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 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.

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.

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.

Autophagy and Exosome Coordinately Enhance Macrophage M1 Polarization and Recruitment in Influenza A Virus Infection.

Background: Influenza A virus infection results in viral pneumonia, which is often accompanied by the infiltration and recruitment of macrophages, overactivation of inflammatory responses, and obvious cell autophagy and exosome production. However, little is known about the roles of autophagy and exosome production in these inflammatory responses. Methods: In this study, multiple methods, such as flow cytometry, real-time quantitative reverse transcription-polymerase chain reaction, immune-fluorescence technology, and western blot, were applied to explore the possible effects of autophagy and exosome production by H1N1-infected host cells. Results: It was observed that a high number of polarized macrophages (CD11b+/F4/80+/CD86+) were recruited to the lung tissues of infected mice, which could be mimicked by tracking the movement of macrophages to H1N1-infected cells in vitro (transwell assays). Furthermore, there was some coordinated upregulation of M1 polarization signs (iNOS/Arg-1 bias) as well as autophagy (LC3) and exosome (CD63) biomarkers in the infected macrophages and epithelial cells. Moreover, exosomes extracted from the supernatant of virus-infected cells were shown to promote the recruitment and polarization of more peritoneal macrophages than the normal group. The fluorescence colocalization of LC3-CD63 and the inhibition of autophagy and exosome signaling pathway further revealed that H1N1 infection seemed to sequentially activate the M1 polarization and recruitment of macrophages via autophagy-exosome dependent pathway. Conclusion: Autophagy and exosome production coordinately enhance the M1 polarization and recruitment of macrophages in influenza virus infection, which also provides potential therapeutic targets.

[Xuebijing injection improve pulmonary vascular barrier function in ARDS by up-regulating claudin-5 expression through PI3K/Akt/FOXO1 signaling pathway].

OBJECTIVE: To study the signaling pathway of the up-regulation of claudin-5 expression by Xuebijing injection. METHODS: Animal and cell models of acute respiratory distress syndrome (ARDS) were induced by lipopolysaccharide (LPS). (1) In vivo study, 20 male Sprague-Dawley (SD) rats were randomly divided into 4 groups: control group, LPS group (LPS injection 10 mg/kg for 12 hours), Xuebijing control group (Xuebijing injection 1 mg/kg, twice a day, for 3 days), and Xuebijing intervention group (LPS injection after pretreatment of Xuebijing injection), according to random number method with 5 rats in each group. The lung tissues were taken to detect lung dry/wet weight ratio (W/D) and the morphological changes in each group. Claudin-5, phosphorylated forkhead box transcription factor O1 (p-FOXO1), total FOXO1 (t-FOXO1), phosphorylated Akt (p-Akt) and total Akt (t-Akt) in lung tissues were detected by immunohistochemical staining (IHC) and Western blotting. (2) In vitro study, human pulmonary microvascular endothelial cells (HPMECs) were divided into 6 groups (5 holes in each group): control group, Xubijing control group (incubated with 2 g/L Xubijing for 24 hours), phosphoinositide 3-kinases (PI3K) signaling pathway LY294002 control group (incubated with 10 µmol/L LY294002 for 1 hour), LPS group (incubated with 1 mg/L LPS for 12 hours), Xubijing intervention group (incubated with 2 g/L Xuebijing for 24 hours, then with 1 mg/L LPS for 12 hours) and LY294002 intervention group (incubated with 10 µmol/L LY294002 for 1 hour, then with 2 g/L and Xubijing for 24 hours, and then with 1 mg/L LPS for 12 hours). The expression levels of claudin-5, p-FOXO1, t-FOXO1, p-Akt and t-Akt of HPMECs in each group were assessed by Western blotting. RESULTS: In vivo study: (1) Compared with the control group, the lung W/D ratio increased significantly in LPS group (6.79±0.42 vs. 4.19±0.13), and decreased significantly after the intervention of Xuebijing (4.92±0.38 vs. 6.79±0.42, P < 0.01). (2) Morphological changes of lung tissue: compared with the control group, the injury of lung tissue in LPS group was more serious, which was significantly improved after Xuebijing intervention. (3) Expression levels of claudin-5, p-Akt/t-Akt and p-FOXO1/t-FOXO1: the expression levels of claudin-5, p-Akt/t-Akt and p-FOXO1/t-FOXO1 in LPS group were significantly decreased as compared with the control group (claudin-5/GAPDH: 0.33±0.03 vs. 1.03±0.07, p-Akt/t-Akt: 0.18±0.02 vs. 1.01±0.13, p-FOXO1/t-FOXO1: 0.16±0.06 vs. 1.00±0.19, all P < 0.01). After the intervention of Xuebijing, the expression levels were significantly increased as compared with the LPS group (claudin-5/GAPDH: 0.53±0.05 vs. 0.33±0.03, p-Akt/t-Akt: 0.56±0.12 vs. 0.18±0.02, p-FOXO1/t-FOXO1: 0.68±0.10 vs. 0.16±0.06, all P < 0.01). In vitro study: compared with the control group, the expression level of claudin-5 in the LPS group was significantly decreased (claudin-5/ß-actin: 0.45±0.03 vs. 1.01±0.15, P < 0.01), and the expression level of claudin-5 in Xuebijing intervention group was also significantly decreased (claudin-5/ß-actin: 0.80±0.08 vs. 1.01±0.15, P < 0.01). After the intervention of LY294002, the expression of claudin-5 was significantly decreased as compared with the Xubijing intervention group (claudin-5/ß-actin: 0.41±0.02 vs. 0.80±0.08, P < 0.01). CONCLUSIONS: Xuebijing injection improve pulmonary vascular barrier function in rats with ARDS by up-regulating claudin-5 expression through PI3K/Akt/FOXO1 signaling pathway.

Practice and experience of regional medical center entrance linkage and closed-loop management under the wartime situation of the COVID-19 in China.

On 28 July 2021, the first indigenous case of novel coronavirus pneumonia (COVID-19) emerged in Yangzhou, marking the beginning of a public health crisis caused by the new coronavirus pneumonia. It is a significant challenge for hospitals to carry out prevention and control measures to ensure the safety of medical professionals and patients when facing the changes in an epidemic situation. Subei People's Hospital, as one of the first group of "Grade III-class A" hospitals in Jiangsu Province and the Yangzhou Regional Medical Centre, responded quickly and scientifically to prevent and control the disease. A closed-loop management system was implemented at the hospital entrance (consisting of the outpatient clinic, emergency clinic, fever clinic, and buffer ward) and an epidemic prevention and control group was established with the assistance of multiple departments. This group optimized the pre-screening and triage system, standardized the fever clinic consultation process, and improved the construction of an information-based prevention and control network so that patients were detected, diagnosed, isolated, and treated early. The emergency management capability was improved to achieve zero missed consultations of patients attending for COVID-19 and to effectively maintain medical order during this critical period. This current report systematically summarizes the operational practices and the effectiveness achieved by implementation of the entrance closed-loop management in the hospital and analyzed the key operational issues for future reference by medical institutions and management departments.

Xuebijing Injection Ameliorates H2S-Induced Acute Respiratory Distress Syndrome by Promoting Claudin-5 Expression.

OBJECTIVE: To investigate the protective effects and underlying mechanisms of Xuebijing Injection (XBJ) on the lung endothelial barrier in hydrogen sulfide (H2S)-induced acute respiratory distress syndrome (ARDS). METHODS: Sprague-Dawley rats were exposed to H2S (300 ppm) to establish ARDS model, while human pulmonary microvascular endothelial cells (HPMECs) were incubated with NaHS (a H2S donor, 500 µmol/L) to establish cell model. H2S and XBJ were concurrently administered to the rat and cell models. Lung hematoxylin and eosin staining, immunohistochemistry, transmission electron microscopy and wet/dry ratio measurement were used to confirm ARDS induced by H2S in vivo. The expression levels of claudin-5, phosphorylated protein kinase B (p-AKT)/t-AKT and p-forkhead box transcription factor O1 (FoxO1)/t-FoxO1 in vivo and in vitro were also assessed. Paracellular permeability and transepithelial electrical resistance (TEER) were measured to evaluate endothelial barrier function in the cell model. RESULTS: The morphological investigation showed that XBJ attenuated H2S-induced ARDS in rats. XBJ significantly ameliorated both the reduction in TEER and the increased paracellular permeability observed in NaHS-treated HPMECs (P<0.05). The protective effects of XBJ were blocked by LY294002, a phosphatidylinositol 3-kinase (PI3K)/AKT/FoxO1 pathway antagonist (P<0.05). Furthermore, XBJ promoted the expression of claudin-5 and increased the levels of p-AKT and p-FoxO1 in vivo and in vitro (P<0.05). CONCLUSIONS: XBJ ameliorated H2S-induced ARDS by promoting claudin-5 expression via the PI3K/AKT/FoxO1 signaling pathway.

Cross Platform Analysis of Volatile Organic Compounds Using Selected Ion Flow Tube and Proton-Transfer-Reaction Mass Spectrometry.

Volatile breath metabolites serve as potential disease biomarkers. Online mass spectrometry (MS) presents real-time quantification of breath volatile organic compounds (VOCs). The study aims to assess the relationship between two online analytical mass spectrometry techniques in the quantification of target breath metabolites: selected ion flow tube mass spectrometry (SIFT-MS) and proton-transfer-reaction time-of-flight mass spectrometry (PTR-ToF-MS). The two following techniques were employed: (i) direct injection with bag sampling using SIFT-MS and PTR-ToF-MS and (ii) direct injection and thermal desorption (TD) tube comparison using PTR-ToF-MS. The concentration of abundant breath metabolites, acetone and isoprene, demonstrated a strong positive linear correlation between both mass spectrometry techniques (r = 0.97, r = 0.89, respectively; p < 0.001) and between direct injection and TD tube (r = 0.97, r = 0.92, respectively; p < 0.001) breath sampling techniques. This was reflected for the majority of short chain fatty acids and alcohols tested (r > 0.80, p < 0.001). Analyte concentrations were notably higher with the direct injection of a sampling bag compared to the TD method. All metabolites produced a high degree of agreement in the detection range of VOCs between SIFT-MS and PTR-ToF-MS, with the majority of compounds falling within 95% of the limits of agreement with Bland-Altman analysis. The cross platform analysis of exhaled breath demonstrates strong positive correlation coefficients, linear regression, and agreement in target metabolite detection rates between both breath sampling techniques. The study demonstrates the transferability of using data outputs between SIFT-MS and PTR-ToF-MS. It supports the implementation of a TD platform in multi-site studies for breath biomarker research in order to facilitate sample transport between clinics and the laboratory.

Bioactive Ingredients and Medicinal Values of Grifola frondosa (Maitake).

Grifola frondosa (G. frondosa), generally known as hen-of-the-woods or maitake in Japanese and hui-shu-hua in Chinese, is an edible mushroom with both nutritional and medicinal properties. This review provides an up-to-date and comprehensive summary of research findings on its bioactive constituents, potential health benefits and major structural characteristics. Since the discovery of the D-fraction more than three decades ago, many other polysaccharides, including ß-glucans and heteroglycans, have been extracted from the G. frondosa fruiting body and fungal mycelium, which have shown significant antitumor and immunomodulatory activities. Another class of bioactive macromolecules in G. frondosa is composed of proteins and glycoproteins, which have shown antitumor, immunomodulation, antioxidant and other activities. A number of small organic molecules such as sterols and phenolic compounds have also been isolated from the fungus and have shown various bioactivities. It can be concluded that the G. frondosa mushroom provides a diverse array of bioactive molecules that are potentially valuable for nutraceutical and pharmaceutical applications. More investigation is needed to establish the structure-bioactivity relationship of G. frondosa and to elucidate the mechanisms of action behind its various bioactive and pharmacological effects.

Baicalin Inhibits Influenza A Virus Infection via Promotion of M1 Macrophage Polarization.

BACKGROUND AND AIMS: The natural compound baicalin (BA) possesses potent antiviral properties against the influenza virus. However, the underlying molecular mechanisms of this antiviral activity and whether macrophages are involved remain unclear. In this study, we, therefore, investigated the effect of BA on macrophages. METHODS: We studied macrophage recruitment, functional phenotypes (M1/M2), and the cellular metabolism via flow cytometry, qRT-PCR, immunofluorescence, a cell culture transwell system, and GC-MS-based metabolomics both in vivo in H1N1 A virus-infected mice and in vitro. RESULTS: BA treatment drastically reduced macrophage recruitment (CD11b+, F4/80+) by approximately 90% while maintaining the proportion of M1-polarized macrophages in the bronchoalveolar lavage fluid of infected mice. This BA-stimulated macrophage M1 phenotype shift was further verified in vitro in ANA-1 and primary peritoneal macrophages by measuring macrophage M1 polarization signals (CD86, iNOS, TNF-α, iNOS/Arg-1 ratio, and IL-1ß cleavage). Meanwhile, we observed an activation of the IFN pathway (upregulation of IFN-ß and IRF-3), an inhibition of influenza virus replication (as measured by the M gene), and distinct cellular metabolic responses in BA-treated cells. CONCLUSION: BA triggered macrophage M1 polarization, IFN activation, and other cellular reactions, which are beneficial for inhibition of H1N1 A virus infection.

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.

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.

[Xuebijing injection attenuates hydrogen sulfide-induced endothelial barrier dysfunction by upregulating claudin-5 expression].

OBJECTIVE: To study the new mechanism of Xuebijing injection improving the function of pulmonary vascular barrier from the perspective of claudin-5 protein. METHODS: Acute lung injury (ALI) model was induced by hydrogen sulfide (H2S) exposure. (1) In vivo study: Sprague-Dawley (SD) rats were divided into control group, H2S exposure group (exposure to 300×10-6 H2S for 3 hours), Xuebijing control group (Xuebijing injection 4 mL/kg , twice a day, for 3 days), and Xuebijing intervention group (H2S exposure after pretreatment of Xuebijing injection) according to random number method, with 6 rats in each group. At different time points (0, 6, 12 and 24 hours) after the model was made successfully, the total protein content in plasma and bronchoalveolar lavage fluid (BALF) of rats were detected respectively, and the pulmonary permeability index (PPI) was calculated (PPI = protein content in BALF/protein content in plasma), lung dry/wet weight ratio (W/D) was detected, and claudin-5 mRNA expression in lung tissue was measured by real time-polymerase chain reaction. (2) In vitro test: human pulmonary microvascular endothelial cells (HPMECs) were divided into blank control group, NaHS treatment group (co-incubated with 500 µmol/L NaHS for 12 hours), Xuebijing control group (2 g/L Xuebijing injection for 24 hours), and Xuebijing intervention group (2 g/L Xuebijing injection pre-treated for 24 hours, then co-incubated with 500 µmol/L NaHS for 12 hours). The HPMECs claudin-5 protein expression and monolayer permeability changes were measured at different co-incubation time (1, 3, 6, 12 and 24 hours) by Western Blot and fluoresceinsodium. RESULTS: (1) In vivo study: compared with the control group, the lung W/D ratio increased significantly at 6 hours and peaked at 12 hours after H2S exposure in rats (4.67±0.11 vs. 4.26±0.06, P < 0.01). The expression of claudin-5 mRNA in lung tissue was significantly decreased, which was 89% of control group 6 hours after exposure (P < 0.01). The total protein content in BALF and PPI at 12 hours after exposure were significantly higher than those in the control group [total protein content (mg/L): 262.31±14.24 vs. 33.30±3.09, PPI: (11.72±0.57)×10-3 vs. (1.21±0.08)×10-3, both P < 0.01], while the results in Xuebijing intervention group were significantly decreased [total protein content (mg/L): 153.25±7.32 vs. 262.31±14.24, PPI: (5.79±0.23)×10-3 vs. (11.72±0.57)×10-3, both P < 0.01]. (2) In vitro test: compared with the blank control group, after incubating HPMECs with NaHS, the permeability of monolayer endothelial cells gradually increased, reaching the highest level in 12 hours, about twice of that in the blank control group, while claudin-5 protein expression decreased to the lowest level at 12 hours (claudin-5/ß-actin: 0.42±0.03 vs. 1.03±0.05, P < 0.01). After intervention with Xuebijing, the permeability of endothelial cells was significantly improved (fluorescence intensity of fluorescein sodium: 1.46±0.10 vs. 1.89±0.11, P < 0.01), and the decrease of claudin-5 protein was reduced (claudin-5/ß-actin: 0.68±0.04 vs. 0.38±0.03, P < 0.01). CONCLUSIONS: Xuebijing injection may improve pulmonary vascular barrier function in ALI by upregulating claudin-5 expression.

Involvement of claudin-5 in H2S-induced acute lung injury.

Acute exposure to hydrogen sulfide (H2S) can cause fatal acute lung injury (ALI). However, the mechanisms of H2S-induced ALI are still not fully understood. This study aims to investigate the role of the tight junction protein claudin-5 in H2S-induced ALI. In our study, Sprague-Dawley (SD) rats were exposed to H2S to establish the ALI model, and in parallel, human pulmonary microvascular endothelial cells (HPMECs) were incubated with NaHS (a H2S donor) to establish a cell model. Lung immunohistochemistry and electron microscopy assays were used to identify H2S-induced ALI, and the expression of claudin-5, p-AKT/t-AKT and p-FoxO1/t-FoxO1 was detected. Our results show that H2S promoted the formation of ALI by morphological investigation and decreased claudin-5 expression. Dexamethasone (Dex) could partly attenuate NaHS-mediated claudin-5 downregulation, and the protective effects of Dex could be partially blocked by LY294002, a PI3K/AKT/FoxO1 pathway antagonist. Moreover, as a consequence of the altered phosphorylation of AKT and FoxO1, a change in claudin-5 with the same trend was observed. Therefore, the tight junction protein claudin-5 might be considered a therapeutic target for the treatment of ALI induced by H2S and other hazardous gases.

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.

Aceso: PICO-guided Evidence Summarization on Medical Literature.

Evidence-Based Medicine (EBM) aims to apply the best available evidence gained from scientific methods to clinical decision making. A generally accepted criterion to formulate evidence is to use the PICO framework, where PICO stands for Problem/Population, Intervention, Comparison, and Outcome. Automatic extraction of PICO-related sentences from medical literature is crucial to the success of many EBM applications. In this work, we present our Aceso system, which automatically generates PICO-based evidence summaries from medical literature. In Aceso 1, we adopt an active learning paradigm, which helps to minimize the cost of manual labeling and to optimize the quality of summarization with limited labeled data. An UMLS2Vec model is proposed to learn a vector representation of medical concepts in UMLS 2, and we fuse the embedding of medical knowledge with textual features in summarization. The evaluation shows that our approach is better on identifying PICO sentences against state-of-the-art studies and outperforms baseline methods on producing high-quality evidence summaries.

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.