Spatially resolved visualization of reprogrammed metabolism in hepatocellular carcinoma by mass spectrometry imaging.

BACKGROUND: Metabolic reprogramming refers to tumor-associated metabolic alterations during tumorigenesis and has been regarded as one of the most important features of cancer. Profiling the altered metabolites and lipids in hepatocellular carcinoma with spatial signature will not only enhance our understanding of tumor metabolic reprogramming, but also offer potential metabolic liabilities that might be exploited for hepatocellular carcinoma therapy. METHODS: We perform matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) analysis on both hepatocellular carcinoma xenograft mouse model and hepatocellular carcinoma patients. Discriminatory metabolites that altered during the development of hepatocellular carcinoma are screened and imaged in xenograft mouse model and are further validated in 21 hepatocellular carcinoma patients. RESULTS: We discover stepwise metabolic alterations and progressively increasing metabolic heterogeneity during the growth of hepatocellular carcinoma. Arginine and its metabolites spermine and spermidine, choline and phosphatidylcholine metabolism, and fatty acids were found to be significantly reprogrammed in hepatocellular carcinoma tissues. CONCLUSIONS: The spatially resolved profiling of the metabolites and lipids in highly heterogeneous hepatocellular carcinoma tissue will contribute to obtaining precise metabolic information for the understanding of tumor metabolic reprogramming.

Transfer RNA halves are found as nicked tRNAs in cells: evidence that nicked tRNAs regulate expression of an RNA repair operon.

Transfer RNA fragments are proposed to regulate numerous processes in eukaryotes, including translation inhibition, epigenetic inheritance, and cancer. In the bacterium Salmonella enterica serovar Typhimurium, 5' tRNA halves ending in 2',3' cyclic phosphate are proposed to bind the RtcR transcriptional activator, resulting in transcription of an RNA repair operon. However, since 5' and 3' tRNA halves can remain base paired after cleavage, the 5' tRNA halves could potentially bind RtcR as nicked tRNAs. Here we report that nicked tRNAs are ligands for RtcR. By isolating RNA from bacteria under conditions that preserve base pairing, we show that many tRNA halves are in the form of nicked tRNAs. Using a circularly permuted tRNA that mimics a nicked tRNA, we show that nicked tRNA ending in 2',3' cyclic phosphate is a better ligand for RtcR than the corresponding 5' tRNA half. In human cells, we show that some tRNA halves similarly remain base paired as nicked tRNAs following cleavage by anticodon nucleases. Our work supports a role for the RNA repair operon in repairing nicked tRNAs and has implications for the functions proposed for tRNA fragments in eukaryotes.

A Cytological Atlas of the Human Liver Proteome from PROTEOMESKY-LIVERHu 2.0, a Publicly Available Database.

The liver plays a unique role as a metabolic center of the body, and also performs other important functions such as detoxification and immune response. Here, we establish a cell type-resolved healthy human liver proteome including hepatocytes (HCs), hepatic stellate cells (HSCs), Kupffer cells (KCs), and liver sinusoidal endothelial cells (LSECs) by high-resolution mass spectrometry. Overall, we quantify total 8354 proteins for four cell types and over 6000 proteins for each cell type. Analysis of this data set and regulatory pathway reveals the cellular labor division in the human liver follows the pattern that parenchymal cells make the main components of pathways, but nonparenchymal cells trigger these pathways. Human liver cells show some novel molecular features: HCs maintain KCs and LSECs homeostasis by producing cholesterol and ketone bodies; HSCs participate in xenobiotics metabolism as an agent deliverer; KCs and LSECs mediate immune response through MHC class II-TLRs and MHC class I-TGFß cascade, respectively; and KCs play a central role in diurnal rhythms regulation through sensing diurnal IGF and temperature flux. Together, this work expands our understandings of liver physiology and provides a useful resource for future analyses of normal and diseased livers.

Effect of circRNA_FOXO3 rs12196996 polymorphism and FOXO3 rs2232365 polymorphism on survival rate and severity of intensive care unit-acquired sepsis.

The expression of circRNA_FOXO3 was found to be positively associated with the expression of Forkhead Box O3 (FOXO3), which is targeted and regulated by miR-23a. Polymorphisms in rs12196996 and rs2232365 have been reported in various diseases. In this study, we recruited intensive care unit (ICU)-acquired sepsis patients and grouped them according to their genotypes of rs12196996 and rs2232365. Quantitative real-time PCR was performed to analyze the expression of circRNA_FOXO3, FOXO3 mRNA, and miR-23a. ELISA was carried out to evaluate the abundance of cytokines and luciferase assay was used to explore the inhibitory role of miR-23a on circRNA_FOXO3 and FOXO3. Accordingly, we found that rs12196996 GG and rs2232365 AA were significantly correlated with prolonged survival of ICU-acquired sepsis patients. Rs12196996 GG and rs2232365 AA were also correlated with increased level of miR-23a, IL-10 and decreased level of TNF, IL-2, IFN, IL-6 and IL-1ß in the peripheral blood cell samples of patients with ICU-acquired sepsis. The luciferase activity of wild-type (WT) circRNA_FOXO3 and FOXO3 were severely reduced by miR-23a. MiR-23a precursors could effectively suppress the expression of circRNA_FOXO3 and FOXO3 in the cells. Moreover, LPS-induced cell viability loss and dysregulation of cytokines were effectively restored by the knockdown of FOXO3 or circRNA_FOXO3 siRNA in the cells. This study revealed that the minor allele of rs12196996 polymorphism and rs2232365 polymorphism collaboratively contributed to the increased survival and suppressed severity of ICU-acquired sepsis.

The Efficacy of Memantine for the Treatment of Migraine: A Meta-Analysis of Randomized Controlled Studies.

INTRODUCTION: The efficacy of memantine for migraine remains controversial. We conduct a systematic review and meta-analysis to explore the influence of memantine versus placebo on treatment in migraine patients. METHODS: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through February 2020 for randomized controlled trials assessing the effect of memantine versus placebo on treatment efficacy in migraine patients. This meta-analysis is performed using the random-effect model. RESULTS: Three randomized controlled trials are included in the meta-analysis. Overall, compared with control group in migraine patients, memantine treatment is associated with substantially reduced monthly attack frequency (mean difference [MD], -2.14; 95% confidence interval [CI], -2.83 to -1.46; P < 0.00001), number of migraine days (MD, -4.17; 95% CI, -6.40 to -1.93; P = 0.0003) and Migraine Disability Assessment (MD, -5.63; 95% CI, -6.46 to -4.79; P < 0.00001), but demonstrates no obvious influence on acute pain medications (MD, -1.23; 95% CI, -4.63 to 2.17; P = 0.48). CONCLUSIONS: Memantine treatment may benefit to the control of migraine.

Optimizing biochar application to improve soil physical and hydraulic properties in saline-alkali soils.

Biochar application has been a promising approach to improve soil quality but their optimal amount in improving physical and hydraulic properties remains contradictory and inconclusive. The objective of this study was to examine and propose an optimal biochar application amount in saline alkali soil considering their impact on soil physical and hydraulic properties. A three-year field experiment was conducted in the saline-alkali soils under plastic film-mulched drip irrigation in Xinjiang, China. The studied physical and hydraulic properties included bulk density, soil porosity, saturated soil water content (θs), permanent wilting point (PWP), field capacity (FC), plant available water (PAW), spatial distribution of soil water content, planar soil water storage (PSWS), and soil evaporation. The treatments included biochar application amounts of 0 (CK), 10 (B10), 50 (B50), and 100 t ha-1 (B100) in 2018. Additional two treatments with 25 t ha-1 (B25) and 30 t ha-1 (B30) were added in 2019 and 2020, respectively. A four-parameter Gaussian function was fitted to the single-peak curves of the studied hydraulic properties vs. biochar application amounts to determine the most optimal biochar application amount. The results indicated that: (1) All of the biochar treatments significantly decreased bulk density and increased soil porosity over CK; (2) B10 and B25 treatments significantly increased θs, FC, PAW, PWP, and PSWS of root zones in the film-mulched zones over CK, but reverse results were observed in the B50 and B100 treatments; (3) Daily and cumulative soil evaporation were increased in no mulch zones of all biochar treatments over CK; (4) A dose of 21.9 t ha-1 was recommended as the most optimal biochar application amount for improving physical and hydraulic properties of saline-alkali soil. This research provided useful information on biochar application amounts for improving physical and hydraulic properties in saline-alkali soil.

Monitoring responses of vegetation phenology and productivity to extreme climatic conditions using remote sensing across different sub-regions of China.

Drought is a major natural disaster that significantly impacts the susceptibility and flexibility of the ecosystem by changing vegetation phenology and productivity. This study aimed to investigate the impact of extreme climatic variation on vegetation phenology and productivity over the four sub-regions of China from 2000 to 2017. Daily rain gauge precipitation and air temperature datasets were used to estimate the trends, and to compute the standardized precipitation-evapotranspiration index (SPEI). Remote sensing-based Enhanced Vegetation Index (EVI) data from a moderate resolution imaging spectroradiometer (MODIS) was used to characterize vegetation phenology. The results revealed that (1) air temperature had significant increasing trends (P < 0.05) in all sub-regions. Precipitation showed a non-significant increasing trend in Northwest China (NWC) and insignificant decreasing trends in North China (NC), Qinghai Tibet area (QTA), and South China (SC). (2) Integrated enhanced vegetation index (iEVI) and SPEI variations depicted that 2011 and 2016 were the extremely driest and wettest years during 2000-2017. (3) Rapid changes were observed in the vegetation phenology and productivity between 2011 and 2016. In 2011, changes in the vegetation phenology with the length of the growing season (ΔLGS) = was - 14 ± 36 days. In 2016, the overall net effect changed at the onset and end of the growing season with ΔLGS of 34 ± 71 days. The change in iEVI per SPEI increased rapidly with a changing rate of 0.16 from arid (NWC, and QTA) to semi-arid (NWC, QTA and NC) and declined with a rate of - 0.04 from semi-humid (QTA, NC, and SC) to humid (SC) region. A higher association was observed between iEVI and SPEI as compared to iEVI and precipitation. Our finding exposed that north China is more sensitive to climatic variation.

Performance and relationship of four different agricultural drought indices for drought monitoring in China's mainland using remote sensing data.

Increasing frequency and intensity of extreme drought events have harmed the environment, ecosystem, and agricultural productivity. However, the characteristics of agricultural drought in China have not been well understood. The remote sensing (RS) based gridded monthly precipitation, soil moisture, land surface temperature (LST), and normalized difference vegetation index (NDVI) datasets over 1982-2018 were utilized to derive standardized precipitation index (SPI), standardized soil moisture index (SSI), multivariate standardized drought index (MSDI), and vegetation health index (VHI). The variation patterns and trends of SPI, SSI, and MSDI at the 1-, 3-, and 6-month timescales against monthly VHI anomaly were compared to identify the best agricultural drought index in China. The drought variations in the four sub-regions (northwest, north, Qinghai-Tibet area, and south area) were also investigated. The results showed that: (1) Temporal patterns of VHI anomaly were similar to relative soil moisture and slightly different from precipitation. The spatial patterns of MSDI matched with VHI the best than SPI and SSI. (2) All three indices showed positive correlations with VHI at the three timescales. The highest correlation coefficients (r) between MSDI and VHI ranged from 0.25 to 0.67, 0.22 to 0.78, 0.23 to 0.69, and 0.19 to 0.74 in northwest China, north China, Qinghai-Tibet Plateau, and south China, respectively. (3) The connections between monthly VHI and the three drought indices were weaker at the 1-month timescale (0.16 < r < 0.25) than the 3-month (0.39 < r < 0.78) and 6-month (0.26 < r < 0.68) timescales. (4) The VHI significantly increased in most of China except north China. Overall, MSDI showed better performance for monitoring agricultural drought in China's mainland.

An RNA Repair Operon Regulated by Damaged tRNAs.

Many bacteria contain an RNA repair operon, encoding the RtcB RNA ligase and the RtcA RNA cyclase, that is regulated by the RtcR transcriptional activator. Although RtcR contains a divergent version of the CARF (CRISPR-associated Rossman fold) oligonucleotide-binding regulatory domain, both the specific signal that regulates operon expression and the substrates of the encoded enzymes are unknown. We report that tRNA fragments activate operon expression. Using a genetic screen in Salmonella enterica serovar Typhimurium, we find that the operon is expressed in the presence of mutations that cause tRNA fragments to accumulate. RtcA, which converts RNA phosphate ends to 2', 3'-cyclic phosphate, is also required. Operon expression and tRNA fragment accumulation also occur upon DNA damage. The CARF domain binds 5' tRNA fragments ending in cyclic phosphate, and RtcR oligomerizes upon binding these ligands, a prerequisite for operon activation. Our studies reveal a signaling pathway involving broken tRNAs and implicate the operon in tRNA repair.

Metallophosphoesterase 1, a novel candidate gene in hepatocellular carcinoma malignancy and recurrence.

BACKGROUND: There is an unmet need to identify novel mechanism-based prognostic genes associated with hepatocellular carcinoma (HCC) recurrence that can predict patient outcomes and provide therapeutic targets. This study aims to identify potential novel driver genes and mutations in HCC. METHODS: Single nucleotide variations (SNVs) contributing to HCC recurrence were identified using whole-exome sequencing of 5 DNA samples extracted from a single HCC patient with HBV-induced cirrhosis. SNVs were verified in primary HCC (n = 87), recurrent HCC (n = 34), and benign liver disease with cirrhosis tissues (n = 43). A candidate gene was identified, and its association and function in HCC development and recurrence were examined. RESULTS: 177 SNVs were identified and 70 SNVs were verified. A MPPE1 missense mutation on chr18_11897016 was the most frequent mutation (16.5%) in primary and recurrent HCC tissues, occurring with a higher frequency in recurrent HCC than primary HCC or benign liver tumor tissues. The MPPE1 mutation was significantly associated with HCC recurrence (P = .003), TNM stage (P = .002), and Child-Pugh classification (P = .039), and was an independent risk factor for HCC recurrence (HR = 1.969; 95%CI = 1.043-3.714, P = .037). Analysis of publically available data deposited in the GEO and TCGA showed MPPE1 expression levels were significantly increased in HCC tumor samples compared to adjacent nontumor tissues. The knockdown of MPPE1 in HCC cell lines significantly inhibited cell proliferation, migration and invasion, induced cell cycle arrest and apoptosis in vitro, and inhibited xenograft tumor growth in nude mice in vivo (P < .05). CONCLUSIONS: MPPE1 is a novel gene associated with HCC malignancy and recurrence.

The Bacterial Ro60 Protein and Its Noncoding Y RNA Regulators.

Ro60 ribonucleoproteins (RNPs), composed of the ring-shaped Ro 60-kDa (Ro60) protein and noncoding RNAs called Y RNAs, are present in all three domains of life. Ro60 was first described as an autoantigen in patients with rheumatic disease, and Ro60 orthologs have been identified in 3% to 5% of bacterial genomes, spanning the majority of phyla. Their functions have been characterized primarily in Deinococcus radiodurans, the first sequenced bacterium with a recognizable ortholog. In D. radiodurans, the Ro60 ortholog enhances the ability of 3'-to-5' exoribonucleases to degrade structured RNA during several forms of environmental stress. Y RNAs are regulators that inhibit or allow the interactions of Ro60 with other proteins and RNAs. Studies of Ro60 RNPs in other bacteria hint at additional functions, since the most conserved Y RNA contains a domain that is a close tRNA mimic and Ro60 RNPs are often encoded adjacent to components of RNA repair systems.

Drought evolution indicated by meteorological and remote-sensing drought indices under different land cover types in China.

Remote sensing freely provides many processed image products such as moderate resolution imaging spectroradiometer (MODIS), and long-term data record (LTDR), for the investigation of drought evolution. Our objectives are to investigate drought evolution and spatiotemporal variations from 1982 to 2017 based on two remote-sensing indices, namely, the normalized difference vegetation index (NDVI) and the vegetation condition index (VCI), and a popular meteorological index-standardized precipitation index (SPI)-under four different land cover types, cropland, forestland, grassland, and desertland in China. The modified Mann-Kendall test was used to detect the significance of a trend. The Pearson correlation method was used to find the relationship between NDVI anomaly, VCI, precipitation, and SPI. The results revealed that (a) both mean monthly and yearly precipitation had a general land cover type rank of forestland > grassland ≈ cropland > desertland. (b) A positive correlation was found between drought indices (NDVI anomaly, VCI, SPI) and precipitation for different land cover types. The NDVI anomaly and VCI were well correlated with 3-month SPI for cropland and were well correlated with 6-month SPI for forestland. VCI performed better than NDVI anomaly when correlating with SPI. (c) The coefficient of determination (R2) was obtained for precipitation and VCI in the driest (2011) and wettest (2016) years. The R2 values for desert and grassland ranged from 0.70 to 0.90 and for cropland and forestland were lower (0.54-0.69). (d) Only precipitation, SPI, and VCI of cropland had significant increasing trends. The spatial distribution patterns of precipitation, NDVI, and VCI increased with the decreased elevation. The study revealed that desert and grassland had been regularly exposed to moderate or extreme droughts conditions and confirmed that desert and grassland are more sensitive to short-term drought.

The efficacy of dexketoprofen for migraine attack: A meta-analysis of randomized controlled studies.

BACKGROUND: The efficacy of dexketoprofen for migraine attack remains controversial. We conduct a systematic review and meta-analysis to explore the influence of dexketoprofen supplementation versus placebo on pain control in migraine attack patients. METHODS: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through March 2019 for randomized controlled trials (RCTs) assessing the effect of dexketoprofen supplementation versus placebo on pain control for migraine attack patients. This meta-analysis is performed using the random-effect model. RESULTS: Five RCTs involving 794 patients are included in the meta-analysis. Overall, compared with control group for migraine attack, dexketoprofen supplementation is associated with substantially increased pain free at 2 hours (RR = 1.90; 95% CI = 1.43-2.53; P < .0001), pain free at 48 hours (RR = 1.63; 95% CI = 1.07-2.49; P = .02), good or excellent treatment (RR = 1.48; 95% CI = 1.24-1.78; P < .0001) and pain relief at 2 hours (RR = 1.80; 95% CI = 1.17-2.77; P = .007), as well as reduced need for rescue drug (RR = 0.64; 95% CI = 0.43-0.94; P = .02), with no significant increase in adverse events (RR = 1.51; 95% CI = 0.87-2.62; P = .14). CONCLUSION: Dexketoprofen supplementation benefits to improve pain control at 48 hours and reduce the need for rescue drug in migraine attack patients.

Protein phosphatase 2 regulatory subunit B''Alpha silencing inhibits tumor cell proliferation in liver cancer.

AIM: To explore the effects of protein phosphatase 2 regulatory subunit B''Alpha (PPP2R3A) on the proliferation and migration of liver cancer cells. METHODS: Expression of PPP2R3A in tumor tissues of hepatocellular carcinoma (HCC) patients was detected by immunohistochemistry and western blotting. In two liver cancer cell lines (HepG2 and HuH7), PPP2R3A expression was silenced and then overexpression with PPP2R3A lentiviral vectors, and the effects of PPP2R3A knockdown or overexpression on the proliferation, cell cycle, migration, and invasion of HCC cells were determined in vitro. In a xenograft cancer model in nude mice, the in vivo effects of PPP2R3A knockdown on tumor growth and cancer cell proliferation were evaluated. RESULTS: PPP2R3A expression was found in tumor foci in six of eight HCC samples, at a level higher than that in the adjacent para-tumor tissues. PPP2R3A expression was observed primarily in the cytoplasm of the cancer cells. Knockdown of PPP2R3A resulted in significant inhibition of hepatoma cell proliferation (P < .05), migration (P < .01), and invasion (P < .01) as well as a significant delay in the G1/S transition in both liver cancer lines (P < .05) and increased p53 expression. Conversely, overexpression of PPP2R3A promoted the proliferation (P < .05) and altered cell cycle progression (P < .05) of both liver cancer cell lines. In vivo, PPP2R3A knockdown in liver cancer cells led to significant reductions in the tumor volume (P < .001) and the expression of Ki-67 in tumor tissues (P < .05). CONCLUSION: PPP2R3A may play a role in liver cancer via the regulation of tumor cell proliferation and invasion.

Efficacy and Safety of Mizoribine Combined With Tacrolimus in Living Donor Kidney Transplant Recipients: 3-Year Results by a Chinese Single Center Study.

BACKGROUND: Mizoribine (MZR) was effective and safe for living Chinese donor kidney transplantation (LDKT) on tacrolimus-based treatment 1 year after transplantation. We investigated whether MZR was effective and safe for LDKT on tacrolimus-based treatment with long follow-up periods. METHODS: We compared 22 LDKT recipients who were administered MZR, tacrolimus, and corticosteroids with a control group (n = 20) treated with mycophenolate mofetil (MMF), tacrolimus, and corticosteroids. Primary efficacy endpoints were 3-year patient survival, 3-year graft survival, and acute rejection (AR) rate within 3 years after transplantation. RESULTS: The 3-year patient and graft survival rates for the MZR and MMF groups were 100%. The AR rate after transplantation was 18.2% for the MZR group and 10.0% for the MMF group; the difference was not significant (P = .665). There was no significant difference in serum creatinine levels, glomerular filtration rates (eGFR), serum urate levels, blood urea nitrogen, and cystatin C levels 12, 24, and 36 months after transplantation. No significant differences in the CD3, CD4, CD8, CD4/CD8, and CD45 were observed between the 2 groups 12, 24, and 36 months after transplantation. There were no significant differences in adverse events among the MZR or the MMF group, whereas the prevalence of gastrointestinal symptoms were significantly lower in the MZR treatment group (P = .003), especially acid reflux (P = .007). Compared with the MMF group, the MZR group should lighten the burden on patients. CONCLUSION: MZR with tacrolimus and corticosteroids provides satisfactory immunosuppression and higher safety for Chinese LDKT over a 3-year follow-up.

Hyperuricemia in Living Donor Kidney Transplantation Patients During Mizoribine Administration Caused Mainly by Changes in Kidney Function.

BACKGROUND: Although mizoribine (MZR) is used as an immunosuppressant after renal transplantation, the occurrence of hyperuricemia has been reported. The onset of hyperuricemia is often observed within the first several months after surgery. Since MZR is a renal excretion-type drug excreted as an unchanged drug from the kidneys, MZR blood concentrations may rise due to the influence of renal function. We investigated whether the onset of hyperuricemia after MZR administration was associated with the direct effect of a change in renal function. METHODS: Serum uric acid (serum UA), serum creatinine (sCr), serum ß2-microglobulin (serum ß2-MG), and serum cystatin C (serum Cys-C) were measured for about 3 months in 22 subjects. Correlation coefficients were calculated using the change rates of serum UA and sCr (Δ serum UA, Δ sCr), serum UA and serum ß2-MG (Δ serum UA, Δ serum ß2-MG), and serum UA and serum Cys-C (Δ serum UA, Δ serum Cys-C) at the onset of hyperuricemia. RESULTS: The correlation coefficients between Δ serum UA and Δ sCr, Δ serum UA and Δ serum ß2-MG, and Δ serum UA and Δ serum Cys-C were 0.723 (P < .001), 0.863 (P < .001) and 0.548 (P < .001), respectively. Further, serum UA and sCr level reached their highest peak on the same day after MZR administration, and the behavior was mostly consistent. CONCLUSION: It was suggested that hyperuricemia occurred about 3 months after MZR administration due mainly to temporary changes in kidney function.

G994T polymorphism in exon 9 of plasma platelet-activating factor acetylhydrolase gene and lung ultrasound score as prognostic markers in evaluating the outcome of acute respiratory distress syndrome.

The present study aimed to discover potential biomarkers for predicting the prognosis of acute respiratory distress syndrome (ARDS) in conjunction with lung ultrasound (LUS). Blood samples from 112 ARDS patients were collected to compare their partial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2), positive end-expiratory pressure (PEEP), lactic acid, sequential organ failure assessment (SOFA) score, clinical pulmonary infection score (CPIS) and APACHE II score. Kaplan-Meier plots and the log-rank test were performed to analyse the association between the platelet-activating factor acetylhydrolase (PAFAH) G994T polymorphism and the outcome of ARDS regarding mortality. A negative correlation between the LUS score and PaO2/FiO2, PEEP and lactic acid, as well as with the SOFA, CPIS and APACHE II score was confirmed with correlation coefficients of -0.493, -0.548, -0.642, -0.598, -0.566 and -0.567, respectively (all P<0.05). The activity of PAFAH and high-density lipoprotein-PAFAH in the serum collected from subjects of the GG genotype was similar to that in subjects of the GT genotype, but the low-density lipoprotein-PAFAH activity in the serum collected from GG subjects was significantly higher than that in GT subjects. An evident reduction in the PEEP, level of lactic acid, as well as the SOFA, CPIS and APACHE II score was observed in GG subjects, accompanied by a significantly increased PaO2/FiO2. Kaplan-Meier analysis indicated that subjects with a high LUS score had a significantly higher survival rate than those with a low LUS score, and the mortality risk for GG subjects was significantly lower than that for GT subjects. Finally, among all groups (genotype and LUS groups), GG subjects with a high LUS score had the lowest mortality risk, whereas GT subjects with a low LUS score had the highest mortality risk. In addition, the survival rate of GT subjects with a high LUS score was higher than that of GG subjects with a low LUS score. In conclusion, the combination of the LUS score and the G994T polymorphism in exon 9 of the PAFAH gene may be used as a potential prognostic marker for ARDS.

RNA Sequencing Reveals the Suitability of Cardiac Death Livers for Transplantation.

BACKGROUND: Organ transplantation is considered the best treatment for end-stage organ failure. However, the lack of available organs for transplantation and the increasing number of patients waiting for transplants are primary issues facing the transplant community. Thus, developing strategies to increase the number of donors, especially for liver transplantation, has become a priority. The use of organs acquired from donors who suffered cardiac related deaths has increased the pool of potential liver donors. However, donation after cardiac death (DCD) livers increases the risk of primary graft dysfunction. METHODS: In the current study, we conducted transcriptome sequencing using livers from a DCD rat to assess the short-term feasibility and functional efficacy of DCD livers. RNA sequencing (RNAseq) data showed that the liver transcriptome varied greatly in rat livers subjected to 15 minutes of cardiac arrest. RESULTS: The livers used in the current study had a significant loss of normal function before transplantation. Functional and network analyses consistently indicated that transcription and translation processes were inhibited after approximately 15 minutes of cardiac arrest. Moreover, the transcriptomic sequencing data provides significant insight for identifying functional genes and testing additional biological questions in DCD liver transplantation in future studies.

Structural Basis for tRNA Mimicry by a Bacterial Y RNA.

Noncoding Y RNAs are present in both animal cells and many bacteria. In all species examined, Y RNAs tether the Ro60 protein to an effector protein to perform various cellular functions. Recently, a new Y RNA subfamily was identified in bacteria. Bioinformatic analyses of these YrlA (Y RNA-like A) RNAs predict that the effector-binding domain resembles tRNA. We present the structure of this domain, the overall folding of which is strikingly similar to canonical tRNAs. The tertiary interactions that are responsible for stabilizing tRNA are present in YrlA, making it a close tRNA mimic. However, YrlA lacks a free CCA end and contains a kink in the stem corresponding to the anticodon stem. Since nucleotides in the D and T stems are conserved among YrlAs, they may be an interaction site for an unknown factor. Our experiments identify YrlA RNAs as a new class of tRNA mimics.

Effect of Palliative Care for Patients with Heart Failure.

Palliative care might be beneficial to heart failure. However, the results remain controversial. We conducted a systematic review and meta-analysis to explore the effect of palliative care on heart failure.PubMed, Embase, Web of Science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of palliative care versus usual care on heart failure were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. The primary outcome was readmission. Meta-analysis was performed using random-effect model.Five RCTs involving 545 patients were included in the meta-analysis. Overall, compared with control intervention, palliative care intervention was found to significantly reduce the readmission [Std. mean difference = 0.79; 95% confidence intervals (CI) = 0.23 to 1.35; P = 0.006], Edmonton Symptom Assessment Scale (ESAS) (Std. mean difference = -2.5; 95% CI = -4.39 to -0.62; P = 0.009), and PHQ-9 (Std. mean difference = -1.16; 95% CI = -1.73 to -0.58; P < 0.005), as well as improve heart failure questionnaire (Std. mean difference = 4.46; 95% CI = 3.44 to 5.47; P < 0.005), but had no influence on mortality (RR = 1.54; 95% CI = 0.80 to 2.96; P = 0.19) and quality of life questionnaire (Std. mean difference = 1.81; 95% CI = -0.14 to 3.77; P = 0.07).Compared with control intervention, palliative care intervention was found to significantly reduce readmission, ESAS, PHQ-9, and improve heart failure questionnaire, but showed no influence on mortality and quality of life questionnaire in patients with heart failure.