Ginseng total saponin improves red blood cell oxidative stress injury by regulating tyrosine phosphorylation and glycolysis in red blood cells.

BACKGROUND: Oxidative stress is the main cause of many diseases, but because of its complex pathogenic factors, there is no clear method for treating it. Ginseng total saponin (GTS) an important active ingredients in Panax ginseng C.A. Mey (PG) and has potential therapeutic ability for oxidative stress due to various causes. However, the molecular mechanism of GTS in the treating oxidative stress damage in red blood cells (RBCs) is still unclear. PURPOSE: This study aimed to examine the protective effect of GTS on RBCs under oxidative stress damage and to determine its potential mechanism. METHODS: The oxidative stress models of rat RBCs induced by hydrogen peroxide (H2O2) and exhaustive swimming in vivo and in vitro was used. We determined the cell morphology, oxygen carrying capacity, apoptosis, antioxidant capacity, and energy metabolism of RBCs. The effect of tyrosine phosphorylation (pTyr) of Band 3 protein on RBCs glycolysis was also examined. RESULTS: GTS reduced the hemolysis of RBCs induced by H2O2 at the lowest concentration. Moreover, GTS effectively improved the morphology, enhanced the oxygen carrying capacity, and increased antioxidant enzyme activity, adenosine triphosphate (ATP) levels, and adenosine triphosphatase (ATPase) activity in RBCs. GTS also promoted the expression of membrane proteins in RBCs, inhibited pTyr of Band 3 protein, and further improved glycolysis, restoring the morphological structure and physiological function of RBCs. CONCLUSIONS: This study shows, that GTS can protect RBCs from oxidative stress damage by improving RBCs morphology and physiological function. Changes in pTyr expression and its related pTyr regulatory enzymes before and after GTS treatment suggest that Band 3 protein is the main target of GTS in the treating endogenous and exogenous oxidative stress. Moreover, GTS can enhance the glycolytic ability of RBCs by inhibiting pTyr of Band 3 protein, thereby restoring the function of RBCs.

Perovskite-based electrochemiluminescence analysis of H2O2.

The detection of hydrogen peroxide (H2O2) represents an extensive requirement across various domains, including food, environmental, and medical fields. This study introduces a highly sensitive technique for the quantification of H2O2, integrating the electrochemiluminescence properties of perovskite with bio-catalyzed precipitation. A water-soluble perovskite-based electrochemiluminescence (ECL) biosensing interface was constructed, wherein H2O2 catalyzes a precipitation reaction that leads to the formation of an insoluble precipitate on the electrode surface. This occurrence effectively quenches the electrochemiluminescence signal of the perovskite, thus facilitating the quantitative detection of H2O2. The modified perovskite demonstrated excellent ECL performance, offering a stable signal source, while the bio-catalyzed precipitation reaction significantly amplified the quenching effect, thereby enhancing detection sensitivity. This strategy exhibits excellent stability and sensitivity, presenting a promising method for the detection of hydrogen peroxide, which holds great potential for applications in various fields.

A CRISPR/Cas12a-assisted array for Helicobacter pylori DNA analysis in saliva.

Helicobacter pylori infection has become a threat to the world populations. This leads to an urgent need of an efficient and convenient approach to accurately diagnose H. pylori infection. Saliva-based diagnoses are particularly welcomed for their efficiency and convenience. Aiming at saliva sample analysis, we proposed a CRISPR/Cas12a-assisted array, which had integrated H. pylori concentration detection and genotype screening functions. Single-nucleotide variations (SNVs) could be distinguished using the screening array with different probes, and an isothermal cycling strategy was combined with the trans-cleavage activity of Cas12a for signal amplification to improve accuracy of the diagnosis. As a demonstration, the SNV screening array was fabricated by utilizing the hybridization efficiency difference caused by mismatched bases. The array was able to successfully distinguish between ten H. pylori genotypes, and combined with the successful SDA biosensing, it had a LOD of as low as 60 fM. It was also able to diagnose H. pylori infection in saliva samples from infected patients. Together, the developed array has a potential in large-scale clinical screening and is a promising tool for the diagnosis and prevention of H. pylori infection-related diseases.

A Nucleophilic Activity-Based Probe Enables Profiling of PLP-Dependent Enzymes.

PLP-dependent enzymes represent an important class of highly "druggable" enzymes that perform a wide array of critical reactions to support all organisms. Inhibition of individual members of this family of enzymes has been validated as a therapeutic target for pathologies ranging from infection with Mycobacterium tuberculosis to epilepsy. Given the broad nature of the activities within this family of enzymes, we envisioned a universally acting probe to characterize existing and putative members of the family that also includes the necessary chemical moieties to enable activity-based protein profiling experiments. Hence, we developed a probe that contains an N-hydroxyalanine warhead that acts as a covalent inhibitor of PLP-dependent enzymes, a linear diazirine for UV crosslinking, and an alkyne moiety to enable enrichment of crosslinked proteins. Our molecule was used to study PLP-dependent enzymes in vitro as well as look at whole-cell lysates of M. tuberculosis and assess inhibitory activity. The probe was able to enrich and identify LysA, a PLP-dependent enzyme crucial for lysine biosynthesis, through mass spectrometry. Overall, our study shows the utility of this trifunctional first-generation probe. We anticipate further optimization of probes for PLP-dependent enzymes will enable the characterization of rationally designed covalent inhibitors of PLP-dependent enzymes, which will expedite the preclinical characterization of these important therapeutic targets.

Paraquat Induces Lung Injury via miR-199-Mediated SET in a Mouse Model.

Objective: To explore the molecular mechanism of lung injury caused by paraquat (PQ) poisoning by investigating miR-199-mediated SET. Methods: A paraquat poisoning model was established in C57BL/6 male mice via intraperitoneal injection of paraquat. The mice were transfected with miR-199 siRNA and or mimic. After 14 days of treatment, pathophysiological changes of the lung were observed and lung tissue was analyzed via Hematoxylin-Eosin staining. The levels of miR-199, SETs, surfactant protein SP-A and SP-B, and inflammatory and oxidative factors were analyzed by qPCR, Western Blot, and ELISA kits. Results: A acute lung-injury (ALI) model was established using PQ treatment and confirmed with edema of pulmonary endothelium with low electronic density of endothelial cytoplasm, presence of protein-rich fluid, and numerous erythrocytes in alveolar space, concentric figures of damaged tubular myelin, alveolar destruction, and increase in inflammatory cell numbers. Compared with the control group, miR-199 and SET levels were reduced in the PQ-treated group. miR-199 siRNA increased the SET level, inflammatory and oxidative levels, and reduced the levels of SP-A and SP-B, and miR-199 mimic reduced the SET level, inflammatory and oxidative levels, and increased the levels of SP-A and SP-B. PQ treatment reduced miR-199 level. Conclusion: Paraquat induces ALI by affecting miR-199-mediated SET.

Synthesis and biological evaluation of orally active prodrugs and analogs of para-aminosalicylic acid (PAS).

Tuberculosis (TB) is one of the world's most deadly infectious diseases resulting in nearly 1.3 million deaths annually and infecting nearly one-quarter of the population. para-Aminosalicylic acid (PAS), an important second-line agent for treating drug-resistant Mycobacterium tuberculosis, has moderate bioavailability and rapid clearance that necessitate high daily doses of up to 12 g per day, which in turn causes severe gastrointestinal disturbances presumably by disruption of gut microbiota and host epithelial cells. We first synthesized a series of alkyl, acyloxy and alkyloxycarbonyloxyalkyl ester prodrugs to increase the oral bioavailability and thereby prevent intestinal accumulation as well as undesirable bioactivation by the gut microbiome to non-natural folate species that exhibit cytotoxicity. The pivoxyl prodrug of PAS was superior to all of the prodrugs examined and showed nearly quantitative absorption. While the conceptually simple prodrug approach improved the oral bioavailability of PAS, it did not address the intrinsic rapid clearance of PAS mediated by N-acetyltransferase-1 (NAT-1). Thus, we next modified the PAS scaffold to reduce NAT-1 catalyzed inactivation by introduction of groups to sterically block N-acetylation and fluorination of the aryl ring of PAS to attenuate N-acetylation by electronically deactivating the para-amino group. Among the mono-fluorinated analogs prepared, 5-fluoro-PAS, exhibited the best activity and an 11-fold decreased rate of inactivation by NAT-1 that translated to a 5-fold improved exposure as measured by area-under-the-curve (AUC) following oral dosing to CD-1 mice. The pivoxyl prodrug and fluorination at the 5-position of PAS address the primary limitations of PAS and have the potential to revitalize this second-line TB drug.

Escherichia coli infection activates the production of IFN-α and IFN-ß via the JAK1/STAT1/2 signaling pathway in lung cells.

Escherichia coli infections can result in lung injury, which may be closely linked to the induction of interferon secretion. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is one of most important pathways that regulate interferon production. Thus, the present study aimed to dissect whether E. coli infections can regulate interferon production and the underlying mechanisms. For this aim, two lung cell lines, a human bronchial epithelial cell line transformed with Ad12-SV40 2B (BEAS-2b) and a human fetal lung fibroblast (HFL1) cell line, were used. The effects of E. coli infections on interferon production were studied using qRT-PCR, Western blot, and siRNA knockdown assays. E. coli infections remarkably promoted the expression levels of IFN-α, IFN-ß, and ISGs. Major components of the JAK/STAT pathway, including JAK1, STAT1, and STAT2, were demonstrated to be regulated by E. coli infections. Importantly, knockdown of JAK1, STAT1, and STAT2 abolished the induction of IFN-α, IFN-ß, and ISGs by E. coli. Therefore, experiments in the present study demonstrated that E. coli infections remarkably promoted interferon production in lung cells, which was closely regulated by the JAK/STAT signaling pathway. The findings in the present study are useful for further understanding the pathogenesis of E. coli infections in the lung and finding novel therapies to treat E. coli-induced lung injury.

The correlation between mental health status, sleep quality, and inflammatory markers, virus negative conversion time among patients confirmed with 2019-nCoV during the COVID-19 outbreak in China: An observational study.

ABSTRACT: The 2019 coronavirus disease (COVID-19) has spread to the whole world. Psychological and sleep problems among confirmed patients have drawn extensive attention which may be highly related to immune function and inflammatory responses of people. The aim of this study is to examine the correlation of mental health status, sleep quality, and inflammatory markers, virus negative conversion time (NCT) among confirmed patients during the COVID-19 outbreak.A cross-sectional survey was conducted in this study. Data from 66 patients assessed with demographic information, anxious symptom, depressive symptom, stress, and sleep quality were collected using a smartphone-based questionnaire platform and then clinical characteristics and laboratory indicators were collected using case review.Nearly 30% of the participants reported depression, anxiety, perceived pressure, and poor sleep quality. Compared with the group without depression, neutrophil count, and ratio of neutrophil count to lymphocyte count (NLR) in the depression disorder group were increased (P = .028, 0.043). There was also a significant difference in NLR and NCT between the anxiety group and the non-anxiety group (P = .021, .024). Similarly, compared with the good sleep quality group, NLR in the poor sleep quality group was increased (P = .011). Correlation analysis indicated that Self-Rating Depression Scale score was positively related to neutrophil count and NLR (r = 0.366, 0.330, P = .016, .031). The total score of Pittsburgh Sleep Quality Index (PSQI) was negatively related to lymphocyte count (r = -0.317, P = .049), and the sleep disturbance as 1 of the 7 dimensions of PSQI scale was positively correlated with NCT and NLR (r = 0.370, 0.340, P = .020, .034).In our study, confirmed patients were prone to have psychological and sleep problems. The level of inflammation in patients with psychological and sleep problems was higher than that in patients without corresponding problems. The inflammatory level increased with the increase of Self-Rating Depression Scale score, and the lymphocyte count decreased with the increase of the PSQI score. NCT was prolonged in the anxiety group and sleep disturbance was positively correlated with NCT.

Chest lesion CT radiological features and quantitative analysis in RT-PCR turned negative and clinical symptoms resolved COVID-19 patients.

BACKGROUND: Many studies have described lung lesion computed tomography (CT) features of coronavirus disease 2019 (COVID-19) patients at the early and progressive stages. In this study, we aim to evaluate lung lesion CT radiological features along with quantitative analysis for the COVID-19 patients ready for discharge. METHODS: From February 10 to March 10, 2020, 125 COVID-19 patients (age: 16-67 years, 63 males) ready for discharge, with two consecutive negative reverse transcription-polymerase chain reaction (RT-PCR) and no clinical symptoms for more than 3 days, were included. The pre-discharge CT was performed on all patients 1-3 days after the second negative RT-PCR test, and the follow-up CTs were performed on 44 patients 2-13 days later. The imaging features and quantitative analysis were evaluated on both the pre-discharge and the follow-up CTs, by both radiologists and an artificial intelligence (AI) software. RESULTS: On the pre-discharge CT, the most common CT findings included ground-glass opacity (GGO) (99/125, 79.2%) with bilateral mixed distribution, and fibrosis (56/125, 44.8%) with bilateral subpleural distribution. Enlarged mediastinal lymph nodes were also commonly observed (45/125, 36.0%). AI enabled quantitative analysis showed the right lower lobe was mostly involved, and lesions most commonly had CT value of -570 to -470 HU consistent with GGO. Follow-up CT showed GGO decrease in size and density (40/40, 100%) and fibrosis reduction (17/26, 65.4%). Compared with the pre-discharge CT results, quantitative analysis shows the lung lesion volume regressed significantly at follow-up. CONCLUSIONS: For COVID-19 patients ready for discharge, GGO and fibrosis are the main CT features and they further regress at follow-up.

A spectroscopic and theoretical investigation of interaction mechanisms of tetracycline and polystyrene nanospheres under different conditions.

Interaction mechanisms of tetracycline (TC, as a typical antibiotic) on polystyrene microsphere (PSs, as a typical nanoplastic) were conducted by the batch, spectroscopic and theoretical techniques. The batch results showed that Na+ and K+ had no obvious effects on TC adsorption towards PSs, whereas Mg2+ significantly inhibited TC adsorption at pH > 5.0 due to its induced aggregations of PSs. The maximum TC adsorption capacity of PSs in the presence of humic acid (50.99 mg/g) was higher than that of PSs (44.77 mg/g) at pH 6.0. The highly effective adsorption was attributed to electrostatic attraction, π-π interaction and hydrophobic effect, which was determined by FT-IR and XPS analysis. According to DFT (density functional theory) calculations, the adsorption energy of TC/TC+ on PSs (1.52 eV) was significantly higher than that of negative TC- (0.57 eV), whereas minimum distance of TC on PSs (3.684 Å) was shorter than that of TC- on PSs (3.988 Å). The results of theoretical calculations indicated that TC was more preferably adsorbed on PSs with more stable configuration compared to TC-. These findings indicated that PSs can be used as a promising adsorbent for immobilization and pre-concentration of TC from aqueous solutions.

Highly efficient high-performance liquid chromatographic separation of xylene isomers and phthalate acid esters on a homemade DUT-67(Zr) packed column.

In this study, the baseline separations of xylene isomers and phthalate acid esters on a homemade DUT-67(Zr) packed column were achieved, respectively. The high selectivity for xylene isomers and phthalate acid esters was obtained with the increase in temperature and decrease in the retention time. The hydrophobicity of xylene isomers and phthalate acid esters resulted in the different separation time on the DUT-67(Zr) packed column. The relative standard deviation values of retention time, peak area, peak height, and half peak width for five repeat separation of the xylene isomers were 0.26-0.35, 2.11-2.26, 1.51-2.03, and 0.29-0.77%, and the values of the phthalate acid esters on DUT-67(Zr) column were 0.1-0.4, 4.4-5.2, 3.9-6.3, and 0.6-2.1%, respectively. The thermodynamic properties indicated that the separation of xylene isomers was controlled by ΔH and ΔS, but the separation of phthalate acid esters was mainly controlled by ΔS.

[Correlation between model for end-stage liver disease score and prognosis in mushroom poisoning patients: a multicenter clinical study].

OBJECTIVE: To find out the clinical indicators related to prognosis in patients with acute mushroom poisoning, and approach its correlation with prognosis. METHODS: Clinical data of patients with mushroom poisoning admitted to the First Hospital of China Medical University, the Ninth People's Hospital of Shenyang, Xiuyan Central People's Hospital, and Fushun Central Hospital from August 2015 to August 2017 were retrospectively analyzed. The biochemical indicators within 24 hours after admission, sequential organ failure assessment (SOFA) score, model for end-stage liver disease (MELD) score, whether plasmapheresis (PE) was carried out or not and 28-day prognosis of patients were collected. According to prognosis, the patients were divided into death group and survival group, and the differences in above parameters between the two groups were compared. Spearman or Pearson correlation method was used to analyze the relationship between MELD score and prognosis. Receiver operating characteristic (ROC) curve was used to analyze the prognostic value of MELD score for prognosis. Further analysis of the patients receiving PE treatment was conducted. RESULTS: A total of four Liaoning hospitals with 89 patients with mushroom poisoning were enrolled, with 6 died within 28 days, and 83 survived. There were 17 patients with severely impaired liver and coagulant functions accepted PE treatment, with 6 patients died within 28 days, and 11 survived. (1) In 89 patients, compared with survival group, MELD score, prothrombin time (PT), activated partial thromboplastin time (APTT), total bilirubin (TBil), international normalized ratio (INR), blood glucose (Glu), alanine aminotransferase (ALT), γ-glutamyltransferase (GGT) in death group were significantly increased [MELD score: 32.34 (28.31, 41.06) vs. 8.76 (3.77, 21.19), PT (s): 53.5 (52.4, 113.2) vs. 14.5 (13.8, 19.5), APTT (s): 58.6 (48.9, 70.8) vs. 36.9 (34.4, 43.2), TBil (µmol/L): 134.8 (31.3, 155.6) vs. 21.5 (15.1, 41.4), INR: 6.0 (5.6, 14.7) vs. 1.2 (1.1, 1.5), Glu (mmol/L): 9.2 (9.0, 11.0) vs. 6.6 (5.7, 7.8), ALT (U/L): 5 923.0 (1 105.0, 6 000.0) vs. 35.0 (18.0, 1 767.0), GGT (U/L): 49.0 (32.0, 57.0) vs. 25.0 (16.0, 41.0), all P < 0.05], but the prothrombin activity (PTA), albumin (ALB), serum Na+, Cl- were significantly decreased [PTA: 13.0% (6.0%, 14.0%) vs. 80.0% (61.0%, 87.0%), ALB (g/L): 31.1 (29.8, 39.0) vs. 42.4 (37.9, 44.3), Na+ (mmol/L): 126.5 (122.4, 131.0) vs. 137.0 (134.9, 141.0), Cl- (mmol/L): 93.5 (87.6, 95.0) vs. 104.0 (101.3, 106.0), all P < 0.05]. Spearson correlation analysis showed that MELD score of patients with mushroom poisoning was positively correlated with the 28-day mortality (r = 0.423, P = 0.001). ROC curve analysis showed that the area under ROC curve (AUC) of MELD score for prognosis of patients with mushroom poisoning was 0.926; when the cut-off value was 27.30, the sensitivity was 100%, and the specificity was 84.3%. (2) In 17 patients who accepted PE treatment, compared with survival group, the MELD score, TBil, Glu, and ALT in the death group were significantly increased [MELD score: 36.81±5.18 vs. 29.01±5.23, TBil (µmol/L): 145.2±13.9 vs. 93.2±44.0, Glu (mmol/L): 9.1±1.9 vs. 6.0±2.7, ALT (U/L): 5 961.5±44.5 vs. 3 932.9±1 625.7, all P < 0.05], and Cl- was significantly lowered (mmol/L: 94.3±1.2 vs. 100.5±5.7, P < 0.05), but SOFA score showed no significant difference (5.83±2.71 vs. 5.91±1.58, P > 0.05). Correlation analysis showed that the MELD score in patients with mushroom poisoning who accepted PE treatment was positively correlated with 28-day mortality (r = 0.355, P = 0.001), but no correlation with SOFA score was found (r = 0.427, P = 0.087). ROC curve analysis showed that the AUC of MELD score in the prediction of mushroom poisoning patients undergoing PE treatment was 0.545; when the cut-off value was 32.19, the sensitivity was 33.3%, and the specificity was 100%. CONCLUSIONS: In mushroom poisoning patients, especially those undergoing PE treatment, the higher the MELD score, the higher the mortality is. MELD score could assess the prognosis of patients with acute mushroom poisoning.

[Evaluation value of oxygenation index of mechanical ventilation on the prognosis of patients with ARDS: a retrospective analysis with 228 patients].

OBJECTIVE: To investigate the evaluation value of oxygenation index at different times of mechanical ventilation (MV) on the prognosis of patients with acute respiratory distress syndrome (ARDS). METHODS: A retrospectively analysis was conducted. A total of 228 patients with ARDS admitted to Department of Emergency of China Medical University Affiliated First Hospital from February 2014 to June 2016 were enrolled. All patients underwent MV treatment, and recruitment maneuver (RM) was performed by pressure-controlled ventilation (PCV) 30 minutes after the implementation of the protective ventilation strategy. Arterial blood gas analysis was performed at MV immediately, after RM and at 6, 12, 24 hours of MV, and oxygenation index was calculated. Vital signs, laboratory data, ultrasonic echocardiography, sequential organ failure assessment (SOFA) score, duration of MV, and ventilator related parameters of patients were collected. The patients were divided into survivors and non-survivors according to the prognosis of 28 days. The survivors were subdivided into high and low oxygenation group (oxygenation index was ≥ 150 mmHg and < 150 mmHg, respectively, 1 mmHg = 0.133 kPa). Differences in clinical indicators between survivors and non-survivors were compared. The correlation between the oxygenation index after RM and the oxygenation index at each time after MV was analyzed by bivariate correlation analysis. Receiver operating characteristic (ROC) curve was plotted to analyze predictive value of oxygenation index measured at different times for the 28-day outcome of patients with ARDS. RESULTS: Among 228 patients, 99 patients died within 28 days, and 129 survived, with mortality rate of 43.4%. (1) The oxygenation index after RM and at 6, 12, 24 hours after MV in survivors and non-survivors showed a continuously increased tendency, which was significantly lower in non-survivors than that in survivors (all P < 0.05). There was no significant difference in the duration of MV between high oxygenation group and low oxygenation group at MV immediately and after RM, but the duration of MV in high oxygenation group was significantly shorter than that of the low oxygenation group at 6, 12, 24 hour of MV (all P < 0.01). (2) After ventilation for 24 hours, serum creatinine (SCr), brain natriuretic peptide (BNP), lactate (Lac), right ventricular internal diameter, and SOFA score in non-survivors were significantly higher than those of survivors, and arterial partial pressure of oxygen (PaO2), platelet (PLT) and right ventricular ejection fraction (RVEF) were significantly lower than those of survivors (all P < 0.05). (3) After 24 hours ventilation, positive end-expiratory pressure (PEEP), tidal volume (VT), and minute ventilation (VE) in non-survivors were significantly higher than those of survivors, and static compliance of thorax (Cdyn) was significantly lower than that of survivors (all P < 0.01). (4) It was shown by correlation analysis that the oxygenation index after RM was positively correlated with those at 6, 12, 24 hours of MV (r values were 0.856, 0.765, and 0.758, respectively, all P < 0.001). (5) It was shown by ROC curve that the area under the ROC curve (AUC) of the oxygenation index after RM for predicting 28-day prognosis was 0.688. When the cut-off value was 80.75 mmHg, the sensitivity was 97.7%, and the specificity was 42.4%, which could only be used for preliminary judgment of prognosis. The AUC of oxygenation index at 6, 12, 24 hours of MV for 28-day survival of ARDS patients were 0.719, 0.727, 0.754, respectively. When the cut-off values were 171.50, 192.14, and 161.75 mmHg, the sensitivity was 69.8%, 67.4%, 86.0%, and the specificity was 78.8%, 78.8%, and 63.6%, respectively. It indicated that the predictive value was higher, and no significant difference was found among the oxygenation index at different time points. CONCLUSIONS: The oxygenation index after the early stage of RM can preliminarily determine the prognosis of patients. The predictive value of oxygenation index after MV for 28-day survival of ARDS patients was higher, so the oxygenation index measured at 6 hours of MV may be considered to evaluate the prognosis of patients with ARDS.

Aldehyde dehydrogenase 2 protects against oxidative stress associated with pulmonary arterial hypertension.

The cardioprotective benefits of aldehyde dehydrogenase 2 (ALDH2) are well established, although the regulatory role of ALDH2 in vascular remodeling in pulmonary arterial hypertension (PAH) is largely unknown. ALDH2 potently regulates the metabolism of aldehydes such as 4-hydroxynonenal (4-HNE), the endogenous product of lipid peroxidation. Thus, we hypothesized that ALDH2 ameliorates the proliferation and migration of human pulmonary artery smooth muscle cells (HPASMCs) by inhibiting 4-HNE accumulation and regulating downstream signaling pathways, thereby ameliorating pulmonary vascular remodeling. We found that low concentrations of 4-HNE (0.1 and 1µM) stimulated cell proliferation by enhancing cyclin D1 and c-Myc expression in primary HPASMCs. Low 4-HNE concentrations also enhanced cell migration by activating the nuclear factor kappa B (NF-κB) signaling pathway, thereby regulating matrix metalloprotein (MMP)-9 and MMP2 expression in vitro. In vivo, Alda-1, an ALDH2 agonist, significantly stimulated ALDH2 activity, reducing elevated 4-HNE and malondialdehyde levels and right ventricular systolic pressure in a monocrotaline-induced PAH animal model to the level of control animals. Our findings indicate that 4-HNE plays an important role in the abnormal proliferation and migration of HPASMCs, and that ALDH2 activation can attenuate 4-HNE-induced PASMC proliferation and migration, possibly by regulating NF-κB activation, in turn ameliorating vascular remodeling in PAH. This mechanism might reflect a new molecular target for treating PAH.

[Plant community patterns of piosphere in the Mu Us Sandland of China].

Piosphere is ubiquitous in drylands. Plant communities of ten paddocks were investigated along transects starting from watering points in the Mu Us Sandland. By using the method of regression and indirect gradient ordination, the richness of plant community and plant functional types were analyzed. The results showed that with the increase of distance from the watering points, the traits of the plant communities varied significantly. The coverage of the community, shrubs and grasses gradually increased and the coverage of forbs decreased with the distance increasing from the watering points. The patterns of the community richness and coverage suggested the grazing gradient surrounding the watering points. The piosphere is a breakthrough point to reveal the degradation pattern of rangeland and its driving forces in northern China.