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Abstract Embryonic axis formation is essential for patterning and morphogenesis in vertebrates and is tightly regulated by the dorsal organizer. Previously, we demonstrated that maternally derived Huluwa (Hwa) acts as a dorsal determinant, dictating axis formation by activating β-catenin signaling in zebrafish and Xenopus. However, the mechanism of activation and fine regulation of the Hwa protein remains unclear. Through candidate screening we identified a mutation at Ser168 in the PPNSP motif of Hwa that dramatically abolishes its axis-inducing activity. Mechanistically, mutating the Ser168 residue reduced its binding affinity to Tankyrase 1/2 and the degradation of the Axin protein, weakening β-catenin signaling activation. We confirmed that Ser168 is phosphorylated and that phosphorylation increases Hwa activity in β-catenin signaling and axis induction. Several kinases including Cdk16, Cdk2, and GSK3β, were found to enhance Ser168 phosphorylation in vitro and in vivo. Both dominant-negative Cdk16 expression and pHwa (Ser168) antibody treatment reduce Hwa function. Lastly, a knock-in allele mutating Ser168 to alanine resulted in embryos lacking body axes, demonstrating that Ser168 is essential to axis formation. In summary, Ser168 acts as a phosphorylation switch in Hwa/β-catenin signaling for embryonic axis induction, regulated by multiple kinases.

High-entropy fluorite oxides (HEFOs) show significant potential for thermal protection applications due to their advantageous combination of low thermal conductivity and high Yong’s modulus. However, the factors influencing its formation have not been well studied, and a systematic method for compositional design has not yet been established. In this paper, the effects of oxygen vacancy concentration (Ovac) and mean cation radius (r¯) on formability of HEFOs were investigated to develop a compositional design approach. The results indicate that an appropriate r¯ and Ovac is crucial for promoting the formability of single-phase (CaxCey1Zry2HfzSnzTiz)O2−δ HEFOs. High mass/size disorder and an appropriate Ovac (10%) result in (Ca0.2Ce0.14Zr0.12Hf0.18Sn0.18Ti0.18)O2−δ exhibiting the lowest thermal conductivity of 1.24 W·m−1·K−1. Building upon these insights and employing a valence combination strategy, three new single-phase HEFOs with low thermal conductivity were successfully designed and synthesized, namely, (La0.28Y0.28Ce0.18Zr0.18W0.08)O2−δ, (La0.3Y0.3Ce0.2Nb0.1Ta0.1)O2−δ, and (Yb0.52Ce0.12Zr0.12Sn0.12Nb0.12)O2−δ. This design approach will provide a valuable reference for the design of other high-entropy oxides.

Abstract Acute anterior uveitis (AAU) is a common extra‐articular manifestation of ankylosing spondylitis (AS), particularly in patients positive for the human leucocyte antigen (HLA)‐B27 genetic marker. To explore the underlying mechanisms of HLA‐B27+ AS‐associated AAU, we employed single‐cell RNA sequencing to profile the transcriptomes of peripheral blood mononuclear cells in three HLA‐B27+ AS‐associated AAU patients and three healthy controls (HCs). We identified 11 distinct immune cell clusters, with a particular focus on monocytes, revealing six subsets, including three previously unidentified subsets, namely, GTPase immune‐associated proteins, Th17‐related, and lncRNA monocytes, with unique gene expression patterns. Significant differences in monocyte composition, activation states, and gene expression were observed between patients and HCs, particularly within HLA monocyte subpopulations. Notably, enhanced expression of X‐inactive specific transcript and myeloid cell nuclear differentiation antigen genes was validated across monocyte subclusters in patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis highlighted significant enrichment in antigen processing and presentation pathways, shedding light on the disease's molecular mechanisms. These findings provide novel insights into the molecular mechanisms of HLA‐B27+ AS‐associated AAU and may contribute to the development of targeted diagnostic and therapeutic strategies. Further clinical validation is essential.

BackgroundGlioma is a highly heterogeneous malignancy of the central nervous system. This heterogeneity is driven by various molecular processes, including neoplastic transformation, cell cycle dysregulation, and angiogenesis. Among these biomolecular events, inflammation and stress pathways in the development and driving factors of glioma heterogeneity have been reported. However, the mechanisms of glioma heterogeneity under stress response remain unclear, especially from a spatial aspect.MethodsThis study employed single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) to explore the impact of oxidative stress response genes in oligodendrocyte precursor cells (OPCs). Our analysis identified distinct pathways activated by oxidative stress in two different types of gliomas: high- and low- grade (HG and LG) gliomas.ResultsIn HG gliomas, oxidative stress induced a metabolic shift from oxidative phosphorylation to glycolysis, promoting cell survival by preventing apoptosis. This metabolic reprogramming was accompanied by epithelial-to-mesenchymal transition (EMT) and an upregulation of stress response genes. Furthermore, SCENIC (Single-Cell rEgulatory Network Inference and Clustering) analysis revealed that oxidative stress activated the AP1 transcription factor in HG gliomas, thereby enhancing tumor cell survival and proliferation.ConclusionOur findings provide a novel perspective on the mechanisms of oxidative stress responses across various grades of gliomas. This insight enhances our comprehension of the evolutionary processes and heterogeneity within gliomas, potentially guiding future research and therapeutic strategies.

Abstract The development of in situ techniques to quantitatively characterize the heterogeneous reactions is essential for understanding physicochemical processes in aqueous phase. In this work, a new approach coupling in situ UV–vis spectroscopy with a two‐step algorithm strategy is developed to quantitatively monitor heterogeneous reactions in a compact closed‐loop incorporation. The algorithm involves the inverse adding‐doubling method for light scattering correction and the multivariate curve resolution‐alternating least squares (MCR‐ALS) method for spectral deconvolution. Innovatively, theoretical spectral simulations are employed to connect MCR‐ALS solutions with chemical molecular structural evolution without prior information for reference spectra. As a model case study, the aqueous adsorption kinetics of bisphenol A onto polyamide microparticles are successfully quantified in a one‐step UV–vis spectroscopic measurement. The practical applicability of this approach is confirmed by rapidly screening a superior adsorbent from commercial materials for antibiotic wastewater adsorption treatment. The demonstrated capabilities are expected to extend beyond monitoring adsorption systems to other heterogeneous reactions, significantly advancing UV–vis spectroscopic techniques toward practical integration into automated experimental platforms for probing aqueous chemical processes and beyond.

Abstract This study aimed to investigate the impact of tactical formations on the physical and technical performance of professional football players in the Chinese Super League (CSL). A sample of 800 games from the 2015–2021 CSL was analyzed, and players' physical (total distance covered, distance covered while ball in play, number of sprints, sprint distance, and high/middle/low-speed running) and technical (gain/loss of possession, ball retention percentage, challenges, challenge success percentage, passes, and pass success percentage) performance was assessed across six team formations: 3-5-2 (n = 137), 4-3-3 (n = 77), 4-2-3-1 (n = 391), 4-4-2 (n = 257), 3-4-3 (n = 41), and 4-1-4-1 (n = 107). Linear mixed models were used to assess variations in performance indicators across positions and formations. The results demonstrated that central defenders traveled significantly more total and low-speed running distances in the 3-5-2 formation than in the 4-2-3-1 formation (ES range: 0.33–0.34, p

Abstract Purpose The health of rhizosphere soil microorganisms is an important indicator to evaluate soil quality. Therefore, understanding the response of rhizosphere soil microorganisms to tobacco crop succession is crucial for promoting the sustainable development of agriculture. Methods The microbial diversity and community structure of rhizosphere soil in continuous cropping and non-cropped tobacco for 7 years were analyzed by the Illumina platform. Result (1) Continuous cropping tobacco cause rhizosphere soil acidification and reduction in alkaline nitrogen (AN) and soil organic matter (SOM). (2) Continuous cropping tobacco reduces the diversity of rhizosphere soil microbial communities, increasing harmful functional microorganisms and declining beneficial ones. (3) The abundance of bacteria that perform nitrification and saprophytic fungi in the rhizosphere soil of continuous cropping areas decreases, inhibiting carbon and nitrogen cycling processes. (4) The composition and diversity of the soil rhizosphere microbial community are affected by the imbalance in the physicochemical property of the rhizosphere. Conclusion Continuous cropping tobacco cause rhizosphere soil acidification and nutrient imbalance, and the carbon and nitrogen cycles involved in microorganisms were damaged. Furthermore, the decreased diversity of rhizosphere soil microorganisms and the increased abundance of pathogenic fungi contribute to the continuous cropping obstacles of tobacco.

IntroductionGlioma, a prevalent and deadly brain tumor, is marked by significant cellular heterogeneity and metabolic alterations. However, the comprehensive cell-of-origin and metabolic landscape in high-grade (Glioblastoma Multiforme, WHO grade IV) and low-grade (Oligoastrocytoma, WHO grade II) gliomas remains elusive.MethodsIn this study, we undertook single-cell transcriptome sequencing of these glioma grades to elucidate their cellular and metabolic distinctions. Following the identification of cell types, we compared metabolic pathway activities and gene expressions between high-grade and low-grade gliomas.ResultsNotably, astrocytes and oligodendrocyte progenitor cells (OPCs) exhibited the most substantial differences in both metabolic pathways and gene expression, indicative of their distinct origins. The comprehensive analysis identified the most altered metabolic pathways (MCPs) and genes across all cell types, which were further validated against TCGA and CGGA datasets for clinical relevance.DiscussionCrucially, the metabolic enzyme phosphodiesterase 8B (PDE8B) was found to be exclusively expressed and progressively downregulated in astrocytes and OPCs in higher-grade gliomas. This decreased expression identifies PDE8B as a metabolism-related oncogene in IDH-mutant glioma, marking its dual role as both a protective marker for glioma grading and prognosis and as a facilitator in glioma progression.

Abstract Proper subcellular localization is crucial for the functioning of biomacromolecules, including proteins and RNAs. Nuclear transport is a fundamental cellular process that regulates the localization of many macromolecules within the nuclear or cytoplasmic compartments. In humans, approximately 60 proteins are involved in nuclear transport, including nucleoporins that form membrane-embedded nuclear pore complexes, karyopherins that transport cargoes through these complexes, and Ran system proteins that ensure directed and rapid transport. Many of these nuclear transport proteins play additional and essential roles in mitosis, biomolecular condensation, and gene transcription. Dysregulation of nuclear transport is linked to major human diseases such as cancer, neurodegenerative diseases, and viral infections. Selinexor (KPT-330), an inhibitor targeting the nuclear export factor XPO1 (also known as CRM1), was approved in 2019 to treat two types of blood cancers, and dozens of clinical trials of are ongoing. This review summarizes approximately three decades of research data in this field but focuses on the structure and function of individual nuclear transport proteins from recent studies, providing a cutting-edge and holistic view on the role of nuclear transport proteins in health and disease. In-depth knowledge of this rapidly evolving field has the potential to bring new insights into fundamental biology, pathogenic mechanisms, and therapeutic approaches.

The retinal pigment epithelium (RPE) and choroid are located behind the human retina and have multiple functions in the human visual system. Knowledge of the RPE and choroid cells and their gene expression profiles are fundamental for understanding retinal disease mechanisms and therapeutic strategies. Here, we sequenced the RNA of about 0.3 million single cells from human RPE and choroids across two regions and seven ages, revealing regional and age differences within the human RPE and choroid. Cell–cell interactions highlight the broad connectivity networks between the RPE and different choroid cell types. Moreover, the transcription factors and their target genes change during aging. The coding of somatic variations increases during aging in the human RPE and choroid at the single-cell level. Moreover, we identified ELN as a candidate for improving RPE degeneration and choroidal structure during aging. The mapping of the molecular architecture of the human RPE and choroid improves our understanding of the human vision support system and offers potential insights into the intervention targets for retinal diseases.

This study aimed to investigate the non-linear evolution of position-specific physical and technical performance indicators across different tactical formations in the Chinese Super League (CSL) from the 2015 to the 2021 seasons. Match data were collected from 800 games played in six common formations (3-5-2, 4-3-3, 4-2-3-1, 4-4-2, 3-4-3, and 4-1-4-1). Players were classified into five positions: central defenders (CD; match observations = 2,219), fullbacks (FB; match observations = 2,060), central midfielders (CM; match observations = 2,786), wide midfielders (WM; match observations = 1,587), and forwards (FW; match observations = 1,680). Generalized additive models (GAMs) were constructed to analyze the nonlinear evolution trends in position-specific physical and technical performance across seasons and formations. The results showed that the total distance covered by CDs in the 3-5-2 formation showed a non-linear upward trend from the 2015 to 2021 seasons (R2 = 0.3, p = 0.006); FBs in the 3-4-3, 4-1-4-1, and 3-5-2 formations exhibited non-linear upward trends in number of sprints and sprint distance from the 2015 to 2021 seasons (R2 = 0.189-0.448; P < 0.03, respectively); the high-speed running of FWs in the 4-2-3-1 formation displayed a non-linear decline trend from the 2015 to 2021 seasons (R2 = 0.477; P < 0.001); CMs in the 4-2-3-1 formation demonstrated a non-linear increasing trend in the ball retention percentage (R2 = 0.369; p = 0.001); WMs in the 4-4-2 formation showed a non-linear decreasing trend in ball retention percentage and passes from the 2015 to 2021 seasons (R2 = 0.259-0.29; P = 0.006, respectively). These findings revealed non-linear evolutionary trends in physical and technical performances across positions and formations, providing an in-depth understanding of the changing match demands placed on players during matches. This enables the optimization of training and tactics by developing targeted strategies tailored to meet the specific requirements of different formations and playing positions.

Human papillomavirus (HPV) is a prevalent cause of mucosal and cutaneous infections and underlying conditions ranging from benign warts to anogenital and oropharyngeal cancers affecting both males and females, notably cervical cancer. Cervical cancer is the fourth leading cause of cancer deaths among women globally and is the most impactful in low- and middle-income countries (LMICs), where the costs of screening and licensed L1-based HPV vaccines pose significant barriers to comprehensive administration. Additionally, the licensed L1-based HPV vaccines fail to protect against all oncogenic HPV types. This study generated three independent lots of an L2-based target antigen (LBTA), which was engineered from conserved linear L2-protective epitopes (aa11–88) from five human alphapapillomavirus genotypes in E. coli under cGMP conditions and adjuvanted with aluminum phosphate. Vaccination of rabbits with LBTA generated high neutralizing antibody titers against all 17 HPV types tested, surpassing the nine types covered by Gardasil®9. Passive transfer of naïve mice with LBTA antiserum revealed its capacity to confer protection against vaginal challenge with all 17 αHPV types tested. LBTA shows stability at room temperature over >1 month. Standard in vitro and in vivo toxicology studies suggest a promising safety profile. These findings suggest LBTA’s promise as a next-generation vaccine with comprehensive coverage aimed at reducing the economic and healthcare burden of cervical and other HPV+ cancers in LMICs, and it has received regulatory approval for a first-in-human clinical study (NCT05672966).

The global football market has grown in the past three decades, and football clubs' sustainable financial operations have gradually gained attention. This study aims to construct a financial risk assessment model applicable to the football industry, explore globally listed football clubs' overall financial operating characteristics, and analyse the leading causes of the club's financial crisis. We selected a sample of 24 currently listed football clubs worldwide and an exploratory factor analysis (EFA) model to construct the model of financial risk assessment for football clubs. The model identified and classified the financial risk components for listed football clubs, thus facilitating risk warning and prevention for modern professional clubs. This study found that football clubs are at higher financial risk overall, with the following general characteristics: (1) small amount of listed capital; (2) high asset-liability ratio; (3) low net profits and a large proportion of clubs make losses; and (4) weak asset liquidity. Finally, the study discussed the leading causes of the financial crises of football clubs in both external and internal dimensions, providing a reference for the self-sustainability of clubs and football authorities.

In recent years, there has been an increase in the scientific production of youth soccer. However, a panoramic map of research on this subject does not exist. The aim of this study was to identify global research trends in youth soccer over time, among the main levels of analysis: sources, authors, documents, and keywords. The bibliometric software Biblioshiny was used to analyze 2606 articles in Web of Science (WoS) published between 2012 and 2021. The main conclusion is that US and UK scholars dominate the research; the topics of research are changing with the real needs, and research on the topic of performance has been of interest to scholars; talent identification and development, performance, injury prevention, and concussion are the studies of interest to scholars in this area. This finding, which offers a global picture of youth soccer research over time, can help future research in this or similar domains.

The classification of fish species has important practical significance for both the aquaculture industry and ordinary people. However, existing methods for classifying marine and freshwater fishes have poor feature extraction ability and do not meet actual needs. To address this issue, we propose a novel method for multi-water fish classification (Fish-TViT) based on transfer learning and visual transformers. Fish-TViT uses a label smoothing loss function to solve the problem of overfitting and overconfidence of the classifier. We also employ Gradient-weighted Category Activation Mapping (Grad-CAM) technology to visualize and understand the features of the model and the areas on which the decision depends, which guides the optimization of the model architecture. We first crop and clean fish images, and then use data augmentation to expand the number of training datasets. A pre-trained visual transformer model is used to extract enhanced features of fish images, which are subsequently cropped into a series of flat patches. Finally, a multi-layer perceptron is used to predict fish species. Experimental results show that Fish-TViT achieves high classification accuracy on both low-resolution marine fish data (94.33%) and high-resolution freshwater fish data (98.34%). Compared with traditional convolutional neural networks, Fish-TViT has better performance.

This work studied the wind load acting on a point focus solar furnace composed of a 110 m2 heliostat and a 77 m2 concentrator through wind tunnel testing. Based on wind tunnel test data under 305 different working conditions, the variation laws of the wind pressure coefficient, power spectral density, and wind load coefficient of the heliostat and concentrator were analyzed. The results showed that due to the interaction between the concentrator and heliostat, the wind speed near the heliostat and concentrator decreased but the turbulence intensity increased, which caused the peak wind load coefficient to rise slightly. The results suggested that a safety factor of 1.1–1.2 should be considered for structural design and optimization of solar furnaces.

Capacitive deionization (CDI) is a promising technique for brackish water desalination. However, its salt electrosorption capacity is insufficient for practical application yet, and little information is available on hardness ion (Mg2+, Ca2+) removal in CDI. Herein, hierarchical porous carbon (HPC) was prepared from low-cost and renewable microalgae via a simple one-pot approach, and both MnO2/HPC and polyaniline/HPC (PANI/HPC) composites were then synthesized using a facile, one-step hydrothermal method. Compared with the MnO2 electrode, the MnO2/HPC electrode presented an improved hydrophilicity, higher specific capacitance, and lower electrode resistance. The electrodes exhibited pseudocapacitive behaviors, and the maximum salt electrosorption capacities of MnO2/HPC-PANI/HPC CDI cell was up to 0.65 mmol g−1 NaCl, 0.71 mmol g−1 MgCl2, and 0.76 mmol g−1 CaCl2, respectively, which were comparable and even higher than those of the previously reported CDI cells. Additionally, the MnO2/HPC electrode presented a selectivity order of Ca2+ ≥ Mg2+ > Na+, and the divalent cation selectivity was found to be attributed to their stronger binding strength in the cavity of MnO2. Multiscale simulations further reveal that the MnO2/HPC electrodes with the unique luminal configuration of MnO2 and HPC as supportive framework could offer a great intercalation selectivity of the divalent cations and exhibit a great promise in hardness ion removal.

Abstract Critical coronavirus disease 2019 (COVID-19) is associated with high mortality and potential genetic factors have been reported to be involved in the development of critical COVID-19. We performed a genome-wide association study to identify the genetic factors responsible for developing critical COVID-19. 632 critical patients with COVID-19 and 3021 healthy controls from the Chinese population were recruited. First, we identified a genome-wide significant difference of IL-6 rs2069837 (p = 9.73 × 10−15, OR = 0.41) between 437 critical patients with COVID-19 and 2551 normal controls in the discovery cohort. When replicated these findings in a set of 195 patients with critical COVID-19 and 470 healthy controls, we detected significant association of rs2069837 with COVID-19 (p = 8.89 × 10−3, OR = 0.67). This variant surpassed the formal threshold for genome-wide significance (combined p = 4.64 × 10−16, OR = 0.49). Further analysis revealed that there was a significantly stronger expression of IL-6 in the serum from patients with critical COVID-19 than in that from patients with asymptomatic COVID-19. An in vitro assay showed that the A to G allele changes in rs2069837 within IL-6 obviously decreased the luciferase expression activity. When analyzing the effect of this variant on the IL-6 in the serum based on the rs2069837 genotype, we found that the A to G variation in rs2069837 decreased the expression of IL-6, especially in the male. Overall, we identified a genetic variant in IL-6 that protects against critical conditions with COVID-19 though decreasing IL-6 expression in the serum.

Müller cell is the most abundant glial cell in mammalian retina, supporting the functions of photoreceptors and other retinal neurons via maintaining environmental homeostasis. In response to injury and/or neuronal degeneration, Müller cells undergo morphological and functional alternations, known as reactive gliosis documented in multiple retinal diseases, including age-related macular degeneration (AMD), retinitis pigmentosa, diabetic retinopathy, and traumatic retinal detachment. But the functional consequences of Müller glia cell reactivation or even the regulatory networks of the retinal gliosis are still controversial. In this study, we reveal different subpopulations of Müller cells with distinct metabolic-mitochondrial signatures by integrating single cell transcriptomic data from Early AMD patients and healthy donors. Our results show that a portion of Müller cells exhibits low mitochondrial DNA (mtDNA) expressions, reduced protein synthesis, impaired homeostatic regulation, decreased proliferative ability but enhanced proangiogenic function. Interestingly, the major alternation of Müller cells in Early AMD retina is the change of subpopulation abundance, rather than generation of new subcluster. Transcription factor enrichment analysis further highlights the key regulators of metabolic-mitochondrial states of Müller glias in Early AMD patients especially. Our study demonstrates new characteristics of retinal gliosis associated with Early AMD and suggests the possibility to prevent degeneration by intervening mitochondrial functions of Müller cells.

We evaluated the immunogenicity and protective ability of a chimpanzee replication-deficient adenovirus vectored COVID-19 vaccine (BV-AdCoV-1) expressing a stabilized pre-fusion SARS-CoV-2 spike glycoprotein in golden Syrian hamsters. Intranasal administration of BV-AdCoV-1 elicited strong humoral and cellular immunity in the animals. Furthermore, vaccination prevented weight loss, reduced SARS-CoV-2 infectious virus titers in the lungs as well as lung pathology and provided protection against SARS-CoV-2 live challenge. In addition, there was no vaccine-induced enhanced disease nor immunopathological exacerbation in BV-AdCoV-1-vaccinated animals. Furthermore, the vaccine induced cross-neutralizing antibody responses against the ancestral strain and the B.1.617.2, Omicron(BA.1), Omicron(BA.2.75) and Omicron(BA.4/5) variants of concern. These results demonstrate that BV-AdCoV-1 is potentially a promising candidate vaccine to prevent SARS-CoV-2 infection, and to curtail pandemic spread in humans.

Multiple myeloma (MM) accounts for ~10% of all haematologic malignancies. Little is known about high intratumour heterogeneities in patients stratified by the Revised International Staging System (R-ISS). Herein, we constructed a single-cell transcriptome atlas to compare differential expression patterns among stages. We found that a novel cytotoxic plasma cell (PC) population exhibited with NKG7 positive was obviously enriched in stage II patients. Additionally, a malignant PC population with significantly elevated expression of MKI67 and PCNA was associated with unfavourable prognosis and Epstein-Barr virus (EBV) infection in our collected samples. Moreover, ribonucleotide reductase regulatory subunit M2 (RRM2) was found and verified to promote proliferation of MM cell lines, suggesting RRM2 may serve as a detrimental marker in MM. The percentages of CD8+ T cells and NKT cells decreased along with R-ISS stages, reflecting the plasticity of the tumour immune microenvironment. Importantly, their crosstalks with myeloid cells and PC identified several potential immunotargets such as SIRPA-CD47 and CD74-MIF, respectively. Collectively, this study provided an R-ISS-related single-cell MM atlas and revealed the clinical significance of novel PC clusters, as well as potential immunotargets in MM progression.

Activation of nodal genes is critical for mesoderm and endoderm induction. Our previous study reported that zebrafish nodal genes ndr1/squint and ndr2/cyclops are coordinately regulated by maternal Eomesa, Hwa-activated β-catenin (Hwa/β-catenin) signaling, and Nodal autoregulation (Nodal/Smad2) signaling. However, the exact contribution and underlying mechanisms are still elusive. Here, we applied “causal inference” to evaluate the causal between the independent and dependent variables, and we found that Hwa/β-catenin and Smad2 are the cause of ndr1 activation, while Eomesa is the cause of ndr2 activation. Mechanistically, the different cis-regulatory regions of ndr1 and ndr2 bound by Eomesa, β-catenin, and Smad2 were screened out via ChIP-qPCR and verified by the transgene constructs. The marginal GFP expression driven by ndr1 transgenesis could be diminished without both maternal Eomesa and Hwa/β-catenin, while Eomesa, not β-catenin, could bind and activate ndr2 demonstrated by ndr2 transgenesis. Thus, the distinct regulation of ndr1/ndr2 relies on different cis-regulatory regions.

Purpose: Age-related macular degeneration (AMD) is a leading cause of vision loss. A Previous study based on the co-localization analysis of the genome-wide association study (GWAS) and eQTL genetic signals have reported that single nucleotide polymorphisms (SNPs), including rs760975, rs11528744, rs3761159, rs7212510, rs6965458, rs7559693, rs56108400, rs28495773, rs9928736, rs11777697, rs4381465 are associated with AMD in Americans. The aim of this study was to investigate the association of these SNPs in a Han Chinese population.Methods: There were 576 patients with wet AMD and 572 healthy controls collected in this study. All SNPs were genotyped by flight mass spectrum. Hardy–Weinberg equilibrium was applied to evaluate allele distributions for both AMD and control groups. The genotype and allele frequencies were evaluated using the χ2 tests. Odds ratio (OR) and 95% confidence intervals (95% CI) were calculated for the risk of genotype and allele.Results: Three of the 11 SNPs (rs11528744 in HTRA1, rs9928736 in BCRA1 and rs4381465 in B3GLCT) were found to be significantly associated with AMD in the allelic model (corrected p = 0.001, OR = 1.391, 95%CI = 1.179–1.640 for rs11528744; corrected p = 0.004, OR = 0.695, 95%CI = 0.544–0.888 for rs9928736; corrected p = 0.002, OR = 0.614, 95%CI = 0.448–0.841 for rs4381465). There were no differences for the remaining eight SNPs between AMD cases and healthy controls.Conclusion: Our results showed that HTRA1 rs11528744, BCRA1 rs9928736, and B3GLCT rs4381465 were associated with wet AMD, suggesting that HTRA1, BCRA1, and B3GLCT genes may be involved in the development of AMD.

Contact guidance for cell outgrowth refers to the phenomenon of the topography of the extracellular matrix regulating cell behaviors and functions. In tissue engineering, scaffolds with appropriate topographic cues for cell contact guidance show great potential in facilitating tissue repair and regeneration. Advanced 3D printing technology enables the fabrication of intricate and accurate structures for the study of the cellular responses and underlying mechanisms of contact guidance. This review focuses on 3D printing topographic cues for cell contact guidance. First, typical 3D printing technologies for manufacturing topographic cues are covered. Subsequently, cellular responses on 3D printing topographic cues in cell culture experiments are summarized. Then, the mechanisms of contact guidance on cell outgrowth are recapitulated. Finally, the major challenges and future perspectives for this field are discussed.

Nodal proteins provide crucial signals for mesoderm and endoderm induction. In zebrafish embryos, the nodal genes ndr1/squint and ndr2/cyclops are implicated in mesendoderm induction. It remains elusive how ndr1 and ndr2 expression is regulated spatiotemporally. Here we investigated regulation of ndr1 and ndr2 expression using Mhwa mutants that lack the maternal dorsal determinant Hwa with deficiency in β-catenin signaling, Meomesa mutants that lack maternal Eomesodermin A (Eomesa), Meomesa;Mhwa double mutants, and the Nodal signaling inhibitor SB431542. We show that ndr1 and ndr2 expression is completely abolished in Meomesa;Mhwa mutant embryos, indicating an essential role of maternal eomesa and hwa. Hwa-activated β-catenin signaling plays a major role in activation of ndr1 expression in the dorsal blastodermal margin, while eomesa is mostly responsible for ndr1 expression in the lateroventral margin and Nodal signaling contributes to ventral expansion of the ndr1 expression domain. However, ndr2 expression mainly depends on maternal eomesa with minor or negligible contribution of maternal hwa and Nodal autoregulation. These mechanisms may help understand regulation of Nodal expression in other species.

Immune checkpoint therapy targeting the PD-1/PD-L1 axis is a potentially novel development in anticancer therapy and has been applied to clinical medicine. However, there are still some problems, including a relatively low response rate, innate mechanisms of resistance against immune checkpoint blockades, and the absence of reliable biomarkers to predict responsiveness. In this study of in vitro and in vivo models, we demonstrate that PD-L1–vInt4, a splicing variant of PD-L1, plays a role as a decoy in anti–PD-L1 antibody treatment. First, we showed that PD-L1–vInt4 was detectable in clinical samples and that it was possible to visualize the secreting variants with IHC. By overexpressing the PD-L1–secreted splicing variant on MC38 cells, we observed that an immune-suppressing effect was not induced by their secretion alone. We then demonstrated that PD-L1–vInt4 secretion resisted anti–PD-L1 antibody treatment, compared with WT PD-L1, which was explicable by the PD-L1–vInt4’s decoying of the anti–PD-L1 antibody. The decoying function of PD-L1 splicing variants may be one of the reasons for cancers being resistant to anti–PD-L1 therapy. Measuring serum PD-L1 levels might be helpful in deciding the therapeutic strategy.

ObjectivesCOVID-19 and Non-Covid-19 (NC) Pneumonia encountered high CT imaging overlaps during pandemic. The study aims to evaluate the effectiveness of image-based quantitative CT features in discriminating COVID-19 from NC Pneumonia.Materials and methods145 patients with highly suspected COVID-19 were retrospectively enrolled from four centers in Sichuan Province during January 23 to March 23, 2020. 88 cases were confirmed as COVID-19, and 57 patients were NC. The dataset was randomly divided by 3:2 into training and testing sets. The quantitative CT radiomics features were extracted and screened sequentially by correlation analysis, Mann-Whitney U test, the least absolute shrinkage and selection operator (LASSO) logistic regression (LR) and backward stepwise LR with minimum AIC methods. The selected features were used to construct the LR model for differentiating COVID-19 from NC. Meanwhile, the differentiation performance of traditional quantitative CT features such as lesion volume ratio, ground glass opacity (GGO) or consolidation volume ratio were also considered and compared with Radiomics-based method. The receiver operating characteristic curve (ROC) analysis were conducted to evaluate the predicting performance.ResultsCompared with traditional CT quantitative features, radiomics features performed best with the highest Area Under Curve (AUC), sensitivity, specificity and accuracy in the training (0.994, 0.942, 1.0 and 0.965) and testing sets (0.977, 0.944, 0.870, 0.915) (Delong test, P < 0.001). Among CT volume-ratio based models using lesion or GGO component ratio, the model combining CT lesion score and component ratio performed better than others, with the AUC, sensitivity, specificity and accuracy of 0.84, 0.692, 0.853, 0.756 in the training set and 0.779, 0.667, 0.826, 0.729 in the testing set. The significant difference of the most selected wavelet transformed radiomics features between COVID-19 and NC might well reflect the CT signs.ConclusionsThe differentiation between COVID-19 and NC could be well improved by using radiomics features, compared with traditional CT quantitative values.

To study the sandstorm resistance design of civil structures and transportation infrastructures, the sandstorm flow fields with various grain concentrations were simulated by the windblown sand tunnel. The results show that the grain concentration profile presents an exponential decay form before the critical wind speed; as the test speed increases, the grain concentration decreases initially and increases afterwards with height, and the characteristic height of moving grain increases while the creep percentage decreases. Moving sand grains reduce wind speed and increase turbulence intensity, and the whole process is affected by grain concentration. The moving grain and the turbulence of the sandstorm flow field form a mutual feedback mechanism, which affects the wind-induced response and impact response to structures. The variation of kinetic energy with height is similar to that of total energy with height in the sandstorm flow fields. Specifically, the grain energy increases with increasing concentration and wind speed, but decreases initially and increases afterwards with height. Furthermore, the critical heights of the grain energy and concentration profile are both about 0.2 m, which has little impact on structures.

Tetracycline (TC) and Cu(II) coexist commonly in various waters, which may infiltrate into the subterranean environment through runoff and leaching, resulting in substantial ecological risks. However, the underlying mechanisms why Cu(II) affects the transport of TC in porous media remain to be further explored and supported by more evidence, especially the role of complexation. In this study, the transport of TC with coexisting Cu(II) was comprehensively explored with column experiments and density functional theory (DFT) calculation. At natural environmental concentrations, Cu(II) significantly inhibited the transport of TC in the quartz sand column. Cu(II) augmented the retention of TC in the column mainly via electrostatic force and complexation. The interaction between TC and TC-Cu complexes on the surface of SiO2 was investigated with first-principles calculations for the first time. There were strong van der Waals forces and coordination bonds on the surface of complexes and SiO2, leading to higher adsorption energy than that of TC and inhibiting its penetration. This study offers novel insights and theoretical framework for the transport of antibiotics in the presence of metal ions to better understand the fate of antibiotics in nature. [ABSTRACT FROM AUTHOR]

The electrochemical selective oxidative transformation of lignin feedstocks into valuable oxygenated aromatics is essential to establish a sustainable biorefinery. In this study, we used a rhombohedral ZnIn2S4 (R-ZIS) electrocatalyst to realise the efficient anodic cleavage of C-O bonds in benzyl phenyl ether (BPE), an a-O-4 lignin model compound, to a series of industrially relevant oxygenated mono-aromatics. The reaction occurred at +2 VAg/AgCl, 65 °C, and atmospheric pressure. In optimised conditions, the reaction achieved over 99% conversion rate with a Faraday efficiency of 51.6% at 91.3% conversion of BPE, that is greater than most known electrocatalytic oxidative cleavage examples. The ZnIn2S4 electrocatalyst was deposited on a carbon cloth support, and its structural properties and surface morphology were extensively investigated. Systematic potential controlled electrolysis coupled with 18O isotopic labelling confirmed that C-O scission occurred exclusively between the benzylic carbon and phenolic oxygen. Furthermore, substrate competition studies were conducted to compare the electrocatalytic performance of the R-ZIS catalyst with that of its structural analogue, hexagonal ZnIn2S4, in terms of BPE and monoaromatics conversion. The experimental results were supported by density functional theory calculations. The substrate scoping study revealed the suitability of the R-ZIS induced electrocatalytic system for a variety of substituted a-O-4/ß-O-4 model dimers. Overall, this work demonstrates an efficient anodic process that can enable the atom-efficient valorisation of lignin to produce oxygenated aromatics. The proposed approach can complement the numerous existing reductive lignin cleavage methods. [ABSTRACT FROM AUTHOR]