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The ejector is a crucial component of the hydrogen circulation system of proton exchange membrane fuel cell (PEMFC), which is widely used because of its simple structure, reliable operation, and no additional power consumption. However, the current research on pulsed ejectors is still lacking and in-depth. In this study, CFD modeling is conducted on the ejector, and the pulsed gas flow is simulated by user define function (UDF), and the influence of the pulsed gas flow on the entrainment performance of the ejector is analyzed. The results show that, compared with the steady-state condition, the entrainment performance of the ejector using pulsed gas flow under different primary flow pressures is improved, and the maximum entrainment ratio is 3.195 under steady-state conditions and 3.507 under transient conditions, which is increased by 9.8%. The effect is especially pronounced at low pressure, where the entrainment ratio increases by 16.6%. And by comparing the gas flow of different pulse frequencies, it is found that when the pulse frequency is 1Hz, the ejector has the best entrainment performance. • The ejector with pulsed gas flow has significantly better entrainment performance. • At the low primary inlet pressure, the pulsed gas flow has a good effect on the entrain ment performance. • Pulsed gas flow can form a lower low-pressure area at the nozzle exit. • When the frequency of the pulsed gas flow is 1Hz, the entrainment ratio is maximum. [ABSTRACT FROM AUTHOR]

In order to cultivate children's computational thinking, researchers have developed many excellent programming systems. Among them, the tangible programming systems combined with graphic output have been widely accepted because of the intuitive input method and diversified visual feedback. However, few of them support collaborative learning or programming. Little is known about children's experiences, emotional states and behaviours on collaborative programming. Motivated by this gap, we present a novel tangible and collaborative enabled programming system named Lighters, which designed for children aged 7–10 and had two types of collaboration modes (block-based and role-based). We conducted an user experiment with 24 children, and collected physiological (EDA), questionnaire, video recording and interview data for analysis. Based on our experiment results, Lighters are effective in helping children learn to program collaboratively. In addition, Lighters can mobilize children's positive emotions and enthusiasm to learn programming. Compared with block-based collaboration, role-based collaboration is more likely to stimulate children's emotional states and has a better effect on learning programming. [ABSTRACT FROM AUTHOR]

Fluorescent imaging and biosensing in the near‐infrared‐II (NIR‐II) window holds great promise for non‐invasive, radiation‐free, and rapid‐response clinical diagnosis. However, it's still challenging to develop bright NIR‐II fluorophores. In this study, we report a new strategy to enhance the brightness of NIR‐II aggregation‐induced emission (AIE) fluorophores through intramolecular electrostatic locking. By introducing sulfur atoms into the side chains of the thiophene bridge in TSEH molecule, the molecular motion of the conjugated backbone can be locked through intramolecular interactions between the sulfur and nitrogen atoms. This leads to enhanced NIR‐II fluorescent emission of TSEH in both solution and aggregation states. Notably, the encapsulated nanoparticles (NPs) of TSEH show enhanced brightness, which is 2.6‐fold higher than TEH NPs with alkyl side chains. The in vivo experiments reveal the feasibility of TSEH NPs in vascular and tumor imaging with a high signal‐to‐background ratio and precise resection for tiny tumors. In addition, polystyrene nanospheres encapsulated with TSEH are utilized for antigen detection in lateral flow assays, showing a signal‐to‐noise ratio 1.9‐fold higher than the TEH counterpart in detecting low‐concentration antigens. This work highlights the potential for developing bright NIR‐II fluorophores through intramolecular electrostatic locking and their potential applications in clinical diagnosis and biomedical research. [ABSTRACT FROM AUTHOR]

Primary pulmonary hyalinizing clear cell carcinoma (HCCC) is a very rare lung tumor that accounts for less than 0.09% of all primary lung tumors and has no specific epidemiology. The correct diagnosis requires imaging, laboratory, pathological, immunohistochemical, and molecular examination. The most typical feature of pulmonary HCCC is the clear cell component with clear stroma. In addition, the fusion gene EWSR1::ATF1 due to t(12;22)(q13;q12) is essential for the pathological diagnosis of pulmonary HCCC. The main treatment for pulmonary HCCC is surgery. This review focus on the pathological features, immunohistochemical examination, mutation analysis and treatment of pulmonary HCCC. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of Schizandrin B on lung injury in rats with acute pancreatitis (AP) via Toll-like receptor 4 (TLR4) /nuclear factor-κB (NF-κB) signaling pathway. Methods: SD rats were taken and induced the establishment of AP lung injury model by retrograde injection of 5% sodium taurocholate into the bile duct. According to random number table method, they were divided into model group, schisandrin B group, TLR4 overexpression vector group, TLR4 empty group, schisandrin B+ TLR4 overexpression vector group, 12 rats per group. Twelve SD rats only flipped the intestines without injecting 5% sodium taurocholate, as the sham operation group. After intervening rats in groups with drugs, pulmonary function of rats in each group, the amount of ascites and lung tissue wet weight/dry weight (W/D) of rats in each group were measured; HE staining was used to detect pathological morphology of lung tissue and score; levels of arterial blood gas indexes of rats in each group were detected by fully automatic biochemical analyser; levels of serum amylase and inflammatory cytokines IL-6 and IL-18 were measured by ELISA; Western blotting was used to detect protein expression of TLR4/NF-κB signaling pathway in lung tissue; expression of TLR4 protein in lung tissue of rat in each group was detected by immunohistochemical staining. Results: Compared with sham operation group, lung tissue of rats in model group showed pathological changes, MV, PEF, PaO2 and OI of model group were significantly reduced (P<0.05), while Ri, ascites volume, W/D, PaCO2, Holfbauer score, serum amylase, IL-6 and IL-18 levels, lung tissue proportion of TLR4 positive cells, expressions of TLR4 and MYD88 protein, p-NF-κB p65/NF-κB p65 level were significantly increased (P<0.05) . Compared with model group and schisandrin B+TLR4 overexpression vector group, respectively, pathological changes of lung tissue of rats in schisandrin B group were reduced, MV, PEF, PaO2 and OI were all increased (P<0.05), while Ri, ascites volume, W/D, PaCO2, Holfbauer score, serum amylase, IL-6 and IL-18 levels, lung tissue proportion of TLR4 positive cells, expressions of TLR4 and MYD88 protein, p-NF-κB p65/NF-κB p65 levels were decreased (P<0.05); in TLR4 overexpression vector group, degree of pathological damage in lung tissue of rats was aggravated, MV, PEF, PaO2 and OI were all decreased (P<0.05), while Ri, ascites volume, W/D, PaCO2, Holfbauer score, serum amylase, IL-6 and IL-18 levels, lung tissue proportion of TLR4 positive cells, expressions of TLR4 and MYD88 protein, p-NF-κB p65/NF-κB p65 level were increased (P<0.05) . Compared with model group, rats in TLR4 empty group showed no significant difference (P>0.05). Conclusion: Schizandrin B can down-regulate TLR4/NF-κB signaling pathway to inhibit inflammation, reduce lung injury in AP rats, and repair lung function. [ABSTRACT FROM AUTHOR]

Self-cleaning coatings need to have a certain degree of breathability to avoid peeling due to interfacial stress. In this study, a multifunctional superhydrophobic breathable DDA-PDA@BNNS/silicon resin coating is successfully designed by modifying sucrose-assisted exfoliation of boron nitride nanosheets (BNNS) with dodecylamine (DDA) and polydopamine (PDA). The coating shows a contact angle as high as 153.6° and a rolling angle as low as 4.8°, which can effectively avoid the adhesion of solid and liquid contaminants and extend the freezing time of ice up to six times. Meanwhile, the porous network structure of boron nitride nanosheets hardly changes the water vapor transmission rate of the substrate material. The DDA-PDA@BNNS/silicon resin breathable superhydrophobic coating is expected to achieve practical applications in long-lasting self-cleaning and antifouling. [Display omitted] • A multifunctional superhydrophobic breathable coating is designed by modifying BNNS. • The porous structure hardly changes water vapor transmission rate of the substrate. • The coating can avoid the adhesion of contaminants and extend the freezing time. • The breathability and universality of coating promise the practical applications. [ABSTRACT FROM AUTHOR]

Remote Sensing Archaeology (RSA) is an innovative sub-discipline within archaeology that utilizes general Remote Sensing (RS) techniques to analyze data from ancient human-made structures. This analysis significantly contributes to understanding various facets of human history, such as cultures, practices, diversity, and evolution. Our study anticipates the forthcoming changes in the roles of RS archaeologists and the research framework of RSA. Emphasizing the necessity for archaeologists to comprehend remote, proximal, in-situ, and instrumental sensing technologies, as well as rapidly evolving digital advancements, such as Artificial Intelligence/Machine Learning (AI/ML), Big Data (BD), Cloud or Cyber Infrastructure (CI), and Digitalization Technology (DT). Drawing upon successful techniques and practices, we argue the efficacy of RSA in addressing historical, contemporary, and future challenges. This effectiveness becomes particularly pronounced as RSA transitions from archaeological prospecting to knowledge discovery using space technologies, represented by RS. Space Archaeology (SA), which we propose as an evolved stage of RSA for archaeological prospecting, builds upon the experiences and lessons gleaned from RSA's century-long journey. It not only extends the legacy of RSA but also signifies a shift in both the implication and methodology of sensing-based archaeological prospecting. SA, while advancing RSA, also aligns with the current trend of spatial thinking in archaeology amidst substantial transformations in RSA research. The perspectives outlined in this review aspire to positively shape the ongoing shift in archaeological spatial thinking. • The recent advance in remote sensing archaeology is reviewed. • The new paradigm of space archaeology is first described. • Specific focus is given to the understanding of past human–environment interactions. • Emerging trends and future perspectives are highlighted in four key areas. [ABSTRACT FROM AUTHOR]

[Display omitted] • FeNC-RM, with excellent physicochemical properties was prepared by two-step pyrolysis. • Performance of AD for treating actual landfill leachate was amplified by FeNC-RM. • Secretion of HS was promoted for constructing an endogenous electronic bridge. • "Endogenous + exogenous" electron transfer mode from a new perspective was established. The presence of recalcitrant compounds and toxic substances in landfill leachate results in low anaerobic digestion (AD) efficiency and poor methane production performance. Strengthening the extracellular electron transfer of microorganisms represents an effective approach to promote the AD of landfill leachate. In this study, a novel redox mediator (FeNC-RM) was synthesized through the combination of metal and non-metal doping, intensifying the stable operation of the landfill leachate AD system. Through characterization techniques including X-ray photoelectron spectroscopy and X-ray diffraction, it was observed that FeNC-RM possesses a larger specific surface area, abundant functional groups, and exceptional electrochemical performance. By adding FeNC-RM, the stability and efficiency of the medium-temperature AD system in the treatment of landfill leachate were improved: Obtained a high removal of chemical oxygen demand which was increased by 30 % compared to the control group and enhanced the specific methanogenic activity by 57.5 % compared to the control group. The electron transport system (ETS) activities of the experimental groups with the addition of RMs were all significantly higher than those of the control group, and the ETS activity of the sludge from the FeNC-RM group was 79.6 % higher than that of the control group. Through a comprehensive analysis of the underlying mechanism, it was determined that three aspects synergistically facilitated electron transfer: FeNC-RM, endowed with electrochemical capabilities, assumed a pivotal role in establishing a conduit for electron transport, thus promoting the synthesis of extracellular humic substances and augmenting electron transport activity. Furthermore, the microbial community was optimized by FeNC-RM, thereby fostering a co-nutritional mechanism between hydrolytic acidification bacteria and methanogens, establishing a direct interspecific electron transport pathway. In this study, an "endogenous + exogenous" electron transport model based on the enhanced extracellular electron transport pathway facilitated by FeNC-RM was proposed. This study offered valuable contributions to the advancement of anaerobic treatment technology for landfill leachate. [ABSTRACT FROM AUTHOR]

This paper focuses on the nonlinear behaviors of offset-halves journal bearings (OHJBs), particularly under dynamic loading and journal misalignment. A new tribo-dynamic model is given to perform transient thermoelastohydrodynamic analysis in the crucial yet understudied domain of this novel structure. Bearing characteristics are compared among bi-directional misalignment, single-direction misalignment as well as alignment. The results demonstrate that the influence of bi-directional misalignment exerts dominance. Moreover, the evolution mechanisms of bi-directional misalignment and step loading on the time-varying stiffness and damping are evaluated. In addition, parametric analyses are done to emphasize key factors in the bearing design, including the horizontal offset and radial clearance, for better transient lubrication performance. This study enriches the structural optimum for dynamically loaded journal bearings. [Display omitted] [ABSTRACT FROM AUTHOR]

Liver cirrhosis can cause disturbances in blood circulation in the liver, resulting in impaired portal blood flow and ultimately increasing portal venous pressure. Portal hypertension induces portal-systemic collateral formation and fatal complications. Extrahepatic angiogenesis plays a crucial role in the development of portal hypertension. Curcumol is a sesquiterpenoid derived from the rhizome of Curcumae Rhizoma and has been confirmed to alleviate liver fibrosis by inhibiting angiogenesis. Therefore, our study was designed to explore the effects of curcumol on extrahepatic angiogenesis and portal hypertension. To induce cirrhosis, Sprague Dawley rats underwent bile duct ligation (BDL) surgery. Rats received oral administration with curcumol (30 mg/kg/d) or vehicle (distilled water) starting on day 15 following surgery, when BDL-induced liver fibrosis had developed. The effect of curcumol was assessed on day 28, which is the typical time of BDL-induced cirrhosis. The results showed that curcumol markedly reduced portal pressure in cirrhotic rats. Curcumol inhibited abnormal splanchnic inflow, mitigated liver injury, improved liver fibrosis, and attenuated portal-systemic collateral shunting in cirrhotic rats. These protective effects were partially attributed to the inhibition on mesenteric angiogenesis by curcumol. Mechanically, curcumol partially reversed the BDL-induced activation of the JAK2/STAT3 signaling pathway in cirrhotic rats. Collectively, curcumol attenuates portal hypertension in liver cirrhosis by suppressing extrahepatic angiogenesis through inhibiting the JAK2/STAT3 signaling pathway. [ABSTRACT FROM AUTHOR]

It remains a challenge for existing financial models to accurately capture the shapes of implied volatility (IV) of options with all maturities simultaneously. Inspired by Chen et al.’s empirical finding, ‘the shorter the option expiry, the higher the IV is’, we propose a novel and simple approach to solve this challenge, by introducing a term-structure-based correction (i.e. an exponential increase function of the options expiry) to the volatility of volatility (vol–vol) term of the classical Heston stochastic volatility model. We derive an approximate formula for the IV under the corrected model with the perturbation method and further apply the formula to predict the IVs of options written on the Shanghai Stock Exchange 50 ETF. Numerical experiments and empirical results show that the introduction of a term-structure-based correction function surely overcomes the deficiency of the classical Heston model in capturing the short-term IVs, thus improving notably its performance of IV forecasting. [ABSTRACT FROM AUTHOR]

Triple‐negative breast cancer (TNBC) is a highly aggressive and metastatic malignancy with poor treatment outcomes. The interaction between the tumor microenvironment (TME) and breast cancer stem cells (BCSCs) plays an important role in the development of TNBC. Owing to their ability of self‐renewal and multidirectional differentiation, BCSCs maintain tumor growth, drive metastatic colonization, and facilitate the development of drug resistance. TME is the main factor regulating the phenotype and metastasis of BCSCs. Immune cells, cancer‐related fibroblasts (CAFs), cytokines, mesenchymal cells, endothelial cells, and extracellular matrix within the TME form a complex communication network, exert highly selective pressure on the tumor, and provide a conducive environment for the formation of BCSC niches. Tumor growth and metastasis can be controlled by targeting the TME to eliminate BCSC niches or targeting BCSCs to modify the TME. These approaches may improve the treatment outcomes and possess great application potential in clinical settings. In this review, we summarized the relationship between BCSCs and the progression and drug resistance of TNBC, especially focusing on the interaction between BCSCs and TME. In addition, we discussed therapeutic strategies that target the TME to inhibit or eliminate BCSCs, providing valuable insights into the clinical treatment of TNBC. [ABSTRACT FROM AUTHOR]

Homeodomains, a 60-amino acid sequence encoded by 180 nucleotides, are highly conserved DNA-binding motifs that are present in a variety of transcription factors in species ranging from yeast to humans. The NKX proteins belong to the homeodomain (HD)-containing transcription factor family. They play vital roles in the regulation of morphogenesis. NKX1-2 is one member of the NKX subfamily. At present, information about its nuclear localization signal (NLS) sequence is limited. We studied the NLS sequence of zebrafish Nkx1.2 by introducing sequence changes such as deletion, mutation, and truncation, and identified an NLS motif (QNRRTKWKKQ) that is localized at the C-terminus of the homeodomain. Moreover, the deletion of two amino acid residues (RR) in this NLS motif prevents Nkx1.2 from entering the nucleus, indicating that the two amino acids are essential for Nkx1.2 nuclear localization. However, the NLS motif alone is unable to target cytoplasmic protein glutathione S-transferase (GST) to the nucleus. An intact homeodomain is necessary for mediating the complete nuclear transport of cytoplasmic protein. Unlike most nuclear import proteins with short NLS sequences, a long NLS is present in zebrafish Nkx1.2. We also demonstrated that the sequences of homeodomain of NKX1.2 are well conserved among different species. This study is informative to verify the function of the NKX1.2 protein. [ABSTRACT FROM AUTHOR]

SUMMARY: Carotenoids are photosynthetic pigments and antioxidants that contribute to different plant colors. However, the involvement of TOPLESS (TPL/TPR)‐mediated histone deacetylation in the modulation of carotenoid biosynthesis through ethylene‐responsive element‐binding factor‐associated amphiphilic repression (EAR)‐containing transcription factors (TFs) in apple (Malus domestica Borkh.) is poorly understood. MdMYB44 is a transcriptional repressor that contains an EAR repression motif. In the present study, we used functional analyses and molecular assays to elucidate the molecular mechanisms through which MdMYB44‐MdTPR1‐mediated histone deacetylation influences carotenoid biosynthesis in apples. We identified two carotenoid biosynthetic genes, MdCCD4 and MdCYP97A3, that were confirmed to be involved in MdMYB44‐mediated carotenoid biosynthesis. MdMYB44 enhanced β‐branch carotenoid biosynthesis by repressing MdCCD4 expression, whereas MdMYB44 suppressed lutein level by repressing MdCYP97A3 expression. Moreover, MdMYB44 partially influences carotenoid biosynthesis by interacting with the co‐repressor TPR1 through the EAR motif to inhibit MdCCD4 and MdCYP97A3 expression via histone deacetylation. Our findings indicate that the MdTPR1‐MdMYB44 repressive cascade regulates carotenoid biosynthesis, providing profound insights into the molecular basis of histone deacetylation‐mediated carotenoid biosynthesis in plants. These results also provide evidence that the EAR‐harboring TF/TPL repressive complex plays a universal role in histone deacetylation‐mediated inhibition of gene expression in various plants. Significance Statement: MdMYB44 regulated carotenoid biosynthesis partially by interacting with co‐repressor TPR1 via EAR motif to inhibit MdCCD4 and MdCYP97A3 expression through histone deacetylation, providing evidence that the EAR‐harboring TF/TPL repressive complex has a universal role in histone deacetylation‐mediated gene expression inhibition in various plants. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is characterized by molecular heterogeneity with various immune cell infiltration patterns, which have been associated with therapeutic sensitivity and resistance. In particular, dendritic cells (DCs) are recently discovered to be associated with prognosis and survival in cancer. However, how DCs differ among ESCC patients has not been fully comprehended. Recently, the advance of single-cell RNA sequencing (scRNA-seq) enables us to profile the cell types, states, and lineages in the heterogeneous ESCC tissues. Here, we dissect the ESCC tumor microenvironment at high resolution by integrating 192,078 single cells from 60 patients, including 4379 DCs. We then used Scissor, a method that identifies cell subpopulations from single-cell data that are associated bulk samples with genomic and clinical information, to stratify DCs into Scissorhi and Scissorlow subtypes. We applied the Scissorhi gene signature to stratify ESCC scRNAseq patient, and we found that PD-L1, TIGIT, PVR and IL6 ligand-receptor-mediated cell interactions existed mainly in Scissorhi patients. Finally, based on the Scissor results, we successfully developed a validated prognostic risk model for ESCC and further validated the reliability of the risk prediction model by recruiting 40 ESCC clinical patients. This information highlights the importance of these genes in assessing patient prognosis and may help in the development of targeted or personalized therapies for ESCC. [ABSTRACT FROM AUTHOR]

Although offset-halves journal bearings (OHJBs) are extensively utilized in the marine powertrain, there is little research on nonlinear dynamic response and transient stability, particularly under conditions involving both thermo-elasto-hydrodynamic (TEHD) effects and sudden loads. To overcome such deficiency, a novel transient tribo-dynamic model and a modified stability criterion are developed. The influences of model parameters such as TEHD effects, load amplitude, offset coefficient, and varying lubricants on transient responses are studied. In addition, the evolution mechanisms of two typical lubricants on the transient stability of OHJBs are revealed. The results show that the model parameters have a significant impact on the nonlinear tribo-dynamic performance and transient stability of OHJBs. This study enriches theoretical foundations for the optimum bearing design. [ABSTRACT FROM AUTHOR]

Semantic segmentation of remote sensing images (RSIs) is pivotal for numerous applications in urban planning, agricultural monitoring, and environmental conservation. However, traditional approaches have primarily emphasized learning within the spatial domain, which frequently leads to less than optimal discrimination of features. Considering the inherent spectral qualities of RSIs, it is essential to bolster these representations by incorporating the spectral context in conjunction with spatial information to improve discriminative capacity. In this paper, we introduce the spectral–spatial context-boosted network (SSCBNet), an innovative network designed to enhance the accuracy semantic segmentation in RSIs. SSCBNet integrates synergetic attention (SYA) layers and cross-fusion modules (CFMs) to harness both spectral and spatial information, addressing the intrinsic complexities of urban and natural landscapes within RSIs. Extensive experiments on the ISPRS Potsdam and LoveDA datasets reveal that SSCBNet surpasses existing state-of-the-art models, achieving remarkable results in F 1 -scores, overall accuracy (OA), and mean intersection over union (mIoU). Ablation studies confirm the significant contribution of SYA layers and CFMs to the model's performance, emphasizing the effectiveness of these components in capturing detailed contextual cues. [ABSTRACT FROM AUTHOR]

Precipitation is a key driver of litter decomposition in arid/semiarid regions; where soils are poor in organic matter, and thus re-incorporation of litter is key for soil nutrient accumulation and soil structure. It remains unclear, though, whether litter decomposition responds symmetrically to precipitation variation (e.g., if precipitation surpluses produce a stimulatory effect of a similar magnitude, but opposite direction to inhibitory effects of precipitation deficits), and whether litter decomposition and litter nutrient dynamics in arid and semiarid ecosystems that differ in climate show similar responses to precipitation. We set up a 5-and-a-half-year experiment that manipulated rainfall along a gradient (7 treatments): increases by 20%, 40%, and 60%, background precipitation, and reductions by the same 3 percentages. We applied such experiment in two sites with different pattens of precipitation (Urat: arid; and Naiman: semiarid) in Inner Mongolia to elucidate our questions. Litter mass loss and all nutrients that we measured (carbon, nitrogen, phosphorous, potassium, plus lignin) decomposed faster at the highest level of surplus precipitation, and more slowly in the two largest precipitation reductions. This indicates that these levels of precipitation constitute thresholds (value of precipitation beyond which ecosystem function is critically altered). Litter decomposition in the semiarid site was faster and more complete, but decomposition in the direr Urat was more efficient per unit cumulative rainfall. Thus, site specific effects played an important role in decomposition. Reductions in precipitation decreased the loss of C, N, P, K, and lignin from litter; and clear precipitation thresholds in the dynamic of these nutrients in litter were observed. Overall, this indicated the importance of precipitation limitation at controlling nutrient release. Our study highlights the importance of long-term studies on litter decomposition in environments with slow decomposition rates, and the importance of taking into account mechanistic effects of water availability on decomposition. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "A 5-and a-half-year-experiment shows precipitation thresholds in litter decomposition and nutrient dynamics in arid and semi-arid regions." The original article was published online on November 27, 2023, with Open Access under a Creative Commons Attribution 4.0 International License. However, the authors later decided to cancel Open Access, and the copyright of the article changed on December 7, 2023, to © The Author(s), under exclusive license to Springer-Verlag GmbH Germany, part of Springer Nature 2023 with all rights reserved. The publisher, Springer Nature, remains neutral regarding jurisdictional claims and institutional affiliations. The authors of the article are Hao Qu, Eduardo Medina-Roldán, Shaokun Wang, Xujun Ma, Xinyuan Wang, Xia Tang, and Liangxu Liu. [Extracted from the article]

Single nucleotide polymorphisms (SNPs) across the genome are remarkably useful resources for investigating the genome architecture, studying the genetic basis of complex traits and implementation of genomic selection. However, information on high-density SNPs is unavailable for most aquaculture species owing to the high costs of whole genome sequencing. Genotype imputation is an attractive approach for obtaining large number of genomic variants at a low cost. In this study, the first haplotype reference panel was constructed for Chlamys farreri , an economically important mollusk species and a major contributor to aquaculture in China. A total of 174 scallops from six populations in the main scallop culture area were selected for whole-genome resequencing. More than 87.47 million SNPs were identified and 3,968,417 SNPs genome-wide were selected for constructing the haplotype reference panel for C. farreri. The number of SNPs per chromosome ranged from 125,000 to 279,981 with an average spacing of 242 bases. Several factors were evaluated based on the imputation performance of the reference panel. The imputation accuracies of 19 chromosomes ranged from 0.91 to 0.95, and there were no significant differences among them (p > 0.05). The imputation accuracies of populations could reach 0.95, 0.93, and 0.90 for ZY, PR, and CS respectively, which confirmed a positive relationship between the kinship within the population and the imputation accuracy. The imputation accuracies increased with sequencing depth and plateaued at 0.5×, reaching accuracies of 0.91–0.93 for artificially breeding populations. Taken together, we constructed a haplotype reference panel for C. farreri , which can provide a cost-effective way to extend the limited number of genotypes for boosting the power of downstream analyses such as genome-wide association studies and genomic selection. • The first haplotype reference panel of Chlamys farreri was constructed and included 3.9 M SNPs. • The imputation accuracy was not different among 19 chromosomes. • The imputation accuracy improved with increasement of kinship between target individuals and reference population. • The imputation accuracies could reach 0.93 with 0.5× sequencing depth. [ABSTRACT FROM AUTHOR]

[Display omitted] • Hydrophobic silibinin was linked to the N-acetylgalactosamine-modified hydrophilic dextran backbone via a phenylboronic acid linkage to produce an amphiphilic polymer. • ROS-responsive liver-targeting NPs for efficient encapsulation of hydrophobic cell-permeable Ca2+ chelator BAPTA-AM agents via hydrophobic/hydrophilic interactions. • The released BAPTA-AM blocked the sterile inflammatory reaction and apoptosis signaling in the upstream link of acute liver injury. • The silibinin exerted synergistic hepatoprotective effects after the ROS-responsive cleavage of phenylboronic acid. Calcium overload in hepatocytes mediates the crosstalk and amplification loop with oxidative stress and severe inflammation that initiate pro-apoptotic and necrotic signaling pathways in acute liver injury (ALI). In this study, an N-acetylgalactosamine-modified amphiphilic dextran-silibinin conjugate (GalNAc-Dex-Sil) with ROS-sensitive phenylboronic acid (PBA) linkage was synthesized. The as-prepared amphiphilic polymer was self-assembled into GalNAc-Dex-Sil nanoparticles, which efficiently encapsulated the membrane-permeable calcium chelator BAPTA-AM (BA), achieving GalNAc-mediated hepatocyte-specific targeting and ROS-responsive release in injured hepatocytes through PBA cleavage. Accordingly, a single low-dose injection of formulation (BA: 150 μg·kg−1) significantly alleviated hepatocyte oxidative stress and inflammation, rescued dying hepatocytes, prevented further hepatocyte damage, and ultimately restored liver function in the ALI mouse model by 1) rapidly and effectively eliminating the overloaded calcium and scavenging excessive ROS via released BA to block the feed-forward vicious cycles of the cell damage, 2) inhibiting the inflammatory cascade by decreasing the expression of the key factor of the NF-κB/NLPR3 axis, 3) inhibiting the key branch of the mitochondrial apoptotic pathway (Cyt C/Bcl-2 family/caspase-3 axis) and death receptor pathway (TNFα/Caspase-8 axis), and 4) stabilizing hepatocyte membranes through the synergistic hepatoprotective effect of silibinin. Taken together, this formulation exhibited great potential as a potent and effective ALI treatment strategy. [ABSTRACT FROM AUTHOR]