High flow nasal cannula oxygen therapy versus non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease with acute-moderate hypercapnic respiratory failure: a randomized controlled non-inferiority trial.

BACKGROUND: Although cumulative studies have demonstrated a beneficial effect of high-flow nasal cannula oxygen (HFNC) in acute hypercapnic respiratory failure, randomized trials to compare HFNC with non-invasive ventilation (NIV) as initial treatment in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients with acute-moderate hypercapnic respiratory failure are limited. The aim of this randomized, open label, non-inferiority trial was to compare treatment failure rates between HFNC and NIV in such patients. METHODS: Patients diagnosed with AECOPD with a baseline arterial blood gas pH between 7.25 and 7.35 and PaCO2 ≥ 50 mmHg admitted to two intensive care units (ICUs) at a large tertiary academic teaching hospital between March 2018 and December 2022 were randomly assigned to HFNC or NIV. The primary endpoint was the rate of treatment failure, defined as endotracheal intubation or a switch to the other study treatment modality. Secondary endpoints were rates of intubation or treatment change, blood gas values, vital signs at one, 12, and 48 h, 28-day mortality, as well as ICU and hospital lengths of stay. RESULTS: 225 total patients (113 in the HFNC group and 112 in the NIV group) were included in the intention-to-treat analysis. The failure rate of the HFNC group was 25.7%, while the NIV group was 14.3%. The failure rate risk difference between the two groups was 11.38% (95% CI 0.25-21.20, P = 0.033), which was higher than the non-inferiority cut-off of 9%. In the per-protocol analysis, treatment failure occurred in 28 of 110 patients (25.5%) in the HFNC group and 15 of 109 patients (13.8%) in the NIV group (risk difference, 11.69%; 95% CI 0.48-22.60). The intubation rate in the HFNC group was higher than in the NIV group (14.2% vs 5.4%, P = 0.026). The treatment switch rate, ICU and hospital length of stay or 28-day mortality in the HFNC group were not statistically different from the NIV group (all P > 0.05). CONCLUSION: HFNC was not shown to be non-inferior to NIV and resulted in a higher incidence of treatment failure than NIV when used as the initial respiratory support for AECOPD patients with acute-moderate hypercapnic respiratory failure. TRIAL REGISTRATION: chictr.org (ChiCTR1800014553). Registered 21 January 2018, http://www.chictr.org.cn.

The effect of short-term training about depth predicting score on the diagnostic ability of invasion depth for differentiated early gastric Cancer among non-expert endoscopists.

BACKGROUND: The depth-predicting score (DPS) was proposed based on conventional white-light imaging (C-WLI) endoscopic features of early gastric cancer (EGC) to determine the invasion depth of the neoplasm. However, the effect of DPS on training endoscopists remains unclear. Therefore, we aimed to investigate the effect of short-term DPS training on improving the diagnostic ability of EGC invasion depth and compare the training effect among non-expert endoscopists at different levels. METHODS: In the training session, the definitions and scoring rules of DPS were instructed, and classic C-WLI endoscopic example graphics were exhibited to the participants. Another C-WLI endoscopic images of 88 cases of histologically proven differentiated EGC were selected as an independent test dataset for evaluating the training effect. Each participant was tested, and the diagnostic accuracy rate of invasion depth was calculated differently one week before the training and after the completion of training. RESULTS: A total of 16 participants were enrolled and completed the training. Participants were divided into a trainee group and a junior endoscopist group according to the total number of C-WLI endoscopies performed. The total number of C-WLI endoscopies performed showed a significant difference between the trainee group and junior endoscopist group (350 vs. 2500, P = 0.001). No significant difference between the trainee group and junior endoscopist group was observed for pre-training accuracy. The overall diagnostic accuracy of invasion depth was improved significantly after completing DPS training compared with before (68.75 ± 5.71% vs. 61.58 ± 9.61%, P = 0.009). In the subgroup analysis, the post-training accuracy was higher than the pre-training accuracy, but significant improvement was observed only in the trainee group (61.65 ± 7.33% vs. 68.32 ± 5.71%, P = 0.034). In addition, no significant difference in post-training accuracy between the two groups was observed. CONCLUSION: Short-term DPS training can improve the diagnostic ability of the invasion depth of EGC and homogenize the diagnostic ability of non-expert endoscopists at different levels. The depth-predicting score was convenient and effective for endoscopist training.

Noninvasive In Situ Ratiometric Imaging of Biometals Based on Self-Assembled Peptide Nanoribbon.

Development of probes for accurate sensing and imaging of biometals in situ is still a growing interest owing to their crucial roles in cellular metabolism, neurotransmission, and apoptosis. Among them, Zn2+ and Cu2+ are two important cooperative biometals closely related to Alzheimer's disease (AD). Herein, we developed a multifunctional probe based on self-assembling peptide nanoribbon for ratiometric sensing of Zn2+, Cu2+, or Zn2+ and Cu2+ simultaneously. Uniform peptide nanoribbon (AQZ@NR) was rationally designed by coassembling a Zn2+-specific ligand AQZ-modified peptide (AQZKL-7) with peptide KL-7. The nanoribbon further combined with Cu2+-sensitive near-infrared quantum dots (NIR QDs) and Alexa Fluor 633 as an inner reference molecule, which was endowed with the capability for ratiometric Zn2+ and Cu2+ imaging at the same time. The peptide-based probe exhibited good specificity to Zn2+ and Cu2+ without interference from other ions. Importantly, the nanoprobe was successfully applied for noninvasive Zn2+ and Cu2+ monitoring in both living cells and zebrafish via multicolor fluorescence imaging. This gives insights into the dynamic Zn2+ and Cu2+ distribution in an intracellular and in vivo mode, as well as understanding the neurotoxicity of high concentration of Zn2+ and Cu2+. Therefore, the self-assembled nanoprobe shows great promise in multiplexed detection of many other biometals and biomolecules, which will benefit the diagnosis and treatment of AD in clinical applications.

Baicalin down-regulating hepatitis B virus transcription depends on the liver-specific HNF4α-HNF1α axis.

Baicalin (BA) inhibits hepatitis B virus (HBV) RNAs production and reduces levels of the related hepatocyte nuclear factors (HNFs), although the underlying mechanism is unclear. In this study, we investigated the specific pathway by which BA regulates HBV transcription through the HBV-related HNFs. Following transfection of HepG2 cells with pHBV1.2, we observed that BA inhibited the production of HBV RNAs and viral proteins in a time- and dose-dependent manner. These effects were consistent with the downregulation of HNF1α, which was abolished by HNF1α-shRNA. The shRNA of HNF4α, the upstream gene of HNF1α, also remarkedly reduced HNF1α expression and impaired the anti-HBV efficacy of BA, indicating that this function of BA depended on HNF4α/HNF1α axis. Furthermore, chromatin immunoprecipitation assay showed that BA significantly reduced HNF4α-HNF1α transactivation activity. The similar effects of BA were observed in entecavir (ETV)-resistant HBVrtM204V/rtLl80M transfected HepG2 cells. Thus, we proposed a mechanism for the anti-HBV activity of BA in an HNF4α-HNF1α-dependent manner, which impaired HNF4α and HNF1α transactivation, and effectively inhibited HBV transcription and viral replication.

High-flow nasal cannula oxygen therapy versus non-invasive ventilation for chronic obstructive pulmonary disease patients after extubation: a multicenter, randomized controlled trial.

BACKGROUND: High-flow nasal cannula (HFNC) oxygen therapy is being increasingly used to prevent post-extubation hypoxemic respiratory failure and reintubation. However, evidence to support the use of HFNC in chronic obstructive pulmonary disease (COPD) patients with hypercapnic respiratory failure after extubation is limited. This study was conducted to test if HFNC is non-inferior to non-invasive ventilation (NIV) in preventing post-extubation treatment failure in COPD patients previously intubated for hypercapnic respiratory failure. METHODS: COPD patients with hypercapnic respiratory failure who were already receiving invasive ventilation were randomized to HFNC or NIV at extubation at two large tertiary academic teaching hospitals. The primary endpoint was treatment failure, defined as either resumption of invasive ventilation or switching to the other study treatment modality (NIV for patients in the NFNC group or vice versa). RESULTS: Ninety-six patients were randomly assigned to the HFNC group or NIV group. After secondary exclusion, 44 patients in the HFNC group and 42 patients in the NIV group were included in the analysis. The treatment failure rate in the HFNC group was 22.7% and 28.6% in the NIV group-risk difference of - 5.8% (95% CI, - 23.8-12.4%, p = 0.535), which was significantly lower than the non-inferior margin of 9%. Analysis of the causes of treatment failure showed that treatment intolerance in the HFNC group was significantly lower than that in the NIV group, with a risk difference of - 50.0% (95% CI, - 74.6 to - 12.9%, p = 0.015). One hour after extubation, the mean respiratory rates of both groups were faster than their baseline levels before extubation (p < 0.050). Twenty-four hours after extubation, the respiratory rate of the HFNC group had returned to baseline, but the NIV group was still higher than the baseline. Forty-eight hours after extubation, the respiratory rates of both groups were not significantly different from the baseline. The average number of daily airway care interventions in the NIV group was 7 (5-9.3), which was significantly higher than 6 (4-7) times in the HFNC group (p = 0.006). The comfort score and incidence of nasal and facial skin breakdown of the HFNC group was also significantly better than that of the NIV group [7 (6-8) vs 5 (4-7), P < 0.001] and [0 vs 9.6%, p = 0.027], respectively. CONCLUSION: Among COPD patients with severe hypercapnic respiratory failure who received invasive ventilation, the use of HFNC after extubation did not result in increased rates of treatment failure compared with NIV. HFNC also had better tolerance and comfort than NIV. TRIAL REGISTRATION: chictr.org ( ChiCTR1800018530 ). Registered on 22 September 2018, http://www.chictr.org.cn/usercenter.aspx.

Characterization of Maca (Lepidium meyenii/Lepidium peruvianum) Using a Mass Spectral Fingerprinting, Metabolomic Analysis, and Genetic Sequencing Approach.

Maca (Lepidium meyenii, synonym L. peruvianum) was analyzed using a systematic approach employing principal component analysis of flow injection mass spectrometry fingerprints (no chromatographic separation) to guide the selection of samples for metabolite profiling and DNA next generation sequencing. Samples consisted of 39 commercial maca supplements from 11 manufacturers, 31 unprocessed maca tubers grown in Peru and China, and a historic non-tuber maca sample from Peru. Principal component analysis of flow injection mass spectrometry fingerprints initially placed all the maca samples in three classes with similar chemical composition: commercial maca samples, tubers grown in Peru, and tubers grown in China. Metabolite profiling identified 67 compounds in the negative mode and 51 compounds in the positive mode. Compounds identified by metabolite profiling (macamides, glucosinolates, amino acids, fatty acids, polyunsaturated fatty acids, saccharides, imidazoles) were then used to identify ions in the flow injection mass spectrometry fingerprints. The tuber fingerprints were analyzed by factorial multivariate analysis of variance revealing that black, red, and yellow maca from Peru and black and yellow maca from China were compositionally different with respect to color and country. Critical ions were identified that allowed for the differentiation of maca between colors from the same country or between two countries with the same color. Genetically, all samples were confirmed to be L. meyenii based on next generation sequencing at three gene regions (ITS2, psbA, and trnL) and comparison to recorded sequences of vouchered standards.

Duration of cardiac arrest requires different ventilation volumes during cardiopulmonary resuscitation in a pig model.

There are few studies examining the ventilation strategies recommended by current CPR guidelines. We investigated the influence of different minute volume applying to untreated cardiac arrest with different duration, on resuscitation effects in a pig model. 32 Landrace pigs with 4 or 8 min (16 pigs each) ventricular fibrillation (VF) randomly received two ventilation strategies during CPR. "Guideline" groups received mechanical ventilation with a tidal volume of 7 ml/kg and a frequency of 10/min, while "Baseline" groups received a tidal volume (10 ml/kg) and a frequency used at baseline to maintain an end-tidal PCO2 (PETCO2) between 35 and 40 mmHg before VF. Mean airway pressures and intrathoracic pressures (PIT) in the Baseline-4 min group were significantly higher than those in the Guideline-4 min group (all P < 0.05). Similar results were observed in the 8 min pigs, except for no significant difference in minimal PIT and PETCO2 during 10 min of CPR. Venous pH and venous oxygen saturation were significantly higher in the Baseline-8 min group compared to the Guideline-8 min group (all P < 0.05). Aortic pressure in the Baseline-8 min group was higher than in the Guideline-8 min group. Seven pigs in each subgroup of 4 min VF models achieved the return of spontaneous circulation (ROSC). Higher ROSC was observed in the Baseline-8 min group than in the Guideline-8 min group (87.5% vs. 37.5%, P = 0.039). For 4 min VF but not 8 min VF, a guideline-recommended ventilation strategy had satisfactory results during CPR. A higher minute ventilation resulted in better outcomes for subjects with 8 min of untreated VF through thoracic pump.

Glycopeptide Nanofiber Platform for Aß-Sialic Acid Interaction Analysis and Highly Sensitive Detection of Aß.

The variation of amyloid ß peptide (Aß) concentration and Aß aggregation are closely associated with the etiology of Alzheimer's diseases (AD). The interaction of Aß with the monosialoganglioside-rich neuronal cell membrane has been suggested to influence Aß aggregation. Therefore, studies on the mechanism of Aß and sialic acids (SA) interaction would greatly contribute to better understanding the pathogenesis of AD. Herein, we report a novel approach for Aß-SA interaction analysis and highly sensitive Aß detection by mimicing the cell surface presentation of SA clusters through engineering of SA-modified peptide nanofiber (SANF). The SANF displayed well-ordered 1D nanostructure with high density of SA on surface. Using FAM-labeled Aß fragments of Aß1-16, Aß16-23, and Aß24-40, the interaction between Aß and SA was evaluated by the fluorescence titration experiments. It was found that the order of the SA-binding affinity was Aß1-16 > Aß24-40 > Aß16-23. Importantly, the presence of full-length Aß1-40 monomer triggered a significant fluorescence enhancement due to the multivalent binding of Aß1-40 to the nanofiber. This fluorescent turn-on response showed high selectivity and sensitivity for Aß1-40 detection and the method was further used for Aß aggregation process monitoring and inhibitor screening. The results suggest the proposed strategy is promising to serve as a tool for mechanism study and the early diagnosis of Alzheimer's disease.

Mass-Spectrometry Analysis of Mixed-Breath, Isolated-Bronchial-Breath, and Gastric-Endoluminal-Air Volatile Fatty Acids in Esophagogastric Cancer.

A noninvasive breath test has the potential to improve survival from esophagogastric cancer by facilitating earlier detection. This study aimed to investigate the production of target volatile fatty acids (VFAs) in esophagogastric cancer through analysis of the ex vivo headspace above underivatized tissues and in vivo analysis within defined anatomical compartments, including analysis of mixed breath, isolated bronchial breath, and gastric-endoluminal air. VFAs were measured by PTR-ToF-MS and GC-MS. Levels of VFAs (acetic, butyric, pentanoic, and hexanoic acids) and acetone were elevated in ex vivo experiments in the headspace above esophagogastric cancer compared with the levels in samples from control subjects with morphologically normal and benign conditions of the upper gastrointestinal tract. In 25 patients with esophagogastric cancer and 20 control subjects, receiver-operating-characteristic analysis for the cancer-specific VFAs butyric acid ( P < 0.001) and pentatonic acid ( P = 0.005) within in vivo gastric-endoluminal air gave an area under the curve of 0.80 (95% confidence interval of 0.65 to 0.93, P = 0.01). Compared with mixed- and bronchial-breath samples, all examined VFAs were found in highest concentrations within esophagogastric-endoluminal air. In addition, VFAs were higher in all samples derived from cancer patients compared with in the controls. Equivalence of VFA levels within the mixed and bronchial breath of cancer patients suggests that their origin within breath is principally derived from the lungs and, by inference, from the systemic circulation as opposed to direct passage from the upper gastrointestinal tract. These findings highlight the potential to utilize VFAs for endoluminal-gas biopsies and noninvasive mixed-exhaled-breath testing for esophagogastric-cancer detection.

Authentication of black cohosh (Actaea racemosa) dietary supplements based on chemometric evaluation of hydroxycinnamic acid esters and hydroxycinnamic acid amides.

Ester and amide derivatives of hydroxycinnamic acids are found in black cohosh (Actaea racemosa) and other Actaea plants. These two compound groups were evaluated for authentication of black cohosh dietary supplements. The hydroxycinnamic acid esters (HCAE) were profiled by ultra-performance liquid chromatography-photodiode array detection (UPLC-PDA). The hydroxycinnamic acid amides (HCAA) were acquired simultaneously by mass spectrometry-multiple reaction monitoring (UPLC-MRM) mode. In contrast with the traditional HCAE method using 8 compounds, profiles of HCAA using only 4 feruloyl dopamine-O-hexosides was more convenient for peak by peak comparison. Partial least square discriminant analysis (PLS-DA) was applied to both HCAE and HCAA datasets. Authenticated plant samples of five Actaea species were randomly divided into training and test sets to build and validate the two PLS-DA models. Both models provided reasonable estimates for the classification of A. racemosa and other Actaea plant samples. However, HCAA model performs better in sensitivity, specificity, and accuracy. Assessment of supplement samples provided quite different results for the solid and liquid dietary supplement samples, indicating the dosage form could affect the composition of marker compounds. Graphical abstract.

Feruloyl dopamine-O-hexosides are efficient marker compounds as orthogonal validation for authentication of black cohosh (Actaea racemosa)-an UHPLC-HRAM-MS chemometrics study.

Due to the complexity and variation of the chemical constituents in authentic black cohosh (Actaea racemosa) and its potential adulterant species, an accurate and feasible method for black cohosh authentication is not easy. A high-resolution accurate mass (HRAM) LC-MS fingerprinting method combined with chemometric approach was employed to discover new marker compounds. Seven hydroxycinnamic acid amide (HCAA) glycosides are proposed as potential marker compounds for differentiation of black cohosh from related species, including two Asian species (A. foetida, A. dahurica) and two American species (A. pachypoda, A. podocarpa). These markers were putatively identified by comparing their mass spectral fragmentation behavior with those of their authentic aglycone compounds and phytochemistry reports. Two isomers of feruloyl methyldopamine 4-O-hexoside ([M + H]+ 506) and one feruloyl tyramine 4-O-hexoside ([M + H]+ 476) contributed significantly to the separation of Asian species in principle component analysis (PCA) score plot. The efficacy of the models built on four reasonable combinations of these markers in differentiating black cohosh and its adulterants were evaluated and validated by partial least-square discriminant analysis (PLS-DA). Two models based on these reduced dataset achieved 100% accuracy based on the current sample collection, including the model that used only three feruloyl dopamine-O-hexoside isomers ([M + H]+ 492) and one feruloyl dopamine-O-dihexoside ([M + H-hexosyl]+ at m/z 492). Graphical abstract Hydroxycinnamic acid amide glycosides are proposed as potential marker compounds for authentication of black cohosh.

Separation of phenolic acids from sugarcane rind by online solid-phase extraction with high-speed counter-current chromatography.

Sugarcane rind contains some functional phenolic acids. The separation of these compounds from sugarcane rind is able to realize the integrated utilization of the crop and reduce environment pollution. In this paper, a novel protocol based on interfacing online solid-phase extraction with high-speed counter-current chromatography (HSCCC) was established, aiming at improving and simplifying the process of phenolic acids separation from sugarcane rind. The conditions of online solid-phase extraction with HSCCC involving solvent system, flow rate of mobile phase as well as saturated extent of absorption of solid-phase extraction were optimized to improve extraction efficiency and reduce separation time. The separation of phenolic acids was performed with a two-phase solvent system composed of butanol/acetic acid/water at a volume ratio of 4:1:5, and the developed online solid-phase extraction with HSCCC method was validated and successfully applied for sugarcane rind, and three phenolic acids including 6.73 mg of gallic acid, 10.85 mg of p-coumaric acid, and 2.78 mg of ferulic acid with purities of 60.2, 95.4, and 84%, respectively, were obtained from 150 mg sugarcane rind crude extracts. In addition, the three different elution methods of phenolic acids purification including HSCCC, elution-extrusion counter-current chromatography and back-extrusion counter-current chromatography were compared.

Use of fuzzy chromatography mass spectrometric (FCMS) fingerprinting and chemometric analysis for differentiation of whole-grain and refined wheat (T. aestivum) flour.

A fuzzy chromatography mass spectrometric (FCMS) fingerprinting method combined with chemometric analysis has been established for rapid discrimination of whole-grain flour (WF) from refined wheat flour (RF). Bran, germ, endosperm, and WF from three local cultivars or purchased from a grocery store were studied. The state of refinement (whole vs. refined) of wheat flour was differentiated successfully by use of principal-components analysis (PCA) and soft independent modeling of class analogy (SIMCA), despite potential confounding introduced by wheat class (red vs. white; hard vs. soft) or resources (different brands). Twelve discriminatory variables were putatively identified. Among these, dihexoside, trihexoside, apigenin glycosides, and citric acid had the highest peak intensity for germ. Variable line plots indicated phospholipids were more abundant in endosperm. Samples of RF and WF from three cultivars (Hard Red, Hard White, and Soft White) were physically mixed to furnish 20, 40, 60, and 80 % WF of each cultivar. SIMCA was able to discriminate between 100 %, 80 %, 60 %, 40 %, and 20 % WF and 100 % RF. Partial least-squares (PLS) regression was used for prediction of RF-to-WF ratios in the mixed samples. When PLS models were used the relative prediction errors for RF-to-WF ratios were less than 6 %. Graphical Abstract Workflow of targeting discriminatory compounds by use of FCMS and chemometric analysis.

Tunable synthesis of hexagram-shaped hematite iron oxide microcrystals with shape-dependent magnetic properties.

Uniform hexagram-shaped alpha-Fe2O3 microcrystals with tunable morphologies were fabricated by a facile hydrothermal method followed by annealing in air. The highly anisotropic hexagram-shaped alpha-Fe2O3 particles with the higher coercivity forces and remannent magnetizations showed weak ferromagnetic behaviors at room temperature and displayed the typical shape-dependent magnetic behaviors.

[Value of arterial lactic acid and buffer excess in predicting the prognosis of patients with paraquat poisoning].

OBJECTIVE: To investigate the early prognostic values of arterial lactate and base excess (BE) in patients with paraquat poisoning. METHODS: Seventy-five patients with paraquat poisoning were divided into sudden death group (n = 10) who died within 24 h after admission, recent death group (n = 31) who died more than 24 h after admission, and survival group (n = 34). Arterial lactate and BE were measured on admission and at 24 h after admission. The prognostic values of arterial lactate and BE were analyzed. RESULTS: The arterial lactate measured on admission was significantly higher in the sudden death group than in the recent death group and survival group (P < 0.01), but there was no significant difference in arterial lactate between the recent death group and survival group (P = 0.309). The BE measured on admission was significantly lower in the sudden death group than in the recent death group and survival group, and it was significantly lower in the recent death group than in the survival group (P < 0.01 or P < 0.05). At 24 h after admission, the recent death group had a significantly higher arterial lactate (P < 0.01) and a significantly lower BE (P < 0.01), as compared with the survival group. The logistic regression analysis showed that the two indices were significantly associated with prognosis (P < 0.01). On admission, the areas under the receiver operating characteristic (ROC) curve (AUCs) of arterial lactate and BE for predicting death were 0.692 and 0.787, respectively, and the cut-off values were 3.25 mmol/L and -1.75 mmol/L, respectively; the AUCs of arterial lactate and BE for predicting sudden death were 0.995 and 1, respectively, and the cut-off values were 7.1 mmol/L and -12.8 mmol/L, respectively. At 24 h after admission, the AUCs of arterial lactate and BE for predicting death were 0.743 and 0.822, respectively, and the cut-off values were 2.15 mmol/L and -5.55 mmol/L, respectively. CONCLUSION: Arterial lactate and BE have certain values in predicting the death, especially the sudden death, in patients with acute paraquat poisoning.

Wounding induces suberin deposition, relevant gene expressions and changes of endogenous phytohormones in Chinese yam (Dioscorea opposita) tubers.

Wounds on Chinese yam (Dioscorea opposita ) tubers can ocurr during harvest and handling, and rapid suberisation of the wound is required to prevent pathogenic infection and desiccation. However, little is known about the causal relationship among suberin deposition, relevant gene expressions and endogenous phytohormones levels in response to wounding. In this study, the effect of wounding on phytohormones levels and the expression profiles of specific genes involved in wound-induced suberisation were determined. Wounding rapidly increased the expression levels of genes, including PAL , C4H , 4CL , POD , KCSs , FARs , CYP86A1 , CYP86B1 , GPATs , ABCGs and GELPs , which likely involved in the biosynthesis, transport and polymerisation of suberin monomers, ultimately leading to suberin deposition. Wounding induced phenolics biosynthesis and being polymerised into suberin poly(phenolics) (SPP) in advance of suberin poly(aliphatics) (SPA) accumulation. Specifically, rapid expression of genes (e.g. PAL , C4H , 4CL , POD ) associated with the biosynthesis and polymerisation of phenolics, in consistent with SPP accumulation 3days after wounding, followed by the massive accumulation of SPA and relevant gene expressions (e.g. KCSs , FARs , CYP86A1 /B1 , GPATs , ABCGs , GELPs ). Additionally, wound-induced abscisic acid (ABA) and jasmonic acid (JA) consistently correlated with suberin deposition and relevant gene expressions indicating that they might play a central role in regulating wound suberisation in yam tubers.

The impact of sarcopenia on overall survival in patients with pan-RAS wild-type colorectal liver metastasis receiving hepatectomy.

Sarcopenia has been associated with conventional chemotherapy-related toxicity, postoperative complications and poor overall survival in patients with genotype-unselected metastatic colorectal cancer (mCRC). This study aimed to evaluate the prognostic implications of sarcopenia and its change after perioperative cetuximab plus doublet chemotherapy and hepatectomy in patients with RAS wild-type colorectal liver metastasis (CRLM). Patients with CRLM from 2007 to 2018 in Chang Gung Research Database were retrospectively analyzed. Baseline characteristics as well as skeletal muscle index (SMI) at baseline and dynamic changes after interventions were collected. A multivariate Cox proportional hazard model was used to evaluate the effect of each parameter on overall survival (OS), and the Kaplan-Meier method was used to establish survival curves. A two-sided p value < 0.05 was considered statistically significance. Of 214 RAS wild-type mCRC patients who received both cetuximab and doublet chemotherapy, 77 who received upfront or subsequent hepatectomy were included in this study. The median follow-up time was 2.3 years. The rate of sarcopenia was higher in the patients who received neoadjuvant cetuximab-containing regimens than in those who received upfront hepatectomy (95% versus 63%, p = 0.001). Increased SMI after perioperative systemic therapy remained independently associated with better OS in multivariate analysis [hazard ratio (HR) = 0.27/10% increase, p = 0.013). The patients with sarcopenia had a trend of worse OS than those without sarcopenia (median OS: 4.5 versus 3.6 years, log-rank p = 0.282). Improvement in sarcopenia ([SMI after intervention - initial SMI]/initial SMI × 100%) is an important prognostic factor for OS. Future research is warranted to investigate direct interventions for sarcopenia and the impact on OS.

Physiological oxygen level is critical for modeling neuronal metabolism in vitro.

In vitro models are important tools for studying the mechanisms that govern neuronal responses to injury. Most neuronal culture methods employ nonphysiological conditions with regard to metabolic parameters. Standard neuronal cell culture is performed at ambient (21%) oxygen levels, whereas actual tissue oxygen levels in the mammalian brain range from 1% to 5%. In this study, we examined the consequences of oxygen level on the viability and metabolism of primary cultures of cortical neurons. Our results indicate that physiological oxygen level (5% O(2)) has a beneficial effect on cortical neuronal survival and mitochondrial function in vitro. Moreover, oxygen level affects metabolic fluxes: glucose uptake and glycolysis was enhanced at physiological oxygen level, whereas glucose oxidation and fatty acid oxidation were reduced. Adenosine monophosphate-activated protein kinase (AMPK) was more activated in 5% O(2) and appears to play a role in these metabolic effects. Inhibiting AMPK activity with compound C decreased glucose uptake, intracellular ATP level, and viability in neurons cultured in 5% O(2). These data indicate that oxygen level is an important parameter to consider when modeling neuronal responses to stress in vitro.

The Determinants of User Acceptance of Mobile Medical Platforms: An Investigation Integrating the TPB, TAM, and Patient-Centered Factors.

Mobile medical platforms (MMPs) can make medical services more accessible and effective. However, the patient-centered factors that influence patients' acceptance of MMPs are not well understood. Our study examined the factors affecting patients' acceptance of MMPs by integrating the theory of planned behavior (TPB), the technology acceptance model (TAM), and three patient-centered factors (i.e., perceived convenience, perceived credibility, and perceived privacy risk). Three hundred and eighty-nine Chinese respondents were recruited in this study and completed a self-administered online questionnaire that included items adapted from validated measurement scales. The partial least squares structural equation modeling results revealed that perceived privacy risk, perceived credibility, and perceived ease of use directly determined the perceived usefulness of an MMP. Perceived convenience, perceived credibility, and perceived usefulness significantly affected the patients' attitudes toward MMPs. Perceived usefulness, attitude, perceived privacy risk, and perceived behavioral control were important determinants of the patients' behavioral intentions to use MMPs. Behavioral intention and perceived behavioral control significantly influenced perceived effective use. Perceived credibility and perceived ease of use significantly affected perceived convenience. However, social influence had no significant effect on attitude and behavioral intention. The study provides important theoretical and practical implications, which could help practitioners enhance the patients' use of MMPs for their healthcare activities.

Liver-Targeted Nanoparticles Facilitate the Bioavailability and Anti-HBV Efficacy of Baicalin In Vitro and In Vivo.

The anti-hepatitis B virus (HBV) efficacy of baicalin (BA) is mediated by HBV-related hepatocyte nuclear factors (HNFs). However, this efficacy is severely limited by the low bioavailability of BA. Therefore, a novel liver-targeted BA liposome was constructed to promote the bioavailability and antiviral ability of BA. The results showed that apolipoprotein A1 (ApoA1)-modified liposomes (BAA1) significantly enhanced BA's cellular uptake and specific distribution in the liver. Furthermore, the substantial inhibitory effects of BAA1 on HBsAg, HBeAg, HBV RNA, and HBV DNA were assessed in HB-infected cells and mice. Western blotting, co-immunoprecipitation, and transcriptomics analysis further revealed that the enhanced anti-HBV efficacy of BAA1 was attributed to the interaction between hepatocyte nuclear factors (HNFs) and estrogen receptors (ERs). Based on the findings, we propose that the ApoA1-modified liposomes aid BA in inhibiting HBV transcription and replication by augmenting its bioavailability and the HNFs-ERs axis.