[Advances in the role of extracellular histones in the inflammatory process of liver injury].

Histones are important structural proteins of chromatin in the nucleus, which can regulate gene transcription, and can be released from the nucleus to the outside of the cell under injury and inflammatory stimulations, thereby causing cytotoxicity and immune stimulation, and aggravating tissue damage. Extracellular histones are involved in the occurrence and development of many diseases, including sepsis, autoimmune diseases, liver injury, and acute lung injury. Therefore, its application not only can be used as a body's biomarker of inflammation, but also it is expected to become a molecular target for the treatment of diseases. This article reviews the role of extracellular histones in the inflammatory process of liver injury.

[Efficacy and safety of ticagrelor versus clopidogrel in Chinese patients with acute coronary syndrome treated with glycoprotein â ¡b/â ¢a receptor antagonist].

Objective: To explore the efficacy and safety of ticagrelor versus clopidogrel in acute coronary syndrome (ACS) Chinese patients using glycoprotein Ⅱb/Ⅲa inhibitor (GPI). Methods: The data from CCC-ACS (Improving Care for Cardiovascular Disease in China-ACS) project were systematically reviewed in ACS patients with GPI. The patients were divided into ticagrelor and clopidogrel groups. A logistic analysis and propensity score matching (PSM) were performed to compare occurrences of major cardiovascular events (MACE) and bleeding events between the two groups during hospitalization. Results: A total of 63 641 ACS patients were collected from 150 hospitals. Logistic regression analyses showed that there was no statistically significant difference in the reduction of MACE between ticagrelor and clopidogrel when using GPI (OR=0.881, 95%CI 0.599-1.296; P=0.521). However, major bleeding rate was higher in the ticagrelor group than that in the clopidogrel group (OR=1.401, 95%CI 1.075-1.852; P=0.013). Similar results were observed after PSM. No statistic difference in MACE between the ticagrelor and clopidogrel group (OR=0.919, 95%CI 0.613-1.376; P=0.681). Major bleeding rate was higher in the ticagrelor group (OR=1.559, 95%CI 1.130-2.150; P=0.007). Conclusion: In ACS patients with GPI, ticagrelor did not reduce MACE, but increased the major bleeding risk compared with clopidogrel.

The gene NtMYC2a acts as a 'master switch' in the regulation of JA-induced nicotine accumulation in tobacco.

The biosynthesis and transport of nicotine has been shown to be coordinately upregulated by jasmonate (JA). MYC2, a member of basic helix-loop-helix (bHLH) transcription factor family, is well-documented as the core player in the JA signalling pathway to regulate diverse plant development processes. Four MYC2 genes were found in the tobacco genome, NtMYC2a/2b and 1a/1b. In this study, we tested whether one of them, NtMYC2a, acts as a 'master switch' in the regulation of nicotine biosynthesis and transport in tobacco. We generated NtMYC2a knockout tobacco plants using the CRISPR-Cas9 technique and analysed the effect of NtMYC2a knockout on expression of the nicotine biosynthesis genes (NtAO, NtQS, NtPMT1a, NtQPT2, NtODC2, NtMPO1, NtA622 and NtBBLa) and transport genes (NtMATE2 and NtJAT1), as well as leaf accumulation of nicotine in the NtMYC2a knockout plants. We found that all the nicotine biosynthesis and transport genes tested in this study were significantly downregulated (>50% reduction compared with wild-type control) in the NtMYC2a knockout plants. Moreover, the leaf nicotine content in knockout plants was dramatically reduced by ca 80% compared with the wild-type control. These results clearly show that NtMYC2a acts as a 'master switch' to coordinate JA-induced nicotine accumulation in tobacco and suggests that NtMYC2a might play an important role in tobacco nicotine-mediated defence against herbivory.

Operating behavior of micro-LEDs on a GaN substrate at ultrahigh injection current densities.

Near-ultraviolet micro-LEDs with different diameters were fabricated on GaN substrates. The electroluminescence and the light output power-current density and current density-voltage relationships were measured. A saturated current density of 358 kA/cm2 was achieved with a 20 µm LED. The ideality factor curves showed steps and peaks when the injection current density was increased from 20 to 150 kA/cm2 and an abnormal efficiency increase. The transport and recombination processes of micro-LEDs at high injection current densities were simulated, and the many-body effect and phase space filling in the integrated quantum drift-diffusion model were considered. Serious current crowding was observed above 100 kA/cm2, even for the 20 µm LED.

Detection of porcine circovirus-like virus P1 in Hebei, China.

Porcine circovirus-like virus P1 is a novel unclassified circovirus that was first detected in China and may be associated with post-weaning multisystemic wasting syndrome (PMWS) and congenital tremor. In this study, we detected P1 infection in pigs in Hebei Province, China, in 2017. One hundred and forty of 500 (28.0%) serum samples from 25 pig farms with different PMWS status in seven cities were P1 positive on PCR. Twelve P1 strains were sequenced, and the complete genomes of 11 P1 strains were 648 nucleotides (nt) in length, whereas that of strain ZJK02 was 647 nt, with a G deletion at position of 183 in its genome. The complete genomic and capsid protein sequences of the 12 P1 strains analysed in this study shared 98.8%-100.0% and 86.5%-100.0% identity, respectively. A phylogenetic analysis based on the complete genomic and capsid sequences of 26 P1 strains showed that the 12 P1 sequences from Hebei Province clustered on two small branches. Further studies of the evolution and pathogenesis of P1 are required.

The Griffiths Development Scales-Chinese (GDS-C): A cross-cultural comparison of developmental trajectories between Chinese and British children.

BACKGROUND: The Griffiths Mental Development Scales (GMDS) are used in many countries to assess the development of children from birth to 8 years. There is a need for accurate and culturally appropriate developmental assessment tools for Chinese children. Here, we adapted the GMDS for use in Chinese children and compare the developmental trajectories between Chinese and British children. METHODS: Children with typical development were recruited from 7 urban cities in China between 2009 and 2013. The Griffiths Mental Development Scales-Chinese (GDS-C) were adapted and used to assess the development of urban Chinese children. Developmental curves were computed for 6 subscales using learning management system methods and compare against the British curves from the Griffiths Mental Development Scales-Extended Revised (GMDS-ER). RESULTS: The GDS-C were used to assess the developmental status of 815 Chinese children. Plots of the 1st, 5th, 10th, 25th, 50th, 75th, 90th, 95th, and 99th percentiles, and full percentile tables were obtained, which showed similar trends to data from the British GMDS-ER. CONCLUSIONS: The Chinese developmental curves obtained from the GDS-C showed similarities and differences to the developmental curves from the British GMDS-ER. The development of urban Chinese children should be assessed with the culturally appropriate GDS-C.

Evidence of porcine circovirus-like virus P1 in piglets with an unusual congenital tremor.

Outbreaks of trembling and shaking were reported among pigs at two pig farms in Jiangsu Province, China. Serum and tissue samples tested positive for porcine circovirus-like virus P1 and negative for classical swine fever virus, porcine circovirus type 2, astrovirus and porcine pestivirus using PCR/RT-PCR and immunohistochemical techniques. High P1 viral genome loads were identified in sera, brain and lymph node tissue samples by qPCR. In addition, one of the most notable pathological changes was dissolution of the nucleus in Purkinje cells. The results of this study provide molecular evidence of an association between congenital tremor in pigs and P1 virus.

[Protective effect of the histone deacetylase inhibitor ACY1215 against brain edema in mice with acute liver failure].

Objective: To investigate the protective effect of ACY1215 (Rocilinostat), a histone deacetylase inhibitor, against brain edema in mice with acute liver failure. Methods: Lipopolysaccharide combined with D-galactosamine was used to establish a mouse model of acute liver failure, and ACY1215 was used for intervention. The effect of ACY1215 on histopathological changes of the liver was observed after 24 hours, as well as the changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood ammonia, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), brain water content, blood-brain barrier structure, NF-κB-p65, histone, acetylated histone, and TNF-α mRNA in brain tissue. Results: The mice with acute liver failure had marked pathological damage in liver tissue, as well as significant increases in the levels of ALT, AST, blood ammonia, TNF-α, and IFN-γ (t≥5.367, all P < 0.05). ACY1215 significantly improved the pathological damage in liver tissue and reduced the serum levels of ALT, AST, blood ammonia, TNF-α, and IFN-γ (t≤-3.515, all P < 0.05). ACY1215 also significantly reduced the expression of NF-κB-p65 (t = -5.871, P = 0.004) and the mRNA expression of TNF-α (t = -11.913, P < 0.01) in brain tissue and brain water content (t = -2.355, P < 0.01). According to the results of electron microscopy, the model group had an abnormal blood-brain barrier structure, and the ACY1215 group had slighter damage than the model group. Compared with the normal group, the model group had significant increases in the acetylation level of histone H3 and H4 in brain tissue (t≥3.009, both P < 0.05), while ACY1215 further upregulated the acetylation levels of histone H3 and H4 (t≥6.682, both P < 0.05). Conclusion: ACY1215 exerts a protective effect against brain edema in mice with acute liver failure, possibly by regulating histone acetylation and inhibiting inflammation.

Annual direct medical costs associated with diabetes-related complications in the event year and in subsequent years in Hong Kong.

AIM: To develop models to estimate the direct medical costs associated with diabetes-related complications in the event year and in subsequent years. METHODS: The public direct medical costs associated with 13 diabetes-related complications were estimated among a cohort of 128 353 people with diabetes over 5 years. Private direct medical costs were estimated from a cross-sectional survey among 1825 people with diabetes. We used panel data regression with fixed effects to investigate the impact of each complication on direct medical costs in the event year and subsequent years, adjusting for age and co-existing complications. RESULTS: The expected annual public direct medical cost for the baseline case was US$1,521 (95% CI 1,518 to 1,525) or a 65-year-old person with diabetes without complications. A new lower limb ulcer was associated with the biggest increase, with a multiplier of 9.38 (95% CI 8.49 to 10.37). New end-stage renal disease and stroke increased the annual medical cost by 5.23 (95% CI 4.70 to 5.82) and 5.94 (95% CI 5.79 to 6.10) times, respectively. History of acute myocardial infarction, congestive heart failure, stroke, end-stage renal disease and lower limb ulcer increased the cost by 2-3 times. The expected annual private direct medical cost of the baseline case was US$187 (95% CI 135 to 258) for a 65-year-old man without complications. Heart disease, stroke, sight-threatening diabetic retinopathy and end-stage renal disease increased the private medical costs by 1.5 to 2.5 times. CONCLUSIONS: Wide variations in direct medical cost in event year and subsequent years across different major complications were observed. Input of these data would be essential for economic evaluations of diabetes management programmes.

Experimental and observational studies find contrasting responses of soil nutrients to climate change.

Manipulative experiments and observations along environmental gradients, the two most common approaches to evaluate the impacts of climate change on nutrient cycling, are generally assumed to produce similar results, but this assumption has rarely been tested. We did so by conducting a meta-analysis and found that soil nutrients responded differentially to drivers of climate change depending on the approach considered. Soil carbon, nitrogen, and phosphorus concentrations generally decreased with water addition in manipulative experiments but increased with annual precipitation along environmental gradients. Different patterns were also observed between warming experiments and temperature gradients. Our findings provide evidence of inconsistent results and suggest that manipulative experiments may be better predictors of the causal impacts of short-term (months to years) climate change on soil nutrients but environmental gradients may provide better information for long-term correlations (centuries to millennia) between these nutrients and climatic features. Ecosystem models should consequently incorporate both experimental and observational data to properly assess the impacts of climate change on nutrient cycling.

NtBRC1 suppresses axillary branching in tobacco after decapitation.

Axillary branching is controlled by a very complex mechanism involving various endogenous and environmental factors. Previous studies have shown that Tb1/BRC1 is the point of integration in the network of molecular mechanisms regulating axillary branching in plants. In this study, we cloned the Tb1/BRC1 ortholog, NtBRC1, from Nicotiana tabacum and functionally analyzed its role in the control of axillary branching in tobacco. Overexpression of NtBRC1 resulted in significant retardation of axillary branching, and downregulation of this gene resulted in significant acceleration of axillary branching after decapitation. This indicates a negative role for this gene in the regulation of axillary branching. In-line with previous reports, NtBRC1 was found to be expressed predominantly in axillary buds. Additionally, as expected, expression was decreased 8 h following decapitation, which further confirms its role in the suppression of axillary branching. Furthermore, the expression of NtBRC1 was significantly downregulated by cytokinin, but was not affected by GR24, a synthetic strigolactone. Based on the data collected in the present study, we demonstrate that NtBRC1 negatively regulates axillary branching in tobacco after decapitation and functions downstream of the cytokinin signaling pathway inside axillary buds.

Long Non-Coding RNA: An Emerging Paradigm of Pancreatic Cancer.

Pancreatic cancer remains a worldwide issue and burden that is hard to resolve given its low resection rate and chemo-resistance. Early diagnosis and early treatment are critical for conquering pancreatic cancer. Therefore, new biomarkers for diagnosis and prognosis are urgently needed. Previously, researchers mainly focused on protein-coding genetic and epigenetic changes in many types of cancers, and regarded the noncoding part as waste. Recently, however, long non-coding RNA (lncRNA) has emerged as a major participant in carcinogenesis, as it regulates cell proliferation, migration, invasion, metastasis, chemo-resistance, etc. The underlying mechanisms are summarized as signaling, decoy, guide and scaffold, yet the specific regulation networks remain to be uncovered. Several studies have revealed that some lncRNAs are dysregulated in pancreatic cancer, participating in biological functions. In this review, we will briefly outline the functional lncRNAs in pancreatic cancer, decipher possible mechanisms of lncRNAs, and further explore their significance in pancreatic cancer.

Effectiveness of the multidisciplinary Risk Assessment and Management Program for Patients with Diabetes Mellitus (RAMP-DM) for diabetic microvascular complications: A population-based cohort study.

AIM: To evaluate the effectiveness of the multidisciplinary Risk Assessment and Management Program for Patients with Diabetes Mellitus (RAMP-DM) in reducing the risks of microvascular complications. METHODS: This prospective cohort study was conducted with 29,670 propensity-score-matched RAMP-DM participants and diabetes patients under the usual primary care (14,835 in each group). Study endpoints were the first occurrence of any diabetic microvascular complications, non-proliferative diabetic retinopathy/preproliferative diabetic retinopathy (NPDR/prePDR), sight-threatening diabetic retinopathy (STDR) or blindness, nephropathy, end-stage renal disease (ESRD), neuropathy and lower-limb ulcers or amputation. Log-rank tests and multivariable Cox proportional-hazards regressions were employed to estimate between-group differences in incidences of study endpoints. RESULTS: After a median follow-up of 36 months with>41,000 person-years in each group, RAMP-DM participants had a lower incidence of microvascular complications (760 vs 935; adjusted hazard ratio [HR]: 0.73; 95% confidence interval [CI]: 0.66-0.81; P<0.001) and lower incidences of all specific microvascular complications except neuropathy (adjusted HR: 0.94; 95% CI: 0.61-1.45; P=0.778). Adjusted HRs for the RAMP-DM vs control group for ESRD, STDR or blindness, and lower-limb ulcers or amputation were 0.40 (95% CI: 0.24-0.69; P<0.001), 0.55 (95% CI: 0.39-0.78; P=0.001) and 0.49 (95% CI: 0.30-0.80; P=0.005), respectively. CONCLUSION: The RAMP-DM intervention was associated with lower incidences of all microvascular complications except neuropathy over a 3-year follow-up. These encouraging results constitute evidence that structured risk assessment and risk-stratified management provided by a multidisciplinary team is effective for reducing microvascular complications in diabetes patients. CLINICAL TRIAL REGISTRY: NCT02034695, www.ClinicalTrials.gov.

Anthropogenic disturbances are key to maintaining the biodiversity of grasslands.

Although anthropogenic disturbances are often perceived as detrimental to plant biodiversity, the relationship between biodiversity and disturbance remains unclear. Opinions diverge on how natural diversity is generated and maintained. We conducted a large-scale investigation of a temperate grassland system in Inner Mongolia and assessed the richness-disturbance relationship using grazing intensity, the primary anthropogenic disturbance in the region. Vascular plant-species richness peaked at an intermediate level of anthropogenic disturbance. Our results support the Intermediate Disturbance Hypothesis, which provides a valid and useful measure of biodiversity at a metacommunity scale, indicating that anthropogenic disturbances are necessary to conserve the biodiversity of grassland systems.

Expression of the 2-dehydro-3-deoxyphosphooc-tonate aldolase (KdsA) gene in mulberry leaves (Morus alba L.) is down-regulated under high salt and drought stress.

The oligosaccharide 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) is a key component of lipopolysaccharide in Gram-negative bacteria, and is also part of the pectic polysaccharide rhamnogalacturonan (RG-II) of the plant cell wall. The enzyme KDO-8-phosphate synthase (KDO8Ps), encoded by the 2-dehydro-3-deoxyphosphooctonate aldolase (KdsA) gene, catalyzes the first step in the synthesis of Kdo. In this study, the complete coding sequence of the KdsA gene from mulberry leaves was cloned and the primary structure of KDO8Ps was deduced. Alignment of the amino acid sequence of KDO8Ps from mulberry with those of five other plant species revealed a high level of evolutionary conservation. A phylogenetic tree analysis demonstrated a short genetic distance among KDO8Ps proteins of different species. Expression of the KdsA gene was higher in the second leaves than in the eighth leaves of mulberry, and was down-regulated under conditions of high salt or drought stress. Our results suggest that KdsA expression is important for the growth of new plant tissues, and is sensitive to harsh environments.

Association between single-nucleotide polymorphisms of fatty acid synthase gene and meat quality traits in Datong Yak (Bos grunniens).

Fatty acid synthase (FASN) is a key enzyme in fatty acid anabolism that plays an important role in the fat deposit of eukaryotic cells. Therefore, in this study, we detected 2 novel single-nucleotide polymorphisms (SNPs) in the FASN gene in 313 adult individuals of Datong yak using polymerase chain reaction-single strand conformation polymorphism and DNA sequencing techniques. SNP g.5477C>T is located in intron 3 of FASN, and 3 genotypes, HH, HG, and GG, were detected in this mutation site. SNP g.16930T>A is located in exon 37 of FASN, and 2 genotypes, EE and EF, were detected in this site. Association analysis of these 2 SNPs with meat quality traits showed that in SNP g.5477C>T, yaks with the HH genotype and HG genotype had significantly higher intramuscular fat content than individuals with the GG genotype (P < 0.01). In SNP g.16930T>A, yaks with the EE genotype also had significantly higher IMF content than individuals with the EF genotype (P < 0.01). The results indicate that FASN may be used as a candidate gene affecting intramuscular fat content in Datong yaks.

Microfluidic laminate-based phantom for diffusion tensor-magnetic resonance imaging (DT-MRI).

This paper reports fabrication of a magnetic resonance imaging (MRI) phantom created by stacking of multiple thin polydimethylsiloxane (PDMS) layers. PDMS is spin coated on SU-8 molds to obtain the desired layer thickness and imprints of the microchannel patterns that define the phantom geometry. This paper also identifies the unique challenges related to the fabrication and assembly of multiple thin layers and reports for the first time assembly of a large number of thin laminates of this nature. Use of photolithography techniques allows us to create a wide range of phantom geometries. The target dimensions of the phantoms reported here are (i) a stack of 30 thin PDMS layers of 10 µm thickness (ii) curved 5 µm × 5 µm microchannels with 8.7 µm spacing, and (iii) straight 5 µm × 5 µm microchannels with 3.6 µm spacing. SEM scans of the assembled phantoms show open microchannels and a monolithic cross-section with no visible interface between PDMS layers. Based on the results of diffusion tensor magnetic resonance imaging (DT-MRI) scan, the anisotropic diffusion of water molecules due to the physical restriction of the microchannels was detected, which means that the phantom can be used to calibrate and optimize MRI instrumentation.