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Abstract Background This study aimed to develop a comprehensive model based on five GLIM variables to predict the individual survival and provide more appropriate patient counseling. Methods This retrospective cohort study included 301 gastric cancer (GC) patients undergoing radical resection. C-reactive protein (CRP) as an inflammatory marker was included in GLIM criteria and a nomogram for predicting 5-year overall survival (OS) in GC patients was established. The Bootstrap repeated sampling for 1000 times was used for internal validation. Results Of the total 301 patients, 20 (6.64%) died within 5 years. CRP improved the sensitivity and accuracy of the survival prediction model (AUC = 0.782, 0.694 to 0.869 for the model without CRP; AUC = 0.880, 0.809 to 0.950 for the model adding CRP). Besides, a GLIM-based nomogram was established with an AUC of 0.889. The C-index for predicting OS was 0.878 (95% CI: 0.823 to 0.934), and the calibration curve fitted well. Decision curve analysis (DCA) showed the clinical utility of the nomogram based on GLIM. Conclusion The addition of CRP improved the sensitivity and accuracy of the survival prediction model. The 5-year survival probability of GC patients undergoing radical resection can be reliably predicted by the nomogram presented in this study.

An innovative approach was pursued for sustainable packaging design using Cycle Generative Adversarial Networks (CycleGANs), tailored for wood packaging engraving. The methodology includes four phases: user participatory design, assembly scheme design, detailed Finite Element Analysis (FEA) optimization, and computer numerical control (CNC) engraving production. Each phase targets sustainability from design to final product, minimizing environmental impact and economic costs. Emphasizing early user participation helps adapt designs to user needs and environmental standards. Innovations such as real-time updates of packaging patterns via cloud-based iterations and an FEA optimization system enhance durability and aesthetics. This approach improves the environmental footprint and recyclability of conventional wood packaging. The research aims to shift perceptions in the packaging industry towards more sustainable practices, showcasing the practical applications of advanced digital tools in traditional manufacturing. It offers a scalable model for integrating sustainability into packaging design, providing valuable insights and inspiring future innovations in environmentally friendly practices across the industry.

Abstract Background Pancreatic cancer (PC) is one of the most malignant cancers with highly aggressiveness and poor prognosis. N6-methyladenosine (m6A) have been indicated to be involved in PC development. Glucan Branching Enzyme 1 (GBE1) is mainly involved in cell glycogen metabolism. However, the function of GBE1 and Whether GBE1 occurs m6A modification in PC progression remains to be illustrated. Methods The clinical prognosis of GBE1 was analyzed through online platform. The expression of GBE1 was obtained from online platform and then verified in normal and PC cell lines. Lentivirus was used to generated GBE1 stable-overexpression or knockdown PC cells. Cell Counting Kit (CCK-8), colony formation assay, sphere formation assay and flow cytometry assay were conducted to analyze cell proliferation and stemness ability in vitro. Subcutaneous and orthotopic mouse models were used to verify the function of GBE1 in vivo. RNA immunoprecipitation (RIP) assay, RNA stability experiment and western blots were conducted to explore the molecular regulation of GBE1 in PC. Results GBE1 was significantly upregulated in PC and associated with poor prognosis of PC patients. Functionally, GBE1 overexpression facilitated PC cell proliferation and stemness-like properties, while knockdown of GBE1 attenuated the malignancy of PC cells. Importantly, we found the m6A modification of GBE1 RNA, and WTAP and IGF2BP3 was revealed as the m6A regulators to increase GBE1 mRNA stability and expression. Furthermore, c-Myc was discovered as a downstream gene of GBE1 and functional rescue experiments showed that overexpression of c-Myc could rescue GBE1 knockdown-induced PC cell growth inhibition. Conclusions Our study uncovered the oncogenic role of GBE1/c-Myc axis in PC progression and revealed WTAP/IGF2BP3-mediated m6A modification of GBE1, which highlight the potential application of GBE1 in the targeted therapy of PC.

An unprecedented electrochemical oxidative trifunctionalization of olefins with diaryl disulfides/aryl thiols and N-chlorosuccinimide in an aqueous system is developed. Two C–Cl bonds, one C–S bond, and one SO bond are produced simultaneously in one step from simple and commercially available starting materials with clean energy. This tandem methodology features as mild reaction conditions, transition metal and additional oxidant free, broad substrate scope, good functional group compatibility, and gram scale preparation.

Abstract RNA splicing is a dynamic molecular process in response to environmental stimuli and is strictly regulated by the spliceosome. Sm proteins, constituents of the spliceosome, are key components that mediate splicing reactions; however, their potential role in hepatocellular carcinoma (HCC) is poorly understood. In the study, SNRPD2 (PD2) is found to be the most highly upregulated Sm protein in HCC and to act as an oncogene. PD2 modulates DDX39A intron retention together with HNRNPL to sustain the DDX39A short variant (39A_S) expression. Mechanistically, 39A_S can mediate MYC mRNA nuclear export to maintain high MYC protein expression, while MYC in turn potentiates PD2 transcription. Importantly, digitoxin can directly interact with PD2 and has a notable cancer‐suppressive effect on HCC. The study reveals a novel mechanism by which DDX39A senses oncogenic MYC signaling and undergoes splicing via PD2 to form a positive feedback loop in HCC, which can be targeted by digitoxin.

Abstract Enhancers and the enhancer RNAs (eRNAs) have been strongly implicated in regulations of transcriptions. Based the multi-omics data (ATAC-seq, ChIP-seq and RNA-seq) from public databases, Pig-eRNAdb is a dataset that comprehensively integrates enhancers and eRNAs for pigs using the machine learning strategy, which incorporates 82,399 enhancers and 37,803 eRNAs from 607 samples across 15 tissues of pigs. This user-friendly dataset covers a comprehensive depth of enhancers and eRNAs annotation for pigs. The coordinates of enhancers and the expression patterns of eRNAs are downloadable. Besides, thousands of regulators on eRNAs, the target genes of eRNAs, the tissue-specific eRNAs, and the housekeeping eRNAs are also accessible as well as the sequence similarity of eRNAs with humans. Moreover, the tissue-specific eRNA-trait associations encompass 652 traits are also provided. It will crucially facilitate investigations on enhancers and eRNAs with Pig-eRNAdb as a reference dataset in pigs.

Abstract Background Despite the critical progress of non-small cell lung cancer (NSCLC) therapeutic approaches, the clinical outcomes remain considerably poor. The requirement of developing novel therapeutic interventions is still urgent. In this study, we showed for the first time that diosbulbin C, a natural diterpene lactone component extracted from traditional Chinese medicine Dioscorea bulbifera L., possesses high anticancer activity in NSCLC. Methods A549 and NCI-H1299 cells were used. The inhibitory effects of the diosbulbin C on NSCLC cell proliferation were evaluated using cytotoxicity, clone formation, EdU assay, and flow cytometry. Network pharmacology methods were used to explore the targets through which the diosbulbin C inhibited NSCLC cell proliferation. Molecular docking, qRT-PCR, and western blotting were used to validate the molecular targets and regulated molecules of diosbulbin C in NSCLC. Results Diosbulbin C treatment in NSCLC cells results in a remarkable reduction in cell proliferation and induces significant G0/G1 phase cell cycle arrest. AKT1, DHFR, and TYMS were identified as the potential targets of diosbulbin C. Diosbulbin C may inhibit NSCLC cell proliferation by downregulating the expression/activation of AKT, DHFR, and TYMS. In addition, diosbulbin C was predicted to exhibit high drug-likeness properties with good water solubility and intestinal absorption, highlighting its potential value in the discovery and development of anti-lung cancer drugs. Conclusions Diosbulbin C induces cell cycle arrest and inhibits the proliferation of NSCLC cells, possibly by downregulating the expression/activation of AKT, DHFR, and TYMS.

Abstract Background Gut microbiota (GM) comprises a vast and diverse community of microorganisms, and recent studies have highlighted the crucial regulatory roles of various GM and their secreted metabolites in pancreatic cancer (PC). However, the causal relationship between GM and PC has yet to be confirmed. Methods In the present study, we used two-sample Mendelian randomization (MR) analysis to investigate the causal effect between GM and PC, with genome-wide association study (GWAS) from MiBioGen consortium as an exposure factor and PC GWAS data from FinnGen as an outcome factor. Inverse variance weighted (IVW) was used as the primary method for this study. Results At the genus level, we observed that Senegalimassilia (OR: 0.635, 95% CI: 0.403–0.998, P = 0.049) exhibited a protective effect against PC, while Odoribacter (OR:1.899, 95%CI:1.157–3.116, P = 0.011), Ruminiclostridium 9(OR:1.976,95%CI:1.128–3.461, P = 0.017), Ruminococcaceae (UCG011)(OR:1.433, 95%CI:1.072–1.916, P = 0.015), and Streptococcus(OR:1.712, 95%CI:1.071–1.736, P = 0.025) were identified as causative factors for PC. Additionally, sensitivity analysis, Cochran’s Q test, the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger regression indicated no heterogeneity, horizontal pleiotropy, or reverse causality between GM and PC. Conclusions Our analysis establishes a causal effect between specific GM and PC, which may provide new insights into the potential pathogenic mechanisms of GM in PC and the assignment of effective therapeutic strategies.

Abstract Background Recurrence after resection is the main factor for poor survival. The relationship between clinicopathological factors and recurrence after curative distal pancreatectomy for PDAC has rarely been reported separately. Methods Patients with PDAC after left‑sided pancreatectomy between May 2015 and August 2021 were retrospectively identified. Results One hundred forty-one patients were included. Recurrence was observed in 97 patients (68.8%), while 44 (31.2%) patients had no recurrence. The median RFS was 8.8 months. The median OS was 24.9 months. Local recurrence was the predominant first detected recurrence site (n = 36, 37.1%), closely followed by liver recurrence (n = 35, 36.1%). Multiple recurrences occurred in 16 (16.5%) patients, peritoneal recurrence in 6 (6.2%) patients, and lung recurrence in 4 (4.1%) patients. High CA19-9 value after surgery, poor differentiation grade, and positive lymph nodes were found to be independently associated with recurrence. The patients receiving adjuvant chemotherapy had a decreased likelihood of recurrence. In the high CA19-9 value cohort, the median PFS and OS of the patients with or without chemotherapy were 8.0 VS. 5.7 months and 15.6 VS. 13.8 months, respectively. In the normal CA19-9 value cohort, there was no significant difference in PFS with or without chemotherapy (11.7 VS. 10.0 months, P = 0.147). However, OS was significantly longer in the patients with chemotherapy (26.4 VS. 13.8 months, P = 0.019). Conclusions Tumor biologic characteristics, such as T stage, tumor differentiation and positive lymph nodes, affecting CA19-9 value after surgery are associated with patterns and timing of recurrence. Adjuvant chemotherapy significantly reduced recurrence and improved survival. Chemotherapy is strongly recommended in patients with high CA199 after surgery.

In landscape appreciation, what tourists directly perceive is the atmosphere of the landscape. This paper introduces the concept of "Ecological Structure" from Gernot Böhme's theory of atmospheric aesthetics into the assessment of landscapes, utilizing atmosphere as a bridge between horticultural ecology, aesthetics, and culture. It examines the relationship between the objective environment and subjective perception. This study conducted a field survey of Xingqing Palace Park and selected the waterside plant landscape that directly reflects the atmosphere of the royal garden as the research object. In the first stage of this study, Scenic Beauty Estimation was used to evaluate the overall beauty of 32 landscape units; in the second stage, the Delphi method and Analytic Hierarchy Process were used to evaluate the ecological structures that affect the garden landscape atmosphere; in the third stage, the two evaluation results of the Kendall's W concord coefficient test Analytic Hierarchy Process and Scenic Beauty Estimation have high consistency, which shows that the atmosphere is great value to the beauty of the landscape. This study provides designers with a means to create a garden atmosphere using ecological structures and provides new ideas for landscape design.

Natural products play a key role in the history of human drug discovery, and especially for the anticancer agents. Copper(I)-catalyzed alkyne-azide [3+2] cycloaddition (CuAAC) reaction is perhaps the most powerful method for the efficient modification of complex natural products, enabling the direct incorporation of various functional groups accompanied by the formation of the multifunctional 1,2,3-triazole motif, which could not only serve as an basic and hydrophilic connecting group but also as a bioisosteres of 5- or 6-membered heterocycles or an amide group, thus facilitating the improvement of anticancer activities and/or drug-like properties. This contribution extensively summarizes the state-of-the-art application of 1,2,3-triazole in the modification of natural products for anticancer activity. The aim is to gain a deep understanding of the fruitful achievements as well as limitations of CuAAC click chemistry in natural product modification for anticancer activity, and provide perspectives and directions regarding future studies in natural product medicinal chemistry.

Alternative polyadenylation (APA) is an important post-transcription regulatory mechanism widely occurring in eukaryotes and has been associated with special traits/diseases by several studies. However, the dynamic roles and patterns of APA in cell differentiation remain largely unknown. Here, we systematically characterized the APA profiles during the differentiation of induced pluripotent stem cells (iPSCs) to cardiomyocytes by the previously published RNA-seq data across 16 time points. We identified 950 differential APA events and found five dynamic APA patterns with fuzzy c-means clustering analysis. Among them, 3′UTR progressive lengthening is the main APA pattern over time, the genes of which are enriched in cell cycle and mRNA metabolic process pathways. By constructing the linear mixed-effects model, we also indicated that TIA1 plays an important role in regulating APA events with this pattern, including genes essential to cardiac function. Additionally, APA and polyA machinery activity with another pattern can immediately respond to developmental signal-mediated stimuli at the early differentiation stage and result in a sharp shortening of the 3′UTR. Finally, a miRNA-APA network is constructed and several hub miRNAs potentially regulating cardiomyocyte differentiation are detected. Our results show the complex APA mechanisms during the differentiation of iPSCs into cardiomyocytes and provide further insights for the understanding of APA regulation and cell differentiation.

Abstract Background Pancreatoduodenectomy is a complex and challenging procedure that requires meticulous tissue dissection and proficient suturing skills. Minimally invasive surgery with the utilization of robotic platforms has demonstrated advantages in perioperative patient outcomes in retrospective studies. The development of robotic pancreatoduodenectomy (RPD) in specific has progressed significantly, since first reported in 2003, and high-volume centers in pancreatic surgery are reporting large patient series with improved pain management and reduced length of stay. However, prospective studies to assess objectively the feasibility and safety of RPD compared to open pancreatoduodenectomy (OPD) are currently lacking. Methods/design The PORTAL trial is a multicenter randomized controlled, patient-blinded, parallel-group, phase III non-inferiority trial performed in seven high-volume centers for pancreatic and robotic surgery in China (> 20 RPD and > 100 OPD annually in each participating center). The trial is designed to enroll and randomly assign 244 patients with an indication for elective pancreatoduodenectomy for malignant periampullary and pancreatic lesions, as well as premalignant and symptomatic benign periampullary and pancreatic disease. The primary outcome is time to functional recovery postoperatively, measured in days. Secondary outcomes include postoperative morbidity and mortality, as well as perioperative costs. A sub-cohort of 128 patients with pancreatic adenocarcinoma (PDAC) will also be compared to assess the percentage of patients who undergo postoperative adjuvant chemotherapy within 8 weeks, in each arm. Secondary outcomes in this cohort will include patterns of disease recurrence, recurrence-free survival, and overall survival. Discussion The PORTAL trial is designed to assess the feasibility and safety of RPD compared to OPD, in terms of functional recovery as described previously. Additionally, this trial will explore whether RPD allows increased access to postoperative adjuvant chemotherapy, in a sub-cohort of patients with PDAC. Trial registration ClinicalTrials.gov NCT04400357 . Registered on May 22, 2020

Abstract Background Structural variants (SVs) significantly drive genome diversity and environmental adaptation for diverse species. Unlike the prevalent small SVs (< kilobase-scale) in higher eukaryotes, large-size SVs rarely exist in the genome, but they function as one of the key evolutionary forces for speciation and adaptation. Results In this study, we discover and characterize several megabase-scale presence-absence variations (PAVs) in the maize genome. Surprisingly, we identify a 3.2 Mb PAV fragment that shows high integrity and is present as complete presence or absence in the natural diversity panel. This PAV is embedded within the nucleolus organizer region (NOR), where the suppressed recombination is found to maintain the PAV against the evolutionary variation. Interestingly, by analyzing the sequence of this PAV, we not only reveal the domestication trace from teosinte to modern maize, but also the footprints of its origin from Tripsacum, shedding light on a previously unknown contribution from Tripsacum to the speciation of Zea species. The functional consequence of the Tripsacum segment migration is also investigated, and environmental fitness conferred by the PAV may explain the whole segment as a selection target during maize domestication and improvement. Conclusions These findings provide a novel perspective that Tripsacum contributes to Zea speciation, and also instantiate a strategy for evolutionary and functional analysis of the “fossil” structure variations during genome evolution and speciation.

Background: Recent studies demonstrate that N6-methyladenosine (m6A) methylation plays a crucial role in colorectal cancer (CRC). Therefore, we conducted a comprehensive analysis to assess the m6A modification patterns and identify m6A-modified genes in patients with CRC recurrence.Methods: The m6A modification patterns were comprehensively evaluated by the NMF algorithm based on the levels of 27 m6A regulators, and tumor microenvironment (TME) cell-infiltrating characteristics of these modification patterns were systematically assessed by ssGSEA and CIBERSORT algorithms. The principal component analysis algorithm based on the m6A scoring scheme was used to explore the m6A modification patterns of individual tumors with immune responses. The weighted correlation network analysis and univariable and multivariable Cox regression analyses were applied to identify m6A-modified gene signatures. The single-cell expression dataset of CRC samples was used to explore the tumor microenvironment affected by these signatures.Results: Three distinct m6A modification patterns with significant recurrence-free survival (RFS) were identified in 804 CRC patients. The TME characterization revealed that the m6A modification pattern with longer RFS exhibited robust immune responses. CRC patients were divided into high- and low-score subgroups according to the m6A score individually, which was obtained from the m6A-related signature genes. The patients with low m6A scores had both longer RFS and overall survival (OS) with altered immune cell infiltration. Notably, m6A-modified genes showed significant differences related to the prognosis of CRC patients in the meta-GEO cohort and TCGA cohort. Single-cell expression indicated that ALVRL1 was centrally distributed in endothelial tip cells and stromal cells.Conclusion: The m6A modification plays an indispensable role in the formation of TME diversity and complexity. Importantly, the signatures (TOP2A, LRRC58, HAUS6, SMC4, ACVRL1, and KPNB1) were identified as m6A-modified genes associated with CRC recurrence, thereby serving as a promising predictive biomarker or therapeutic target for patients with CRC recurrence.

BackgroundLaparoscopic radical antegrade modular pancreatosplenectomy (LRAMPS) is a validated surgical treatment for patients with left-sided pancreatic ductal adenocarcinoma (PDAC). In addition, laparoscopic distal pancreatectomy (LDPS) has purported benefits. However, there is a limited analysis comparing the results between LRAMPS and LDPS. Thus, this study aims to compare the short-term and long-term outcomes of patients who underwent LRAMPS and LDPS for PDAC treatment.MethodsPatients with left-sided PDAC that underwent LRAMPS or LDPS from 2015 to 2021 were retrospectively identified. Demographic and clinic pathologic data were collected. Disease-free survival (DFS) and overall survival (OS) probabilities were obtained.ResultsThe number of lymph nodes retrieved was significantly greater in the LRAMPS group than in the LDPS group. Several clinicopathological factors, including CA19-9 levels greater than 37 U/ml, positive lymph nodes, moderate to poor tumor differentiation, and peripancreas fat invasion, were associated with DFS. Moderate with poor tumor differentiation was associated with poor DFS (HR 0.568; 95% CI 0.373–0.921; P = 0.021). Levels of CA19-9 greater than 37 U/ml, CEA levels greater than 5 μg/ml, larger tumor size, positive lymph nodes, moderate with poor tumor differentiation, peripancreas fat invasion, and adjuvant chemotherapy were all associated with OS. LRAMPS nearly improved OS but did not reach statistical significance. Serum carcinoembryonic antigen (CEA) levels greater than 5 ug/ml (HR 1.693; 95% CI 1.200–1.132; P = 0.001), and positive lymph nodes (HR 2.410; 95% CI 1.453–3.995; P = 0.001) were independently associated with poor OS. Treatment with adjuvant chemotherapy was associated with improved OS (HR 0.491; 95% CI 0.248–0.708; P = 0.001).ConclusionsThe LRAMPS procedure achieved comparable results to standard LDPS in terms of postoperative outcomes. Treatment with chemotherapy is important for the prognosis of patients with left-sided pancreatic cancer.

Macropinocytosis, a unique endocytosis pathway characterized by nonspecific internalization, has a vital role in the uptake of extracellular substances and antigen presentation. It is known to have dual effects on cancer cells, depending on cancer type and certain microenvironmental conditions. It helps cancer cells survive in nutrient-deficient environments, enhances resistance to anticancer drugs, and promotes invasion and metastasis. Conversely, overexpression of the RAS gene alongside drug treatment can lead to methuosis, a novel mode of cell death. The survival and proliferation of cancer cells is closely related to macropinocytosis in the tumor microenvironment (TME), but identifying how these cells interface with the TME is crucial for creating drugs that can limit cancer progression and metastasis. Substantial progress has been made in recent years on designing anticancer therapies that utilize the effects of macropinocytosis. Both the induction and inhibition of macropinocytosis are useful strategies for combating cancer cells. This article systematically reviews the general mechanisms of macropinocytosis, its specific functions in tumor cells, its occurrence in nontumor cells in the TME, and its application in tumor therapies. The aim is to elucidate the role and therapeutic potential of macropinocytosis in cancer treatment.

Ferroptosis is an iron-dependent cell death process characterized by excessive accumulation of reactive oxygen species and lipid peroxidation. The elucidation of ferroptosis pathways may lead to novel cancer therapies. Current evidence suggests that the mechanism of ferroptosis can be summarized as oxidative stress and antioxidant defense mechanisms. During this process, ferrous ions play a crucial role in cellular oxidation, plasma membrane damage, reactive oxygen species removal imbalance and lipid peroxidation. Although, disregulation of intracellular cations (Fe2+, Ca2+, Zn2+, etc.) and anions (Cl-, etc.) have been widely reported to be involved in ferroptosis, their specific regulatory mechanisms have not been established. To further understand the crosstalk effect between ferrous and other ions in ferroptosis, we reviewed the ferroptosis process from the perspective of ions metabolism. In addition, the role of ferrous and other ions in tumor therapy is briefly summarized.

BackgroundColorectal cancer (CRC) is one of the most common malignancies and its incidence and mortality are increasing yearly. 5-Fluorouracil (5-FU) has long been used as a standard first-line treatment for CRC patients. Although 5-FU-based chemotherapy is effective for advanced CRC, the consequent resistance remains a key problem and causes the poor prognosis of CRC patients. Thus, there is an urgent need to identify new biomarkers to predict the response to 5-FU-based chemotherapy.MethodsCRC samples were retrieved from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). The immune-related genes were retrieved from the ImmPort database. Single-cell sequencing results from colorectal cancer were obtained by the ArrayExpress database. 5-FU resistance-related genes were filtered and validated by R packages. ESTIMATE algorithms were used to assess the tumor microenvironment (TME). KEGG and GO analysis were performed to explore the biological signaling pathway for resistant-response patients and sensitive-response patients in the tumor microenvironment. pRRophetic algorithms were used to predict 5-FU sensitivity. GSEA and GSVA analysis was performed to excavate the biological signaling pathway of the RBP7 gene.ResultsNine immune-related genes were identified to be associated with 5-FU resistance and poor disease-free survival (DFS) of CRC patients and the signature of these genes was developed in a DFS-prognostic model. Four immune-related genes were determined to be associated with 5-FU resistance and overall survival (OS) of CRC patients. The signature of these genes was developed an OS-prognostic model. ESTIMATE scores showed a significant difference between 5-FU resistant and 5-FU sensitive CRC patients. Resistant-response patients and sensitive-response patients to 5-FU based chemotherapy showed different GO and KEGG enrichment on the tumor microenvironment. RBP7, as a tumor immune microenvironment (TIME) related gene, was found to have the potential of predicting chemotherapy resistance and poor prognosis of CRC patients. GSEA analysis showed multiple signaling differences between the high and low expression of RBP7 in CRC patients. Hypoxia and TNFα signaling via NFκB gene sets were significantly different between chemotherapy resistant (RBP7High) and chemotherapy sensitive (RBP7Low) patients. Single-cell RNA-seq suggested RBP7 was centrally distributed in endothelial stalk cells, endothelial tip cells, and myeloid cells.ConclusionsImmune-related genes will hopefully be potential prognostic biomarkers to predict chemotherapy resistance for CRC. RBP7 may function as a tumor microenvironment regulator to induce 5-FU resistance, thereby affecting the prognosis of CRC patients.

Maize (Zea mays) doubled haploid (DH) breeding is a technology that can efficiently generate inbred lines with homozygous genetic backgrounds. Haploids are usually produced through in vivo induction by haploid inducer lines in maize. Currently, two approaches are usually used to develop maize haploid inducer lines. One is through the conventional breeding improvement based on the Stock6 germplasm, and this strategy is extensively used to induce maternal haploids in commercial maize DH breeding. Another strategy, newly developed but less utilized so far, is by genetic manipulation of the Centromeric Histone3 (CENH3) in regular lines. However, whether both approaches can be combined to develop the haploid inducer line with higher maternal haploid induction rate (HIR) has not been reported. In this study, we manipulated the Stock6-derived inducer lines by overexpressing maize CENH3 fused with different fluorescent protein tags and found that the engineered Stock6-derived lines showed an obvious increase in the maternal HIR. Intriguingly, this above strategy could be further improved by substituting a tail-altered CENH3 for the full-length CENH3 in the tagged expression cassette, resulting in a maternal HIR up to 16.3% that was increased by ~6.1% than Stock6-derived lines control. These results suggested that integration of two in vivo haploid induction methods could rapidly and effectively improve the maternal HIRs of maize Stock6-derived inducer lines, and provided a potentially feasible solution for further optimizing the process of commercial maize DH breeding.

Abstract Background Overexpression of Wilms’ tumor-1 (WT1) transcription factor facilitates proliferation in acute myeloid leukemia (AML). However, whether WT1 is enriched in the leukemia-initiating cells (LICs) and leukemia stem cells (LSCs) and facilitates the self-renewal of LSCs remains poorly understood. Methods MLL-AF9-induced murine leukemia model was used to evaluate the effect of knockdown of wt1 on the self-renewal ability of LSC. RNA sequencing was performed on WT1-overexpressing cells to select WT1 targets. Apoptosis and colony formation assays were used to assess the anti-leukemic potential of a deubiquitinase inhibitor WP1130. Furthermore, NOD/SCID-IL2Rγ (NSG) AML xenotransplantation and MLL-AF9-induced murine leukemia models were used to evaluate the anti-leukemogenic potential of WP1130 in vivo. Results We found that wt1 is highly expressed in LICs and LSCs and facilitates the maintenance of leukemia in a murine MLL-AF9-induced model of AML. WT1 enhanced the self-renewal of LSC by increasing the expression of BCL2L2, a member of B cell lymphoma 2 (BCL2) family, by direct binding to its promoter region. Loss of WT1 impaired self-renewal ability in LSC and delayed the progression of leukemia. WP1130 was found to modify the WT1-BCL2L2 axis, and WP1130-induced anti-leukemic activity was mediated by ubiquitin proteasome-mediated destruction of WT1 protein. WP1130 induced apoptosis and decreased colony formation abilities of leukemia cells and prolonged the overall survival in the THP1-based xenograft NSG mouse model. WP1130 also decreased the frequency of LSC and prolonged the overall survival in MLL-AF9-induced murine leukemia model. Mechanistically, WP1130 induced the degradation of WT1 by positively affecting the ubiquitination of WT1 protein. Conclusions Our results indicate that WT1 is required for the development of AML. WP1130 exhibits anti-leukemic activity by inhibiting the WT1-BCL2L2 axis, which may represent a new acute myeloid leukemia therapy target.

To explore the therapeutic effect of aerobic exercise combined with metformin on ischemic cerebral infarction (ICI) and its effect on the molecular level, 100 patients with ICI who were treated in our hospital from January 2014 to December 2018 were selected as the study objects. According to the principle of random grouping, they were divided into the control group (50 cases, treated by metformin alone) and the observation group (50 cases, treated by aerobic exercise combined with metformin). Before and after treatment, the relevant indicators of the two groups were collected and analyzed statistically. The results showed that the total effective rate of the observation group was significantly higher than that of the control group (P

The cloud-cavitation shedding mechanism was numerically investigated around the NACA 0015 hydrofoil of α = 7° and σ = 0.7, 0.67 under the identical computational conditions as in Paper I [W. Jin, AIP Adv. 11, 065028 (2021)]. We discovered the invisible tail wing and self-inhibition effects of cloud cavitation. As the invisible tail wing of cloud cavitation swings up, the generated re-entrant jet causes cavitation shedding or collapse by the “sweeping and ejection” processes and simultaneously moves away turbulence kinetic energy (TKE) from the near-wall flow fields of the leeward hydrofoil surface, stopping the cavitation generation. In low pressure regions, non-uniform TKE intensity distributions cause different water-vapor volume fractions, resulting in discontinuity of cavitation generation. The attached vortex accompanying an individual cavity is defined, which causes fluctuations and cavitation instability on the bottom of the cavity. The cavity-bubble truncation and stretching are two primary transition mechanisms from the sheet to cloud cavitation. Compared with the invisible tail wing of cloud cavitation, the fixed unilateral wing can more effectively inhibit the cloud shedding because it can redistribute energies to two hydrofoil surfaces and transfer the strong TKE intensity from the minimum to the high-pressure region, which inhibits flow boundary layer separation and achieves non-cavitation control of the hydrofoil. Energy transfer and balance are the most effective mechanisms for inhibiting cloud cavitation. Larger unilateral wing sizes result in weaker TKE intensity along the leeward hydrofoil surface as well as more significant cloud-cavitation inhibition. The TKE intensity in the leading edge of the leeward hydrofoil surface determines the fluid boundary layer separation and cloud-cavitation stability.

Genomic imprinting is a classic epigenetic phenomenon related to the uniparental expression of genes. Imprinting variability exists in seeds and can contribute to observed parent-of-origin effects on seed development. Here, we conducted allelic expression of the embryo and endosperm from four crosses at 11 days after pollination (DAP). First, the F1 progeny of B73(♀) × Mo17(♂) and the inducer line CAU5 were used as parents to obtain reciprocal crosses of BM-C/C-BM. Additionally, the F1 progeny of Mo17(♀) × B73(♂) and CAU5 were used as parents to obtain reciprocal crosses of MB-C/C-MB. In total, 192 and 181 imprinted genes were identified in the BM-C/C-BM and MB-C/C-MB crosses, respectively. Then, by comparing the allelic expression of these imprinted genes in the reciprocal crosses of B73 and CAU5 (BC/CB), fifty-one Mo17-added non-conserved genes were identified as exhibiting imprinting variability. Fifty-one B73-added non-conserved genes were also identified by comparing the allelic expression of imprinted genes identified in BM-C/C-BM, MB-C/C-MB and MC/CM crosses. Specific Gene Ontology (GO) terms were not enriched in B73-added/Mo17-added non-conserved genes. Interestingly, the imprinting status of these genes was less conserved across other species. The cis-element distribution, tissue expression and subcellular location were similar between the B73-added/Mo17-added conserved and B73-added/Mo17-added non-conserved imprinted genes. Finally, genotypic and phenotypic analysis of one non-conserved gene showed that the mutation and overexpression of this gene may affect embryo and kernel size, which indicates that these non-conserved genes may also play an important role in kernel development. The findings of this study will be helpful for elucidating the imprinting mechanism of genes involved in maize kernel development.

Abstract Histone deacetylases (HDACs) are widely involved in many biological processes, as well as in control of brown and beige adipose physiology, but the precise molecular mechanisms by which HDACs are assembled into transcriptional machinery to fine‐tune thermogenic program remain ill‐defined. PWWP domain containing 2b (PWWP2B), which is identified as a component of the nucleosome remodeling and deacetylation complex (NuRD), interacts and stabilizes HDAC1/2 at the thermogenic gene promoters to suppress their expression. Ablation of Pwwp2b promotes adipocyte thermogenesis and ameliorates diet‐induced obesity in vivo. Intriguingly, Pwwp2b is not only a brown fat‐enriched gene but also dramatically induced by cold and sympathetic stimulation, which may serve as a physiological brake to avoid over‐activation of thermogenesis in brown and beige fat cells.

Through energy conservation and transformation perspectives, we numerically investigated the physical mechanism of cavitation generation surrounding the two-dimensional NACA 0015 hydrofoil using the mass-transfer cavitation model and modified-RNG k-epsilon model. Cavitation generation is triggered by strong turbulent kinetic energy (TKE) with pressure below the saturation pressure. However, cavitation development absorbs TKE as phase-change energy and decreases kinetic energy in near-wall flow fields, thereby increasing pressure according to the energy conservation law. The increased pressure closes the cavity and generates an attached vortex or re-entrant jet, which causes cavitation collapse, conversely decreasing the pressure to the saturation pressure in the leading edge. Simultaneously, the cavitation collapse releases phase-change energy that increases TKE to a maximum so that a new period begins. Cavitation evolution is an interaction between the vapor and liquid flow fields associated with energy conservation and transformation among TKE, pressure, and phase-change energy. Beyond 50% of the chord length, the TKE and pressure-energy in the near-wall flow fields decrease, resulting in the cavitation instability. Within the cavity, the relationship between the local TKE intensity and the volume fraction of water vapor is quantitatively defined as a linear function. Two designs are proposed for the verification of the mechanism and cavitation inhibition, namely, grooves on the hydrofoil surface and bilateral wings in the tail. Grooves do not affect TKE intensity significantly and hence cannot change the cavitating flows. Bilateral tail-wings transfer TKEs from the leading edge to the wake flows and inhibit the cavitation remarkably. The TKE distribution is the dominant mechanism for cavitation generation and stability.

Abstract Background A growing body of evidence supports the use of laparoscopic pancreaticoduodenectomy (LPD) as an efficient and feasible surgical technique. However, few studies have investigated its applicability in pancreatic ductal adenocarcinoma (PDAC), and the long-term efficacy of LPD on PDAC remains unclear. This study aimed to compare the short- and long-term outcomes between LPD and open pancreaticoduodenectomy (OPD) for PDAC. Methods The data of patients who had OPD or LPD for PDAC between January 2013 and September 2017 were retrieved. Their postoperative outcomes and survival were compared after propensity score matching. Results A total of 309 patients were included. After a 2:1 matching, 93 cases in the OPD group and 55 in the LPD group were identified. Delayed gastric emptying (DGE), particularly grade B/C DGE, occurred less frequently in the LPD group than in the OPD group (1.8% vs. 36.6%, P

Abstract Simple and consistent production of haploid is always an appealing pursuit for both crop breeders and researchers. Although diverse strategies have been developed to produce haploids over the past decades, most of them are applicable in only a limited number of plant species. In 2010, Ravi and Chan reported that haploid Arabidopsis thaliana plants can be efficiently induced through the introduction of a single genetic alteration in centromere histone H3 (CENH3). Subsequent studies demonstrated that haploids can be efficiently induced either through genetic engineering of CENH3 N-terminal tail or histone fold domain or by replacing CENH3 with an ortholog. The mutation of a pollen-specific phospholipase gene, MATRILINEAL (MTL) has been revealed to trigger the haploid induction (HI) in maize, which present another promising HI approach by the editing of MTL in plant. Here, we review the progress of the CENH3-medialed HI and propose a revised centromere-size model by suggesting a competitive loading process between wild-type and mutant CENH3 during HI. This model can explain both the findings of HI failure when wild-type and mutant CENH3 genes are coexpressed and the alien centromere loading of CENH3 in stable hybrids. In addition, we review the current understanding of MTL-mediated HI in plant. The conservation of CENH3 and MTL in plants indicates wide potential application for HI. We discuss the utility and potential of these two methods in crops by comparing their mechanisms and applications to date in plants. This review will promote the study and application of both CENH3- and MTL-mediated haploid induction in plants.

Abstract Background Clementine mandarin (Citrus clementina Hort. ex Tan.) is one of the most famous and widely grown citrus cultivars worldwide. Variations in relation to the composition and distribution of repetitive DNA sequences that dominate greatly in eukaryote genomes are considered to be species-, genome-, or even chromosome-specific. Repetitive DNA-based fluorescence in situ hybridization (FISH) is a powerful tool for molecular cytogenetic study. However, to date few studies have involved in the repetitive elements and cytogenetic karyotype of Clementine. Results A graph-based similarity sequence read clustering methodology was performed to analyze the repetitive DNA families in the Clementine genome. The bioinformatics analysis showed that repetitive DNAs constitute 41.95% of the Clementine genome, and the majority of repetitive elements are retrotransposons and satellite DNAs. Sequential multicolor FISH using a probe mix that contained CL17, four satellite DNAs, two rDNAs and an oligonucleotide of (TTTAGGG)3 was performed with Clementine somatic metaphase chromosomes. An integrated karyotype of Clementine was established based on unequivocal and reproducible chromosome discriminations. The distribution patterns of these probes in several Citrus, Poncirus and Fortunella species were summarized through extensive FISH analyses. Polymorphism and heterozygosity were commonly observed in the three genera. Some asymmetrical FISH loci in Clementine were in agreement with its hybrid origin. Conclusions The composition and abundance of repetitive elements in the Clementine genome were reanalyzed. Multicolor FISH-based karyotyping provided direct visual proof of the heterozygous nature of Clementine chromosomes with conspicuous asymmetrical FISH hybridization signals. We detected some similar and variable distribution patterns of repetitive DNAs in Citrus, Poncirus, and Fortunella, which revealed notable conservation among these genera, as well as obvious polymorphism and heterozygosity, indicating the potential utility of these repetitive element markers for the study of taxonomic, phylogenetic and evolutionary relationships in the future.

Abstract Background The anther cuticle, which is primarily composed of lipid polymers, is crucial for pollen development and plays important roles in sexual reproduction in higher plants. However, the mechanism underlying the biosynthesis of lipid polymers in maize (Zea mays. L.) remains unclear. Results Here, we report that the maize male-sterile mutant shrinking anther 1 (sa1), which is allelic to the classic mutant male sterile 33 (ms33), displays defective anther cuticle development and premature microspore degradation. We isolated MS33 via map-based cloning. MS33 encodes a putative glycerol-3-phosphate acyltransferase and is preferentially expressed in tapetal cells during anther development. Gas chromatography-mass spectrometry revealed a substantial reduction in wax and cutin in ms33 anthers compared to wild type. Accordingly, RNA-sequencing analysis showed that many genes involved in wax and cutin biosynthesis are differentially expressed in ms33 compared to wild type. Conclusions Our findings suggest that MS33 may contribute to anther cuticle and microspore development by affecting lipid polyester biosynthesis in maize.

BackgroundAdenocarcinoma of the ampulla of Vater (AAV) is standardly treated using a complex operation, a pancreatoduodenectomy (PD), to remove the tumor. However, dicision-making in AAV clinical treatment remains difficult due to the broad range of AAV types, outcomes, and responses to special chemotherapeutics. Thus, this study aimed to explore clinicopathological prognostic factors associated with overall survival, as well as post-chemotherapeutic effects related to curative resection of AAV.MethodsWe retrospectively reviewed data for clinicopathological outcome of 47 patients diagnosed with AAV that had underwent a PD. Overall survival probabilities were obtained using the Kaplan–Meier estimate method and a Cox proportional hazards model.ResultsForty-five patients underwent LPD (laparoscopic pancreatoduodenectomy) and two patients underwent PD. The patient group was composed of 31 males (66%) and 16 females (34%) with a mean age of 65(34–91)years. We selected 45 patients for long-term survival analysis. One- and three-year overall survival rates after resection were 97.6% and 58.9% respectively. The median survival was 37.7 months for the intestinal-type and 26.9 months in pancreatobiliary-type ampullary tumors. Serum carbohydrate antigen (CA) 19-9 greater than 37 U/ml (HR 0.140, P = 0.007), perineural invasion (HR 0.141, P = 0.003), and classification as pancreatobiliary-type (HR 6.633, P = 0.006) were independently associated with poor survival. Serum carcinoembryonic antigen (CEA) greater than 5 µg/ml (P = 0.031), serum CA 19-9 greater than 37 U/ml (P = 0.002), tumor sizes greater than 2.5cm (P=0.002), and positive perineural invasion (P=0.003) were all associated with a poor prognosis in the histopathological subgroup. Serum CA 19-9 greater than 37 U/ml (P=0.002) and positive perineural invasion (P=0.001) were significantly associated with poor survival in of patients with intestinal-type ampullary tumors. Serum CEA greater than 5 µg/ml (P=0.013) and tumor sizes greater than 2.5cm (P=0.002) were significantly associated with poor survival in patients with pancreatobiliary-type ampullary tumors.ConclusionsPancreatobiliary-type ampullary tumors were associated with poor survival. Serum CA 19-9 in the intestinal-type and CEA in the pancreatobiliary-type were significantly associated with poor survival. Ajuvant chemotherapy could not predict the survival of AAV patients.

One of the European gold standard measurement of vascular ageing, a risk factor for cardiovascular disease, is the carotid-femoral pulse wave velocity (cfPWV), which requires an experienced operator to measure pulse waves at two sites. In this work, two machine learning pipelines were proposed to estimate cfPWV from the peripheral pulse wave measured at a single site, the radial pressure wave measured by applanation tonometry. The study populations were the Twins UK cohort containing 3,082 subjects aged from 18 to 110 years, and a database containing 4,374 virtual subjects aged from 25 to 75 years. The first pipeline uses Gaussian process regression to estimate cfPWV from features extracted from the radial pressure wave using pulse wave analysis. The mean difference and upper and lower limits of agreement (LOA) of the estimation on the 924 hold-out test subjects from the Twins UK cohort were 0.2 m/s, and 3.75 m/s & -3.34 m/s, respectively. The second pipeline uses a recurrent neural network (RNN) to estimate cfPWV from the entire radial pressure wave. The mean difference and upper and lower LOA of the estimation on the 924 hold-out test subjects from the Twins UK cohort were 0.05 m/s, and 3.21 m/s & -3.11m/s, respectively. The percentage error of the RNN estimates on the virtual subjects increased by less than 2% when adding 20% of random noise to the pressure waveform. These results show the possibility of assessing the vascular ageing using a single peripheral pulse wave (e.g. the radial pressure wave), instead of cfPWV. The proposed code for the machine learning pipelines is available from the following online depository (https://github.com/WeiweiJin/Estimate-Cardiovascular-Risk-from-Pulse-Wave-Signal).

Objective and Motivation: Pulse wave velocity (PWV) is known to be associated with vascular ageing, a risk factor for cardiovascular disease (CVD) [1]. The European gold standard measurement of PWV requires an experienced operator to measure pulse waveforms at multiple sites, sometimes together with an electrocardiogram [2,3]. This study aims to estimate PWV from the radial pulse waveform using machine learning. Methods: Radial pulse waveforms and carotid-femoral PWVs were acquired in 3,082 unselected twins (https://twinsuk.ac.uk). 14 fiducial points on each pulse waveform were extracted using an in-house algorithm [4]. LASSO regression and principal component analysis (PCA) were used to identify the key features (timing and magnitude of the fiducial points) associated with PWV and exclude outliers. Finally, Gaussian process regression was used to estimate the PWV based on those key features only. Results: Results show that PWV can be estimated from the radial pulse waveform only with an overall root mean squared error (RMSE) of 1.82 m/s (Figure A). Most of the measured PWV values were within the 95% confidence interval range of the estimated PWV. The difference between measured and estimated PWV values increased with the increasing PWV. PWV estimation on a subgroup of twins with a healthy range of blood pressure and PWV values [5] was achieved with a RMSE of 1.38 m/s (Figure B). Conclusion: In this proof-of-concept study we have shown the possibility of estimating PWV from the radial pulse waveform using machine learning. This approach could make CVD detection more accessible to the wider population.

Vascular-targeted PDT (vPDT) has produced promising results in the treatment of many cancers, including drug-resistant ones, but little is known about its efficacy in lymphoma. Unfortunately, the lack of a specific therapeutic target and a hypoxic microenvironment for lymphoma jeopardizes the efficacy of vPDT severely. In this study, we designed a lymphoma tissue factor-targeted “O2-evolving” strategy combining PDT with catalase and HMME-encapsulated, EGFP-EGF1-modified PEG-PLGA nanoparticles (CENPs) to boost PDT efficiency; this combination takes advantage of the low oxygen tension of lymphoma. In our results, CENPs accumulated effectively in the vascular lymphoma in vivo and in vitro, and this accumulation increased further with PDT treatment. Per positron emission tomography imaging, combining CENPs with PDT inhibited lymphoma glucose metabolism significantly. The expression of hypoxia-inducible factor (HIF)-1α in the entrapped catalase groups reduced markedly. These data show that the combined administration of PDT and CENPs can prompt tissue factor-cascade-targeted and self-supply of oxygen and that it has a good therapeutic effect on malignant lymphoma.

Objective and Motivation: Endothelial dysfunction is thought to underpin atherosclerotic cardiovascular diseases. However, the widely used flow mediated dilation (FMD) in-vivotest of endothelial function relates poorly to clinical outcomes. In this study, we investigated potential confounding factors affecting the FMD test that could prevent FMD from evaluating true endothelial cell function. Methods: Haemodynamics in the larger 116 systemic arteries was simulated using one-dimensional modelling [1] coupled to an endothelial function model relating changes in wall shear stress to changes in local vascular stiffness. Haemodynamics during cuff inflation and deflation were simulated by prescribing time-varying i) transmural pressure changes in the right radial and ulnar 1-D model arterial segments, and ii) peripheral resistances in all right-hand segments. Simulated results were qualitatively tested by comparison against in-vivo data [2]. Results: Our main findings were two. Firstly, by turning off the endothelial function in the model we showed that vasoconstriction immediately after cuff deflation is entirely due to a change in transmural pressure, which offsets shear-mediated vasodilation and leads to a peak dilator response occurring after peak blood flow. Secondly, for the same endothelial function, FMD test values dropped with decreasing peripheral vasodilation, increasing arterial stiffness, and decreasing central blood pressure. Conclusion: The influence of confounding factors on FMD test results suggests that the current FMD test does not assess true endothelial cell function.

A reproductive barrier between japonica and indica rice subspecies hinders hybrid breeding. Here, the authors reveal that structural and copy number variations of a pollen-essential gene, which encodes a DUF1618-domain protein, result in allelic suppression and subsequently cause hybrid male sterility.

An abdominal aortic aneurysm (AAA) is usually asymptomatic until rupture, which is associated with extremely high mortality. Consequently, the early detection of AAAs is of paramount importance in reducing mortality; however, most AAAs are detected by medical imaging only incidentally. The aim of this study was to investigate the feasibility of machine learning-based pulse wave (PW) analysis for the early detection of AAAs using a database of in silico PWs. PWs in the large systemic arteries were simulated using one-dimensional blood flow modelling. A database of in silico PWs representative of subjects (aged 55, 65 and 75 years) with different AAA sizes was created by varying the AAA-related parameters with major impacts on PWs—identified by parameter sensitivity analysis—in an existing database of in silico PWs representative of subjects without AAAs. Then, a machine learning architecture for AAA detection was trained and tested using the new in silico PW database. The parameter sensitivity analysis revealed that the AAA maximum diameter and stiffness of the large systemic arteries were the dominant AAA-related biophysical properties considerably influencing the PWs. However, AAA detection by PW indexes was compromised by other non-AAA related cardiovascular parameters. The proposed machine learning model produced a sensitivity of 86.8 % and a specificity of 86.3 % in early detection of AAA from the photoplethysmogram PW signal measured in the digital artery with added random noise. The number of false positive and negative results increased with increasing age and decreasing AAA size, respectively. These findings suggest that machine learning-based PW analysis is a promising approach for AAA screening using PW signals acquired by wearable devices.

Plant breeders can produce haploid maize lines using haploid inducer lines as pollen donors. Here, by sequencing the genomes of single pollen nuclei, Li et al. show that haploid inducer spermatids are frequently aneuploid and suggest chromosome fragmentation as a possible cause of haploid induction.

Video synthetic aperture radar (VideoSAR) technology, which has fine resolution and high frame rate, is used to obtain the dynamic information of the observation scene. However, the height information of the target produces some additional offsets of target location in the digital elevation model under multiangle VideoSAR image sequence. This study analyses the reason for the target location displacement in VideoSAR, which includes the deduction of the mathematical relation between the location displacement and VideoSAR imaging geometry, as well as the influence of target height. Finally, the simulation results validate the theoretical analysis.

Objective and motivation: Endothelial dysfunction is associated with cardiovascular diseases. Flow mediated dilation (FMD), assesses the endothelial function by measuring the brachial artery vasodilation following deflation of a sphygmomanometer cuff around the forearm. Vasodilation is assumed to be due to an increase in wall shear stress (WSS) only. However, there is evidence that the vasodilation may be affected by other confounding factors1. We aim to investigate the effects of confounding factors on the results of FMD. Methods: A dynamic simulation of FMD was carried out using a one-dimensional haemodynamic solver of blood flow in the arm arterial vasculature (Fig. 1a) 2. Haemodynamics during cuff deflation was simulated by prescribing a decrease in peripheral resistance (Fig. 1b) in a novel mathematical model which dynamically couples increasing WSS (Fig. 1c) to decreasing arterial wall Young’s modulus (Fig. 1d), taking into account endothelial function. Results: Our results show that the initial increase in flow velocity (Fig. 1e) is caused by the prescribed decrease in peripheral resistance and leads to an initial pressure drop affecting the FMD value. WSS induces a drop in Young’s modulus leading to vasodilation (Fig. 1f). In addition, for the same prescribed endothelial function (relating WSS to Young’s modulus variation) and decreased peripheral resistance, FMD increases with decreasing arterial stiffness (3.17% vs 5.31% vs 8.56% (Fig. 1f)). ConclusionOur numerical model successfully described FMD haemodynamics and highlighted one of the important confounding factors of FMD values: arterial stiffness. We are currently investigating other factors and ways of correcting those factors.

Densest-packed structures of identical ellipses within a parallel strip have been obtained through Monte Carlo simulations and analytic derivations. Each of such structures is an affine transformation of a particular densest-packed structure of identical circular disks. Three types of structures have been identified: Types X and Y correspond, respectively, to affine stretches along the perpendicular and axial directions of the parallel strip, and type M corresponds to affine stretches of locally densest structures. Our findings enrich the field of condensed matter physics with a class of confinement-induced, orientationally ordered crystal structures, and offer possibilities of developing low-dimensional materials with specific orientational ordering.

In the subtribe Maydeae, Tripsacum and Zea are closely related genera. Tripsacum is a horticultural crop widely used as pasture forage. Previous studies suggested that Tripsacum might play an important role in maize origin and evolution. However, our understanding of the genomics and the evolution of Tripsacum remains limited. In this study, two diploids, T. dactyloides var. meridionale (2n = 36, MR) and T. dactyloides (2n = 36, DD), and one tetraploid, T. dactyloides (2n = 72, DL) were sequenced by low-coverage genome sequencing followed by graph-based cluster analysis. The results showed that 63.23%, 59.20%, and 61.57% of the respective genome of MR, DD, and DL were repetitive DNA sequence. The proportions of different repetitive sequences varied greatly among the three species. Fluorescence in situ hybridization (FISH) analysis of mitotic metaphase chromosomes with satellite repeats as the probes showed that the FISH signal patterns of DL were more similar to that of DD than to that of MR. Comparative analysis of the repeats also showed that DL shared more common repeat families with DD than with MR. Phylogenetic analysis of internal transcribed spacer region sequences further supported the evolutionary relationship among the three species. Repetitive sequences comparison showed that Tripsacum shared more repeat families with Zea than with Coix and Sorghum. Our study sheds new light on the genomics of Tripsacum and differential speciation in the Poaceae family.

The hydration of nitriles to amides in a water extract of pomelo peel ash (WEPPA) was realized with moderate to excellent yields without using external transition metals, bases or organic solvents. This reaction features a broad substrate scope, wide functional group tolerance, prominent chemoselectivity, and good reusability. Notably, a magnification experiment in this bio-based solvent at 100 mmol further demonstrated its practicability.

Nitrogen dioxide (NO2) is recognized as a toxic gaseous air pollutant. However, atmospheric NO2 can be absorbed by plant leaves and subsequently participate in plant nitrogen metabolism. The metabolism of atmospheric NO2 utilizes and consumes the light energy that leaves absorb. As such, it remains unclear whether the consumption of photosynthetic energy through nitrogen metabolism can decrease the photosynthetic capacity of plant leaves or not. In this study, we fumigated mulberry (Morus alba L.) plants with 4 μL·L−1 NO2 and analyzed the distribution of light energy absorbed by plants in NO2 metabolism using gas exchange and chlorophyll a fluorescence technology, as well as biochemical methods. NO2 fumigation enhanced the nitrogen metabolism of mulberry leaves, improved the photorespiration rate, and consumed excess light energy to protect the photosynthetic apparatus. Additionally, the excess light energy absorbed by the photosystem II reaction center in leaves of mulberry was dissipated in the form of heat dissipation. Thus, light energy was absorbed more efficiently in photosynthetic carbon assimilation in mulberry plants fumigated with 4 μL·L−1 NO2, which in turn increased the photosynthetic efficiency of mulberry leaves.

Dynamic exercise influences the cardiovascular system in various ways, and the attitude of our body also affect the hemodynamics. In this study, we adopted and integrated a double-closed-loop model consisting of the cardiovascular system (CVS), and the autonomic nervous system (ANS), along with the mathematical models of exercise and body attitude for hemodynamic prediction and cardiovascular regulation. The CVS-ANS-exercise coupling model is validated with two cases of the hemodynamic response to exercises: two different kinds of exercises (one-leg extension and one-leg cycling), and the recovery from one-leg cycling under two different attitudes (supine and standing). The results show that the transition of blood pressure varies during different exercises; the recovery from exercise is more rapid in the supine attitude. We confirmed by comparing simulation results to experimental data, that the simulation model in this study is effective. Furthermore, a simulation-based exercise model can potentially reduce the risk of performing an exercise test in clinical practice.

Etiolated seedlings initiate grana stacking and chlorophyll biosynthesis in parallel with the first exposure to light, during which phytochromes play an important role. Functional phytochromes are biosynthesized separately for two components. One phytochrome is biosynthesized for apoprotein and the other is biosynthesized for the chromophore that includes heme oxygenase (HO).We isolated a ho1 homolog by map-based cloning of a maize elongated mesocotyl2 (elm2) mutant. cDNA sequencing of the ho1 homolog in elm2 revealed a 31 bp deletion. De-etiolation responses to red and far-red light were disrupted in elm2 seedlings, with a pronounced elongation of the mesocotyl. The endogenous HO activity in the elm2 mutant decreased remarkably. Transgenic complementation further confirmed the dysfunction in the maize ho1 gene. Moreover, non-appressed thylakoids were specifically stacked at the seedling stage in the elm2 mutant.The 31 bp deletion in the ho1 gene resulted in a decrease in endogenous HO activity and disrupted the de-etiolation responses to red and far-red light. The specific stacking of non-appressed thylakoids suggested that the chlorophyll biosynthesis regulated by HO1 is achieved by coordinating the heme level with the regulation of grana stacking.

The Cucurbitaceae includes important crops such as cucumber, melon, watermelon, squash and pumpkin. However, few genetic and genomic resources are available for plant improvement. Some cucurbit species such as cucumber have a narrow genetic base, which impedes construction of saturated molecular linkage maps. We report herein the development of highly polymorphic simple sequence repeat (SSR) markers originated from whole genome shotgun sequencing and the subsequent construction of a high-density genetic linkage map. This map includes 995 SSRs in seven linkage groups which spans in total 573 cM, and defines approximately 680 recombination breakpoints with an average of 0.58 cM between two markers. These linkage groups were then assigned to seven corresponding chromosomes using fluorescent in situ hybridization (FISH). FISH assays also revealed a chromosomal inversion between Cucumis subspecies [C. sativus var. sativus L. and var. hardwickii (R.) Alef], which resulted in marker clustering on the genetic map. A quarter of the mapped markers showed relatively high polymorphism levels among 11 inbred lines of cucumber. Among the 995 markers, 49%, 26% and 22% were conserved in melon, watermelon and pumpkin, respectively. This map will facilitate whole genome sequencing, positional cloning, and molecular breeding in cucumber, and enable the integration of knowledge of gene and trait in cucurbits.