Search

During our investigation of saprobic fungi in southwestern China, three micro-hyphomycetous fungi were isolated from dead wood in freshwater and terrestrial habitats in Guizhou Province. Phylogenetic analyses of ITS, LSU, and SSU sequences, performed using Maximum Likelihood and Bayesian Inference methods, confirmed that these isolates belong to Kirschsteiniothelia. Based on distinct morphological characteristics and molecular phylogenetic evidence, we describe three new species: Kirschsteiniothelia guizhouensis, K. weiningensis, and K. xishuiensis. Furthermore, the effectiveness of three DNA markers for species-level identification within Kirschsteiniothelia was evaluated using Assemble Species by Automatic Partitioning (ASAP) analysis, which identified the ITS nucleotide sequences as the most reliable marker for species differentiation within the genus.

Saprobic hyphomycetes with high density and species diversity were observed on plant debris. During our mycological surveys in southern China, numerous strains were isolated from dead branches of unidentified plants in the forest of Jiangxi and Fujian provinces, China. Phylogenetic analyses of ITS, LSU, RPB2, and TEF1 sequence data using maximum-likelihood (ML) and Bayesian inference (BI) methods revealed the systematic placement of several Sporidesmium-like species within Distoseptispora. Based on morphological characteristics and molecular evidence, four new species of Distoseptispora, namely D. fujianensis, D. ganzhouensis, D. nanpingensis and D. subtropica, are introduced, and two known species, D. clematidis and D. yunjushanensis, are reported. This study enhances our knowledge of the species diversity of Distoseptispora in southern China.

Fungal diversity is rapidly expanding, with numerous species being discovered worldwide. While plant debris is a habitat favoring the survival and multiplication of various microbial species. In this study, several kirschsteiniothelia-like isolates were collected from dead branches of unidentified perennial dicotyledonous plants. Based on morphological examination and phylogenetic analyses of combined ITS, LSU, and SSU sequences data using maximum-likelihood and Bayesian inference, three new species of Kirschsteiniothelia, namely K. ganzhouensis, K. jiangxiensis, and K. jiulianshanensis, were introduced, and one known species, K. inthanonensis, was recorded for the first time from China. To improve our comprehensive knowledge of the species diversity of Kirschsteiniothelia, all accepted Kirschsteiniothelia species with morphological characteristics, sequence data, asexual morphs, habitat, host, and locality are listed.

Abstract The early evolution of the South Atlantic Ocean following the Cretaceous break-up of Gondwana is extensively recorded in rift basins along the conjugate margins of Africa and Brazil. For the Brazil side, divergent views of the source and pathway of the initial seawater incursion persist due to a paucity of recognized transitional sequences that document marine transgressive deposits over the continental interior. To address this, we conducted a high-resolution sedimentological and geochemical study through a core in the Campos Basin that encompasses the key lithologic switch from lacustrine carbonate to marine evaporite settings. Steroid lipid biomarkers, derived from pelagophyte marine algae, make a striking appearance in concert with a pronounced negative shift of 87Sr/86Sr ratios and coincident with the appearance of anhydrite. Importantly, the sulfur-sequestered biomarkers reveal a dynamic system where redox-stratified and anoxic conditions were amplified along with a deepening chemocline through the marine transition.

Abstract Respiratory tract infections caused by various pathogens remain a significant public health concern due to their high prevalence and potential for severe complications. This study systematically analyzed the epidemiological characteristics of six common respiratory pathogens—Chlamydia pneumoniae (CP), Mycoplasma pneumoniae (MP), Adenovirus (AdV), Influenza A virus (FluA), Influenza B virus (FluB), and Respiratory Syncytial Virus (RSV)—in patients from Sichuan Jinxin Xinan Women and Children’s Hospital between April 2023 and March 2024. Throat swab samples were collected from a total of 22,717 individuals. Each sample was processed using the AUTOMOLEC 3000 analyzer and the PCR-fluorescent probe method. The results showed that 10,171 (44.8%) individuals tested positive for at least one pathogen. MP had the highest overall positive rate (21.83%), followed by FluA (17.50%) and FluB (14.84%). MP showed the highest mean monthly (average) positive rate (16.84% ± 8.41). Significant differences were found between MP and AdV, CP and RSV in average positive rate (p

During our investigations of saprobic fungi, five fungal collections from terrestrial habitats in China and Thailand were examined using both morphological and multi-gene phylogenetic approaches (LSU, ITS, tef1-α, and rpb2), resulting in the identification of three novel species: Helicosporium rubrum, Neohelicomyces maolanensis, and N. subtropicus. Helicosporium and Neohelicomyces are morphologically similar in their asexual morphs but can be distinguished based on their molecular phylogenetic data. In this study, our new species, Helicosporium rubrum, represents the fourth sexual species within the genus, characterized by yellow-brown ascomata and fusiform ascospores. Detailed descriptions, illustrations, phylogenetic analysis results, and corresponding notes are provided to clarify the distinctions between these new species and related taxa.

Abstract In this study, a multi-source data fusion method was proposed for the development of a Hybrid seismic hazard model (HSHM) in China by using publicly available data of the 5th Seismic Ground Motion Parameter Zoning Map (NSGM) and historical seismic catalogues and integrating with modern ground motion prediction equations (GMPEs). This model incorporates the characteristics of smoothed seismicity and areal sources for regional seismic hazard assessment. The probabilistic seismic hazard for the North China Plain earthquake belt was investigated through sensitivity analysis related to the seismicity model and GMPEs. The analysis results indicate that the Hybrid model can produce a consistent result with the NSGM model in many cases. However, the NSGM model tends to overestimate hazard values in locations where no major events have occurred and underestimate hazard values in locations where major events have occurred. The Hybrid model can mitigate the degree of such biases. Compared to the modern GMPEs, the GMPE with epicentral distance measures significantly underestimate the seismic hazard under near-field and large-magnitude scenarios. In addition, a comparison of the uniform hazard spectra (UHS) obtained by the models, with China’s design spectrum, shows that the current design spectrum is more conservative than the calculated UHS.

Abstract Spinal cord injury (SCI) is a profound affliction of the central nervous system that often remains inadequately addressed. Prior research has indicated that endoplasmic reticulum stress (ERS), associated with apoptotic signaling, plays a part in subsequent injuries post-SCI. However, the exact mechanisms are still unclear. ERS-related genes and SCI-associated datasets were sourced from the Genecard and GEO databases. We identified 68 ERSDEGs and pinpointed 6 marker genes vital for SCI diagnosis (CYBB, PRDX6, PTGS1, GCH1, TLR2 and PIK3CG) which were all upregulated in SCI based on bioinformatics and qRT-PCR. The nomogram exhibited that these genes could effectively predict the occurrence of SCI. Functional analysis revealed the potential roles of these genes was closely related to neuron cells and immune response. Immune infiltration research underscored the substantial roles of macrophage and CD56 dim NK cells in SCI. The ceRNA network analysis further revealed the complex interplay among marker genes, lncRNAs and miRNAs in SCI. We screened six marker genes with great diagnostic value, and found that these genes may affect the occurrence of SCI by affecting the immune response and recovery of neurons.

Abstract 53BP1 plays an important role in DNA double-strand break (DSB) repair and this activity is negatively regulated by its interaction with Tudor interacting repair regulator (TIRR). However, how the TIRR-53BP1 repair axis is regulated in response to DNA damage remains elusive. Here, we demonstrate that TIRR is translocated to the cytoplasm and degraded upon DNA damage. Ubiquitination of TIRR at lysine 187 by DTX3L is a critical process that regulates NHEJ pathway activity and PARP inhibitor sensitivity by facilitating XPO1-mediated TIRR nuclear export and degradation after DNA damage. We show that DTX3L is overexpressed in prostate cancers in patients and that decreased expression of TIRR due to DTX3L overexpression impairs the negative regulatory effect of TIRR on 53BP1, which consequently induces HR deficiency and chromosomal instability and sensitizes prostate cancer cells to poly (ADP-ribose) polymerase (PARP) inhibitors. Our work reveals a dual action of DTX3L on TIRR degradation and nuclear exportation and identifies DTX3L as an upstream regulator of the TIRR-53BP1 axis that governs DNA repair pathway choice and PARP inhibitor sensitivity. These findings suggest that TIRR ubiquitination and DTX3L overexpression could be viable biomarkers predicting PARP inhibitor sensitivity in cancers.

Nanobody (Nb) is derived from the variable domain of heavy-chain antibody (HCAb), naturally displaying notable properties like nano-scale size, exceptional stability, high specificity, low immunogenicity, and cryptic epitope accessibility. These features contribute to its great therapeutic potential as a valuable research tool across diverse diseases, especially autoimmune diseases (AIDs). Caplacizumab (Cablivi®) is the first nanobody drug approved for treating acquired thrombotic thrombocytopenic purpura (aTTP). This review summarizes the biomolecular structure, usage of Nb as a foundation of recombinant constructs, and biochemical properties of nanobodies. As attractive therapeutic candidates, many clinical trials of Nbs have been conducted, elucidating potential therapeutic strategies for AIDs. Therefore, the preclinical development and application of Nbs in AIDs are emphasized throughout this review.

Objective: The presence of complex components in Chinese herbal medicine (CHM) hinders identification of the primary active substances and understanding of pharmacological principles. This study was aimed at developing a big-data-based, knowledge-driven in silico algorithm for predicting central components in complex CHM formulas. Methods: Network pharmacology (TCMSP) and clinical (GEO) databases were searched to retrieve gene targets corresponding to the formula ingredients, herbal components, and specific disease being treated. Intersections were determined to obtain disease-specific core targets, which underwent further GO and KEGG enrichment analyses to generate non-redundant biological processes and molecular targets for the formula and each component. The ratios of the numbers of biological and molecular events associated with a component were calculated with a formula, and entropy weighting was performed to obtain a fitting score to facilitate ranking and improve identification of the key components. The established method was tested on the traditional CHM formula Danggui Sini Decoction (DSD) for gastric cancer. Finally, the effects of the predicted critical component were experimentally validated in gastric cancer cells. Results: An algorithm called Chinese Herb Medicine-Formula vs. Ingredients Efficacy Fitting & Prediction (CHM-FIEFP) was developed. Ferulic acid was identified as having the highest fitting score among all tested DSD components. The pharmacological effects of ferulic acid alone were similar to those of DSD. Conclusions: CHM-FIEFP is a promising in silico method for identifying pharmacological components of CHM formulas with activity against specific diseases. This approach may also be practical for solving other similarly complex problems. The algorithm is available at http://chm-fiefp.net/.

Abstract Prehistoric settlement patterns on the Tibetan Plateau, particularly in the Qaidam Basin, have drawn significant scholarly interest. Yet, limited data have hindered a comprehensive understanding the Bronze Age chronology and landscape exploitation in this region. This paper presents 24 newly obtained radiocarbon dates from eight archaeological sites within the Qaidam Basin on the Tibetan Plateau. Integrated with existing 14 C data and spatial analysis, these findings reveal an overall continuous occupation of the basin from ca. 3600–2500 calBP, with a gradual shift from expansive lowland settlements to smaller, ephemeral high-altitude structures, identified around 3350 calBP. This change is consistent with demonstrated periods of climate degradation which likely drove strategic adaptations in landscape management and subsistence methods. Overall, this research not only establishes a more robust chronology for the Qaidam Basin’s Bronze Age, but also advances the discussion on human-environment interactions in high-altitude areas during late prehistory.

Abstract The formation of human collagen requires the presence of Prolyl 3-hydroxylase 1 (P3H1), but the regulatory mechanism of P3H1 remained insufficiently understood. Our study aimed to identify the role of P3H1 in clear cell renal cell carcinoma (ccRCC). P3H1 expression in ccRCC was validated using multiple databases and in vitro experiments. We performed a correlation analysis of P3H1 with drug sensitivity, immune checkpoints, and immune cell infiltration using transcriptome and single-cell sequencing. Drawing upon the Encyclopedia of RNA Interactomes database, we selected P3H1 as the focal point of our investigation, meticulously uncovering the intricate network of microRNAs and lncRNAs that potentially orchestrate ceRNA mechanisms. This study employs a multidimensional approach integrating vitro assays and multi-omics bioinformatics analyses to investigate P3H1’s impact on ccRCC prognosis, immune modulation, immune checkpoints, ceRNA regulatory network, drug sensitivity, and therapeutic responses, aiming to uncover new insights into its therapeutic potential and inform future clinical strategies.

Plants play an important role in maintaining the ecological balance of the biosphere, but often suffer from pathogenic fungi during growth. During our continuing mycological surveys of plant pathogens from terrestrial plants in Jiangxi and Yunnan provinces, China, 24 strains of Pestalotiopsis isolated from diseased and healthy tissues of plant leaves represented eight new species, viz. P. alpinicola, P. camelliicola, P. cyclosora, P. eriobotryae, P. gardeniae, P. hederae, P. machiliana and P. mangifericola. Multi-locus (ITS, tef1-α and tub2) phylogenetic analyses were performed using maximum-likelihood and Bayesian inference to reveal their taxonomic placement within Pestalotiopsis. Both molecular phylogenetic analyses and morphological comparisons supported them as eight independent taxa within Pestalotiopsis. Illustrations and descriptions of these eight taxa were provided, in conjunction with comparisons with closely related taxa in the genus. This work highlights the large potential for new fungal species associated with diseased plant leaves.

Abstract Explicit identification of hydrochemical processes and their controlling factors within groundwater systems is critical for the sustainable utilization of water resources in coastal urban areas. This study was undertaken in the North Coastal Region of Jiaozhou Bay (NCRJB), located in the eastern part of Shandong Province, China, an area grappling with significant issues of groundwater quality degradation and water scarcity. A total of 105 groundwater samples and 34 surface water samples, collected from 2020 to 2024, were analyzed and studied using various hydrogeological tools, multivariate statistical analyses, and water quality assessment methods. These include the Piper diagram, hydrochemical facies evolution diagram (HFE-D), Principal Components Analysis (PCA), correlation analysis, stable isotope analysis, Water Quality Index (WQI), and USSL diagrams. The results indicated that all surface water and pore groundwater samples were categorized as Na-Cl type, exhibiting high Total Dissolved Solids (TDS) and Electrical Conductivity (EC) values, characteristics that render them poor to unsuitable for drinking and irrigation purposes. The fracture groundwater is predominantly of the Ca-Na-Cl mixed type, with average suitability for irrigation and a limited proportion (22.5%) deemed suitable for drinking. Seawater intrusion, primarily through the surface water system, and the impact of human activities were identified as the predominant controlling factors con-tributing to the degradation of the local groundwater environment. Field empirical investigations further validated the results derived from hydrogeological assessments, multivariate statistical analyses, and isotopic approaches. The long-term shifts in hydrochemical properties, along with the latent threat of seawater intrusion, exhibit an upward trend during the dry season and show a certain degree of mitigation during the wet season. This study highlights that field investigations, in conjunction with hydrochemical tools, multivariate statistical analyses, and stable isotope analysis, can successfully furnish reliable insights into the predominant mechanisms governing regional groundwater evolution within the context of long-term and intricate envi-ronmental settings.

Abstract Despite the pivotal role of stannum doping in achieving ultrahigh piezoelectric performance in barium titanate-based ceramics, the fundamental mechanisms underlying this enhancement remain elusive. Here, we introduce a single variable nonstoichiometric stannum strategy in lead-free barium titanate-based ceramics with giant piezoelectricity, revealing that stannum doping contributes intrinsically and extrinsically to enhance piezoelectricity. Density functional theory calculations elucidate the intrinsic enhancement of polarization arising from lattice distortion and increased space for titanium-oxygen bonds induced by optimal stannum doping, which is corroborated by Rayleigh analysis. A phase transition from ferroelectric multiphase coexistence to paraelectric phase is observed, alongside a rapid miniaturized and eventually disappeared domains with increasing stannum doping. This evolution in phase structure and domain configuration induces a nearly vanishing polarization anisotropy and low domain wall energy, facilitating easy polarization rotation and domain wall motion, thereby significantly contributing to the extrinsic piezoelectric response. Consequently, the origins of ultrahigh performance can be attributed to the synergistic effect of stannum-induced intrinsic and extrinsic contributions in barium titanate-based ceramics. This study provides fundamental insights into the role of doping elements and offers guidance for the design of high-performance piezoelectrics.

Abstract Genome differential positioning within interphase nuclei remains poorly explored. We extended and validated Tyramide Signal Amplification (TSA)-seq to map genomic regions near nucleoli and pericentric heterochromatin in four human cell lines. Our study confirmed that smaller chromosomes localize closer to nucleoli but further deconvolved this by revealing a preference for chromosome arms below 36-46 Mbp in length. We identified two lamina associated domain subsets through their differential nuclear lamina versus nucleolar positioning in different cell lines which showed distinctive patterns of DNA replication timing and gene expression across all cell lines. Unexpectedly, active, nuclear speckle-associated genomic regions were found near typically repressive nuclear compartments, which is attributable to the close proximity of nuclear speckles and nucleoli in some cell types, and association of centromeres with nuclear speckles in human embryonic stem cells (hESCs). Our study points to a more complex and variable nuclear genome organization than suggested by current models, as revealed by our TSA-seq methodology.

The traditional net-laying operation is highly dependent on manual labor, which not only has high labor intensity and high safety risks, but also has low efficiency, which has become an important factor restricting the balance of mining and excavation. Therefore, the core objective of this study is to design and implement a standardized mesh-laying strategy for underground coal mine robots, which improves the efficiency of mesh-laying operation, reduces the labor load of workers, enhances the safety of operation through the introduction of automation and intelligent technology, and then promotes the efficient, green and sustainable development of coal mine production. In order to realize the above research objectives, this study adopts a combination of simulation and experimental methods, based on the special environment and operating characteristics of underground, and designs a remote-controlled manipulator structure that assists the net-laying operation of digging-anchor integrated machine. The structure adopts a seven-axis articulated robotic arm with a top gripper in order to realize the multi-angle and high-precision laying of anchor nets. In addition, advanced computer simulation technology is used to analyze the dynamic performance, motion trajectory planning and force characteristics of the robotic arm, and the structural design and control algorithm of the robotic arm are optimized iteratively to ensure its stability and reliability in the complex underground environment. At the same time, a set of adaptive adjustment strategy is developed for the motion control of the robotic arm, so that the robotic arm can automatically adjust the motion parameters according to the actual working conditions (tunnel shape, mesh material), and realize accurate and efficient net-laying operation. The results show that the automated net-laying equipment significantly improves the efficiency of net-laying operation, compared with the traditional manual net-laying method, the efficiency is increased by more than 20%. Through automated operation, it realizes the goal of reducing the number of workers by more than 33%, which effectively alleviates the problem of tense human resources in underground coal mines. The labor intensity of workers has been greatly reduced, reducing the high degree of climbing work, reducing the risk of work-related injuries, and the labor intensity has been reduced by more than 80%. At the same time, the automated net-laying process reduces the possibility of human error and significantly improves operational safety. In the future, with the continuous iteration and improvement of the technology, this technology is expected to play a more important role in the intelligent construction of coal mines, and promote the development of coal mine production in the direction of safer, greener and more efficient.

ABSTRACT Under global warming, cloud change and its radiative feedback have often been considered to evolve from thermodynamic processes; however, cloud feedback may also force sea surface temperature to trigger such air–sea interactions. Due to complex cloud physics in air–sea coupling, this contributes to the surface warming pattern formation with significant uncertainty. Here we develop a novel overriding technique for climate projections that substitutes specific variables in control runs to isolate such feedback mechanisms, decoupling thermodynamic, dynamical and radiative responses of the surface ocean to the atmosphere. We apply this to the Community Earth System Model version 2 (CESM2) and perform a series of 150‐year simulations with 1% CO2 increase per year (1pctCO2). In real time, the key variables under 1pctCO2 are replaced with those from the current climate, such as downwelling shortwave radiation, wind speed in latent and sensible heat and wind stress. These experiments provide monthly output of global distributions including surface temperatures, winds and precipitation, with a spatial resolution of 1.9° × 2.5° in latitude and longitude and 32 levels for the atmosphere and of ~1° and 60 layers designated as gx1v7 for the ocean. This open access dataset for partial air–sea coupling under climate change can help understand the tropical and polar warming patterns and quantify the relative contributions of forcing and triggering mechanisms.

In this note, the stability of neutral delay reaction–diffusion systems (NDRDS) was concerned by applying the matrix pencil and the Kronecker product. A new computing method for the distribution of imaginary axis eigenvalues on general n-dimensional NDRDS will be introduced. A practical, checkable criterion for the asymptotic stability will be derived. The main contribution of this paper is that we provide a computational method for determining imaginary axis eigenvalues and minimal delay margin on general NDRDS.

One-quarter of the world’s population is infected with Mycobacterium tuberculosis (Mtb). After initial exposure, more immune-competent persons develop asymptomatic latent tuberculosis infection (LTBI) but not active diseases, creates an extensive reservoir at risk of developing active tuberculosis. Previously, we constructed a novel recombinant Sendai virus (SeV)-vectored vaccine encoding two dominant antigens of Mtb, which elicited immune protection against acute Mtb infection. In this study, nine Mtb latency-associated antigens were screened as potential supplementary vaccine candidate antigens, and three antigens (Rv2029c, Rv2028c, and Rv3126c) were selected based on their immune-therapeutic effect in mice, and their elevated immune responses in LTBI human populations. Then, a recombinant SeV-vectored vaccine, termed SeV986A, that expresses three latency-associated antigens and Ag85A was constructed. In murine models, the doses, titers, and inoculation sites of SeV986A were optimized, and its immunogenicity in BCG-primed and BCG-naive mice were determined. Enhanced immune protection against the Mtb challenge was shown in both acute-infection and latent-infection murine models. The expression levels of several T-cell exhaustion markers were significantly lower in the SeV986A-vaccinated group, suggesting that the expression of latency-associated antigens inhibited the T-cell exhaustion process in LTBI infection. Hence, the multistage quarter-antigenic SeV986A vaccine holds considerable promise as a novel post-exposure prophylaxis vaccine against tuberculosis.

Abstract Chloroplasts are key players in photosynthesis and immunity against microbial pathogens. However, the precise and timely regulatory mechanisms governing the control of photosynthesis-associated nuclear genes (PhANGs) expression in plant immunity remain largely unknown. Here we report that TaPIR1, a Pst-induced RING-finger E3 ubiquitin ligase, negatively regulates Pst resistance by specifically interacting with TaHRP1, an atypical transcription factor histidine-rich protein. TaPIR1 ubiquitinates the lysine residues K131 and K136 in TaHRP1 to regulate its stability. TaHRP1 directly binds to the TaHRP1-binding site elements within the PhANGs promoter to activate their transcription via the histidine-rich domain of TaHRP1. PhANGs expression induces the production of chloroplast-derived ROS. Although knocking out TaHRP1 reduces Pst resistance, TaHRP1 overexpression contributes to photosynthesis, and chloroplast-derived ROS production, and improves disease resistance. TaPIR1 expression inhibits the downstream activation of TaHRP1 and TaHRP1-induced ROS accumulation in chloroplasts. Overall, we show that the TaPIR1-mediated ubiquitination and degradation of TaHRP1 alters PhANGs expression to disrupt chloroplast function, thereby increasing plant susceptibility to Pst.

ObjectivesThis study seeks to explore the influence of water depth on the drag reduction effect and optimal drag reduction height of an interceptor. Based on the numerical solution approach of the RANS equations, the flow field around a high-speed monohull ship with various height interceptors is numerically simulated. MethodsFirst, the validity of the numerical method is verified by a DTMB 5415 high-speed ship. Next, the flow field around a high-speed monohull ship is numerically simulated under different interceptor heights and water depths. Based on the numerical results, the resistance, navigation state and flow field characteristics under different working conditions are analyzed. ResultsThe results show that the drag reduction effect of the interceptor has an obvious shallow water effect. The optimal drag reduction height and reduction of trim angle of the interceptor is unchanged with the change in water depth. The interceptor has a certain effect on reducing wave-making behind the ship, but the effect decreases with the decrease in water depth. ConclusionsThis study has certain practical reference value for the application of interceptors in shallow water.

Abstract Urbanization is one of the milestones in the development of human society. Many regions in the southern parts of ‘the old world’ demonstrating an early emergence of agriculture also witnessed the flourishing of some of the earliest cities. Recent, yet still sparse, archaeological evidence appears to indicate a relatively later time for early urbanism in central Eurasia. However, given its vital geographic location and cultural nexus between East and West, more attention should be paid to the sedentary communities and their cities in oases amid the vast droughty desert, particularly in light of the rapidly increasing number of publications on early pastoralism and related communication routes along mountain chains and rivers. This study reveals the trajectory of urbanization and its role in the establishment of an exchange network in Xinjiang’s oasis region via reconstruction of the chronological sequence of the local societal history of the Baiyang River Basin along the southern piedmont of the Eastern Tianshan Mountains. A thorough archaeological investigation and refined radiocarbon dating programme was carried out and coupled with information from historical documentation within a Bayesian statistical framework. The results indicate three pulses of local urbanization during: the Early Iron Age, Tang–Yuan period, and Qing Dynasty, respectively. Combining this with evidence from other parts of Xinjiang, we re-evaluate the role of oasis urbanism in the promotion of trans-regional exchange.

Neohelicomyces species are a group of helicosporous hyphomycetes with the potential to produce secondary metabolites. During our investigation of helicosporous fungi, six collections were isolated from both terrestrial and freshwater habitats in Guizhou Province, China. Based on multigene phylogenetic analysis (ITS, LSU, tef1α and rpb2), coupled with morphological data, three new Neohelicomyces species, viz. N. guizhouensis, N. helicosporus and N. hydei were established. A list of accepted Neohelicomyces species with molecular data was provided. The strain of Neohelicomyces pallidus (UAMH 10535) was synonymised under N. denticulatus based on molecular data.

Abstract Background There are significant geographic inequities in COVID-19 case fatality rates (CFRs), and comprehensive understanding its country-level determinants in a global perspective is necessary. This study aims to quantify the country-specific risk of COVID-19 CFR and propose tailored response strategies, including vaccination strategies, in 156 countries. Methods Cross-temporal and cross-country variations in COVID-19 CFR was identified using extreme gradient boosting (XGBoost) including 35 factors from seven dimensions in 156 countries from 28 January, 2020 to 31 January, 2022. SHapley Additive exPlanations (SHAP) was used to further clarify the clustering of countries by the key factors driving CFR and the effect of concurrent risk factors for each country. Increases in vaccination rates was simulated to illustrate the reduction of CFR in different classes of countries. Findings Overall COVID-19 CFRs varied across countries from 28 Jan 2020 to 31 Jan 31 2022, ranging from 68 to 6373 per 100,000 population. During the COVID-19 pandemic, the determinants of CFRs first changed from health conditions to universal health coverage, and then to a multifactorial mixed effect dominated by vaccination. In the Omicron period, countries were divided into five classes according to risk determinants. Low vaccination-driven class (70 countries) mainly distributed in sub-Saharan Africa and Latin America, and include the majority of low-income countries (95.7%) with many concurrent risk factors. Aging-driven class (26 countries) mainly distributed in high-income European countries. High disease burden-driven class (32 countries) mainly distributed in Asia and North America. Low GDP-driven class (14 countries) are scattered across continents. Simulating a 5% increase in vaccination rate resulted in CFR reductions of 31.2% and 15.0% for the low vaccination-driven class and the high disease burden-driven class, respectively, with greater CFR reductions for countries with high overall risk (SHAP value > 0.1), but only 3.1% for the ageing-driven class. Conclusions Evidence from this study suggests that geographic inequities in COVID-19 CFR is jointly determined by key and concurrent risks, and achieving a decreasing COVID-19 CFR requires more than increasing vaccination coverage, but rather targeted intervention strategies based on country-specific risks.

Abstract Background Wheat is one of the important grain crops in the world. The formation of lesion spots related to cell death is involved in disease resistance, whereas the regulatory pathway of lesion spot production and resistance mechanism to pathogens in wheat is largely unknown. Results In this study, a pair of NILs (NIL-Lm5 W and NIL-Lm5 M) was constructed from the BC1F4 population by the wheat lesion mimic mutant MC21 and its wild genotype Chuannong 16. The formation of lesion spots in NIL-Lm5 M significantly increased its resistance to stripe rust, and NIL-Lm5 M showed superiour agronomic traits than NIL-Lm5 W under stripe rust infection.Whereafter, the NILs were subjected to transcriptomic (stage N: no spots; stage S, only a few spots; and stage M, numerous spots), metabolomic (stage N and S), and hormone analysis (stage S), with samples taken from normal plants in the field. Transcriptomic analysis showed that the differentially expressed genes were enriched in plant-pathogen interaction, and defense-related genes were significantly upregulated following the formation of lesion spots. Metabolomic analysis showed that the differentially accumulated metabolites were enriched in energy metabolism, including amino acid metabolism, carbohydrate metabolism, and lipid metabolism. Correlation network diagrams of transcriptomic and metabolomic showed that they were both enriched in energy metabolism. Additionally, the contents of gibberellin A7, cis-Zeatin, and abscisic acid were decreased in leaves upon lesion spot formation, whereas the lesion spots in NIL-Lm5 M leaves were restrained by spaying GA and cytokinin (CTK, trans-zeatin) in the field. Conclusion The formation of lesion spots can result in cell death and enhance strip rust resistance by protein degradation pathway and defense-related genes overexpression in wheat. Besides, the formation of lesion spots was significantly affected by GA and CTK. Altogether, these results may contribute to the understanding of lesion spot formation in wheat and laid a foundation for regulating the resistance mechanism to stripe rust.

Abstract Background Wheat grain endosperm is mainly composed of proteins and starch. The contents and the overall composition of seed storage proteins (SSP) markedly affect the processing quality of wheat flour. Polyploidization results in duplicated chromosomes, and the genomes are often unstable and may result in a large number of gene losses and gene rearrangements. However, the instability of the genome itself, as well as the large number of duplicated genes generated during polyploidy, is an important driving force for genetic innovation. In this study, we compared the differences in starch and SSP, and analyzed the transcriptome and metabolome among Aegilops sharonensis (R7), durum wheat (Z636) and amphidiploid (Z636×R7) to reveal the effects of polyploidization on the synthesis of seed reserve polymers. Results The total starch and amylose content of Z636×R7 was significantly higher than R7 and lower than Z636. The gliadin and glutenin contents of Z636×R7 were higher than those in Z636 and R7. Through transcriptome analysis, there were 21,037, 2197, 15,090 differentially expressed genes (DEGs) in the three comparison groups of R7 vs Z636, Z636 vs Z636×R7, and Z636×R7 vs R7, respectively, which were mainly enriched in carbon metabolism and amino acid biosynthesis pathways. Transcriptome data and qRT-PCR were combined to analyze the expression levels of genes related to storage polymers. It was found that the expression levels of some starch synthase genes, namely AGP-L, AGP-S and GBSSI in Z636×R7 were higher than in R7 and among the 17 DEGs related to storage proteins, the expression levels of 14 genes in R7 were lower than those in Z636 and Z636×R7. According to the classification analysis of all differential metabolites, most belonged to carboxylic acids and derivatives, and fatty acyls were enriched in the biosynthesis of unsaturated fatty acids, niacin and nicotinamide metabolism, one-carbon pool by folate, etc. Conclusion After allopolyploidization, the expression of genes related to starch synthesis was down-regulated in Z636×R7, and the process of starch synthesis was inhibited, resulting in delayed starch accumulation and prolongation of the seed development process. Therefore, at the same development time point, the starch accumulation of Z636×R7 lagged behind that of Z636. In this study, the expression of the GSe2 gene in Z636×R7 was higher than that of the two parents, which was beneficial to protein synthesis, and increased the protein content. These results eventually led to changes in the synthesis of seed reserve polymers. The current study provided a basis for a greater in-depth understanding of the mechanism of wheat allopolyploid formation and its stable preservation, and also promoted the effective exploitation of high-value alleles.

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a devastating disease in wheat worldwide. Discovering and characterizing new resistance genes/QTL is crucial for wheat breeding programs. In this study, we fine-mapped and characterized a stripe rust resistance gene, YRAYH, on chromosome arm 5BL in the Chinese wheat landrace Anyuehong (AYH). Evaluations of stripe rust response to prevalent Chinese Pst races in near-isogenic lines derived from a cross of Anyuehong and Taichung 29 showed that YrAYH conferred a high level of resistance at all growth stages. Fine mapping using a large segregating population of 9748 plants, narrowed the YRAYH locus to a 3.7 Mb interval on chromosome arm 5BL that included 61 annotated genes. Transcriptome analysis of two NIL pairs identified 64 upregulated differentially expressed genes (DEGs) in the resistant NILs (NILs-R). Annotations indicated that many of these genes have roles in plant disease resistance pathways. Through a combined approach of fine-mapping and transcriptome sequencing, we identified a serine/threonine-protein kinase SRPK as a candidate gene underlying YrAYH. A unique 25 bp insertion was identified in the NILs-R compared to the NILs-S and previously published wheat genomes. An InDel marker was developed and co-segregated with YrAYH. Agronomic trait evaluation of the NILs suggested that YrAYH not only reduces the impact of stripe rust but was also associated with a gene that increases plant height and spike length.

Abstract This study presents a probabilistic seismic risk model for the Beijing–Tianjin–Hebei region in China. The model comprises a township-level residential building exposure model, a vulnerability model derived from the Chinese building taxonomy, and a regional probabilistic seismic hazard model. The three components are integrated by a stochastic event-based method of the OpenQuake engine to assess the regional seismic risk in terms of average annual loss and exceedance probability curve at the city, province, and regional levels. The novelty and uniqueness of this study are that a probabilistic seismic risk model for the Beijing–Tianjin–Hebei region in China is developed by considering the impact of site conditions and epistemic uncertainty from the seismic hazard model.

Abstract Leveraging the Chinese capital market, we investigate the relationship between a CEO’s scientific research background and the level of digitalization within enterprises. Our results demonstrate robust findings indicating that a CEO’s scientific research background significantly enhances the level of enterprise digitalization. Moreover, we observe that this correlation is more pronounced in companies controlled by non-state-owned enterprises, those operating within a more advanced digital economy, and those engaged in high levels of regional integration. Furthermore, we establish that the positive impact of a CEO’s research background on a company’s digitalization level is primarily driven by fostering the organization’s innovation drive. Overall, our research suggests that CEOs with scientific research backgrounds are instrumental in encouraging a culture of innovation within their firms, thereby enhancing enterprise digitalization performance. This study contributes to the literature by exploring the factors influencing enterprise digitalization levels through the lens of managerial experience and analyzing the economic implications of management experience on enterprise digital transformation. Methodologically, we have refined and enhanced the measurement approach for assessing enterprise digitalization levels. Practically, our findings underscore the importance of promoting cross-industry and cross-regional exchanges of high-caliber talent for executives, enterprises, and governmental entities alike.

Objectives The sodium index is an index that converts the estimated sodium intake calculated using a verified and reliable sodium estimation formula. This study aimed to determine the relationship between the sodium index and obesity indicators and the potential impact of excessive sodium consumption on obesity. Methods Obesity indicators, such as body mass index (BMI), body fat percentage, waist-to-hip ratio (WHR), and visceral fat levels, were analyzed in 120 university students (60 men and 60 women). The sodium index was calculated by indexing the estimated sodium intake according to age, sex, BMI, salt-eating habits, and salt-eating behaviors. The relationship between sodium index and obesity indicators was analyzed using multiple logistic regression. Results The estimated sodium intake was 3,907.1 mg, with 76.7% of the participants categorized under the “careful” level of sodium index and 10.8% under the “moderate” level. As the sodium index increased, the BMI, body fat percentage, WHR, and visceral fat levels significantly increased. All obesity indicators significantly increased in patients with a “severe” sodium index than in those with a “moderate” sodium index. In addition, a strong positive correlation was identified between obesity indicators and sodium index. When the “severe” sodium index was compared with the “moderate” sodium index, the risk of obesity based on body fat percentage increased by 2.181 times (95% confidence interval [CI], 1.526–3.118), while the risk of obesity based on visceral fat level increased by 4.073 times (95% CI, 2.097–7.911). Conclusions Our findings suggest a correlation between excessive sodium intake and obesity. Moreover, the sodium index can be used to determine sodium intake.

Abstract Reliable projections of the tropical Pacific sea surface temperature (SST) warming (TPSW) patterns are critically important for exploring the future climate change. However, climate models suffer from long‐standing common biases in simulating the present‐day climate, raising doubts about the model projected TPSW patterns. Here by using outputs from 30 CMIP6 models, we find the projected TPSW patterns are significantly correlated with the simulated present‐day SST in the tropical North Atlantic (TNA), with higher present‐day TNA SSTs tending to project more weakened zonal SST gradients by producing more present‐day low‐level clouds and the resultant positive cloud–shortwave–SST feedbacks over the eastern equatorial Pacific. An emergent constraint using observed TNA SST reveals a consistent El Niño‐like warming pattern in all models with more weakened zonal SST gradient than before in most models, together with a reduction of the inter‐model uncertainty in the zonal SST gradient change by more than 20%.

Advanced metastatic cardia cancer is an intractable malignance with poor prognosis. It is often accompanied by upper digestive tract obstruction, which seriously affects the quality of patients. Therefore, effective relief of eating obstruction is an important goal in the treatment of cardia cancer. Immune checkpoint inhibitors (ICIs) have shown significant efficacy in cardia cancer, but only a small percentage of patients will benefit from them due to immune resistance. Oncolytic viruses have been shown to enhance the efficacy of ICIs by altering the immune microenvironment. This indicates that oncolytic virus has the potential value of overcoming the immune resistance of cardia cancer. Here, we present a case with local recurrent and multiple metastatic cardia cancer accompanied by eating obstruction. After 4 cycles of chemotherapy plus ICI therapy, the patient´s metastases were significant shrink, but the recurrent carida lesion were almost unchanged. Then we implemented exploratory local injection of recombinant human adenovirus type 5(H101) into recurrent cardia lesion by painless gastroscopy. Surprisingly, the cardia lesion shrank significantly, and the eating obstruction was greatly relieved. We also observed a significant increase of infiltrated CD4+T cells in biopsy tissues after H101 treatment. Our study not only conformed the value of oncolytic viruses to reverse ICI resistance in patients with gastric cancer, but also revealed its underlying impact on immune microenvironment.

Chinese bayberry residue (CBR) is a by-product of processing, which can be used as an auxiliary material during the processing of quinoa rice wine. In this study, the effects of CBR on the chemical profile, bioactive function, taste traits, and flavor of Chinese quinoa rice wine (CQRW) were investigated. The results showed that adding CBR increased the total phenolics, the total flavonoids, and antioxidant capacity. Malic acid content was the highest in Chinese rice wine (CRW), while the total content of components detected in HPLC-MS/MS was the highest in 10%CBR + CQRW. The CQRW exhibited the highest amino acid content, followed by 20%CBR + CQRW. E-tongue analysis results showed that 10%CBR + CQRW, 20%CBR + CQRW, and CQRW had the closest taste traits. Moreover, GC–MS analysis identified 72 aroma compounds in 10%CBR + CQRW sample, more than other samples. In summary, adding 10% CBR significantly improved the quality of CQRW.

Metallurgical defects in metal laser additive manufacturing (LAM) are inevitable due to complex non-equilibrium thermodynamics. A laser ultrasonic system was designed for detecting surface/near-surface defects in the layer-by-layer LAM process. An approach was proposed for ultrasonic imaging of defects based on variable time window intensity mapping with adaptive 2σ threshold denoising. The Gaussian mixture model hypothesis and expectation-maximization algorithm can automatically differentiate between components dominated by defects and background noises, thereby providing an adaptive threshold that accommodates detection environments and surface roughness levels. Results show that the ultrasonic wave reflection at defect boundaries diminishes far-field ultrasonic intensity upon pulsed laser irradiation on surface defects, enabling defect size and location characterization. This method is applicable to LAM samples with a significant surface roughness of up to 37.5 μm. It can detect superficial and near-surface defects down to 0.5 mm in diameter and depth, making it significant for online defect detection in additive manufacturing.

Several studies have documented a relationship between short-term exposure to atmospheric sulfur dioxide (SO2) and chronic obstructive pulmonary disease (COPD). However, findings vary across different regions. This meta-analysis employed a random-effects model to calculate the combined risk estimate for each 10-μg/m3 increase in ambient SO2 concentration. Subgroup analysis aimed to identify sources of heterogeneity. To assess potential bias, studies were evaluated using a domain-based assessment tool developed by the World Health Organization. Sensitivity analyses, based on bias risk, explored how model assumptions influenced associations. An evidence certainty framework was used to evaluate overall evidence quality. The study protocol was registered with PROSPERO (CRD42023446823). We thoroughly reviewed 191 full-text articles, ultimately including 15 in the meta-analysis. The pooled relative risk for COPD was 1.26 (95 % CI 0.94–1.70) per 10-μg/m3 increase in ambient SO2. Eleven studies were deemed high risk due to inadequate handling of missing data. Overall evidence certainty was rated as medium. Given SO2's significant public health implications, continuous monitoring is crucial. Future research should include countries in Africa and Oceania to enhance global understanding of atmospheric SO2-related health issues.

The objective of current experiment was to study the potential influence of hydrolysable tannin supplementation on slaughter performance, meat quality, intestinal digestive enzyme activity, antioxidant ability and barrier function in fattening lambs. In total, 36 male Hu sheep lambs with similar body weight (15.83 ± 0.48 kg) and days in age (55 ± 2 d) were randomly assigned to one of three groups of 12 animals each: control without tannin (CON) and tannin supplementation groups (TA1, 3 g/d per lamb; TA2, 6 g/d per lamb). All the lambs were reared in individual hutches, and the experiment lasted for 60 d. On d 61, 8 lambs from each group were randomly selected to slaughter. Results showed that the serum diamine oxidase and lipopolysaccharide contents of TA2 group were higher (p

CTNNB1 encodes beta-catenin, which plays a crucial role in Wnt signaling pathway. Mutations in CTNNB1 involve in tumor developing, Primary Aldosteronism, Neurodevelopmental disorders (NDDs), etc. NDDs is a class of disorders that impact brain development and function, manifesting symptom including autism spectrum disorder (ASD), intellectual disability (ID), schizophrenia (SCZ), and epilepsy. Here, we generated an iPSC line (CTUi005-A) from a patient diagnosed with NDDs, carrying a heterozygous mutation of the CTNNB1 gene. CTUi005-A exhibits typical iPSC characteristics, and holds potential as a cellular tool for investigating the pathogenic mechanisms underlying NDDs.

Grape seed extract (GSE) has a variety of biological functions. At present, there has been limited information on the utilization of GSE as a feed additive in weaned lambs. The aim of this experiment was to study the potential influence of dietary supplementation with GSE on the growth performance, rumen fermentation characteristics, apparent digestibility, blood parameters and immunity in weaned lambs. In total, 30 male Hu sheep lambs with similar body weight (15.43 ± 0.49 kg) and age (48 ± 2 days) were randomly divided into two treatments: control (CON, fed basal ration) and GSE [fed basal ration and 0.6 g/d GSE (main compositions: proanthocyanidin 50%, catechin 24%, gallic acid 16% and epicatechin 6%) per lamb]. The feeding experiment lasted for 60 d. Results showed that GSE supplementation significantly increased (p = 0.008) the average daily gain of lambs. Compared with CON group, the ruminal propionate and butyrate concentrations were significantly increased (p

IntroductionFat grafting often yields inconsistent and suboptimal results, necessitating improved fat processing techniques. A stromal vascular fraction (SVF) gel created using mechanical emulsification demonstrates superior retention rates to conventional Coleman fat grafts.MethodsThis study investigated the mechanisms at play by transplanting fat aspirates from liposuction patients—either processed as Coleman fat grafts or further refined into an SVF gel via mechanical shear force—onto the backs of nude mice.ResultsThe retention rate of the SVF gel after transplantation surpassed that observed for Coleman fat. Hematoxylin and eosin (HE) staining and immunofluorescence results demonstrated that the SVF gel group could form new adipose tissue characterized by well-organized mature fat structures. Mechanical shear force application induced increased mesenchymal stem cell abundance. Rather than merely surviving regeneration, fat was regenerated after transplantation, and the regenerated cells were mainly from mice, which was supported by microarray analysis. RNA-seq highlighted 601 genes expressed between SVF gel and Coleman fat groups, with 164 genes upregulated (cell cycle processes), and 437 genes downregulated (lipid metabolism).DiscussionThe application of mechanical shear force reduces the risk of complications and fosters cell proliferation and division, thereby enhancing the retention and regeneration of transplanted fat.

Abstract Discovering new treatments for melanoma will benefit human health. The mechanism by which deoxyhypusine synthase (DHPS) promotes melanoma development remains elucidated. Multi‐omics studies have revealed that DHPS regulates m6A modification and maintains mRNA stability in melanoma cells. Mechanistically, DHPS activates the hypusination of eukaryotic translation initiation factor 5A (eIF5A) to assist METTL3 localizing on its mRNA for m6A modification, then promoting METTL3 expression. Structure‐based design, synthesis, and activity screening yielded the hit compound GL‐1 as a DHPS inhibitor. Notably, GL‐1 directly inhibits DHPS binding to eIF5A, whereas GC‐7 cannot. Based on the clarification of the mode of action of GL‐1 on DHPS, it is found that GL‐1 can promote the accumulation of intracellular Cu2+ to induce apoptosis, and antibody microarray analysis shows that GL‐1 inhibits the expression of several cytokines. GL‐1 shows promising antitumor activity with good bioavailability in a xenograft tumor model. These findings clarify the molecular mechanisms by which DHPS regulates melanoma proliferation and demonstrate the potential of GL‐1 for clinical melanoma therapy.

Abstract Background Previous studies have shown that protein kinase MoKin1 played an important role in the growth, conidiation, germination and pathogenicity in rice blast fungus, Magnaporthe oryzae. ΔMokin1 mutant showed significant phenotypic defects and significantly reduced pathogenicity. However, the internal mechanism of how MoKin1 affected the development of physiology and biochemistry remained unclear in M. oryzae. Result This study adopted a multi-omics approach to comprehensively analyze MoKin1 function, and the results showed that MoKin1 affected the cellular response to endoplasmic reticulum stress (ER stress). Proteomic analysis revealed that the downregulated proteins in ΔMokin1 mutant were enriched mainly in the response to ER stress triggered by the unfolded protein. Loss of MoKin1 prevented the ER stress signal from reaching the nucleus. Therefore, the phosphorylation of various proteins regulating the transcription of ER stress-related genes and mRNA translation was significantly downregulated. The insensitivity to ER stress led to metabolic disorders, resulting in a significant shortage of carbohydrates and a low energy supply, which also resulted in severe phenotypic defects in ΔMokin1 mutant. Analysis of MoKin1-interacting proteins indicated that MoKin1 really took participate in the response to ER stress. Conclusion Our results showed the important role of protein kinase MoKin1 in regulating cellular response to ER stress, providing a new research direction to reveal the mechanism of MoKin1 affecting pathogenic formation, and to provide theoretical support for the new biological target sites searching and bio-pesticides developing.

Continuous alumina fiber-reinforced alumina (Al2O3/Al2O3) composite is a very promising candidate for thermal structural materials in aerospace vehicles and other applications. Alumina fibers used in Al2O3/Al2O3 composites play a crucial role in enhancing their mechanical properties and thermostability. In this article, the effect of annealing on the tensile strength and microstructure of Morlion735 alumina fiber was investigated. The results showed that the phase transformation occurs at 1147 °C, resulting in a mullite phase with an orthogonal lattice structure. As the annealing temperature increases, the crystal domain size of the mullite gradually increases. Both the phase transformation and the increasing crystal domain size lead to more lattice defects, which significantly affect the tensile strength and tensile modulus of alumina fibers. A 0.67 GPa reduction in tensile strength (from 1.14 GPa to 0.47 GPa) was observed when the annealing temperature increased from 1200 °C to 1400 °C. Weibull statistical analysis revealed that as the annealing temperature increased, the tensile strength dispersion of Morlion735 fiber also increased. This can be attributed to the volume-dependent flaw distributions. These results provide an in-depth understanding of the tensile strength evolution mechanism under high temperatures.

Abstract Hepatitis B virus is a globally distributed pathogen and the history of HBV infection in humans predates 10000 years. However, long-term evolutionary history of HBV in Eastern Eurasia remains elusive. We present 34 ancient HBV genomes dating between approximately 5000 to 400 years ago sourced from 17 sites across Eastern Eurasia. Ten sequences have full coverage, and only two sequences have less than 50% coverage. Our results suggest a potential origin of genotypes B and D in Eastern Asia. We observed a higher level of HBV diversity within Eastern Eurasia compared to Western Eurasia between 5000 and 3000 years ago, characterized by the presence of five different genotypes (A, B, C, D, WENBA), underscoring the significance of human migrations and interactions in the spread of HBV. Our results suggest the possibility of a transition from non-recombinant subgenotypes (B1, B5) to recombinant subgenotypes (B2 - B4). This suggests a shift in epidemiological dynamics within Eastern Eurasia over time. Here, our study elucidates the regional origins of prevalent genotypes and shifts in viral subgenotypes over centuries.

Abstract Endometrial cancer (EC) cells exhibit abnormal glucose metabolism, characterized by increased aerobic glycolysis and decreased oxidative phosphorylation. Targeting cellular glucose metabolism in these cells could be an effective therapeutic approach for EC. This study aimed to assess the roles of LIN28B, PCAT5, and IGF2BP3 in the glucose metabolism, proliferation, migration, and invasion of EC cells. LIN28B highly expressed in EC, binds and stabilizes PCAT5. PCAT5, overexpressed in EC, and its 1485-2288nt region can bind to the KH1-2 domain of IGF2BP3 to prevent MKRN2 from binding to the K294 ubiquitination site of IGF2BP3, thus stabilizing IGF2BP3. Finally, IGF2BP3 promotes the aerobic glycolysis, proliferation, migration and invasion of EC cells by stabilizing the key enzymes of glucose metabolism HK2 and PKM2. Taken together, our data reveal that the LIN28B/PCAT5/IGF2BP3 axis is critical for glucose reprogramming and malignant biological behavior in EC cells. Therefore, targeting this axis may contribute to the development of a novel therapeutic strategy for EC metabolism.

Abstract Despite the dominance of lead-based piezoelectric materials with ultrahigh electric-field-induced strain in actuating applications, seeking eco-friendly substitutes with an equivalent performance remains an urgent demand. Here, a strategy of regulating the irreversible non-180° domain via phase engineering is introduced to optimize the available strain (the difference between the maximum strain and the remnant strain in a unipolar strain curve) in the lead-free potassium–sodium niobate-based piezoelectric ceramics. In situ synchrotron X-ray diffraction and Rayleigh analysis reveal the contribution of the non-180° domain to available strain in the tetragonal–orthorhombic–rhombohedral phase boundary. The reducing orthorhombic phase and increasing rhombohedral/tetragonal phase accompanied by the reduced irreversible non-180° domain are obtained with increasing doping of Sb5+, resulting in an enlarged available strain due to the significantly lowered remnant strain. This optimization is mainly attributed to the reduced irreversible non-180° domain wall motion and the increased lattice distortion, which are beneficial to decrease extrinsic contribution and enhance intrinsic contribution. The mesoscopic structure of miniaturized nanosized domain with facilitated domain switching also contributes to the enhancement of available strain due to the improved random field and decreased energy barrier. The study will shed light on the design of lead-free high-performance piezoelectric ceramics for actuator applications.