With continued climate changes, soil drought stress has become the main limiting factor for crop growth in arid and semi‐arid regions. A typical characteristic of drought stress is the burst of ...reactive oxygen species (ROS), causing oxidative damage. Plant‐associated microbes, such as arbuscular mycorrhizal fungi (AMF), can regulate physiological and molecular responses to tolerate drought stress, and they have a strong ability to cope with drought‐induced oxidative damage via enhanced antioxidant defence systems. AMF produce a limited oxidative burst in the arbuscule‐containing root cortical cells. Similar to plants, AMF modulate a fungal network in enzymatic (e.g. GmarCuZnSOD and GintSOD1) and non‐enzymatic (e.g. GintMT1, GinPDX1 and GintGRX1) antioxidant defence systems to scavenge ROS. Plants also respond to mycorrhization to enhance stress tolerance via metabolites and the induction of genes. The present review provides an overview of the network of plant − arbuscular mycorrhizal fungus dialogue in mitigating oxidative stress. Future studies should involve identifying genes and transcription factors from both AMF and host plants in response to drought stress, and utilize transcriptomics, proteomics and metabolomics to clarify a clear dialogue mechanism between plants and AMF in mitigating oxidative burst.
The dialogue of arbuscular mycorrhizal fungi and host plants confers a mitigating drought‐induced oxidative burst in hosts.
•Poor sleep quality is prevalent (e.g., 1/3 of this sample) in Chinese university students.•Those with higher smartphone addiction (SA) tendency report worse sleep quality.•Poor self-regulation and ...bedtime procrastination are risk factors for sleep quality.•Bedtime procrastination mediates the effects of SA onto sleep quality.
The steep rise of smartphone use has raised public concerns about smartphone addiction and its associated negative health consequences, such as poor sleep quality; however, limited research has examined the psychological mechanisms underlying these associations. The current study tested the effects of smartphone addiction on poor sleep quality, through self-regulation and bedtime procrastination, among 427 Chinese undergraduate students, aged 18 or older (M = 19.36; female = 66%), who voluntarily completed an anonymous online questionnaire. The results showed that 1/3 of participants reported poor subjective sleep quality. Smartphone addiction and bedtime procrastination had a significant positive relationship, whereas self-regulation had a significant negative association, with poor sleep quality (which was assessed by sleep latency, sleep duration, and subjective sleep quality). Despite its nonsignificant direct effects, the indirect effects of smartphone addiction, via both self-regulation and bedtime procrastination, on the three indicators of poor sleep quality were statistically significant. The findings have supported the premise that both bedtime procrastination and poor self-regulation are risk-enhancing mediators on the association between smartphone addiction on poor sleep quality. Therefore, they should be considered in intervention programs (e.g., self-regulation skill training) to reduce smartphone addiction and improve sleep quality and physical wellbeing among university students.
In this paper, three data-preprocessing techniques, moving average (MA), singular spectrum analysis (SSA), and wavelet multi-resolution analysis (WMRA), were coupled with artificial neural network ...(ANN) to improve the estimate of daily flows. Six models, including the original ANN model without data preprocessing, were set up and evaluated. Five new models were ANN-MA, ANN-SSA1, ANN-SSA2, ANN-WMRA1, and ANN-WMRA2. The ANN-MA was derived from the raw ANN model combined with the MA. The ANN-SSA1, ANN-SSA2, ANN-WMRA1 and ANN-WMRA2 were generated by using the original ANN model coupled with SSA and WMRA in terms of two different means. Two daily flow series from different watersheds in China (Lushui and Daning) were used in six models for three prediction horizons (i.e., 1-, 2-, and 3-day-ahead forecast). The poor performance on ANN forecast models was mainly due to the existence of the lagged prediction. The ANN-MA, among six models, performed best and eradicated the lag effect. The performances from the ANN-SSA1 and ANN-SSA2 were similar, and the performances from the ANN-WMRA1 and ANN-WMRA2 were also similar. However, the models based on the SSA presented better performance than the models based on the WMRA at all forecast horizons, which meant that the SSA is more effective than the WMRA in improving the ANN performance in the current study. Based on an overall consideration including the model performance and the complexity of modeling, the ANN-MA model was optimal, then the ANN model coupled with SSA, and finally the ANN model coupled with WMRA.
Global demethylation is required for early zygote development to establish stem cell pluripotency, yet our findings reiterate this epigenetic reprogramming event in somatic cells through ectopic ...introduction of mir-302 function. Here, we report that induced mir-302 expression beyond 1.3-fold of the concentration in human embryonic stem (hES) H1 and H9 cells led to reprogramming of human hair follicle cells (hHFCs) to induced pluripotent stem (iPS) cells. This reprogramming mechanism functioned through mir-302-targeted co-suppression of four epigenetic regulators, AOF2 (also known as KDM1 or LSD1), AOF1, MECP1-p66 and MECP2. Silencing AOF2 also caused DNMT1 deficiency and further enhanced global demethylation during somatic cell reprogramming (SCR) of hHFCs. Re-supplementing AOF2 in iPS cells disrupted such global demethylation and induced cell differentiation. Given that both hES and iPS cells highly express mir-302, our findings suggest a novel link between zygotic reprogramming and SCR, providing a regulatory mechanism responsible for global demethylation in both events. As the mechanism of conventional iPS cell induction methods remains largely unknown, understanding this microRNA (miRNA)-mediated SCR mechanism may shed light on the improvements of iPS cell generation.
In recent years, goose gout, a severe infectious disease, has affected the development of the goose industry in China. Two different genotypes of goose astrovirus (GAstV), named as GAstV-1 and ...GAstV-2, were identified. GAstV-2 viruses are known to be the causative agent of goose gout; however, GAstV-1 has not been isolated, and the relationship between GAstV-1 and goose gout is unknown. One full genome sequence, designated as GAstV/CHN/TZ03/2019 (TZ03), was determined from the clinical tissue samples of a diseased gosling using next-generation sequencing. The complete genome of TZ03 was 7,262 nucleotides in length with typical genomic characteristics of avastroviruses. The TZ03 strain shares the highest identity (96.6%) with the GAstV-1 strain FLX, but only 51.5 to 61.3% identity with other astroviruses in Avastrovirus. Phylogenetic analysis revealed that the TZ03 strain clustered together with the GAstV-1 strains FLX and AHDY and was highly divergent from GAstV-2 viruses. The TZ03 strain was successfully isolated from goose embryos and caused 100% mortality of goose embryos after 5 passages. Electron microscopy showed that the virus particles were spherical with a diameter of ∼22 nm. The clinical symptoms were reproduced by experimental infection of healthy goslings, which were similar to those caused by GAstV-2 strains. Our data show that GAstV-1 is one of the causative agents of the ongoing goose gout disease in China. These findings enrich our understanding of the evolution of GAstVs that cause gout and provide potential options for developing biological products to treat goose gout.
Background and Aim
Patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) I148M (rs738409) genotype influences clinical/biochemical characteristics in patients with nonalcoholic fatty liver ...disease (NAFLD), but whether PNPLA3‐I148M (rs738409) genotype also influences the diagnostic performance of noninvasive diagnostic tests for NAFLD is uncertain. Our aim was to investigate the differences in diagnostic performance of noninvasive diagnostic tests for NAFLD according to PNPLA3‐I148M (rs738409) genotype.
Methods
Fifty‐eight healthy controls and 349 patients with biopsy‐proven NAFLD were included. Areas under the receiver operating characteristic curve (AUROCs) were calculated to predict hepatic steatosis (fatty liver index and hepatic steatosis index), nonalcoholic steatohepatitis (cytokeratin‐18 M30 and M65), and significant fibrosis (≥F2 fibrosis) (fibrosis‐4 and BARD), stratifying by rs738409 genotypes (CC and CG + GG groups).
Results
Fatty liver index and hepatic steatosis index showed good diagnostic performance for diagnosing steatosis only in the CG + GG group with AUROCs ranging from 0.819 to 0.832. Cytokeratin‐18 M30 (AUROC = 0.688) and M65 (AUROC = 0.678) had suboptimal performance for diagnosing nonalcoholic steatohepatitis in the CG + GG group, whereas both had good performance (AUROC = 0.814 and 0.813, respectively) in the CC group. BARD score showed good performance in the CG + GG group compared with the CC group (AUROC = 0.805 and 0.532, respectively). Fibrosis‐4 had suboptimal performance in the CG + GG group and good performance in the CC group (AUROC = 0.662 and 0.801, respectively).
Conclusions
Diagnostic performance of noninvasive tests for NAFLD varied markedly according to PNPLA3 genotypes. Clinicians should be aware that PNPLA3 genotype limits the clinical utility of noninvasive diagnostic tests for diagnosing NAFLD.
Chronic hepatitis C virus (HCV) infection is associated with chronic inflammation of liver, which leads to the development of cirrhosis and hepatocellular carcinoma (HCC). Because of severe side ...effects and only a 50–70% cure rate in genotype 1 HCV‐infected patients upon current standard treatment with pegylated interferon‐α plus ribavirin, new therapeutic regimens are still needed. San‐Huang‐Xie‐Xin‐Tang (SHXT) is a transitional Chinese herbal formula, composed of Rhei rhizoma, Scutellaria radix and Coptidis rhizome, and possesses anti‐inflammatory effect. Here, we describe a (+)‐catechin‐containing fraction extracted from SHXT, referred as SHXT‐frC, exhibited effective inhibition of HCV replication, with selectivity index value (SI; CC50/EC50) of 84, and displayed synergistic anti‐HCV effects when combined with interferon‐α, HCV protease inhibitor telaprevir or polymerase inhibitor 2′‐C‐methylcytidine. The activation of factor‐κB (NF‐κB) and cyclooxygenase‐2 (COX‐2) signalling pathway has particular relevance to HCV‐associated HCC. SHXT‐frC treatment also caused a concentration‐dependent decrease in the induction of COX‐2 and NF‐κB expression caused by either HCV replication or HCV NS5A protein. Collectively, SHXT‐frC could be an adjuvant treatment for patients with HCV‐induced liver diseases.
Neonatal hypoxic-ischemic encephalopathy is an important cause of death as well as long-term disability in survivors. Erythropoietin has been hypothesized to have neuroprotective effects in infants ...with hypoxic-ischemic encephalopathy, but its effects on neurodevelopmental outcomes when given in conjunction with therapeutic hypothermia are unknown.
In a multicenter, double-blind, randomized, placebo-controlled trial, we assigned 501 infants born at 36 weeks or more of gestation with moderate or severe hypoxic-ischemic encephalopathy to receive erythropoietin or placebo, in conjunction with standard therapeutic hypothermia. Erythropoietin (1000 U per kilogram of body weight) or saline placebo was administered intravenously within 26 hours after birth, as well as at 2, 3, 4, and 7 days of age. The primary outcome was death or neurodevelopmental impairment at 22 to 36 months of age. Neurodevelopmental impairment was defined as cerebral palsy, a Gross Motor Function Classification System level of at least 1 (on a scale of 0 normal to 5 most impaired), or a cognitive score of less than 90 (which corresponds to 0.67 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition.
Of 500 infants in the modified intention-to-treat analysis, 257 received erythropoietin and 243 received placebo. The incidence of death or neurodevelopmental impairment was 52.5% in the erythropoietin group and 49.5% in the placebo group (relative risk, 1.03; 95% confidence interval CI, 0.86 to 1.24; P = 0.74). The mean number of serious adverse events per child was higher in the erythropoietin group than in the placebo group (0.86 vs. 0.67; relative risk, 1.26; 95% CI, 1.01 to 1.57).
The administration of erythropoietin to newborns undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy did not result in a lower risk of death or neurodevelopmental impairment than placebo and was associated with a higher rate of serious adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT02811263.).
SUMMARY
Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease caused by a novel coronavirus, but its immunopathological mechanisms have not yet been fully elucidated. We ...investigated changes in plasma T helper (Th) cell cytokines, inflammatory cytokines and chemokines in 20 patients diagnosed with SARS. Cytokine profile of SARS patients showed marked elevation of Th1 cytokine interferon (IFN)‐γ, inflammatory cytokines interleukin (IL)‐1, IL‐6 and IL‐12 for at least 2 weeks after disease onset, but there was no significant elevation of inflammatory cytokine tumour necrosis factor (TNF)‐α, anti‐inflammatory cytokine IL‐10, Th1 cytokine IL‐2 and Th2 cytokine IL‐4. The chemokine profile demonstrated significant elevation of neutrophil chemokine IL‐8, monocyte chemoattractant protein‐1 (MCP‐1), and Th1 chemokine IFN‐γ‐inducible protein‐10 (IP‐10). Corticosteroid reduced significantly IL‐8, MCP‐1 and IP‐10 concentrations from 5 to 8 days after treatment (all P < 0·001). Together, the elevation of Th1 cytokine IFN‐γ, inflammatory cytokines IL‐1, IL‐6 and IL‐12 and chemokines IL‐8, MCP‐1 and IP‐10 confirmed the activation of Th1 cell‐mediated immunity and hyperinnate inflammatory response in SARS through the accumulation of monocytes/macrophages and neutrophils.
It is a sad fact that despite being almost completely preventable through human papillomavirus (HPV) vaccination and screening, cervical cancer remains the fourth most common cancer to affect women ...worldwide. Persistent high-risk HPV (hrHPV) infection is the primary etiologic factor for cervical cancer. Upward of 70% of cases are driven by HPV types 16 and 18, with a dozen other hrHPVs associated with the remainder of cases. Current standard-of-care treatments include radiotherapy, chemotherapy, and/or surgical resection. However, they have significant side effects and limited efficacy against advanced disease. There are a few treatment options for recurrent or metastatic cases. Immunotherapy offers new hope, as demonstrated by the recent approval of programmed cell death protein 1-blocking antibody for recurrent or metastatic disease. This might be augmented by combination with antigen-specific immunotherapy approaches, such as vaccines or adoptive cell transfer, to enhance the host cellular immune response targeting HPV-positive cancer cells. As cervical cancer progresses, it can foster an immunosuppressive microenvironment and counteract host anticancer immunity. Thus, approaches to reverse suppressive immune environments and bolster effector T-cell functioning are likely to enhance the success of such cervical cancer immunotherapy. The success of nonspecific immunostimulants like imiquimod against genital warts also suggest the possibility of utilizing these immunotherapeutic strategies in cervical cancer prevention to treat precursor lesions (cervical intraepithelial neoplasia) and persistent hrHPV infections against which the licensed prophylactic HPV vaccines have no efficacy. Here, we review the progress and challenges in the development of immunotherapeutic approaches for the prevention and treatment of cervical cancer.
PDF
