K6-linked ubiquitylation marks formaldehyde-induced RNA-protein crosslinks for resolution.

Reactive aldehydes are produced by normal cellular metabolism or after alcohol consumption, and they accumulate in human tissues if aldehyde clearance mechanisms are impaired. Their toxicity has been attributed to the damage they cause to genomic DNA and the subsequent inhibition of transcription and replication. However, whether interference with other cellular processes contributes to aldehyde toxicity has not been investigated. We demonstrate that formaldehyde induces RNA-protein crosslinks (RPCs) that stall the ribosome and inhibit translation in human cells. RPCs in the messenger RNA (mRNA) are recognized by the translating ribosomes, marked by atypical K6-linked ubiquitylation catalyzed by the RING-in-between-RING (RBR) E3 ligase RNF14, and subsequently resolved by the ubiquitin- and ATP-dependent unfoldase VCP. Our findings uncover an evolutionary conserved formaldehyde-induced stress response pathway that protects cells against RPC accumulation in the cytoplasm, and they suggest that RPCs contribute to the cellular and tissue toxicity of reactive aldehydes.

A recurrent chromosomal inversion suffices for driving escape from oncogene-induced senescence via subTAD reorganization.

Oncogene-induced senescence (OIS) is an inherent and important tumor suppressor mechanism. However, if not removed timely via immune surveillance, senescent cells also have detrimental effects. Although this has mostly been attributed to the senescence-associated secretory phenotype (SASP) of these cells, we recently proposed that "escape" from the senescent state is another unfavorable outcome. The mechanism underlying this phenomenon remains elusive. Here, we exploit genomic and functional data from a prototypical human epithelial cell model carrying an inducible CDC6 oncogene to identify an early-acquired recurrent chromosomal inversion that harbors a locus encoding the circadian transcription factor BHLHE40. This inversion alone suffices for BHLHE40 activation upon CDC6 induction and driving cell cycle re-entry of senescent cells, and malignant transformation. Ectopic overexpression of BHLHE40 prevented induction of CDC6-triggered senescence. We provide strong evidence in support of replication stress-induced genomic instability being a causative factor underlying "escape" from oncogene-induced senescence.

2D TiS2-Nanosheet-Coated Concave Gold Arrays with Triple-Coupled Resonances as Sensitive SERS Substrates.

Herein, a hybrid substrate for surface-enhanced Raman scattering (SERS) is fabricated, which couples localized surface plasmon resonance (LSPR), charge transfer (CT) resonance, and molecular resonance. Exfoliated 2D TiS2 nanosheets with semimetallic properties accelerate the CT with the tested analytes, inducing a remarkable chemical mechanism enhancement. In addition, the LSPR effect is coupled with a concave gold array located underneath the thin TiS2 nanosheet, providing a strong electromagnetic enhancement. The concave gold array is prepared by etching silicone nanospheres assembled on larger polystyrene nanospheres, followed by depositing a gold layer. The LSPR intensity near the gold layer can be adjusted by changing the layer thickness to couple the molecular and CT resonances, in order to maximize the SERS enhancement. The best SERS performance is recorded on TiS2-nanosheet-coated plasmonic substrates, with a detectable methylene blue concentration down to 10-13 m and an enhancement factor of 2.1 × 109 and this concentration is several orders of magnitude lower than that of the TiS2 nanosheet (10-11 m) and plasmonic substrates (10-9 m). The present hybrid substrate with triple-coupled resonance further shows significant advantages in the label-free monitoring of curcumin (a widely applied drug for treating multiple cancers and inflammations) in serum and urine.

Effect and mechanism analysis of surface hydrogenation and fluorination on the electronic properties of th-GeC2.

A two-dimensional (2D) tetrahex-GeC2 nanosheet demonstrates excellent electronic properties such as a finite direct band gap and high carrier mobilities, as predicted from theoretical calculations. To further expand its potential applications, various strategies can be employed to tailor its electronic properties. These strategies include alloying, strain application, and edge and surface functionalization. This work specifically focuses on the impact of surface functionalization with hydrogen and fluorine adsorption on the 2D tetrahex-GeC2 nanostructures. It was discovered that the electronic properties of these nanostructures undergo significant alterations through surface functionalization by adjusting the adsorption sites and coverage of H/F species. The underlying mechanisms responsible for these property changes have been thoroughly analyzed and discussed in detail. Our calculations, based on density functional theory, reveal that the band gap of tetrahex-GeC2 widens as the surface coverage of H atoms increases. Conversely, the band gap narrows in the case of F adsorption. Additionally, the indirect-direct band gap transition can be triggered through surface functionalization. Such modifications in the electronic band structure are primarily due to the disappearance of the π bond when the C atom is converted from sp2 to sp3 hybridization through the adsorption of surface functionalized species. Furthermore, the results indicate that surface adsorption can regulate the effective mass of carriers, electron affinity, and work function in the 2D tetrahex-GeC2 nanostructure.

Exploring the adaptability of the secondary structure of mRNA to temperature in intertidal snails based on SHAPE experiments.

RNA-based thermal regulation is an important strategy for organisms to cope with temperature changes. Inhabiting the intertidal rocky shore, a key interface of the ocean, atmosphere and terrestrial environments, intertidal species have developed variable thermal adaptation mechanisms; however, adaptions at the RNA level remain largely uninvestigated. To examine the relationship between mRNA structural stability and species distribution, in the present study, the secondary structure of cytosolic malate dehydrogenase (cMDH) mRNA of Echinolittorina malaccana, Echinolittorina radiata and Littorina brevicula was determined using selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE), and the change in folding free energy of formation (ΔGfold) was calculated. The results showed that ΔGfold increased as the temperature increased. The difference in ΔGfold (ΔΔGfold) between two specific temperatures (25 versus 0°C, 37 versus 0°C and 57 versus 0°C) differed among the three species, and the ΔΔGfold value of E. malaccana was significantly lower than those of E. radiata and L. brevicula. The number of stems of cMDH mRNA of the snails decreased with increasing temperature, and the breakpoint temperature of E. malaccana was the highest among these. The number of loops was also reduced with increasing temperature, while the length of the loop structure increased accordingly. Consequently, these structural changes can potentially affect the translational efficiency of mRNA. These results imply that there were interspecific differences in the thermal stability of RNA secondary structures in intertidal snails, and these differences may be related to snail distribution.

Acetylation of citrate synthase inhibits Bombyx mori nucleopolyhedrovirus propagation by affecting energy metabolism.

Many studies have confirmed that virus infection cause changes in the expression level and post-translational modifications of tricarboxylic acid cycle (TCA) enzymes. In a previous study, we found that the acetylation level of lysine 336 of Bombyx mori citrate synthase (BmCS) was remarkably unregulated after Bombyx mori nucleopolyhedrovirus (BmNPV) infection. In the present study, we found that BmN cells infected with BmNPV could up-regulate BmCS transient expression and promote the acetylation modification of BmCS. Transient expression vectors for over-expression of wild-type Bmcs and K336 acetylation mimic mutant (K336Q) were constructed to analyze enzyme activity, revealing that acetylation of K336 significantly reduced its activity. The obtained results indicated that BmCS knock-down or K336 acetylation similarly suppressed BmN cellular ATP production and mitochondrial membrane potential. Furthermore, the acetylation of K336 and the reduction of BmCS expression contributed to weakening the replication lever of the BmNPV proliferation and the generation of progeny viruses. In sum, our study on the single lysine 336 acetylation and knock-down of Bmcs revealed the potential mechanism for inhibiting the proliferation of BmNPV, which may provide novel insights for the development of antiviral strategies.

Acetylation of fructose-bisphosphate aldolase-mediated glycolysis is essential for Bombyx mori nucleopolyhedrovirus infection.

Bombyx mori nucleopolyhedrovirus (BmNPV) is a baculovirus that infects silkworms, and its interaction with silkworm has been considered an important model in the field of insect virology. Accumulating evidence indicates that most viruses promote glycolytic metabolism in host cells to favor infection. However, similar reports are lacking in insects, especially in the area of post-translational modifications of proteins. In this study, we found that BmNPV infection induced the acetylation of fructose-bisphosphate aldolase (ALDO) on lysine 42 (K42) to promote its enzyme activity. To explore the underlying mechanisms, site-directed mutagenesis of deacetylated mimic (K/R) was performed. The results demonstrated that K42 acetylation promoted viral proliferation by exacerbating the glycolytic flux induced by BmNPV infection, which resulted in increased ATP, glucose uptake and lactate accumulation. Inhibiting glycolysis with 2-deoxygucose (2DG) revealed that glycolysis was essential for optimal BmNPV infection. Finally, we showed that BmNPV-infected cells enhanced the transcription of glycolysis-related genes, including Glut1, Hk2 and Ldh. In parallel, K42 acetylation of ALDO also promoted the expression of these genes. Therefore, acetylation of ALDO could be considered a regulator of BmNPV-induced glycolysis. These finding provide insights into the interaction between silkworm and BmNPV.

Acetylation of late expression factor 4 is crucial for the transcription and proliferation of Bombyx mori nucleopolyhedrovirus.

Late expression factor 4 (LEF4), RNA polymerase subunit of Bombyx mori nucleopolyhedrovirus (BmNPV), plays an enzymatic role to enhance the capping of pre-mRNA of late and very late genes. Lysine acetylation is a post-translational modification process having many important functions associated with the regulation of a gene expression. Our previous study on lysine acetylome in BmNPV infected BmN cells showed that LEF 4 was acetylated at lysine 76 (K76). However, it is still unclear whether the modification of K76 residue contributes to the modulation of viral gene transcription. To elucidate the role played by acetylation or deacetylation of LEF4 K76 in the transcription of viral genes, we constructed acetylation mimicking and deacetylation mimicking mutant virus, K76Q and K76R, respectively. We then transfected BmN cells with these mutants and analyzed the level of pre-mRNA at different times. The K76R showed a significant decrease in the mRNA transcription level of vp39 and p10 genes at 48 and 72 h post-transfection, while K76Q did not show any significant changes compared with lef4-Wt. We further detected the virus titer of lef4-Wt, K76Q [et] K76R, and it was found that K76R impaired the virus infectivity ability at 72 and 96 h, while K76Q did not affect the virus infectivity. Moreover, the yeast two hybrid technique (Y2H) showed that both mutants (K76Q [et] K76R) affected the association of LEF 4 with the P47 protein. Taken together, these results indicated that acetylation modification of K76 is important for the proper transcription of late and very late genes, and the effectiveness of viral infection. Keywords: BmNPV lef4 gene; lysine acetylation, late genes transcription; BmNPV p47 gene; infectivity.

Role of the Bombyx mori nucleopolyhedrovirus LEF3 acetylation on viral replication.

Late expression factor 3 (LEF3) is a single-stranded DNA binding protein of Bombyx mori nucleopolyhedrovirus (BmNPV) with multiple functions. It is an essential factor for viral DNA replication and plays an important regulatory role during BmNPV infection. Our recent quantitative analysis of protein acetylome revealed for the first time that LEF3 can be acetylated at four lysine residues during the viral infection, but the underlying mechanism is unknown. Among the modification sites, two of them (K18 and K27) are located in the conserved nuclear localization sequence region. The acetylation level for K18 especially was up-regulated approximately 7.4 times after 36 h of post-infection. To understand the regulatory function of this modification, site-direct mutagenesis for acetylated mimic (K18Q) or deacetylated mimic (K18R) mutants was performed on LEF3. The fluorescence analysis results showed that the replication capacity of the virus was significantly reduced after K18 acetylation. Meanwhile, co-localization analysis revealed that acetylation at K18 caused LEF3 to lose its nuclear targeting ability and affected the interaction between LEF3 and P143, retaining P143 in the cytoplasm. And further Yeast two-hybrid analysis results also confirmed that the acetylation at K18 did affect the interaction between LEF3 and P143. In conclusion, the acetylation of LEF3 at K18 might act as one of the antiviral strategies for silkworm host by affecting nuclear localization of LEF3, interaction with P143, and then blocking viral replication.

HSP/HSC70 activity is required for Bombyx mori nucleopolyhedrovirus replication at the early infectious phase.

Bombyx mori nucleopolyhedrovirus caused large amounts of silk loss annually, although it also could be used as silkworm bioreactor expression vector effectively and efficiently. Many heat shock (cognate) proteins 70 (HSP/HSC70) were induced by baculovirus and found existence in viral structure assembly. However, the concrete mechanism still need further elucidation for understanding host and virus interaction. In this study, the application of HSP/HSC70 inhibitor VER155008 is virus infectious phase-dependent for figuring out the role of intact molecular chaperone HSP/HSC70 activity in different stages of BmNPV proliferation progress. All the data had shown that HSP/HSC70 played a vital role in viral genome replication, virus protein abundance, BmNPV proliferation and budded virus production at the early infectious phase. This finding may provide new insights to unravel the interaction between baculovirus and silkworm in the initial infectious stage.

Deacetylation of BmAda3 is required for cell apoptosis caused by Bombyx mori nucleopolyhedrovirus infection.

Silkworm is not only an ideal insect model with a biological significance, but it is also crucially important in sericulture and bioreactors. Bombyx mori nucleopolyhedrovirus (BmNPV) is a principal pathogen of silkworm. However, the molecular mechanism underlying BmNPV invasion is still unclear. Based on our previous acetylome research findings of B. mori after BmNPV infection, here, we focused on silkworm alteration/deficiency in activation-3 (BmAda3). The acetylation of K124 and K128 were significantly reduced (0.66-fold) upon the virus challenge. Due to the interaction between Ada3 and P53, acetylation-mimic K124Q/K128Q and deacetylation-mimic K124R/K128R mutants of BmAda3 were constructed to explore the roles exerted by the acetylation modification of BmAda3 on P53. Yeast two-hybrid and IP results revealed that both BmAda3 and its deacetylation mutants (K124R/K128R) interacted with P53. Interestingly, we found that the deacetylation mutants (K124R/K128R) of BmAda3 significantly promoted the stability of P53. Since P53 is a proapoptotic factor, cell apoptosis was detected. We established that the deacetylation of BmAda3 at K124/K128 facilitated cellular apoptosis during BmNPV infection. Finally, viral proliferation was analyzed, and the results indicated that virus generation was reduced by K124/K128 deacetylation. Our report, based on the deacetylation of two lysine sites 124/128 of BmAda3, shows possible regulatory pathways of BmNPV proliferation and provides novel insights into the development of antiviral agents.

An Evaluation of a Perinatal Education and Support Program to Increase Breastfeeding in a Chinese American Community.

INTRODUCTION: In 2015, a community health center implemented a multipronged, Chinese language, health education initiative to increase breastfeeding. Perinatal education, hospital visits after delivery, and postpartum support were implemented to provide informational and emotional support. This study evaluates the impact of the breastfeeding program for Chinese American women. METHODS: This is a quasi-experimental study to assess the change in any and exclusive breastfeeding at 4-6 weeks postpartum. A difference-in-differences regression analysis was used to determine change in breastfeeding attributable to the program at an intervention site after adjusting for change in a control site during the same period. Change in breastfeeding was also examined by sociodemographic characteristics. RESULTS: A total of 1475 women who received perinatal care at two community center sites in 2014 and 2016 were included in the study. Within the women who received the intervention, any breastfeeding increased by 24 percentage points to 71% and exclusive breastfeeding increased by 13 percentage points to 27%. After adjusting for the change in the control group during the same period, the increases in any and exclusive breastfeeding attributable to the program were 17 (p < 0.01) and 9 percentage points (p < 0.05), respectively. Primiparous women and those who have been in the US longer than 5 years experienced the highest increase in any breastfeeding from the program. Exclusive breastfeeding was most improved in those with non-Medicaid insurance. CONCLUSIONS: A bilingual and bicultural breastfeeding program incorporated into routine pregnancy care at an intervention site experienced increases in both any and exclusive breastfeeding, even after adjusting for changes in breastfeeding in a control group. SIGNIFICANCE STATEMENT: What is known on this subject? Chinese Americans are the least likely to breastfeed among all ethnicities in New York City. Cultural and language barriers plus the lack of Chinese language resources contribute to low breastfeeding rates. What this study adds? A bilingual and bicultural breastfeeding program of perinatal education and postpartum support incorporated into routine pregnancy care increased both any and exclusive breastfeeding in a Chinese American population. Increase in any breastfeeding was the greatest in primiparous women and those who had been in the US for a longer time and increase in exclusive breastfeeding was greatest in women not using Medicaid insurance.

Acetylation of nucleopolyhedrovirus P35 is crucial for its anti-apoptotic activity in silkworm, Bombyx mori.

Apoptosis is a characteristic feature of a nucleopolyhedrovirus infected insect cells. This defensive strategy of the insect cells also affects the viral infectivity. On the contrary, the P35 baculovirus apoptosis inhibitor impedes the insect cell apoptosis induced by viral infection. Our previous investigation of the Bombyx mori nucleopolyhedrovirus (BmNPV) acetylome showed that 3 lysine (K) (70, 127 and 256) sites of P35 were acetylated during infection. How these modifications affect the interaction between the insect cells and BmNPV is still unknown. In order to explore the underlying mechanism of P35 lysine acetylation, mutants with glutamine or arginine substitution were constructed to mimic the acetylated (Q) and deacetylated (R) state. ELISA and DNA fragmentation assay were used to ascertain the acetylation effects on apoptosis. Subsequently the results showed that acetylation of K70 upregulated the anti-apoptotic activity, thereby preventing apoptosis induced by insect cells. Caspase 1 activity assay further confirmed that, acetylated K70 exhibited a strong anti-apoptotic activity in cell lines infected with BmNPV. Intriguingly, an examination with the yeast 2 hybrid (Y2H) assay revealed an interaction with the silkworm caspase 1. Taken together, we demonstrated that acetylation of P35 is crucial for an interaction with caspase 1 and the upregulation of anti-apoptotic activity. Keywords: Bombyx mori; BmNPV; P35; acetylation; anti-apoptotic; caspase 1.

Regulating the Local Charge Distribution of Ni Active Sites for the Urea Oxidation Reaction.

In electrochemical energy storage and conversion systems, the anodic oxygen evolution reaction (OER) accounts for a large proportion of the energy consumption. The electrocatalytic urea oxidation reaction (UOR) is one of the promising alternatives to OER, owing to its low thermodynamic potential. However, owing to the sluggish UOR kinetics, its potential in practical use has not been unlocked. Herein, we developed a tungsten-doped nickel catalyst (Ni-WOx ) with superior activity towards UOR. The Ni-WOx catalyst exhibited record fast reaction kinetics (440 mA cm-2 at 1.6 V versus reversible hydrogen electrode) and a high turnover frequency of 0.11 s-1 , which is 4.8 times higher than that without W dopants. In further experiments, we found that the W dopant regulated the local charge distribution of Ni atoms, leading to the formation of Ni3+ sites with superior activity and thus accelerating the interfacial catalytic reaction. Moreover, when we integrated Ni-WOx into a CO2 flow electrolyzer, the cell voltage is reduced to 2.16 V accompanying with ≈98 % Faradaic efficiency towards carbon monoxide.

Clemastine improves hypomyelination in rats with hypoxic-ischemic brain injury by reducing microglia-derived IL-1ß via P38 signaling pathway.

BACKGROUND: Microglia activation is associated with the development of hypoxic-ischemic brain injury (HIBI). Neuroinflammation suppression might be a suitable therapeutic target in hypoxic oligodendrocyte injury. This study aims to determine whether clemastine can improve hypomyelination by suppressing the activated microglia and promoting the maturation of oligodendrocyte progenitor cells (OPCs) in HIBI. METHODS: A bilateral common carotid artery occlusion (BCCAO) rat model that received continuous intraperitoneal injection (1 mg/kg) for 14 days was employed to elaborate the neuroprotection effects of clemastine. Interleukin-1ß (IL-1ß), nod-like receptor protein 3 (NLRP3), histamine H1 receptor, and OPC differentiation levels in the corpus callosum were measured. Primary cultured OPCs and co-culture of microglia and OPCs were used to explore the link between microglia activation and hypomyelination. Data were evaluated by one-way ANOVA with Fisher's protected least significant difference test. RESULTS: Clemastine treatment could reverse hypomyelination and restrain the upregulation of IL-1ß and NLRP3 in the corpus callosum of BCCAO rats. Primary cultured OPCs treated with IL-1ß showed failed maturation. However, clemastine could also reverse the OPC maturation arrest by activating the extracellular signal-regulated kinase (ERK) signaling pathway. Co-culture of microglia and OPCs with oxygen glucose deprivation treatment exhibited IL-1ß and NLRP3 upregulation. Clemastine could downregulate NLRP3 and IL-1ß and reverse hypomyelination by inhibiting the p38 signaling pathway. CONCLUSIONS: Clemastine could restrain microglia activation, improve axonal hypomyelination in BCCAO rats, and thus might be a viable strategy to inhibit hypomyelination in the corpus callosum of patients with HIBI.

Learning multimorbidity patterns from electronic health records using Non-negative Matrix Factorisation.

Multimorbidity, or the presence of several medical conditions in the same individual, has been increasing in the population - both in absolute and relative terms. Nevertheless, multimorbidity remains poorly understood, and the evidence from existing research to describe its burden, determinants and consequences has been limited. Previous studies attempting to understand multimorbidity patterns are often cross-sectional and do not explicitly account for multimorbidity patterns' evolution over time; some of them are based on small datasets and/or use arbitrary and narrow age ranges; and those that employed advanced models, usually lack appropriate benchmarking and validations. In this study, we (1) introduce a novel approach for using Non-negative Matrix Factorisation (NMF) for temporal phenotyping (i.e., simultaneously mining disease clusters and their trajectories); (2) provide quantitative metrics for the evaluation of these clusters and trajectories; and (3) demonstrate how the temporal characteristics of the disease clusters that result from our model can help mine multimorbidity networks and generate new hypotheses for the emergence of various multimorbidity patterns over time. We trained and evaluated our models on one of the world's largest electronic health records (EHR) datasets, containing more than 7 million patients, from which over 2 million where relevant to, and hence included in this study.

Deep learning for electronic health records: A comparative review of multiple deep neural architectures.

Despite the recent developments in deep learning models, their applications in clinical decision-support systems have been very limited. Recent digitalisation of health records, however, has provided a great platform for the assessment of the usability of such techniques in healthcare. As a result, the field is starting to see a growing number of research papers that employ deep learning on electronic health records (EHR) for personalised prediction of risks and health trajectories. While this can be a promising trend, vast paper-to-paper variability (from data sources and models they use to the clinical questions they attempt to answer) have hampered the field's ability to simply compare and contrast such models for a given application of interest. Thus, in this paper, we aim to provide a comparative review of the key deep learning architectures that have been applied to EHR data. Furthermore, we also aim to: (1) introduce and use one of the world's largest and most complex linked primary care EHR datasets (i.e., Clinical Practice Research Datalink, or CPRD) as a new asset for training such data-hungry models; (2) provide a guideline for working with EHR data for deep learning; (3) share some of the best practices for assessing the "goodness" of deep-learning models in clinical risk prediction; (4) and propose future research ideas for making deep learning models more suitable for the EHR data. Our results highlight the difficulties of working with highly imbalanced datasets, and show that sequential deep learning architectures such as RNN may be more suitable to deal with the temporal nature of EHR.

Soil Properties and Microbial Diversity at the Frontier of Laohugou Glacier Retreat in Qilian Mountains.

Glacier retreat may result in the decomposition of old organic carbon stored at the frontier of glacier retreat and the release of greenhouse gases such as CO2 and methane into the atmosphere. This process may gradually transform the soil in the region from its original status as a carbon sink into a carbon source, thus producing a positive feedback effect on global warming. In this study, Laohugou Glacier No. 12, Qilian Mountains, China, was taken as the research object, and the newly melted soil (Q1) at the frontier of glacier retreat and the sandy soil (Q2) on the bank of the nearby river were collected. The content of accumulation of organic matter (AOM) in Q1 soil was 5.56 ± 0.27 g/kg, and the total nitrogen was 0.60 ± 0.03 g/kg, which was significantly higher than that in Q2. The soil microbial carbon metabolism of Q2 was significantly (P < 0.01) higher than that of Q1 and the ability of organic matter to decompose was greater. The alpha diversity index of bacteria, fungi and archaea of Q2 was significantly higher than that of Q1. It may be that there were dominant species in Q1 causing the lower species evenness. The archaea metabolic function genes in Q1 were higher than those in Q2 because archaea are better adapted to a frozen environment. Bacterial carbohydrate and amino acid metabolism was abundant in Q2 and was related to microbial transformation of the carbon source into CO2.

KIAA0101 mRNA overexpression in peripheral blood mononuclear cells acts as predictive marker for hepatic cancer.

KIAA0101 always overexpresses in tumor tissues, which is also a marker of tumor recurrence. This study aims to explore whether overexpression of KIAA0101 mRNA in peripheral blood mononuclear cells (PBMCs) could act as a noninvasive and predictive biomarker of hepatic cancer. Real-time polymerase chain reaction (RT-PCR) was employed to detect KIAA0101 mRNA expression in PBMCs isolated from 93 hepatic cancer patients and 55 healthy individuals. The diagnostic sensitivity and specificity of KIAA0101 mRNA, CEA, and CD44V were analyzed and compared. A multivariate logistic regression analysis was utilized to analyze risk factors for overall survival of hepatic cancer patients. A concordance analysis was employed to compare the overexpression of KIAA0101 mRNA with clinicopathological diagnosis. All of the 93 hepatic cancer patients were followed up routinely at least 36 months or until death to analyze the 3-year overall survival rate. The results indicated that KIAA0101 mRNA expression was increased significantly in hepatic patients' PBMCs, when compared with that of healthy individuals (P < 0.05). Both the sensitivity and specificity of KIAA0101 mRNA in PBMCs were enhanced significantly compared with those of the CEA and CD44V biomarkers. The multivariate logistic regression analysis indicated that the KIAA0101 mRNA level and pTNM stage were significantly related with the overall survival of the hepatic patients. There was a better concordance between KIAA0101 mRNA overexpression and clinicopathological diagnosis for hepatic cancer (kappa = 0.914, P < 0.001). KIAA0101 mRNA overexpression in PBMCs decreased the 3-year survival rate significantly. In conclusion, overexpression of KIAA0101 mRNA in PBMCs could act as a predictive biomarker for hepatic cancer and has a better sensitivity and specificity.

Solvolysis mechanisms of RNA phosphodiester analogues promoted by mononuclear zinc(II) complexes: mechanisic determination upon solvent medium and ligand effects.

The solvolysis mechanisms of RNA phosphodiester model 2-(hydroxypropyl)-4-nitrophenyl phosphate (HpPNP) catalyzed by mononuclear zinc(II) complexes are investigated in the paper via a theoretical approach. The general-base-catalyzed (GBC) and specific-base-catalyzed (SBC) mechanisms are thoroughly discussed in the paper, and the calculations indicate a SBC mechanism (also named as the direct nucleophilic attack mechanism) when the cyclization of HpPNP is promoted by the Zn:[12]aneN3 complex ([12]aneN3 = 1,5,9-triazacyclododecane). The ligand effect is considered by involving two different catalysts, and the results show that the increasing size catalyst provides a lower energy barrier and a significant mechanistic preference to the SBC mechanism. The solvent medium effect is also explored, and reduced polarity/dielectric constant solvents, such as light alcohols methanol and ethanol, are more favorable. Ethanol is proven to be a good solvent medium because of its low dielectric constant. The computational results are indicative of concerted pathways. Our theoretical results are consistent with and well interpret the experimental observations and, more importantly, provide practical suggestions on the catalyst design and selection of reaction conditions.