantly altered during dynamic in vitro digestion. Remarkably, the ordered structure of digestive products significantly decreased in oral-gastric phase, while the ordered structure was increased in oral-gastric-small intestinal phase. The molecular weight of A-LS-CA complexes decreased gradually in oral, oral-gastric and oral-gastric-small intestinal phase, which were 7.40 ± 0.57, 2.23 ± 0.98 and 0.46 ± 0.10 × 10 7  g/mol, respectively. In addition, chlorogenic acid was attached to the surface of starch by hydrogen bonding during dynamic in vitro digestion, improving the bioavailability of chlorogenic acid. Interestingly, the dynamically digested A-LS-CA complexes stimulated the proliferation of Bifidobacterium longum subsp. infantis, Bifidobacterium adolescentis, Lacticaseibacillus rhamnosus and Lacticaseibacillus casei, and promoted to produce acetic acid, which was 1.07-1.49 folds that of the controls. In summary, this study provided a new insight for the structural and functional properties of starch-polyphenol complexes., 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.)

Duck plague (DP), which is caused by duck plague virus (DPV), is an infectious disease that severely harms the waterfowl breeding industry. The UL14 protein (pUL14) is a tegument protein encoded by the UL14 gene, which is located in the unique long (UL) region of the DPV genome. DPV pUL14 plays a crucial role in viral replication, likely by interacting with host and viral proteins that have yet to be identified. In this study, glutathione-S-transferase (GST) pull-down combined with liquid chromatography-mass spectrometry (LC-MS/MS) was employed to identify pUL14-interacting proteins in DPV-infected cells. A total of 281 host proteins and 58 viral proteins that interacted with pUL14 were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that the identified proteins could be assigned to several different subcellular locations and functional classes. These proteins are associated mainly with the regulation of biological processes, RNA biosynthetic processes, and nuclear export. In addition, four viral proteins of interest, the α-gene transducing factor (α-TIF) pUL48, the nuclear egress complex (NEC) proteins pUL31/34, and pUL51, a protein involved in secondary envelopment, were validated by coimmunoprecipitation (co-IP) to interact with DPV pUL14. Additionally, the nuclear export signal (NES) was identified in a leucine-rich region at aa 77-87 ( 77 VQTKIEEQLAI 87 ) of DPV pUL14. The interactome data between DPV pUL14 and host/viral proteins contribute to understanding the role of DPV pUL14 in the replication of DPV., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

A universal method is demonstrated for the fabrication of large-area highly ordered microporous arrayed metal oxides based on a high-quality self-assembly opal template combined with a sucrose-assisted sol-gel technique. Sucrose as a chelating agent optimizes precursor infiltration and regulates both oxide formation and the melting process of polystyrene templates, thus preventing crack formation during infiltration and calcination. As a result, over 20 metal element-based 3DOM oxides with arbitrary compositions are successfully prepared. Therein, a champion electrocatalyst RuCoO x -IO exhibits outstanding bifunctional oxygen activity with an ultra-narrow oxygen potential gap of 0.598 V, and the Zn-air batteries based on RuCoO x -IO air cathode operates for 1380 h under fast-charging cycling (50 mA cm -2 ), and reaches a high energy efficiency of 69.5% in discharge-charge cycling. In situ spectroscopy characterizations and density functional theory reveal that the rational construction of Ru─O─Co heterointerface with decoupled multi-active sites and mutual coupling of RuO 2 and Co 3 O 4 facilitate interfacial electron transfer, leading to an optimized d-band centers of active Ru/Co and a weakened spin interaction between oxygen intermediates and Co sites, so as to enhance the adsorption ability of * OOH on interfacial Co sites for fast ORR kinetics while favoring the desorption of oxygen intermediates on interfacial Ru during OER., (© 2024 Wiley‐VCH GmbH.)

Since its emergence in 2010, Tembusu virus (TMUV) has rapidly spread across poultry populations in Asia, leading to substantial economic losses in these areas. Here, we investigate the codon usage patterns (CUPs) underlying TMUV's adaptation and evolutionary dynamics within host environments. Phylogenetic and compositional analyses consistently classify TMUV into four evolutionary lineages-Clusters 1, 2, 3, and ancestral TMUV-with Cluster 2 emerging as the dominant lineage. Codon adaptation index (CAI) analysis reveals that this lineage of TMUV show best adapted to the CUPs of duck than other lineages, underscoring the role of natural selection in shaping viral evolution, a finding in line with evidence that CUPs in the TMUV genome is predominantly shaped by natural selection. Furthermore, TMUV exhibits markedly higher adaptation to the CUPs of poultry hosts (duck, goose, and chicken) compared to potential host humans or vector mosquito. Thus, species-specific adaptability to the host environment may be a reason account for the distinct infectivity and clinic outcome of TMUV acted on hosts. Analysis of dinucleotide distribution reveals significant suppression of CpG and UpA dinucleotides in the TMUV genome, reflecting adaptive pressures to evade vertebrate immune responses. During transmission, TMUV shows increasing alignment with host CUPs and a continuous reduction in CpG dinucleotides, potentially enhancing its fitness within host microenvironments. This work advances our understanding of the basic biology underlying TMUV epidemiology, pathogenicity, and species-specific adaptation., Competing Interests: DISCLOSURES We utilized sequence data that is publicly accessible through NCBI, negating the need for ethical approval. Detailed sequence information is provided in Supplementary table 1. Regarding author contributions, FG developed the study concept, oversaw the research, and drafted the manuscript. HT, KF, JY and LW handled data collection and analysis. KF provided the main funding for the research. RW contributed essential scripts required for the analysis. RJ, YL, FP and WX performed formal validation, and contributed to manuscript review and editing. All authors have read and given final approval for the manuscript. The authors declare no commercial or financial conflicts of interest in relation to this research., (Copyright © 2024. Published by Elsevier Inc.)

Inspired by our previous finding that targeting the 150-cavity with a multisite-binding strategy emerged as an effective approach to obtain more potent and selective neuraminidase (NA) inhibitors against influenza virus, we present here the design, synthesis, and optimization of novel boron-containing N-substituted oseltamivir (OSC) derivatives. Exploratory structure-activity relationship (SAR) studies led to the identification of compounds 27c and 33c as the most potent NA inhibitors, surpassing OSC in potency against both wild-type group-1 NAs and oseltamivir-resistant NAs. These compounds demonstrated significant antiviral activity against several wild-type strains and H1N1pdm09 strains (EC 50 = 0.03 ± 0.005 and 0.03 ± 0.0008 μM, respectively). Additionally, these compounds did not exhibit significant toxicity (CC 50 > 200 μM in CEF cells; CC 50 > 250 μM in MDCK cells). These findings highlight 27c and 33c as promising next-generation anti-influenza agents.

The study investigates the causal relationship between gut microbes and female genital tract polyps, exploring the potential mediating role of immune cells via Mendelian randomization (MR) analysis. Our MR study was designed following the STROBE-MR guidelines. We combined data from a large-scale GWAS meta-analysis, including 731 immune profiles and female genital tract polyps, with gut microbiology data sourced from the MiBioGen consortium. Univariate Mendelian randomization was employed to identify gut microbes and immune profiles significantly associated with female genital tract polyps causally. A 2-step MR analysis was utilized to investigate the potential mediating role of immune cells. Furthermore, we utilized the multivariable MR approach based on Bayesian model averaging (MR-BMA) to further assess the prioritization of gut microbiota vs immune characteristics in the development of female genital tract polyps. Through univariate MR analysis, we identified a significant causal link between 12 gut microbiota, 31 immune features, and female genital tract polyps. Four causal pathways involving gut microbiota, immune cells, and polyps were identified among them. MR-BMA analysis indicated marginal inclusion probability (MIP) values exceeding 0.1 for 5 gut microbiota groups: Victivallaceae (model-averaged causal estimate [MACE] = 0.060, MIP = 0.581, P = .0089), Ruminococcus gautreuii (MACE = 0.052, MIP = 0.346, P = .0640), Lachnoclostrium (MACE = 0.0380, MIP = 0.225, P = .1875), Alphaprobacter (MACE = 0.0186, MIP = 0.140, P = .3934), and Fusicatenibacter (MACE = 0.013, MIP = 0.110, P = .5818). Six immune features exhibit high priority, with MIP values exceeding 0.5, including HLA DR on CD33+ HLA DR+ CD14dim (MACE = -0.015, MIP = 0.753, P = .0853), HVEM on naive CD4+ T cell (MACE = 0.024, MIP = 0.737, P = .0053), CD80 on CD62L+ plastic cytoplasmic dendritic cell (MACE = 0.024, MIP = 0.721, P = .0228), CD28 on activated and secret CD4 regulatory T cell (MACE = 0.0054, MIP = 0.706, P = .3245), HLA DR on CD14+ CD16 monocyte (MACE = -0.0003, MIP = 0.520, P = .7927), HLA DR on CD14+ monocyte (MACE = -0.0029, MIP = 0.509, P = .5576). Our research indicates that gut microbiota exerts an independent causal influence on female genital tract polyps, potentially impacting them via various immune cells., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: CRISPR/Cas13 system, recognized for its compact size and specificity in targeting RNA, is currently employed for RNA degradation. However, the potential of various CRISPR/Cas13 subtypes, particularly concerning the knockdown of endogenous transcripts, remains to be comprehensively characterized in plants., Results: Here we present a full spectrum of editing profiles for seven Cas13 orthologs from five distinct subtypes: VI-A (LwaCas13a), VI-B (PbuCas13b), VI-D (RfxCas13d), VI-X (Cas13x.1 and Cas13x.2), and VI-Y (Cas13y.1 and Cas13y.2). A systematic evaluation of the knockdown effects on two endogenous transcripts (GhCLA and GhPGF in cotton) as well as an RNA virus (TMV in tobacco) reveals that RfxCas13d, Cas13x.1, and Cas13x.2 exhibit enhanced stability with editing efficiencies ranging from 58 to 80%, closely followed by Cas13y.1 and Cas13y.2. Notably, both Cas13x.1 and Cas13y.1 can simultaneously degrade two endogenous transcripts through a tRNA-crRNA cassette approach, achieving editing efficiencies of up to 50%. Furthermore, different Cas13 orthologs enable varying degrees of endogenous transcript knockdown with minimal off-target effects, generating germplasms that exhibit a diverse spectrum of mutant phenotypes. Transgenic tobacco plants show significant reductions in damage, along with mild oxidative stress and minimal accumulation of viral particles after TMV infection., Conclusions: In conclusion, our study presents an efficient and reliable platform for transcriptome editing that holds promise for plant functional research and future crop improvement., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Competing interests: Shuangxia Jin is an Editorial Board Member for Genome Biology but was not involved in the editorial process of this manuscript., (© 2024. The Author(s).)

Tembusu virus (TMUV) is a member of genus flavivirus, which mainly causes decrease in production in egg ducks and neurological symptom in meatducks, causing serious economic losses to the poultry industry. Recently, the commercialized TMUV vaccines are mainly the WF100 live vaccine and the attenuated live vaccine (FX2010-180P), so it is particularly important to find new methods to combat TMUV. The capsid-targeted viral inactivation (CTVI) strategy is based on a viral core protein and an exogenous factor that can destroy viral DNA or RNA. Lentivirus vectors are an effective tool for transferring the recombinant lentiviruses to target cells and are a promising system for efficient gene delivery. This study injected recombinant lentivirus carrying the Cap-SNase and Cap-Linker-SNase fusion proteins into duck early embryos at 10 9 TU/mL, achieving widespread expression of the fusion proteins in duck embryo tissues. After TMUV infection, the symptoms of the ducks in the Cap-SNase and Cap-Linker-SNase groups were significantly alleviated to the 1640 group. Pathological sections showed that compared with the 1640 group, the pathological damage in the Cap-SNase and Cap-Linker-SNase groups was greatly alleviated, and the virus loads in the feces, blood and tissues of Cap-SNase or Cap-Linker-SNase groups were significantly lower than those in the 1640 group. The results indicate that the Cap-SNase or Cap-Linker-SNase fusion proteins delivered by lentivirus have anti-TMUV effect. This study combines lentiviral vectors with CTVI strategy for the first time, which could be a simple and practical technology to treating human or animal diseases or biomedical animals., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2024. Published by Elsevier B.V.)

The progression of periodontitis, a bacteria-driven inflammatory and bone-destructive disease, involves myriad cellular and molecular mechanisms. Protein regulation significantly influences the pathogenesis and management of periodontitis. However, research regarding its regulatory role in periodontitis remains relatively limited. The ubiquitin-proteasome system (UPS), which mainly involves ubiquitination by E3 ubiquitin ligases (E3s) and deubiquitination by deubiquitinating enzymes (DUBs), is the primary intracellular and non-lysosomal mechanism of protein degradation. Recent studies have provided compelling evidence to support the involvement of UPS in periodontitis progression. Increasing evidence indicated that E3s, such as CUL3, Nedd4-2, Synoviolin, FBXL19, PDLIM2, TRIMs and TRAFs, modulate inflammatory responses and bone resorption in periodontitis through multiple classical signalling pathways, including NLRP3, GSDMD, NF-κB, Wnt/β-catenin and Nrf2. Meanwhile, DUBs, including OTUD1, A20, CYLD, UCH-L1 and USPs, also broadly modulate periodontitis progression by regulating signalling pathways such as NF-κB, Wnt/β-catenin, NLRP3, and BMP2. Therefore, the modulation of E3s and DUBs has proven to be an effective therapy against periodontitis. This review provides a comprehensive overview of the regulatory role of ubiquitinating and deubiquitinating enzymes in periodontitis progression and the underlying mechanisms. Finally, we summarise several chemical and genetic methods that regulate UPS enzymes and pave the way for the development of targeted therapies for periodontitis., (© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Podocyte injury is a critical event in the pathogenesis of diabetic nephropathy (DN). Hyperglycemia, oxidative stress, inflammation, and other factors contribute to podocyte damage in DN. In this study, we demonstrate that signaling regulatory protein alpha (SIRPα) plays a pivotal role in regulating the metabolic and immune homeostasis of podocytes. Deletion of SIRPα in podocytes exacerbates, while transgenic overexpression of SIRPα alleviates, podocyte injury in experimental DN mice. Mechanistically, SIRPα downregulation promotes pyruvate kinase M2 (PKM2) phosphorylation, initiating a positive feedback loop that involves PKM2 nuclear translocation, NF-κB activation, and oxidative stress, ultimately impairing aerobic glycolysis. Consistent with this mechanism, shikonin ameliorates podocyte injury by reducing PKM2 nuclear translocation, preventing oxidative stress and NF-κB activation, thereby restoring aerobic glycolysis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Limin Li reports financial support was provided by the National Natural Science Foundation of China (32170897). Limin Li reports a relationship with the National Natural Science Foundation of China (32170897) that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In this study, a maleic acid (MA) hydrolysis one-pot method is proposed to prepare carboxylated silk nanofibers (MA-SNFs). The MA concentration, hydrolysis temperature, and processing time were optimized. Combined with high-pressure homogenization, MA-SNFs with a carboxyl content of 0.617±0.019 mmol/g and length of 333±116 nm were obtained with a yield of 54.90±1.98 % at the optimal conditions: 50 wt% of MA concentration, 110 °C of hydrolysis temperature and 120 min of processing time. The morphology, chemical structure, and crystal structure of raw silk fibroin (SF), acid-hydrolyzed silk fibroin and nanofibers were studied. Furthermore, MA was reused several times with a recovery rate of >94 % and maintained almost the same treatment effect. Finally, due to the presence of carboxyl groups, MA-SNF hydrogels were successfully prepared by an acetic coagulation vapor bath which exhibited excellent self-supporting ability and mechanical properties as well as a more sensitive pH response compared with regenerated silk fibroin solution and other non-carboxylated silk nanofibers. The MA-SNF aerogels had the characteristics of light weight, high strength and porous with cross-linked nanostructures., 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 B.V.)

Background: Ischemic stroke is a common cerebrovascular disease characterized by high incidence, disability, mortality, and recurrence. The limitations of current pharmacological treatments, which have primarily single neuroprotective action and a narrow therapeutic time window, lead to unsatisfactory therapeutic efficacy. Activation of autophagy can facilitate neural regeneration., Objective: To clarify whether salidroside can promote axonal sprouting through autophagy resulting in protecting neurons., Methods: In vivo, a Middle Cerebral Artery Occlusion/reperfusion (MCAO/IR) model was used, and in vitro, an Oxygen-Glucose Deprivation/Reoxygenation (OGD/R)-induced primary neuronal cell model was employed to evaluate the neuroprotective effects of salidroside. BDA neurotracer, immunofluorescence, and Western blot (WB) were utilized to determine its impact on axonal sprouting and the levels of related proteins (MAP2, GAP43, and PSD-95). Proteomics, transmission electron microscopy (TEM), and WB were applied to identify the effects on autophagy-related proteins (beclin1, LC3, p62, and LAMP2), autophagosomes and lysosomes. The mechanism of salidroside in promoting axonal sprouting through inducing autophagy was further confirmed by blocking with the autophagy inhibitor 3-MA., Results: Salidroside reduced neurologic deficits and infarct volume induced by MCAO/IR in vivo and protected OGD/R induced primary neuronal cells in vitro. Both in vivo and in vitro, it increased the number and length of axons and upregulated the expression of key axonal proteins (MAP2, GAP43, and PSD-95) and mediated autophagy-related proteins. Mechanistic studies showed that the promoting effects of salidroside on autophagy and axonal sprouting disappeared after the blockade by 3-MA., Conclusion: This study reports for the first time that the neuroprotective effect of salidroside in ischemic stroke can be executed through mediating autophagy-related protein (beclin1, LC3, p62, and LAMP2), resulting in induced axonal sprouting or mature protein (MAP2, GAP43, and PSD-95)., Competing Interests: Declaration of competing interest Authors have no conflicts of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Depression has been linked to ferritinophagy-induced synaptic damage, which affects the emotional circuitry and can ultimately lead to depressive symptoms. It has been suggested that Hesperidin might improve depression disorders. However, the relationship between the therapeutic effects of the sympathetic nervous system in alleviating depression-like behaviors and ferritinophagy is still unknown., Purpose: The objective of this study is to investigate the possible impact of Hesperidin in alleviating dendritic spines through the inhibition of ferritinophagy via HERC2-NCOA4 ubiquitination in mice exposed to chronic unpredictable mild stress (CUMS)., Methods: C57BL/6 and NCOA4 +/+ mice were exposed to CUMS for 42 days. During the last 3 weeks of the CUMS procedure, the mice were administered Hesperidin (50, 100, 200 g/kg/d) or fluoxetine (10 mg/kg/d) once daily. Following the behavioral tests, Golgi staining, tissue iron concentration test, and perls staining were conducted to assess the therapeutic effect of Hesperidin. Additionally, ultrahigh-performance liquid chromatography-high-resolution tandem mass spectrometry (UPLC-Q-TOF/MS) and ultrahigh-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was utilized to analyze the metabolic components of Hesperidin in both blood and brain tissue. To investigate mechanism of Hesperidin, the cells were subjected to different concentrations of Hesperidin (25, 50, 100 µM), its metabolites (Eriodictyol (10, 20, 50 µM), Homoeriodictyol (0.1, 0.5, 1 µM)) and si-HERC2. Furthermore, HERC2-NCOA4 ubiquitination, and ferritinophagy-related proteins was explored through techniques such as western blot, immunofluorescence, co-immunoprecipitation, and molecular docking., Results: Hesperidin has demonstrated the potential to alleviate symptoms of depression by regulating dendritic spines through the inhibition of NCOA4-ferritinophagy, while NCOA4 overexpression could reverse these results. Importantly, the content of Hesperidin metabolites (Homoeriodictyol and Eriodictyol) was relatively high in brain tissue. The Hesperidin and its metabolites, Eriodictyol and Homoeriodictyol, were able to regulate GluR2 and SYN protein expression. Additionally, they inhibited ferritinophagy involving NCOA4, P62, LC3, and FTH. but this phenomenon was reversed by si-HERC2 following Hesperidin and its metabolite administration. Furthermore, the binding of HERC2 and NCOA4 protein was found to be inhibited by Hesperidin and its metabolites., Conclusions: Hesperidin alleviated dendritic spines through inhibiting ferritinophagy via HERC2-NCOA4 ubiquitination in CUMS mice., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

A desirable ratiometric fluorescent probe was designed by using 3-carboxyphenylboronic acid functionalized polyethyleneimine ethoxylated modified copper nanoclusters (CPBA@PEI-CuNCs) for detecting luteolin (LTL, cis-diols structure) with sensitivity and selectivity. Characterization techniques were carried out with the TEM, PSD, FT-IR, XPS and XRD, confirming its successful formation with a quantum yield of 40.49 %. As the optimal excitation wavelength at 386 nm, the fluorescence intensity was detected by fluorophotometer. Meanwhile, the nanoprobe has two emission wavelengths 396 and 473 nm. According to the fluorescence quenching intensity ratio (F 473 /F 396 ), the LOD reached as low as 1.22 nM within the range from 0.11 to 600 μM. The CPBA@PEI-CuNCs exhibited pH-controlled, covalent, and reversible binding properties. Using PEI capped by CuNCs, cytotoxicity is reduced for potential treatment purposes. Additionally, the developed probe was used for LTL detection, HepG2 cell imaging and pH-responsive drug delivery in real samples with carrot leaves, peanut shells, and perilla leaves samples. CPBA@PEI-CuNCs demonstrated repeatability and reproducibility, making it a cost-effective and practical tool for fluorescence analysis in detection., 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 Inc. All rights reserved.)

The combined effects of the novel antifouling biocide tralopyril (TP) nitrile and ocean acidification (OA) on marine organisms are still not well understood, despite the increasing attention given to the toxic effects of emerging pollutants and OA on marine organisms in recent years. In this study, Crassostrea gigas (C. gigas) was exposed to TP, OA, and a combination of TP and OA for 21 days with a 14-day depuration. This study investigated the inter-tissue variability in energy metabolism responses and the impacts on gonadal development in C. gigas under both single and combined exposures to TP and OA. The results indicate that TP exposure and OA resulted in up-regulation of energy metabolism genes in the C. gigas, with tissues exhibiting enhanced aerobic metabolism. Furthermore, OA influences the sex determination of C. gigas, promoting the development of female individuals. Moreover, following depuration, C. gigas is able to restore normal energy metabolism and sexual development through the accumulation of suitable energy reserves. This study provides a valuable reference for the environmental and ecological risk assessment of TP, addressing the research gap in understanding the combined toxicity of TP and OA on aquatic organisms., 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.)

Flavivirus nonstructural protein 2A (NS2A) is a small endoplasmic reticulum (ER)-resident, hydrophobic transmembrane protein that function in viral replication, virion assembly and evasion of the host immune response. Despite previous studies on the role of duck Tembusu virus (DTMUV) NS2A in inhibiting the host immune response, its membrane topology has not been clearly addressed (Zhang et al., 2020; Zhang et al., 2022). Here, we present the first report on the membrane topology model and functional characterization of DTMUV NS2A. Our findings demonstrate that DTMUV NS2A localizes to the endoplasmic reticulum (ER) and associates with viral double-stranded RNA, with a single segment (TMD3, amino acids 72 to 95) spanning the ER membrane. To better delineate the residues in NS2A-TMD3 related to viral properties, specific mutations were introduced to generate DTMUV replicons and infectious cDNA clones. Functional analysis indicates that L77, Q86 and L89 of NS2A are crucial for viral RNA synthesis, while residues M79 and F83 are crucial for the assembly or release of viral particles. Moreover, these mutations attenuated the virulence of DTMUV in vivo. Collectively, our results shed light on the relationship between the transmembrane of DTMUV NS2A and its functions in virus proliferation, providing insights for further understanding the molecular mechanisms of NS2A in the virus life cycle., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

Duck plague virus (DPV), which is the causative agent of duck viral enteritis, is highly infectious and can cause severe disease and death in ducks, geese and other waterfowl. Several tegument proteins of DPV have been shown to affect the cyclic GMP-AMP synthase (cGAS)-STING signaling pathway to modulate host innate immune responses. DPV UL24, an important DPV tegument protein, can inhibit the activity of the IFN-β promoter. However, the mechanism by which the DPV UL24 protein regulates the host innate immune response remains unclear. In this study, we found that the UL24 protein can significantly inhibit the activity of the interferon-β promoter induced by poly(I:C) and reduce the production of IFN-β, interferon-stimulated genes (OASL, Mx), and the cellular inflammatory factor IL-6. 2) The UL24 protein can widely inhibit the mRNA level of immune signaling molecules. The UL24 protein can also downregulate the protein expression of RIG-I, MDA5, MAVS, cGAS, STING, TBK1 and IRF7 in DEFs. RT-qPCR results revealed that UL24 significantly inhibited the mRNA accumulation for the immune signaling molecules cGAS, STING, TBK1 and IRF7. 3) The UL24 protein induced the degradation of IRF7 via ubiquitination. After the DEFs were treated with the ubiquitin proteasome inhibitor MG132, the degradation of IRF7 by the UL24 protein was alleviated. Coimmunoprecipitation results revealed that DPV UL24 induced the K48/K63-linked ubiquitination of IRF7, which promoted its degradation and thus antagonized the host innate immune response., Competing Interests: DISCLOSURES All the authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Duck plague virus (DPV) is the only herpes virus known to be transmissible among aquatic animals, leading to immunosuppression in ducks, geese and swans. Long noncoding RNAs (LncRNA) are known to participate in viral infections, acting as either immune defenders or viral targets to evade the host response, but their precise roles in waterfowl virus infections are yet to be fully understood. This study aimed to investigate the role of LncRNA in DPV-induced innate immune responses. Results showed that DPV infection greatly upregulated Lnc BTU expression in duck embryo fibroblasts (DEF) and Lnc BTU promoted DPV replication. Mechanically, 4 DPV proteins, namely UL46, UL42, VP22 and US10, interacted with Lnc BTU, leading to its upregulation. Specifically, Lnc BTU facilitated the production of DNA polymerase by enhancing UL42 expression, thereby promoting DPV replication. Additionally, Lnc BTU suppressed STAT1 expression by targeting the DNA binding domain (DBD) and promoting STAT1 degradation through the proteasome pathway. Furthermore, Lnc BTU inhibited the production of key antiviral factors such as IFN-α, IFN-β, MX and OASL during DPV infection. Treatment with 2 JAK-STAT pathway activators in DEFs resulted in the inhibition of Lnc BTU expression and DPV replication. Interestingly, DPV infection led to a decrease in STAT1 levels, which was reversed by Si-Lnc BTU. These findings suggest that DPV relies on Lnc BTU to inhibit the activation of the JAK-STAT pathway and limit the production of type 1 interferons (IFN) to complete immune evasion. Our study highlights the novel role of DPV proteins UL46, UL42, VP22, US10 as RNA-binding proteins in modulating the innate antiviral immune response, and discover the role of a new host factor, Lnc BTU, in DPV immune evasion, Lnc BTU and STAT1 can be used as a potential therapeutic target for DPV infection and immune evasion., Competing Interests: DISCLOSURES The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)