Acute cardiac tamponade after Endostar treatment of non-small cell lung cancer: A case report.

RATIONALE: Recombinant human endostatin (Endostar) is extensively utilized in China for the clinical management of patients with driver gene-negative non-small cell lung cancer (NSCLC) at stage TNM IV. This report describes the case of a lung cancer patient treated exclusively with Endostar maintenance therapy, who experienced a rapid deterioration in respiratory function. PATIENT CONCERNS: The case involved a patient with a pathologically confirmed squamous cell carcinoma of the left lung, treated in our department. Following 1 month of albumin-bound paclitaxel chemotherapy and localized radiotherapy for the left lung lesion, the patient initiated treatment with a single agent, Endostar 30mg, on October 19, 2021. The medication was administered via intravenous infusion over a 7 days. DIAGNOSIS: On October 23, 2021, the patient exhibited symptoms of chest constriction, discomfort, coughing, and sputum production. By October 28, the patient presented with pronounced dyspnea and respiratory distress. An emergency CT scan detected pericardial tamponade and significant deviations in several blood parameters from pretreatment values. INTERVENTIONS: Percardial puncture and catheter drainage were recommended as therapeutic intervention. OUTCOMES: Considering the patient advanced age, the patient and their family opted to refuse this medical procedure, leading to the patient unfortunate demise on November 2, 2021. LESSONS: Medical professionals should remain vigilant for the potential, albeit rare, risk of Endostar inducing acute pericardial tamponade, a severe and potentially fatal complication.

Sudden aortic dissection: A cautionary tale for the unexplained back pain during bevacizumab treatment.

Bevacizumab is widely used in the treatment of colorectal cancer, liver cancer, and other advanced solid tumors because of its multiple targets, no genetic testing and better safety. Globally, the use of bevacizumab in the clinic has been climbing year by year based on several large-scale, multicenter prospective studies. While bevacizumab undeniably has a good clinical safety profile, it has also been associated with adverse effects such as drug-related hypertension and anaphylaxis. In our recent clinical work, we met a female patient with acute aortic coarctation previously treated with multiple cycles of bevacizumab, who was admitted with sudden onset of back pain. Because the patient had just had an enhanced CT of the chest and abdomen a month earlier, no abnormal lesions apparently associated with low back pain were found. So when the patient was seen on this occasion, our clinical diagnosis was first considered to be neuropathic pain, but a further multiphase enhancement CT was done again for further exclusion and the final diagnosis was acute aortic dissection. The patient later died within 1 hour after the chest pain had worsened again while waiting for a surgical blood supply within 72 hours of presentation. The risk of fatal acute aortic dissection is not sufficiently emphasized in the revised instructions for bevacizumab, although the adverse effects associated with aortic dissection and aneurysm are mentioned. Our report is of high practical value in raising clinicians' vigilance and safe management of patients using bevacizumab worldwide.

Global transcriptome dissection of pollen-pistil interactions induced self-incompatibility in dragon fruit (Selenicereus spp.).

Self-incompatibility (SI) is a major issue in dragon fruit (Selenicereus spp.) breeding and production. Therefore, a better understanding of the dragon fruit SI mechanism is needed to improve breeding efficiency and ultimate production costs. To reveal the underlying mechanisms of SI in dragon fruit, plant anatomy, de novo RNA sequencing-based transcriptomic analysis, and multiple bioinformatic approaches were used to analyze gene expression in the pistils of the self-pollinated and cross-pollinated dragon fruit flowers at different intervals of time after pollination. Using fluorescence microscopy, we observed that the pollen of 'Hongshuijing', a self-incompatible dragon fruit variety (S. monacanthus), germinated on its own stigma. However, the pollen tube elongation has ceased at 1/2 of the style, confirming that dragon fruit experiences gametophyte self-incompatibility (GSI). We found that the pollen tube elongation in vitro was inhibited by self-style glycoproteins in the SI variety, indicating that glycoproteins were involved in SI. That is to say the female S factor should be homologous of S-RNase or PrsS (P. rhoeas stigma S factor), both of which are glycoproteins and are the female S factors of the two known GSI mechanism respectively. Bioinformatics analyses indicated that among the 43,954 assembled unigenes from pistil, there were six S-RNase genes, while 158 F-box genes were identified from a pollen transcriptomic dataset. There were no P. rhoeas type S genes discovered. Thus, the identified S-RNase and F-box represent the candidate female and male S genes, respectively. Analysis of differentially expressed genes (DEGs) between the self and cross-pollinated pistils at different time intervals led to the identification of 6,353 genes. We then used a weighted gene co-expression network analysis (WGCNA) to find some non-S locus genes in SI responses in dragon fruit. Additionally, 13 transcription factors (TFs) (YABBY4, ANL2, ERF43, ARF2, BLH7, KNAT6, PIF3, two OBF1, two HY5 and two LHY/CCA) were identified to be involved in dragon fruit GSI. Thus, we uncovered candidate S and non-S genes and predicted more SI-related genes for a more detailed investigation of the molecular mechanism of dragon fruit SI. Our findings suggest that dragon fruit possesses a GSI system and involves some unique regulators. This study lays the groundwork for future research into SI mechanisms in dragon fruit and other plant species.

Construction of a miRNA-mRNA Network Related to Exosomes in Colon Cancer.

Background: The competing endogenous RNA (CeRNA) network plays important roles in the occurrence and development of colon cancer. This research is aimed at constructing a miRNA-mRNA network associated with exosomes in colon cancer. Methods: We explored the GEO database and then analyzed the RNAs of 722 samples to obtain differentially expressed miRNAs (DEMs) and mRNAs (DEGs) alongside the progress of colon cancer. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEM target genes and DEGs were performed. In addition, a miRNA-mRNA network related to exosomes in colon cancer was constructed based on DEMs and DEGs. Finally, the expression of miRNA and mRNA in the network was verified by GEPIA2 on the base of TCGA database. Results: Through our analysis, 19 DEMs (17 up and 2 down) and 1672 DEGs (954 up and 718 down) were screened. The GO and KEGG results show that these DEGs were mainly enriched in ribonucleoprotein complex biogenesis, noncoding RNA metabolic process, cell-substrate junction, cadherin binding, transcription coregulator activity, and regulation of the human T-cell leukemia virus 1 infection-related pathway. Besides, a miRNA-mRNA network, including 4 miRNAs (hsa-miR-623, hsa-miR-320c, hsa-miR-486-5p, and hsa-miR-1290) and 7 mRNAs (GNAI1, CADM1, PGRMC2, etc.), was constructed. Three of these seven mRNAs were downregulated in colon cancer. Ultimately, the GNAI1, CADM1, and PGRMC2 expression levels were verified by TCGA database. Conclusions: This study reveals the network relationship between colon cancer exosome-derived miRNA and targeted mRNA. It deepens our understanding of new molecular mechanisms and pathways that may play a role in the occurrence and metastasis of colon cancer.

Metabolomics and Transcriptomics Analysis of Pollen Germination Response to Low-Temperature in Pitaya (Hylocereus polyrhizus).

Cross-pollination can improve the percentage of fruit set and fruit weight for most red flesh varieties in pitaya. The technology of pollen storage was very important for successful cross-pollination. However, till present, the technology of pollen storage is unsatisfactory in pitaya production. In this study, pitaya pollen stored at low temperature was taken as the research object, and its physicochemical indexes, metabolomics, and transcriptomics were studied. The results showed that in vitro pollen germination rate decreased significantly with the increase in storage time. Soluble sugar and soluble protein content of pollen peaked on the first day of storage, whereas its relative conductivity, and manlondialdehyde (MDA) and proline contents increased gradually during storage. At the same time, the antioxidant enzyme system of pollen was also affected. Superoxide dismutase (SOD) activity decreased, while the activities of catalase (CAT) and peroxidase (POD) increased and superoxide anion generation rate increased gradually during storage. According to the metabolomics results, amino acid, peptide, nucleotide, plant hormone, terpene, alcohol, phenol, flavonoid, sterol, vitamin, ester, sphingolipid, and ketone contents increased significantly during storage, whereas flavonoid and pigment contents declined gradually. During pollen storage, the gene expressions related to carbohydrate metabolism, protein metabolism, acid and lipid metabolism, sterol metabolism, plant hormone metabolism, and signal transductions were significantly downregulated. With KEGG pathway analysis, isoquinoline alkaloid biosynthesis, tyrosine metabolism, alanine, aspartate, and glutamate metabolism of pollen were affected significantly during low-temperature storage. Correlation analysis showed that the gene expression patterns of HuRP2, HuUPL1, and HuAAT2 had significant effects on pollen germination. D-arabinose 5-phosphate and myricetin were positively correlated with pollen germination rate, which was valuable for studying preservation agents. In this study, the changes in pollen during low-temperature storage were described from the level of metabolites and genes, which could provide theoretical support for the research and development of pollen long-term storage technology in pitaya.

A chromosome-scale genome sequence of pitaya (Hylocereus undatus) provides novel insights into the genome evolution and regulation of betalain biosynthesis.

Pitaya (Hylocereus) is the most economically important fleshy-fruited tree of the Cactaceae family that is grown worldwide, and it has attracted significant attention because of its betalain-abundant fruits. Nonetheless, the lack of a pitaya reference genome significantly hinders studies focused on its evolution, as well as the potential for genetic improvement of this crop. Herein, we employed various sequencing approaches, namely, PacBio-SMRT, Illumina HiSeq paired-end, 10× Genomics, and Hi-C (high-throughput chromosome conformation capture) to provide a chromosome-level genomic assembly of 'GHB' pitaya (H. undatus, 2n = 2x = 22 chromosomes). The size of the assembled pitaya genome was 1.41 Gb, with a scaffold N50 of ~127.15 Mb. In total, 27,753 protein-coding genes and 896.31 Mb of repetitive sequences in the H. undatus genome were annotated. Pitaya has undergone a WGT (whole-genome triplication), and a recent WGD (whole-genome duplication) occurred after the gamma event, which is common to the other species in Cactaceae. A total of 29,328 intact LTR-RTs (~696.45 Mb) were obtained in H. undatus, of which two significantly expanded lineages, Ty1/copia and Ty3/gypsy, were the main drivers of the expanded genome. A high-density genetic map of F1 hybrid populations of 'GHB' × 'Dahong' pitayas (H. monacanthus) and their parents were constructed, and a total of 20,872 bin markers were identified (56,380 SNPs) for 11 linkage groups. More importantly, through transcriptomic and WGCNA (weighted gene coexpression network analysis), a global view of the gene regulatory network, including structural genes and the transcription factors involved in pitaya fruit betalain biosynthesis, was presented. Our data present a valuable resource for facilitating molecular breeding programs of pitaya and shed novel light on its genomic evolution, as well as the modulation of betalain biosynthesis in edible fruits.

Contribution of anthocyanin pathways to fruit flesh coloration in pitayas.

BACKGROUND: Color formation in Hylocereus spp. (pitayas) has been ascribed to the accumulation of betalains. However, several studies have reported the presence of anthocyanins in pitaya fruit and their potential role in color formation has not yet been explored. In this study, we profiled metabolome and transcriptome in fruit of three cultivars with contrasting flesh colors (red, pink and white) to investigate their nutritional quality and the mechanism of color formation involving anthocyanins. RESULTS: Results revealed that pitaya fruit is enriched in amino acid, lipid, carbohydrate, polyphenols, vitamin and other bioactive components with significant variation among the three cultivars. Anthocyanins were detected in the fruit flesh and accumulation levels of Cyanidin 3-glucoside, Cyanidin 3-rutinoside, Delphinidin 3-O-(6-O-malonyl)-beta-glucoside-3-O-beta-glucoside and Delphinidin 3-O-beta-D-glucoside 5-O-(6-coumaroyl-beta-D-glucoside) positively correlated with the reddish coloration. Transcriptome data showed that the white cultivar tends to repress the anthocyanin biosynthetic pathway and divert substrates to other competing pathways. This perfectly contrasted with observations in the red cultivar. The pink cultivar however seems to keep a balance between the anthocyanin biosynthetic pathway and the competing pathways. We identified several active transcription factors of the MYB and bHLH families which can be further investigated as potential regulators of the anthocyanin biosynthetic genes. CONCLUSIONS: Collectively, our results suggest that anthocyanins partly contribute to color formation in pitaya fruit. Future studies aiming at manipulating the biosynthetic pathways of anthocyanins and betalains will better clarify the exact contribution of each pathway in color formation in pitayas. This will facilitate efforts to improve pitaya fruit quality and appeal.

The characterization and geographical distribution of the genes responsible for vernalization requirement in Chinese bread wheat.

The frequency and distribution of the major vernalization requirement genes and their effects on growth habits were studied. Of the 551 bread wheat genotypes tested, seven allelic combinations of the three Vrn-1 genes were found to be responsible for the spring habit, three for the facultative habit and one for the winter habit. The three Vrn-1 genes behaved additively with the dominant allele of Vrn-A1 exerting the strongest effect. The allele combinations of the facultative genotypes and the discovery of spring genotypes with "winter" allele of Vrn-1 implied the presence of as yet unidentified alleles/genes for vernalization response. The dominant alleles of the three Vrn-1 genes were found in all ten ecological regions where wheat is cultivated in China, with Vrn-D1 as the most common allele in nine and Vrn-A1 in one. The combination of vrn-A1vrn-B1Vrn-D1 was the predominant genotype in seven of the regions. Compared with landraces, improved varieties contain a higher proportion of the spring type. This was attributed by a higher frequency of the dominant Vrn-A1 and Vrn-B1 alleles in the latter. Correlations between Vrn-1 allelic constitutions and heading date, spike length, plant type as well as cold tolerance were established.