The association between frailty and in-hospital mortality in critically ill patients with congestive heart failure: results from MIMIC-IV database.

Background: Frailty correlates with adverse outcomes in many cardiovascular diseases and is prevalent in individuals with heart failure (HF). The Hospital Frailty Risk Score (HFRS) offers an integrated, validated solution for frailty assessment in acute care settings, but its application in critically ill patients with congestive HF lacks exploration. This study aimed to identify the association between frailty assessed by the HFRS and in-hospital mortality in critically ill patients with congestive HF. Methods: This observational study retrospectively enrolled 12,179 critically ill patients with congestive HF. Data from the Medical Information Mart for Intensive Care IV database was used. The HFRS was calculated to assess frailty. Patients were categorized into three groups: non-frailty (HFRS < 5, n = 7,961), pre-frailty (5 ≤ HFRS < 15, n = 3,684), and frailty (HFRS ≥ 15, n = 534). Outcomes included in-hospital mortality, length of intensive care unit stay, and length of hospital stay. Multiple logistic regression and Locally Weighted Scatterplot Smoothing (LOWESS) smoother were used to investigate the association between frailty and outcomes. Subgroup analysis was employed to elucidate the correlation between frailty levels and in-hospital mortality across diverse subgroups. Results: 12,179 patients were enrolled, 6,679 (54.8%) were male, and the average age was 71.05 ± 13.94 years. The overall in-hospital mortality was 11.7%. In-hospital mortality increased with the escalation of frailty levels (non-frailty vs. pre-frailty vs. frailty: 9.7% vs. 14.8% vs. 20.2%, P < 0.001). The LOWESS curve demonstrated that the HFRS was monotonically positively correlated with in-hospital mortality. Upon controlling for potential confounders, both pre-frailty and frailty statuses were found to be independently linked to a heightened risk of mortality during hospitalization (odds ratio [95% confidence interval]: pre-frailty vs. non-frailty: 1.27 [1.10-1.47], P = 0.001; frailty vs. non-frailty: 1.40 [1.07-1.83], P = 0.015; P for trend < 0.001). Significant interactions between frailty levels and in-hospital mortality were observed in the following subgroups: race, heart rate, creatinine, antiplatelet drug, diabetes, cerebrovascular disease, chronic renal disease, and sepsis. Conclusion: In critically ill patients with congestive HF, frailty as assessed by the HFRS emerged as an independent predictor for the risk of in-hospital mortality. Prospective, randomized studies are required to determine whether improvement of frailty levels could improve clinical prognosis.

Zanthoxylum bungeanum Waste-Derived High-Nitrogen Self-Doped Porous Carbons as Efficient Adsorbents for Methylene Blue.

In this study, we prepared high-nitrogen self-doped porous carbons (NPC1 and NPC2) derived from the pruned branches and seeds of Zanthoxylum bungeanum using a simple one-step method. NPC1 and NPC2 exhibited elevated nitrogen contents of 3.56% and 4.22%, respectively, along with rich porous structures, high specific surface areas of 1492.9 and 1712.7 m2 g-1 and abundant surface groups. Notably, both NPC1 and NPC2 demonstrated remarkable adsorption abilities for the pollutant methylene blue (MB), with maximum monolayer adsorption capacities of 568.18 and 581.40 mg g-1, respectively. The adsorption kinetics followed the pseudo-second-order kinetics and the adsorption isotherms conformed to the Langmuir isotherm model. The adsorption mechanism primarily relied on the hierarchical pore structures of NPC1 and NPC2 and their diverse strong interactions with MB molecules. This study offers a new approach for the cost-effective design of nitrogen self-doped porous carbons, facilitating the efficient removal of MB from wastewater.

Genome-wide analysis and expression profiling of the HD-ZIP gene family in kiwifruit.

The homeodomain-leucine zipper (HD-Zip) gene family plays a pivotal role in plant development and stress responses. Nevertheless, a comprehensive characterization of the HD-Zip gene family in kiwifruit has been lacking. In this study, we have systematically identified 70 HD-Zip genes in the Actinidia chinensis (Ac) genome and 55 in the Actinidia eriantha (Ae) genome. These genes have been categorized into four subfamilies (HD-Zip I, II, III, and IV) through rigorous phylogenetic analysis. Analysis of synteny patterns and selection pressures has provided insights into how whole-genome duplication (WGD) or segmental may have contributed to the divergence in gene numbers between these two kiwifruit species, with duplicated gene pairs undergoing purifying selection. Furthermore, our study has unveiled tissue-specific expression patterns among kiwifruit HD-Zip genes, with some genes identified as key regulators of kiwifruit responses to bacterial canker disease and postharvest processes. These findings not only offer valuable insights into the evolutionary and functional characteristics of kiwifruit HD-Zips but also shed light on their potential roles in plant growth and development.

Photosynthetic physiological characteristics, growth performance, and element concentrations reveal the calcicole-calcifuge behaviors of three Camellia species.

We grew three yellow Camellia species (the calcifuge C. nitidissima and C. tunghinensis, and the calcicole C. pubipetala) in acidic and calcareous soils for 7 months and assessed their photosynthetic physiological characteristics, growth performance, and element concentrations in this developmental context. The calcifuge C. nitidissima and C. tunghinensis species exhibited poor growth with leaf chlorosis, growth stagnation, and root disintegration in calcareous soils, and with their P n, G s, T r, F v/F m, ΦPSII, ETR, qP, leaf Chla, Chlb, and Chl(a + b) concentrations, and root, stem, leaf, and total biomass being significantly lower when grown in calcareous soils relative to in acidic soils. In contrast, the calcicole C. pubipetala grew well in both acidic and calcareous soils, with few differences in the above parameters between these two soil substrates. The absorption and/or transportation of nutrient elements such as N, K, Ca, Mg, and Fe by the two calcifuge Camellia species plants grown in calcareous soils were restrained. Soil type plays a major role in the failure of the two calcifuge Camellia species to establish themselves in calcareous soils, whereas other factors such as competition and human activity are likely more important limiting factors in the reverse case. This study furthers our understanding of the factors influencing the distribution of these rare and endangered yellow Camellia species, allowing for improved management of these species in conservation projects and horticultural production.

Identification and functional analysis of the LEAFY gene in longan flower induction.

BACKGROUND: Flowering at the right time is a very important factor affecting the stable annual yield of longan. However, a lack of knowledge of the regulatory mechanism and key genes of longan flowering restricts healthy development of the longan industry. Therefore, identifying relevant genes and analysing their regulatory mechanism are essential for scientific research and longan industry development. RESULTS: DlLFY (Dimocarpus longan LEAFY) contains a 1167 bp open reading frame and encodes 388 amino acids. The amino acid sequence has a typical LFY/FLO family domain. DlLFY was expressed in all tissues tested, except for the leaf, pericarp, and pulp, with the highest expression occurring in flower buds. Expression of DlLFY was significantly upregulated at the early flower induction stage in "SX" ("Shixia"). The results of subcellular localization and transactivation analysis showed that DlLFY is a typical transcription factor acting as a transcriptional activator. Moreover, overexpression of DlLFY in Arabidopsis promoted early flowering and restrained growth, resulting in reduced plant height and rosette leaf number and area in transgenic plants. DNA affinity purification sequencing (DAP-Seq) analysis showed that 13 flower-related genes corresponding to five homologous genes of Arabidopsis may have binding sites and be putative target genes. Among these five flower-related genes, only AtTFL1 (terminal flower 1) was strongly inhibited in transgenic lines. CONCLUSION: Taken together, these results indicate that DlLFY plays a pivotal role in controlling longan flowering, possibly by interacting with TFL1.

Establishment of a machine learning predictive model for non-alcoholic fatty liver disease: A longitudinal cohort study.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease, which lacks effective drug treatments. This study aimed to construct an eXtreme Gradient Boosting (XGBoost) prediction model to identify or evaluate potential NAFLD patients. METHODS AND RESULTS: We conducted a longitudinal study of 22,140 individuals from the Beijing Health Management Cohort. Variable filtering was performed using the least absolute shrinkage and selection operator. Random Over Sampling Examples was used to address imbalanced data. Next, the XGBoost model and the other three machine learning (ML) models were built using balanced data. Finally, the variable importance of the XGBoost model was ranked. Among four ML algorithms, we got that the XGBoost model outperformed the other models with the following results: accuracy of 0.835, sensitivity of 0.835, specificity of 0.834, Youden index of 0.669, precision of 0.831, recall of 0.835, F-1 score of 0.833, and an area under the curve of 0.914. The top five variables with the greatest impact on the onset of NAFLD were aspartate aminotransferase, cardiometabolic index, body mass index, alanine aminotransferase, and triglyceride-glucose index. CONCLUSION: The predictive model based on the XGBoost algorithm enables early prediction of the onset of NAFLD. Additionally, assessing variable importance provides valuable insights into the prevention and treatment of NAFLD.

Association between nonalcoholic fatty liver disease and type 2 diabetes: A bidirectional two-sample mendelian randomization study.

OBJECTIVE: The aim of this study was to explore the mutually causal relationship between NAFLD and type 2 diabetes. METHODS: Based on the data obtained from GWAS, this study employed bidirectional two-sample MR analysis to investigate the causal relationship between NAFLD and type 2 diabetes, and also examined the causal relationship between liver fat accumulation and type 2 diabetes as well as the relationship between NAFLD and FPG, IR. RESULTS: In MR analysis of NAFLD and type 2 diabetes, when NAFLD as an exposure and type 2 diabetes as a result, the OR (95 % CI) was 1.10890 (1.00135-1.22801); in the reverse analysis, the OR value was not statistically significant. In MR analysis of NAFLD, FPG and IR, there was no statistical significance in both directions. In MR analysis of liver fat accumulation and type 2 diabetes, when liver fat as an exposure and type 2 diabetes as a result, the OR (95 % CI) was 1.17516 (1.02054-1.35321); in the reverse analysis, the OR value (95 % CI) was 1.06283 (1.02879-1.09799). CONCLUSION: There is a unidirectional causal relationship between NAFLD and type 2 diabetes. Furthermore, a bidirectional causal relationship exists between liver fat accumulation and type 2 diabetes.

Determination of the effects of pre-harvest bagging treatment on kiwifruit appearance and quality via transcriptome and metabolome analyses.

Bagging is an effective cultivation strategy to produce attractive and pollution-free kiwifruit. However, the effect and metabolic regulatory mechanism of bagging treatment on kiwifruit quality remain unclear. In this study, transcriptome and metabolome analyses were conducted to determine the regulatory network of the differential metabolites and genes after bagging. Using outer and inner yellow single-layer fruit bags, we found that bagging treatment improved the appearance of kiwifruit, increased the soluble solid content (SSC) and carotenoid and anthocyanin levels, and decreased the chlorophyll levels. We also identified 41 differentially expressed metabolites and 897 differentially expressed genes (DEGs) between the bagged and control 'Hongyang' fruit. Transcriptome and metabolome analyses revealed that the increase in SSC after bagging treatment was mainly due to the increase in D-glucosamine metabolite levels and eight DEGs involved in amino sugar and nucleotide sugar metabolic pathways. A decrease in glutamyl-tRNA reductase may be the main reason for the decrease in chlorophyll. Downregulation of lycopene epsilon cyclase and 9-cis-epoxycarotenoid dioxygenase increased carotenoid levels. Additionally, an increase in the levels of the taxifolin-3'-O-glucoside metabolite, flavonoid 3'-monooxygenase, and some transcription factors led to the increase in anthocyanin levels. This study provides novel insights into the effects of bagging on the appearance and internal quality of kiwifruit and enriches our theoretical knowledge on the regulation of color pigment synthesis in kiwifruit.

The Genetic Diversity and Genetic Structure of the Germplasm Resources of the Medicinal Orchid Plant Habenaria dentata.

Habenaria dentata has medicinal and ornamental value, but the number of wild populations is decreasing dramatically. Thus, conducting research on its genetic diversity and structure is necessary to provide a basis for its conservation. This study aimed to explore the genetic diversity of the wild plant H. dentata and protect and optimize its wild resources. The genetic diversity of 133 samples from six wild populations of H. dentata was analyzed using Inter Simple Sequence Repeat molecular markers to provide a scientific basis for the screening of improved germplasm resources. The results showed that the average number of alleles was 1.765, the average number of effective alleles was 1.424, the average Nei's gene diversity index was 0.252, the average Shannon diversity index was 0.381, and the average percentage of polymorphic loci was 76.499%. The variation within the populations was 77.34%, and the variation between the populations was 22.66%. The gene flow was 1.705, which was greater than 1. The results of the cluster analysis showed that the six populations were mainly divided into four clusters and were not classified according to their geographical location. There was no significant correlation between the geographical location and genetic distance between the populations (r = 0.557, p > 0.05). The genetic diversity of H. dentata is high. Among the six wild populations, the genetic diversity of the Mulun population was the highest and this population can be used as a key protection unit. The study on the genetic diversity of H. dentata can not only reveal the reasons for the decrease in the number of individuals in the population to a certain extent, and put forward the protection strategy, but also provide a scientific basis for the breeding of excellent seed resources.

Genome-wide diversity evaluation and core germplasm extraction in ex situ conservation: A case of golden Camellia tunghinensis.

Whether ex situ populations constructed in the limited nursery resources of botanical gardens can preserve enough genetic diversity of endangered plants in the wild remains uncertain. Here, a case study was conducted with Camellia tunghinensis, which is one of the species with the lowest natural distribution area in the sect. Chrysantha (golden camellia) of the family Theaceae. We investigated the genetic diversity and population structure of 229 samples from wild and ex situ populations using genotyping by sequencing (GBS). Core germplasm was constructed from these samples. The results showed that wild C. tunghinensis exhibited high genetic diversity, with observed heterozygosity of 0.257-0.293 and expected heterozygosity of 0.247-0.262. Compared with wild populations, the genetic diversity of ex situ populations established by transplanting wild seedlings was close to or even higher. However, the genetic diversity of those established by seed or cuttings of a few superior trees was lower. The Admixture analysis revealed that the structure of the ex situ populations derived from seeds and cuttings was relatively simple compared with the ex situ populations derived from transplanted wild seedlings and wild populations. These results suggested that direct transplanting of wild seedlings was more conducive to preserving the genetic diversity of endangered plants in the wild. In addition, wild populations demonstrated a small differentiation (mean F ST = 0.044) among themselves, possibly due to long-term and frequent gene flow between the wild populations. In contrast, moderate differentiation (mean F ST > 0.05) was detected among ex situ populations and between ex situ and wild populations. This may be the combined result of the absence of gene flow pathways and strong selection pressure in various ex situ environments. Finally, 77 core germplasms were extracted from 229, likely representing the genetic diversity of C. tunghinensis. This study provides future strategies for the ex situ conservation and management of the golden camellia species and other rare and endangered plants.

Integrated analyses of metabolomics and transcriptomics reveal the potential regulatory roles of long non-coding RNAs in gingerol biosynthesis.

BACKGROUND: As the characteristic functional component in ginger, gingerols possess several health-promoting properties. Long non-coding RNAs (lncRNAs) act as crucial regulators of diverse biological processes. However, lncRNAs in ginger are not yet identified so far, and their potential roles in gingerol biosynthesis are still unknown. In this study, metabolomic and transcriptomic analyses were performed in three main ginger cultivars (leshanhuangjiang, tonglingbaijiang, and yujiang 1 hao) in China to understand the potential roles of the specific lncRNAs in gingerol accumulation. RESULTS: A total of 744 metabolites were monitored by metabolomics analysis, which were divided into eleven categories. Among them, the largest group phenolic acid category contained 143 metabolites, including 21 gingerol derivatives. Of which, three gingerol analogs, [8]-shogaol, [10]-gingerol, and [12]-shogaol, accumulated significantly. Moreover, 16,346 lncRNAs, including 2,513, 1,225, and 2,884 differentially expressed (DE) lncRNA genes (DELs), were identified in all three comparisons by transcriptomic analysis. Gene ontology enrichment (GO) analysis showed that the DELs mainly enriched in the secondary metabolite biosynthetic process, response to plant hormones, and phenol-containing compound metabolic process. Correlation analysis revealed that the expression levels of 11 DE gingerol biosynthesis enzyme genes (GBEGs) and 190 transcription factor genes (TF genes), such as MYB1, ERF100, WRKY40, etc. were strongly correlation coefficient with the contents of the three gingerol analogs. Furthermore, 7 and 111 upstream cis-acting lncRNAs, 1,200 and 2,225 upstream trans-acting lncRNAs corresponding to the GBEGs and TF genes were identified, respectively. Interestingly, 1,184 DELs might function as common upstream regulators to these GBEGs and TFs genes, such as LNC_008452, LNC_006109, LNC_004340, etc. Furthermore, protein-protein interaction networks (PPI) analysis indicated that three TF proteins, MYB4, MYB43, and WRKY70 might interact with four GBEG proteins (PAL1, PAL2, PAL3, and 4CL-4). CONCLUSION: Based on these findings, we for the first time worldwide proposed a putative regulatory cascade of lncRNAs, TFs genes, and GBEGs involved in controlling of gingerol biosynthesis. These results not only provide novel insights into the lncRNAs involved in gingerol metabolism, but also lay a foundation for future in-depth studies of the related molecular mechanism.

Genomic evidence reveals high genetic diversity in a narrowly distributed species and natural hybridization risk with a widespread species in the genus Geodorum.

BACKGROUND: Understanding genetic diversity is a core issue in conservation genetics. However, previous genetic diversity evaluations of narrowly distributed species have rarely used closely related widespread species as a reference. Furthermore, identifying natural hybridization signals between narrowly and widely distributed sympatric species is of great importance for the development of species conservation programs. METHODS: In this study, population genotyping by sequencing (GBS) was performed for a narrowly distributed species, Geodorum eulophioides (endemic and endangered in Southwest China), and a widespread species, G. densiflorum. A total of 18,490 high-quality single nucleotide polymorphisms (SNPs) were identified at the whole-genome level. RESULTS: The results showed that the nucleotide diversity and heterozygosity of G. eulophioides were significantly higher than those of G. densiflorum, confirming that narrowly distributed species can still preserve high genetic diversity. Consistent with taxonomic boundaries, all sampled individuals from the two species were divided into two genetic clusters and showed high genetic differentiation between species. However, in a sympatric population, a few G. eulophioides individuals were detected with genetic components from G. densiflorum, suggesting potential interspecific natural hybridization. This hypothesis was supported by Treemix analysis and hand-hybridization trials. Invasion of the habitat of G. eulophioides invasion by G. densiflorum under anthropogenic disturbance may be the main factor causing interspecific hybridization. CONCLUSIONS: Therefore, reducing or avoiding habitat disturbance is a key measure to protect the G. eulophioides populations. This study provides valuable information for future conservation programs for narrowly distributed species.

Serum uric acid to creatinine ratio and metabolic syndrome in middle-aged and elderly population: Based on the 2015 CHARLS.

BACKGROUND AND AIMS: Serum uric acid to creatinine ratio (SUA/Cr) may be associated with metabolic syndrome (MS). Here, we investigated the correlation between SUA/Cr and MS in Chinese residents aged ≥ 45 years. METHODS AND RESULTS: Data were obtained from the 2015 China Health and Retirement Longitudinal Study (CHARLS) database. MS was diagnosed using the Chinese Diabetes Society 2017 criteria. We grouped the population according to SUA/Cr quartiles and compared the index differences between groups. We used spearman correlation analysis and binary logistic regression. The possible dose-response association of SUA/Cr with MS were analyzed using restricted cubic spline model. Of 12,946 included participants, 3370 (26.0%) had MS, and 1900 (56.4%) were female. After adjusting for multiple confounders, binary logistic regression analysis showed that compared with Quartile 1, the odds ratio (95% confidence interval) of the MS risk was 1.29 (1.09-1.52), 1.47 (1.25-1.74), and 1.80 (1.53-2.12) in Quartiles 2, 3, and 4, respectively. The restricted cubic spline model indicated a significant nonlinear dose-response association (Poverall < 0.001, Pnon-linearity = 0.029) between SUA/Cr and strength of MS prevalence association; MS risk began increasing when SUA/Cr > 6.22. CONCLUSIONS: A significant positive correlation existed between SUA/Cr and MS risk in Chinese individuals aged ≥ 45 years, which may be a new predictive marker for MS risk.

Sweet-Potato-Vine-Based High-Performance Porous Carbon for Methylene Blue Adsorption.

In this study, sweet-potato-vine-based porous carbon (SPVPC) was prepared using zinc chloride as an activating and pore-forming agent. The optimised SPVPC exhibited abundant porous structures with a high specific surface area of 1397.8 m2 g-1. Moreover, SPVPC exhibited excellent adsorption characteristics for removing methylene blue (MB) from aqueous solutions. The maximum adsorption capacity for MB reached 653.6 mg g-1, and the reusability was satisfactory. The adsorption kinetics and isotherm were in good agreement with the pseudo-second-order kinetics and Langmuir models, respectively. The adsorption mechanism was summarised as the synergistic effects of the hierarchically porous structures in SPVPC and various interactions between SPVPC and MB. Considering its low cost and excellent adsorption performance, the prepared porous carbon is a promising adsorbent candidate for dye wastewater treatment.

Hypoxia-Regulated lncRNA USP2-AS1 Drives Head and Neck Squamous Cell Carcinoma Progression.

The role of hypoxia-regulated long non-coding RNA (lncRNA) in the development of head and neck squamous cell carcinoma (HNSCC) remains to be elucidated. In the current study, we initially screened hypoxia-regulated lncRNA in HNSCC cells by RNA-seq, before focusing on the rarely annotated lncRNA USP2 antisense RNA 1 (USP2-AS1). We determined that USP2-AS1 is a direct target of HIF1α and is remarkably elevated in HNSCC compared with matched normal tissues. Patients with a higher level of USP2-AS1 suffered a poor prognosis. Next, loss- and gain-of-function assays revealed that USP2-AS1 promoted cell proliferation and invasion in vitro and in vivo. Mechanically, RNA pulldown and LC-MS/MS demonstrated that the E3 ligase DDB1- and CUL4-associated factor 13 (DCAF13) is one of the binding partners to USP2-AS1 in HNSCC cells. In addition, we assumed that USP2-AS1 regulates the activity of DCAF13 by targeting its substrate ATR. Moreover, the knockdown of DCAF13 restored the elevated cell proliferation and growth levels achieved by USP2-AS1 overexpression. Altogether, we found that lncRNA USP2-AS1 functions as a HIF1α-regulated oncogenic lncRNA and promotes HNSCC cell proliferation and growth by interacting and modulating the activity of DCAF13.

Structure and diversity of mycorrhizal fungi communities of different part of Bulbophyllum tianguii in three terrestrial environments.

Mycorrhizal fungi plays important roles in the seed germination and subsequent growth of orchids. The research of fungi in orchid roots, especially dominant mycorrhizal fungi is critical for orchids protection. In this study, the fungal community and composition of mycorrhizal fungi in roots, rhizomes and rhizosphere soil of Bulbophyllum tianguii grown in three terrestrial environments were analyzed by the second generation sequencing technology. The results of OTU clustering and α and ß diversity analysis showed that there were significant differences in fungal communities in roots, rhizomes and rhizosphere soil of B. tianguii. The total number of OTUs in rhizomes was much less than that in roots and rhizosphere soil. The number of OTUs in rhizosphere soil and the diversity of mycorrhizal fungi were the highest. Meanwhile, the species and abundance of mycorrhizal fungi in roots and rhizomes of B. tianguii were different from those in rhizosphere soil. For different elevations, compared with B. tianguii that grow in middle of Tiankeng and top of Tiankeng, the OTUs number of B. tianguii in orchid garden is richest, and the diversity of mycorrhizal fungi in orchid garden was significantly higher than other locations. Among the three different habitats of B. tianguii, the number of OTUs in humus soil and stone habitats was notably higher than tree habitats, and the diversity of mycorrhizal fungi in humus soil was the highest. The analysis of mycorrhizal fungi in different habitats and altitudes of B. tianguii showed that Sebacina and Exophiala were the dominant mycorrhizal fungi in B. tianguii. The results of species annotation, phylogenetic tree and co-occurrence network analysis showed the dominant mycorrhizal fungi of B. tianguii mainly included Sebacina, Cladosporium, Exophiala, Fusarium. This study reveals the symbiotic relationship between Sebacina, Exophiala, Cladosporium and the B. Tianguii. It will provide a theoretical basis for the protection and biological function study of B. Tianguii.

Identifying key mutations of radioresponsive genes in esophageal squamous cell carcinoma.

Background: Radiotherapy plays an important effect on the standard therapy of esophageal squamous cell carcinoma (ESCC). However, the efficacy of the therapy is limited and a few patients do not achieve satisfactory treatment results due to the existence of radiation resistance. Therefore, it is necessary to identify the potential predictive biomarkers and treatment targets for ESCC. Methods: We performed the whole-exome sequencing to determine the germline and somatic mutations in ESCC. Functional enrichment and pathway-based protein-protein interaction analyses were used to ascertain potential regulatory networks. Cell survival and cell death after treatment with radiotherapy were determined by CCK-8 and LDH release assays in ESCC cells. The correlations of NOTCH1 and tumor immune infiltration were also analyzed in ESCC. Results: Our results showed that 344 somatic and 65 germline differentially mutated genes were detected to be radiosensitivity-related loci. The tumor mutational burdens (TMB) or microsatellite instability (MSI) were not significantly correlated with the response to radiotherapy in ESCC patients. Pathway-based protein-protein interaction analyses implied several hub genes with most nodes (such as PIK3CA, NOTCH1, STAT3 and KDR). The in vitro studies showed that the knockdown of NOTCH1 inhibited cell survival and rendered more cell death after the treatment with radiotherapy in ESCC cells, while NOTCH1 overexpression had the opposite effects. Moreover, NOTCH1, frequently up-regulated in ESCC, was negatively correlated with activated B cell and immature dendritic cell in ESCC. High expression of NOTCH1 was accompanied with the low levels of some immunotherapy-related cells, including CD8(+) T cells and NK cells. Conclusions: These results indicate the differences of the germline mutations and somatic mutations between the radiosensitive and radioresistence groups in ESCC and imply that NOTCH1 plays important roles in regulating the radiosensitivity of ESCC. The findings might provide the biomarkers and potential treatment targets for improving the sensitivity to radiotherapy in ESCC.

The complete chloroplast genome sequence of Habenaria dentata (Orchidaceae).

Habenaria dentata is a rare species with high ornamental value in China. In this study, we report the complete chloroplast (cp) genome of H. dentata using the Illumina sequencing data. The total genome of H. dentata is 153,682 bp in length and the GC content is 36.62%, with a pair of inverted repeats (IRs) regions of 26,339 bp each, a large single-copy (LSC) region of 83,963 bp and a small single-copy (SSC) region of 17,041 bp. The cp genome encoded 133 genes, including 87 protein-coding genes (PCG), eight rRNA genes, and 38 tRNA genes. The maximum-likelihood phylogenetic analysis based on 12 cp genomes showed that H. dentata was sister to Habenaria chejuensis and Habenaria ciliolaris. This work will be valuable for genetic and phylogenetic studies on H. dentata.

D-dimer to Creatinine Ratio: A Novel Biomarker Associated with Gensini Score in ST-Segment Elevation Myocardial Infarction Patients.

OBJECTIVE: We propose for the first time that D-dimer to creatinine ratio (DCR) may serve as a new clinical biomarker and explore its association with ST-segment elevation myocardial infarction (STEMI). METHODS: 347 STEMI patients with complete D-dimer and creatinine were included in the analysis. According to the median of DCR value, patients were divided into the lower DCR group (DCR < 1.402, n = 173) and the higher DCR group (DCR ≥ 1.402, n = 174), and the differences between the two groups were compared. In addition, patients were divided into four groups according to the quartiles of Gensini score: Group 1(Gensini score ≤ 34, n = 88); Group 2(34 < Gensini score ≤ 65, n = 88); Group 3(65 < Gensini score ≤100, n = 87); Group 4(Gensini score ＞100, n = 84). Multivariate linear and multivariate logistic regression analyzes were performed to determine independent predictors of the Gensini score. RESULTS: High DCR group had higher Gensini score compared with the low DCR group (P < .05). DCR was positively correlated with Gensini score (r = 0.493, P < .001). Multiple linear regression analysis showed that Previous MI (r = 11.312, P = .035) and DCR (r = 5.129, P < .001) were independent risk factors associated with the Gensini score. Multivariate logistic regression analysis showed that, compared to Group 1, DCR was an independent risk factor in Group 2, Group 3, Group 4 (P < .001). CONCLUSIONS: As a new and useful clinical biomarker, DCR was positively correlated with coronary Gensini score in STEMI patients.