Decision fatigue experience of front-line nurses in the context of public health emergency: an interpretative phenomenological analysis.

BACKGROUND: Decision fatigue is a new concept in the field of psychology and refers to a state of fatigue alongside impaired cognitive processing and emotional regulation ability. Previous studies have confirmed that nurses are prone to decision fatigue, and nurses who experience decision fatigue may implement nursing measures that are inconsistent with clinical evidence, thus affecting patients' benefits. COVID-19, as a large-scale global public health emergency, increased the workload and burden of nurses and aggravated decision fatigue. However, the factors leading to decision fatigue among nurses have not yet been identified. METHODS: This study is guided by interpretative phenomenology. During the epidemic period of COVID-19: From November 2022 to February 2023, a one-to-one, semi-structured in-depth interview was conducted among nurses with decision fatigue experience who were participating in front-line work in Jilin Province using homogenous sampling. The interview recordings and related data were transcribed into text within 24 h, and data analysis was assisted by NVivo 12.0 software. RESULTS: After a total of 14 front-line nurses were analyzed in this study, The thematic level reaches saturation, the findings present a persuasive and coherent narrative, and the study is terminated, and finally extracted and formed three core themes: "Cognition, influence and attitude of decision fatigue", "Approaching factors of decision fatigue" and "Avoidant factors of decision fatigue". CONCLUSION: This study confirmed that decision fatigue was widespread in the work of front-line nurses, affecting the physical and psychological health of nurses, the quality of nursing work, the degree of benefit of patients and the clinical outcome. However, nursing staff do not know enough about decision fatigue, so the popularization and research of decision fatigue should be strengthened. Improve the attention of medical institutions, nursing managers and nursing staff.Some suggestions are put forward for the intervention of decision fatigue through personnel, task, tool and technology, organization and environment.

Population genomics of Fusarium graminearum isolates from the Americas.

Fusarium head blight (FHB) is a major disease of wheat and barley worldwide and is caused by different species in the genus Fusarium, Fusarium graminearum being the most important. We conducted population genomics analyses using SNPs obtained through genotyping by sequencing of over 500 isolates of F. graminearum from the US Upper Midwest, New York, Louisiana, and Uruguay. PCA and STRUCTURE analyses group our isolates into four previously described populations: NA1, NA2, Southern Louisiana (SLA) and Gulf Coast (GC). Some isolates were not assigned to populations because of mixed ancestry. Population structure was associated with toxin genotype and geographic origin. The NA1, NA2, and SLA populations are differentiated (FST 0.385 - 0.551) but the presence of admixed isolates indicates that the populations are not reproductively isolated. Patterns of linkage disequilibrium (LD) decay suggest frequent recombination within populations. Fusarium graminearum populations from the US have great evolutionary potential given the high recombination rate and a large proportion of admixed isolates. The NA1, NA2, and Southern Louisiana (SLA) populations separated from their common ancestral population roughly at the same time in the past and are evolving with moderate levels of subsequent gene flow between them. Genome-wide selection scans in all three populations revealed outlier regions with the strongest signatures of recent positive natural selection. These outlier regions include many genes with unknown function and some genes with known roles in plant-microbe interaction, fungicide/drug resistance, cellular transport and genes that are related to cellular organelles. Only a very small proportion of outlier regions are shared as outliers among the three populations, suggesting unique host-pathogen interactions and environmental adaptation.

Jianpi Jiedu Recipe Inhibits Proliferation through Reactive Oxygen Species-Induced Incomplete Autophagy and Reduces PD-L1 Expression in Colon Cancer.

BACKGROUND: Jianpi Jiedu Recipe has been used to treat digestive tract tumors in China since ancient times, and its reliability has been proven by clinical research. Currently, the specific biological mechanism of JPJDR in treating tumors is unclear. METHODOLOGY: CCK-8 assay was used to detect cell viability. Clone formation assay and EdU assay were used to detect cell proliferation potential. DCFH-DA probe and JC-1 probe were used to detect total intracellular reactive oxygen species and mitochondrial membrane potential, respectively. Western blotting and immunofluorescence were used to detect protein expression level and subcellular localization of cells. The RFP-GFP-LC3B reporter system was used to observe the type of autophagy in cells. The xenograft tumor model was used to study the therapeutic effect of JPJDR in vivo. RESULTS: JPJDR has an excellent inhibitory effect on various colorectal cancer cells and effectively reduces the proliferation ability of HT29 cells. After treatment with JPJDR, the amount of reactive oxygen species in HT29 cells increased significantly, and the mitochondrial membrane potential decreased. JPJDR induced the accumulation of autophagosomes in HT29 cells and was shown to be incomplete autophagy. At the same time, JPJDR reduced the expression of PD-L1. Meanwhile, JPJDR can exert an excellent therapeutic effect in xenograft tumor mice. CONCLUSION: JPJDR is a low-toxicity and effective anti-tumor agent that can effectively treat colon cancer in vitro and in vivo. Its mechanism may be inducing mitochondrial dysfunction and incomplete autophagy injury to inhibit the proliferation of colon cancer cells.

Influence of climatic variables on maize grain yield and its components by adjusting the sowing date.

Yield and its components are greatly affected by climate change. Adjusting the sowing date is an effective way to alleviate adverse effects and adapt to climate change. Aiming to determine the optimal sowing date of summer maize and clarify the contribution of climatic variables to grain yield and its components, a consecutive 4-year field experiment was conducted from 2016 to 2019 with four sowing dates at 10-day intervals from 5 June to 5 July. Analysis of historical meteorological data showed that more solar radiation (SR) was distributed from early June to mid-August, and the maximum temperature (Tmax) > 32°C appeared from early July to late August, which advanced and lasted longer in 1991-2020 relative to 1981-1990. Additionally, the precipitation was mainly distributed from early June to late July. The climate change in the growing season of summer maize resulted in optimal sowing dates ranging from 5 June to 15 June, with higher yields and yield stability, mainly because of the higher kernel number per ear and 1,000-grain weight. The average contribution of kernel number per ear to grain yield was 58.7%, higher than that of 1,000-grain weight (41.3%). Variance partitioning analysis showed that SR in 15 days pre-silking to 15 days post-silking (SS) and silking to harvest (SH) stages significantly contributed to grain yield by 63.1% and 86.4%. The extreme growing degree days (EDD) > 32°C, SR, precipitation, and diurnal temperature range (DTR) contributed 20.6%, 22.9%, 14.5%, and 42.0% to kernel number per ear in the SS stage, respectively. Therefore, we concluded that the early sowing dates could gain high yield and yield stability due to the higher SR in the growing season. Meanwhile, due to the decreasing trend in SR and increasing Tmax trend in this region, in the future, new maize varieties with high-temperature resistance, high light efficiency, shade tolerance, and medium-season traits need to be bred to adapt to climate change and increased grain yield.

Predicting the prognosis of hepatic arterial infusion chemotherapy in hepatocellular carcinoma.

Hepatic artery infusion chemotherapy (HAIC) has good clinical efficacy in the treatment of advanced hepatocellular carcinoma (HCC); however, its efficacy varies. This review summarized the ability of various markers to predict the efficacy of HAIC and provided a reference for clinical applications. As of October 25, 2023, 51 articles have been retrieved based on keyword predictions and HAIC. Sixteen eligible articles were selected for inclusion in this study. Comprehensive literature analysis found that methods used to predict the efficacy of HAIC include serological testing, gene testing, and imaging testing. The above indicators and their combined forms showed excellent predictive effects in retrospective studies. This review summarized the strategies currently used to predict the efficacy of HAIC in middle and advanced HCC, analyzed each marker's ability to predict HAIC efficacy, and provided a reference for the clinical application of the prediction system.

Modulatory effects of cancer stem cell-derived extracellular vesicles on the tumor immune microenvironment.

Cancer stem cells (CSCs), accounting for only a minor cell proportion (< 1%) within tumors, have profound implications in tumor initiation, metastasis, recurrence, and treatment resistance due to their inherent ability of self-renewal, multi-lineage differentiation, and tumor-initiating potential. In recent years, accumulating studies indicate that CSCs and tumor immune microenvironment act reciprocally in driving tumor progression and diminishing the efficacy of cancer therapies. Extracellular vesicles (EVs), pivotal mediators of intercellular communications, build indispensable biological connections between CSCs and immune cells. By transferring bioactive molecules, including proteins, nucleic acids, and lipids, EVs can exert mutual influence on both CSCs and immune cells. This interaction plays a significant role in reshaping the tumor immune microenvironment, creating conditions favorable for the sustenance and propagation of CSCs. Deciphering the intricate interplay between CSCs and immune cells would provide valuable insights into the mechanisms of CSCs being more susceptible to immune escape. This review will highlight the EV-mediated communications between CSCs and each immune cell lineage in the tumor microenvironment and explore potential therapeutic opportunities.

Discovery of a terpene synthase synthesizing a nearly non-flexible eunicellane reveals the basis of flexibility.

Eunicellane diterpenoids, containing a typical 6,10-bicycle, are bioactive compounds widely present in marine corals, but rarely found in bacteria and plants. The intrinsic macrocycle exhibits innate structural flexibility resulting in dynamic conformational changes. However, the mechanisms controlling flexibility remain unknown. The discovery of a terpene synthase, MicA, that is responsible for the biosynthesis of a nearly non-flexible eunicellane skeleton, enable us to propose a feasible theory about the flexibility in eunicellane structures. Parallel studies of all eunicellane synthases in nature discovered to date, including 2Z-geranylgeranyl diphosphate incubations and density functional theory-based Boltzmann population computations, reveale that a trans-fused bicycle with a 2Z-configuration alkene restricts conformational flexibility resulting in a nearly non-flexible eunicellane skeleton. The catalytic route and the enzymatic mechanism of MicA are also elucidated by labeling experiments, density functional theory calculations, structural analysis of the artificial intelligence-based MicA model, and mutational studies.

Polyoxygenated cembrane-type diterpenes from the Hainan soft coral Lobophytum crassum as a promising source of anticancer agents with ErbB3 and ROR1 inhibitory potential.

A detailed chemical investigation of the Hainan soft coral Lobophytum crassum led to the identification of a class of polyoxygenated cembrane-type macrocyclic diterpenes (1-28), including three new flexible cembranoids, lobophycrasins E-G (2-4), and twenty-five known analogues. Their structures were elucidated by combining extensive spectroscopic data analysis, quantum mechanical-nuclear magnetic resonance (QM-NMR) methods, the modified Mosher's method, X-ray diffraction analysis, and comparison with data reported in the literature. Bioassays revealed that sixteen cembranoids inhibited the proliferation of H1975, MDA-MB231, A549, and H1299 cells. Among them, Compounds 10, 17, and 20 exhibited significant antiproliferative activities with IC50 values of 1.92-8.82 µM, which are very similar to that of the positive control doxorubicin. Molecular mechanistic studies showed that the antitumour activity of Compound 10 was closely related to regulation of the ROR1 and ErbB3 signalling pathways. This study may provide insight into the discovery and utilization of marine macrocyclic cembranoids as lead compounds for anticancer drugs.

Planting halophytes increases the rhizosphere ecosystem multifunctionality via reducing soil salinity.

Soil salinization poses a significant global challenge, exerting adverse effects on both agriculture and ecosystems. Planting halophytes has the potential ability to improve saline-alkali land and enhance ecosystem multifunctionality (EMF). However, it remains unclear which halophytes are effective in improving saline-alkali land and what impact they have on the rhizosphere microbial communities and EMF. In this study, we evaluated the Na+ absorption capability of five halophytes (Grubovia dasyphylla, Halogeton glomeratus, Suaeda salsa, Bassia scoparia, and Reaumuria songarica) and assessed their rhizosphere microbial communities and EMF. The results showed that S. salsa possessed the highest shoot (3.13 mmol g-1) and root (0.92 mmol g-1) Na+ content, and its soil Na+ absorption, along with B. scoparia, was significantly higher than that of other plants. The soil pH, salinity, and Na+ content of the halophyte rhizospheres decreased by 6.21%, 23.49%, and 64.29%, respectively, when compared to the bulk soil. Extracellular enzymes in the halophyte rhizosphere soil, including α-glucosidase, ß-glucosidase, ß-1,4-N-acetyl-glucosaminidase, neutral phosphatase, and alkaline phosphatase, increased by 70.1%, 78.4%, 38.5%, 79.1%, and 64.9%, respectively. Furthermore, the halophyte rhizosphere exhibited higher network complexity of bacteria and fungi and EMF than bulk soil. The relative abundance of the dominant phyla Proteobacteria, Firmicutes, and Ascomycota in the halophyte rhizosphere soil increased by 9.4%, 8.3%, and 22.25%, respectively, and showed higher microbial network complexity compared to the bulk soil. Additionally, keystone taxa, including Muricauda, Nocardioides, and Pontibacter, were identified with notable effects on EMF. This study confirmed that euhalophytes are the best choice for saline-alkali land restoration. These findings provided a theoretical basis for the sustainable use of saline-alkali cultivated land.

Ceramic-added lime and cement mortars: A review of applications in building products.

Ceramic-added air lime mortars have been used since ancient times owing to the pozzolanic effect provided by crushed ceramic particles that impart hydraulic properties. This work reviews the historical use, composition, reaction mechanisms, characterization techniques, and performance properties of ceramic-added air lime mortars. The fine ceramic powder composed of silica and alumina phases reacts with calcium hydroxide released during lime hydration to form calcium silicate hydrates (CSH) and calcium aluminate hydrates (CAH) via pozzolanic reaction. This provides hydraulicity and reduces setting time compared to pure air lime mortars. The coarser ceramic particles also serve as aggregate and refine the microstructure as filler. The reactivity depends on the ceramic composition, amorphous phase content, particle size distribution, and firing temperature. Optimal proportioning of the fine ceramic powder and coarse ceramic aggregate is necessary to achieve desired properties. Ceramic addition enhances the durability of air lime mortars against weathering while maintaining compatibility with lime-based masonry structures. Key novelties of this review include: (i) in-depth analysis of the influence of ceramic characteristics (mineralogy, particle size, pozzolanicity) and processing on reaction kinetics and phase evolution; (ii) systematic assessment of mechanical, physical and durability properties in comparison to conventional air lime mortars and cement-based grouts; (iii) elucidation of microstructural mechanisms governing performance using advanced characterization techniques; (iv) critical appraisal of test methods and standards for evaluation; and (v) rigorous discussion on potential applications in construction, conservation and repair, with case studies.

Gut microbiota profiling reflects the renal dysfunction and psychological distress in patients with diabetic kidney disease.

Background: The gut microbiota plays a pivotal role in the development of diabetes and kidney disease. However, it is not clear how the intestinal microecological imbalance is involved in the context of diabetic kidney disease (DKD), the leading cause of renal failure. Objectives: To elucidate the gut microbial signatures associated with DKD progression towards end-stage renal disease (ESRD) and explore whether they could reflect renal dysfunction and psychological distress. Methods: A cross-sectional study was conducted to explore the gut microbial signatures of 29 DKD non-ESRD patients and 19 DKD ESRD patients compared to 20 healthy controls. Differential analysis was performed to detect distinct gut microbial alterations in diversities and taxon abundance of DKD with and without ESRD. Renal dysfunction was estimated by urea, creatinine, and estimated glomerular filtration rate. Psychological distress was assessed using the Self-Rating Anxiety Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale, and Hamilton Depression Rating Scale. Results: Alpha diversity indexes were reduced in DKD patients, particularly those with ESRD. Beta diversity analysis revealed that the gut microbial compositions of DKD patients were different with healthy individuals whereas similar compositions were observed in DKD patients. Taxon differential analysis showed that when compared with the controls, DKD patients exhibit distinct microbial profiles including reduced abundances of butyrate-produced, anti-inflammatory bacteria Faecalibacterium, Lachnospira, Roseburia Lachnoclostridium, and increased abundances of pro-inflammatory bacteria Collinsella, Streptococcus etc. These distinctive genera presented consistent associations with renal dysfunction, as well as psychological distress, especially in DKD patients. Conclusions: DKD patients, especially those who have progressed to ESRD, exhibit unique characteristics in their gut microbiota that are associated with both renal dysfunction and psychological distress. The gut microbiota may be a significant factor in the deterioration of DKD and its eventual progression to ESRD.

The First Discovery of Marine Polyoxygenated Cembranolides as Potential Agents for the Treatment of Ulcerative Colitis.

Cembranolides are characteristic metabolites in marine soft corals, with complex structures and widespread biological activities. However, seldom has an intensive pharmacological study been done for these intriguing marine natural products. In this work, systematic chemical investigation was performed on Sinularia pedunculata by HSQC-based small molecule accurate recognition technology (SMART), resulting in the isolation and identification of 31 cembrane-type diterpenoids, including six new ones. In the bioassay, several compounds showed significant anti-inflammatory activities on the inhibition of NO production. The structure-activity relationship (SAR) was comprehensively analyzed, and two most bioactive and less toxic compounds 8 and 9 could inhibit inflammation through suppressing NF-κB and MAPK signaling pathways, and reduce the secretion of inflammatory cytokines. In a mouse model of dextran sodium sulfate (DSS)-induced acute colitis, 8 and 9 exhibited good anti-inflammatory effects and the ability to repair the colon epithelium, giving insight into the application of cembranolides as potential ulcerative colitis (UC) agents.

Effects of sugary drinks, coffee, tea and fruit juice on incidence rate, mortality and cardiovascular complications of type2 diabetes patients: a systematic review and meta-analysis.

Aims: Despite more and more studies indicate that beverages play an important role in type 2 diabetes mellitus(T2DM), the efficacy of intaking different beverages for T2DM has not been clearly stated in one article. The meta-analysis was performed, which aims to assess the effects of beverages on mortality and cardiovascular complications in patients with type 2 diabetes and the incidence of T2DM. Method: PubMed, Embase, Web of Science and Cochrane Library databases were search up to March, 2023 to identify relevant studies, including studies researching beverage consumption, the incidence and mortality of T2DM and incidence of cardiovascular disease, a kind of complication of T2DM. The way to explore the source of heterogeneity is performing subgroup analyses and sensitivity analyses. Funnel plots and Egger's regression test were performed to assess publication bias. The Hazard ratio (HR) and 95% confidence intervals (95% CIs) were used to analysis the results. Fifteen observational studies were included in our meta-analysis. Results: Fifteen eligible articles were included sugar-sweetened beverages(SSB) consumption increased the mortality and incidence of T2DM ( Hazard ratio (HR), 1.20; 95% confidence interval (CI), 1.05-1.38; P = 0.01 and HR, 1.15; 95% CI,1.06-1.24; P = 0.001), respectively. Artificially-sweetened beverages (ASB) consumption was not associated with the mortality and incidence of T2DM (HR,0.96;95%CI, 0.86-1.07; P = 0.464 and HR, 1.15; 95% CI,1.05-1.26; P = 0.003), respectively. Fruit juice consumption increased the incidence of T2DM (HR,1.08;95%CI,1.02-1.14, P = 0.296).Tea or coffee consumption can reduce the incidence of T2DM (HR, 0.89; 95%CI,0.81-0.98; P = 0.016). Tea or coffee consumption was associated with a lower risk of mortality of T2DM (HR,0.84; 95% Cl, 0.75-0.94; P = 0.002 and HR,0.75; 95% CI, 0.65-0.87; P < 0.001), respectively. Additionally, beverage consumption was not associated with cardiovascular disease in T2DM patients (HR,1.03; 95% Cl, 0.82-1.30, P > 0.05). Conclusions: High consumption of SSBs led to a higher risk and mortality of T2DM, while high consumption of coffee or tea showed significant associations with a lower risk of the incidence and mortality of T2DM. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01396-5.

[Research progress of three-dimensional bioprinting technology in auricle repair and reconstruction].

Objective: To review the research progress on the application of three-dimensional (3D) bioprinting technology in auricle repair and reconstruction. Methods: The recent domestic and international research literature on 3D printing and auricle repair and reconstruction was extensively reviewed, and the concept of 3D bioprinting technology and research progress in auricle repair and reconstruction were summarized. Results: The auricle possesses intricate anatomical structure and functionality, necessitating precise tissue reconstruction and morphological replication. Hence, 3D printing technology holds immense potential in auricle reconstruction. In contrast to conventional 3D printing technology, 3D bioprinting technology not only enables the simulation of auricular outer shape but also facilitates the precise distribution of cells within the scaffold during fabrication by incorporating cells into bioink. This approach mimics the composition and structure of natural tissues, thereby favoring the construction of biologically active auricular tissues and enhancing tissue repair outcomes. Conclusion: 3D bioprinting technology enables the reconstruction of auricular tissues, avoiding potential complications associated with traditional autologous cartilage grafting. The primary challenge in current research lies in identifying bioinks that meet both the mechanical requirements of complex tissues and biological criteria.

Comparative analysis of dexmedetomidine, midazolam, and propofol impact on epilepsy-related mortality in the ICU: insights from the MIMIC-IV database.

BACKGROUND: Dexmedetomidine (Dex), midazolam, and propofol are three distinct sedatives characterized by varying pharmacological properties. Previous literature has indicated the positive impact of each of these sedatives on ICU patients. However, there is a scarcity of clinical evidence comparing the efficacy of Dex, midazolam, and propofol in reducing mortality among people with epilepsy (PWE). This study aimed to assess the impact of Dex, midazolam, and propofol on the survival of PWE. METHODS: The data were retrospectively retrieved from the Medical Information Mart for Intensive Care (MIMIC)-IV database (version 2.0). PWE were categorized into Dex, midazolam, and propofol groups based on the intravenously administered sedatives. PWE without standard drug therapy were included in the control group. Comparative analyses were performed on the data among the groups. RESULTS: The Dex group exhibited a significantly lower proportion of in-hospital deaths and a markedly higher in-hospital survival time compared to the midazolam and propofol groups (p < 0.01) after propensity score matching. Kaplan-Meier curves demonstrated a significant improvement in survival rates for the Dex group compared to the control group (p = 0.025). Analysis of Variance (ANOVA) revealed no significant differences in survival rates among the Dex, midazolam, and propofol groups (F = 1.949, p = 0.143). The nomogram indicated that compared to midazolam and propofol groups, Dex was more effective in improving the survival rate of PWE. CONCLUSION: Dex might improve the survival rate of PWE in the ICU compared to no standard drug intervention. However, Dex did not exhibit superiority in improving survival rates compared to midazolam and propofol.

The potassium puzzle: exploring the intriguing connection to albuminuria.

Background: Studies have revealed a relationship between dietary potassium intake and albuminuria, despite the fact that the human body needs a lot of potassium. Our study concentrated on the link between dietary potassium intake and albuminuria. Methods: This study used subgroup analysis and weighted multivariate regression analysis. Data from the National Health and Nutrition Examination Survey (NHANES) were examined to determine the urinary albumin-to-creatinine ratio (ACR) and participant age (20 years or older). ACR >30 mg/g was the threshold for albuminuria. Results: 7,564 individuals in all were included in the study. The link between the two was significant in both our original model (OR = 0.99; 95% CI, 0.98-0.99, p < 0.0001) and the minimum adjusted model (OR = 0.99; 95% CI, 0.98-0.99, p < 0.0001). A fully adjusted model did not change the significance of the negative correlation between potassium consumption and albuminuria (OR = 0.99; 95% CI, 0.98-1.00, p = 0.0005), indicating that each unit increase in potassium intake was related with a 1% decrease in the chance of developing albuminuria. The negative correlation between potassium intake and albuminuria was not significantly influenced by sex, age, BMI, hypertension, diabetes, or smoking, according to interaction tests (p for interaction >0.05). Conclusion: Reduced risk of albuminuria was linked to higher dietary potassium intake. The particular mechanism linking the two still has to be explained by several inventive and prospective studies.

Self-Powered Autonomous Electrostatic Dust Removal for Solar Panels by an Electret Generator.

Solar panels often suffer from dust accumulation, significantly reducing their output, especially in desert regions where many of the world's largest solar plants are located. Here, an autonomous dust removal system for solar panels, powered by a wind-driven rotary electret generator is proposed. The generator applies a high voltage between one solar panel's output electrode and an upper mesh electrode to generate a strong electrostatic field. It is discovered that dust particles on the insulative glass cover of the panel can be charged under the high electrical field, assisted by adsorbed water, even in low-humidity environments. The charged particles are subsequently repelled from the solar panel with the significant Coulomb force. Two panels covered with sand dust are cleaned in only 6.6 min by a 15 cm diameter rotary electret generator at 1.6 m s-1 wind speed. Experimental results manifest that the system can work effectively in a wide range of environmental conditions, and doesn't impact the panel performance for long-term operation. This autonomous system, with its high dust removal efficiency, simplicity, and low cost, holds great potential in practical applications.

Identifying lncRNAs and mRNAs related to survival of NSCLC based on bioinformatic analysis and machine learning.

Non-small cell lung cancer (NSCLC) is the most common histopathological type, and it is purposeful for screening potential prognostic biomarkers for NSCLC. This study aims to identify the lncRNAs and mRNAs related to survival of non-small cell lung cancer (NSCLC). The expression profile data of lung adenocarcinoma and lung squamous cell carcinoma were downloaded in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset. A total of eight survival related long non-coding RNAs (lncRNAs) and 262 survival related mRNAs were filtered. By gene set enrichment analysis, 17 significantly correlated Gene Ontology signal pathways and 14 Kyoto Encyclopedia of Genes and Genomes signal pathways were screened. Based on the clinical survival and prognosis information of the samples, we screened eight lncRNAs and 193 mRNAs by single factor Cox regression analysis. Further single and multifactor Cox regression analysis were performed, 30 independent prognostication-related mRNAs were obtained. The PPI network was further constructed. We then performed the machine learning algorithms (Least absolute shrinkage and selection operator, Recursive feature elimination, and Random forest) to screen the optimized DEGs combination, and a total of 17 overlapping mRNAs were obtained. Based on the 17 characteristic mRNAs obtained, we firstly built a Nomogram prediction model, and the ROC values of training set and testing set were 0.835 and 0.767, respectively. By overlapping the 17 characteristic mRNAs and PPI network hub genes, three genes were obtained: CDC6, CEP55, TYMS, which were considered as key factors associated with survival of NSCLC. The in vitro experiments were performed to examine the effect of CDC6, CEP55, and TYMS on NSCLC cells. Finally, the lncRNAs-mRNAs networks were constructed.

Anti-HBV Activities of Cembranoids from the South China Sea Soft Coral Sinularia pedunculata and Their Structure Activity Relationship.

Hepatitis B Virus (HBV) infection is a global public health challenge that seriously endangers human health. Soft coral, as a major source of terpenoids, contains many structurally novel and highly bioactive compounds. Sixteen cembranoids (1-16), including a new one named sinupedunol B (16), were isolated from the South China Sea Soft coral Sinularia pedunculata. The structure of the sinupedunol B (16) was determined through a combination of spectroscopic analysis and X-ray single-crystal diffraction. In this study, cembranoids isolated from Sinularia pedunculata were found of anti-HBV activity for the first time. Among them, flexilarin D (6) showed significant anti-HBV activity with an IC50 value of 5.57 µM without cytotoxicity. We then analyzed the structure-activity relationship (SAR). Furthermore, it is demonstrated that flexilarin D (6) can accelerate the formation of capsid, inhibit HBeAg, HBV core particle DNA, HBV total RNA and pregenomic RNA in a dose dependent manner. We also confirmed the anti-HBV activity of 6 in HepG2-NTCP infection system. Finally, we demonstrated the anti-HBV mechanism of these compounds by inhibiting the ENI/Xp enhancer/promoter.

Apelin-13 improves pulmonary epithelial barrier function in a mouse model of LPS-induced acute lung injury by inhibiting Chk1-mediated DNA damage.

Apelin-13, a type of active peptide, can alleviate lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, the specific mechanism is unclear. Cell cycle checkpoint kinase 1 (Chk1) plays an important role in DNA damage. Here, we investigated the regulatory effect of Apelin on Chk1 in ALI. Chk1-knockout and -overexpression mice were used to explore the role of Chk1 in LPS-induced ALI mice treated with or without Apelin-13. In addition, A549 cells were also treated with LPS to establish a cell model. Chk1 knockdown inhibited the destruction of alveolar structure, the damage of lung epithelial barrier function, and DNA damage in the ALI mouse model. Conversely, Chk1 overexpression had the opposite effect. Furthermore, Apelin-13 reduced Chk1 expression and DNA damage to improve the impaired lung epithelial barrier function in the ALI model. However, the high expression of Chk1 attenuated the protective effect of Apelin-13 on ALI. Notably, Apelin-13 promoted Chk1 degradation through autophagy to regulate DNA damage in LPS-treated A549 cells. In summary, Apelin-13 regulates the expression of Chk1 by promoting autophagy, thereby inhibiting epithelial DNA damage and repairing epithelial barrier function.