RGD Density on Tadpole Nanostructures Regulates Cancer Stem Cell Proliferation and Stemness.

Cancer stem cells (CSCs) make up a small population of cancer cells, primarily responsible for tumor initiation, metastasis, and drug resistance. They overexpress Arg-Gly-Asp (RGD) binding integrin receptors that play crucial roles in cell proliferation and stemness through interaction with the extracellular matrix. Here, we showed that monodisperse polymeric tadpole nanoparticles covalently coupled with different RGD densities regulated colon CSC proliferation and stemness in a RGD density-dependent manner. These tadpoles penetrated deeply and evenly into tumor spheroids and specifically entered cells with cancer stem markers CD24 and CD133. Low RGD density tadpoles triggered integrin α5 expression that further activated TGF-ß3 and TGF-ß2 signaling pathways, confirmed by the increase of pERK and Bcl-2 protein levels. This process is associated with the RGD cluster presentation controlled by the RGD density on the tadpole surface.

Corrigendum: Disease spectrum, prevalence, genetic characteristics of inborn errors of metabolism in 21,840 hospitalized infants in Chongqing, China, 2017-2022.

[This corrects the article DOI: 10.3389/fgene.2024.1395988.].

[Corrigendum] Enhanced antitumor activity by the combination of dasatinib and combretastatin A­4 in vitro and in vivo.

Following the publication of this article, an interested reader drew to the authors' attention that the flow cytometric (FCM) plots in Fig. 2A on p. 2278 showing the 'Dasatinib' and 'CA­4' experiments were duplicates of each other. After having re­examined their original data, and due to the overall similarity of the data, the authors have realized that these data were inadvertently assembled incorrectly in the figure. They realize that they also made a further mistake regarding the writing of the ratios of mitochondrial membrane­depolarized HO­8910 cells for these FCM plots (essentially, these were written the wrong way around): The percentage of mitochondrial membrane­depolarized HO­8910 cells should have been written as 22.50% for the dasatinib­treated cells (the centre­left FCM plot) and 15.71% for the CA­4­treated cells (centre­right plot). A revised version of Fig. 2 now showing alternative data for the FCM experiments shown in Fig. 2A, is shown on the next page. Note that the errors made in terms of assembling the data in Fig. 2A did not greatly affect either the results or the conclusions reported in this paper, and all the authors agree with the publication of this corrigendum. The authors regret that these errors went unnoticed prior to the publication of their article, and are grateful to the Editor of Oncology Reports for granting them this opportunity to publish a corrigendum. Furthermore, they apologize to the readership for any inconvenience caused. [Oncology Reports 29: 2275­2282, 2013; DOI: 10.3892/or.2013.2405].

Vertical directional coupling based grating emission engineering for optical phased arrays.

In this Letter, a novel, to the best of our knowledge, vertical directional coupling waveguide grating (VDCWG) architecture is proposed to increase the length of waveguide grating antennas for large aperture on-chip optical phased arrays (OPAs). In this new architecture, the grating emission strength is engineered by the vertical directional coupler, which provides additional degrees of design freedom. Theoretical analysis and numerical simulation show that the VDCWG can adjust the grating strength in the range of more than two orders of magnitude, corresponding to an effective grating length more than a centimeter. For proof-of-concept, a VDCWG antenna with a length of 1.5 mm is experimentally demonstrated. The grating strength is measured to be 0.17 mm-1, and the far-field divergence angle is 0.061°. A 16-channel OPA is also developed based on the proposed VDCWG, which proves the potential of the new architecture for large aperture OPAs.

The possible association of mitochondrial fusion and fission in copper deficiency-induced oxidative damage and mitochondrial dysfunction of the heart.

INTRODUCTION: As an essential trace element, Copper (Cu) participates in numerous physiological and biological reactions in the body. Cu is closely related to heart health, and an imbalance of Cu will cause cardiac dysfunction. The research aims to examine how Cu deficiency affects the heart, assess mitochondrial function in the hearts, and disclose possible mechanisms of its influence. METHODS: Weaned mice were fed Cu-deficient diets and intraperitoneally given copper sulfate (CuSO4) to correct the Cu deficiency. The pathological change of the heart was assessed using histological inspection. Cardiac function and oxidative stress levels were evaluated by biochemical assay kits. ELISA and ATP detection kits were used to detect the levels of complexes I-IV in the mitochondrial respiratory chain (MRC) and ATP, respectively. Real time PCR was utilized to determine mRNA expressions, and Western blotting was adopted to determine protein expressions, of molecules related to mitochondrial fission and fusion. RESULTS: Cu deficiency gave rise to elevated heart index, cardiac histological alterations and oxidation injury, increased serum levels of creatine kinase (CK), lactic dehydrogenase (LDH), and creatine kinase isoenzyme MB (CK-MB) together with increased malondialdehyde (MDA) production, decreased the glutathione (GSH), Superoxide Dismutase (SOD), and Catalase (CAT) activities or contents. Besides, Cu deficiency caused mitochondrial damage characterized by decreased contents of complexes I-IV in the MRC and ATP in the heart. In the meantime, Cu deficiency also reduced protein and mRNA expressions of factors associated with mitochondrial fusion, including Mfn1 and Mfn2, while significantly increased factors Drip1 and Fis1 related to mitochondrial fission. However, adding CuSO4 improved the above changes significantly. CONCLUSION: According to research results, Cu deficiency can cause heart damage in mice, along with oxidative damage and mitochondrial dysfunction, which are closely related to mitochondrial fusion and fission disorders.

Discovery of Novel 2-Oxoacetamide Derivatives as B3GAT3 Inhibitors for the Treatment of Hepatocellular Carcinoma.

Beta-1,3-glucuronosyltransferase (B3GAT3), overexpressed in hepatocellular carcinoma (HCC) and negatively correlated to prognosis, is a promising target for cancer therapy. Currently, no studies have reported small molecule inhibitors of B3GAT3. In this study, we designed and synthesized a series of small-molecule inhibitors of B3GAT3 through virtual screening and structure optimization. The lead compound TMLB-C16 exhibited potent B3GAT3 inhibitory activity (KD = 3.962 µM) by effectively suppressing proliferation and migration, and inducing cell cycle arrest and apoptosis in MHCC-97H (IC50= 6.53 ± 0.18 µM) and HCCLM3 (IC50= 6.22 ± 0.23 µM) cells. Furthermore, compound TMLB-C16 demonstrated favorable pharmacokinetic properties with a relatively high bioavailability of 68.37%. It significantly inhibited tumor growth in both MHCC-97H and HCCLM3 xenograft tumor models without causing obvious toxicity. These results indicate that compound TMLB-C16 is an effective small molecule inhibitor of B3GAT3, providing a basis for the future development of B3GAT3-targeted drugs.

Disease spectrum, prevalence, genetic characteristics of inborn errors of metabolism in 21,840 hospitalized infants in Chongqing, China, 2017-2022.

Inborn errors of metabolism (IEMs) are uncommon. Although some studies have explored the distribution and characteristics of IEMs in newborns, the impact of these disorders on hospitalized newborns remains unclear. In this study, we gathered data from 21,840 newborn patients admitted for various medical conditions at the Children's Hospital of Chongqing Medical University from January 2017 and December 2022. Liquid chromatography-tandem mass spectrometry (LC-MS/MS), gas chromatography-mass spectrometry (GC-MS/MS), and genetic analysis were used to elucidate the disease spectrum, incidence rate, and genetic characteristics of IEMs in hospitalized newborns. The results revealed that the incidence of IEMs in hospitalized newborns was 1/377 (58/21,840), with a higher incidence in full-term infants (1/428) than in premature infants (1/3,120). Among the diagnosed genetic metabolic diseases, organic acid metabolism disorders (1/662), amino acid metabolism disorders (1/950), and fatty acid oxidation disorders (1/10,920) were the most prevalent. Methylmalonic acidemia (MMA), especially the isolated form, emerged as the most common IEM, while neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and ornithine transcarbamylase deficiency (OTCD) were prevalent in premature infants. Of the 58 confirmed cases of IEMs, 72 variants were identified, of which 31.94% (23/72) had not been reported previously. This study contributes to understanding the incidence and clinical features of IEMs in hospitalized newborns, offering more efficient strategies for screening and diagnosing these disorders.

Uncovering ghost introgression through genomic analysis of a distinct eastern Asian hickory species.

Ghost introgression, or the transfer of genetic material from extinct or unsampled lineages to sampled species, has attracted much attention. However, conclusive evidence for ghost introgression, especially in plant species, remains scarce. Here, we newly assembled chromosome-level genomes for both Carya sinensis and Carya cathayensis, and additionally re-sequenced the whole genomes of 43 C. sinensis individuals as well as 11 individuals representing 11 diploid hickory species. These genomic datasets were used to investigate the reticulation and bifurcation patterns within the genus Carya (Juglandaceae), with a particular focus on the beaked hickory C. sinensis. By combining the D-statistic and BPP methods, we obtained compelling evidence that supports the occurrence of ghost introgression in C. sinensis from an extinct ancestral hickory lineage. This conclusion was reinforced through the phylogenetic network analysis and a genome scan method VolcanoFinder, the latter of which can detect signatures of adaptive introgression from unknown donors. Our results not only dispel certain misconceptions about the phylogenetic history of C. sinensis but also further refine our understanding of Carya's biogeography via divergence estimates. Moreover, the successful integration of the D-statistic and BPP methods demonstrates their efficacy in facilitating a more precise identification of introgression types.

GhMPK9-GhRAF39_1-GhWRKY40a Regulates the GhERF1b- and GhABF2-Mediated Pathways to Increase Cotton Disease Resistance.

Mitogen-activated protein kinase (MAPK) cascade is the center of plant signal transduction system that amplify immune signals into cellular responses by phosphorylating diverse substrates. The MAPK cascade consisting of MAPK kinase kinases (MAPKKKs), MAPK kinases (MAPKKs), and MAPKs is well characterized in plants, in which Raf-like kinases are generally regarded as MAPKKKs. However, it is rarely reported that Raf-like MAPKKKs function as middle regulators to link MAPK and its downstream transcription factors in plant immunity. Verticillium wilt, caused by the soil-borne vascular fungus Verticillium dahliae, is a serious disease in many plants, including cotton. The previous studies showed that GhMPK9 (a MAPK) is involved in the response to Verticillium wilt. Here, the Raf-like kinase GhRAF39_1 is reported as helper regulates the phosphorylation of WRKY transcription factor GhWRKY40a by GhMPK9. The phosphorylated GhWRKY40a can further activate the transcription of GhERF1b to up-regulate defense-related genes while inhibit the transcription of GhABF2 to regulate the stomatal opening, thus improving the resistance to Verticillium wilt in cotton. This study reveals a new signaling module of GhMPK9-GhRAF39_1-GhWRKY40a to regulate GhERF1b- and GhABF2-mediated defense responses, which triggers plant defense against Verticillium wilt.

Prognostic Value and Clinical Significance of Vesicular Transport-Related Genes in Clear Cell Renal Cell Carcinoma.

INTRODUCTION: Vesicular transport (VT) has a complex relationship with tumor progression and immunity. But prognostic significance of VT in clear cell renal cell carcinoma (ccRCC) is unclear. Thus, we aimed to establish a prognostic model according to VT to predict overall survival of ccRCC patients. METHODS: We used patient data from TCGA database and built a prognostic model with 13 VT-related genes (VTRGs) by differential expression analysis, LASSO regression, and univariate/multivariate Cox analysis. The model was validated internally and externally, and survival analysis and ROC curves depicted excellent predictive ability. Furthermore, higher modeled riskscores corresponded to more advanced tumor progression. To further understand the potential reasons for different prognoses in patients, we did enrichment analysis on differentially expressed genes identified by the model in risk groups. The expression levels and roles of SAA1 and KIF18B in ccRCC were verified by qRT-PCR and cell function experiments. RESULTS: Humoral immune response and cAMP signaling pathway may be the biological processes and pathways leading to poor prognosis. Further analysis of immune microenvironment presented that ccRCC patients with poor prognoses had highly immune-infiltrated characteristics. We compared the drug response data of samples from different prognostic patients in the GDSC database and identified drug sensitivity differences associated with prognosis. Finally, we demonstrated that SAA1 and KIF18B could increase the proliferation, migration, and invasion ability of ccRCC cells using cellular experiments. CONCLUSION: In summary, we further revealed the importance of VTRGs in ccRCC prognosis.

A dataset to measure global climate physical risk.

Extreme climate events have become more frequent and have had serious impacts on the global community. Consequently, the risk associated with climate change has gained increasing attention and has been considered as a new source of risk factors. To understand the socio-economic impacts of this new risk, systematically measuring risk around the world is critical for researchers and policymakers. Building on daily observations from meteorological stations, a Climate Physical Risk Index (CPRI) dataset is constructed for 170 countries, paying special attention to four extreme climate events: extreme low temperature (LTD), extreme high temperature (HTD), extreme rainfall (ERD), and extreme drought (EDD). A comprehensive index of climate physical risk for each country has also been constructed, covering the period from 1993 to 2023. The dataset will be updated regularly. Subnational indices or more detailed regional indices are available upon request.

Liver injury and prolonged hospitalization as indicators of severity in patients with adenovirus infections.

BACKGROUND: Adenovirus (ADV) is a prevalent infective virus in children, accounting for around 5-10% of all cases of acute respiratory illnesses and 4-15% of pneumonia cases in children younger than five years old. Without treatment, severe ADV pneumonia could result in fatality rates of over 50% in cases of emerging strains or disseminated disease. This study aims to uncover the relationship of clinical indicators with primary ADV infection severity, regarding duration of hospitalization and liver injury. METHODS: In this retrospective study, we collected and analyzed the medical records of 1151 in-patients who met the inclusion and exclusion criteria. According to duration of hospitalization, all patients were divided into three groups. Then the difference and correlation of clinical indicators with ADV infection were analyzed, and the relationship among liver injury, immune cells and cytokines was evaluated. RESULTS: The study revealed that patients with a duration of hospitalization exceeding 14 days had the highest percentage of abnormalities across most indicators. This was in contrast to the patients with a hospitalization duration of either less than or equal to 7 days or between 7 and 14 days. Furthermore, correlation analysis indicated that a longer duration of body temperature of ≥ 39°C, bilateral lung lobes infiltration detected by X ray, abnormal levels of AST, PaO2, and SPO2, and a lower age were all predictive of longer hospital stays. Furthermore, an elevated AST level and reduced liver synthesis capacity were related with a longer hospital stay and higher ADV copy number. Additionally, AST/ALT was correlated positively with IFN-γ level and IFN-γ level was only correlated positively with CD4+ T cells. CONCLUSIONS: The study provided a set of predicting indicators for longer duration of hospitalization, which responded for primary severe ADV infection, and elucidated the possible reason for prolonged duration of hospitalization attributing to liver injury via higher ADV copy number, IFN-γ and CD4+ T cells, which suggested the importance of IFN-γ level and liver function monitoring for the patients with primary severe ADV infection.

Flexible Broadband Organic Photodetectors with Ternary Planar-Mixed Heterojunction Semiconductors and Solution-Processed Polymeric Electrode.

Flexible organic photodetectors (OPDs) hold immense promise in health monitoring sensors, flexible imaging sensors, and portable optical communication. Nevertheless, the actualization of high-performance flexible electronics has been hindered by rigid electrodes such as metals or metal oxides. In this work, we constructed a flexible broadband organic photodetector using a solution-processed polymeric electrode, which exhibits flexibility surpassing that of conventional indium tin oxide (ITO) electrodes. Additionally, we employed a planar-mixed heterojunction (PMHJ) through a sequential deposition method and introduced PC71BM as the third constituent into the PM6/Y6 binary active layer, resulting in enhanced photodetection performance and a broadend spectral range. The optimized OPDs demonstrated remarkable detectivity (D*) exceeding 1012 Jones in brodband from 300 to 900 nm, with a champion D* of 6.31 × 1012 Jones at 790 nm. Furthermore, after undergoing 500 cycles of bending, the D* retained approximately 78% of its original performance, highlighting the outstanding mechanical stability. This work presents a promising pathway toward the development of flexible broadband OPDs using a straightforward method, offering enhanced compatibility in diverse application scenarios and propelling the frontier of flexible optoelectronic research.

Silicon Hybridization for the Preparation of Room-Temperature Curing and High-Temperature-Resistant Epoxy Resin.

Specialized epoxy resin, capable of achieving room-temperature profound curing and sustaining prolonged exposure to high-temperature environments, stands as a pivotal material in modern high-end manufacturing sectors including aerospace, marine equipment fabrication, machinery production, and the electronics industry. Herein, a silicon-hybridized epoxy resin, amenable to room-temperature curing and designed for high-temperature applications, was synthesized using a sol-gel methodology with silicate esters and silane coupling agents serving as silicon sources. Resin characterization indicates a uniform distribution of silicon elements in the obtained silicon hybrid epoxy resin. In comparison to the non-hybridized epoxy resin, notable improvements are observed in room-temperature curing performance, heat resistance, and mechanical strength.

Discovery of Novel N-(Anthracen-9-ylmethyl) Benzamide Derivatives as ZNF207 Inhibitors Promising in Treating Glioma.

Targeting tumor stemness is an innovative approach to cancer treatment. Zinc Finger Protein 207 (ZNF207) is a promising target for weakening the stemness of glioma cells. Here, a series of novel N-(anthracen-9-ylmethyl) benzamide derivatives against ZNF207 were rationally designed and synthesized. The inhibitory activity was evaluated, and their structure-activity relationships were summarized. Among them, C16 exhibited the most potent inhibitory activity, as evidenced by its IC50 values ranging from 0.5-2.5 µM for inhibiting sphere formation and 0.5-15 µM for cytotoxicity. Furthermore, we found that C16 could hinder tumorigenesis and migration and promote apoptosis in vitro. These effects were attributed to the downregulation of stem-related genes. The in vivo evaluation demonstrated that C16 exhibited efficient permeability across the blood-brain barrier and potent efficacy in both subcutaneous and orthotopic glioma tumor models. Hence, C16 may serve as a potential lead compound targeting ZNF207 and has promising therapeutic potential for glioma.

Spatial-temporal evolution of population aging in the yangtze river delta urban agglomeration of China.

The Yangtze River Delta urban agglomeration (YRDUA) is China's most representative region with remarkable economic development vitality. The purpose of this study is to provide valuable data analysis to actively respond to the population aging in China. We mainly focus on the spatial and temporal evolution of population aging in YRDUA from 2000 to 2020 using city-level population data. This study constructs a multi-dimensional index system to measure population aging including population aging degree, speed, and density. It finds out: (1) the elderly population rate (EPR), the elder-child ratio (ECR), and the elderly dependency ratio (EDR) in the YRDUA area are gradually increasing from 2000 to 2020. In addition, the trends of these indicators in various cities and regions are relatively consistent. All 27 cities in YRDUA entered an aging society, from the primary to the moderate aging stage from 2000 to 2010 and from the moderate to the hyper aging stage from 2010 to 2020. (2) the absolute and relative growth rate of EPR is increasing from 2000 to 2020. However, the absolute and relative growth rate of ECR is increasing from 2000 to 2010 and then decreasing from 2010 to 2020. These results indicate that the two-child policy adopted by the Chinese government plays a positive role. (3) the density level of the elderly population in the YRDUA evolved from low in 2000 to middle in 2010 and then to high in 2020. (4) There are remarkable differences in the process of population aging among three provinces and one city. The contribution of this study is mainly reflected in two aspects: firstly, it constructs a multi-dimensional index system to measure population aging; secondly, using this multi-dimensional index system, it systematically observes the spatial and temporal evolution of population aging from 2000 to 2020 in the Yangtze River Delta Urban Agglomeration.

Detection of Ghost Introgression Requires Exploiting Topological and Branch Length Information.

In recent years, the study of hybridization and introgression has made significant progress, with ghost introgression-the transfer of genetic material from extinct or unsampled lineages to extant species-emerging as a key area for research. Accurately identifying ghost introgression, however, presents a challenge. To address this issue, we focused on simple cases involving 3 species with a known phylogenetic tree. Using mathematical analyses and simulations, we evaluated the performance of popular phylogenetic methods, including HyDe and PhyloNet/MPL, and the full-likelihood method, Bayesian Phylogenetics and Phylogeography (BPP), in detecting ghost introgression. Our findings suggest that heuristic approaches relying on site-pattern counts or gene-tree topologies struggle to differentiate ghost introgression from introgression between sampled non-sister species, frequently leading to incorrect identification of donor and recipient species. The full-likelihood method BPP uses multilocus sequence alignments directly-hence taking into account both gene-tree topologies and branch lengths, by contrast, is capable of detecting ghost introgression in phylogenomic datasets. We analyzed a real-world phylogenomic dataset of 14 species of Jaltomata (Solanaceae) to showcase the potential of full-likelihood methods for accurate inference of introgression.

Optimizing concentration and interaction mechanism of Demodesmus sp. and Achromobacter pulmonis sp. consortium to evaluate their potential for dibutyl phthalate removal from synthetic wastewater.

A green approach of Desmodesmus sp. to Achromobacter pulmonis (1:1) coculture ratios was optimized to improve the removal efficiency of dibutyl phthalate (DBP) from simulated wastewater. High DBP resistance bacterial strains and microalgae was optimized from plastic contaminated water and acclimation process respectively. The influence of various factors on DBP removal performance was comprehensively investigated. Highest DBP removal 93 % was recorded, when the ratios algae-bacteria 1:1, with sodium acetate, pH-6, shaking speed-120 rpm and lighting periods L:D-12:12. Enough nutrient (TN/TP/TOC) availability and higher protein-108 mg/L and sugar-40 mg/L were observed in presences of 50 mg/L DBP. The degradation and sorption were calculated 81,12; 27,39 & 43,12 % in algae-bacteria, only algae and only bacteria system respectively. The degradation kinetics t1/2 3.74,22.15,12.86 days were evaluated, confirming that algae-bacteria effectively degrade the DBP. This outcome leading to promote a green sustainable approach to remove the emerging contamination from wastewater.