Ocular A-to-I RNA editing signatures associated with SARS-CoV-2 infection.

Ophthalmic manifestations have recently been observed in acute and post-acute complications of COVID-19 caused by SARS-CoV-2 infection. Our precious study has shown that host RNA editing is linked to RNA viral infection, yet ocular adenosine to inosine (A-to-I) RNA editing during SARS-CoV-2 infection remains uninvestigated in COVID-19. Herein we used an epitranscriptomic pipeline to analyze 37 samples and investigate A-to-I editing associated with SARS-CoV-2 infection, in five ocular tissue types including the conjunctiva, limbus, cornea, sclera, and retinal organoids. Our results revealed dramatically altered A-to-I RNA editing across the five ocular tissues. Notably, the transcriptome-wide average level of RNA editing was increased in the cornea but generally decreased in the other four ocular tissues. Functional enrichment analysis showed that differential RNA editing (DRE) was mainly in genes related to ubiquitin-dependent protein catabolic process, transcriptional regulation, and RNA splicing. In addition to tissue-specific RNA editing found in each tissue, common RNA editing was observed across different tissues, especially in the innate antiviral immune gene MAVS and the E3 ubiquitin-protein ligase MDM2. Analysis in retinal organoids further revealed highly dynamic RNA editing alterations over time during SARS-CoV-2 infection. Our study thus suggested the potential role played by RNA editing in ophthalmic manifestations of COVID-19, and highlighted its potential transcriptome impact, especially on innate immunity.

Microplitis bicoloratus parasitism promotes cyclophilin D-p53 interaction to induce apoptosis of hemocytes in Spodoptera litura.

Microplitis bicoloratus parasitism can induce apoptosis of hemocytes in the M. bicolortus host, Spodoptera litura. However, it is unclear how M. bicolortus parasitism regulates host signaling pathways to induce apoptosis. Expression of cyclophilin D (CypD) and p53 was significantly upregulated in S. litura hemocytes at 6 days postparasitization. In the parasitized hemocytes, there was mitochondrial membrane potential (△Ψm ) loss, cytochrome c (Cyt C) release from mitochondria, and caspase-3 activation. These occurred while hemocytes were undergoing upregulation of CypD and p53. Parasitism also promoted the interaction between CypD and p53. CypD silencing could rescue the apoptotic phenotypes induced by parasitism, but had no effect on apoptosis in unparasitized S. litura. These findings suggest that the CypD-p53 pathway may be an important component of the parasitism-induced immunosuppressive response and establish a basis for further studies of parasitoid/host interactions.

Microplitis bicoloratus bracovirus regulates cyclophilin A-apoptosis-inducing factor interaction to induce cell apoptosis in the insect immunosuppressive process.

Microplitis bicoloratus bracovirus (MbBV) induces apoptosis in hemocytes of the host (Spodoptera litura) via the cyclophilin A (CypA)-mediated signaling pathway. However, the mechanisms underlying CypA-mediated signaling during apoptosis remain largely unknown. Therefore, in this study, we investigated how CypA and apoptosis-inducing factor (AIF) interact during MbBV-mediated apoptosis. Our findings showed that MbBV induces apoptosis through the CypA-AIF axis of insect immune suppression. In MbBV-infected Spli221 cells, both the expression of the cypa gene and the release of AIF from the mitochondria increased the number of apoptotic cells. CypA and AIF underwent concurrent cytoplasm-nuclear translocation. Conversely, blocking of AIF release from mitochondria not only inhibited the CypA-AIF interaction but also inhibited the cytoplasmic-nuclear translocation of AIF and CypA. Importantly, the survival of the apoptotic phenotype was significantly rescued in MbBV-infected Spli221 cells. In addition, we found that the cyclosporine A-mediated inhibition of CypA did not prevent the formation of the CypA and AIF complex; rather, this only suppressed genomic DNA fragmentation. In vitro experiments revealed direct molecular interactions between recombinant CypA and AIF. Taken together, our results demonstrate that the CypA-AIF interaction plays an important role in MbBV-induced innate immune suppression. This study will help to clarify aspects of insect immunological mechanisms and will be relevant to biological pest control.

A comprehensive association analysis between homocysteine metabolic pathway gene methylation and ischemic stroke in a Chinese hypertensive population.

BACKGROUND: Ischemic stroke (IS) is a serious global health burden. In order to improve our understanding of the risk factors associated with IS, we investigated the combined effect of the methylation of five genes related to the metabolism of homocysteine on developing IS. METHODS: Quantitative methylation-specific PCR was used to measure the levels of promoter methylation in hypertensive and stroke patients. The cutoff value calculated by the maximum Youden index was used to classify the levels of gene methylation as hypomethylation and hypermethylation. Logistic regression was used to explore the relationship between gene methylation and IS. RESULTS: The methylation levels of the genes encoding methylenetetrahydrofolate dehydrogenase 1 [MTHFD1], cystathionine ß-synthase [CBS], and dihydrofolate reductase [DHFR] in hypertensive patients were higher than those in stroke patients (all p < 0.01). MTHFD1 hypermethylation, CBS hypermethylation, and DHFR hypermethylation were protective factors for stroke after adjustment for confounding factors. Compared with individuals carrying none of the biomarkers, the ORs [95% CIs] for stroke of those with 1 and 2 elevated biomarkers were 4.068 [1.670-9.913] and 15.345 [6.198-37.994] after adjustment for confounding factors. The participants with a larger number of biomarkers had an increased risk of stroke (p for trend <0.001). For the combination biomarkers, the area under the curve of the receiver operating characteristic was 0.716. CONCLUSION: A significant linear relationship between the number of elevated biomarkers and the risk of stroke has been observed, suggesting that elevations of these biomarkers could be used for potentially predicting the disease.

Intra-Molecular Homologous Recombination of Scarless Plasmid.

Although many methods have been reported, plasmid construction compromises transformant efficiency (number of transformants per ng of DNAs) with plasmid accuracy (rate of scarless plasmids). An efficient method is two-step PCR serving DNA amplification. An accurate method is ExnaseII cloning serving homology recombination (HR). We combine DNA amplification and HR to develop an intra-molecular HR by amplifying plasmid DNAs to contain homology 5'- and 3'-terminus and recombining the plasmid DNAs in vitro. An example was to construct plasmid pET20b-AdD. The generality was checked by constructing plasmid pET21a-AdD and pET22b-AdD in parallel. The DNAs having 30-bp homology arms were optimal for intra-molecular HR, and transformation of which created 14.2 transformants/ng and 90% scarless plasmids, more than the two-step PCR and the ExnaseII cloning. Transformant efficiency correlated with the component of nicked circular plasmid DNAs of HR products, indicating nick modification in vivo leads to scar plasmids.

Effects of berberine on blood glucose in patients with type 2 diabetes mellitus: a systematic literature review and a meta-analysis.

We conducted a systematic review and meta-analysis to evaluate the effect of Berberine on glucose in patients with type 2 diabetes mellitus and identify potential factors may modifying the hypoglycemic effect. We searched PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database to identify randomized controlled trials that investigated the effect of Berberine. We calculated weighted mean differences (WMD) and 95% confidence interval (CI) for fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and glycated haemoglobin (HbA1c) levels. Twenty-eight studies were identified for analysis, with a total of 2,313 type 2 diabetes mellitus (T2DM) patients. The pool data showed that Berberine treatment was associated with a better reduction on FPG (WMD = -0.54 mmol/L, 95% CI: -0.77 to -0.30), PPG (WMD = -0.94 mmol/L, 95% CI: -1.27 to -0.61), and HbA1c (WMD = -0.54 mmol/L, 95% CI: -0.93 to -0.15) than control groups. Subgroup-analyses indicated that effects of Berberine on blood glucose became unremarkable as the treatment lasted more than 90 days, the daily dosage more than 2 g/d and patients aged more than 60 years. The efficiency of Berberine combined with hypoglycaemics is better than either Berberine or hypoglycaemic alone. The dosage and treatment duration of Berberine and patients' age may modify the effect.

MiR-18a and miR-17 are positively correlated with circulating PD-1+ICOS+ follicular helper T cells after hepatitis B vaccination in a chinese population.

BACKGROUND: While vaccination remains the most effective method to control hepatitis B virus (HBV) infection, 5-10% of recipients exhibit non-responsiveness to the HB vaccine. Immunological analysis of strong, weak or absent protective antibody responses to the HB vaccine should provide insights into the mechanisms that contribute to non-responsiveness. RESULTS: We investigated the potential involvement of follicular helper T (Tfh) cells in the immune response to HB vaccine, and associations between the miR-17-92 cluster and Tfh cells. We recruited 12 adults who had completed the HB vaccination course during childhood. Following a booster dose of HB vaccine, hepatitis B surface antibody (HBsAb) titers, percentage of PD-1+ICOS+ circulating Tfh (cTfh) and plasma cells, and expression of miR-17-92 were assessed at baseline (before immunization) and after vaccination on days 7 and 14. Notably, the HBsAb level gradually increased after HB vaccination while the proportion of PD-1+ICOS+ cTfh cells was significantly increased on day 7 relative to baseline, so as plasma cells. Expression of miR-18a and miR-17 within the miR-17-92 cluster and HBsAb titers in CD4+ T cells were positively correlated with the PD-1+ICOS+ cTfh cells proportions after HB vaccination. CONCLUSIONS: The increase in HBsAb titers was positively associated with expression of all the components of the miR-17-92 cluster except miR-19a. Our findings indicate that the miR-17-92 cluster contributes to antibody production, and miR-18a and miR-17 are involved in Tfh cells differentiation after HB vaccination.

Arabidopsis glutamate:glyoxylate aminotransferase 1 (Ler) mutants generated by CRISPR/Cas9 and their characteristics.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (CRISPR/Cas9) technology provides an efficient tool for editing the genomes of plants, animals and microorganisms. Glutamate:glyoxylate aminotransferase 1 (GGAT1) is a key enzyme in the photorespiration pathway; however, its regulation mechanism is largely unknown. Given that EMS-mutagenized ggat1 (Col-0 background) M2 pools have been generated, ggat1 (Ler background) should be very useful in the positional cloning of suppressor and/or enhancer genes of GGAT1. Unfortunately, such ggat1 (Ler) mutants are not currently available. In this study, CRISPR/Cas9 was used to generate ggat1 (Ler) mutants. Two GGAT1 target single-guide RNAs (sgRNAs) were constructed into pYLCRISPR/Cas9P35S-N, and flowering Arabidopsis (Ler) plants were transformed using an Agrobacterium tumefaciens-mediated floral dip protocol. Eleven chimeric and two heterozygous GGAT1-edited T1 lines of target 1 were separately screened from positive transgenic lines. Two ggat1 homozygous mutants, CTC-deletion and T-deletion at target 1, were generated from T2 generations of the 13 T1 lines. The edited mutation sites were found to be stable through generations regardless of whether the T-DNA was present. In addition, the genetic segregation of the mutation sites obeyed the Mendelian single gene segregation rule, and no mutations were detected at the possible off-target site. Also, the two independent ggat1 mutants had similar photorespiration phenotypes and down-regulated GGAT enzyme activity. Together, these results indicate that genetically stable ggat1 (Ler) mutants were generated by CRISPR/Cas9 genome editing, and these mutants will be used to promote the positional cloning of suppressor and/or enhancer genes of GGAT1 in our subsequent study.

A more comprehensive investigation of disability and associated factors among older adults receiving home-based care in rural Dongguan, China.

BACKGROUND: No previous study has evaluated disability in older persons according to the International Classification of Functioning, Disability and Health Framework guidelines. We conducted a more comprehensive investigation of disability and associated factors among older adults receiving home-based care in rural Dongguan, a city in the central Guangdong Province of Southern China. METHODS: A total of 819 individuals aged ≥60 years were recruited from Dongguan home-based care system of via a two-stage selection process. We interviewed participants and assessed their ability level using the Ability Assessment for Older Adults, which defined by a combination of activity of daily living, sensory perception, mental status and social involvement. Conditional probability and Logistic regression approaches were used to assess the strength of association between each pair of conditions. Factors significantly associated with disability were identified via χ2 tests and multinomial ordinal logistic regression. RESULTS: Of the 819 included participants (mean age 87 ±4.7 years), 75.5% were female, 76.7% had any disability, and 62.3% had a mild disability. The occurrence of any deficits significantly increased the likelihood of the co-occurrence of other deficits (odds ratio [OR] > 1, P < 0.05), with the lowest prevalence odds ratio observed among individuals with sensory and communication deficiency (OR: 2.99; 95% confidence interval [CI]: 2.21-4.05). Multivariable ordinal logistic regression analysis indicated that physical activity (OR: 0.96; 95% CI: 0.93-0.99), sedentary behavior (OR: 1.25; 95% CI: 1.13-1.38), not watching television (OR: 1.7; 95% CI: 1.07-2.72) and age (OR: 1.09; 95% CI: 1.02-1.17) were significantly associated with disability. CONCLUSIONS: Impairment of ADL, sensory perception, mental status or social involvement increased the likelihood of risk of the co-occurrence of other deficits. Comprehensive disability among older adults receiving home-based care is associated with age, sedentariness, physical activity and TV viewing.

[Risk assessment of different grades of hypertension during the treatment of patients with acute pulpitis].

OBJECTIVE: To evaluate the vital signs changes, influence factors in different grades of hypertension patients during the treatment of acute pulpitis, in order to obtain the risk prevention measures. METHODS: In this study, 90 different grades of hypertension patients with acute pulpitis were recruited from February 2014 to February 2015 in the Department of Oral Emergency, Peking University School and Hospital of Stomatology. The information about the patients'general health, oral treatment, life signs of change information was collected. Patients were divided into high risk group, middle risk group, and low risk group (30 patients for each group). RESULTS: (1) Compared with the preoperative, systolic blood pressure (90%), diastolic blood pressure (80%), heart rate increase (100%) were increased in the high risk group. The increase rates of the middle risk group and the low risk group were significantly lower than those of the high risk group (P<0.01). At the same time, the systolic blood pressure of 1/4 (26.7%) patients in high risk group increased more than 20 mmHg (1 mmHg=0.133 kPa), and the diastolic blood pressure of 2/5 patients in high risk group increased more than 10 mmHg, the difference was statistically significant compared with the other two groups (P<0.05). (2) Compared with the preoperative, the average increase of the maximum peak were increased [systolic blood pressure (18.0 ± 1.5) mmHg, diastolic blood pressure (8.0 ± 1.7) mmHg], the mean of heart rate changes [(7.0 ± 0.3) beats per minute] was also increased in the high risk group, while these two indicators were decreased in the low risk group and the middle risk group. The electrocardiogram (ECG) was changed in 6 cases during the treatment in the high risk group. No significantly changed were observed in the low risk group and the middle risk group. (3) Compared the risk assessment in preoperative with that in postoperative, in the middle risk group, 23 cases were evaluated as medium risk in final evaluation, 6 as low risk, and 1 as high risk (risk assessment increased); in the high risk group, 20 cases were evaluated as high risk, 7 as very high risk, and 3 as medium risk (risk assessment decreased). CONCLUSION: Oral treatment is very safe for patients with hypertension, but the risk factor, target organ damage, and complications will also increase the risk of cardiovascular events in elderly patients during the acute pulpitis treatment. Dentist should take some measures to avoid the risks.

Inhibitory Effects of Amorphigenin on the Mitochondrial Complex I of Culex pipiens pallens Coquillett (Diptera: Culicidae).

Previous studies in our laboratory found that the extract from seeds of Amorpha fruticosa in the Leguminosae family had lethal effects against mosquito larvae, and an insecticidal compound amorphigenin was isolated. In this study, the inhibitory effects of amorphigenin against the mitochondrial complex I of Culex pipiens pallens (Diptera: Culicidae) were investigated and compared with that of rotenone. The results showed that amorphigenin and rotenone can decrease the mitochondrial complex I activity both in vivo and in vitro as the in vivo IC50 values (the inhibitor concentrations leading to 50% of the enzyme activity lost) were determined to be 2.4329 and 2.5232 µmol/L, respectively, while the in vitro IC50 values were 2.8592 and 3.1375 µmol/L, respectively. Both amorphigenin and rotenone were shown to be reversible and mixed-I type inhibitors of the mitochondrial complex I of Cx. pipiens pallens, indicating that amorphigenin and rotenone inhibited the enzyme activity not only by binding with the free enzyme but also with the enzyme-substrate complex, and the values of KI and KIS for amorphigenin were determined to be 20.58 and 87.55 µM, respectively, while the values for rotenone were 14.04 and 69.23 µM, respectively.

Toxicity of amorphigenin from the seeds of Amorpha fruticosa against the larvae of Culex pipiens pallens (Diptera: Culicidae).

The larvicidal activity of the crude petroleum ether, ethyl acetate, acetone, chloroform and ethanol extracts of Amorpha fruticosa seeds was individually assayed for toxicity against the early fourth-instar larva of the mosquito, Culex pipiens pallens after 24 h exposure. Of the tested extracts, the ethanol one exhibited the highest larvicidal activity (LC50 = 22.69 mg/L). Amorphigenin (8'-hydroxyrotenone), a rotenoid compound which exhibits a strong larvicidal activity with LC50 and LC90 values of 4.29 and 11.27 mg/L, respectively, was isolated from the ethanol extract by column chromatograpy. Its structure was elucidated by 1H-NMR, UV and IR spectral data. Furthermore, investigation of amorphigenin's effects on mitochondrial complex I activity and protein synthesis in C. pipiens pallens larvae reveals that amorphigenin decreases mitochondrial complex I activities to 65.73% at 10.45 µmol/L, compared to the control, when NADH were used as the substrate. Meanwhile, amorphigenin at 10.45 µmol/L also caused a 1.98-fold decrease in protein content, compared to the control larvae treated with acetone only.

Treatment of primary chronic glomerulonephritis with Rehmannia glutinosa acteosides in combination with the angiotensin receptor blocker irbesartan: a randomized controlled trial.

This study aims to assess the efficacy and safety of Rehmannia glutinosa acteosides used in combination with the angiotensin receptor blocker irbesartan to treat primary chronic glomerulonephritis. A total of 479 patients diagnosed with primary chronic glomerulonephritis were recruited from outpatient clinics and were randomly assigned to the treatment group (Rehmannia glutinosa acteosides, two 200-mg capsules, bid; and irbesartan, one 150-mg tablet, qd) or the control group (irbesartan, one 150-mg tablet, qd). The primary outcome was 24-h urinary protein. Secondary outcome measures included blood pressure, estimated glomerular filtration rate, erythrocyturia, serum alanine aminotransferase, aspartate transaminase and electrolytes. After 8 weeks of treatment, the treatment group showed a mean reduction in 24-h proteinuria of 36.42% compared to baseline, which was significantly higher than the mean reduction from baseline of 27.97% in the control group (P = 0.0278).Adverse drug reactions occurred at a similarly low rate in the treatment group (0.4%) and control group (1.2%, P = 0.3724). In the treatment of chronic glomerulonephritis, the combination of Rehmannia glutinosa acteosides and irbesartan can reduce proteinuria more effectively than irbesartan alone.

A case of focal segmental glomerulosclerosis syndrome secondary to high-altitude polycythemia.

In recent years, focal segmental glomerulosclerosis has become the commonest cause of the nephrotic syndrome seen in adults. Secondary focal segmental glomerulosclerosis is observed when glomerular workload is increased. We report a case of focal segmental glomerulosclerosis with nephrotic syndrome secondary to high-altitude polycythemia (HAPC). Our case points out that for patients with focal segmental glomerulosclerosis, who presented with nephrotic syndrome secondary to HAPC, treatments for HAPC are crucial for the reduction of proteinuria and renal protection instead of glucocorticoid and immunosuppressive drugs.

Chronic toxicity of broflanilide in Daphnia magna: changes in molting, behavior, and gene expression.

Broflanilide is a novel pesticide used in agriculture that binds to unique receptors on pests; however, the widespread use of broflanilide has led to toxicity in Daphnia magna. At present, little information on the potential threats broflanilide imposes on D. magna is available. Therefore, the present study examined the chronic toxicity of broflanilide in D. magna by comparing changes in molting, neurotransmitter function, and behavior. The results showed that broflanilide caused chronic toxicity in D. magna at a concentration of 8.45 µg/L, and growth, development, reproduction, and the development of offspring were affected. In addition, broflanilide affected the molting of D. magna by significantly inhibiting the expression of chitinase, ecdysteroid, and related genes. Broflanilide also affected the expression of γ-glutamic acid, glutamine, gamma-aminobutyric acid, 5-hydroxytryptamine, 5-hydroxytryptophan, dopa, and dopamine. Furthermore, the swimming distance and speed of D. magna were reduced. Taken together, the results demonstrate the chronic toxicity and exposure risk of broflanilide in D. magna.

Microplitis bicoloratus Bracovirus Promotes Cyclophilin D-Acetylation at Lysine 125 That Correlates with Apoptosis during Insect Immunosuppression.

Cyclophilin D (CypD) is regulated during the innate immune response of insects. However, the mechanism by which CypD is activated under innate immunosuppression is not understood. Microplitis bicoloratus bracovirus (MbBV), a symbiotic virus in the parasitoid wasp, Microplitis bicoloratus, suppresses innate immunity in parasitized Spodoptera litura. Here, we demonstrate that MbBV promotes the CypD acetylation of S. litura, resulting in an immunosuppressive phenotype characterized by increased apoptosis of hemocytes and MbBV-infected cells. Under MbBV infection, the inhibition of CypD acetylation significantly rescued the apoptotic cells induced by MbBV, and the point-mutant fusion proteins of CypDK125R-V5 were deacetylated. The CypD-V5 fusion proteins were acetylated in MbBV-infected cells. Deacetylation of CypDK125R-V5 can also suppress the MbBV-induced increase in apoptosis. These results indicate that CypD is involved in the MbBV-suppressed innate immune response via the CypD-acetylation pathway and S. litura CypD is acetylated on K125.

Feasibility of Two-Screw Anterior Fixation for Odontoid Fractures in a Chinese Population: A Morphometric Study Based on Computed Tomography.

Background: To evaluate the feasibility of treating odontoid fractures in the Chinese population with two cortical screws based on computed tomography (CT) scans and describe a new measurement strategy to guide screw insertion in treating these fractures. Methods: A retrospective review of cervical computed tomographic scans of 128 patients (aged 18-76 years; men, 55 [43.0%]) was performed. The minimum external transverse diameter (METD), minimum external anteroposterior diameter (MEAD), maximum screw length (MSL), and screw projection back angle (SPBA) of the odontoid process were measured on coronal and sagittal CT images. Results: The mean values of METD and MEAD were 10.0 ± 1.1 mm and 12.0 ± 1.0 mm, respectively, in men and 9.2 ± 1.0 mm and 11.0 ± 1.0 mm, respectively, in women. Both measurements were significantly higher in men (p < 0.001). In total, 87 individuals (68%) had METD > 9.0 mm that could accommodate two 3.5-mm cortical screws. The mean MSL value and SPBA range were 34.4 ± 2.9 mm and 13.5°-24.2°, respectively, with no statistically significant difference between men and women. Conclusions: The insertion of two 3.5-mm cortical screws was possible for anterior fixation of odontoid fractures in 87 patients (68%) in our study, and there was a statistically significant difference between men and women.

Synergistic Enhancement of Isoforskolin and Dexamethasone Against Sepsis and Acute Lung Injury Mouse Models.

Background: Sepsis is initiated by the dysfunctional response of the host immune system to infection. Septic shock and acute lung injury (ALI) are the main etiology of death caused by sepsis. Glucocorticoids, which are commonly used in clinic to antagonize the inflammatory response of sepsis, may cause serious side effects. Isoforskolin (ISOF) from the plant Coleus forskohlii stimulates adenylyl cyclase, increases the cAMP level and inhibits inflammatory response. The aim of this study was to investigate the synergistic effect of ISOF with dexamethasone (DEX) to prevent and ameliorate septic inflammation. Methods: Lipopolysaccharide (LPS) of 30 and 5 mg/kg (iv.) was used to induce sepsis and ALI mice model respectively in vivo. BEAS-2B cells stimulated by LPS were applied as cell model in vitro. The cumulative survival of mice with LPS-induced sepsis and the histopathological changes of lungs in mice with acute lung injury were observed, and the secretion of pro-inflammatory cytokines was analyzed by ELISA. The expression of RGS2 in BEAS-2B cells was detected by immunoblotting assay and PCR. Results: In the sepsis mice model, ISOF (10 mg/kg) combined with DEX (10 mg/kg.) (ip.) pretreatment significantly increased mice survival rate from 33.3% to 58.3%, which was significantly higher than that of ISOF or DEX treated alone. In the ALI mice model, ISOF, DEX pretreatment alone and combined application attenuated pulmonary pathological changes in ALI mice. Furthermore, ISOF, DEX alone or combined administration decreased MPO, MDA, IL-6, and IL-8 levels, while significantly synergistic effects were observed in the combined treatment group compared with ISOF or DEX alone. In BEAS-2B cells, combined pretreatment with ISOF and DEX significantly decreased the expression of IL-8 and increased the expression of RGS2. Conclusion: The results indicated that ISOF in combination with DEX synergistically improves survival rate and attenuates ALI in mice model through anti-inflammatory and antioxidant effects.

Transcriptomic analysis of OsRUS1 overexpression rice lines with rapid and dynamic leaf rolling morphology.

Moderate leaf rolling helps to form the ideotype of rice. In this study, six independent OsRUS1-GFP overexpression (OsRUS1-OX) transgenic rice lines with rapid and dynamic leaf rolling phenotype in response to sunlight were constructed. However, the mechanism is unknown. Here, RNA-Seq approach was utilized to identify differentially expressed genes between flag leaves of OsRUS1-OX and wildtype under sunlight. 2920 genes were differentially expressed between OsRUS1-OX and WT, of which 1660 upregulated and 1260 downregulated. Six of the 16 genes in GO: 0009415 (response to water stimulus) were significantly upregulated in OsRUS1-OX. The differentially expressed genes between WT and OsRUS1-OX were assigned to 110 KEGG pathways. 42 of the 222 genes in KEGG pathway dosa04075 (Plant hormone signal transduction) were differentially expressed between WT and OsRUS1-OX. The identified genes in GO:0009415 and KEGG pathway dosa04075 were good candidates to explain the leaf rolling phenotype of OsRUS1-OX. The expression patterns of the 15 genes identified by RNA-Seq were verified by qRT-PCR. Based on transcriptomic and qRT-PCR analysis, a mechanism for the leaf rolling phenotype of OsRUS1-OX was proposed. The differential expression profiles between WT and OsRUS1-OX established by this study provide important insights into the molecular mechanism behind the leaf rolling phenotype of OsRUS1-OX.

Repeated Winning and Losing Experiences in Chronic Social Conflicts Are Linked to RNA Editing Pattern Difference.

Winner-loser effects influence subsequent agonistic interactions between conspecifics. Previous winning experiences could strengthen future aggression and increase the chance of winning the next agonistic interaction, while previous losing experiences could have the opposite effect. Although the role of A-to-I RNA editing has been recently implicated in chronic social defeat stress and aggressive behavior, it remains to be further elucidated in chronic social conflicts in agonistic interactions, especially in the repeated aggression (winners) and repeated defeat (losers) resulted from these conflicts. In the current study, transcriptome-wide A-to-I RNA editing in the dorsal striatum was investigated in a mouse model of chronic social conflicts, and compared between mice repeatedly winning and losing daily agonistic interactions. Our analysis identified 622 A-to-I RNA editing sites in the mouse dorsal striatum, with 23 to be differentially edited in 22 genes, most of which had been previously associated with neurological, psychiatric, or immune disorders. Among these differential RNA editing (DRE) sites four missense variants were observed in neuroligin 2 (Nlgn2), Cdc42 guanine nucleotide exchange factor 9 (Arhgef9) BLCAP apoptosis inducing factor (Blcap), and cytoplasmic FMR1 interacting protein 2 (Cyfip2), as well as two noncoding RNA sites in small nucleolar RNA host gene 11 (Snhg11) and the maternally expressed 3 (Meg3) gene. Moreover, significant changes were observed in gene functions and pathways enriched by genes with A-to-I RNA editing in losers and especially winners compared to controls. Our results demonstrate that repeated winning and losing experiences in chronic social conflicts are linked to A-to-I RNA editing pattern difference, underlining its role in the molecular mechanism of agonistic interactions between conspecifics.