Red blood cells from patients with ST-elevation myocardial infarction and elevated C-reactive protein levels induce endothelial dysfunction.

Endothelial dysfunction is an early consequence of vascular inflammation and a driver of coronary atherosclerotic disease leading to myocardial infarction. The red blood cells (RBCs) mediate endothelial dysfunction in patients at cardiovascular risk, but their role in patients with acute myocardial infarction is unknown. This study aimed to investigate if RBCs from patients with ST-elevation myocardial infarction (STEMI) induced endothelial dysfunction and the role of systemic inflammation in this effect. RBCs from patients with STEMI and aged-matched healthy controls were co-incubated with rat aortic segments for 18h followed by evaluation of endothelium-dependent (EDR) and -independent relaxation (EIDR). RBCs and aortic segments were also analyzed for arginase and oxidative stress. The patients were divided into groups depending on C-reactive protein (CRP) levels at admission. RBCs from patients with STEMI and CRP levels >2 mg/L induced impairment of EDR, but not EIDR, compared to RBCs from STEMI and CRP <2 mg/L and healthy controls. Aortic expression of arginase 1 was increased following incubation with RBCs from patients with STEMI and CRP >2, and arginase inhibition prevented the RBC-induced endothelial dysfunction. RBCs from patients with STEMI and CRP >2 had increased reactive oxygen species compared to RBCs from patients with CRP <2 and healthy controls. Vascular inhibition of NADPH oxidases and increased dismutation of superoxide improved EDR. RBCs from patients with STEMI and low-grade inflammation induce endothelial dysfunction through a mechanism involving arginase 1 as well and increased RBC and vascular superoxide by NADPH oxidases.

A hybrid deep learning approach to predict hourly riverine nitrate concentrations using routine monitored data.

With high-frequency data of nitrate (NO3-N) concentrations in waters becoming increasingly important for understanding of watershed system behaviors and ecosystem managements, the accurate and economic acquisition of high-frequency NO3-N concentration data has become a key point. This study attempted to use coupled deep learning neural networks and routine monitored data to predict hourly NO3-N concentrations in a river. The hourly NO3-N concentration at the outlet of the Oyster River watershed in New Hampshire, USA, was predicted through neural networks with a hybrid model architecture coupling the Convolutional Neural Networks and the Long Short-Term Memory model (CNN-LSTM). The routine monitored data (the river depth, water temperature, air temperature, precipitation, specific conductivity, pH and dissolved oxygen concentrations) for model training were collected from a nested high-frequency monitoring network, while the high-frequency NO3-N concentration data obtained at the outlet were not included as inputs. The whole dataset was separated into training, validation, and testing processes according to the ratio of 5:3:2, respectively. The hybrid CNN-LSTM model with different input lengths (1d, 3d, 7d, 15d, 30d) displayed comparable even better performance than other studies with lower frequencies, showing mean values of the Nash-Sutcliffe Efficiency 0.60-0.83. Models with shorter input lengths demonstrated both the higher modeling accuracy and stability. The water level, water temperature and pH values at monitoring sites were main controlling factors for forecasting performances. This study provided a new insight of using deep learning networks with a coupled architecture and routine monitored data for high-frequency riverine NO3-N concentration forecasting and suggestions about strategies about variable and input length selection during preprocessing of input data.

Recovery of ammonia assimilating microbiome after Cr (VI) shock by bio-accelerators.

The pretreatment process is often unable to completely intercept heavy metals in wastewater, facing a huge risk of leakage, increasing the difficulty of treating pollutants in the subsequent biochemical process or even leading to the collapse of the system, and facing the difficulty of inoperability and rehabilitation. Heterotrophic ammonia assimilation has the potential to maintain some stability after heavy metal shock, thanks to its rapid microbial proliferation, robust resistance to high loads, remarkable environmental adaptability, and inherent stability. Bio-accelerators dosing strategies could strengthen the performance recovery ability of traditional bio-system after heavy metal impact. However, no recovery strategies for inhibiting HAA have been reported. Herein, three bio-accelerants, specifically, vitamin A, 6-benzylaminopurine, and α-ketoglutaric acid, were investigated for their potential to restore the HAA system impacted by 20 mg/L Cr (VI). The three bio-accelerants effectively mitigated the toxicity of the HAA system, resulting in a 60.4% increase in NH4+-N removal efficiency within just 6 days with cytokinin. During toxicity remediation, three bio-accelerants facilitated the production of extracellular protein components in soluble microbial products and stimulated the secretion of extracellular polymeric substances. The three bio-accelerants enhanced competition among genera and influenced community assembly processes to regulate community structure and enhance functional gene expression. This study offers a practical approach to enhancing the HAA process and remediating microbial toxicity.

The red blood cell as a mediator of endothelial dysfunction in patients with familial hypercholesterolemia and dyslipidemia.

BACKGROUND: Patients with familial hypercholesterolemia (FH) display high levels of low-density lipoprotein cholesterol (LDL-c), endothelial dysfunction, and increased risk of premature atherosclerosis. We have previously shown that red blood cells (RBCs) from patients with type 2 diabetes induce endothelial dysfunction through increased arginase 1 and reactive oxygen species (ROS). OBJECTIVE: To test the hypothesis that RBCs from patients with FH (FH-RBCs) and elevated LDL-c induce endothelial dysfunction. METHODS AND RESULTS: FH-RBCs and LDL-c >5.0 mM induced endothelial dysfunction following 18-h incubation with isolated aortic rings from healthy rats compared to FH-RBCs and LDL-c <2.5 mM or RBCs from healthy subjects (H-RBCs). Inhibition of vascular but not RBC arginase attenuated the degree of endothelial dysfunction induced by FH-RBCs and LDL-c >5.0 mM. Furthermore, arginase 1 but not arginase 2 was elevated in the vasculature of aortic segments after incubation with FH-RBCs and LDL-c >5.0 mM. A superoxide scavenger, present throughout the 18-h incubation, attenuated the degree of endothelial dysfunction induced by FH-RBCs and LDL-c >5.0 mM. ROS production was elevated in these RBCs in comparison with H-RBCs. Scavenging of vascular ROS through various antioxidants also attenuated the degree of endothelial dysfunction induced by FH-RBCs and LDL-c >5.0 mM. This was corroborated by an increase in the lipid peroxidation product 4-hydroxynonenal. Lipidomic analysis of RBC lysates did not reveal any significant changes across the groups. CONCLUSION: FH-RBCs induce endothelial dysfunction dependent on LDL-c levels via arginase 1 and ROS-dependent mechanisms.

Erythrocytes from patients with ST-elevation myocardial infarction induce cardioprotection through the purinergic P2Y13 receptor and nitric oxide signaling.

Red blood cells (RBCs) are suggested to play a role in cardiovascular regulation by exporting nitric oxide (NO) bioactivity and ATP under hypoxia. It remains unknown whether such beneficial effects of RBCs are protective in patients with acute myocardial infarction. We investigated whether RBCs from patients with ST-elevation myocardial infarction (STEMI) protect against myocardial ischemia-reperfusion injury and whether such effect involves NO and purinergic signaling in the RBCs. RBCs from patients with STEMI undergoing primary coronary intervention and healthy controls were administered to isolated rat hearts subjected to global ischemia and reperfusion. Compared to RBCs from healthy controls, RBCs from STEMI patients reduced myocardial infarct size (30 ± 12% RBC healthy vs. 11 ± 5% RBC STEMI patients, P < 0.001), improved recovery of left-ventricular developed pressure and dP/dt and reduced left-ventricular end-diastolic pressure in hearts subjected to ischemia-reperfusion. Inhibition of RBC NO synthase with L-NAME or soluble guanylyl cyclase (sGC) with ODQ, and inhibition of cardiac protein kinase G (PKG) abolished the cardioprotective effect. Furthermore, the non-selective purinergic P2 receptor antagonist PPADS but not the P1 receptor antagonist 8PT attenuated the cardioprotection induced by RBCs from STEMI patients. The P2Y13 receptor was expressed in RBCs and the cardioprotection was abolished by the P2Y13 receptor antagonist MRS2211. By contrast, perfusion with PPADS, L-NAME, or ODQ prior to RBCs administration failed to block the cardioprotection induced by RBCs from STEMI patients. Administration of RBCs from healthy subjects following pre-incubation with an ATP analog reduced infarct size from 20 ± 6 to 7 ± 2% (P < 0.001), and this effect was abolished by ODQ and MRS2211. This study demonstrates a novel function of RBCs in STEMI patients providing protection against myocardial ischemia-reperfusion injury through the P2Y13 receptor and the NO-sGC-PKG pathway.

Therapeutic Potential of Sunitinib in Ameliorating Endothelial Dysfunction in Type 2 Diabetic Rats.

INTRODUCTION: Sunitinib, a multi-targeted tyrosine kinase receptor inhibitor used to treat renal-cell carcinoma and gastrointestinal stromal tumor, was recently shown to have a beneficial effect on metabolism in type 2 diabetes (T2D). Endothelial dysfunction is a key factor behind macro- and microvascular complications in T2D. The effect of sunitinib on endothelial function in T2D remains, however, unclear. We therefore tested the hypothesis that sunitinib ameliorates endothelial dysfunction in T2D. METHODS: Sunitinib (2 mg/kg/day, by gavage) was administered to T2D Goto-Kakizaki (GK) rats for 6 weeks, while water was given to GK and Wistar rats as controls. Hemodynamic, inflammatory, and metabolic parameters as well as endothelial function were measured. RESULTS: Systolic, mean arterial blood pressures, plasma tumor necrosis factor α levels, kidney weight to body weight (BW) ratio, and glucose levels were higher, while BW was lower in GK rats than in Wistar rats. Six-week treatment with sunitinib in GK rats did not affect these parameters but suppressed the increase in glucose levels. Endothelium-dependent relaxations were reduced in both aortas and mesenteric arteries isolated from GK as compared to Wistar rats, which was markedly reversed in both types of arteries from GK rats treated with sunitinib. CONCLUSIONS: This study demonstrates that sunitinib has a glucose-lowering effect and ameliorates endothelial dysfunction in both conduit and resistance arteries of GK rats.

Patterns of post-drought recovery are strongly influenced by drought duration, frequency, post-drought wetness, and bioclimatic setting.

Understanding vegetation recovery after drought is critical for projecting vegetation dynamics in future climates. From 1997 to 2009, Australia experienced a long-lasting drought known as the Millennium Drought (MD), which led to widespread reductions in vegetation productivity. However, vegetation recovery post-drought and its determinants remain unclear. This study leverages remote sensing products from different sources-fraction of absorbed photosynthetically active radiation (FPAR), based on optical data, and canopy density, derived from microwave data-and random forest algorithms to assess drought recovery over Australian natural vegetation during a 20-year period centered on the MD. Post-drought recovery was prevalent across the continent, with 6 out of 10 drought events seeing full recovery within about 6 months. Canopy density was slower to recover than leaf area seen in FPAR. The probability of full recovery was most strongly controlled by drought return interval, post-drought hydrological condition, and drought length. Full recovery was seldom observed when drought events occurred at intervals of 3 months or less, and moderately dry (standardized water balance anomaly [SWBA] within [-1, -0.76]) post-drought conditions resulted in less complete recovery than wet (SWBA > 0.3) post-drought conditions. Press droughts, which are long term but not extreme, delayed recovery more than pulse droughts (short term but extreme) and led to a higher frequency of persistent decline. Following press droughts, the frequency of persistent decline differed little among biome types but peaked in semi-arid regions across aridity levels. Forests and savanna required the longest recovery times for press drought, while grasslands were the slowest to recover for pulse drought. This study provides quantitative thresholds that could be used to improve the modeling of ecosystem dynamics post-drought.

Phosphatase Cdc25A Negatively Regulates the Antiviral Immune Response by Inhibiting TBK1 Activity.

The phosphatase Cdc25A plays an important role in cell cycle regulation by dephosphorylating its substrates, such as cyclin-dependent kinases. In this study, we demonstrate that Cdc25A negatively regulates RIG-I-mediated antiviral signaling. We found that ectopic expression of Cdc25A in 293T cells inhibits the activation of beta interferon (IFN-ß) induced by Sendai virus and poly(I·C), while knockdown of Cdc25A enhances the transcription of IFN-ß stimulated by RNA virus infection. The inhibitory effect of Cdc25A on the antiviral immune response is mainly dependent on its phosphatase activity. Data from a luciferase assay indicated that Cdc25A can inhibit TBK1-mediated activation of IFN-ß. Further analysis indicated that Cdc25A can interact with TBK1 and reduce the phosphorylation of TBK1 at S172, which in turn decreases the phosphorylation of its downstream substrate IRF3. Consistently, knockdown of Cdc25A upregulates the phosphorylation of both TBK1-S172 and IRF3 in Sendai virus-infected or TBK1-transfected 293T cells. In addition, we confirmed that Cdc25A can directly dephosphorylate TBK1-S172-p. These results demonstrate that Cdc25A inhibits the antiviral immune response by reducing the active form of TBK1. Using herpes simplex virus 1 (HSV-1) infection, an IFN-ß reporter assay, and reverse transcription-quantitative PCR (RT-qPCR), we demonstrated that Cdc25A can also inhibit DNA virus-induced activation of IFN-ß. Using a vesicular stomatitis virus (VSV) infection assay, we confirmed that Cdc25A can repress the RIG-I-like receptor (RLR)-mediated antiviral immune response and influence the antiviral status of cells. In conclusion, we demonstrate that Cdc25A negatively regulates the antiviral immune response by inhibiting TBK1 activity.IMPORTANCE The RLR-mediated antiviral immune response is critical for host defense against RNA virus infection. However, the detailed mechanism for balancing the RLR signaling pathway in host cells is not well understood. We found that the phosphatase Cdc25A negatively regulates the RNA virus-induced innate immune response. Our studies indicate that Cdc25A inhibits the RLR signaling pathway via its phosphatase activity. We demonstrated that Cdc25A reduces TBK1 activity and consequently restrains the activation of IFN-ß transcription as well as the antiviral status of nearby cells. We showed that Cdc25A can also inhibit DNA virus-induced activation of IFN-ß. Taken together, our findings uncover a novel function and mechanism for Cdc25A in regulating antiviral immune signaling. These findings reveal Cdc25A as an important negative regulator of antiviral immunity and demonstrate its role in maintaining host cell homeostasis following viral infection.

Activation of adenosine A2A but not A2B receptors is involved in uridine adenosine tetraphosphate-induced porcine coronary smooth muscle relaxation.

Activation of both adenosine A2A and A2B receptors (A2BR) contributes to coronary vasodilation. We previously demonstrated that uridine adenosine tetraphosphate (Up4A) is a novel vasodilator in the porcine coronary microcirculation, acting mainly on A2AR in smooth muscle cells (SMC). We further investigated whether activation of A2BR is involved in Up4A-mediated coronary SMC relaxation. Both A2AR and A2BR may stimulate H2O2 production leading to activation of KATP channels in SMCs, we also studied the involvement of H2O2 and KATP channels in Up4A-mediated effect. Coronary small arteries dissected from the apex of porcine hearts were mounted on wire myograph for Up4A concentration responses. Up4A-induced coronary SMC relaxation was attenuated by A2AR but not A2BR antagonism or non-selective P2R antagonism, despite greater endogenous A2BR expression vs. A2AR in both coronary small arteries and primary cultured coronary SMCs. Moreover, Up4A-induced coronary SMC relaxation was blunted by H2O2 catabolism. This effect was not altered by KATP channel blockade. Combination of H2O2 catabolism and A2AR antagonism attenuated Up4A-induced coronary SMC relaxation to the similar extent as A2AR antagonism alone. Collectively, Up4A-induced porcine coronary SMC relaxation is mediated by activation of A2AR-H2O2 pathway. This process does not involve A2BR, P2R or KATP channels.

HDM2 Promotes NEDDylation of Hepatitis B Virus HBx To Enhance Its Stability and Function.

Hepatitis B virus (HBV)-encoded X protein (HBx) plays a critical role in HBV-related hepatocarcinoma development. In this study, we demonstrate that HBx is specifically modified by NEDD8. We found that E3 ligase HDM2 promotes NEDDylation of HBx to enhance HBx stability by preventing its ubiquitination-mediated degradation. Consistently, analysis of 160 hepatocellular carcinoma patient specimens indicated that the amount of HDM2 protein correlates with HBx protein level. We identified that HBx K91 and K95 as the key HBx NEDDylation sites and observed that the NEDDylation-deficient HBx has shorter half-life. We generated Huh7 cell lines which ectopically express wild-type and NEDDylation-deficient HBx and found that NEDDylation-deficient HBx showed less chromatin localization and less DDB1 binding. Consistently, the expression of HBx-regulated genes (IL-8, MMP9, and YAP) and HBV transcription (the activity of HBV enhancer and the amount of pgRNA transcribed from cccDNA) were significantly higher in cells expressing wild-type (WT) HBx than that in cells expressing mutant HBx. In addition, HBx-expressing cells proliferated faster than control and mutant HBx-expressing cells. We also showed that the ability of WT HBx-expressing cells to form tumors in nude mice was significantly higher than that of mutant HBx-expressing cells. In conclusion, we revealed that E3 ligase HDM2 promotes NEDDylation of HBx to enhance HBx stability and chromatin localization, which in turn favors HBx-dependent transcriptional regulation, cell proliferation, and HBV-driven tumor growth.IMPORTANCE Hepatitis B virus (HBV) HBx protein plays a critical role in viral replication and hepatocarcinogenesis. However, the regulation of HBx stability is not well understood. We found that HBx is modified by NEDD8 and that the HDM2 E3 ligase promotes HBx NEDDylation to enhance HBx stability by inhibiting its ubiquitination. We provide a new evidence to show the positive correlation between HDM2 and HBx in clinical hepatocellular carcinoma (HCC) samples. We also identified the major NEDDylation sites on HBx. Our studies indicate that the defective NEDDylation of HBx negatively affects its ability to activate the transcription of downstream genes and promote cell proliferation and tumor growth in vivo Taken together, our findings reveal a novel posttranslational modification of HBx by HDM2 which regulates its stability, subcellular localization, and functions. These findings indicate that HDM2 is an important regulator on HBx and a potential diagnosis/therapeutic marker for HBV-associated HCC.

Altered Purinergic Receptor Sensitivity in Type 2 Diabetes-Associated Endothelial Dysfunction and Up4A-Mediated Vascular Contraction.

Purinergic signaling may be altered in diabetes accounting for endothelial dysfunction. Uridine adenosine tetraphosphate (Up4A), a novel dinucleotide substance, regulates vascular function via both purinergic P1 and P2 receptors (PR). Up4A enhances vascular contraction in isolated arteries of diabetic rats likely through P2R. However, the precise involvement of PRs in endothelial dysfunction and the vasoconstrictor response to Up4A in diabetes has not been fully elucidated. We tested whether inhibition of PRs improved endothelial function and attenuated Up4A-mediated vascular contraction using both aortas and mesenteric arteries of type 2 diabetic (T2D) Goto Kakizaki (GK) rats vs. control Wistar (WT) rats. Endothelium-dependent (EDR) but not endothelium-independent relaxation was significantly impaired in both aortas and mesenteric arteries from GK vs. WT rats. Non-selective inhibition of P1R or P2R significantly improved EDR in aortas but not mesenteric arteries from GK rats. Inhibition of A1R, P2X7R, or P2Y6R significantly improved EDR in aortas. Vasoconstrictor response to Up4A was enhanced in aortas but not mesenteric arteries of GK vs. WT rats via involvement of A1R and P2X7R but not P2Y6R. Depletion of major endothelial component nitric oxide enhanced Up4A-induced aortic contraction to a similar extent between WT and GK rats. No significant differences in protein levels of A1R, P2X7R, and P2Y6R in aortas from GK and WT rats were observed. These data suggest that altered PR sensitivity accounts for endothelial dysfunction in aortas in diabetes. Modulating PRs may represent a potential therapy for improving endothelial function.

Hepatitis B virus regulates apoptosis and tumorigenesis through the microRNA-15a-Smad7-transforming growth factor beta pathway.

UNLABELLED: Hepatitis B virus (HBV) infection causes chronic hepatitis in hundreds of millions of people worldwide, which can eventually lead to hepatocellular carcinoma (HCC). Previously, we found that HBV mRNAs can absorb microRNA-15a (miR-15a) to affect apoptosis through the Bcl-2 pathway. We asked whether HBV could inhibit apoptosis and promote tumorigenesis through different pathways. In this study, we found that the transforming growth factor ß (TGF-ß) pathway-inhibitory factor Smad7 is a novel target of miR-15a. We demonstrated that HBV can upregulate the level of Smad7 by downregulating miR-15a. Furthermore, we examined the level of Smad7 in liver samples from HBV-infected HCC patients and found that HBV mRNAs are positively correlated with the level of Smad7. By taking the approach of using immunoblotting and luciferase reporter assays, we revealed that HBV can abrogate TGF-ß signaling via upregulating Smad7. By using annexin V staining and caspase 3/7 activity assays, we found that HBV can inhibit TGF-ß-induced apoptosis of HepG2 cells. We also showed that HBV can promote tumor growth in BALB/c nude mice through upregulating the expression of Smad7. In conclusion, we demonstrated that HBV can upregulate Smad7 expression and inhibit TGF-ß signaling, which makes the cells resistant to TGF-ß-induced apoptosis and promotes tumorigenesis. IMPORTANCE: Hepatitis B virus (HBV) infection causes chronic hepatitis, which can eventually lead to hepatocellular carcinoma (HCC). TGF-ß signaling is closely linked to liver fibrosis, cirrhosis, and subsequent HCC progression and plays a unique role in the pathogenesis of HCC. At the early stage of tumor formation, TGF-ß functions as a tumor suppressor that inhibits cell proliferation and induces apoptosis. Previously, we found that HBV mRNAs can sponge off miR-15a to affect apoptosis through the Bcl-2 pathway. In this study, we identified that the TGF-ß-inhibitory factor Smad7 is a novel target of miR-15a. We reveal that HBV can abrogate TGF-ß signaling via upregulating Smad7, inhibit TGF-ß-induced apoptosis, as well as promote tumor development. Our study provides evidence to support the idea that viral RNAs can exert their functions as competing endogenous RNAs (ceRNAs) toward microRNA and participate in important cellular processes.

Development of a Distributed Crack Sensor Using Coaxial Cable.

Cracks, the important factor of structure failure, reflect structural damage directly. Thus, it is significant to realize distributed, real-time crack monitoring. To overcome the shortages of traditional crack detectors, such as the inconvenience of installation, vulnerability, and low measurement range, etc., an improved topology-based cable sensor with a shallow helical groove on the outside surface of a coaxial cable is proposed in this paper. The sensing mechanism, fabrication method, and performances are investigated both numerically and experimentally. Crack monitoring experiments of the reinforced beams are also presented in this paper, illustrating the utility of this sensor in practical applications. These studies show that the sensor can identify a minimum crack width of 0.02 mm and can measure multiple cracks with a spatial resolution of 3 mm. In addition, it is also proved that the sensor performs well to detect the initiation and development of cracks until structure failure.

Epidemiological characteristics and clinical features of sporadic viral hepatitis E (HEV).

OBJECTIVE: The study aims to analyze the epidemiological characteristics and clinical features of sporadic viral hepatitis E. METHODS: The 1,000 cases of sporadic viral hepatitis E patients treated in 20 hospitals from May 2013 to May 2016 were selected as research subjects, with their clinical data retrospectively analyzed. RESULTS: (1) Epidemiological characteristics: Seen from the disease time, the 1,000 patients have morbidity throughout the year, but morbidity in hot and rainy summer is significantly higher than other seasons, there exists statistically difference in comparison between the groups (P<0.05); sporadic viral hepatitis E has no family aggregation; male morbidity is greater than female. In the study, there were male 782 cases, 218 female cases, with male/female ratio at 3.6: 1; morbidity was 13.7% (137/1000) for patients under 18, 62.9% (629/1000) for patients aged 18-60, 23.4% (234/1000) for patients over 60; there were 692 cases of simplex hepatitis E (simplex infection), 308 cases of hepatitis E complicated with chronic liver disease (super infection), of which, complicated viral hepatitis B took up the majority. (2) Clinical features: In the early stage, patients had symptoms of fever, stuffy nose, sore throat; 784 (78.4%) patients had jaundice during illness; 527 (52.7%) patients had loss of appetite, nausea and other gastrointestinal symptoms; ALT, AST of patients with hepatitis E plus posthepatitic cirrhosis were significantly lower than patients with simplex infection (all P<0.01); total bilirubin in patients over 60 was significantly higher than that of young and middle-aged patients, statistical difference in statistical analysis was (P <0.05); in the study, 274(27.4%) patients had complications, complication probability of patients aged over 60 was higher than young and middle-aged patients, difference comparison was statistically significant (P<0.05); complication probability of super infected patients was higher than those with simplex infection (P<0.01). All the patients underwent liver protection, jaundice removal and other symptomatic treatments, achieving good treatment effect: 315 cases were cured, 678 cases had improved condition, 7 cases died. CONCLUSION: There exists obvious correlation between morbidity of sporadic viral hepatitis E and season, gender and age; once sicken, one needs to take early symptomatic treatment, to avoid more severe damage to liver function.

Hepatitis B virus inhibits apoptosis of hepatoma cells by sponging the MicroRNA 15a/16 cluster.

Hepatitis B virus (HBV) causes chronic hepatitis in hundreds of millions of people worldwide, which can eventually lead to hepatocellular carcinoma (HCC). The molecular mechanisms underlying HBV persistence are not well understood. In this study, we found that HBV inhibited the chemotherapy drug etoposide-induced apoptosis of hepatoma cells. Further analysis revealed that HBV mRNAs possess a microRNA 15a/16 (miR-15a/16)-complementary site (HBV nucleotides [nt] 1362 to 1383) that acts as a sponge to bind and sequester endogenous miR-15a/16. Consequently, Bcl-2, known as the target of miR-15a/16, was upregulated in HBV-infected cells. The data from HBV-transgenic mice further confirmed that HBV transcripts cause the reduction of miR-15a/16 and increase of Bcl-2. More importantly, we examined the levels of HBV transcripts and miR-15a/16 in HBV-infected HCC from patients and found that the amount of HBV mRNA and the level of miR-15a/16 were negatively correlated. Consistently, the level of Bcl-2 mRNA was upregulated in HBV-infected patients. In conclusion, we identified a novel HBV mRNA-miR-15a/16-Bcl-2 regulatory pathway that is involved in inhibiting etoposide-induced apoptosis of hepatoma cells, which may contribute to facilitating chronic HBV infection and hepatoma development.

Enhancing regenerative potential: A comprehensive review of stem cell transplantation for sports-related neuronal injuries, with a focus on spinal cord injuries and peripheral nervous system damage.

Neuronal injuries, as one of the consequences of sports-related incidents, exert a profound influence on the athletes' future, potentially leading to complete immobility and impeding their athletic pursuits. In cases of severe damage inflicted upon the spinal cord (SC) and peripheral nervous systems (PNS), the regenerative process is notably compromised, rendering it essentially inefficient. Among the pivotal therapeutic approaches for the enhancement and prevention of secondary SC injuries (SCI), stem cell transplantation (SCT) stands out prominently. Stem cells, whether directly involved in replacement and reconstruction or indirectly through modification and secretion of crucial bioenvironmental factors, engage in the intricate process of tissue regeneration. Stem cells, through the secretion of neurotrophic factors (NTFs) (aiming to modulate the immune system), reduction of inflammation, axonal growth stimulation, and myelin formation, endeavor to facilitate the regeneration of damaged SC tissue. The fundamental challenges of this approach encompass the proper selection of suitable stem cell candidates for transplantation and the establishment of an appropriate microenvironment conducive to SC repair. In this article, an attempt has been made to explore sports-related injuries, particularly SCI, to comprehensively review innovative methods for treating SCI, and to address the existing challenges. Additionally, some of the stem cells used in neural injuries and the process of their utilization have been discussed.

Vascular disease and risk of fall-related injuries in Parkinson's disease: A nationwide cohort study in Sweden.

INTRODUCTION: Parkinson's disease (PD) patients are prone to fall and fall-related injuries (FI). Vascular disease is common in PD and is positively associated with falls in elderly. We aimed to evaluate the association of vascular disease with FI risk in PD. METHODS: A nationwide cohort study of patients with primary PD diagnosis in Sweden was performed using Swedish national registers. Patients with and without vascular disease were followed from PD diagnosis until subsequent FI or 2013-12-31. The association of vascular disease with FI risk was estimated as hazard ratio (HR) and 95 % confidence interval (CI) by Cox regression using attained age as underlying timescale. RESULTS: We identified 2734 and 6979 incident FI from 8025 PD patients with and 20,543 without vascular disease, respectively. Overall, vascular disease associated positively with subsequent FI, which was mainly driven by the significant risk elevation within the first 6 months following vascular disease (HR < 0.5year [95 % CI] for PD diagnosed ≤75 years is 1.61 [1.39-1.87] and for PD diagnosed >75 years is 1.48 [1.32-1.65]). Thereafter, the association attenuated to null before it rebounded five years after exposure in PD diagnosed ≤75 years (HR > 5year = 1.26, 95 % CI: 1.10-1.45); whereas for PD diagnosed >75 years, it dropped remarkably and remained non-significant 6 months after exposure. When vascular disease was restricted to stroke, we saw a similar temporal pattern except that the short-term HRs among younger patients were stronger, lasted longer, and declined continuously without rebound. CONCLUSIONS: Fall prevention is crucial to PD patients immediately after a vascular event.

Recovery mechanism of heterotrophic ammonia assimilation system under chromium hexavalent stress.

Heterotrophic ammonia assimilation (HAA), an innovative technology for high-salinity wastewater treatment, demonstrates self-recovery capability following Cr (VI) stress. This study investigated the inhibitory effects and self-restoration mechanisms of Cr (VI) at various stress levels. The removal efficiencies of NH4+-N and Cr (VI) in the HAA gradually decreased with increasing influent Cr (VI) concentration. Exposure to Cr (VI) increased the amounts of high-molecular-weight proteins in soluble microbial products and stimulated the generation of extracellular polymeric substances. Heterotrophic functional microorganisms with Cr (VI) tolerance, such as Marinobacter and Planktosalinus, were enriched. An assimilation pathway gene (glnA) and a Cr (VI)-related gene (atoB) were also upregulated. After ceasing Cr (VI) addition, the HAA system demonstrated a 17.1 % increase in the removal efficiency of NH4+-N, which was attributable to its self-recovery ability. This study provides a scientific and theoretical foundation for the HAA process in resisting the impact of heavy-metal-containing wastewater and self-recovery.

Nutrients recovery by coupled bioreactor of heterotrophic ammonia assimilation and microbial fuel cell in saline wastewater.

Heterotrophic ammonia assimilation (HAA) process had been widely used in the treatment of high salt wastewater, but the electro enhanced coupling process and electron transfer process were rarely studied. In this study, a HAA process coupled microbial fuel cell (MFC) system was established to treat ammonia-containing wastewater under increasing salinity to achieve nitrogen recovery and electricity generation. Up to 95.4 % NH4+-N and 96.4 % COD removal efficiencies were achieved at 2 % salinity in HAA-MFC. The maximum power density and current density at 2 % salinity were 29.93 mW/m2 and 182.37 mA/m2, respectively. The residual organic matter in the cathode effluent was effectively removed by the anode. The increase of salinity not only enhanced the sludge settling performance and activity, but also promoted the enzyme activity and amino acid production of the ammonia assimilation pathway. Marinobacter and Halomonas were gradually enriched at the anode and cathode with increased salinity to promote ammonia assimilation and electron production. This research offered a promising solution to overcome salinity-related challenges in wastewater treatment and resource recovery.

Identification and validation of LINC01322 as a potential prognostic biomarker and oncogene promoting tumor progression in lung adenocarcinoma.

Our study identified a novel long noncoding RNA, LINC01322, that acts as an oncogene in lung adenocarcinoma progression. Cytoplasmic and nuclear RNA purification assays indicated that LINC01322 was localized in the cytoplasm and nucleus. Gene set enrichment analysis revealed the involvement of LINC01322 in the regulation of cell proliferation, migration, and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. LINC01322 may promote lung adenocarcinoma proliferation and migration through the Janus kinase/signal transducer and activator of transcription signaling pathway. In vitro experiments demonstrated that the knockdown of LINC01322 significantly suppressed lung adenocarcinoma cell proliferation, migration, and activation of the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway, whereas overexpression had the opposite effects. Inhibition of the Janus kinase 2/signal transducer and activator of transcription 3 pathway activity partially reversed the enhancement of cell proliferation and migration caused by LINC01322 overexpression. In vivo experiments further verified the oncogene role of LINC01322. Altogether, our findings suggest that LINC01322 promotes lung adenocarcinoma progression by activating the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway and that it could be a therapeutic target.