The Effect of Low Irradiance on Leaf Nitrogen Allocation and Mesophyll Conductance to CO2 in Seedlings of Four Tree Species in Subtropical China.

Low light intensity can lead to a decrease in photosynthetic capacity. However, could N-fixing species with higher leaf N contents mitigate the effects of low light? Here, we exposed seedlings of Dalbergia odorifera and Erythrophleum fordii (N-fixing trees), and Castanopsis hystrix and Betula alnoides (non-N-fixing trees) to three irradiance treatments (100%, 40%, and 10% sunlight) to investigate the effects of low irradiance on leaf structure, leaf N allocation strategy, and photosynthetic physiological parameters in the seedlings. Low irradiance decreased the leaf mass per unit area, leaf N content per unit area (Narea), maximum carboxylation rate (Vcmax), maximum electron transport rate (Jmax), light compensation point, and light saturation point, and increased the N allocation proportion of light-harvesting components in all species. The studied tree seedlings changed their leaf structures, leaf N allocation strategy, and photosynthetic physiological parameters to adapt to low-light environments. N-fixing plants had a higher photosynthesis rate, Narea, Vcmax, and Jmax than non-N-fixing species under low irradiance and had a greater advantage in maintaining their photosynthetic rate under low-radiation conditions, such as under an understory canopy, in a forest gap, or when mixed with other species.

Coupling coordination relationship between ecosystem services and water-land resources for the Daguhe River Basin, China.

Water and land resource utilization is an important driving force of changes in ecosystem services; therefore, research on multi-parameter coupling systems that consider "ecosystem services, water resources, and land resources" together has key significance for river basins. This study aims to reveal the interaction and mutual influence of ecosystem services and water and land resources in the Daguhe River Basin, China, based on the coupling coordination degree model. The results showed that during the period from 2000 to 2010, the coupling coordination degree values for the years 2000, 2005, and 2010 were 0.6005, 0.7292, and 0.8037. The corresponding coupling coordination classifications were categorized as "primary coordinated development", "intermediate coordinated development," and "well-coordinated development", respectively. These results reflected the fact that the relationship between water and land resource utilization and the environment tends to evolve in the direction of coordinated development (an improvement in one part corresponds to an improvement in another part) with variation in water and land utilization types, and eventually pushes the whole resource, as well as ecological and environmental systems, from low to high levels of coupling coordination degrees as observed in case of the Daguhe River Basin, China. Our research provides an overview of the interaction between ecosystem services and water and land resources in the Daguhe Basin and even in the Shandong Province. With our results, we offer new perspectives on river basin management and for planning future eco-environmental policies (the policy is specifically designed for the ecological environment) by combining water and land resource utilization.

Protective effect of taurine on sepsis­induced lung injury via inhibiting the p38/MAPK signaling pathway.

Sepsis, a leading cause of acute lung injury (ALI), is characterized by an overwhelming systemic inflammatory response and widespread organ injury, particularly in the lungs. Taurine, an intracellular free amino acid, has been used for the treatment of various diseases, including lung injury; however, the underlying mechanisms are unclear. The present study aimed to investigate the protective effect of taurine on septic ALI and the underlying mechanism. A septic ALI model was established by performing cecal ligation and puncture (CLP) surgery on Sprague Dawley rats. Following successful model establishment, rats were treated with taurine. The results of hematoxylin and eosin, respiratory function detection, malondialdehyde level and superoxide dismutase activity determination and ELSIA demonstrated that taurine significantly alleviated lung injury, restored respiratory function, reduced oxidation and decreased the concentrations of inflammatory factors in CLP­induced septic ALI model rats. In addition, compared with that in the ALI group, western blotting results indicated that taurine ameliorated lung epithelial injury by significantly increasing the expression levels of lung epithelial markers, E­cadherin and occludin. The western blotting results demonstrated that, compared with the control group, the p38/MAPK and NF­κB signaling pathways were significantly activated in CLP­induced septic ALI model rats, but taurine significantly suppressed ALI­mediated signaling pathway activation. To investigate the mechanism underlying taurine in the treatment of septic ALI, CLP­induced septic ALI model rats were treated with an antagonist of the p38/MAPK signaling pathway (SB203580). The effects of SB203580 on CLP­induced septic ALI model rats were similar to those of taurine. SB203580 significantly attenuated sepsis­induced lung injury and increases in IL­1ß and TNF­α concentrations in the lung tissue. In addition, SB203580 promoted restoration of the injured lung tissue and respiratory function in CLP­induced septic ALI model rats. The western blotting results indicated that SB203580 significantly decreased the ratios of phosphorylated (p)­p38/p38 and p­p65/065, and increased the protein expression levels of E­cadherin and occludin compared with those in the ALI group. In summary, the present study demonstrated that taurine alleviated sepsis­induced lung injury, which was associated with suppression of the inflammatory response and oxidative stress via inhibiting the p38/MAPK signaling pathway. Therefore, the p38/MAPK signaling pathway may serve as a potential therapeutic target for the treatment of sepsis­induced ALI.

Identification and Prediction of Novel Clinical Phenotypes for Intensive Care Patients With SARS-CoV-2 Pneumonia: An Observational Cohort Study.

Background: Phenotypes have been identified within heterogeneous disease, such as acute respiratory distress syndrome and sepsis, which are associated with important prognostic and therapeutic implications. The present study sought to assess whether phenotypes can be derived from intensive care patients with coronavirus disease 2019 (COVID-19), to assess the correlation with prognosis, and to develop a parsimonious model for phenotype identification. Methods: Adult patients with COVID-19 from Tongji hospital between January 2020 and March 2020 were included. The consensus k means clustering and latent class analysis (LCA) were applied to identify phenotypes using 26 clinical variables. We then employed machine learning algorithms to select a maximum of five important classifier variables, which were further used to establish a nested logistic regression model for phenotype identification. Results: Both consensus k means clustering and LCA showed that a two-phenotype model was the best fit for the present cohort (N = 504). A total of 182 patients (36.1%) were classified as hyperactive phenotype, who exhibited a higher 28-day mortality and higher rates of organ dysfunction than did those in hypoactive phenotype. The top five variables used to assign phenotypes were neutrophil-to-lymphocyte ratio (NLR), ratio of pulse oxygen saturation to the fractional concentration of oxygen in inspired air (Spo2/Fio2) ratio, lactate dehydrogenase (LDH), tumor necrosis factor α (TNF-α), and urea nitrogen. From the nested logistic models, three-variable (NLR, Spo2/Fio2 ratio, and LDH) and four-variable (three-variable plus TNF-α) models were adjudicated to be the best performing, with the area under the curve of 0.95 [95% confidence interval (CI) = 0.94-0.97] and 0.97 (95% CI = 0.96-0.98), respectively. Conclusion: We identified two phenotypes within COVID-19, with different host responses and outcomes. The phenotypes can be accurately identified with parsimonious classifier models using three or four variables.

Effects of soil nitrogen (N) deficiency on photosynthetic N-use efficiency in N-fixing and non-N-fixing tree seedlings in subtropical China.

Soil nitrogen (N) deficiencies can affect the photosynthetic N-use efficiency (PNUE), mesophyll conductance (gm), and leaf N allocation. However, lack of information about how these physiological characteristics in N-fixing trees could be affected by soil N deficiency and the difference between N-fixing and non-N-fixing trees. In this study, we chose seedlings of two N-fixing (Dalbergia odorifera and Erythrophleum fordii) and two non-N-fixing trees (Castanopsis hystrix and Betula alnoides) as study objects, and we conducted a pot experiment with three levels of soil N treatments (high nitrogen, set as Control; medium nitrogen, MN; and low nitrogen, LN). Our results showed that soil N deficiency significantly decreased the leaf N concentration and photosynthesis ability of the two non-N-fixing trees, but it had less influence on two N-fixing trees. The LN treatment had lower gm in D. odorifera and lower leaf N allocated to Rubisco (PR), leaf N allocated to bioenergetics (PB), and gm in B. alnoides, eventually resulting in low PNUE values. Our findings suggested that the D. odorifera and E. fordii seedlings could grow well in N-deficient soil, and adding N may increase the growth rates of B. alnoides and C. hystrix seedlings and promote the growth of artificial forests.

Seedling leaves allocate lower fractions of nitrogen to photosynthetic apparatus in nitrogen fixing trees than in non-nitrogen fixing trees in subtropical China.

Photosynthetic-nitrogen use efficiency (PNUE) is a useful trait to characterize leaf physiology and survival strategy. PNUE can also be considered as part of 'leaf economics spectrum' interrelated with leaf nutrient concentrations, photosynthesis and respiration, leaf life-span and dry-mass investment. However, few studies have paid attention to PNUE of N-fixing tree seedlings in subtropical China. In this study, we investigated the differences in PNUE, leaf nitrogen (N) allocation, and mesophyll conductance (gm) in Dalbergia odorifera and Erythrophleum fordii (N-fixing trees), and Betula alnoides and Castanopsis hystrix (non-N-fixing trees). PNUE of D. odorifera and E. fordii were significantly lower than those of B. alnoides and C. hystrix mainly because of their allocation of a lower fraction of leaf N to Rubisco (PR) and bioenergetics (PB). Mesophyll conductance had a significant positive correlation with PNUE in D. odorifera, E. fordii, and B. alnoides, but the effect of gm on PNUE was different between species. The fraction of leaf N to cell wall (PCW) had a significant negative correlation with PR in B. alnoides and C. hystrix seedling leaves, but no correlation in D. odorifera and E. fordii seedling leaves, which may indicate that B. alnoides and C. hystrix seedling leaves did not have enough N to satisfy the demand from both the cell wall and Rubisco. Our results indicate that B. alnoides and C. hystrix may have a higher competitive ability in natural ecosystems with fertile soil, and D. odorifera and E. fordii may grow well in N-poor soil. Mixing these non-N-fixing and N-fixing trees for afforestation is useful for improving soil N utilization efficiency in the tropical forests.

HBXIP up-regulates ACSL1 through activating transcriptional factor Sp1 in breast cancer.

The oncoprotein hepatitis B X-interacting protein (HBXIP) results in the dysregulation of lipid metabolism to enhance the development of breast cancer. Acyl-CoA synthetase long-chain family member 1 (ACSL1) is required for thioesterification of long-chain fatty acids into their acyl-CoA derivatives. In this study, we present a hypothesis that HBXIP might be involved in the regulation of ACSL1 in breast cancer. Interestingly, we found that the overexpression of HBXIP was able to up-regulate ACSL1 at the levels of mRNA and protein in a dose-dependent manner in breast cancer cells. Conversely, silencing of HBXIP led to the opposite results. Mechanistically, HBXIP as a coactivator interacted with transcriptional factor Sp1 through binding to the promoter of ACSL1 by ChIP assays analysis, leading to the transcription of ACSL1 in breast cancer cells. Immunohistochemistry staining revealed that the positive rate of ACSL1 was 71.4% (35/49) in clinical breast cancer tissues, HBXIP 79.6% (39/49), in which the positive rate of ACSL1 was 76.9% (30/39) in the HBXIP-positive specimens. But, few positive rate of ACSL1 10% (1/10) was observed in normal breast tissues. The mRNA levels of ACSL1 were significantly higher in clinical breast cancer tissues than those in their corresponding peritumor tissues. The mRNA levels of ACSL1 were positively associated with those of HBXIP in clinical breast cancer tissues. Thus, we conclude that the oncoprotein HBXIP is able to up-regulate ACSL1 through activating the transcriptional factor Sp1 in breast cancer.

A long noncoding RNA perturbs the circadian rhythm of hepatoma cells to facilitate hepatocarcinogenesis.

Clock circadian regulator (CLOCK)/brain and muscle arnt-like protein-1 (BMAL1) complex governs the regulation of circadian rhythm through triggering periodic alterations of gene expression. However, the underlying mechanism of circadian clock disruption in hepatocellular carcinoma (HCC) remains unclear. Here, we report that a long noncoding RNA (lncRNA), highly upregulated in liver cancer (HULC), contributes to the perturbations in circadian rhythm of hepatoma cells. Our observations showed that HULC was able to heighten the expression levels of CLOCK and its downstream circadian oscillators, such as period circadian clock 1 and cryptochrome circadian clock 1, in hepatoma cells. Strikingly, HULC altered the expression pattern and prolonged the periodic expression of CLOCK in hepatoma cells. Mechanistically, the complementary base pairing between HULC and the 5' untranslated region of CLOCK mRNA underlay the HULC-modulated expression of CLOCK, and the mutants in the complementary region failed to achieve the event. Moreover, immunohistochemistry staining and quantitative real-time polymerase chain reaction validated that the levels of CLOCK were elevated in HCC tissues, and the expression levels of HULC were positively associated with those of CLOCK in clinical HCC samples. In functional experiments, our data exhibited that CLOCK was implicated in the HULC-accelerated proliferation of hepatoma cells in vitro and in vivo. Taken together, our data show that an lncRNA, HULC, is responsible for the perturbations in circadian rhythm through upregulating circadian oscillator CLOCK in hepatoma cells, resulting in the promotion of hepatocarcinogenesis. Thus, our finding provides new insights into the mechanism by which lncRNA accelerates hepatocarcinogenesis through disturbing circadian rhythm of HCC.

Long noncoding RNA HULC modulates abnormal lipid metabolism in hepatoma cells through an miR-9-mediated RXRA signaling pathway.

HULC is a long noncoding RNA overexpressed in hepatocellular carcinoma (HCC), but its functional contributions in this setting have not been determined. In this study, we explored the hypothesis that HULC contributes to malignant development by supporting abnormal lipid metabolism in hepatoma cells. HULC modulated the deregulation of lipid metabolism in HCC by activating the acyl-CoA synthetase subunit ACSL1. Immunohistochemical analysis of tissue microarrays revealed that approximately 77% (180/233) of HCC tissues were positive for ACSL1. Moreover, HULC mRNA levels correlated positively with ACSL1 levels in 60 HCC cases according to real-time PCR analysis. Mechanistic investigations showed that HULC upregulated the transcriptional factor PPARA, which activated the ACSL1 promoter in hepatoma cells. HULC also suppressed miR-9 targeting of PPARA mRNA by eliciting methylation of CpG islands in the miR-9 promoter. We documented the ability of HULC to promote lipogenesis, thereby stimulating accumulation of intracellular triglycerides and cholesterol in vitro and in vivo. Strikingly, ACSL1 overexpression that generates cholesterol was sufficient to enhance the proliferation of hepatoma cells. Further, cholesterol addition was sufficient to upregulate HULC expression through a positive feedback loop involving the retinoid receptor RXRA, which activated the HULC promoter. Overall, we concluded that HULC functions as an oncogene in hepatoma cells, acting mechanistically by deregulating lipid metabolism through a signaling pathway involving miR-9, PPARA, and ACSL1 that is reinforced by a feed-forward pathway involving cholesterol and RXRA to drive HULC signaling.

The role of p38 MAPK in acute paraquat-induced lung injury in rats.

CONTEXT: Paraquat (PQ; 1,1'-dimethyl-4,4'-bipyridinium dichloride) is highly toxic and accounts for a large proportion of the herbicide poisonings seen in clinic. The major cause of mortality is respiratory failure. The p38 mitogen-activated protein kinase (MAPK) signal transduction pathway coordinates various cellular stress responses that have been shown to participate in the pathogenesis of PQ-induced lung injury. OBJECTIVE: To evaluate the effect of the specific p38 MAPK inhibitor SB203580 on PQ-induced lung injury and cytokine secretion. METHODS: In groups of 24, rats were treated with PQ, PQ and SB203580 (SB + PQ), SB203580 alone (SB) or normal saline (control group). Six rats from each group were euthanized at 1, 3, 5 or 7 d. Pathology of lung specimens was scored through hematoxylin and eosin staining. Edema in the lung was quantified from wet-to-dry weight ratios. p38 and p-p38MAPK proteins were measured via electrochemiluminescent Western blots. tumor necrosis factor (TNF)-alpha and interleukin-1 beta (IL-1ß) concentrations in lung specimens and bronchoalveolar lavage fluid (BALF) were quantified via enzyme-linked immunosorbent assay. RESULTS: The mortality rate of the SB + PQ group (16.7%) was significantly lower than that of the PQ group (33.3%; p < 0.05). The PQ group had significantly higher pulmonary histology scores, wet-to-dry weight ratios and phosphorylated p-p38 MAPK levels, as well as higher IL-1ß and TNF-alpha levels in BALF and lung tissues, that did the SB + PQ and control groups (p < 0.05, all). CONCLUSION: The data suggest that the p38 MAPK signaling pathway has an important role in regulating the production of IL-1ß and TNF-alpha in PQ-induced lung injury in rats.

MiR-506 suppresses proliferation of hepatoma cells through targeting YAP mRNA 3'UTR.

AIM: MiR-506 is a miRNA involved in carcinogenesis of several kinds of cancer. In this study, we explored whether miR-506 played a critical role in hepatocellular carcinoma (HCC). METHODS: Twenty HCC and adjacent normal liver tissue samples were collected. Human hepatoma cell lines HepG2 and H7402 were used for in vitro studies. The expression of miR-506 and transcriptional co-activator YAP was examined using qRT-PCR. Western blot analysis was used to measure the expression of YAP and its target genes. Luciferase reporter gene assay was used to identify YAP as a target gene of miR-506. MTT and EdU assays were carried out for functional analysis. RESULTS: The expression of miR-506 was significantly lower in HCC than in adjacent normal liver tissues. Bioinformatics analysis revealed that YAP mRNA might be one of the targets of miR-506, and miR-506 in HCC tissues was found to be negatively correlated with YAP (r=-0.605). In both HepG2 and H7402 cells, miR-506 dose-dependently down-regulated YAP and its target genes c-Myc and the connective tissue growth factor (CTGF). Luciferase reporter gene assays demonstrated that miR-506 targeted the wild type 3'UTR of YAP mRNA, but not a 3'UTR with a mutant seed site. Furthermore, miR-506 significantly inhibited the proliferation of HepG2 and H7402 cells, while anti-miR-506 enhanced the cell proliferation, which was blocked by YAP siRNA. CONCLUSION: MiR-506 suppresses the proliferation of hepatoma cells by targeting YAP mRNA.

Intestinal trefoil factor activates the PI3K/Akt signaling pathway to protect gastric mucosal epithelium from damage.

Intestinal trefoil factor (ITF, also named as trefoil factor 3, TFF3) is a member of the TFF-domain peptide family, which plays an essential role in the regulation of cell survival, cell migration and maintains mucosal epithelial integrity in the gastrointestinal tract. However, the underlying mechanisms and associated molecules remain unclear. The aim of this study was to explore the protective effects of ITF on gastric mucosal epithelium injury and its possible molecular mechanisms of action. In the present study, we show that ITF was able to promote the proliferation and migration of GES-1 cells via a mechanism that involves the PI3K/Akt signaling pathway. Western blot results indicated that ITF induced a dose- and time-dependent increase in the Akt signaling pathway. ITF also plays an essential role in the restitution of GES-1 cell damage induced by lipopolysaccharide (LPS). LPS induced the apoptosis of GES-1 cells, decreased cell viability significantly (P<0.01) and led to epithelial tight junction damage, which is attenuated via ITF treatment. The protective effect of ITF on the integrity of GES-1 was abrogated by inhibition of the PI3K/Akt pathway. Taken together, our results demonstrate that ITF promotes the proliferation and migration of gastric mucosal epithelial cells and preserves gastric mucosal epithelial integrity after damage is mediated by activation of the PI3K/Akt signaling pathway. This study suggested that the PI3K/Akt pathway could act as a key intracellular pathway in the gastric mucosal epithelium that may serve as a therapeutic target to preserve epithelial integrity during injury.

The oncoprotein HBXIP up-regulates SCG3 through modulating E2F1 and miR-509-3p in hepatoma cells.

Hepatitis B X-interacting protein (HBXIP) is an important oncoprotein in hepatocarcinogenesis. Here, we found that the expression levels of HBXIP were positively associated with those of Secretogranin III (SCG3) in clinical hepatocellular carcinoma tissues. We identified that HBXIP up-regulated the expression of SCG3 through modulating both E2F transcription factor 1 (E2F1) and miR-509-3p. HBXIP suppressed miR-509-3p through activating NF-κB. In function, we showed that SCG3 increased the proliferation of hepatoma cells and HBXIP enhanced the proliferation of the cells via SCG3 in vitro and in vivo. Thus, we conclude that HBXIP facilitates the proliferation of hepatoma cells through up-regulating SCG3.

Involvement of cholesterol in hepatitis B virus X protein-induced abnormal lipid metabolism of hepatoma cells via up-regulating miR-205-targeted ACSL4.

Hepatitis B virus X protein (HBx) plays crucial roles in the development of hepatocellular carcinoma (HCC). The abnormal lipid metabolism is involved in the hepatocarcinogenesis. We previously reported that HBx suppressed miR-205 in hepatoma cells. In this study, we supposed that HBx-decreased miR-205 might contribute to the abnormal lipid metabolism according to the bioinformatics analysis. Interestingly, we showed that the expression levels of acyl-CoA synthetase long-chain family member 4 (ACSL4) were negatively associated with those of miR-205 in clinical HCC tissues. Then, we validated that miR-205 was able to inhibit the expression of ACSL4 at the levels of mRNA and protein through targeting its 3'UTR. Strikingly, we found that HBx was able to increase the levels of cellular cholesterol, a metabolite of ACSL4, in hepatoma cells, which could be blocked by miR-205 (or Triacsin C, an inhibitor of ACSL4). However, anti-miR-205 could increase the levels of cholesterol in the cells. Moreover, we demonstrated that the levels of cholesterol were increased in the liver of HBx transgenic mice in a time course manner. Functionally, oil red O staining revealed that HBx promoted lipogenesis in HepG2 cells, which could be abolished by miR-205 (or Triacsin C). However, anti-miR-205 was able to accelerate lipogenesis in the cells. Interestingly, the treatment with Triacsin C could remarkably block the role of anti-miR-205 in the event. Thus, we conclude that miR-205 is able to target ACSL4 mRNA. The HBx-depressed miR-205 is responsible for the abnormal lipid metabolism through accumulating cholesterol in hepatoma cells.

MiR-205 modulates abnormal lipid metabolism of hepatoma cells via targeting acyl-CoA synthetase long-chain family member 1 (ACSL1) mRNA.

The abnormal lipid metabolism is considered as a hallmarker of tumorigenesis. Liver is the central organ for metabolic homeostasis. Hence, the development of hepatocellular carcinoma (HCC) always exhibits alterations of metabolism. MicroRNAs emerge as key post-transcriptional modulators of gene expression in physiologic and pathologic states. Here, we aim to explore the mechanism of abnormal lipid metabolism of hepatoma cells. Previously, our group reported that miR-205 as a tumor suppressor was down-regulated in HCC. Therefore, we supposed that miR-205 might be involved in the event. Interestingly, in this study we uncover that miR-205 deregulates lipid metabolism in HCC through targeting acyl-CoA synthetase long-chain family member 1 (ACSL1) mRNA, which is an important and abundant lipid metabolism enzyme in liver. We identified that miR-205 was able to down-regulate ACSL1 via targeting its 3'UTR in the cells. Oil red O staining showed that miR-205 disordered the lipogenesis in hepatoma cells and anti-miR-205 resulted in the accumulation of triglyceride in the cells depending on ACSL1. Moreover, we validated that the low levels of miR-205 were negatively related to high levels of ACSL1 in clinical HCC tissues. The expression levels of ACSL1 and its metabolite triglyceride levels were remarkably increased in hepatitis B virus X protein (HBx)-induced liver cancer tissues from the HBx transgenic mice model. Thus, we conclude that miR-205-targeted ACSL1 may contribute to the abnormal lipid metabolism of liver cancer. Our finding provides new insights into the dysregulation of lipid metabolism in HCC mediated by miR-205 targeting ACSL1 mRNA.

S100B protein in serum is elevated after global cerebral ischemic injury.

BACKGROUND: S100B protein in patients with cardiac arrest, hemorrhagic shock and other causes of global cerebral ischemic injury will be dramatically increased. Ischemic brain injury may elevate the level of serum S100B protein and the severity of brain damage. METHODS: This article is a critical and descriptive review on S100B protein in serum after ischemic brain injury. We searched Pubmed database with key words or terms such as "S100B protein", "cardiac arrest", "hemorrhagic shock" and "ischemia reperfusion injury" appeared in the last five years. RESULTS: S100B protein in patients with cardiac arrest, hemorrhagic shock and other causes of ischemic brain injury will be dramatically increased. Ischemic brain injury elevated the level of serum S100B protein, and the severity of brain damage. CONCLUSION: The level of S100B protein in serum is elevated after ischemic brain injury, but its mechanism is unclear.