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Abstract Background Phenylalanine ammonia-lyase (PAL) serves as a key gateway enzyme, bridging primary metabolism and the phenylpropanoid pathway, and thus playing an indispensable role in flavonoid, anthocyanin and lignin biosynthesis. PAL gene families have been extensively studied across species using public genomes. However, a comprehensive exploration of PAL genes in Epimedium species, especially those involved in prenylated flavonol glycoside, anthocyanin, or lignin biosynthesis, is still lacking. Moreover, an in-depth investigation into PAL gene family evolution is warranted. Results Seven PAL genes (EpPAL1-EpPAL7) were identified. EpPAL2 and EpPAL3 exhibit low sequence identity to other EpPALs (ranging from 61.09 to 64.38%) and contain two unique introns, indicating distinct evolutionary origins. They evolve at a rate ~ 10 to ~ 54 times slower compared to EpPAL1 and EpPAL4-7, suggesting strong purifying selection. EpPAL1 evolved independently and is another ancestral gene. EpPAL1 formed EpPAL4 through segmental duplication, which lead to EpPAL5 and EpPAL6 through tandem duplications, and EpPAL7 through transposed duplication, shaping modern EpPALs. Correlation analysis suggests EpPAL1, EpPAL2 and EpPAL3 play important roles in prenylated flavonol glycosides biosynthesis, with EpPAL2 and EpPAL3 strongly correlated with both Epimedin C and total prenylated flavonol glycosides. EpPAL1, EpPAL2 and EpPAL3 may play a role in anthocyanin biosynthesis in leaves. EpPAL2, EpPAL3, EpPAL6, and EpPAL7 might be engaged in anthocyanin production in petals, and EpPAL2 and EpPAL3 might also contribute to anthocyanin synthesis in sepals. Further experiments are needed to confirm these hypotheses. Novel insights into the evolution of PAL gene family suggest that it might have evolved from a monophyletic group in bryophytes to large-scale sequence differentiation in gymnosperms, basal angiosperms, and Magnoliidae. Ancestral gene duplications and vertical inheritance from gymnosperms to angiosperms likely occurred during PAL evolution. Most early-diverging eudicotyledons and monocotyledons have distinct histories, while modern angiosperm PAL gene families share similar patterns and lack distant gene types. Conclusions EpPAL2 and EpPAL3 may play crucial roles in biosynthesis of prenylated flavonol glycosides and anthocyanins in leaves and flowers. This study provides novel insights into PAL gene family evolution. The findings on PAL genes in E. pubescens will aid in synthetic biology research on prenylated flavonol glycosides production.

Abstract Phosphorus, a crucial macronutrient essential for plant growth and development. Due to widespread phosphorus deficiency in soils, phosphorus deficiency stress has become one of the major abiotic stresses that plants encounter. Despite the evolution of adaptive mechanisms in plants to address phosphorus deficiency, the specific strategies employed by species such as Epimedium pubescens remain elusive. Therefore, this study observed the changes in the growth, physiological reponses, and active components accumulation in E. pubescensunder phosphorus deficiency treatment, and integrated transcriptome and miRNA analysis, so as to offer comprehensive insights into the adaptive mechanisms employed by E. pubescens in response to phosphorus deficiency across various stages of phosphorus treatment. Remarkably, our findings indicate that phosphorus deficiency induces root growth stimulation in E. pubescens, while concurrently inhibiting the growth of leaves, which are of medicinal value. Surprisingly, this stressful condition results in an augmented accumulation of active components in the leaves. During the early stages (30 days), leaves respond by upregulating genes associated with carbon metabolism, flavonoid biosynthesis, and hormone signaling. This adaptive response facilitates energy production, ROS scavenging, and morphological adjustments to cope with short-term phosphorus deficiency and sustain its growth. As time progresses (90 days), the expression of genes related to phosphorus cycling and recycling in leaves is upregulated, and transcriptional and post-transcriptional regulation (miRNA regulation and protein modification) is enhanced. Simultaneously, plant growth is further suppressed, and it gradually begins to discard and decompose leaves to resist the challenges of long-term phosphorus deficiency stress and sustain survival. In conclusion, our study deeply and comprehensively reveals adaptive strategies utilized by E. pubescens in response to phosphorus deficiency, demonstrating its resilience and thriving potential under stressful conditions. Furthermore, it provides valuable information on potential target genes for the cultivation of E. pubescens genotypes tolerant to low phosphorus.

Abstract Background Combined serplulimab and chemotherapy demonstrated improved clinical survival outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) and PD-L1 combined positive scores (CPS) ≥ 1. The present study aimed to evaluate the economic viability of integrating serplulimab in combination with chemotherapy as a potential therapeutic approach for treating ESCC in China. Methods A Markov model was constructed to evaluate the economic and health-related implications of combining serplulimab with chemotherapy. With the incremental cost-effectiveness ratio (ICER), costs and results in terms of health were estimated. For assessing parameter uncertainty, one-way and probabilistic sensitivity studies were carried out. Results The combination of serplulimab and chemotherapy yielded incremental costs and QALYs of $3,163 and 0.14, $2,418 and 0.10, and $3,849 and 0.15, respectively, for the overall population as well as patients with PD-L1 CPS1-10 and PD-L1 CPS ≥ 10. This corresponds to ICER values per QALY of $23,657, $23,982, and $25,134. At the prespecified WTP limit, the probabilities of serplulimab with chemotherapy being the preferred intervention option were 74.4%, 61.3%, and 78.1% for the entire patient population, those with PD-L1 1 ≤ CPS

Aluminum (Al) is a common neurotoxicant in the environment, but the molecular mechanism of its toxic effects is still unclear. Studies have shown that aluminum exposure causes an increase in neuronal apoptosis. The aim of this study was to investigate the mechanism and signaling pathway of neuronal apoptosis induced by aluminum exposure. The rat model was established by intraperitoneal injection of maltol aluminum for 90 days. The results showed that the escape latency of the three groups exposed to maltol aluminum was higher than that of the control group on the 3rd, 4th and 5th days of the positioning cruise experiment (P

Background: Thyroid dysfunction is common in critical illness and may influence prognosis. However, the value of TSH in patients with severe diseases remains unclear. The aim of this study was to investigate the association between TSH and the clinical prognosis of critically ill patients. Methods: This retrospective study identified patients who were admitted to the ICU in the Medical Information Mart for Intensive Care (MIMIC-IV) database (version 2.2). A total of 6432 patients were divided into four groups based on TSH quartiles (Q1, 3.10 mIU/L). The clinical outcomes were defined as all-cause 7-, 30-, and 90-year mortality after ICU admission. Restricted cubic splines (RCSs) for nonlinear associations were generated to visualize the relationship between TSH levels and clinical outcomes. The survival differences among the four groups were also analyzed using Kaplan‒Meier curves and log rank tests. Univariable and multivariable Cox proportional hazards regression were further used to assess the association between TSH levels and clinical outcomes. Results: After multivariate adjustment, a U-shaped relationship was observed between TSH levels and all-cause 7-, 30-, and 90- mortality among patients with severe disease (all P

In this paper, we study the attracting sets for two plankton models perturbed by bounded noises which are modeled by the Ornstein-Uhlenbeck process. Specifically, we prove the existence and uniqueness of the solutions for these random models, as well as the existence of the attracting sets for the random dynamical systems generated by the solutions. In order to further reveal the survival of plankton species in a fluctuating environment, we analyze the internal structure of the attracting sets and give sufficient conditions for the persistence and extinction of the plankton species. Some numerical simulations are shown to support our theoretical results.

Herba Epimedii (Epimedium) leaves are rich in prenylated flavonol glycosides (PFGs) with high medicinal value. However, the dynamics and regulatory network of PFG biosynthesis remain largely unclear. Here, we combined metabolite profiling (targeted to PFGs) and a high-temporal-resolution transcriptome to elucidate PFGs’ regulatory network in Epimedium pubescens and identified key candidate structural genes and transcription factors (TFs) involved in PFG accumulation. Chemical profile analysis revealed that PFG content was quite different between buds and leaves and displayed a continuous decline with leaf development. The structural genes are the determinant reasons, and they are strictly regulated by TFs under temporal cues. We further constructed seven time-ordered gene co-expression networks (TO-GCNs) of PFG biosynthesis genes (including EpPAL2, EpC4H, EpCHS2, EpCHI2, EpF3H, EpFLS3, and EpPT8), and three flavonol biosynthesis routines were then predicted. The TFs involved in TO-GCNs were further confirmed by WGCNA analysis. Fourteen hub genes, comprising 5 MYBs, 1 bHLH, 1 WD40, 2 bZIPs, 1 BES1, 1 C2H2, 1 Trihelix, 1 HD-ZIP, and 1 GATA were identified as candidate key TFs. The results were further validated by TF binding site (TFBS) analysis and qRT-PCR. Overall, these findings provide valuable information for understanding the molecular regulatory mechanism of PFGs biosynthesis, enriching the gene resources, which will guide further research on PFG accumulation in Epimedium.

Abstract Triboelectric nanogenerators (TENGs) can directly harvest energy via solid–liquid interface contact electrification, making them very suitable for harvesting raindrop energy and as active rainfall sensors. This technology is promising for realizing a fully self-powered system for autonomous rainfall monitoring combined with energy harvesting/sensing. Here, we report a raindrop energy-powered autonomous rainfall monitoring and wireless transmission system (R-RMS), in which a raindrop-TENG (R-TENG) array simultaneously serves as a raindrop energy harvester and rainfall sensor. At a rainfall intensity of 71 mm/min, the R-TENG array can generate an average short-circuit current, open-circuit voltage, and maximum output power of 15 μA, 1800 V, and 325 μW, respectively. The collected energy can be adjusted to act as a stable 2.5 V direct-current source for the whole system by a power management circuit. Meanwhile, the R-TENG array acts as a rainfall sensor, in which the output signal can be monitored and the measured data are wirelessly transmitted. Under a rainfall intensity of 71 mm/min, the R-RMS can be continuously powered and autonomously transmit rainfall data once every 4 min. This work has paved the way for raindrop energy-powered wireless hyetometers, which have exhibited broad prospects in unattended weather monitoring, field surveys, and the Internet of Things.

Epimedium L. is an important genus in the family Berberidaceae. Epimedium trifoliolatobinatum (Koidz.) Koidz. 1939 is inhabited on the west side of the Shikoku, Japan. In this study, the first complete chloroplast genome of E. trifoliolatobinatum was assembled with Illumina paired-end sequencing data, which was 157,272 bp in length with a total GC content of 38.70%. A total of 112 unique genes were annotated, comprising 78 protein-coding genes, 30 tRNA genes, and four rRNA genes. The phylogenetic analysis suggested that E. trifoliolatobinatum was sister to E. koreanum. The current results provided fundamental information for further conducting molecular systematics and phylogenetic research of Epimedium genus.

Epimedium L. is an important medicinal herbaceous genus that belongs to the family Berberidaceae. Epimedium campanulatum Ogisu is a plant species only inhabited in the northwestern part of Sichuan province, China. Here, we reported the complete chloroplast genome sequence, assembly, and characterization of E. campanulatum. The chloroplast genome of E. campanulatum was 157,343 bp in length, and a total of 112 unique genes were identified. Phylogenetic results revealed that E. campanulatum formed a sister relationship with the cluster of Epimedium ecalcaratum, Epimedium davidii, and Epimedium chlorandrum. Our findings provided valuable data for future taxonomic and phylogenetic research within the genus Epimedium.

Epimedium pubescens is a species of the family Berberidaceae in the basal eudicot lineage, and a main plant source for the traditional Chinese medicine “Herba Epimedii”. The current study achieved a chromosome-level genome assembly of E. pubescens with the genome size of 3.34 Gb, and the genome guided discovery of a key prenyltransferase (PT) in E. pubescens. Our comparative genomic analyses confirmed the absence of Whole Genome Triplication (WGT-γ) event shared in core eudicots and further revealed the occurrence of an ancient Whole Genome Duplication (WGD) event approximately between 66 and 81 Million Years Ago (MYA). In addition, whole genome search approach was successfully applied to identify 19 potential flavonoid PT genes and an important flavonoid PT (EpPT8) was proven to be an enzyme for the biosynthesis of medicinal compounds, icaritin and its derivatives in E. pubescens. Therefore, our results not only provide a good reference genome to conduct further molecular biological studies in Epimedium genus, but also give important clues for synthetic biology and industrial production of related prenylated flavonoids in future.

Introduction This study aimed to evaluate the publication delays and correlative factors of peer-reviewed ophthalmology journals. Methods The ophthalmology journals listed in the Journal Citation Report 2020 were retrieved from the Web of Science database. The first original research article of each journal issue from January to December 2020 was extracted, and its submission, final revision, acceptance, and publication dates were obtained. Information on impact factors, advance online publication (AOP) status, open access (OA) rate and acceptance rate in 2020 was also collected. The correlations between publication delays and potential associated factors were analyzed. Results A total of 58 ophthalmology journals were included and information on 685 articles was collected. The median times from submission to acceptance, from acceptance to publication, and from submission to publication were 118.0 (IQR, 74.0–185.0) days, 31.0 (IQR, 15.0–64.0) days, and 161.0 (IQR, 111.0–232.0) days, respectively. A higher impact factor was correlated with shorter delays of acceptance and publication (P < 0.05). There was a positive correlation between acceptance rates and publication delays (r = 0.726, P = 0.007). Forty-seven (81.03%) journals provided AOP. There was no statistically significant difference for impact factors and publication delays between journal with and without AOP (all P > 0.05). No correlation between OA rate and publication delays or impact factors was detected (all P > 0.05). Conclusions Journals with higher impact factors and lower acceptance rates tend to have quicker publication processes. No significant associations were detected between publication delays and AOP or OA rate.

Phytochemical investigation was carried out for the flowers of Epimedium acuminatum Franchet. by first conducting LC-MS analysis, leading to the identification of 32 compounds. Furthermore, guided by LC-MS profiling, three new 8-prenylated quercetin glycosides (3′-hydroxylikarisoside C, 3′-hydroxylepimedoside E, 3′-hydroxyldiphylloside B), one new anthocyanin (delphinidin-3-O-p-coumaroyl-sophoroside) and six known compounds were isolated from the flowers of E. acuminatum for the first time, and their structures were characterized based on spectroscopic methods including 1D and 2D NMR, and HRESIMS. Combining our discoveries and literature survey, a revised classification of Epimedium flavonols was proposed as Type A (8-prenylated kaempferol based), which was further subdivided into subtype icaritin and subtype demethylicaritin, and Type B (8-prenylated quercetin based), which was further subdivided into subtype 3′-hydroxylicaritin and subtype 3′-hydroxyldemethylicaritin. The structure-activity relationship (SAR) study was carried out by comparing testosterone production-promoting activities of all the new compounds along with nine related Epimedium flavonols, revealing that the new 8-prenylated quercetin glycosides (subtype 3′-hydroxyldemethylicaritin in Type B) exhibited lower testosterone production-promoting activities in rat primary Leydig cells than Epimedium flavonols of subtype demethylicaritin in Type A, but possessed higher activities than the Epimedium flavonols of subtype icaritin in Type A. These results suggested that either methylation at C-4′ position or hydroxylation at C-3′ position of ring B could significantly reduce the testosterone production-promoting activities of Epimedium flavonols.

Abstract Genome‐wide association studies (GWAS) have reported a handful of loci associated with lung cancer risk, of which the pathogenic pathways are largely unknown. We performed cis‐expression quantitative trait loci (eQTL) mapping for 376 lung cancer related GWAS loci in 227 TCGA lung adenocarcinoma (LUAD) and reported two risk loci as eQTL of miRNA. Among the miRNAs in association with lung cancer risk, we further predicted and validated miR‐3130‐5p as an intermediate modulator of risk loci 2q33 and the tumor suppressor NDUFS1. We assessed the phenotypic impacts of the interaction between miR‐3130‐5p and NDUFS1 in both lung cancer cell lines and mice xenograft models. As a result, miR‐3130‐5p directly regulates the expression of NDUFS1 and the corresponding tumor invasiveness, migration and epithelial‐mesenchymal transition (EMT). Our findings provide important clues for the pathogenic mechanism of 2q33 in lung carcinogenesis which informs clinical diagnosis and prognosis of LUAD. We performed a cis‐eQTL analysis for 376 lung cancer risk loci based on the expression profiles of 251 miRNAs in a cohort of 227 TCGA lung adenocarcinoma. We report a novel pathogenic pathway of 2q33 via miR‐3130‐5p and NDUFS1.

Abstract Background Allelic imbalance (AI) in tumors is caused by chromosomal and sub-chromosomal gains and losses. Results We evaluated AI at 109,086 germline exonic SNP loci in four cancer types, and identified a set of SNPs that demonstrate strong tumor allele specificity in AI events. Further analyses demonstrated that these alleles show consistently different frequencies in the cancer population compared to the healthy population and are significantly enriched for predicted protein-damaging variants. Moreover, genes harboring SNPs that demonstrate allele specificity are enriched for cancer-related biological processes and are more likely to be essential in cancer cells. Conclusions In summary, our study provides a unique and complementary method to identify genes and variants that are relevant to carcinogenesis.

Human motions often contain information that is useful for orthopedic/neural disease diagnosis, rehabilitation, and prevention. Here, the authors show a badge-reel-like stretch sensing device with a grating-structured triboelectric nanogenerator for joints/spine bending or stretching sensing.

Abstract Background Overexpressed vascular endothelial growth factor A (VEGFA) and phosphorylated signal transducer and activator of transcription 3 (P-STAT3) cause unrestricted tumor growth and angiogenesis of breast cancer (BRCA), especially triple-negative breast cancer (TNBC). Hence, novel treatment strategy is urgently needed. Results We found sphingosine 1 phosphate receptor 1 (S1PR1) can regulate P-STAT3/VEGFA. Database showed S1PR1 is highly expressed in BRCA and causes the poor prognosis of patients. Interrupting the expression of S1PR1 could inhibit the growth of human breast cancer cells (MCF-7 and MDA-MB-231) and suppress the angiogenesis of human umbilical vein endothelial cells (HUVECs) via affecting S1PR1/P-STAT3/VEGFA axis. Siponimod (BAF312) is a selective antagonist of S1PR1, which inhibits tumor growth and angiogenesis in vitro by downregulating the S1PR1/P-STAT3/VEGFA axis. We prepared pH-sensitive and tumor-targeted shell-core structure nanoparticles, in which hydrophilic PEG2000 modified with the cyclic Arg-Gly-Asp (cRGD) formed the shell, hydrophobic DSPE formed the core, and CaP (calcium and phosphate ions) was adsorbed onto the shell; the nanoparticles were used to deliver BAF312 (BAF312@cRGD-CaP-NPs). The size and potential of the nanoparticles were 109.9 ± 1.002 nm and − 10.6 ± 0.056 mV. The incorporation efficacy for BAF312 was 81.4%. Results confirmed BAF312@cRGD-CaP-NP could dramatically inhibit tumor growth and angiogenesis in vitro and in MDA-MB-231 tumor-bearing mice via downregulating the S1PR1/P-STAT3/VEGFA axis. Conclusions Our data suggest a potent role for BAF312@cRGD-CaP-NPs in treating BRCA, especially TNBC by downregulating the S1PR1/P-STAT3/VEGFA axis. Graphic abstract

Epimedium L. is a medicinally important herbaceous genus in the family Berberidaceae. Epimedium fargesii Franch. is only narrowly inhabited in the Daba Mountains in China. Here, we sequenced and assembled the first complete chloroplast genome of Epimedium fargesii Franch. The chloroplast genome of E. fargesii was 157,208 bp in length, with a total GC content of 38.77%. A total of 112 unique genes were identified, including 78 protein-coding genes, 30 tRNA genes, and four rRNA genes. Phylogenetic analysis indicated that E. fargesii formed a sister relationship with E. wushanense T. S. Ying. Our results provided fundamental data for further taxonomic and phylogenetic research of the genus Epimedium.

Epimedium L. is the largest herbaceous genus in the family Berberidaceae which comprises more than 60 species. Epimedium sutchuenense Franch. is narrowly inhabited in the Daba Mountains of China. In the current study, we assembled the first complete chloroplast genome of E. sutchuenense through Illumina paired-end sequencing. The complete chloroplast genome of E. sutchuenense was 157,218 bp in length and the total GC content was 38.78%. A total of 112 unique genes were identified, including 78 protein-coding genes, 30 tRNA genes and 4 rRNA genes. The phylogenetic analysis demonstrated that E. sutchuenense was sister to Epimedium wushanense T. S. Ying. Our results provided valuable information for further phylogenetic research and germplasm exploration of Epimedium genus.

Epimedium L. is an important medicinal herbaceous genus in the family Berberidaceae. Epimedium platypetalum K. Mey. is a plant species only narrowly distributed in the western part of China. Here, the complete chloroplast genome of Epimedium platypetalum was assembled. The chloroplast genome of E. platypetalum was 159,088 bp in length, with a total GC content of 38.79%. A total of 112 unique genes were identified, among which 78 are protein-coding genes, 30 tRNA genes, and four rRNA genes. Phylogenetic results revealed that E. platypetalum formed a sister relationship with E. membranaceum K. Mey. Our findings provided valuable data for future research on phylogenetic relationship and germplasm exploration within the genus Epimedium.

Tobacco smoking is the major cause of non-small-cell-lung cancer (NSCLC). However, it is barely known how smoking impact the tumor immune environment (TIME) of lung cancer.We integrated single-cell RNA-seq and bulk RNA-seq data from several studies to systematically study the impact of smoking on T cells in treatment naïve NSCLC patients. We defined a set of smoking-induced differentially expressed genes (SIDEGs) in different cells in TIME.. Specifically, we defined a smoking-related tumor-specific Treg subset, ADAM12+ CTLA4+ Tregs according to the trajectory analysis and highly express genes in cell adhesion pathways and lipid metabolism. Using independent datasets from treatment naïve patients, we found that the fraction of ADAM12+ CTLA4+ Tregs are significantly increased in patients with smoking history. Moreover, the fraction of ADAM12+ CTLA4+ Tregs are positively correlated with the fraction of exhausted T cells. Additionally, we reconstructed the spatial organization of the tumor immune microenvironment and found that ADAM12+ CTLA4+ Tregs more actively communicate with LAYN+CD8+ exhausted T cells compared with ADAM12−CTLA4+ Tregs.Our data demonstrate that smoking induced a unique subset of tumor-specific activated Tregs which interact with exhausted T cells in the TIME. Our findings not only explained how smoking impact the TIME but also provide new targets and biomarkers for precision immunotherapy of lung cancer.

Preparation and application of sustainable polymers derived from renewable resources are of great significance. The aim of this study is to synthesize a kind of sustainable polymeric micelles from rosin and vegetable oils via atom transfer radical polymerization (ATRP) and to investigate the doxorubicin delivery properties of these micelles. Dehydroabietic acid–based poly lauryl methacrylate (DA-PLMA) with narrow PDI of 1.13 was prepared in a well-controlled process using rosin as an ATRP initiator. Thereafter, carboxylic groups were introduced to form poly methacrylic acid (PMAA) moieties in DA-PLMA polymer via acid hydrolysis. The resulted DA-PLMA-PMAA could self-assemble in water to form pH-dependent polymeric micelles with a diameter of ∼65 nm and PDI as low as 0.105. Owing to the existence of rosin, DA-PLMA-PMAA micelles also showed self-fluorescence properties. In addition, Dox-loaded micelles were prepared in aqueous solution with the drug-loading capacity as high as 16.0% and showed sustained-release characteristics. These results demonstrate great promise for designing polymeric micellar from rosin and vegetable oils.

Abstract Triboelectric nanogenerator (TENG) is suitable for collecting low frequency and weak mechanical energy, which has great prospects in powering distributed wireless sensor network nodes. Seeking economical, simple, and efficient fabrication method is highly interesting for researchers who focus on green innovation energy development. Here, we proposed a one‐stop fabrication method of the TENG based on three‐dimensional (3D) printing. A series of functional printing inks were first prepared by doping nickel powders and polytetrafluoroethylene micro particles into the Dragon Slow Skin 10 (DSS10) substrate with different proportions. Each layer of the TENG in contact‐separation mode can be printed in sequence with prepared inks at a programmable three‐axis translation stage, which is of complete encapsulation, isotropy, flexibility, and stretchability. On the basis, the 3D‐printed plantar energy collector and energy‐harvesting bracelet are fabricated and implanted on the soles and wrists, respectively, which can collect biomechanical energy and continuously power portable electronic devices including electronic watch and thermometer. This work provides the advanced fabrication strategy for TENG with low cost and environmental friendliness, which demonstrates great prospects of TENG in standardized and mass manufacturing.

Many cancer risk loci act as expression quantitative trait loci (eQTLs) of transcripts including non-coding RNA. Long non-coding RNAs (lncRNAs) are implicated in various human cancers. However, the pathological and clinical impacts of the genetic determinants of lncRNAs in cancers remain largely unknown. In this study, we performed eQTL mapping of lncRNA expression (elncRNA) in 11 TCGA cancer types and characterized the biological processes of elncRNAs in the setting of genomic location, cancer treatment responses, and immune microenvironment. As a result, 10.86% of the cis-eQTLs and 1.67% of the trans-eQTLs of lncRNA were related to known genome-wide association studies (GWAS) cancer risk loci. The elncRNAs are significantly enriched for those which are previously annotated as predictive of drug sensitivities in cancer cell lines. We further revealed the downstream transcriptomic effectors of eQTL-elncRNA pairs. Our data specifically suggested that the genes affected by eQTL-elncRNA associations are enriched in the immune system processes and eQTL-elncRNA associations influence the constitution of tumor infiltrating lymphocytes. In ovarian cancer, the “rs34631313-AC092580.4” pair was associated with increased fraction of CD8+ T cells and M1 Macrophage; whereas in KIRC, the “rs9546285-LINC00426” pair was associated with increased fraction of CD8+ T cells and a decreased fraction of M2 macrophages. Our findings provide a systematic view of the transcriptomic impacts of the eQTL landscape of lncRNA in human cancers and suggest its strong potential relevance to cancer immunity and treatment.

Epimedium xichangense, a critically endangered herb with limited population, mainly distributes in Sichuan province, China. In our study, we obtained the complete chloroplast genome of E. xichangense with a length of 158,955 bp, including a large single copy region of 86,478 bp, small single copy region of 17,027 bp, and a pair of inverted repeat regions of 27,725 bp. The GC content in the whole chloroplast genome of E. xichangense is 38.81%. Among the 112 unique genes in the circular genome, 30 tRNA, four rRNA and 78 protein-coding genes were successfully annotated. We constructed the Maximum likelihood (ML) tree with 26 species, and came to the conclusion that E. xichangense was phylogenetically closely related to E. acuminatum and E. chlorandrum.

Background: KRAS-mutant lung adenocarcinomas (LUADs) are heterogeneous and frequently occur in smokers. The heterogeneity of KRAS-mutant LUAD has been an obstacle for the drug discovery. Methods: We integrated multiplatform datatypes and identified two corresponding subtypes in the patients and cell lines. We further characterized the features of these two subtypes and performed drug screening to identify subtype-specific drugs. Finally, we used the defining features of the KRAS subtypes for drug sensitivity prediction. Findings: Patient-Subtype 1 (PS1) was characterized by increased smoking-related mutational signature activity, a low tumor-infiltrating lymphocyte (TIL)-associating score and STK11/KEAP1 co-mutations. Patient-Subtype 2 (PS2) was characterized by an increased smoking-related methylation signature activity, a high TIL-associating score and increased KRAS dependency. The cell line subtypes faithfully recapitulated all the patients' features. Drug screening of the two cell line subtypes yielded several potential candidates, such as cytarabine and enzastaurin for Cell-line-Subtype 1 (CS1) and a BTK inhibitor QL-XII-61 for Cell-line-Subtype 2 (CS2). The defining features, such as smoking-related methylation signature, were significantly associated with the sensitivity to several drugs. Interpretation: The heterogeneity of KRAS-mutant LUAD is associated with smoking-related genomic and epigenomic aberration along with other features such as immunogenicity, KRAS dependency and STK11/KEAP1 co-mutations. These features might be used as biomarkers for drug sensitivity prediction. Fund: This research was funded by the Young Scientists Fund of the National Natural Science Foundation of China, the Natural Science Foundation of Fujian Province, China and the Education and Research Foundation for Young Scholars of Education Department of Fujian Province, China. Keywords: KRAS-mutant lung adenocarcinoma, KRAS subtypes, TIL-associating score, Smoking-related methylation signature, Smoking-related mutational signature, Drug sensitivity prediction

The fluxgate magnetometer has the advantages of having a small volume and low power consumption and being light weight and is commonly used to detect weak magnetic targets, including ferrous metals, unexploded bombs (UXOs), and underground corrosion pipelines. However, the detection accuracy of the fluxgate magnetometer is affected by its own error. To obtain more accurate detection data, the sensor must be error-corrected before application. Previous researchers easily fell into the local minimum when solving error parameters. In this paper, the error correction method was proposed to tackle the problem, which combines the Dragonfly algorithm (DA) and the Levenberg–Marquardt (LM) algorithm, thereby solving the problem of the LM algorithm and improving the accuracy of solving error parameters. Firstly, we analyzed the error sources of the three-axis magnetic sensor and established the error model. Then, the error parameters were solved by using the LM algorithm and DA–LM algorithm, respectively. In addition, by comparing the results of the two methods, we found that the error parameters solved by using the DA–LM algorithm were more accurate. Finally, the magnetic measurement data were corrected. The simulation results show that the DA–LM algorithm can accurately solve the error parameters of the triaxial magnetic sensor, proving the effectiveness of the proposed algorithm. The experimental results show that the difference between the corrected and the ideal total value was decreased from 300 nT to 5 nT, which further verified the effectiveness of the DA–LM algorithm.

The ocean is a very important arena in modern warfare where all marine powers deploy their military forces. Due to the complex environment of the ocean, underwater equipment has become a very threatening means of surprise attack in modern warfare. Therefore, the timely and effective detection of underwater moving targets is the key to obtaining warfare advantages and has important strategic significance for national security. In this paper, magnetic flux induction technology was studied with regard to the difficulty of detecting underwater concealed moving targets. Firstly, the characteristics of a magnetic target were analyzed and an equivalent magnetic dipole model was established. Secondly, the structure of the rectangular induction coil was designed according to the model, and the relationship between the target’s magnetism and the detection signal was deduced. The variation curves of the magnetic flux and the electromotive force induced in the coil were calculated by using the numerical simulation method, and the effects of the different motion parameters of the magnetic dipole and the size parameters of the coil on the induced electromotive force were analyzed. Finally, combined with the wavelet threshold filter, a series of field tests were carried out using ships of different materials in shallow water in order to verify the moving target detection method based on magnetic flux induction technology. The results showed that this method has an obvious response to moving targets and can effectively capture target signals, which verifies the feasibility of the magnetic flux induction detection technology.

The genus of Epimedium belongs to Berberidaceae family, which is famous for their medicinal and ornamental value. In recent years, Epimedium has attracted increasing attention due to their medicinal and nutritive value. In this research, we reported the complete chloroplast (cp) genome of Epimedium enshiense. The complete chloroplast of this species is 157,076 bp in length, including a pair of invert repeat regions (IRS) (25,833 bp) that is divided by a large single copy area (LSC) (88,340 bp) and a small single copy area (SSC) (17,070 bp). The circular chloroplast genome of E. enshiense contains 112 unique genes, composing of 78 protein-coding genes, 30 tRNA, and four rRNA genes. Phylogenetic analysis indicates that E. enshiense has a closer relationship with E. dolichostmon.

Epimedium rhizomatosum is a rare endemic plant species inhabited in some high-elevation mountain area in the Sichuan province of China. In this study, we assembled the complete chloroplast genome of E. rhizomatosum from Illumina short-read sequencing data. The chloroplast genome of E. rhizomatosum was 159,151 bp in length, which comprises of a large single copy (LSC) region of 86,604 bp, a small single copy (SSC) region of 17,071 bp and two inverted repeat regions (IRa and IRb) of 27,737 bp for each. The total GC content of E. rhizomatosum chloroplast genome was 38.8%, while the corresponding values of LSC, SSC, and IR regions were 37.3%, 32.8%, and 43.0%, respectively. A total of 112 unique genes was identified from the chloroplast genome of E. rhizomatosum, including 78 protein-coding genes, four ribosomal RNA genes, and 30 tRNA genes. The phylogenetic analysis showed that E. rhizomatosum closely related to E. acuminatum. Our study will provide useful information on further clarifying the phylogenetic and evolutionary relationship in the genus Epimedium.

Molecular dynamics simulation is employed to study the formation of NiTi thin films on Ni (001) substrates simultaneously deposited with Ni and Ti atoms in this work. The effects of different deposition parameters on surface morphology and atomic distribution of deposited NiTi films are investigated. The deposition parameters mainly include incident energy, incident angle and substrate temperature. The simulation results indicate that incident energy and substrate temperature have a significant effect on the surface roughness of deposited NiTi film. However, incident angles below 30° have little influence on surface roughness of NiTi film. The simulation results show that increasing substrate temperature and incident energy can enhance the intermixing between substrate and film. The content of Ni on the NiTi film surface increase significantly with the raise of incident energy. The defect analysis of the deposited film demonstrates that incident angle mainly affects the number of voids and vacancies in the film. For film samples of different deposition conditions, the films deposited at larger incident angles contain more voids and vacancies. While the films deposited at higher substrate temperatures contain fewer voids and vacancies. Keywords: Deposition, NiTi, Thin films, Molecular dynamics simulation

Piezoelectric energy harvesting technology using the piezoelectric circular diaphragm (PCD) has drawn much attention because it has great application potential in replacing chemical batteries to power microelectronic devices. In this article, we have found a non-uniform strain distribution inside the PCD energy harvester. From the edge to the center of the ceramic disk, its output voltage first increases and then decreases. This uneven output voltage reduces the output power of the PCD energy harvester. Based on this phenomenon, we reduce the ceramic disk diameter and dig a hole in the center, analyzing the effect of removing the ceramic disk’s low output voltage part on the PCD energy harvester. The experimental results show that removing the ceramic disk’s low output voltage part can improve the output power, reduce the resonance frequency, and increase the optimal impedance of the PCD energy harvester. Under the conditions of 10 g proof mass, 9.8 m/s2 acceleration, the PCD energy harvester with a 19-mm diameter and a 6-mm hole can reach a maximum output power of 8.34 mW.

Epimedium mikinorii is a vulnerable species in the Epimedium genus of Berberaceae. Here, we sequenced the complete chloroplast genome of E. mikinorii, which is 157,136 bp in length, and is a typical quadripartite circular molecule composed of two inverted repeats (IRs) of 25,896 bp for each, a large single-copy region (LSC) of 88,395 bp, and a small single-copy region (SSC) of 16,949 bp. The complete chloroplast genome of E. mikinorii contains 134 genes, including 83 protein-coding genes, 38 tRNA genes, 8 rRNA genes, and 5 pseudogenes. Phylogenetic analysis showed that E. mikinorii was closely related to E. dolichostemon.

Epimedium qingchengshanense G. Y. Zhong & B. L. Guo is an endangered species with high ornamental value and medicinal value in China. In this study, we reported the first complete chloroplast (cp) genome of E. qingchengshanense. The whole cp genome of E. qingchengshanense is 159,087 bp in length, comprising a pair of inverted repeat regions (IRs) (27,709 bp) that are separated by a large single-copy (LSC) region (86,607 bp) and a small single-copy (SSC) region (17,062 bp). The circular genome contains 112 unique genes, of which 78 are protein-coding genes, 30 tRNA, and 4 rRNA genes. Phylogenetic analysis shows that E. qingchengshanense has a closer relationship with other Epimedium species.

Epimedii Folium has been used as a common traditional Chinese medicine for more than 2000 years in China. In this study, we assembled the complete chloroplast (cp) genome of Epimedium brevicornu. The whole cp genome of E. brevicornu is 158,658 bp in length, comprising a pair of inverted repeat (IR) regions (27,699 bp) separated by a large single copy (LSC) region (86,558 bp) and a small single copy (SSC) region (16,702bp). The E. brevicornu cp genome contains 129 genes, of which 84 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis shows that E. brevicornu is closely clustered with E. wushanense, E. lishihchenii, and E. sagittatum. The published E. brevicornu chloroplast genome will provide useful information for the phylogenetic and evolutionary study on Epimedium family of Berberidaceae.

Epimedium elachyphyllum, which belongs to Berberidaceae, is only distributed in Guizhou province of China. In this study, the complete chloroplast (cp)genome of E. elachyphyllum was sequenced and assembled. The circular genome is 157,201 bp in length, which comprises of a large single-copy region (LSC, 88,519 bp), a small single-copy region (SSC, 17,042 bp), and a pair of inverted repeat regions (IRa and IRb, 25,820 bp). The genome of E. elachyphyllum contains 112 unique genes, of which 78 protein-coding genes, 30 tRNA genes, and four rRNA genes. Phylogenetic analysis based on 18 complete cp genome sequences indicated that E. elachyphyllum was closely related to E. dolichostemon.

In this study, the complete chloroplast (cp) genome of Epimedium tianmenshanense was sequenced and assembled. The circular genome is 157,066 bp in size. The whole chloroplast genome of E. tianmenshanense contains 112 unique genes, of which 78 protein-coding genes, 30 tRNA genes, and four rRNA genes. The phylogenetic analysis based on 17 complete chloroplast genomes demonstrated a closer relationship between E. tianmenshanense and E. lishihchenii.

Chinese jujube (Ziziphus jujuba Mill.) is an economically important deciduous tree that has high therapeutic value and health benefits. However, a lack of sequence data and molecular markers have constrained genetic and breeding studies for better fruit quality and other traits in Chinese jujube. In this study, two combined cDNA libraries of 'Dongzao' fruit representing the early and late stages of fruit development were constructed and sequenced on the 454 GS FLX Titanium platform. In total, 1,124,197 reads were generated and then de novo assembled into 97,479 unigenes. A total of 52,938 unigenes were homologous to genes in the NCBI non-redundant sequence database. A total of 33,123 unigenes were assigned to one or more Gene Ontology terms, and 16,693 unigenes were classified into 319 Kyoto Encyclopedia of Genes and Genomes pathways. The results showed that the Smirnoff-Wheeler pathway was the main pathway for the biosynthesis of ascorbic acid in Chinese jujube. The number of differentially expressed genes between the two stages of fruit development was 1,764, among which 974 and 790 genes were up-regulated and down-regulated, respectively. Furthermore, 9,893 sequences were identified containing SSRs. 93 primer pairs designed from the sequences with a tri-nucleotide repeat showed successful PCR amplification and could be validated in Chinese jujube accessions and Z. mauritiana Lam and Z. acidojujuba as well, of which 71 primer pairs were polymorphic. The obtained transcriptome provides a most comprehensive resource currently available for gene discovery and the development of functional markers in Z. jujuba. The newly developed microsatellite markers could be used in applications such as genetic linkage analysis and association studies, diversity analysis, and marker-assisted selection in Chinese jujube and related species.

A special predator-prey system is investigated in which the prey population exhibits herd behavior in order to provide a self-defense against predators, while the predator is intermediate and its population shows individualistic behavior. Considering the fact that there always exists a time delay in the conversion of the biomass of prey to that of predator in this system, we obtain a delayed predator-prey model with square root functional response and quadratic mortality. For this model, we mainly investigate the stability of positive equilibrium and the existence of Hopf bifurcation by choosing the time delay as a bifurcation parameter.

We present a stochastic simple chemostat model in which the dilution rate was influenced by white noise. The long time behavior of the system is studied. Mainly, we show how the solution spirals around the washout equilibrium and the positive equilibrium of deterministic system under different conditions. Furthermore, the sufficient conditions for persistence in the mean of the stochastic system and washout of the microorganism are obtained. Numerical simulations are carried out to support our results.

Aims To establish and evaluate predictive models for glaucoma-related adverse events (GRAEs) following secondary intraocular lens (IOL) implantation in paediatric eyes. Methods 205 children (356 aphakic eyes) receiving secondary IOL implantation at Zhongshan Ophthalmic Center with a 3-year follow-up were enrolled. Cox proportional hazard model was used to identify predictors of GRAEs and developed nomograms. Model performance was evaluated with time-dependent receiver operating characteristic (ROC) curves, decision curve analysis, Kaplan-Meier curves and validated internally through C-statistics and calibration plot of the bootstrap samples. Results Older age at secondary IOL implantation (HR=1.5, 95% CI: 1.03 to 2.19), transient intraocular hypertension (HR=9.06, 95% CI: 2.97 to 27.67) and ciliary sulcus implantation (HR=14.55, 95% CI: 2.11 to 100.57) were identified as risk factors for GRAEs (all p<0.05). Two nomograms were established. At postoperatively 1, 2 and 3 years, model 1 achieved area under the ROC curves (AUCs) of 0.747 (95% CI: 0.776 to 0.935), 0.765 (95% CI: 0.804 to 0.936) and 0.748 (95% CI: 0.736 to 0.918), and the AUCs of model 2 were 0.881 (95% CI: 0.836 to 0.926), 0.895 (95% CI: 0.852 to 0.938) and 0.848 (95% CI: 0.752 to 0.945). Both models demonstrated fine clinical net benefit and performance in the interval validation. The Kaplan-Meier curves showing two distinct risk groups were well discriminated and robust in both models. An online risk calculator was constructed. Conclusion Two nomograms could sensitively and accurately identify children at high risk of GRAEs after secondary IOL implantation to help early identification and timely intervention. [ABSTRACT FROM AUTHOR]

Since the aquatic organisms are very sensitive to the increasing copper contamination in water, this paper focuses on investigating the effects of copper contamination on the interaction between phytoplankton and zooplankton species within both deterministic and stochastic environments. We first construct a deterministic phytoplankton-zooplankton interaction model coupled with the copper concentration and analyze its dynamics, including existence and stability of equilibria, as well as the existence of Hopf bifurcation. A new stochastic model is derived in the form of continuous-time Markov chain (CTMC), and branching process theory is applied to the CTMC model to estimate the extinction probability of zooplankton species. Analytical and numerical findings show that the destiny of species is closely related to the copper concentration, and the predictions of the deterministic and stochastic models may be different in some cases. [ABSTRACT FROM AUTHOR]