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An acid polysaccharide, named HP, was produced by endophytic Penicillium javanicum MSC-R1 isolated from southern medicine Millettia speciosa Champ. The molecular weight of HP was 37.8 kDa and consisted of Ara f, Galр, Glcр, Manр, and GlcрA with a molar ratio of 1.09: 3.47: 68.48: 16.59: 8.85. The glycosidic linkage of HP was proven to be →3, 4)-α-D-Glcр-(1→6)-α-D-Manр-(1→, →3, 4)-α-D-Glcр-(1→4)-α-D-Glcр-(1→, →3), →6)-α-D-Manр-(1→4)-α-D-Glcр-(1→, →3), β-D-Galр-(1→3)-α-D-Glcр-(1→, →4), →5)-α-L-Ara f -(1→3)-α-D-Glcр-(1→, →4), →6)-α-D-Manр-(1→4)-α-D-GlcAр-(1→ and →4)-α-D-GlcAр-(1→4)-α-D-Glcр-(1→, →3). Additionally, 250 μg/mL of HP possessed nontoxicity to RAW 264.7 cells and exhibited anti-inflammation activity. HP could significantly restrain the amount of tumor necrosis factor-α, interleukin-6 and NO release in RAW264.7, which property is possibly associated with its abundant glucosidic linkage. These results indicated that HP could be regarded as a ponderable ingredient for the health-beneficial functional foods.

Aim: A novel design for non-reversible as well as reversible parity generator and detector in Quantum-dot Cellular Automata (QCA) technology is presented in this research article. Parity generator and detector circuits are reliable error-checking components of a nano-communication system. Objective: The main focus of this research is to design an ultra-low-power fault-tolerant reversible gate implementation of the parity logic function in QCA. An efficient QCA design layout with minimal area, less latency and the least energy dissipation is desired. Methods: The proposed designs are developed using Quantum-dot Cellular Automata (QCA) technology. The circuits are optimized using majority gate reduction and clock zone reduction techniques. Also, the cell-cell interaction technique is employed to further optimize the QCA circuit. To increase the fault tolerance and ultra-low power operation, reversible QCA circuits are designed using cascaded Feynman gates. Results Conclusion: The efficiency of the parity generator and detector is calculated to be more than 25% compared to existing QCA layouts. It is demonstrated in this paper that the proposed circuits perform exceptionally well on every design parameter. The design parameters under consideration are cell count, cell area, complexity, crossover count, latency and energy dissipation. Conclusion: Using reversible logic, a fault-tolerant and defect-sensitive circuit are developed for parity generation and detection.

Background: The discovery of cuproptosis provides a new way to make full use of the pathophysiological effects of copper for anticancer therapy and could help identify a therapeutic target in bladder cancer. Methods: In this study, 411 BLCA tumor samples from the Cancer Genome Atlas (TCGA) cohort were obtained. Differentially expressed genes (DEGs) between chemotherapy-sensitive and chemotherapy-resistant mouse bladder cancers were also obtained. Sixteen genes were defined as cuproptosis-related genes (CRGs), and the cutoff score was calculated based on LASSO Cox regression. CCK-8 and Transwell assays were used to detect the migration and proliferation of 5637 and T24 cells, respectively. Liarozole dihydrochloride (L-D), a mild P450, inhibits the expression of CYP26B1. Multiple immunohistochemistry analyses were used to explore the association between the immune microenvironment and CRGs.Results: A higher Cuproptosis score was significantly associated with worse overall survival in BLCA (pCYP26B1andCYP26B1may be negatively associated with DNA damage and repair. In vitro experiments indicated that overexpression of CYP26B1 enhanced the migration and proliferation of BLCA cells, while L-D inhibited the migration and proliferation of BLCA cells. A higher expression level of Dihydrolipoamide S-Succinyltransferase (DLST) serves could as a risk factor in patients treated with atezolizumab and higher expression ofDLSTsuggest an immunosuppressive microenvironment. Conclusions:CYP26B1may be a therapeutic target for bladder cancer, and the higher expression of DLST may suggest an immunosuppressive microenvironment in BLCA.

It is well-known that parity symmetry is broken in the weak interaction but conserved for Einstein's general relativity and Maxwell's electromagnetic theory. Nevertheless, parity symmetry could also be violated in the gravitational/electromagnetic sectors if a fundamental scalar field couples to the parity-violating gravitational/electromagnetic curvature terms. Such parity-violating terms, which flip signs under reversed spatial directions, can inevitably lead to a negative effective mass squared for the scalar field perturbations near nonspherical black holes and thus are expected to trigger tachyonic instability. As illustrative examples, we show that the scalar field coupled to gravitational/electromagnetic Chern-Simons terms near a Kerr-Newmann spacetime can develop tachyonic instabilities, leading to equilibrium scalar field configurations in certain parameter region of black holes. This instability, which is an indication of the black hole scalarization process, can occur in a broad class of nonspherical black holes and parity-violating theories., 6 pages, 3 figures, 1 table

The uniform Tur\'an density $\pi_{1}(F)$ of a $3$-uniform hypergraph $F$ is the supremum over all $d$ for which there is an $F$-free hypergraph with the property that every linearly sized subhypergraph with density at least $d$. Determining $\pi_{1}(F)$ for given hypergraphs $F$ was suggested by Erd\H{o}s and S\'os in 1980s. In particular, they raised the questions of determining $\pi_{1}(K_4^{(3)-})$ and $\pi_{1}(K_4^{(3)})$. The former question was solved recently in [Israel J. Math. 211 (2016), 349-366] and [J. Eur. Math. Soc. 20 (2018), 1139-1159], while the latter is still a major open problem. In addition to $K_4^{(3)-}$, there are very few hypergraphs whose uniform Tur\'an density has been determined. In this paper, we give a sufficient condition for $3$-uniform hypergraphs $F$ satisfying $\pi_{1}(F)=1/4$. In particular, currently all known $3$-uniform hypergraphs whose uniform Tur\'an density is $1/4$, such as $K_4^{(3)-}$ and the $3$-uniform hypergraphs $F^{\star}_5$ studied in [arXiv:2211.12747], satisfy this condition. Moreover, we find some intriguing $3$-uniform hypergraphs whose uniform Tur\'an density is also $1/4$., Comment: 23 pages

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Background Urinary bladder cancer (UBC) is a common malignancy of the urinary tract; however, the mechanism underlying its high recurrence and responses to immunotherapy remains unclear, making clinical outcome predictions difficult. Epigenetic alterations, especially DNA methylation, play important roles in bladder cancer development and are increasingly being investigated as biomarkers for diagnostic or prognostic predictions. However, little is known about hydroxymethylation since previous studies based on bisulfite-sequencing approaches could not differentiate between 5mC and 5hmC signals, resulting in entangled methylation results. Methods Tissue samples of bladder cancer patients who underwent laparoscopic radical cystectomy (LRC), partial cystectomy (PC), or transurethral resection of bladder tumor (TURBT) were collected. We utilized a multi-omics approach to analyze both primary and recurrent bladder cancer samples. By integrating various techniques including RNA sequencing, oxidative reduced-representation bisulfite sequencing (oxRRBS), reduced-representation bisulfite sequencing (RRBS), and whole exome sequencing, a comprehensive analysis of the genome, transcriptome, methylome, and hydroxymethylome landscape of these cancers was possible. Results By whole exome sequencing, we identified driver mutations involved in the development of UBC, including those in FGFR3, KDMTA, and KDMT2C. However, few of these driver mutations were associated with the down-regulation of programmed death-ligand 1 (PD-L1) or recurrence in UBC. By integrating RRBS and oxRRBS data, we identified fatty acid oxidation-related genes significantly enriched in 5hmC-associated transcription alterations in recurrent bladder cancers. We also observed a series of 5mC hypo differentially methylated regions (DMRs) in the gene body of NFATC1, which is highly involved in T-cell immune responses in bladder cancer samples with high expression of PD-L1. Since 5mC and 5hmC alternations are globally anti-correlated, RRBS-seq-based markers that combine the 5mC and 5hmC signals, attenuate cancer-related signals, and therefore, are not optimal as clinical biomarkers. Conclusions By multi-omics profiling of UBC samples, we showed that epigenetic alternations are more involved compared to genetic mutations in the PD-L1 regulation and recurrence of UBC. As proof of principle, we demonstrated that the combined measurement of 5mC and 5hmC levels by the bisulfite-based method compromises the prediction accuracy of epigenetic biomarkers.

A $k$-graph (or $k$-uniform hypergraph) $H$ is uniformly dense if the edge distribution of $H$ is uniformly dense with respect to every large collection of $k$-vertex cliques induced by sets of $(k-2)$-tuples. Reiher, R\"odl and Schacht [Int. Math. Res. Not., 2018] proposed the study of the uniform Tur\'an density $\pi_{k-2}(F)$ for given $k$-graphs $F$ in uniformly dense $k$-graphs. Meanwhile, they [J. London Math. Soc., 2018] characterized $k$-graphs $F$ satisfying $\pi_{k-2}(F)=0$ and showed that $\pi_{k-2}(\cdot)$ ``jumps" from 0 to at least $k^{-k}$. In particular, they asked whether there exist $3$-graphs $F$ with $\pi_{1}(F)$ equal or arbitrarily close to $1/27$. Recently, Garbe, Kr\'al' and Lamaison [arXiv:2105.09883] constructed some $3$-graphs with $\pi_{1}(F)=1/27$. In this paper, for any $k$-graph $F$, we give a lower bound of $\pi_{k-2}(F)$ based on a probabilistic framework, and provide a general theorem that reduces proving an upper bound on $\pi_{k-2}(F)$ to embedding $F$ in reduced $k$-graphs of the same density using the regularity method for $k$-graphs. By using this result and Ramsey theorem for multicolored hypergraphs, we extend the results of Garbe, Kr\'al' and Lamaison to $k\ge 3$. In other words, we give a sufficient condition for $k$-graphs $F$ satisfying $\pi_{k-2}(F)=k^{-k}$. Additionally, we also construct an infinite family of $k$-graphs with $\pi_{k-2}(F)=k^{-k}$., Comment: 25 pages

Coronaviruses can have a devastating impact on the health of humans and animals. Porcine epidemic diarrhea virus (PEDV) causes extremely high fatality rates in neonatal piglets, whereas severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic in humans. As a critical component of the host antiviral innate immune response, type I interferon production and signaling play a very important role, especially in the initial phase of the antiviral responses. Coronaviruses have evolved multiple ways to counteract type I interferon responses. Although the primary functions of the nucleocapsid protein are to facilitate viral RNA replication and package viral genomic RNA into virions, recent studies have shown that the nucleocapsid protein is also involved in virus-host interactions. The aim of this review is to summarize our current understanding of how the nucleocapsid proteins of PEDV and SARS-CoV-2 modulate type I interferon responses. This knowledge will be useful for developing strategies to combat coronavirus infections.

Brain iron overload is positively correlated with the pathogenesis of Alzheimer's disease (AD). However, the role of iron in AD pathology is not completely understood. Furin is the first identified mammalian proprotein convertase that catalyzes the proteolytic maturation of large numbers of prohormones and proproteins. The correlation between altered furin expression and AD pathology has been suggested, but the underlying mechanism remains to be clarified. Here, we found that the expression of furin in the hippocampus of Alzheimer's model APP/PS1 mice was significantly reduced, and we demonstrated that the reduction of furin was directly caused by hippocampal iron overload using wild-type mice with intrahippocampal injection of iron. In cultured neuronal cells, this suppression effect was observed as transcriptional inhibition. Regarding the changes of furin-mediated activities caused by hippocampal iron overload, we found that the maturation of brain-derived neurotrophic factor (BDNF) was impeded and the expression levels of synaptogenesis-related proteins were downregulated, leading to cognitive decline. Furthermore, iron chelation or furin overexpression in the hippocampus of APP/PS1 mice increased furin expression, restored synapse plasticity, and ameliorated cognitive decline. Therefore, the inhibitory effect of hippocampal iron accumulation on furin transcription may be an important pathway involved in iron-mediated synapse damage and memory loss in AD. This study provides new insights into the molecular mechanisms of the toxic effects of iron in neurons and AD pathophysiology and renders furin as a potential target for treatment of iron overload-related neurodegenerative diseases.

Background: Both apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) inhibition and melatonin suppress prostate cancer (PCa) growth. This study evaluated the therapeutic efficiency of self-assembled and prostate-specific membrane antigen (PSMA)-targeted nanocarrier loading 125I radioactive particles and encapsulating siRNA targeting APE1 (siAPE1) and melatonin for PCa. Methods: The linear polyarginine R12 polypeptide was prepared using Fmoc-Arg-Pbf-OH. The PSMA-targeted polymer was synthesized by conjugating azide-modified R12 peptide to PSMA monoclonal antibody (mAb). Before experiments, the PSMA-R12 nanocarrier was installed with melatonin and siAPE1, which were subsequently labeled by 125I radioactive particles. In vitro biocompatibility and cytotoxicity of nanocomposites were examined in LNCaP cells and in vivo biodistribution and pharmacokinetics were determined using PCa tumor-bearing mice. Results: PSMA-R12 nanocarrier was ~120 nm in size and was increased to ~150 nm by melatonin encapsulation. PSMA-R12 nanoparticles had efficient loading capacities of siAPE1, melatonin, and 125I particles. The co-delivery of melatonin and siAPE1 by PSMA-R12-125I showed synergistic effects on suppressing LNCaP cell proliferation and Bcl-2 expression and promoting cell apoptosis and caspase-3 expression. Pharmacokinetics analysis showed that Mel@PSMA-R12-125I particles had high uptake activity in the liver, spleen, kidney, intestine, and tumor, and were accumulated in the tumor sites within the first 8 h p.i., but was rapidly cleared from all the tested organs at 24 h p.i. Administration of nanoparticles to PCa tumors in vivo showed that Mel@PSMA-R12-125I/siAPE1 had high efficiency in suppressing PCa tumor growth. Conclusion: The PSMA-targeted nanocarrier encapsulating siAPE1 and melatonin is a promising therapeutic strategy for PCa.

Anomaly detection on attributed graphs is a crucial topic for its practical application. Existing methods suffer from semantic mixture and imbalance issue because they mainly focus on anomaly discrimination, ignoring representation learning. It conflicts with the assortativity assumption that anomalous nodes commonly connect with normal nodes directly. Additionally, there are far fewer anomalous nodes than normal nodes, indicating a long-tailed data distribution. To address these challenges, a unique algorithm,Decoupled Self-supervised Learning forAnomalyDetection (DSLAD), is proposed in this paper. DSLAD is a self-supervised method with anomaly discrimination and representation learning decoupled for anomaly detection. DSLAD employs bilinear pooling and masked autoencoder as the anomaly discriminators. By decoupling anomaly discrimination and representation learning, a balanced feature space is constructed, in which nodes are more semantically discriminative, as well as imbalance issue can be resolved. Experiments conducted on various six benchmark datasets reveal the effectiveness of DSLAD.

Despite the success of targeted therapies in cancer treatment, therapy-induced resistance remains a major obstacle to a complete cure. Tumor cells evade treatments and relapse via phenotypic switching driven by intrinsic or induced cell plasticity. Several reversible mechanisms have been proposed to circumvent tumor cell plasticity, including epigenetic modifications, regulation of transcription factors, activation or suppression of key signaling pathways, as well as modification of the tumor environment. Epithelial-to-mesenchymal transition, tumor cell and cancer stem cell formation also serve as roads towards tumor cell plasticity. Corresponding treatment strategies have recently been developed that either target plasticity-related mechanisms or employ combination treatments. In this review, we delineate the formation of tumor cell plasticity and its manipulation of tumor evasion from targeted therapy. We discuss the non-genetic mechanisms of targeted drug-induced tumor cell plasticity in various types of tumors and provide insights into the contribution of tumor cell plasticity to acquired drug resistance. New therapeutic strategies such as inhibition or reversal of tumor cell plasticity are also presented. We also discuss the multitude of clinical trials that are ongoing worldwide with the intention of improving clinical outcomes. These advances provide a direction for developing novel therapeutic strategies and combination therapy regimens that target tumor cell plasticity.

Recently zero-dimensional (0-D) inorganic–organic metal halides (IOMHs) have become a promising class of optoelectronic materials. Herein, we report a new photoluminescent (PL) 0-D antimony(III)-based IOMH single crystal, namely [H2BPZ][SbCl5]·H2O (BPZ = benzylpiperazine). Photophysical characterizations indicate that [H2BPZ][SbCl5]·H2O exhibits singlet/triplet dual-band emission. Density functional theory (DFT) calculations suggest that [H2BPZ][SbCl5]·H2O has the large energy difference between singlet and triplet states, which might induce the dual emission in this compound. Temperature-dependent PL spectra analyses suggest the soft lattice and strong electron–phonon coupling in this compound. Thermogravimetric analysis shows that the water molecules in the lattice of the title crystal could be removed by thermal treatment, giving rise to a dehydrated phase of [H2BPZ][SbCl5]. Interestingly, such structural transformation is accompanied by a reversible PL emission transition between red light (630 nm, dehydrated phase) and yellow light (595 nm, water-containing phase). When being exposed to an environment with 77% relative humidity, the emission color of the dehydrated phase was able to change from red to yellow within 20 s, and the red emission could be restored after reheating. The red to yellow emission switching could be achieved in acetone with water concentration as low as 0.2 vol%. The reversible PL transition phenomenon makes [H2BPZ][SbCl5]·H2O a potential material for luminescent water-sensing.

The prolyl 3-hydroxylase family member 4 gene (P3H4) is involved in the development of human cancers. The association of P3H4 with bladder cancer (BC) prognosis is unclear. This study aimed to analyze the association of P3H4 with BC prognosis.RNA-Seq data were downloaded from The Cancer Genome Atlas project and BC microarray datasets (GSE13507, GSE31684, and GSE32548) were downloaded from the Gene Expression Omnibus database. We analyzed the differences in P3H4 expression levels between BC tumors and non-tumor tissues and between samples with different clinical information. The association of P3H4 and P3H4-related genes with BC prognosis and the possibility of using P3H4 expression as a prognostic biomarker in BC patients were also analyzed. RevMan was used to perform the meta-analysis.P3H4 was upregulated in BC tissues compared with the adjacent non-tumor tissues (p = 4.06e-08). Univariate Cox regression analysis and meta-analysis showed that high P3H4 expression level contributed to a poor BC prognosis (Hazard ratio, HR = 1.348, 95% CI 1.140-1.594, p = 4.89e-04; meta-analysis: HR = 1.45, 95% CI 1.10-1.91; p = 9.00e-03). Among the genes related to P3H4, the PLOD1 gene was closely associated with P3H4 expression (r = 0.620, p = 2.49e-44). Also, a meta-analysis showed that PLOD1 expression was associated with a poor prognosis in BC patients (HR = 1.77, 95% CI 1.31-2.38; p = 2.00e-04).The P3H4 and PLOD1 genes might be used as reliable prognostic biomarkers for BC.

Purpose The overall response of cisplatin-based chemotherapy in bladder urothelial carcinoma (BUC) remains unsatisfactory due to the complex pathological subtypes, genomic difference, and drug resistance. The genes that associated with cisplatin resistance remain unclear. Herein, we aimed to identify the cisplatin resistance associated genes in BUC. Experimental design The cytotoxicity of cisplatin was evaluated in six bladder cancer cell lines to compare their responses to cisplatin. The T24 cancer cells exhibited the lowest sensitivity to cisplatin and was therefore selected to explore the mechanisms of drug resistance. We performed genome-wide CRISPR screening in T24 cancer cells in vitro, and identified that the gene heterogeneous nuclear ribonucleoprotein U (HNRNPU) was the top candidate gene related to cisplatin resistance. Epigenetic and transcriptional profiles of HNRNPU-depleted cells after cisplatin treatment were analyzed to investigate the relationship between HNRNPU and cisplatin resistance. In vivo experiments were also performed to demonstrate the function of HNRNPU depletion in cisplatin sensitivity. Results Significant correlation was found between HNRNPU expression level and sensitivity to cisplatin in bladder cancer cell lines. In the high HNRNPU expressing T24 cancer cells, knockout of HNRNPU inhibited cell proliferation, invasion, and migration. In addition, loss of HNRNPU promoted apoptosis and S-phase arrest in the T24 cells treated with cisplatin. Data from The Cancer Genome Atlas (TCGA) demonstrated that HNRNPU expression was significantly higher in tumor tissues than in normal tissues. High HNRNPU level was negatively correlated with patient survival. Transcriptomic profiling analysis showed that knockout of HNRNPU enhanced cisplatin sensitivity by regulating DNA damage repair genes. Furthermore, it was found that HNRNPU regulates chemosensitivity by affecting the expression of neurofibromin 1 (NF1). Conclusions Our study demonstrated that HNRNPU expression is associated with cisplatin sensitivity in bladder urothelial carcinoma cells. Inhibition of HNRNPU could be a potential therapy for cisplatin-resistant bladder cancer.

Introduction Correction of leg length discrepancy (LLD) in skeletally mature patients with osteosarcoma was rarely reported and quite challenging. This study aimed to propose a treatment strategy of staged lengthening and reconstruction with a standard static prosthesis to address LLD and restore limb function. It also evaluated the effectiveness of the strategy in terms of leg lengthening, functional outcomes, and complications. Methods The strategy for lengthening included three stages. In stage 1, the previous prosthesis was removed and an external fixator with a temporary rod-cement spacer was placed. In this stage, the external fixator was used to lengthen the limb to the appropriate length. In stage 2, the external fixator was removed and the old rod-cement spacer was replaced with a new one. In stage 3, the rod-cement spacer was removed and the standard static prosthesis was planted. Nine skeletally mature distal femoral osteosarcoma patients with unacceptable LLD were treated in our institution from 2019 to 2021. We performed a chart review on nine patients for the clinical and radiographic assessment of functional outcomes, LLD, and complications. Results The mean (range) leg lengthening was 7.3 cm (3.6–15.6). The mean (range) LLD of the lower limbs decreased from 7.6 cm (4.1–14.2) before the lengthening to 0.3 cm (–0.3 to 2.1) at the final follow-up with statistical significance (P = 0.000). The mean (range) Musculoskeletal Tumor Society score improved from 30.3% (16.7%–53.3%) before the lengthening to 96.3% (86.7%–100%) at the final follow-up with statistical significance (P = 0.000). Three patients (33.3%) had a minor complication; none needed additional surgical intervention. Conclusions In the short term, the current staged lengthening and reconstruction with standard static prosthesis provided satisfactory functional outcomes and LLD correction with few complications. The long-term effects of this method need further exploration. Level of Evidence Level IV, therapeutic study

Members of the Doublesex and Mab-3-related transcription factor (Dmrt) gene family handle various vital functions in several biological processes, including sex determination/differentiation and gonad development. Dmrt1 and Sox9 (SoxE in invertebrates) exhibit a very conserved interaction function during testis formation in vertebrates. However, the dynamic expression pattern and functional roles of the Dmrt gene family and SoxE have not yet been identified in any echinoderm species. Herein, five members of the Dmrt gene family (Dmrt1, 2, 3a, 3b and 5) and the ancestor SoxE gene were identified from the genome of Apostichopus japonicus. Expression studies of Dmrt family genes and SoxE in different tissues of adult males and females revealed different expression patterns of each gene. Transcription of Dmrt2, Dmrt3a and Dmrt3b was higher expressed in the tube feet and coelomocytes instead of in gonadal tissues. The expression of Dmrt1 was found to be sustained throughout spermatogenesis. Knocking-down of Dmrt1 by means of RNA interference (RNAi) led to the downregulation of SoxE and upregulation of the ovarian regulator foxl2 in the testes. This indicates that Dmrt1 may be a positive regulator of SoxE and may play a role in the development of the testes in the sea cucumber. The expression level of SoxE was higher in the ovaries than in the testes, and knocking down of SoxE by RNAi reduced SoxE and Dmrt1 expression but conversely increased the expression of foxl2 in the testes. In summary, this study indicates that Dmrt1 and SoxE are indispensable for testicular differentiation, and SoxE might play a functional role during ovary differentiation in the sea cucumber.

Background: Urinary bladder cancer is one of the most common malignancies of the urinary tract; however, the mechanism of its high recurrence and responses to immunotherapy remains unclear, resulting in difficulties in clinical outcome prediction. Epigenetic alterations, especially DNA methylation, play important roles in bladder cancer development and are increasingly investigated as biomarkers for diagnostic or prognostic predictions. However, little is known regarding hydroxymethylation since previous studies based on bisulfite-sequencing approaches could not differentiate between 5mC and 5hmC signals, resulting in entangled methylation results. Methods: Here, we used a multi-omics approach to provide the genome, transcriptome, methylome, and hydroxymethylome landscape of both primary and recurrent bladder cancers. Results: By whole exome sequencing, we identified driver mutations that are involved in the UBC development, such as FGFR3, KDMTA and KDMT2C. However, few of these driver mutations are associated with the recurrence or the PD-L1 down-regulation in UBC. By integrating RRBS and oxRRBS-seq data, we identified fatty acid oxidation-related genes significantly enriched in 5hmC-associated transcription alterations in recurrent bladder cancers. We also observed a serial of 5mC hypomethylation DMRs in the gene body of NFATC1, a gene that is highly involved in the T-cell immune response, in bladder cancer samples with high expression of PD-L1. And since 5mC and 5hmC alternations are globally anti-correlated, RRBS-seq based markers which combine the 5mC and 5hmC signals, attenuate the cancer-related signals and therefore are not optimal to be used as clinical biomarkers. Conclusions: By multi-omics profiling of UBC samples, we showed that epigenetic alternations are more involved than genetic mutations in the recurrence and PD-L1 regulation of UBC. In addition, as a proof of principle, we demonstrated that the combined measurement of 5mC and 5hmC level by bisulfite-based method will compromise the prediction accuracy of epigenetic biomarkers.

Additional file 2: Fig. S11. Syntenic block dotplot within F. esculentum genome. Fig. S12. Syntenic block dotplot between F. esculentum and S. oleracea genomes. Fig. S13. Gene ontology (GO) enrichment analysis of the expanded gene families in F. tataricum. Fig. S14. GO enrichment analysis of the expanded gene families in F. esculentum. Fig. S15. Overview of the rutin biosynthetic pathway in F. tataricum and F. esculentum with expression profiles of key enzyme genes. Fig. S16. Multiple sequence alignment of the UGT2 proteins for the 4 assemblies. Red box indicates the position of UDP-glycosyltransferase functional domian (PF00201). Fig. S17. Sequence alignment of UGT2 promoter sequences in F. tataricum and F. esculentum haplotyped genomes. Fig. S18. Gene collinear relationship between F. tataricum (n=8) and F. esculentum (n=8) genomes. Red lines indicate S-RNase genes loci while blue lines indicate SLF genes loci. Fig. S19 Multiple sequence alignment of the S-RNase proteins for the 2 assemblies. Fig. S20 Sequence alignment of S-RNase promoter sequences in F. tataricum and F. esculentum genomes. Fig. S21. The number of different families within the Copia (a) and Gypsy (b) superfamilies. Fig. S22. The genome comparison between the 2 Mb to 3 Mb interval of Chromosome 8 of Fe-haplotype 1 and FES_r1.0.

Copper-doped titanium dioxide nanotubes were prepared by a one-step solvothermal method and exhibited high photocatalytic activity and stability.

An efficient, simple and reusable electrochemiluminescence biosensor was constructed based on a NiFe-LDH@AuNPs composite material and tetrahedral DNA nanostructure probe for highly sensitive detection of miRNA.

A $k$-graph (or $k$-uniform hypergraph) $H$ is uniformly dense if the edge distribution of $H$ is uniformly dense with respect to every large collection of $k$-vertex cliques induced by sets of $(k-2)$-tuples. Reiher, Rödl and Schacht [Int. Math. Res. Not., 2018] proposed the study of the uniform Turán density $π_{k-2}(F)$ for given $k$-graphs $F$ in uniformly dense $k$-graphs. Meanwhile, they [J. London Math. Soc., 2018] characterized $k$-graphs $F$ satisfying $π_{k-2}(F)=0$ and showed that $π_{k-2}(\cdot)$ ``jumps" from 0 to at least $k^{-k}$. In particular, they asked whether there exist $3$-graphs $F$ with $π_{1}(F)$ equal or arbitrarily close to $1/27$. Recently, Garbe, Král' and Lamaison [arXiv:2105.09883] constructed some $3$-graphs with $π_{1}(F)=1/27$. In this paper, for any $k$-graph $F$, we give a lower bound of $π_{k-2}(F)$ based on a probabilistic framework, and provide a general theorem that reduces proving an upper bound on $π_{k-2}(F)$ to embedding $F$ in reduced $k$-graphs of the same density using the regularity method for $k$-graphs. By using this result and Ramsey theorem for multicolored hypergraphs, we extend the results of Garbe, Král' and Lamaison to $k\ge 3$. In other words, we give a sufficient condition for $k$-graphs $F$ satisfying $π_{k-2}(F)=k^{-k}$. Additionally, we also construct an infinite family of $k$-graphs with $π_{k-2}(F)=k^{-k}$., 25 pages

Supplementary Material 1: Table S1 Primer sequences.

Background. Clear cell renal cell carcinoma’s (ccRCC) occurrence and development are strongly linked to the metabolic reprogramming of tumors, and thus far, neither its prognosis nor treatment has achieved satisfying clinical outcomes. Methods. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, respectively, provided us with information on the RNA expression of ccRCC patients and their clinical data. Cuproptosis-related genes (CRGS) were discovered in recent massive research. With the help of log-rank testing and univariate Cox analysis, the prognostic significance of CRGS was examined. Different cuproptosis subtypes were identified using consensus clustering analysis, and GSVA was used to further investigate the likely signaling pathways between various subtypes. Univariate Cox, least absolute shrinkage and selection operator (Lasso), random forest (RF), and multivariate stepwise Cox regression analysis were used to build prognostic models. After that, the models were verified by means of the C index, Kaplan–Meier (K-M) survival curves, and time-dependent receiver operating characteristic (ROC) curves. The association between prognostic models and the tumor immune microenvironment as well as the relationship between prognostic models and immunotherapy were next examined using ssGSEA and TIDE analysis. Four online prediction websites-Mircode, MiRDB, MiRTarBase, and TargetScan-were used to build a lncRNA-miRNA-mRNA ceRNA network. Results. By consensus clustering, two subgroups of cuproptosis were identified that represented distinct prognostic and immunological microenvironments. Conclusion. A prognostic risk model with 13 CR-lncRNAs was developed. The immune microenvironment and responsiveness to immunotherapy are substantially connected with the model, which may reliably predict the prognosis of patients with ccRCC.

The uniform Turán density $π_{1}(F)$ of a $3$-uniform hypergraph $F$ is the supremum over all $d$ for which there is an $F$-free hypergraph with the property that every linearly sized subhypergraph with density at least $d$. Determining $π_{1}(F)$ for given hypergraphs $F$ was suggested by Erdős and Sós in 1980s. In particular, they raised the questions of determining $π_{1}(K_4^{(3)-})$ and $π_{1}(K_4^{(3)})$. The former question was solved recently in [Israel J. Math. 211 (2016), 349-366] and [J. Eur. Math. Soc. 20 (2018), 1139-1159], while the latter is still a major open problem. In addition to $K_4^{(3)-}$, there are very few hypergraphs whose uniform Turán density has been determined. In this paper, we give a sufficient condition for $3$-uniform hypergraphs $F$ satisfying $π_{1}(F)=1/4$. In particular, currently all known $3$-uniform hypergraphs whose uniform Turán density is $1/4$, such as $K_4^{(3)-}$ and the $3$-uniform hypergraphs $F^{\star}_5$ studied in [arXiv:2211.12747], satisfy this condition. Moreover, we find some intriguing $3$-uniform hypergraphs whose uniform Turán density is also $1/4$., 23 pages

Additional file 1: Fig. S1. PacBio long reads (2 cell) length distribution of F. esculentum. Fig. S2. Genome size and heterozygosity estimation for F. esculentum. Fig. S3. Hi-C map of the Fe-haplotype 1 showing genome-wide all-by-all interactions. The map shows a high resolution of individual chromosomes that are scaffolded and assembled independently. Fig. S4. Hi-C map of the Fe-haplotype 2 showing genome-wide all-by-all interactions. The map shows a high resolution of individual chromosomes that are scaffolded and assembled independently. Fig. S5. Genome size and heterozygosity estimation for F. tataricum. Fig. S6. PacBio long reads (1 cell) length distribution of F. tataricum. Fig. S7. Hi-C map of the Ft-haplotype 1 showing genome-wide all-by-all interactions. The map shows a high resolution of individual chromosomes that are scaffolded and assembled independently. Fig. S8. Hi-C map of the Ft-haplotype 2 showing genome-wide all-by-all interactions. The map shows a high resolution of individual chromosomes that are scaffolded and assembled independently. Fig. S9. Genome alignment between F. tataricum cv. Pinku1 and Ft-haplotype 1. Fig. S10. Genome alignment between F. tataricum cv. Pinku1 and Ft-haplotype 2.

The financial system is a complex, nonlinear chaotic dynamic system caused by its operating mechanism. Therefore, the application of previous forecasting models cannot explain the existence of various interference factors in the financial market and the chaotic characteristics of the financial system. With the help of financial market stability, the article establishes a series of differential equation models that reflect changes in interest rates in the financial system. The article introduces the factor of macro-control on the premise of respecting market regulation to regulate and intervene in economic relations and economic operation status. We apply the Logistic model and stability theory to analyse the positive equilibrium point characteristics of the system and obtain the interest rate liquidity equation with a time-lag financial network.

Alzheimer’s Disease (AD) is a neurodegenerative disease featured by cognitive impairment. This bioinformatic analysis was used to identify hub genes related to cognitive dysfunction in AD. The gene expression profile GSE48350 in the hippocampus of AD patients aged >70 years was obtained from the Gene Expression Omnibus (GEO) database. A total of 96 differentially expressed genes (DEGs) were identified, and subjected to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses; a protein–protein interaction (PPI) network was constructed. The DEGs were enriched in synapse-related changes. A protein cluster was teased out of PPI. Furthermore, the cognition ranked the first among all the terms of biological process (BP). Next, 4 of 10 hub genes enriched in cognition were identified. The function of these genes was validated using APP/PS1 mice. Cognitive performance was validated by Morris Water Maze (MWM), and gene expression by RT-qPCR, Cholecystokinin (CCK), Tachykinin precursor 1 (TAC1), Calbindin 1 (CALB1) were downregulated in the hippocampus. These genes can provide new directions in the research of the molecular mechanism of AD.