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Abstract Reversing the hypoxic microenvironment of tumors is an important method to enhance the synergistic effect of tumor treatment. In this work, we developed the nanoparticles called Ce6@HGMOF, which consists of a photosensitizer (Ce6), glucose oxidase (GOX), chemotherapy drugs (HCPT) and an iron-based metal-organic framework (MOF). Ce6@HGMOF can consume glucose in tumor cells through “starvation therapy”, cut off their nutrition source, and produce gluconic acid and hydrogen peroxide (H2O2). Utilizing this feature, Ce6@HGMOF can produce oxygen through catalase-like catalytic activity, thereby reversing the hypoxic microenvironment of tumors. This strategy of changing the hypoxic environment can help to slow down the growth of tumor blood vessels and improve the drug-resistant microenvironment to some extent. Meanwhile, increasing the supply of oxygen can enhance the effect of photodynamic therapy (PDT) and enhance the oxidative stress damage caused by reactive oxygen species (ROS) in tumor cells. On the other hand, cancer cells usually produce higher levels of glutathione (GSH) to adapt to high oxidative stress and protect themselves. The Ce6@HGMOF we designed can also consume GSH and induce ferroptosis of tumor cells through Fenton reaction with H2O2, while enhancing the effect of PDT. This innovative synergistic strategy, the combination of PDT/ferroptosis /starvation therapy, can complement each other and enhance each other. It has great potential as a powerful new anti-tumor paradigm in the future.

Abstract Background Patients with glioblastoma (GBM) have a poor prognosis and limited treatment options. The mRNA decapping enzyme scavenger (DCPS) is a cap-hydrolyzing enzyme. The DCPS inhibitor RG3039 exhibited excellent central nervous system bioavailability in vivo and was safe and well tolerated in healthy volunteers in a phase 1 clinical trial. In this study, we investigated the expression of DCPS in GBM and the anti-tumor activity of RG3039 in various preclinical models of GBM. Methods DCPS expression was examined in human GBM and paired peritumoral tissues. Its prognostic role was evaluated together with clinicopathological characteristics of patients. The anti-GBM effect of RG3039 was determined using GBM cell lines, patient-derived organoids, and orthotopic mouse models. The therapeutic mechanisms of DCPS inhibition were explored. Results DCPS is overexpressed in GBM and is associated with poor survival of patients with GBM. The DCPS inhibitor RG3039 exhibited robust anti-GBM activities in GBM cell lines, patient-derived organoids and orthotopic mouse models, with drug exposure achievable in humans. Mechanistically, RG3039 downregulated STAT5B expression, thereby suppressing proliferation, survival and colony formation of GBM cells. Conclusions DCPS is a promising target for GBM. Inhibition of DCPS with RG3039 at doses achievable in humans downregulates STAT5B expression and reduces proliferation, survival and colony formation of GBM cells. Given the excellent anti-cancer activity and central nervous system bioavailability in vivo and good tolerance in humans, RG3039 warrants further study as a potential GBM therapy.

Abstract Objective The impact of nitric oxide (NO) administered via cardiopulmonary bypass (CPB) on pediatric heart surgery remains controversial. The objective of this study is to conduct a comprehensive systematic review and meta-analysis to examine the impact of NO administered via CPB on pediatric heart surgery. Methods This study searched 7 electronic databases to identify Randomized Controlled Trials (RCTs) on the impact of NO administration during CPB on postoperative outcomes in pediatric heart surgery. The searched databases included Embase, Medline (though PubMed), Cochrane Library, Web of Science, Wan Fang database, China National Knowledge Infrastructure (CNKI), and ClinicalTrials.gov from their inception to November 2, 2022. The included RCTs compared NO administration during CPB with standard CPB procedures or placebo gas treatment in pediatric heart surgery. fixed-effects models and/or random-effects models were used to estimate the effect size with 95% confidence interval (CI). Heterogeneity among studies was indicated by p-values and I2. All analyses were performed using Review Manager software (version 5.4) in this study. Results A total of 6 RCTs including 1,739 children were identified in this study. The primary outcome was duration of postoperative mechanical ventilation, with the length of hospital and intensive care unit (ICU) stay as the second outcomes. Through a pooled analysis, we found that exogenous NO administered via CPB for pediatric heart surgery could not shorten the duration of postoperative mechanical ventilation when compared with the control group (standardized mean difference (SMD) -0.07, CI [–0.16, 0.02], I2 = 45%, P = 0.15). Additionally, there were also no difference between the two groups in terms of length of hospital stay (mean difference (MD) -0.29, CI [–1.03, 0.46], I2 = 32%, P = 0.45) and length of ICU stay (MD -0.22, CI [–0.49 to 0.05], I2 = 72%, P = 0.10). Conclusions This meta-analysis showed that exogenous NO administration via CBP had no benefits on the duration of mechanical ventilation, the length of postoperative hospital, and ICU stay after pediatric heart surgery.

This review underscores the role of natural products in inducing immunogenic cell death (ICD) as a key strategy in tumor immunotherapy. It reveals that natural products can activate ICD through multiple pathways—apoptosis, autophagy, pyroptosis, and necroptosis—leading to the release of danger-associated molecular patterns (DAMPs), dendritic cell activation, and improved antigen presentation, which together stimulate a potent anti-tumor immune response. The study also demonstrates the enhanced therapeutic potential of combining natural products with immune checkpoint inhibitors. With a focus on translating preclinical findings into clinical practice, this review consolidates recent discoveries and suggests future research paths, offering both theoretical insights and practical guidance for advancing cancer immunotherapy.

Objective: Hypertension has become a public health challenge for Yunnan children and adolescents. The study aims is to assess the dietary and activity habits associated with hypertension in Kunming children and adolescents and to develop effective strategies for preventing and controlling, Southwest China. Methods: Conducted in 2019, the cross-sectional study involved 3,150 students, aged 13.25 ± 2.77 years, multistage, stratified, randomly sampled from Chenggong and Fumin areas, Southwest China. Results: Among 3,150 participants, 6.19 % never drank milk, 3.46 % never consumed fresh fruit. 2.67 % never consumed fresh vegetables, 2.48 % never ate breakfast and 10.06 % frequently drank sugary beverages (soft drinking). Additionally, 21.56 % engaged in moderate-intensity exercise less than one Day a week, and 31.97 % performed high-intensity exercise less than one Day a week. The intraclass correlation coefficient indicated that 49.40 % of the total variance was attributed to the dietary level and 42.10 % was attributed to the activity level. Eating fresh vegetables and fruit, taking physical education classes they attended per week and the frequency of moderate-intensity and high-intensity exercise per week were independent protective factors for hypertension (P

There has been debate about whether individuals with different color phenotypes should have different taxonomic status. In order to determine whether the different color phenotypes of Nedyopus patrioticus require separate taxonomic status or are simply synonyms, here, the complete mitochondrial genomes (mitogenomes) of two different colored N. patrioticus, i.e., red N. patrioticus and white N. patrioticus, are presented. The two mitogenomes were 15,781 bp and 15,798 bp in length, respectively. Each mitogenome contained 13 PCGs, 19 tRNAs, 2 rRNAs, and 1 CR, with a lack of trnI, trnL2, and trnV compared to other Polydesmida species. All genes were located on a single strand in two mitogenomes. Mitochondrial DNA analyses revealed that red N. patrioticus and white N. patrioticus did not show clear evolutionary differences. Furthermore, no significant divergence was discovered by means of base composition analysis. As a result, we suggest that white N. patrioticus might be regarded as a synonym for red N. patrioticus. The current findings confirmed the existence of color polymorphism in N. patrioticus, which provides exciting possibilities for future research. It is necessary to apply a combination of molecular and morphological methods in the taxonomy of millipedes.

ABSTRACT4-coumaric acid coenzyme A ligase (4CL) plays an important role in plant growth, development and resistance. Based on the Musa acuminata (A genome) genome database, we performed genome-wide identification and evolutionary analysis of the 4CL gene family.The results showed that there were 20 members of 4CL, and the amino acids encoded ranged from 160 to 700, all of which were hydrophobic proteins. All the members of the 4CL gene family had no signal peptide, and phosphorylation sites ranged from 10 to 60. The 4CL genes were uniformly distributed and disordered in the chromosomes. All protein members can interact with each other.Transcriptome expression analysis showed that Ma4CL3-2 expression was down-regulated and Ma4CL11-1 expression was up-regulated. Musa acuminata genomics has 22 and 19 pairs of co-linear members with Musa balbisiana and Musa itinerans genomics, respectively.The above results provide a good foundation for further research on the function of the 4CL genes and resistance breeding.Highlights Twenty 4CL gene family members were found in banana (Musa acuminata) genomes.Banana 4CLs were expressed in response to low temperature stress.The members of the banana 4CL gene family were found to be relatively structurally diverse, and it was further hypothesised that 4CL may be involved in plant lignin synthesis and closely related to the process of plant differentiation into monocotyledons and dicotyledons, based on the hypothesis of Huang et al.

β-galactosidase (BGAL) is a glycosyl hydrolase that participates in cell wall modification, playing an essential role in plant growth, development and environmental stress adaptation. However, the function of BGALs in longan remains unclear. In this study, a total of 20 BGAL genes were identified from the longan (Dimocarpus longan Lour.) genome, which were distributed to eight chromosomes. Transcript profiles revealed that the majority of 11 detected DlBGAL genes were highly expressed in the embryogenic callus (EC) (four) and globular embryos (GE) (six), and responsive to heat stress. Combined with RNA-seq, ATAC-seq, and ChIP-seq results, most DlBGAL genes differentially expressed during early somatic embryogenesis (SE) were related with chromatin accessibility and high levels of H3K4me1. DlBGAL9 was selected for further analysis. Dual-luciferase assays and transient transformation indicated that the transcription factor (TF) DlAGL61 and DlAGL80 might bind to the DlBGAL9 promoters to activate DlBGAL9 transcription. Overexpression of DlBGAL9 and TF DlAGL80 induces longan hairy roots β-GAL activity and thickening of cell walls. The expression levels of DlBGAL9 and TF DlAGL80 in longan hairy roots were significantly increased under heat stress, and ROS scavengers related genes were significantly upregulated in overexpressing DlBGAL9 and TF DlAGL80 hairy roots. This study proposes the significance of the regulatory network composed of DlBGAL9 and TF DlAGL80 in regulating the early longan SE and heat stress response.

With the deepening of people’s understanding of lung cancer, the research of lung cancer immunotherapy has gradually become the focus of attention. As we all know, the treatment of many diseases relies on the rich sources, complex and varied compositions and wide range of unique biological properties of natural products. Studies have shown that natural products can exert anticancer effects by inducing tumor cell death, inhibiting tumor cell proliferation, and enhancing tumor cell autophagy. More notably, natural products can adjust and strengthen the body’s immune response, which includes enhancing the function of NK cells and promoting the differentiation and proliferation of T lymphocytes. In addition, these natural products may enhance their anticancer effects by affecting inhibitory factors in the immune system, hormone levels, enzymes involved in biotransformation, and modulating other factors in the tumor microenvironment. The importance of natural products in lung cancer immunotherapy should not be underestimated. However, the specific links and correlations between natural products and lung cancer immunity are not clear enough, and further studies are urgently needed to clarify the relationship between the two. In this paper, we will focus on the correlation between natural products and lung cancer immune responses, with a view to providing new research perspectives for immunotherapy of lung cancer.

Abstract Longan (Dimocarpus longan Lour.) is an economically important subtropical fruit tree. Its fruit quality and yield are affected by embryo development. As a plant seed germination marker gene, the germin-like protein (GLP) gene plays an important role in embryo development. However, the mechanism underlying the role of the GLP gene in somatic embryos is still unclear. Therefore, we conducted genome-wide identification of the longan GLP (DlGLP) gene and preliminarily verified the function of DlGLP1-5–1. Thirty-five genes were identified as longan GLP genes and divided into 8 subfamilies. Based on transcriptome data and qRT‒PCR results, DlGLP genes exhibited the highest expression levels in the root, and the expression of most DlGLPs was upregulated during the early somatic embryogenesis (SE) in longan and responded to high temperature stress and 2,4-D treatment; eight DlGLP genes were upregulated under MeJA treatment, and four of them were downregulated under ABA treatment. Subcellular localization showed that DlGLP5-8–2 and DlGLP1-5–1 were located in the cytoplasm and extracellular stroma/chloroplast, respectively. Overexpression of DIGLP1-5–1 in the globular embryos (GEs) of longan promoted the accumulation of lignin and decreased the H2O2 content by regulating the activities of ROS-related enzymes. The results provide a reference for the functional analysis of DlGLPs and related research on improving lignin accumulation in the agricultural industry through genetic engineering.

Polygonatum cyrtonema Hua (P. cyrtonema) rhizomes are rich in flavonoids and other secondary metabolites, exhibiting remarkable antioxidant, anti-tumor, and immunomodulatory effects. Polygonatum flavonoid-biosynthesis-related genes have been characterized already. However, a comprehensive overview of Polygonatum flavonoid biosynthesis pathways is still absent. To articulate the accumulation of the flavonoid biosynthesis pathways, we examined transcriptome changes using Illumina HiSeq from five different tissues and the RNA-seq of 15 samples had over 105 Gb of a clean base, generating a total of 277,955 unigenes. The cDNA libraries of the fruits (F), leaves (L), roots (R), stems (S), and rhizomes (T) of three-year-old P. cyrtonema plants generated 57,591, 53,578, 60,321, 51,530, and 54,935 unigenes. Comparative transcriptome analysis revealed that 379 differentially expressed genes (DEGs) were in the group of F _vs_ T, L _vs_ T, R _vs_ T, and S _vs_ T, and the transcripts of flavonoid-biosynthesis-related DEGs were principally enriched in rhizomes. In addition, combined with WGCNA and the FPKM of five tissues’ transcription, nine differentially expressed transcription factor families (MYB, WRKY, AP2/ERF, etc.) were characterized in the red module, the red module positively correlated with rhizome flavonoid accumulation. Quantitative real-time PCR (qRT-PCR) further indicated that BZIP1, C3H31, ERF114, and DREB21 are differentially expressed in rhizomes, accompanied in rhizome development in P. cyrtonema. Therefore, this study provides a foundation for further research into uncovering the accumulation of flavonoid biosynthesis in the rhizomes of P. cyrtonema.

Benzoxazinoids (BXs) are tryptophan-derived indole metabolites and play a role in various physiological processes, such as auxin metabolism. Auxin is essential in the process of somatic embryogenesis (SE) in plants. In this study, we used bioinformatics, transcriptome data, exogenous treatment experiments, and qPCR analysis to study the evolutionary pattern of Bx genes in green plants, the regulatory mechanism of DlBx genes during early SE, and the effect of 2,4-dihydroxy-7-methoxy-1,4-benzoxazine-3-one (DIMBOA) on the early SE in Dimocarpus longan Lour. The results showed that 27 putative DlBxs were identified in the longan genome; the Bx genes evolved independently in monocots and dicots, and the main way of gene duplication for the DlBx was tandem duplication (TD) and the DlBx were strongly constrained by purification selection during evolution. The transcriptome data indicated varying expression levels of DlBx during longan early SE, and most DlBxs responded to light, temperature, drought stress, and 2,4-dichlorophenoxyacetic acid (2,4-D) treatment; qRT-PCR results showed DlBx1, DlBx6g and DlBx6h were responsive to auxin, and treatment with 0.1mg/L DIMBOA for 9 days significantly upregulated the expression levels of DlBx1, DlBx3g, DlBx6c, DlBx6f, DlB6h, DlBx7d, DlBx8, and DlBx9b. The correlation analysis showed a significantly negative correlation between the expression level of DlBx1 and the endogenous IAA contents; DIMBOA significantly promoted the early SE and significantly changed the endogenous IAA content, and the IAA content increased significantly at the 9th day and decreased significantly at the 13th day. Therefore, the results suggested that DIMBOA indirectly promote the early SE by changing the endogenous IAA content via affecting the expression level of DlBx1 and hydrogen peroxide (H2O2) content in longan.

Dendrobium officinale Kimura et Migo (D. officinale) is one of the most important traditional Chinese medicinal herbs, celebrated for its abundant bioactive ingredients. This study demonstrated that the diurnal temperature difference (DIF) (T1: 13/13 °C, T2: 25/13 °C, and T3: 25/25 °C) was more favorable for high chlorophyll, increased polysaccharide, and total flavonoid contents compared to constant temperature treatments in D. officinale PLBs. The transcriptome analysis revealed 4251, 4404, and 4536 differentially expressed genes (DEGs) in three different comparisons (A: 25/13 °C vs. 13/13 °C, B: 13/13 °C vs. 25/25 °C, and C: 25/13 °C vs. 25/25 °C, respectively). The corresponding up-/down-regulated DEGs were 1562/2689, 2825/1579, and 2310/2226, respectively. GO and KEGG enrichment analyses of DEGs showed that the pathways of biosynthesis of secondary metabolites, carotenoid biosynthesis, and flavonoid biosynthesis were enriched in the top 20; further analysis of the sugar- and flavonol-metabolism pathways in D. officinale PLBs revealed that the DIF led to a differential gene expression in the enzymes linked to sugar metabolism, as well as to flavonol metabolism. Certain key metabolic genes related to ingredient accumulation were identified, including those involved in polysaccharide metabolism (SUS, SUT, HKL1, HGL, AMY1, and SS3) and flavonol (UGT73C and UGT73D) metabolism. Therefore, these findings indicated that these genes may play an important role in the regulatory network of the DIF in the functional metabolites of D. officinale PLBs. In a MapMan annotation of abiotic stress pathways, the DEGs with significant changes in their expression levels were mainly concentrated in the heat-stress pathways, including heat-shock proteins (HSPs) and heat-shock transcription factors (HSFs). In particular, the expression levels of HSP18.2, HSP70, and HSF1 were significantly increased under DIF treatment, which suggested that HSF1, HSP70 and HSP18.2 may respond to the DIF. In addition, they can be used as candidate genes to study the effect of the DIF on the PLBs of D. officinale. The results of our qPCR analysis are consistent with those of the transcriptome-expression analysis, indicating the reliability of the sequencing. The results of this study revealed the transcriptome mechanism of the DIF on the accumulation of the functional metabolic components of D. officinale. Furthermore, they also provide an important theoretical basis for improving the quality of D. officinale via the DIF in production.

IntroductionCultivated banana are polyploid, with low pollen fertility, and most cultivars are male sterile, which leads to difficulties in banana breeding research. The selection of male parent with excellent resistance and pollen fertility is therefore essential for banana breeding. Wild banana (Musa itinerans) have developed many good characteristics during natural selection and constitute an excellent gene pool for breeding. Therefore, research on wild banana breeding is very important for banana breeding.ResultsIn the current analysis, we examined the changes in viability of wild banana pollens at different temperatures by in vitro germination, and found that the germination ability of wild banana pollens cultured at 28°C for 2 days was higher than that of pollens cultured at 23°C (pollens that could not germinate normally under low temperature stress), 24°C (cultured at a constant temperature for 2 days) and 32°C (cultured at a constant temperature for 2 days). To elucidate the molecular mechanisms underlying the germination restoration process in wild banana pollens, we selected the wild banana pollens that had lost its germination ability under low temperature stress (23°C) as the control group (CK) and the wild banana pollens that had recovered its germination ability under constant temperature incubation of 28°C for 2 days as the treatment group (T) for transcriptome sequencing. A total of 921 differentially expressed genes (DEGs) were detected in CK vs T, of which 265 were up-regulated and 656 were down-regulated. The combined analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that the activation, metabolism of various substances (lipids, sugars, amino acids) play a major role in restoring pollen germination capacity. TCA cycle and the sesquiterpenoid and triterpenoid biosynthetic pathways were also significantly enriched in the KEGG pathway. And we found that some DEGs may be associated with pollen wall formation, DNA methylation and DNA repair. The cysteine content, free fatty acid (FFA) content, H2O2 content, fructose content, and sucrose content of pollen were increased at treatment of 28°C, while D-Golactose content was decreased. Finally, the GO pathway was enriched for a total of 24 DEGs related to pollen germination, of which 16 DEGs received targeted regulation by 14 MYBs.DiscussionsOur study suggests that the balance between various metabolic processes, pollen wall remodelling, DNA methylation, DNA repairs and regulation of MYBs are essential for germination of wild banana pollens.

IntroductionNF-YB transcription factor is an important regulatory factor in plant embryonic development.ResultsIn this study, 15 longan NF-YB (DlNF-YB) family genes were systematically identified in the whole genome of longan, and a comprehensive bioinformatics analysis of DlNF-YB family was performed. Comparative transcriptome analysis of DlNF-YBs expression in different tissues, early somatic embryogenesis (SE), and under different light and temperature treatments revealed its specific expression profiles and potential biological functions in longan SE. The qRT-PCR results implied that the expression patterns of DlNF-YBs were different during SE and the zygotic embryo development of longan. Supplementary 2,4-D, NPA, and PP333 in longan EC notably inhibited the expression of DlNF-YBs; ABA, IAA, and GA3 suppressed the expressions of DlNF-YB6 and DlNF-YB9, but IAA and GA3 induced the other DlNF-YBs. Subcellular localization indicated that DlNF-YB6 and DlNF-YB9 were located in the nucleus. Furthermore, verification by the modified 5'RNA Ligase Mediated Rapid Amplification of cDNA Ends (5' RLM-RACE) method demonstrated that DlNF-YB6 was targeted by dlo-miR2118e, and dlo-miR2118e regulated longan somatic embryogenesis (SE) by targeting DlNF-YB6. Compared with CaMV35S- actuated GUS expression, DlNF-YB6 and DlNF-YB9 promoters significantly drove GUS expression. Meanwhile, promoter activities were induced to the highest by GA3 but suppressed by IAA. ABA induced the activities of the promoter of DlNF-YB9, whereas it inhibited the promoter of DlNF-YB6.DiscussionHence, DlNF-YB might play a prominent role in longan somatic and zygotic embryo development, and it is involved in complex plant hormones signaling pathways.

Accidents caused by operators failing to wear safety gloves are a frequent problem at electric power operation sites, and the inefficiency of manual supervision and the lack of effective supervision methods result in frequent electricity safety accidents. To address the issue of low accuracy in glove detection with small-scale glove datasets. This article proposes a real-time glove detection algorithm using video surveillance to address these issues. The approach employs transfer learning and an attention mechanism to enhance detection average precision. The key ideas of our algorithm are as follows: (1) introducing the Combine Attention Partial Network (CAPN) based on convolutional neural networks, which can accurately recognize whether gloves are being worn, (2) combining channel attention and spatial attention modules to improve CAPN’s ability to extract deeper feature information and recognition accuracy, and (3) using transfer learning to transfer human hand features in different states to gloves to enhance the small sample dataset of gloves. Experimental results show that the proposed network structure achieves high performance in terms of detection average precision. The average precision of glove detection reached 96.59%, demonstrating the efficacy of CAPN.

Efficient metabolic regulation is key for parasite growth. Here, the authors report that Toxoplasma alters its AMPK phosphorylation during the lytic cycle, which reprograms parasite’s metabolism to ensure metabolic needs at different stages are met.

IntroductionGRAS, named after GAI, RGA, and SCR, is a class of plant-specific transcription factors family that plays a crucial role in growth and development, signal transduction, and various stress responses.MethodsTo understand the biological functions of the banana GRAS gene family, a genome-wide identification and bioinformatics analysis of the banana GRAS gene family was performed based on information from the M. acuminata, M. balbisiana, and M. itinerans genomic databases.ResultIn the present study, we identified 73 MaGRAS, 59 MbGRAS, and 58 MiGRAS genes in bananas at the whole-genome scale, and 56 homologous genes were identified in the three banana genomes. Banana GRASs can be classified into 10 subfamilies, and their gene structures revealed that most banana GRAS gDNAs lack introns. The promoter sequences of GRASs had a large number of cis-acting elements related to plant growth and development, phytohormone, and adversity stress responsiveness. The expression pattern of seven key members of MaGRAS response to low-temperature stress and different tissues was also examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The microRNAs-MaGRASs target prediction showed perfect complementarity of seven GRAS genes with the five mac-miRNAs. The expression of all seven genes was lowest in roots, and the expression of five genes was highest in leaves during low-temperature stress. The expression of MaSCL27-2, MaSCL27-3, and MaSCL6-1 was significantly lower under low-temperature stress compared to the control, except for MaSCL27-2, which was slightly higher than the 28°C control at 4 h. The expression of MaSCL27-2, MaSCL27-3, and MaSCL6-1 dropped to the lowest levels at 24 h, 12 h, and 4 h, respectively. The MaSCL27-4 and MaSCL6-2 expression was intermittently upregulated, rising to the highest expression at 24h, while the expression of MaSCL22 was less variable, remaining at the control level with small changes.DiscussionIn summary, it is tentatively hypothesized that the GRAS family has an important function in low-temperature stress in bananas. This study provides a theoretical basis for further analyzing the function of the banana GRAS gene and the resistance of bananas to cold temperatures.

Purpose: Evaluation of the variabilities in apparent diffusion coefficient (ADC) measurements of the spleen (ADCspleen) and the paraspinal muscles (ADCmuscle) to identify the reference organ for normalizing the ADC from the abdominal diffusion weighted imaging (DWI). Methods: Two MRI scanners, with 314 abdominal exams on the GE and 929 on the Siemens system, were used for MRI examinations including DWI (b-values, 50 and 800 s/mm2). For a subset of 73 exams on the Siemens system a second exam was conducted. Four regions of interest (ROIs) in each exam were placed to measure the ADCspleen and the bilateral ADCmuscle. ADC variability between patients (on each scanner separately), ADC variability due to ROI placement between the two ROIs in each organ, and variability in the subset between the first and second exams were assessed. Results: The ADCspleen was more scattered and variable than the ADCmuscle in the comparability (n = 929 and 314 for two MRI scanners, respectively) and repeatability (n = 73) datasets. The Bland-Altmann bias and limits of agreement (LoAs) for the ADCspleen (ICC, 0.47; CV, 0.070) and ADCmuscle (ICC, 0.67; CV, 0.023) in the repeatability datasets (n = 73) were −0.1 (−25.7%–25.6%) and −0.3 (−8.8%–8.1%), respectively. For the Siemens system, the Bland-Altmann bias and LoAs for the ADCspleen (ICC, 0.72; CV, 0.061) and ADCmuscle (ICC, 0.53; CV, 0.030) in the comparability datasets (n = 929) were 2.1 (−20.0%–24.2%) and 0.7 (−10.0%–11.4%), respectively. Similar findings have been found in the GE system (n = 314). The CVs for the ADCmuscle measurements were lower than those of the ADCspleen both in the repeatability and the comparability analyses (all p

Primary liver cancer (PLC) is one type of cancer with high incidence rate and high mortality rate in the worldwide. Systemic therapy is the major treatment for PLC, including surgical resection, immunotherapy and targeted therapy. However, mainly due to the heterogeneity of tumors, responses to the above drug therapy differ from person to person, indicating the urgent needs for personalized treatment for PLC. Organoids are 3D models derived from adult liver tissues or pluripotent stem cells. Based on the ability to recapitulate the genetic and functional features of in vivo tissues, organoids have assisted biomedical research to make tremendous progress in understanding disease origin, progression and treatment strategies since their invention and application. In liver cancer research, liver organoids contribute greatly to reflecting the heterogeneity of liver cancer and restoring tumor microenvironment (TME) by co-organizing tumor vasculature and stromal components in vitro. Therefore, they provide a promising platform for further investigation into the biology of liver cancer, drug screening and precision medicine for PLC. In this review, we discuss the recent advances of liver organoids in liver cancer, in terms of generation methods, application in precision medicine and TME modeling.

Articular cartilage, composed of collagen type II as a major extracellular matrix and chondrocyte as a unique cell type, is a specialized connective tissue without blood vessels, lymphatic vessels and nerves. This distinctive characteristic of articular cartilage determines its very limited ability to repair when damaged. It is well known that physical microenvironmental signals regulate many cell behaviors such as cell morphology, adhesion, proliferation and cell communication even determine chondrocyte fate. Interestingly, with increasing age or progression of joint diseases such as osteoarthritis (OA), the major collagen fibrils in the extracellular matrix of articular cartilage become larger in diameter, leading to stiffening of articular tissue and reducing its resistance to external tension, which in turn aggravates joint damage or progression of joint diseases. Therefore, designing a physical microenvironment closer to the real tissue and thus obtaining data closer to the real cellular behaviour, and then revealing the biological mechanisms of chondrocytes in pathological states is of crucial importance for the treatment of OA disease. Here we fabricated micropillar substrates with the same topology but different stiffnesses to mimic the matrix stiffening that occurs in the transition from normal to diseased cartilage. It was first found that chondrocytes responded to stiffened micropillar substrates by showing a larger cell spreading area, a stronger enhancement of cytoskeleton rearrangement and more stability of focal adhesion plaques. The activation of Erk/MAPK signalling in chondrocytes was detected in response to the stiffened micropillar substrate. Interestingly, a larger nuclear spreading area of chondrocytes at the interface layer between the cells and top surfaces of micropillars was observed in response to the stiffened micropillar substrate. Finally, it was found that the stiffened micropillar substrate promoted chondrocyte hypertrophy. Taken together, these results revealed the cell responses of chondrocytes in terms of cell morphology, cytoskeleton, focal adhesion, nuclei and cell hypertrophy, and may be beneficial for understanding the cellular functional changes affected by the matrix stiffening that occurs during the transition from a normal state to a state of osteoarthritis.

The basic leucine zip (bZIP) transcription factors (TFs) are a group of highly conserved gene families that play important roles in plant growth and resistance to adversity stress. However, studies on hormonal regulatory pathways and functional analysis during somatic embryogenesis (SE) in Dimocarpus longan is still unavailable. In this study, a total of 51 bZIP family members were systematically identified in the whole genome of longan, a comprehensive bioinformatics analysis of DlbZIP (bZIP family members of D. longan) was performed, and subcellular localization and profiles patterns after transiently transformed DlbZIP60 were analyzed. The combined analysis of RNA-seq, ATAC-seq and ChIP-seq showed that four members have different H3K4me1 binding peaks in early SE and differentially expressed with increased chromatin accessibility. Comparative transcriptome analysis of bZIPs expression in early SE, different tissues and under 2,4-D treatment revealed that DlbZIP family might involved in growth and development during longan early SE. The qRT-PCR results implied that DlbZIP family were subjected to multiple hormonal responses and showed different degrees of up-regulated expression under indole-3-acetic acid (IAA), abscisic acid (ABA) and methyl jasmonate (MeJA) treatments, which indicated that they played an important role in the hormone synthesis pathways associated with the early SE of longan. Subcellular localization showed that DlbZIP60 was located in the nucleus, and the contents of endogenous IAA, MeJA and ABA were up-regulated in transiently DlbZIP60 overexpressed cell lines. These results suggest that DlbZIP60 may mediate hormones pathways that functions the development during early SE in longan.

Ran GTPases play essential roles in plant growth and development. Our previous studies revealed the nuclear localization of DlRan3A and DlRan3B proteins and proposed their functional redundancy and distinction in Dimocarpus longan somatic embryogenesis, hormone, and abiotic stress responses. To further explore the possible roles of DlRan3A and DlRan3B, gene expression analysis by qPCR showed that their transcripts were both more abundant in the early embryo and pulp in longan. Heterologous expression of DlRan3A driven by its own previously cloned promoter led to stunted growth, increased root hair density, abnormal fruits, bigger seeds, and enhanced abiotic stress tolerance. Conversely, constitutive promoter CaMV 35S (35S)-driven expression of DlRan3A, 35S, or DlRan3B promoter-controlled expression of DlRan3B did not induce the alterations in growth phenotype, while they rendered different hypersensitivities to abiotic stresses. Based on the transcriptome profiling of longan Ran overexpression in tobacco plants, we propose new mechanisms of the Ran-mediated regulation of genes associated with cell wall biosynthesis and expansion. Also, the transgenic plants expressing DlRan3A or DlRan3B genes controlled by 35S or by their own promoter all exhibited altered mRNA levels of stress-related and transcription factor genes. Moreover, DlRan3A overexpressors were more tolerant to salinity, osmotic, and heat stresses, accompanied by upregulation of oxidation-related genes, possibly involving the Ran-RBOH-CIPK network. Analysis of a subset of selected genes from the Ran transcriptome identified possible cold stress-related roles of brassinosteroid (BR)-responsive genes. The marked presence of genes related to cell wall biosynthesis and expansion, hormone, and defense responses highlighted their close regulatory association with Ran.

Dwarfing is one of the common phenotypic variations in asexually reproduced progeny of banana, and dwarfed banana is not only windproof and anti-fallout but also effective in increasing acreage yield. As a key gene in the strigolactone signalling pathway, DWARF53 (D53) plays an important role in the regulation of the height of plants. In order to gain insight into the function of the banana D53 gene, this study conducted genome-wide identification of banana D53 gene based on the M. acuminata, M. balbisiana and M. itinerans genome database. Analysis of MaD53 gene expression under high temperature, low temperature and osmotic stress based on transcriptome data and RT-qPCR was used to analyse MaD53 gene expression in different tissues as well as in different concentrations of GA and SL treatments. In this study, we identified three MaD53, three MbD53 and two MiD53 genes in banana. Phylogenetic tree analysis showed that D53 Musa are equally related to D53 Asparagales and Poales. Both high and low-temperature stresses substantially reduced the expression of the MaD53 gene, but osmotic stress treatments had less effect on the expression of the MaD53 gene. GR24 treatment did not significantly promote the height of the banana, but the expression of the MaD53 gene was significantly reduced in roots and leaves. GA treatment at 100 mg/L significantly promoted the expression of the MaD53 gene in roots, but the expression of this gene was significantly reduced in leaves. In this study, we concluded that MaD53 responds to GA and SL treatments, but “Yinniaijiao” dwarf banana may not be sensitive to GA and SL.

Three-dimensional cell culture technology (3DCC) sits between two-dimensional cell culture (2DCC) and animal models and is widely used in oncology research. Compared to 2DCC, 3DCC allows cells to grow in a three-dimensional space, better simulating the in vivo growth environment of tumors, including hypoxia, nutrient concentration gradients, micro angiogenesis mimicism, and the interaction between tumor cells and the tumor microenvironment matrix. 3DCC has unparalleled advantages when compared to animal models, being more controllable, operable, and convenient. This review summarizes the comparison between 2DCC and 3DCC, as well as recent advances in different methods to obtain 3D models and their respective advantages and disadvantages.

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is critical in cancer immunity. Autophagy is a highly conserved process that is responsible for the degradation of cytoplasmic material and is involved in both innate and adaptive immunity. Recently, cGAS-STING and autophagy have been shown to be interconnected, which may influence the progression of cancer. Although cGAS-STING and autophagy have been shown to be interrelated in innate immunity, little has been reported about cancer immunity. As cancer immunity is key to treating tumors, it is essential to summarize the relationship and interactions between the two. Based on this, we systematically sorted out the recent findings of cGAS-STING and autophagy in cancer immunity and explored the interactions between cGAS-STING and autophagy, although these interactions have not been extensively studied. Lastly, we provide an outlook on how cGAS-STING and autophagy can be combined, with the hope that our research can help people better understand their potential roles in cancer immunity and bring light to the treatment of cancer.

Abstract According to the EPOC study, chemotherapy could improve 5-year disease-free survival of stage IV colon cancer patients by 8.1%. However, more molecular biomarkers are required to identify patients who need neoadjuvant chemotherapy. DENND2D expression was evaluated by immunohistochemistry in 181 stage IV colon cancer patients. The prognosis was better for patients with DENND2D expression than patients without DENND2D expression (5-year overall survival [OS]: 42% vs. 12%, p = 0.038; 5-year disease-free survival: 20% vs. 10%, p = 0.001). Subgroup analysis of the DENND2D-negative group showed that patients treated with neoadjuvant chemotherapy achieved longer OS than patients without neoadjuvant chemotherapy (RR = 0.179; 95% CI = 0.054–0.598; p = 0.003). DENND2D suppressed CRC proliferation in vitro and in vivo. Downregulation of DENND2D also promoted metastasis to distant organs in vivo. Mechanistically, DENND2D suppressed the MAPK pathway in CRC. Colon cancer patients who were DENND2D negative always showed a worse prognosis and were more likely to benefit from neoadjuvant chemotherapy. DENND2D may be a new prognostic factor and a predictor of the need for neoadjuvant chemotherapy in stage IV colon cancer.

Abstract Genu recurvatum in stroke patients with hemiplegia causes readily cumulative damage and degenerative changes in the knee cartilage. It is important to detect early cartilage lesions for appropriate treatment and rehabilitation. The purpose of this cross-sectional study was to provide a theoretical basis for the early rehabilitation of hemiplegia patients. We used a zero TE double-echo imaging sequence to analyse the water content in knee joint cartilage at 12 different sites of 39 stroke patients with genu recurvatum and 9 healthy volunteers using a metric similar to the porosity index. When comparing the hemiplegic limb vs. the nonhemiplegic limb in patients, the ratios of the deep/shallow free water content of the femur cartilages at the anterior horn (1.16 vs. 1.06) and posterior horn (1.13 vs. 1.25) of the lateral meniscus were significantly different. Genu recurvatum in stroke patients with hemiplegia can cause changes in the moisture content of knee cartilage, and the changes in knee cartilage are more obvious as the genu recurvatum increases. The "healthy limb" can no longer be considered truly healthy and should be considered simultaneously with the affected limb in the development of a rehabilitation treatment plan.

In this paper, the conglomerate reservoir is selected as the object to investigate the micropore structure and the compatibility of polymer solutions. Firstly, the characteristics of complex mode pore structure are analyzed based on casting thin sections, scanning electron microscope, and capillary pressure curve. Then the conglomerate reservoir is divided into five types by use of the K-means clustering algorithm, and the differences in micropore structure among the different reservoir types are also clarified. Secondly, the dynamic light scattering technology is used to directly determine the hydrodynamic diameter of different polymer formulations. As the polymer molecular weight increases, the average hydrodynamic diameter becomes larger, and with the same polymer molecular weight, the average hydrodynamic diameter becomes gradually larger as the solution concentration increases. Based on the above research results, the matching relationship between five reservoir types and polymer solutions is determined through laboratory experiments. The experimental results show that when the polymer molecular weight is determined, the volume of pore volume that can be effectively swept by polymer hydration molecules gradually decreases as the concentration of the solution increases. When the polymer molecular weight and its concentration are both determined, the pore volume of effective displacement of polymer-hydrated molecules also gradually reduces with becoming worse reservoir pore structure. The scope of application of different polymer formulations becomes progressively smaller as the microscopic pore structure of type I to type V reservoirs becomes deteriorated. The compatibility between the micropore structure of different conglomerate reservoir types and polymer solution is determined to provide the geological basis for the reasonable formulation of the polymer flooding scheme.

PurposeTo evaluate the diagnostic performance of radiomics model based on fully automatic segmentation of pancreatic tumors from non-enhanced magnetic resonance imaging (MRI) for differentiating pancreatic adenosquamous carcinoma (PASC) from pancreatic ductal adenocarcinoma (PDAC).Materials and methodsIn this retrospective study, patients with surgically resected histopathologically confirmed PASC and PDAC who underwent MRI scans between January 2011 and December 2020 were included in the study. Multivariable logistic regression analysis was conducted to develop a clinical and radiomics model based on non-enhanced T1-weighted and T2-weighted images. The model performances were determined based on their discrimination and clinical utility. Kaplan-Meier and log-rank tests were used for survival analysis.ResultsA total of 510 consecutive patients including 387 patients (age: 61 ± 9 years; range: 28–86 years; 250 males) with PDAC and 123 patients (age: 62 ± 10 years; range: 36–84 years; 78 males) with PASC were included in the study. All patients were split into training (n=382) and validation (n=128) sets according to time. The radiomics model showed good discrimination in the validation (AUC, 0.87) set and outperformed the MRI model (validation set AUC, 0.80) and the ring-enhancement (validation set AUC, 0.74).ConclusionsThe radiomics model based on non-enhanced MRI outperformed the MRI model and ring-enhancement to differentiate PASC from PDAC; it can, thus, provide important information for decision-making towards precise management and treatment of PASC.

PurposeThis paper conducts sentiment analysis on the evaluation discourse of business English translation based on language big data mining of public health environment, and aims to find a reasonable algorithm to conduct detailed research on all aspects of sentiment analysis.MethodologyThis paper focuses on three areas of sentiment information, extraction, sentiment information retrieval, and sentiment information submission, using scale analysis and feedback analysis, combined with related algorithms of big data mining technology, such as decision trees and clustering algorithms, through the level of emotional words appearing in the corpus, phrase-level, text-level, etc., and combine the text model with the combined reliability to output the evaluation object and evaluation feature separately, and propose an evaluation method to calculate the sensitivity of the evaluation feature, so as to accurately improve the sensitivity of the evaluation feature. It is mainly divided into two categories for data analysis. One is to focus on the public health environment of the characteristics of business English translation itself, and the other is to conduct research on the application of big data mining in the evaluation of translation discourse.Research findingsThe research data show that the smallest gap between the sentiment orientation of the discourse evaluation perspective is the output of the language discourse, and the smallest gap in the attributes of the evaluation object is at the phrase level, and the gap value is 3.5; for the evaluation object, the maximum difference is 3.4.Research implicationsWith the development of science and technology and the economy, the public health environment has become more and more complex, and business English translation has received more and more attention. The sentiment analysis of evaluation discourse in this field is a means of expressing language characteristics. In order to enrich research in this field, the study of this article is necessary.Practical implicationsThis study has a deeper understanding of the affective analysis of evaluation discourse in public health environment business English translation. The clustering algorithm of big data mining technology applied can provide an important guarantee for the actual conclusion of this research and quantitative analysis of the positive evaluation and criticism of evaluation. To solve the various problems encountered in translation, so as to improve the translator's own translation level, and promote the research of translation methods in Chinese translation.

Mitogen-activated protein kinases (MAPKs and MPKs) are important in the process of resisting plant stress. In this study, 21, 12, 18, 16, and 10 MPKs were identified from Musa acuminata, Musa balbisiana, Musa itinerans, Musa schizocarpa, and Musa textilis, respectively. These MPKs were divided into Group A, B, C, and D. Phylogenetic analysis revealed that this difference in number was due to the gene shrinkage of the Group B subfamily of Musa balbisiana and Musa textilis. KEGG annotations revealed that K14512, which is involved in plant hormone signal transduction and the plant–pathogen interaction, was the most conserved pathway of the MPKs. The results of promoter cis-acting element prediction and focTR4 (Fusarium oxysporum f. sp. cubense tropical race 4) transcriptome expression analysis preliminarily confirmed that MPKs were relevant to plant hormone and biotic stress, respectively. The expression of MPKs in Group A was significantly upregulated at 4 °C, and dramatically, the MPKs in the root were affected by low temperature. miR172, miR319, miR395, miR398, and miR399 may be the miRNAs that regulate MPKs during low-temperature stress, with miR172 being the most critical. miRNA prediction and qRT-PCR results indicated that miR172 may negatively regulate MPKs. Therefore, we deduced that MPKs might coordinate with miR172 to participate in the process of the resistance to low-temperature stress in the roots of the banana. This study will provide a theoretical basis for further analysis of the mechanism of MPKs under low-temperature stress of bananas, and this study could be applied to molecular breeding of bananas in the future.

Glyoxal and methylglyoxal are important volatile organic compounds in the atmosphere. The gas–particle partitioning of these carbonyl compounds makes significant contributions to O3 formation. In this study, both the gas- and particle-phase glyoxal and methylglyoxal concentrations at the foot and top of Mount Hua were determined simultaneously. The results showed that the gaseous-phase glyoxal and methylglyoxal concentrations at the top were higher than those at the foot of the mountain. However, the concentrations for the particle phase showed the opposite trend. The average theoretical values of the gas–particle partitioning coefficients of the glyoxal and methylglyoxal concentrations (4.57 × 10−10 and 9.63 × 10−10 m3 μg−1, respectively) were lower than the observed values (3.79 × 10−3 and 6.79 × 10−3 m3 μg−1, respectively). The effective Henry’s law constants (eff.KH) of the glyoxal and methylglyoxal were in the order of 108 to 109 mol/kgH2O/atm, and they were lower at the foot than they were at the top. The particle/gas ratios (P/G ratios) of the glyoxal and methylglyoxal were 0.039 and 0.055, respectively, indicating more glyoxal and methylglyoxal existed in the gas phase. The factors influencing the partitioning coefficients of the glyoxal and methylglyoxal were positively correlated with the relative humidity (RH) and negatively correlated with the PM2.5 value. Moreover, the partitioning coefficient of the glyoxal and methylglyoxal was more significant at the top than at the foot of Mount Hua.

Unconventional reservoirs are normally characterized by dual porous media, which has both multi-scale pore and fracture structures, such as low permeability or tight oil reservoirs. The seepage characteristics of such reservoirs is mainly determined by micro-fractures, but conventional laboratory experimental methods are difficult to measure it, which is attribute to the dynamic cracking of these micro-fractures. The emerging digital core technology in recent years can solve this problem by developing an accurate pore network model and a rational simulation approach. In this study, a novel pore-fracture dual network model was established based on percolation theory. Fluid flow in the pore of two scales, micro-fracture and matrix pore, were considered, also with the impact of micro-fracture opening and closing during flow. Some seepage characteristic parameters, such as fluid saturations, capillary pressure, relative permeabilities, displacement efficiency in different flow stage, can be predicted by proposed calculating method. Through these work, seepage characteristics of dual porous media can be achieved.

Abstract Background Somatic embryogenesis (SE) is a process of somatic cells that dedifferentiate to totipotent embryonic stem cells and generate embryos in vitro. Longan SE has been established and wildly used as model system for studying embryogenesis in woody plants, SE-related genes had been characterized. In spite of that, a comprehensive overview of SE at a molecular level is still absent. To understand the molecular mechanisms during longan SE, we examined the transcriptome changes by using Illumina HiSeq from the four distinct developmental stages, including non-embryogenic callus (NEC), embryogenic callus (EC), incomplete compact pro-embryogenic cultures (ICpEC), globular embryos (GE). Results RNA-seq of the four samples generated a total of 243.78 million high quality reads, approximately 81.5% of the data were mapped to longan genome. The cDNA libraries of NEC, EC, ICpEC and GE, generated 22,743, 19,745, 21,144, 21,102 expressed transcripts, 1935, 1710, 1816, 1732 novel transcripts, 2645, 366, 505, 588 unique genes, respectively. Comparative transcriptome analysis showed that a total of 10,642, 4180, 5846 and 1785 genes were differentially expressed in the pairwise comparisons of NEC_vs_EC, EC_vs_ICpEC, EC_vs_GE, ICpEC_vs_GE, respectively. Among them, plant hormones signalling related genes were significantly enriched, especially the auxin and cytokinin signalling components. The transcripts of flavonoid biosynthesis related genes were mainly expressed in NEC, while fatty acid biosynthesis related genes mainly accumulated in early SE. In addition, the extracelluar protein encoding genes LTP, CHI, GLP, AGP, EP1 were related to longan SE. Combined with the FPKM value of longan nine tissues transcription, 27 SE specific or preferential genes (LEC1, LEC1-like, PDF1.3, GH3.6, AGL80, PIN1, BBM, WOX9, WOX2, ABI3, et al.) and 28 NEC preferential genes (LEA5, CNOT3, DC2.15, PR1–1, NsLTP2, DIR1, PIP1, PIP2.1, TIP2–1, POD-P7 and POD5 et al.) were characterized as molecular markers for longan early SE. qRT-PCR validation of SE-related genes showed a high correlation between RNA-seq and qRT-PCR data. Conclusion This study provides new insights into the role of the transcriptome during early SE in longan. Differentially expressed genes reveal that plant hormones signalling, flavonoid and fatty acid biosynthesis, and extracelluar protein related genes were involved in longan early SE. It could serve as a valuable platform resource for further functional studies addressing embryogenesis in woody plants.

Bone age is an important metric to monitor children’s skeleton development in pediatrics. As the development of deep learning DL-based bone age prediction methods have achieved great success. However, it also faces the issue of huge computation overhead in deep features learning. Aiming at this problem, this paper proposes a new DL-based bone age assessment method based on the Tanner-Whitehouse method. This method extracts limited and useful regions for feature learning, then utilizes deep convolution layers to learn representative features in these interesting regions. Finally, to realize the fast computation speed and feature interaction, this paper proposes to use an extreme learning machine algorithm as the basic architecture in the final bone age assessment study. Experiments based on publicly available data validate the feasibility and effectiveness of the proposed method.

Abstract Background To investigate and compare the diagnostic performance in T staging for patients with esophagogastric junction cancer using high-resolution magnetic resonance imaging (HR MRI), as compared with conventional MRI at 3 Tesla. Methods A total of 118 patients with pathologically confirmed esophagogastric junction cancer were included and underwent multiparameter HR MRI (Cohort 1, 62 patients) or conventional MRI (Cohort 2, 56 patients). T2-weighted, T1-weighted, diffusion-weighted and contrast-enhanced T1-weighted images of each patient were evaluated by two radiologists who determined the preoperative T staging by consensus. Using pathologic staging as the gold standard, the consistency between HR MRI and pathology and between conventional MRI and pathology in T staging was calculated and compared. The overall accuracy, overstatement and understatement of HR MRI and conventional MRI in T staging of patients with esophagogastric junction cancer were computed and compared. Moreover, the diagnostic performance of HR MRI and conventional MRI in T staging (≤ T1 and ≥ T4) of patients with esophagogastric junction cancer were evaluated. Results There were no significant differences in age (p = 0.465) and sex (p = 0.175) between Cohorts 1 and 2. Excellent agreement was observed in the T staging of patients with esophagogastric junction cancer between pathology and HR MRI (kappa = 0.813), while moderate agreement was observed between pathology and conventional MRI (kappa = 0.486). Significant differences were observed in overall accuracy (88.7% vs 64.3%, p = 0.002) and understatement (1.6% vs 26.8%, p

Background: Endolymphatic hydrops (EH) become visible in vertigo patients, particularly in those with Meniere's disease (MD), in vivo using gadolinium-enhanced MRI. However, the image quality is not satisfying after intravenous injection of gadolinium chelate (GdC), and occasional failure in GdC uptake has been noticed after traditional intratympanic injection. In the present report, targeted delivery of GdC and using a cost-effective MRI system to obtain high quality images of EH in only 8 min will be introduced. Methods: 39 MD patients were recruited in the study. First, 0.1 ml of 20-fold diluted gadolinium-diethylenetriamine acid (Gd-DTPA) was delivered onto the posterior upper part of the tympanic medial wall using a soft-tipped micro-irrigation catheter through an artificially perforated tympanic membrane. Inner ear MRI was performed 24 h after Gd-DTPA administration using a 3T MR machine and a 20-channel head/neck coil with an 8 min sequence of medium inversion time inversion recovery imaging with magnitude reconstruction (MIIRMR). The parameters were as follows: TR 16000 ms, TE 663 ms, inversion time 2700 ms, flip angle 180°, slices per slab 60. Results: Efficient inner ear uptake of Gd-DTPA was detected 24 h after delivery and it created excellent contrast in the inner ear of all cases. High quality images demonstrating EH in the vestibule and cochlea were obtained. Conclusion: Targeted delivery of minimum Gd-DTPA (0.1 ml, 20-fold dilution) onto the posterior upper portion of the tympanic medial wall and MRI with MIIRMR in a 3T machine and 20-channel head/neck coil are clinically practical to obtain high quality images displaying EH. Keywords: Meniere's disease, Endolymphatic hydrops, MRI, Drug delivery, Targeting

PurposeTo investigate the feasibility of a fast liver magnetic resonance imaging (MRI) protocol for lesion detection in adults using 3.0-T MRI.MethodsA fast liver MRI exam protocol was proposed. The protocol included motion-resistant coronal T2-w sequence, axial T2-w fast spin echo sequence with fat suppression, axial in-op phase gradient recalled echo (GRE) T1, axial diffusion weighted imaging (DWI), and axial contrast-enhanced T1 sequences. To evaluate the diagnostic capacity of the proposed protocol, 31 consecutive patients (20 males and 11 females; mean age, 53.2 years) underwent a liver MRI exam with conventional sequences, including the proposed protocol as a subset. Images from the conventional protocol and extracted abbreviated protocol were independently read, and the diagnostic concordance rate was assessed for each patient. The concordance analysis is presented as the proportion of concordant cases between the two protocols.ResultsThe net measurement time of the fast liver MRI protocol without adjustment and waiting time were 4 min and 28 s. In the 31 patients included in this study, 139 suspicious findings were found from both the conventional liver MR protocol and the fast liver MRI protocol. The diagnostic concordance rate was 96.4%.ConclusionsThe fast liver MRI protocol is feasible at 3.0-T, with a shorter exam time and high diagnostic concordance compared to the conventional liver MRI workflow.

Esophageal squamous cell carcinoma (ESCC) is a recalcitrant cancer. The Chinese herbal monomer fangchinoline (FCL) has been reported to have anti-tumor activity in several human cancer cell types. However, the therapeutic efficacy and underlying mechanism on ESCC remain to be elucidated. In the present study, for the first time, we demonstrated that FCL significantly suppressed the growth of ESCC both in vitro and in vivo. Mechanistic studies revealed that FCL-induced G1 phase cell-cycle arrest in ESCC which is dependent on p21 and p27. Moreover, we found that FCL coordinatively triggered Noxa-dependent intrinsic apoptosis and DR5-dependent extrinsic apoptosis by transactivating ATF4, which is a novel mechanism. Our findings elucidated the tumor-suppressive efficacy and mechanisms of FCL and demonstrated FCL is a potential anti-ESCC agent.

In this paper, the dynamic model of periodically coupled plate structure is formulated by the dynamic stiffness method (DSM). Geometrical construction is assumed to vary periodically in the whole plate structure. According to the coupling condition, the whole periodic plate structure is divided into appropriate individual rectangular plates firstly. To the individual plate, the displacement fields both of in-plane and out-of-plane are derived from the governing equation with a strong-form methodology. The dynamic stiffness matrix is developed by the Projection method. Once the dynamic stiffness matrixes of the individual plates are obtained, the global dynamic stiffness matrix of the whole periodic structure can be assembled in the similar manner with the finite element method (FEM). Several examples are presented to validate the convergence and accuracy of the present formulation. From the harmonic responses, the band gap behaviors can be observed obviously. Furthermore, a parametric analysis is implemented to study the effects of geometrical distributions and plate dimensions on the vibration characteristics. Keywords: Dynamic model, Periodic plate structure, Dynamic stiffness matrix, Vibration suppression

The core of cross-modal hashing methods is to map high dimensional features into binary hash codes, which can then efficiently utilize the Hamming distance metric to enhance retrieval efficiency. Recent development emphasizes the advantages of the unsupervised cross-modal hashing technique, since it only relies on relevant information of the paired data, making it more applicable to real-world applications. However, two problems, that is intro-modality correlation and inter-modality correlation, still have not been fully considered. Intra-modality correlation describes the complex overall concept of a single modality and provides semantic relevance for retrieval tasks, while inter-modality correction refers to the relationship between different modalities. From our observation and hypothesis, the dependency relationship within the modality and between different modalities can be constructed at the object level, which can further improve cross-modal hashing retrieval accuracy. To this end, we propose a Visual-textful Correlation Graph Hashing (OVCGH) approach to mine the fine-grained object-level similarity in cross-modal data while suppressing noise interference. Specifically, a novel intra-modality correlation graph is designed to learn graph-level representations of different modalities, obtaining the dependency relationship of the image region to image region and the tag to tag in an unsupervised manner. Then, we design a visual-text dependency building module that can capture correlation semantic information between different modalities by modeling the dependency relationship between image object region and text tag. Extensive experiments on two widely used datasets verify the effectiveness of our proposed approach.

Longan (Dimocarpus longan Lour.) is an important commercial fruit tree in southern China. The embryogenesis of longan affects the quality and yield of fruit. A large number of alternative splicing events occurs during somatic embryogenesis (SE), which is regulated by serine/arginine-rich (SR) proteins. However, the functions of SR proteins in longan are poorly understood. In this study, 21 Dlo-SR gene family members belonging to six subfamilies were identified, among which Dlo-RSZ20a, Dlo-SR30, Dlo-SR17, Dlo-SR53 and Dlo-SR32 were localized in the nucleus, Dlo-RSZ20b, Dlo-RSZ20c, Dlo-RSZ20d, Dlo-SC18, Dlo-RS2Z29, Dlo-SCL41, and Dlo-SR33 were localized in chloroplasts, and Dlo-RS43, Dlo-SC33, Dlo-SC37, Dlo-RS2Z33, Dlo-RS2Z16, Dlo-RS2Z24, Dlo-SCL43, Dlo-SR112, and Dlo-SR59 were localized in the nucleus and chloroplasts. The Dlo-SR genes exhibited differential expression patterns in different tissues of longan. The transcript levels of Dlo-RSZ20a, Dlo-SC18, Dlo-RS2Z29, DLo-SR59, Dlo-SR53, and Dlo-SR17 were low in all analyzed tissues, whereas Dlo-RS43, Dlo-RS2Z16, Dlo-RS2Z24, and Dlo-SR30 were highly expressed in all tissues. To clarify their function during SE, the transcript levels of Dlo-SR genes were analyzed at different four stages of SE, comprising non-embryonic callus (NEC), friable-embryogenic callus (EC), incomplete compact pro-embryogenic culture (ICpEC) and globular embryo (GE). Interestingly, the transcript levels of Dlo-RS2Z29 and Dlo-SR112 were increased in embryogenic cells compared with the NEC stage, whereas transcript levels of Dlo-RSZ20a, Dlo-RS43, Dlo-SC37, and Dlo-RS2Z16 were especially increased at the GE stage compared with the other stages. Alternative splicing events of Dlo-SR mRNA precursors (pre-mRNAs) was detected during SE, with totals of 41, 29, 35, and 44 events detected during NEC, EC, ICpEC, and GE respectively. Protein-protein interaction analysis showed that SR proteins were capable of interaction with each other. The results indicate that the alternative splicing of Dlo-SR pre-mRNAs occurs during SE and that Dlo-SR proteins may interact to regulate embryogenesis of longan.

Altered gut microbiota has been identified during psychological stress, which causes severe health issues worldwide. The integrity of the intestinal barrier and blood–brain barrier regulates the process of bacterial translocation and can supply the nervous system with real-time information about the environment. However, the association of gut microbiota with psychological stress remains to be fully interpreted. In this study, we established a psychological stress model using an improved communication box and compared the expression of tight junction proteins in multiple regions of the intestinal (duodenum, jejunum, ileum) and blood–brain (amygdala, hippocampus) barriers between model and control rats. We also conducted fecal microbiota analysis using 16S rRNA gene sequencing. Expression levels of the stress-related indicators adrenocorticotropic hormone, NR3C1,2, and norepinephrine were increased in the model group compared to control group. Psychological stress reduced brain and intestinal levels of tight junction proteins, including claudin5, occludin, α-actin, and ZO-1. Microbiota analysis revealed elevated microbial diversity and fecal proportions of Intestinimonas, Catenisphaera, and Globicatella in the model group. Further analysis indicated a negative correlation of Allisonella and Odoribacter, as well as a positive correlation of norank_f__Peptococcaceae, Clostridium_sensu_stricto_1, and Coprococcus_2, with claudin5, occludin, α-actin, and ZO-1. Our use of a rodent model to explore the association between compromised intestinal and blood–brain barriers and altered fecal microbiota under psychological stress improves our understanding of the gut–brain axis. Here, cues converge to control basic developmental processes in the intestine and brain such as barrier function. This study provides new directions for investigating the pathogenesis of emotional disorders and the formulation of clinical treatment.

Hamming space retrieval is a hot area of research in deep hashing because it is effective for large-scale image retrieval. Existing hashing algorithms have not fully used the absolute boundary to discriminate the data inside and outside the Hamming ball, and the performance is not satisfying. In this paper, a boundary-aware contrastive loss is designed. It involves an exponential function with absolute boundary (i.e., Hamming radius) information for dissimilar pairs and a logarithmic function to encourage small distance for similar pairs. It achieves a push that is bigger than the pull inside the Hamming ball, and the pull is bigger than the push outside the ball. Furthermore, a novel Boundary-Aware Hashing (BAH) architecture is proposed. It discriminatively penalizes the dissimilar data inside and outside the Hamming ball. BAH enables the influence of extremely imbalanced data to be reduced without up-weight to similar pairs or other optimization strategies because its exponential function rapidly converges outside the absolute boundary, making a huge contrast difference between the gradients of the logarithmic and exponential functions. Extensive experiments conducted on four benchmark datasets show that the proposed BAH obtains higher performance for different code lengths, and it has the advantage of handling extremely imbalanced data.

Abstract Background To explore the effect of b-value distributions on the repeatability and diagnostic performance of the ADC value in rectal cancer patients using multiple b-values and mono-exponential model diffusion-weighted imaging (DWI). Methods Thirty-two preoperative rectal cancer patients, without receiving neoadjuvant therapy, were scanned on a 3 Tesla magnetic resonance imaging scanner using DWI with 10 b-values ranging from 0 to 2000 s/mm2. The apparent diffusion coefficient (ADC) value was calculated using a mono-exponential model and 31 b-value combinations consisting of 2 to 10 b-values were explored. Regions of interest with the maximum cross-sectional tumour size were outlined on the ADC map by two independent observers. Intraclass correlation coefficients (ICC), coefficient of variation (CV), and Bland-Altman plots between the two observers were calculated and evaluated to determine repeatability. Areas under receiver operating characteristic curves (AUCs) were evaluated for rectal cancer characterization. Correlations between the mean ADC values and T stage were assessed using the Spearman correlation coefficient (ρ). α (= ICC + AUC + |ρ|- CV - |bias|) was defined and used to assess the optimal b-value distribution. Results Postoperative pathology tests revealed 4 patients with T1, 10 patients with T2, and 18 patients with T3 stages. There were no significant difference in age and sex between the two groups (T1–2 vs. T3). Excellent reproducibility was observed for ADC values between two observers with ICC and CV values ranging from 0.920 to 0.998, and 1.475 to 5.568%, respectively. The mean percent difference and ρ between the paired measurements was ranged from − 2.7 to 1.2% and from − 0.759 to − 0.407, respectively. The b-value combinations with the top three α values were b(0, 1000 s/mm2), b(500, 1500, 2000 s/mm2) and b(100, 1000, 1500 s/mm2) for α = 2.581, 2.571 and 2.569, respectively. Conclusions The number of b-values and their distributions influenced the repeatability of the ADC values and their diagnostic performance. The optimal b-value combination was 0 and 1000 s/mm2 for DWI examination of rectal cancer patients.

Abstract Background Long non-coding RNAs (lncRNAs) are involved in variable cleavage, transcriptional interference, regulation of DNA methylation and protein modification. However, the regulation of lncRNAs in plant somatic embryos remains unclear. The longan (Dimocarpus longan) somatic embryogenesis (SE) system is a good system for research on longan embryo development. Results In this study, 7643 lncRNAs obtained during early SE in D. longan were identified by high-throughput sequencing, among which 6005 lncRNAs were expressed. Of the expressed lncRNAs, 4790 were found in all samples and 160 were specifically expressed in embryogenic callus (EC), 154 in incomplete embryogenic compact structures (ICpECs), and 376 in globular embryos (GEs). We annotated the 6005 expressed lncRNAs, and 1404 lncRNAs belonged to 506 noncoding RNA (ncRNA) families and 4682 lncRNAs were predicted to target protein-coding genes. The target genes included 5051 cis-regulated target genes (5712 pairs) and 1605 trans-regulated target genes (3618 pairs). KEGG analysis revealed that most of the differentially expressed target genes (mRNAs) of the lncRNAs were enriched in the “plant-pathogen interaction” and “plant hormone signaling” pathways during early longan SE. Real-time quantitative PCR confirmed that 20 selected lncRNAs showed significant differences in expression and that five lncRNAs were related to auxin response factors. Compared with the FPKM expression trends, 16 lncRNA expression trends were the same in qPCR. In lncRNA-miRNA-mRNA relationship prediction, 40 lncRNAs were predicted to function as eTMs for 15 miRNAs and 7 lncRNAs were identified as potential miRNA precursors. In addition, we verified the lncRNA-miRNA-mRNA regulatory relationships by transient expression of miRNAs (miR172a, miR159a.1 and miR398a). Conclusion Analyses of lncRNAs during early longan SE showed that differentially expressed lncRNAs were involved in expression regulation at each SE stage, and may form a regulatory network with miRNAs and mRNAs. These findings provide new insights into lncRNAs and lay a foundation for future functional analysis of lncRNAs during early longan SE.

Abstract Background Active learning (AL) has shown the promising potential to minimize the annotation cost while maximizing the performance in building statistical natural language processing (NLP) models. However, very few studies have investigated AL in a real-life setting in medical domain. Methods In this study, we developed the first AL-enabled annotation system for clinical named entity recognition (NER) with a novel AL algorithm. Besides the simulation study to evaluate the novel AL algorithm, we further conducted user studies with two nurses using this system to assess the performance of AL in real world annotation processes for building clinical NER models. Results The simulation results show that the novel AL algorithm outperformed traditional AL algorithm and random sampling. However, the user study tells a different story that AL methods did not always perform better than random sampling for different users. Conclusions We found that the increased information content of actively selected sentences is strongly offset by the increased time required to annotate them. Moreover, the annotation time was not considered in the querying algorithms. Our future work includes developing better AL algorithms with the estimation of annotation time and evaluating the system with larger number of users.