Search

Abstract Loss of ARID1A has been reported to drive the progression of lung adenocarcinoma, yet the underlying mechanism remains elusive. In this study, we performed secretome analysis to identify the key secreted proteins regulating lung adenocarcinoma progression. We showed that the VASN level was significantly elevated in the conditioned medium from ARID1A-depleted A549 and H1299 cells. Restoration of ARID1A in ARID1A-depleted lung adenocarcinoma cells prevented the upregulation and secretion of VASN. Clinical analysis demonstrated a negative correlation between ARID1A and VASN expression in ARID1A-mutated lung adenocarcinomas. The patients with ARID1A-mutated lung adenocarcinoma had significantly higher concentrations of serum VASN than healthy controls. Moreover, serum VASN concentrations were associated with TNM stage, lymph node metastasis, and overall survival of the patients with ARID1A-mutated lung adenocarcinoma. Functional studies indicated that VASN overexpression potentiated the proliferation, invasion, and tumorigenesis of lung adenocarcinoma cells. Antibody neutralization of VASN suppressed the aggressiveness of ARID1A-depleted lung adenocarcinoma cells both in vitro and in vivo. Addition of recombinant VASN protein promoted the proliferation and invasion of lung adenocarcinoma cells. Additionally, knockdown of Notch1 blocked the aggressive phenotype induced by recombinant VASN protein. In conclusion, our data uncover the role of VASN in mediating the progression of ARID1A-depleted lung adenocarcinoma and highlight VASN as a promising therapeutic target for this disease.

ObjectiveTo understand the relationship between proactive health behaviors and quality of life among middle-aged and elderly residents in Laiwu district, Jinan city, Shandong province, and to provide a reference for improving the quality of life of middle-aged and elderly people in the region. MethodsFrom August to October 2022, a multi-stage random cluster sampling method was used to select 867 middle-aged and elderly residents aged ≥ 45 years old in Laiwu district, Jinan city for a questionnaire survey. The European Five-Dimensional Health Scale (EQ-5D) was used to obtain health utility values based on the Chinese population health utility scoring system to evaluate quality of life. A multivariate Tobit regression model was used to analyze the relationship between proactive health behaviors and quality of life among middle-aged and elderly residents. ResultsThe health utility values of the 702 middle-aged and elderly residents aged ≥ 45 years old finally included in Laiwu district, Jinan city, Shandong province ranged from – 0.216 to 1.000, with an average health utility value of 0.942 (0.862, 1.000). After adjusting for confounding factors such as gender, age, education level, marital status, average monthly household income, type of medical insurance, smoking status, and presence of chronic diseases, the results of the multivariate Tobit regression model showed that the health utility values of middle-aged and elderly residents who never drank alcohol (β = 0.019, 95%CI: 0.011 – 0.027) and had quit drinking (β = 0.015, 95%CI: 0.003 – 0.028) were higher than those of middle-aged and elderly residents who drank alcohol. The health utility values of the middle-aged and the elderly residents who ate fresh vegetables and fruits ≥ 4 times/week (β = 0.158, 95%CI: 0.017 – 0.299) were higher than those who did not eat fresh vegetables and fruits. The health utility values of middle-aged and elderly residents who engaged in moderate physical activity in the past week (β = 0.057, 95%CI: 0.023 – 0.090) were higher than those who did not exercise. The health utility values of the middle-aged and the elderly residents who went to bed between 20 : 00 – 22 : 00 (β = 0.074, 95%CI: 0.029 – 0.119) were higher than those who went to bed before 20 : 00. The health utility values of the middle-aged and the elderly residents who believed they needed health management very much (β = 0.020, 95%CI: 0.005 – 0.036) and believed they could try health management (β = 0.014, 95%CI: 0.002 – 0.030) were higher than those who held the attitude of not needing it. ConclusionThe proactive health behaviors of the middle-aged and the elderly residents in Laiwu district, Jinan city, Shandong province, such as the frequency of eating fresh vegetables and fruits per week, engaging in moderate physical activity, and the need for their own health management, were positively correlated with their quality of life.

Abstract Effective representation of molecules is a crucial factor affecting the performance of artificial intelligence models. This study introduces a flexible, fragment-based, multiscale molecular representation framework called t-SMILES (tree-based SMILES) with three code algorithms: TSSA (t-SMILES with shared atom), TSDY (t-SMILES with dummy atom but without ID) and TSID (t-SMILES with ID and dummy atom). It describes molecules using SMILES-type strings obtained by performing a breadth-first search on a full binary tree formed from a fragmented molecular graph. Systematic evaluations using JTVAE, BRICS, MMPA, and Scaffold show the feasibility of constructing a multi-code molecular description system, where various descriptions complement each other, enhancing the overall performance. In addition, it can avoid overfitting and achieve higher novelty scores while maintaining reasonable similarity on labeled low-resource datasets, regardless of whether the model is original, data-augmented, or pre-trained then fine-tuned. Furthermore, it significantly outperforms classical SMILES, DeepSMILES, SELFIES and baseline models in goal-directed tasks. And it surpasses state-of-the-art fragment, graph and SMILES based approaches on ChEMBL, Zinc, and QM9.

Abstract The biomechanical aspects of adjacent segment degeneration after Adult Idiopathic Scoliosis (AdIS) corrective surgery involving postoperative changes in motion and stress of adjacent segments have yet to be investigated. The objective of this study was to evaluate the biomechanical effects of corrective surgery on adjacent segments in adult idiopathic scoliosis by finite element analysis. Based on computed tomography data of the consecutive spine from T1–S1 of a 28-year-old male patient with adult idiopathic scoliosis, a three-dimensional finite element model was established to simulate the biomechanics. Two posterior long-segment fixation and fusion operations were designed: Strategy A, pedicle screws implanted in all segments of both sides, and Strategy B, alternate screws instrumentation on both sides. The range of motion (ROM), Maximum von Mises stress value of intervertebral disc (IVD), and Maximum von Mises stress of the facet joint (FJ) at the fixation adjacent segment were calculated and compared with data of the preoperative AdIS model. Corrective surgery decreased the IVD on the adjacent segments, increased the FJ on the adjacent segments, and decreased the ROM of the adjacent segments. A greater decrease of Maximum von Mises stress was observed on the distal adjacent segment compared with the proximal adjacent segment. The decrease of Maximum von Mises stress and increment of Maximum von Mises stress on adjacent FJ in strategy B was greater than that in strategy A. Under the six operation modes, the change of the Maximum von Mises stress on the adjacent IVD and FJ was significant. The decrease in ROM in the proximal adjacent segment was greater than that of the distal adjacent segment, and the decrease of ROM in strategy A was greater than that in strategy B. This study clarified the biomechanical characteristics of adjacent segments after AdIS corrective surgery, and further biomechanical analysis of two different posterior pedicle screw placement schemes by finite element method. Our study provides a theoretical basis for the pathogenesis, prevention, and treatment of adjacent segment degeneration after corrective surgery for AdIS.

The flounder (Paralichthys olivaceus) is a highly nutritious, cultured bony fish with a high economic value. The health of the fish is closely related to its blood cells, which are critical for oxygen transport, natural defense, and immunity. The microstructures, classification, counting and size of peripheral blood cells in P. olivaceus were observed and measured by Wright-Giemsa staining, and the cytochemical characteristics of peripheral blood cells were investigated by different cytochemical staining methods including periodic acid-Schiff (PAS), Sudan black B (SBB), acid phosphatase (ACP), alkaline phosphatase (ALP), peroxidase (POX), and α-naphthol acetate esterase (NAE). Besides, the ultrastructures of different cells were detected by the transmission electron microscope. The results showed that erythrocytes, thrombocytes, lymphocytes, monocytes, and neutrophils constituted the peripheral blood cells in P. olivaceus. More heterochromatins were found in erythrocytes, thrombocytes and neutrophils; however, more organelles with fewer heterochromatins were found in monocytes. Endoplasmic reticulums and phagocytic vesicles were abundant in neutrophils. Lymphocytes were the most abundant in leukocytes, followed by monocytes and neutrophils. The cytochemical staining results showed that all leukocytes were positive for SBB. Most of the lymphocytes were positive for PAS, and monocytes were positive for PAS, ACP, and POX. As for neutrophils, ACP and POX were positive. Both monocytes and neutrophils showed positive for SBB, ACP and POX, indicating that the two kinds of cells play a vital role in phagocytosis and bactericidal action. Only lymphocytes were positive for ALP, indicating that they were important in inflammation and immune response. Some characteristics similarities in peripheral blood cells were showed in P. olivaceus just as the other fishes.

Background In terms of hospitalization risk for the elderly, the evidences for adverse effects and economic losses of air pollutants on different types of cardiovascular diseases (CVDs) are limited. This study aims to quantify the economic losses of five major CVDs affected by air pollutants in Southwestern China.Methods Hospitalization information of 358,271 participants in the top five CVDs among the elderly population was collected over a 4-year time span. The generalized additive model (GAM) was used to estimate the short-term exposure response relationship between air pollutants and elderly inpatients with CVDs. The cost of illness method (COI) was used to evaluate the corresponding direct and indirect costs, and we refer to this in the text as economic losses.Results Air pollutants significantly increase the risk of hospitalisation in elderly patients with coronary heart disease (CHD), myocardial ischaemia (MI), pulmonary heart disease (PHD), hypertension, and cardiac arrhythmia. CO, NO2, PM10 and SO2 were significant increase the risk of CHD, with the RRs were 0.09, 2.59, 0.31, and 6.54, respectively; CO, NO2, O3, PM10, PM2.5, and SO2 were notably increased the risk of MI， with the RRs were 0.16, 4.19, 0.76, 0.79, 0.92, and 7.49, respectively; CO, NO2, PM10, PM2.5, and SO2 were distinctly increased the risk of PHD, with the RRs were 0.14, 2.79, 0.75, 1.00, and 3.86, respectively; NO2 and SO2 significant increase the risk of hypertension, with the RRs were 1.41 and 5.94, respectively; CO, NO2, PM10, and SO2 were distinctly increased the risk of arrhythmia, with the RRs were 0.09, 2.23, 0.36, and 5.41, respectively. Furthermore, we quantify the economic losses of five major CVDs affected by air pollutants. The economic burden of air pollution on patients with CHD, hypertension, PHD, cardiac arrhythmia, and MI were 66.38, 36.58, 5.76, 5.66 5.21 million yuan, respectively.Conclusion Our study found that short-term exposure to pollutants can have a significant impact on hospital admissions for all types of CVDs in the elderly. In terms of hospitalisation rates, SO2 and NO2 had a significant effect on different types of CVDs. Moreover, we found that air pollutants cause a heavy economic burden on patients with hypertension and CHD. It follows that reducing the concentration of air pollutants is an effective way to bring potential health benefits as well as economic benefits to local residents. Government departments should actively formulate relevant policies to reduce the physical and mental damage caused by air pollution.

Rivers are constantly disturbed by anthropogenic stressors. Developing robust biotic indicators to assess river environments across large spatial scales is important. In the subtropical Liuxi River of China, 34 native fish indicators, including 4 genera and 30 species, were selected from 108 fish species by linear discriminant analysis. These indicators were grouped into 19 ecological items and assigned evaluation scores according to the roles they played in the food web (e.g., keystoneness and trophic level) and their positive feedback on the environment (e.g., requirements for feeding, spawning/nursing, and migrating). Three formulae for calculating the index of fish indicators (IFI) were developed based on the scoring of each indicator and weighted by relative abundance (individual number, i.e., IFIN) and relative biomass (wet weight, i.e., IFIB). Spearman correlation analysis showed that IFIB, which had positive (P< 0.05) correlations with elevation (m), dissolved oxygen (mg/L), flow velocity (cm/s), Shannon-Wiener diversity, benthic index of biotic integrity, exhibited a more powerful explanation of biodiversity and environmental factors than IFIN and unweighted IFI. Therefore, IFIB was most suitable for constructing a scoring system to evaluate ecological status (e.g., water and habitat quality). These results suggested that fish indicator-based scoring and evaluation system was effectively in not only assessing the site- or region-specific ecological status bot also reflecting the fluvial biodiversity and food web integrity. Further application and promotion of this indicator-based evaluation method may improve field investigation efficiency and contribute greatly to the conservation and management of river ecosystems.

Abstract Integrating different modification strategies into a single step to achieve the desired properties of metal–organic frameworks (MOFs) has been very synthetically challenging, especially in developing advanced MOF/polymer mixed matrix membranes (MMMs). Herein, we report a polymer–MOF (polyMOF) system constructed from a carboxylated polymer with intrinsic microporosity (cPIM-1) ligand. This intrinsically microporous ligand could coordinate with metals, leading to ~100 nm-sized polyMOF nanoparticles. Compared to control MOFs, these polyMOFs exhibit enhanced ultramicroporosity for efficient molecular sieving, and they have better dispersion properties in casting solutions to prepare MMMs. Ultimately, integrating coordination chemistries through the cPIM-1 and polymer-based functionality into porous materials results in polyMOF/PIM-1 MMMs that display excellent CO2 separation performance (surpassing the CO2/N2 and CO2/CH4 upper bounds). In addition to exploring the physicochemical and transport properties of this polyMOF system, scalability has been demonstrated by converting the developed MMM material into large-area (400 cm2) thin-film nanocomposite (TFN) membranes.

Abstract Fish are vital in river ecosystems; however, traditional investigations of fish usually cause ecological damage. Extracting DNA from aquatic environments and identifying DNA sequences offer an alternative, noninvasive approach for detecting fish species. In this study, the effects of environmental DNA (eDNA), coupled with PCR and next‐generation sequencing, and electrofishing for identifying fish community composition and diversity were compared. In three subtropical rivers of southern China, fish specimens and eDNA in water were collected along the longitudinal (upstream–downstream) gradient of the rivers. Both fish population parameters, including species abundance and biomass, and eDNA OTU richness grouped 38 sampling sites into eight spatial zones with significant differences in local fish community composition. Compared with order‐/family‐level grouping, genus‐/species‐level grouping could more accurately reveal the differences between upstream zones I−III, midstream zones IV−V, and downstream zones VI–VIII. From the headwaters to the estuary, two environmental gradients significantly influenced the longitudinal distribution of the fish species, including the first gradient composed of habitat and physical water parameters and the second gradient composed of chemical water parameters. The high regression coefficient of alpha diversity between eDNA and electrofishing methods as well as the accurate identification of dominant, alien, and biomarker species in each spatial zone indicated that eDNA could characterize fish community attributes at a level similar to that of traditional approaches. Overall, our results demonstrated that eDNA metabarcoding can be used as an effective tool for revealing fish composition and diversity, which is important for using the eDNA technique in aquatic field monitoring.

Objective: The increasing identification of pulmonary nodules has led to a growing emphasis on segmentectomy. Nevertheless, the surgical process for segmentectomy is complex and optimizing segmentectomy is a critical clinical concern. This study aimed to evaluate the safety and short- and long-term efficacy of V6-preserving superior segmentectomy. Methods: We performed a retrospective analysis of patients who underwent thoracoscopic superior segmentectomy at our hospital between January 2019 and June 2020. Eligible patients were categorized into an V6 vein-preserving segmentectomy (VVPS) group and a Non V6 vein-preserving segmentectomy (NVVPS) group depending on the preservation of V6. Primary outcome measures encompassed the evaluation of surgical safety (surgical margins, 3-year overall survival, and disease-free survival), whereas secondary measures included postoperative complication rates, operative time, estimated intraoperative blood loss, length of hospital stay, and associated costs. Results: The analysis included a final cohort of 78 patients. In the NVVPS group (n = 43), 95.3 % of patients exceeded the tumor diameter, and no positive surgical margins were observed. The 3-year overall survival (OS) and disease-free survival (DFS) rates for the NVVPS group were 95.3 %, with no significant differences in OS (p = 0.572) and DFS (P = 0.800) compared with the VVPS group. Additionally, the median total hospitalization cost for the NVVPS group was 41,400 RMB (IQR, 38,800–43,400), which was significantly lower than that of the VVPS group, showing statistical significance (P 0.05). Conclusion: V6-preserving superior segmentectomy is a secure and optimized surgical alternative. Its streamlined procedure facilitates easier adoption in primary healthcare facilities, rendering it a superior choice for superior segmentectomy.

Abstract Insects and pathogens release effectors into plant cells to weaken the host defense or immune response. While the imports of some bacterial and fungal effectors into plants have been previously characterized, the mechanisms of how caterpillar effectors enter plant cells remain a mystery. Using live cell imaging and real-time protein tracking, we show that HARP1, an effector from the oral secretions of cotton bollworm (Helicoverpa armigera), enters plant cells via protein-mediated endocytosis. The entry of HARP1 into a plant cell depends on its interaction with vesicle trafficking components including CTL1, PATL2, and TET8. The plant defense hormone jasmonate (JA) restricts HARP1 import by inhibiting endocytosis and HARP1 loading into endosomes. Combined with the previous report that HARP1 inhibits JA signaling output in host plants, it unveils that the effector and JA establish a defense and counter-defense loop reflecting the robust arms race between plants and insects.

Abstract Background Minerals have crucial biological functions in metabolism and are primarily obtained through diet. As a result, various dietary patterns can impact blood mineral levels. The aim of this study was to investigate the correlation between dietary patterns and the concentration of calcium, magnesium, iron, zinc, and copper in the bloodstream. Methods Three hundred eighty healthy children (53.7% male) were recruited in a region of Hunan Province in September 2019. We gathered basic information and measured physical proportions, along with completing a food frequency questionnaire (FFQ). Using principal component analysis (PCA), we determined dietary patterns. To analyze mineral levels in the blood, we used flame atomic absorption spectrometry (FAAS). We utilized linear regression models to investigate if certain dietary patterns are related to mineral concentration. Results Three dietary patterns were identified: ‘Vegetables/Nuts,’ ‘Snacks/Beverages,’ and ‘Cereal/Beans.’ Children from high-income families (annual average income > 50,000 yuan) prefer the ‘Vegetables/Nuts’ dietary pattern (P = 0.004). In comparison, those from low-income families (annual average income

Abstract Aim The aim of this study was to synthesize the self‐management theory, model and frameworks of patients with chronic heart failure, focusing on construction process, methods and existing problems. Background Although the self‐management theories have been created and verified for those patients with chronic heart failure, no reviews have been performed to integrate these theories. Design A scoping review of recent literature (without a date limit) was conducted. Methods A comprehensive literature search was performed. If the study reported the construction of a self‐management theory, model or framework about chronic heart failure cases, it would be included in the review. Results Fourteen studies were included, which could be categorized into situation‐specific theory, middle‐range theory and other theory models (including conceptual model, hypothetic regression model and identity description model). It also includes the update and validation of theories, the situation‐specific theoretical of caregiver contributions extended from situation‐specific theories and the nurse‐led situation‐specific theory in different contexts. Conclusion Self‐management might contribute to start an education programme before patients with chronic heart failure (CHF) begin their chronic disease live as an individual. Our scoping review indicates that a series of self‐management theories, models and frameworks for CHF patients have been developed, but more studies are still needed to validate and support these theories according to their cultural contexts.

Background: The gut microbiota may affect mood through the microbiota-gut-brain axis. The purpose of this study was to examine the effect of the gut microbiota and its metabolites, such as short-chain fatty acids (SCFAs), on prenatal depression and to determine the role of 5-hydroxytryptamine (5-HT) on prenatal depression in association with the gut microbiota and its metabolites (i.e. SCFAs). Methods: Eighty-six pregnant women in the third trimester were recruited. Prenatal depression was determined by a score of 10 via the Edinburgh Postpartum Depression Scale. Demographic data, stool, and blood samples were collected. The gut microbiota and its metabolites SCFAs were determined by 16S rRNA gene sequencing and liquid chromatography-mass spectrometry analysis. Plasma 5-HT was determined by gas chromatography-mass spectrometry analysis. Results: After controlling relevant covariates, our results found the higher the abundance of Candidatus_Soleaferrea, the lower the risk of prenatal depression; the higher the concentration of propanoic acid, the higher risk of prenatal depression. Our results also found the lower the plasma 5-HT, the higher the risk of prenatal depression, and 5-HT was related to unclassified_c_Clostridia and NK4A214_group. However, results of this study did not support the moderating effect of plasma 5-HT on the association of Candidatus_Soleaferrea or propionic acid with prenatal depression. Conclusions: Results of this study supported that changes in certain gut microbiota, SCFAs, and plasma 5-HT during pregnancy were associated with prenatal depression. This finding provides new ideas for interventions based on diet or probiotics to regulate mood during pregnancy.

Due to its traditional fermentation, there are obvious limits on the quality improvements in black tea. However, microbial fermentation can provide an abundance of metabolites and improve the flavor of tea. The “golden flower” fungi are widely used in the microbial fermentation of tea and has unique uses in healthcare. To further explore the improvements in black tea quality achieved via microbial fermentation, we used widely targeted metabolomics and metagenomics analyses to investigate the changes in and effects of metabolites and other microorganisms during the interaction between the “golden flower” fungi and black tea. Five key flavor metabolites were detected, the levels of catechin, epigallocatechin gallate, (−)-epicatechin gallate were decreased by different degrees after the inoculation of the “golden flower” fungus, whereas the levels of caffeine and (+)-gallocatechin increased. Botryosphaeriaceae, Botryosphaeriales, Dothideomycetes, Aspergillaceae, Trichocomaceae, and Lecanoromycetes play a positive role in the black tea fermentation process after inoculation with the “golden flower” fungi. D-Ribose can prevent hypoxia-induced apoptosis in cardiac cells, and it shows a strong correlation with Botryosphaeriaceae and Botryosphaeriales. The interaction between microorganisms and metabolites is manifested in tryptophan metabolism, starch and sucrose metabolism, and amino sugar and nucleotide sugar metabolism. In conclusion, the changes in metabolites observed during the fermentation of black tea by “golden flower” fungi are beneficial to human health. This conclusion extends the knowledge of the interaction between the “golden flower” fungi and black tea, and it provides important information for improving the quality of black tea.

The catastrophic coronavirus disease 2019 (COVID-19) pandemic has raised many health questions, and whether breast milk from SARS-CoV-2 infected mothers may be a vector for SARS-CoV-2 transmission has become a hot topic of concern worldwide. Currently, there are extremely limited and conflicting data on the risk of infection in infants through breastfeeding. For this reason, we investigated almost all current clinical studies and systematically analyzed the presence of SARS-CoV-2 and antibodies in the breast milk of mothers infected with SARS-CoV-2, their effects on newborns, and the mechanisms involved. A total of 82 studies were included in this review, of which 66 examined the presence of SARS-CoV-2 in breast milk samples from mothers diagnosed with COVID-19, 29 reported results of antibody detection of SARS-CoV-2 in breast milk, and 13 reported both nucleic acid and antibody test results. Seventeen studies indicated the presence of detectable SARS-CoV-2 nucleic acid in breast milk samples, and only two studies monitored viral activity, both of which reported that infectious viruses could not be cultured from RNA-positive breast milk samples. All 29 studies indicated the presence of at least one of the three antibodies, IgA, IgG and IgM, in breast milk. Five studies indicated the presence of at least one antibody in the serum of breastfed newborns. No COVID-19-related deaths were reported in all 1,346 newborns. Our study suggests that direct breastfeeding does not pose an additional risk of infection to newborns and that breast milk is a beneficial source of anti-SARS-CoV-2 antibodies that provide passive immune protection to infants. In addition, direct breastfeeding would provide maternal benefits. Our review supports the recommendation to encourage direct breastfeeding under appropriate infection control guidelines.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier: 458043.

Invertebrates play vital roles in maintaining biodiversity and food web structure. However, it is difficult to identify invertebrate taxa across complex habitats due to the limitation of traditional morphology. In subtropical wetlands, environmental DNA (eDNA) metabarcoding was used to characterize the composition and diversity of aquatic invertebrates and analyze the environmental impacts on invertebrate community structure. According to the relative abundance (%) of invertebrate OTU richness, 30 sampling sites in wetlands were clustered into six zones, which exhibited significant spatial (i.e., wetland type-specific) differences in taxonomic composition. The relative OTU abundance (%) at the phylum level showed that Cnidaria (48.5%) > Porifera (19.4%) > Rotifera (11.0%) > Mollusca (9.2%) > Annelida (5.3 ± 2.8%) > others (less than 2.2%). Of the five alpha diversity indexes, ‘Simpson’ was the most effective index to distinguish the spatial differences in invertebrate diversity, and the class-level alpha diversity showed higher recognition than other taxonomic levels. The class-level biomarkers that could indicate the habitat-specific composition of local invertebrates were Insecta, Cnidaria, Hydrozoa, and Gastropoda in the inflow river; Ascidiacea and Demospongiae in the fluvial wetland; Clitellata, Gymnolaemata, and Monogononta in the lacustrine wetland; and Echinoidea in the estuarine wetland. The associations between environmental factors and invertebrate OTU richness based on redundancy analysis showed the taxon-level tendency of phylum (78.5%) > class (73.4%) > order (69.3%) > family (64.9%) > genus (61.2%). Our results demonstrated that aquatic invertebrate diversity profiling by environmental DNA metabarcoding can effectively reflect the composition, diversity and biomarkers of invertebrate communities. In the future, because of its great application potential, the eDNA technique may play an important role in biomonitoring complex water environments.

Biotransformation of ursonic acid (1) by two fungal strains Aspergillus ochraceus CGMCC 3.5324 and Aspergillus oryzae CGMCC 3.407 yielded thirteen new compounds (4, 5, 7–10, and 13–19), along with five recognized ones. The structural details of new compounds were determined through spectroscopic examination (NMR, IR, and HR-MS) and X-ray crystallography. Various modifications, including hydroxylation, epoxidation, lactonization, oxygen introduction, and transmethylation, were identified on the ursane core. Additionally, the anti-neuroinflammatory efficacy of these derivatives was assessed on BV-2 cells affected by lipopolysaccharides. It was observed that certain methoxylated and epoxylated derivatives (10, 16, and 19) showcased enhanced suppressive capabilities, boasting IC50 values of 8.2, 6.9, and 5.3 μM. Such ursonic acid derivatives might emerge as potential primary molecules in addressing neurodegenerative diseases.

Abstract The ‘angiogenic switch’ is critical for tumor progression. However, the pathological details and molecular mechanisms remain incompletely characterized. In this study, we established mammal xenografts in zebrafish to visually investigate the first vessel growth (angiogenic switch) in real-time, by inoculating tumor cells into the perivitelline space of live optically transparent Transgenic (flk1:EGFP) zebrafish larvae. Using this model, we found that hypoxia and hypoxia-inducible factor (HIF) signaling were unnecessary for the angiogenic switch, whereas vascular endothelial growth factor A gene (Vegfa) played a crucial role. Mechanistically, transcriptome analysis showed that the angiogenic switch was characterized by inhibition of translation, but not hypoxia. Phosphorylation of eukaryotic translation initiation factor 2 alpha (Eif2α) and the expression of Vegfa were increased in the angiogenic switch microtumors, and 3D tumor spheroids, and puromycin-treated tumor cells. Vegfa overexpression promoted early onset of the angiogenic switch, whereas Vegfa knockout prevented the first tumor vessel from sprouting. Pretreatment of tumor cells with puromycin promoted the angiogenic switch in vivo similarly to Vegfa overexpression, whereas Vegfa knockdown suppressed the increase. This study provides direc and dynamic in vivo evidences that inhibition of translation, but not hypoxia or HIF signaling promotes the angiogenic switch in tumor by increasing Vegfa transcription.

BackgroundThere is no consensus on whether intravenous rehydration must be added after preoperative phenoxybenzamine (PXB) administration for pheochromocytoma. The aim of this study is to investigate whether abandonment of intravenous volume expansion after PXB administration is associated with intraoperative hemodynamic instability.Methods83 Patients with pheochromocytoma received surgical treatment in the Department of Urology, Handan First Hospital, between October 2014 and July 2022. All patients were subclassified into either the hemodynamic stability group (HS group) or the hemodynamic instability group (HU group) according to whether intraoperative hemodynamic instability occurred, with 51 cases in HS group and 32 cases in HU group. Differences in data between the two groups were examined, and the risk factors for intraoperative hemodynamic instability were analyzed using logistic regression.ResultsThe results of the analysis showed no statistically significant differences in age, sex, location of the tumor, surgical method, body mass index (BMI) ≥ 24 kg/m2, blood and urine catecholamine test results, preoperative oral PXB followed by combined intravenous volume expansion, proportion of patients with hypertension or diabetes mellitus or coronary heart disease between the two groups (P>0.05). The size of the tumor in the HS group was smaller than that in the HU group (5.3 ± 1.9 cm vs 6.2 ± 2.4 cm P=0.010). Multivariate analyses demonstrated that abandonment of intravenous volume expansion after preoperative receipt of α-blockers in patients with adrenal pheochromocytoma was not an independent risk factor for intraoperative hemodynamic instability. Only the tumor size (P=0.025) was an independent risk factor for intraoperative hemodynamic instability.ConclusionThe purpose of general preoperative intravenous fluid expansion is to prevent hypotension after the tumor has been resected. In the current study, we indicated that preoperative management of pheochromocytomas using the α-blocker PXB in combination with intravenous volume expansion does not further reduce the risk of intraoperative hemodynamic instability or postoperative complications compared with oral PXB alone. Therefore, our study supports preoperative management of pheochromocytoma with a single α-blocker, PXB, as sufficient.

Chloropropanols, one of the major contaminants in food, and the corresponding esters or glycidyl esters (GEs) are of great concern in terms of product safety due to their potential carcinogenicity. During heat processing, glycerol, allyl alcohol, chloropropanol esters, sucralose, and carbohydrate in mixed foodstuffs are probable precursors of chloropropanol. The standard analytical techniques for chloropropanols or their esters are GC–MS or LC-MS following sample derivatization pretreatment. By comparing modern data against that five-year-old before, it appears that the levels of chloropropanols and their esters/GEs in food products have somewhat decreased. 3-MCPD esters or GEs may yet exceed the permitted intake set, however, especially in newborn formula which requires particularly stringent regulatory measures. Citespace (6.1. R2) software was employed in this study to examine the research focii of chloropropanols and their corresponding esters/GEs in the literature.

Brain-derived neurotrophic factor(BDNF)is a basic protein, and a member of neurotrophic factor family, which plays an important role in the development, differentiation and maintenance of neurons. A large number of studies have confirmed that BDNF is involved in the occurrence and development of neurodegenerative diseases such as Parkinson's disease and Alheimer's disease, and has a neuroprotective effect. In the retina, BDNF is mainly produced by retinal ganglion cells, amacrine cells, astrocytes, retinal glial cells(Müller cells)and photoreceptors. In recent years, related studies have found that BDNF is involved in the occurrence and development of glaucoma, diabetic retinopathy(DR)and other ocular diseases, and may have a diagnostic role, which will be beneficial to early intervention of patients to avoid the development of advanced glaucoma or DR. On the other hand, BDNF-based therapies have achieved good results in in vitro and in vivo experiments of glaucoma, DR and amblyopia, which may provide more choices for the treatment of these ocular diseases. In this manuscript, the research progresses of BDNF in ocular diseases in recent years were reviewed.

Background Current antiretroviral regimens have, for the most part, achieved optimal antiretroviral efficacy and tolerability, transforming HIV infection from a deadly disease into a manageable chronic condition. However, adherence to daily oral drug intake remains an issue, as it is the most important determinant for sustained viral suppression and prevention of the emergence of drug-resistant viral strains. The long-acting injection antiretroviral cabotegravir and rilpivirine combination, a novel drug delivery approach, is about to revolutionise the therapy for people living with HIV. In this protocol, we aim to generate a clinically useful summary of the interventions based on their efficacy.Methods and analysis We searched the literature for eligible studies published from inception up to 16 August 2022 through PubMed, EMBASE, Cochrane Library, Scopus and ClinicalTrials.gov. Two methodologically trained researchers will select the qualified studies for data extraction independently. Cochrane Risk of Bias tool will be used to assess the risk of bias in included studies. Statistical heterogeneity will be computed by Cochrane X2 and I2 tests. Sensitivity analysis will be conducted to evaluate the stability of the results. Publication biases will be evaluated by Begg’s and Egger’s tests. The quality of evidence will be assessed by the Grading of Recommendations Assessment, Development and Evaluation system. The RevMan V.5.3 and Stata V.14.0 software will be applied for statistical analyses.Ethics and dissemination Ethical approval will not be required for this systematic review because the data used are not linked to the individual patient. The results of this review will be disseminated by being published in a peer-reviewed journal.PROSPERO registration number CRD42022310414

Abstract Invasion and metastasis are the main causes of colorectal cancer (CRC)‐related death. Accumulating evidence suggested that sphingosine kinase 1 (SphK1) promoted the metastasis of CRC and autophagy played an important role in SphK1 promoting the metastasis of malignancy. However, the mechanism by which SphK1‐driven autophagy promotes invasion and metastasis in CRC remains to be clarified. In the present study, immunohistochemical detection showed the expression of SphK1 and paxillin was higher in human CRC tissues than those of normal colorectal mucosal tissues, they were both associated with TNM staging, lymphatic, and distance metastasis. In addition, study of in situ tumor transplantation model in nude mice showed that the suppression of SphK1 inhibited the growth of colonic orthotopic implantation tumors and the expression of paxillin, p‐paxillin, LC3 in the tumor. So, SphK1 may promote CRC metastasis via inducing the expression of paxillin expression and its phosphorylation, in vivo. Furthermore, results of CCK8 assay, transwell and wound healing assays showed that SphK1 promoted the viability, invasion, and metastasis of CRC cells. Transmission electron microscopy detection showed that SphK1 is the key factor in autophagy induction in CRC cells. Moreover, western blot examination indicated that the expression of LC3Ⅱ/Ⅰ, paxillin, p‐paxillin, MMP‐2, and vimentin was enhanced in SphK1‐overexpressed CRC cells and suppressed in SphK1 knockdown CRC cells, meanwhile, the expression of E‐cadherin was suppressed in SphK1‐overexpressed CRC cells and enhanced in SphK1 knockdown CRC cells. Suppression of autophagy by 3MA reversed the expression of paxillin and its phosphorylation in SphK1‐overexpressed CRC cells, indicated that SphK1‐driven autophagy induced the expression of paxillin and its phosphorylation in CRC cells. Together, these findings reveal that SphK1‐driven autophagy may promote the invasion and metastasis of CRC via promoting the expression of focal adhesion paxillin and its phosphorylation.

BackgroundIt is critical to investigate the underlying pathophysiological mechanisms in the development of atopic dermatitis. The microbiota hypothesis suggested that the development of allergic diseases may be attributed to the gut microbiota of mother-offspring pairs. The purpose of this study was to investigate the relationship among maternal-offspring gut microbiota and the subsequent development of atopic dermatitis in infants and toddlers at 2 years old.MethodsA total of 36 maternal-offspring pairs were enrolled and followed up to 2 years postpartum in central China. Demographic information and stool samples were collected perinatally from pregnant mothers and again postpartum from their respective offspring at the following time intervals: time of birth, 6 months, 1 year and 2 years. Stool samples were sequenced with the 16S Illumina MiSeq platform. Logistic regression analysis was used to explore the differences in gut microbiota between the atopic dermatitis group and control group.ResultsOur results showed that mothers of infants and toddlers with atopic dermatitis had higher abundance of Candidatus_Stoquefichus and Pseudomonas in pregnancy and that infants and toddlers with atopic dermatitis had higher abundance of Eubacterium_xylanophilum_group at birth, Ruminococcus_gauvreauii_group at 1 year and UCG-002 at 2 years, and lower abundance of Gemella and Veillonella at 2 years. Additionally, the results demonstrated a lower abundance of Prevotella in mothers of infants and toddlers with atopic dermatitis compared to mothers of the control group, although no statistical difference was found in the subsequent analysis.ConclusionThe results of this study support that gut microbiota status among mother-offspring pairs appears to be associated with the pathophysiological development of pediatric atopic dermatitis.

Recanalization therapy is the most effective treatment for eligible patients with acute ischemic stroke (AIS). Gut microbiota are involved in the pathological mechanisms and outcomes of AIS. However, the association of gut microbiota features with adverse recanalization therapy outcomes remains unclear. Herein, we investigated gut microbiota features associated with neurological deficits in patients with AIS after recanalization therapy and whether they predict the patients’ functional outcomes. We collected fecal samples from 51 patients with AIS who received recanalization therapy and performed 16S rRNA gene sequencing (V3–V4). We compared the gut microbiota diversity and community composition between mild to moderate and severe disability groups. Next, the characteristic gut microbiota was compared between groups, and we noted that the characteristic gut microbiota in patients with mild to moderate disability included Bilophila, Butyricimonas, Oscillospiraceae_UCG-003, and Megamonas. Moreover, the relative abundance of Bacteroides fragilis, Fusobacterium sp., and Parabacteroides gordonii was high in patients with severe disability. The characteristic gut microbiota was correlated with neurological deficits, and areas under the receiver operating characteristic curves confirmed that the characteristic microbiota predicted adverse recanalization therapy outcomes. In conclusion, gut microbiota characteristics are correlated with recanalization therapy outcomes in patients with AIS. Gut microbiota may thus be a promising biomarker associated with early neurological deficits and predict recanalization therapy outcomes.

Bidirectional communication of the microbiota–gut–brain axis is crucial in stroke. Recanalization therapy, namely intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT), are recommended for eligible patients with acute ischemic stroke (AIS). It remains unclear whether gut microbiota metabolites, namely trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), can predict the prognosis after recanalization therapy. This prospective study recruited patients with AIS receiving IVT, EVT, or both. The National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) scores were used to assess the severity and functional outcomes of AIS, respectively. A functional outcome of mild-to-moderate disability was defined as a mRS score of 0–3 at discharge. Plasma TMAO and SCFA levels were measured through liquid chromatography with triple-quadrupole mass spectrometry. Fifty-six adults undergoing recanalization therapy for AIS were enrolled. Results showed that TMAO levels were not associated with stroke severity and functional outcomes, while isovalerate levels (one of the SCFAs) were negatively correlated with NIHSS scores at admission and discharge. In addition, high isovalerate levels were independently associated with a decreased likelihood of severe disability. The study concluded that an elevated plasma isovalerate level was correlated with mild stroke severity and disability after recanalization therapy for AIS.

Klebsiella pneumoniae is a common pathogen of nosocomial pneumonia worldwide and community-acquired pneumonia (CAP) in Asia. Previous studies have shown that K. pneumoniae bacteremic CAP is associated with high mortality. We aimed to revisit K. pneumoniae bacteremic pneumonia in the current era and determine the risk factors associated with 28-day mortality. Between January 2014 and August 2020, adult patients with K. pneumoniae bacteremic pneumonia in a medical center in Taiwan were identified. Clinical and microbiological characteristics were compared between CAP and nosocomial pneumonia. Risk factors for 28-day mortality were analyzed using multivariate logistic regression. Among 150 patients with K. pneumoniae bacteremic pneumonia, 52 had CAP and 98 had nosocomial pneumonia. The 28-day mortality was 52% for all patients, 36.5% for CAP, and 60.2% for nosocomial pneumonia. Hypervirulent K. pneumoniae was more prevalent in CAP (61.5%) than in nosocomial pneumonia (16.3%). Carbapenem-resistant K. pneumoniae was more prevalent in nosocomial pneumonia (58.2%) than in CAP (5.8%). Nosocomial pneumonia, a higher Severe Organ Failure Assessment score, and not receiving appropriate definitive therapy were independent risk factors for 28-day mortality. In conclusion, revisiting K. pneumoniae bacteremic pneumonia in the current era showed a high mortality rate. Host factors, disease severity, and timely effective therapy affect the treatment outcomes of these patients.

BackgroundBoth obstructive sleep apnea (OSA) and periodic limb movements of sleep (PLMS) are common in the sleep laboratory. The severity of OSA can be improved by using continuous positive airway pressure (CPAP). However, increasing evidence has shown an elevated periodic limb movement index (PLMI) in patients with OSA who use CPAP, although the pathophysiology is still unknown. This meta-analysis aimed to investigate changes in PLMS after using CPAP and the potential pathophysiology of these changes.MethodsClinical trials in adult humans investigating the comorbidity between PLMS and CPAP were identified and analyzed using random-effects model meta-analysis.ResultsThis meta-analysis included 14 studies comprising 2,938 patients with OSA. The PLMI was significantly increased after using CPAP with a difference in means of 1.894 (95% confidence interval = 0.651–3.138, p = 0.003). Subgroup analysis showed that CPAP was only significantly associated with an increase in PLMI in the patients without PLMS at baseline (p = 0.045) and in those with a baseline body-mass index

E3 ubiquitin ligases play essential roles in plant defense responses. However, their roles in other plant species have not been investigated extensively. Here, we used a gain-of-function approach to interrogate the function of GmSAUL1 (Senescence-Associated E3 Ubiquitin Ligase 1) homologs in soybeans. Ectopic over-expression of GmSAUL1a in Nicotiana tabacum resulted in autoimmune responses that could be suppressed by high temperature, which is a hallmark of NLR (nucleotide-binding leucine-rich repeat protein)-mediated resistance. Interestingly, an elevated activation of NtMPK6, but reduced activation of NtMPK4, responding to flg22 treatment, was observed in these GmSAUL1a-over-expressing tobacco lines, suggesting that over-expressing GmSAUL1a activates immune signaling through activating NtMPK6, but suppressing NtMPK4 kinase activity. Collectively, these results demonstrated that GmSAUL1 plays a positive and pivotal role in soybean immunity that is likely governed by NLR proteins.

E3 ubiquitin ligases play important roles in plant immunity, but their role in soybean has not been investigated previously. Here, we used Bean pod mottle virus (BPMV)-mediated virus-induced gene silencing (VIGS) to investigate the function of GmSAUL1 (Senescence-Associated E3 Ubiquitin Ligase 1) homologs in soybean. When two closely related SAUL1 homologs were silenced simultaneously, the soybean plants displayed autoimmune phenotypes, which were significantly alleviated by high temperature, suggesting that GmSAUL1a/1b might be guarded by an R protein. Interestingly, silencing GmSAUL1a/1b resulted in the decreased activation of GmMPK6, but increased activation of GmMPK3 in response to flg22, suggesting that the activation of GmMPK3 is most likely responsible for the activated immunity observed in the GmSAUL1a/1b-silenced plants. Furthermore, we provided evidence that GmSAUL1a is a bona fide E3 ligase. Collectively, our results indicated that GmSAUL1 plays a negative role in regulating cell death and immunity in soybean.

A series of Tb3+-activated NaLa(MoO4)2 phosphates were synthesized by solid-state reaction at 800 ℃ for 5 h. Comprehensive characterization of these samples included X-ray diffraction characteristics, luminescence spectra, scanning electron microscopy and analysis of luminescence decay curves. The luminescence analysis indicated that the strongest emissions occurred at wavelengths of 544 nm, 591 nm, and 615 nm. The colour of the fluorescence emission can change from red-orange to red and then to yellow-green light depending on the cvaoncentration ratio of Eu3+ and Tb3+ under different excitations. The CIE chromaticity coordinates demonstrated variability across different color ranges, showcasing the phosphor's capacity for color tuning. The energy yield was 94% when Eu3+ was 0.3 in direct comparison.The versatility in color tuning and high energy efficiency of this bis-molybdate phosphor make it a promising candidate for diverse applications in color display technologies and illumination. [ABSTRACT FROM AUTHOR]

Abstract The association between sleep apnea (SA) and depression had been reported in a few previous studies. However, whether SA increases the risk of major depressive disorder (MDD) has not been studied comprehensively in a large-scale study. We performed this population-based cohort study to assess the association between SA and MDD. We identified adult patients having SA from the Taiwan National Health Insurance Research Database and excluded those having MDD before SA diagnosis. Thirty control subjects were randomly selected to match to each SA patient by age and sex. Totally, 10,259 SA patients were matched to 102,590 control subjects. The incidence rate and cumulative incidence of MDD were significantly higher in SA patients than in the control subjects (both p

Serous ovarian carcinoma (SOC) is a gynecological malignancy with high mortality rates. Currently, there is a lack of reliable biomarkers for accurate SOC patient prognosis. Here, we analyzed SOC RNA-Seq data from The Cancer Genome Atlas (TCGA) to identify prognostic biomarkers. Through the pearson correlation analysis, univariate Cox regression analysis, and LASSO-penalized Cox regression analysis, we identified nine lncRNAs significantly associated with four types of RNA modification writers (m6A, m1A, APA, and A-I) and with the prognosis of SOC patients (P

Background: Tanshinone IIA(TA) could be used for the treatment of some diseases. However, the clinical application of TA was hindered by its poor water - solubility and low oral bioavailability, etc. The aim of this study was to improve its oral bioavailability and dissolution by encapsulating TA with hydroxypropyl–beta–cyclodextrin (HP-β-CD). Methods: The encapsulation composite of HP-β-CD/TA was prepared through solution method with optimization of response surface test design by taking encapsulation efficiency and drug loading as the goals; the in-vitro dissolution and in-vivo metabolism of the composite in rats were evaluated. Results: The optimal concentration of HP-β-CD in water was 0.4 g/mL; the optimal ratio of TA to HP-β-CD was 1:7 in weight for the encapsulating process at 50°C with stirring for 2h; the encapsulation efficiency and drug loading were 84.06% and 7.38%, respectively; the cumulative release of TA from HP–β -CD TA composite in vitro dissolution reached to 72% within 90 min, which was 3.78 times of that of the original TA substance; the area under the curves of AUC(0-t) and AUC(0-∞) of the HP–β –CD -TA inclusion composite were 3.71 and 3.42 times of the original TA substance under p

Abstract Background Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare and heterogeneous clinico-neuroradiological syndrome characterized by headache, altered mental status, seizures, and visual disturbances. Hypertension and immunosuppression are two of the main factors that predispose an individual to RPLS. However, RPLS can develop when no major risk factors are present. RPLS has been reported in pediatric nephrotic patients, but rarely in adults. Case presentation A 42-year-old Asian woman with nephrotic syndrome presented with seizures, headaches, and nausea. Her blood pressure was controlled, and no immunosuppressants had been prescribed. All symptoms and tests indicated RPLS following infection with pneumonia, which was successfully treated by immediate administration antibiotic and anti-epileptic medications. Seizures did not recur during a 2-year follow-up period. Conclusions When patients with nephrotic syndrome have an infection, RPLS symptoms should be investigated thoroughly. With early diagnosis and appropriate treatment of RPLS, morbidity and mortality can be prevented.

Delayed healing of diabetic corneal epithelial wound is a commonly encountered condition, and persistent corneal epithelial defects may give rise to recurrent epithelium erosion, corneal ulceration, and subsequent perforation as well as affecting visual loss. The current review focused on the pathological basis, updates of the pathogenesis, and recent advances in the treatment of delayed healing of diabetic corneal epithelial wounds, wherein the roles of hyperglycemia, tear film, proteases, cytokines, corneal nerves and genes were elaborated, and the latest views on treatment strategies, for the delayed healing were summarized as well. Recent advances in research on delayed corneal epithelial wound healing in diabetes mellitus.

Abstract Background Evidence-based practice (EBP) education or training are considered fundamental to building and strengthening an EBP culture, as well as to encouraging evidence-based academic and clinical practice in the nursing community. However, few valid and reliable instruments are available for the assessment of EBP teaching and learning in clinical nurses in China. Translation, reliability, and validity testing of the English Evidence-Based Practice Profile Questionnaire (EBP2Q), which has strong psychometric properties, may encourage evaluation and promote the implementation of EBP in Mainland China. Methods Based on established guidelines for the development of questionnaires, the English EBP2Q was translated and cross-culturally adapted. The Chinese version of the EBP2Q (EBP2Q-C) was validated using a sample of 543 nurses. Structural validity was evaluated through exploratory factor analysis and confirmatory factor analysis, and the questionnaire was tested for convergent and criterion validity. The internal consistency and test-retest reliability were also evaluated. Results The content validity index demonstrated good content validity (≥0.98). An eight-factor structure was obtained in the exploratory factor analysis, and verified by a three-order factor model from the confirmatory factor analysis (χ 2 /df = 2.001; RMSEA = 0.065; SRMR = 0.077; and CFI = 0.884). The Spearman’s rank correlation analysis of the EBP2Q-C with the Evidence-Based Practice Questionnaire showed moderate correlations for Practice (0.58) and Confidence (0.68) and a low correlation for Sympathy (0.32). Criterion validity was demonstrated by significant differences in terms of nurses’ highest education, present position, EBP training, involvement in research programs, and level of understanding of English. Both the overall Cronbach’s α and the Cronbach’s α for the domains exceeded 0.70. The intraclass correlation coefficients for the domains ranged between 0.75 and 0.96, indicating satisfactory repeatability. Conclusions Except for the convergent validity of the Sympathy domain, the EBP2Q-C provided evidence of validity and reliability. Therefore, it can be applied in EBP education or training assessment in Mainland China.

Abstract Background Prader–Willi syndrome (PWS) is a neurodevelopmental disorder characterized by multiple respiratory, cognitive, endocrine, and behavioral symptoms, such as central apnea, intellectual disabilities, exaggerated stress responses, and temper tantrums. The locus coeruleus noradrenergic system (LC-NE) modulates a diverse range of behaviors, including arousal, learning, pain modulation, and stress-induced negative affective states, which are possibly correlated with the pathogenesis of PWS phenotypes. Therefore, we evaluated the LC-NE neuronal activity of necdin-deficient mice, an animal model of PWS. Methods Heterozygous necdin-deficient mice (B6.Cg-Ndntm1ky) were bred from wild-type (WT) females to generate WT (+m/+p) and heterozygotes (+m/−p) animals, which were examined of LC-NE neuronal activity, developmental reflexes, and plethysmography. Results On slice electrophysiology, LC-NE neurons of Ndn tm1ky mice with necdin deficiency showed significantly decreased spontaneous activities and impaired excitability, which was mediated by enhanced A-type voltage-dependent potassium currents. Ndn tm1ky mice also exhibited the neonatal phenotypes of PWS, such as hypotonia and blunt respiratory responses to hypercapnia. Conclusions LC-NE neuronal firing activity decreased in necdin-deficient mice, suggesting that LC, the primary source of norepinephrine in the central nervous system, is possibly involved in PWS pathogenesis.

Introduction The function of the C6orf120 gene, which encodes an N-glycosylated protein, remains unknown. The study was performed to characterize the utility of the C6orf120 gene in carbon tetrachloride-induced acute liver injury and to elucidate the potential underlying mechanisms by establishing a C6orf120 gene-knockout (C6orf120 –/– ) rat model. Material and methods C6orf120 -/- and wild-type (WT) rats were intraperitoneally administered with CCl 4 (1 : 1 v/v in olive oil, 2 µl/g). Rats were sacrificed 24 h after CCl 4 administration. Liver tissues were collected for H&E, IHC, qRT-PCR, and Western blot analysis. Results C6orf120 gene deficiency may be vulnerable to CCl 4 -induced acute liver injury in rats as indicated by the high levels of alanine aminotransferase (WT: 388.7 ±55.96 vs. C6orf120 –/– : 915.9 ±118.8, p < 0.001) and greater degree of pathological damage. Quantitative reverse transcription polymerase chain reaction showed that the mRNA levels of inflammation-associated cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-, in liver tissues were increased in C6orf120 –/– rats compared with those in WT rats. Moreover, western blot showed that the protein expression of cytokines nucleotide-binding oligomerization domain leucine rich repeat and pyrin domain containing 3 (NLRP3), caspase-1, IL-1β, nuclear factor-κB, c-Jun N-terminal kinases, and Bax were increased in C6orf120 –/– rats compared with those in WT rats. Conclusions C6orf120 –/– rats were susceptible to CCl 4 -induced liver injury, which may be related to NLRP3 inflammasome and JNK signaling pathway activation.

Background Myocardial dysfunction is a major cause of poor outcomes in the post-cardiac arrest period. Omecamtiv mecarbil (OM) is a selective small molecule activator of cardiac myosin that prolongs myocardial systole and increases stroke volume without apparent effects on myocardial oxygen demand. OM administration is safe and improves cardiac function in patients with acute heart failure. Whether OM improves post-resuscitation myocardial dysfunction remains unclear. This study investigated the effect of OM treatment on post-resuscitation myocardial dysfunction and outcomes. Methods and results Adult male rats were resuscitated after 9.5 min of asphyxia-induced cardiac arrest. OM and normal saline was continuously intravenously infused after return of spontaneous circulation (ROSC) at 0.25 mg/kg/h for 4 h in the experimental group and control group, respectively (n = 20 in each group). Hemodynamic parameters were measured hourly and monitored for 4 h after cardiac arrest. Recovery of neurological function was evaluated by neurological functioning scores (0–12; favorable: 11–12) for rats 72 h after cardiac arrest. OM treatment prolonged left ventricular ejection time and improved post-resuscitation cardiac output. Post-resuscitation heart rate and left ventricular systolic function (dp/dt40) were not different between groups. Kaplan-Meier analysis showed non-statistically higher 72-h survival in the OM group (72.2% [13/18] and 58.8% [10/17], p = 0.386). The OM group had a higher chance of having favorable neurological outcomes in surviving rats 72 h after cardiac arrest (84.6% [11/13] vs. 40% [4/10], p = 0.026). The percentage of damaged neurons was lower in the OM group in a histology study at 72 h after cardiac arrest (55.5±2.3% vs. 76.2±10.2%, p = 0.004). Conclusions OM treatment improved post-resuscitation myocardial dysfunction and neurological outcome in an animal model. These findings support further pre-clinical studies to improve outcomes in post-cardiac arrest care.