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Sphingolipids comprise a class of lipids, which are composed of a sphingoid base backbone and are essential structural components of cell membranes. Beyond their role in maintaining cellular integrity, several sphingolipids are pivotally involved in signaling pathways controlling cell proliferation, differentiation, and death. The brain exhibits a particularly high concentration of sphingolipids and dysregulation of the sphingolipid metabolism due to ischemic injury is implicated in consecutive pathological events. Experimental stroke studies revealed that the stress sphingolipid ceramide accumulates in the ischemic brain post-stroke. Specifically, counteracting ceramide accumulation protects against ischemic damage and promotes brain remodeling, which translates into improved behavioral outcome. Sphingomyelin substantially influences cell membrane fluidity and thereby controls the release of extracellular vesicles, which are important vehicles in cellular communication. By modulating sphingomyelin content, these vesicles were shown to contribute to behavioral recovery in experimental stroke studies. Another important sphingolipid that influences stroke pathology is sphingosine-1-phosphate, which has been attributed a pro-angiogenic function, that is presumably mediated by its effect on endothelial function and/or immune cell trafficking. In experimental and clinical studies, sphingosine-1-phosphate receptor modulators allowed to modify clinically significant stroke recovery. Due to their pivotal roles in cell signaling, pharmacological compounds modulating sphingolipids, their enzymes or receptors hold promise as therapeutics in human stroke patients.

Abstract Roses are consistently ranked at the forefront in cut flower production. Increasing demands of market and changing climate conditions have resulted in the need to further improve the diversity and quality of traits. However, frequent hybridization leads to highly heterozygous nature, including the allelic variants. Therefore, the absence of comprehensive genomic information leads to them making it challenging to molecular breeding. Here, two haplotype-resolved chromosome genomes for Rosa chinensis ‘Chilong Hanzhu’ (2n = 14) which is high heterozygous diploid old Chinese rose are generated. An amount of genetic variation (1,605,616 SNPs, 209,575 indels) is identified. 13,971 allelic genes show differential expression patterns between two haplotypes. Importantly, these differences hold valuable insights into regulatory mechanisms of traits. RcMYB114b can influence cyanidin-3-glucoside accumulation and the allelic variation in its promoter leads to differences in promoter activity, which as a factor control petal color. Moreover, gene family expansion may contribute to the abundance of terpenes in floral scents. Additionally, RcANT1, RcDA1, RcAG1 and RcSVP1 genes are involved in regulation of petal number and size under heat stress treatment. This study provides a foundation for molecular breeding to improve important characteristics of roses.

Abstract Myeloperoxidase (MPO) plays critical role in the pathology of cerebral ischemia–reperfusion (I/R) injury via producing hypochlorous acid (HOCl) and inducing oxidative modification of proteins. High-mobility group box 1 (HMGB1) oxidation, particularly disulfide HMGB1 formation, facilitates the secretion and release of HMGB1 and activates neuroinflammation, aggravating cerebral I/R injury. However, the cellular sources of MPO/HOCl in ischemic brain injury are unclear yet. Whether HOCl could promote HMGB1 secretion and release remains unknown. In the present study, we investigated the roles of microglia-derived MPO/HOCl in mediating HMGB1 translocation and secretion, and aggravating the brain damage and blood-brain barrier (BBB) disruption in cerebral I/R injury. In vitro, under the co-culture conditions with microglia BV cells but not the single culture conditions, oxygen–glucose deprivation/reoxygenation (OGD/R) significantly increased MPO/HOCl expression in PC12 cells. After the cells were exposed to OGD/R, MPO-containing exosomes derived from BV2 cells were released and transferred to PC12 cells, increasing MPO/HOCl in the PC12 cells. The HOCl promoted disulfide HMGB1 translocation and secretion and aggravated OGD/R-induced apoptosis. In vivo, SD rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) plus different periods of reperfusion. Increased MPO/HOCl production was observed at the reperfusion stage, accomplished with enlarged infarct volume, aggravated BBB disruption and neurological dysfunctions. Treatment of MPO inhibitor 4-aminobenzoic acid hydrazide (4-ABAH) and HOCl scavenger taurine reversed those changes. HOCl was colocalized with cytoplasm transferred HMGB1, which was blocked by taurine in rat I/R-injured brain. We finally performed a clinical investigation and found that plasma HOCl concentration was positively correlated with infarct volume and neurological deficit scores in ischemic stroke patients. Taken together, we conclude that ischemia/hypoxia could activate microglia to release MPO-containing exosomes that transfer MPO to adjacent cells for HOCl production; Subsequently, the production of HOCl could mediate the translocation and secretion of disulfide HMGB1 that aggravates cerebral I/R injury. Furthermore, plasma HOCl level could be a novel biomarker for indexing brain damage in ischemic stroke patients.

ObjectiveTo assess the impact of blended learning, based on the ADDIE model, on theoretical and practical aspects of nursing staff training.MethodsRetrospective analysis of data from 87 nursing staff members in Xi’an Qinhuang Hospital divided into control (n = 43) and observation (n = 44) groups. The control group received conventional training, while the observation group underwent blended learning. Comparative analysis included theoretical knowledge, practical skills, self-directed learning, critical thinking, and teaching satisfaction.ResultsThe observation group showed significantly higher theoretical knowledge, practical skills, self-directed learning, critical thinking, and teaching satisfaction compared to the control group (p

The double flower developmental process is regulated via a complex transcriptional regulatory network. To understand this highly dynamic and complex developmental process of Dianthus spp., we performed a comparative analysis of floral morphology and transcriptome dynamics in simple flowers and double flowers. We found that the primordium of double flowers of ‘X’ was larger in size compared to that of simple flowers of ‘L’ in Dianthus chinensis. RNA-seq and Weighted Gene Co-expression Network Analysis (WGCNA) during flower development, identified stage-specific gene network modules. Expression analysis by RNA-seq indicated that a group of genes related to floral meristem identity, primordia position and polarity were highly expressed in double flowers genotypes compared to simple flowers genotypes, suggesting their roles in double-petal formation. A total of 21 DEGs related to petal number were identified between simple and double flowers. The experiments of in situ hybridization revealed that DcaAP2L, DcaLFY and DcaUFO genes were expressed in the intra-sepal boundary and petal boundary. We proposed a potential transcriptional regulatory network for simple and double flower development. This study provides novel insights into the molecular mechanism underlying double flower formation in Dianthus spp.

Abstract Passiflora is a plant genus known for its extremely distinctive and colorful flowers and a wide range of genome size variation. However, how genome characteristics are related to flower traits among Passiflora species remains poorly understood. Here, we assembled a chromosome-scale genome of P. foetida, which belongs to the same subgenus as the commercial passionfruit P. edulis. The genome of P. foetida is smaller (424.16 Mb) and contains fewer copies of long terminal repeat retrotransposons (LTR-RTs). The disparity in LTR-RTs is one of the main contributors to the differences in genome sizes between these two species and possibly in floral traits. Additionally, we observed variation in insertion times and copy numbers of LTR-RTs across different transposable element (TE) lineages. Then, by integrating transcriptomic data from 33 samples (eight floral organs and flower buds at three developmental stages) with phylogenomic and metabolomic data, we conducted an in-depth analysis of the expression, phylogeny, and copy number of MIKC-type MADS-box genes and identified essential biosynthetic genes responsible for flower color and scent from glandular bracts and other floral organs. Our study pinpoints LRT-RTs as an important player in genome size variation in Passiflora species and provides insights into future genetic improvement. Graphical Abstract

ObjectivesTo evaluate the effects of platinum-based neoadjuvant chemotherapy (NACT) on the STING/IFN pathway and tumor-infiltrating lymphocytes (TILs) in non-small cell lung cancer (NSCLC), as well as clinicopathological factors affecting patient survival.Materials and methodsA total of 68 patients aged 34-77 years with NSCLC who received neoadjuvant chemotherapy and surgical treatment from March 2012 to February 2019 were reviewed, and the clinical pathological data and paired tissue specimens before and after NACT were collected. Immunohistochemistry and immunofluorescence were used to detect the protein levels of STING, PD-L1 and IFN-β, and the infiltration density of CD3+ TILs and CD8+TILs. The correlation between the expression of STING, PD-L1, IFN-β and the infiltration density of CD3+ TILs and CD8+ TILs as well as the clinicopathological characteristics before and after NACT was analyzed. The relationship between the related indexes, clinicopathological features and prognosis was also discussed.ResultsNACT increased the expression of STING, IFN-β and PD-L1 in tumor cells, and the infiltration of CD3+ and CD8+ TILs. In addition, ypTNM stage, ypN stage, changes in CD3+ TILs and in PD-L1 were associated with DFS (disease-free survival). CD3+ TILs changes and ypN stage were associated with OS (overall survival). Notably, ypN stage and CD3+ TILs changes were independent prognostic factors for DFS and OS.ConclusionNACT stimulates STING/IFN-β pathway, promotes infiltration of CD3+ and CD8+ TILs, triggers innate and adaptive immunity, and also upregulates PD-L1, which complemented the rationale for neoadjuvant chemotherapy in combination with immunotherapy. In addition, DFS was longer in patients with ypTNM I, ypN0-1, and elevated CD3+TILs after NACT. Patients with ypN0 and elevated CD3+ TILs after NACT had better OS benefits.

With the increasing throughput of modern sequencing instruments, the cost of storing and transmitting sequencing data has also increased dramatically. Although many tools have been developed to compress sequencing data, there is still a need to develop a compressor with a higher compression ratio. We present a two-step framework for compressing sequencing data in this paper. The first step is to repack original data into a binary stream, while the second step is to compress the stream with a LZMA encoder. We develop a new strategy to encode the original file into a LZMA highly compressed stream. In addition an FPGA-accelerated of LZMA was implemented to speedup the second step. As a demonstration, we present repaq as a lossless non-reference compressor of FASTQ format files. We introduced a multifile redundancy elimination method, which is very useful for compressing paired-end sequencing data. According to our test results, the compression ratio of repaq is much higher than other FASTQ compressors. For some deep sequencing data, the compression ratio of repaq can be higher than 25, almost four times of Gzip. The framework presented in this paper can also be applied to develop new tools for compressing other sequencing data. The open-source code of repaq is available at: https://github.com/OpenGene/repaq.

Dianthus caryophyllus is an economic species often considered excellent cut flowers and is suitable for bouquets and gardens. Here, we assembled the haplotype-resolved genome of D. caryophyllus ‘Aili’ at the chromosome level for the first time. The total lengths of the two assembled haplotypes of carnation were 584.88 Mb for haplotype genome 1 (hap1) and 578.78 Mb for haplotype genome 2 (hap2), respectively. We predicted a total of 44,098 and 42,425 protein-coding genes, respectively. The remarkable structure variation was identified between two haplotypes. Moreover, we identified 403.80 Mb of transposable elements (TEs) in hap1, which accounted for 69.34% of the genome. In contrast, hap2 had 402.70 Mb of TEs, representing 69.61% of the genome. Long terminal repeats were the predominant transposable elements. Phylogenetic analysis showed that the species differentiation time between carnation and gypsophila was estimated to be ~54.43 MYA. The unique gene families of carnation genomes were identified in ‘Aili’ and previously published ‘Francesco’ and ‘Scarlet Queen’. The assembled and annotated haplotype-resolved D. caryophyllus genome not only promises to facilitate molecular biology studies but also contributes to genome-level evolutionary studies.

The SEPALLATA (SEP) gene, as a 'glue' for the 'floral quartets model', plays an important role in floral organ development by forming tetramers with class A-, B-, and C- genes. The functional differentiation of class E genes has been reported in different species. Carnation (Dianthus spp.) is a world-famous economic flower that has been extensively used in landscaping, but the roles of SEP genes in carnation are unclear. Here, we found that the class E genes of D. chinensis cultivar 'L' showed different expression patterns during floral organ primordium development by transcriptome analysis. Combined with quantitative real-time PCR, its tissue and specific stage expression patterns were also different in different subclades. In addition, a yeast two-hybrid experiment was carried out to explore the interaction patterns of class E genes with other class A-, B-, and C- genes. Only DcSEP3s and DcSEP4s proteins interacted with all three classes of A-, B-, and C- proteins, and interestingly, is that DcSEP3-1 only interacted with the DcAP1 protein of class A, while the DcSEP3-2 protein only interacted with DcFUL1. Transgenic experiments showed that overexpression of DcSEP3-2 genes in Arabidopsis resulted in early flowering, smaller rosettes, dwarfism and abnormal floral organs. The transgenic line overexpressing of DcSEP3-1 only showed an early flowering phenotype. All these results indicated that the two DcSEP3s of class E genes in D. chinensis may undergo sub-functionalization. These findings advance our understanding of the molecular mechanisms of flower development in carnation.

The ChangKang (Heathy Bowel) project was established to collect molecular and clinical information of a thousand Chinese colorectal cancer patients. Here, the authors present the genomic landscape of the ChangKang cohort and find a subgroup of patients defined by abnormal mitochondrial copy numbers.

Next-generation sequencing-based genomic profiling facilitates biomarker detection by cell-free DNA (cfDNA) liquid biopsy. However, the efficiency of mutation calling and the prognostic value of cfDNA biomarkers are disputed. We investigated 24 patients with gastric cancer in this study, using a 605-gene sequencing panel to sequence their plasma cfDNA and tumor tissue DNA. The mutation concordance between plasma cfDNA and tumor tissue DNA was 70.6% in stage IV gastric cancer and 30.2% in stage III gastric cancer, indicating insufficient mutation detection rates in stage III and early-stage cancer. When compared with total cfDNA load and blood tumor mutation burden (bTMB), the variant allele frequencies (VAF) of commonly mutated genes are highly accurate in representing disease burden. Further, VAF are a better prognostic indicator compared with serum biomarkers including carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), cancer antigen 125 (CA125), and alpha-fetoprotein (AFP). The use of cfDNA in molecular profiling of patients allows prediction of patient survival and clinical response, as well as the development of personalized therapy regimens.

The security of industrial control systems is increasingly prominent, and the performance of intrusion detection classifiers depends more on hyper-parameters. This paper proposes an improved multiple population genetic algorithm (IMPGA) used to intelligently search hyper-parameters of classifiers, and the simulated annealing algorithm (SAA) is used to control the evolution rate among various populations. In addition, the hash fitness value is used to reduce resource consumption and the directional evolution operator is introduced to optimize the population. This method can effectively avoid the algorithm falling into local optimal solution and save the optimal solution in the process of evolution. Thus, the optimal or approximate optimal combinations of hyper-parameters of classifiers are obtained and the accuracy of the classifiers is finally improved. In this paper, experiments are conducted on the following datasets: the natural gas pipeline experimental dataset of Mississippi State University from 2014 (a gas dataset), the intrusion detection systems dataset of Canadian Institute for Cybersecurity from 2017 (CICIDS2017 dataset) and an oil depot dataset. The experimental results of those three datasets show that the area under curve (AUC) of the back propagation neural network (BPNN) is more than 98%, of the extreme gradient boosting (XGBoost) is more than 99%, and of the support vector machines (SVM) is more than 98%. This selection method can effectively detect the intrusion attacks.

ObjectiveTo examine the risk factors for falls in elderly patients with visual impairment (VI) and assess the predictive performance of these factors.MethodsBetween January 2019 and March 2021, a total of 251 elderly patients aged 65–92 years with VI were enrolled and then prospectively followed up for 12 months to evaluate outcomes of accidental falls via telephone interviews. Information of demographics and lifestyle, gait and balance deficits, and ophthalmic and systemic conditions were collected during baseline visits. Forward stepwise multivariable logistic regression analysis was performed to identify independent risk factors of falls in elderly patients with VI, and a derived nomogram was constructed.ResultsA total of 143 falls were reported in 251 elderly patients during follow-up, with an incidence of 56.97%. The risk factors for falls in elderly patients with VI identified by multivariable logistic regression were women [odds ratio (OR), 95% confidence interval (CI): 2.71, 1.40–5.27], smoking (3.57, 1.34–9.48), outdoor activities/3 months (1.31, 1.08–1.59), waking up frequently during the night (2.08, 1.15–3.79), disorders of balance and gait (2.60, 1.29–5.24), glaucoma (3.12, 1.15–8.44), other retinal degenerations (3.31, 1.16–9.43) and best-corrected visual acuity (BCVA) of the better eye (1.79, 1.10–2.91). A nomogram was developed based on the abovementioned multivariate analysis results. The area under receiver operating characteristic curve of the predictive model was 0.779.ConclusionsGender, smoking, outdoor activities, waking up at night, disorders of balance and gait, glaucoma, other retinal degeneration and BCVA of the better eye were independent risk factors for falls in elderly patients with VI. The predictive model and derived nomogram achieved a satisfying prediction of fall risk in these individuals.

Carnations are one of the most popular ornamental flowers in the world with varied flower colors that have long attracted breeders and consumers alike. The differences in carnation flower color are mainly the result of the accumulation of flavonoid compounds in the petals. Anthocyanins are a type of flavonoid compound that produce richer colors. The expression of anthocyanin biosynthetic genes is mainly regulated by MYB and bHLH transcription factors. However, these TFs have not been comprehensively reported in popular carnation cultivars. Herein, 106 MYB and 125 bHLH genes were identified in the carnation genome. Gene structure and protein motif analyses show that members of the same subgroup have similar exon/intron and motif organization. Phylogenetic analysis combining the MYB and bHLH TFs from Arabidopsis thaliana separates the carnation DcaMYBs and DcabHLHs into 20 subgroups each. Gene expression (RNAseq) and phylogenetic analysis shows that DcaMYB13 in subgroup S4 and DcabHLH125 in subgroup IIIf have similar expression patterns to those of DFR, ANS, and GT/AT, which regulate anthocyanin accumulation, in the coloring of carnations, and in red-flowered and white-flowered carnations, DcaMYB13 and DcabHLH125 are likely the key genes responsible for the formation of red petals in carnations. These results lay a foundation for the study of MYB and bHLH TFs in carnations and provide valuable information for the functional verification of these genes in studies of tissue-specific regulation of anthocyanin biosynthesis.

We present an enhanced method for synthesizing sheets of borophane. Despite the challenges associated with low efficiency, we discovered that incorporating hydrochloric acid into the ion-exchange reaction significantly improved the production yield from 20% to over 50%. After a thorough examination of the reaction, we gained insight into the underlying mechanisms and found that the use of hydrochloric acid provides two key benefits: accelerated production of borophene and isolation of high-purity products. This method has the potential to pave the way for the production of novel topological 2D materials with potential industrial applications.

We have extensively searched for a cyclic hydrogenated boron molecule that has a three-center two-electron bond at the center. Using first-principles calculations, we discovered a stable molecule of 2:4:6:8:-2H-1,5:1,5-μH-B8H10 and propose its existence. This molecule can be regarded as a building block for sheets of topological hydrogen boride (borophane), which was recently theoretically proposed and experimentally discovered. The electronic structure of the cyclic hydrogenated boron molecule is discussed in comparison with that of cyclic hydrogenated carbon molecules.

Background: Malnutrition’s prognostic impact in patients with severe stroke requiring ICU admission is not well known. This study aimed to assess the nutritional status of severe stroke patients using the geriatric nutritional risk index (GNRI) and examine the association of GNRI with mortality in that population. Methods: We identified 1145 severe stroke patients requiring ICU admission from the Medical Information Mart for Intensive Care (MIMIC-III) database and divided them into low GNRI (≤98) or high GNRI (>98) groups. We used a propensity score matching (PSM) method to reduce confounding. Cox proportional hazards regression and restricted cubic splines were used to elucidate the association between GNRI and mortality. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Results: A total of 397 (35%) patients were in the low GNRI group (at risk of malnutrition). After PSM, patients in the low GNRI group still suffered higher mortality compared with the high GNRI group at 28 days (27.9 vs. 20.8%), 90 days (35.5 vs. 25.7%), and 1 year (43.4 vs. 30.9%) (p < 0.05). A low GNRI was significantly associated with an increased mortality (HR: 1.38, 95% CI 1.03–1.86 in 28 days; HR: 1.45, 95% CI 1.11–1.89 in 90 days; HR: 1.51, 95% CI 1.19–1.92 in 1 year). Sensitivity analyses yielded consistent results. Restricted cubic splines showed a progressively decreasing risk of mortality with increasing GNRI scores up to 110, approximately. Conclusion: Severe stroke patients with malnutrition experienced an increased risk of death compared to those without malnutrition. GNRI, as a simple and practical nutritional screening tool, can be used as a routine approach to the nutritional status of stroke patients.

Dianthus spp. is a genus with high economic and ornamental value in the Caryophyllaceae, which include the famous fresh-cut carnation and the traditional Chinese herbal medicine, D. superbus. Despite the Dianthus species being seen everywhere in our daily lives, its genome information and phylogenetic relationships remain elusive. Thus, we performed the assembly and annotation of chloroplast genomes for 12 individuals from seven Dianthus species. On this basis, we carried out the first comprehensive and systematic analysis of the chloroplast genome sequence characteristics and the phylogenetic evolution of Dianthus. The chloroplast genome of 12 Dianthus individuals ranged from 149,192 bp to 149,800 bp, containing 124 to 126 functional genes. Sequence repetition analysis showed the number of simple sequence repeats (SSRs) ranged from 75 to 80, tandem repeats ranged from 23 to 41, and pair-dispersed repeats ranged from 28 to 43. Next, we calculated the synonymous nucleotide substitution rates (Ks) of all 76 protein coding genes to obtain the evolution rate of these coding genes in Dianthus species; rpl22 showed the highest Ks (0.0471), which suggested that it evolved the swiftest. By reconstructing the phylogenetic relationships within Dianthus and other species of Caryophyllales, 16 Dianthus individuals (12 individuals reported in this study and four individuals downloaded from NCBI) were divided into two strongly supported sister clades (Clade A and Clade B). The Clade A contained five species, namely D. caryophyllus, D. barbatus, D. gratianopolitanus, and two cultivars (‘HY’ and ‘WC’). The Clade B included four species, in which D. superbus was a sister branch with D. chinensis, D. longicalyx, and F1 ‘87M’ (the hybrid offspring F1 from D. chinensis and ‘HY’). Further, based on sequence divergence analysis and hypervariable region analysis, we selected several regions that had more divergent sequences, to develop DNA markers. Additionally, we found that one DNA marker can be used to differentiate Clade A and Clade B in Dianthus. Taken together, our results provide useful information for our understanding of Dianthus classification and chloroplast genome evolution.

Hepatic metastases were reported in up to 70% of colorectal cancer patients, among which multifocal hepatic metastasis represents one of the complications that lead to poor prognosis. The majority of the patients carrying multifocal hepatic metastases required pharmaceutical treatments to reduce the tumor size prior to surgical resection. However, the clinical responses to pharmaceutical agents were difficult to predict due to the heterogeneous nature of the multifocal tumors. Here, we report a case with multifocal hepatic metastases from colorectal cancer that was resistant to the primary chemotherapy and Bevacizumab plus chemotherapy, but responded to the combined therapy of Cetuximab and FOLFOX. Genetic tests had revealed that the tumor was highly metastatic due to the mutations of the WNT signaling pathway, and the metastatic tumors might be sensitive to Cetuximab. Consistent with the molecular characterizations, the metastatic tumors continue to emerge after chemotherapy, and rapidly relapsed in great numbers after liver resection. However, the combined therapy of Cetuximab and FOLFOX guided by the genetic tests significantly reduced the size and number of metastatic tumors. To conclude, deciphering the mutation profiles of multifocal metastatic tumors may guide the determination of treatment tactics, which may benefit the patients with non-resectable advanced carcinoma.

Abstract Evaluating the therapeutic response and survival of lung cancer patients receiving first‐line chemotherapy has always been difficult. Limited biomarkers for evaluation exist and as a result histology represents an empiric tool to guide therapeutic decision making. In this study, molecular signatures associated with response and long‐term survival of lung cancer patients receiving first‐line chemotherapy are discovered. Whole‐exome sequencing is performed on pretherapeutic tissue samples of 186 patients [145 non‐small cell lung cancer (NSCLC) and 41 small cell lung cancer (SCLC)]. On the basis of genomic alteration characteristics, NSCLC patients can be classified into four subtypes (C1–C4). The long‐term survival is similar among different subtypes. SCLC patients are also divided into four subtypes and significant difference in their progression free survival is revealed (P < 0.001). NSCLC patients can be divided into three subtypes (S1–S3) based on TMB. A trend of worse survival associated with higher TMB in subtype S3 than in S1+S2 is found. In contrast, no significant correlations between molecular subtype and therapeutic response are observed. In conclusion, this study identifies several molecular signatures associated with response and survival to first‐line chemotherapy in lung cancer.

BackgroundBladder cancer (BLCA) is the 11th most common malignancy worldwide. Although significant improvements have been made in screening, diagnosis, and precise management in recent years, the prognosis of BLCA remains bleak.ObjectivesThis study aimed to investigate the prognostic significance of tumor-infiltrating immune cells and construct ceRNA networks in BLCA patients.MethodsThe expression data of BLCA patients were obtained from The Cancer Genome Atlas (TCGA) database. A competing endogenous RNA (ceRNA) network was constructed to identify the hub genes involved in the prognosis of BLCA. The CIBERSORT algorithm was utilized to investigate the infiltration levels of 22 subsets of immune cells. Ultimately, the nomogram was generated to visualize the survival probability of each patient, with the calibration curve being performed to assess its performance. Furthermore, the Pearson correlation test was used to explore the correlation between the identified hub genes in the ceRNA network and the prognostic-related immune cells.ResultsA total of eight elements in the ceRNA network were considered as key members and correlated with the prognosis of BLCA, including ELN, SREBF1, DSC2, TTLL7, DIP2C, SATB1, hsa-miR-20a-5p, and hsa-miR-29c-3p. T cells CD8, T cells follicular helper (Tfh), and neutrophils were identified as independent prognostic factors in BLCA. The co-expression analysis showed that there was a significant correlation between the identified hub genes and immune cells.ConclusionOur results suggest that the mechanism of hsa-miR-29c-3p regulates the expression of ELN and DSC2, and the infiltration of Tfh and neutrophils might play pivotal roles in the progression of BLCA.

The search for free-standing 2D materials has been one of the most important subjects in the field of studies on 2D materials and their applications. Recently, a free-standing monolayer of hydrogenated boron (HB) sheet has been synthesized by hydrogenation of borophene. The HB sheet is also called borophane, and its application is actively studied in many aspects. Here, we review recent studies on the electronic structures of polymorphic sheets of borophane. A hydrogenated boron sheet with a hexagonal boron frame was shown to have a semimetallic electronic structure by experimental and theoretical analyses. A tight-binding model that reproduces the electronic structure was given and it allows easy estimation of the properties of the material. Hydrogenated boron sheets with more complicated nonsymmorphic boron frames were also analyzed. Using the symmetry restrictions from the nonsymmorphic symmetry and the filling factor of hydrogenated boron sheets, the existence of a Dirac nodal line was suggested. These studies provide basic insights for research on and device applications of hydrogenated boron sheets.

Abstract Objectives Approximately, half of the acute stroke patients with minor symptoms were excluded from thrombolysis in some randomized controlled trials (RCTs). There is little evidence on treating minor strokes with rt‐PA. Here, we performed a systematic review and meta‐analysis to assess the safety and efficacy of thrombolysis in these patients. Methods PubMed, Embase, Web of Science, and Cochrane Library were searched in July 2018. All available RCTs and retrospective comparative studies that compared thrombolysis with nonthrombolysis' for acute minor stroke (NIHSS ≤ 5) with quantitative outcomes were included. Results Ten studies, including a total of 4,333 patients, were identified. The risk of intracranial hemorrhage (ICH) was higher in the rt‐PA group as compared with that in the non‐rt‐PA group (3.8% vs. 0.6%; p = .0001). However, there is no significant difference in the rate of mortality between the two groups (p = .96). The pooled rate of a good outcome in 90 days was 67.8% in those with rt‐PA and 63.3% in those without rt‐PA (p = .07). Heterogeneity was 43% between the studies (p = .08). After adjusting for the heterogeneity, thrombolysis was associated with good outcome (68.3% vs. 63.0%, OR 1.47; 95% CI 1.14–1.89; p = .003). In post hoc analyses, including only RCTs, the pooled rate of good outcome had no significant differences between the two groups (86.6% vs. 85.7%, 95% CI 0.44–3.17, p = .74; 87.4% vs. 91.9%, 95% CI 0.35–1.41, p = .32; before and after adjusting separately). Conclusions Although thrombolysis might increase the risk of ICH based on existing studies, patients with acute minor ischemic stroke could still benefit from thrombolysis at 3 months from the onset.

Flowers with more petals are of more ornamental value. It is well known that AGAMOUS (AG) is the core member of the C-class gene which plays an essential role in double flower formation and identification of stamens and carpels in Arabidopsis thaliana. We searched C-class genes in the genome of the carnation, and found two AG orthologs (DcaAGa, DcaAGb). Phylogenetic analysis showed that the two genes were closely related to the euAG subclade. Then we searched the genomes of other Caryophyllales plants (Beta vulgaris, Spinacia oleracea, Chenopodium quinoa) for C-class genes, and found that their C-class genes all belonged to the euAG subclade. Semi-quantitative PCR (sq-PCR) analysis indicated that the expression of DcaAG genes in the single flower phenotype was higher than that in the double flower phenotype. Quantitative real-time RT-PCR (qRT-PCR) analysis showed that the expressions of DcaAG genes in the flower bud were significantly different from those in the root, stem, and leaf between the single and double flower phenotype carnations, and that DcaAG genes were specifically expressed in the stamen and carpel of carnation. Moreover, the expression of other floral organ identity genes (AP1 and AP2, PI and AP3, SEP1 and SEP3 corresponding to the A-, B-, and E-class of genes, respectively) showed no significant difference in all floral organs between the single and double flower phenotype carnations, suggesting that C-class (DcaAG) genes might play an important role in the double flower phenotype in carnation. Petal loss or decrease, precocious flowering, silique shortening, and seed sterility were observed in 35S::DcaAGa and 35S::DcaAGb transgenic Arabidopsis plants. All these results show that DcaAG genes might affect the petal number negatively and have a specific function in stamen and carpel development in carnation.

Euphorbia helioscopia Linn. known as a traditional Chinese medicine of Euphorbiaceae, which contains terpenes, steroids, flavonoids, acetophenones, tannins, phenylpropanoids, cerebrosides and so on. Euphorbia helioscopia L. was used to treat malignant tumors and chronic obstructive pulmonary diseases such as cough, phlegm-turbidity, asthma, and chronic bronchitis. The complete chloroplast genome was assembled by Illumina paired-end reads data. The length of circular cp genome distribution in 160,041 bp, containing a large single-copy region (LSC) of 88,832 bp, a small single-copy region (SSC) of 17,145 bp and a pair of inverted repeat (IR) regions of 27,032 bp. In addition, 11 genes possess a single intron, while the other two genes (ycf3, clpP) have a couple of introns. The GC content of entire Euphorbia helioscopia L. cp genome, LSC, SSC and IR regions are 35.9, 33.1, 30.3, and 42.3%, respectively. From the NJ phylogenetic tree analysis showed that Euphorbia helioscopia L. and Euphorbia esula are closely related to each other within the family Euphorbiaceae.

The Malcolm Baldrige National Quality Award (MBNQA) is well known to assess quality and business processes in a variety of sectors, including government. In this study, we investigate the relationship between aspects of the MBNQA’s leadership triad and knowledge management in an e-government context. Specifically, we survey 1,100 employees of a medium-sized city government in the United States to investigate the relationship between leadership triad components, leadership strategic planning, and customer/market focus, with knowledge management. Our results show that these components are significantly related to knowledge management and are important in the delivery of e-government applications to the citizenry.