Miracle-dz/UniFAR-FTUs huggingface dataset:
microRPM: a microRNA prediction model based only on plant small RNA sequencing data

Motivation MicroRNAs (miRNAs) are endogenous non-coding small RNAs (of about 22 nucleotides), which play an important role in the post-transcriptional regulation of gene expression via either mRNA cleavage or translation inhibition. Several machine learning-based approaches have been developed to identify novel miRNAs from next generation sequencing (NGS) data. Typically, precursor/genomic sequences are required as references for most methods. However, the non-availability of genomic sequences is often a limitation in miRNA discovery in non-model plants. A systematic approach to determine novel miRNAs without reference sequences is thus necessary. Results In this study, an effective method was developed to identify miRNAs from non-model plants based only on NGS datasets. The miRNA prediction model was trained with several duplex structure-related features of mature miRNAs and their passenger strands using a support vector machine algorithm. The accuracy of the independent test reached 96.61% and 93.04% for dicots (Arabidopsis) and monocots (rice), respectively. Furthermore, true small RNA sequencing data from orchids was tested in this study. Twenty-one predicted orchid miRNAs were selected and experimentally validated. Significantly, 18 of them were confirmed in the qRT-PCR experiment. This novel approach was also compiled as a user-friendly program called microRPM (miRNA Prediction Model). Availability and implementation This resource is freely available at http://microRPM.itps. ncku.edu.tw. Contact nslin@sinica.edu.tw or sarah321@mail.ncku.edu.tw. Supplementary information Supplementary data are available at Bioinformatics online.
Genetic Polymorphisms of Cytotoxic T-Lymphocyte Antigen 4 in Primary Biliary Cholangitis: A Meta-Analysis

Background and Aim The connection between gene polymorphisms of cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and primary biliary cholangitis (PBC) is still vague and blurred. The purpose of this study is to precisely estimate the association of the polymorphisms of CTLA4 with the risk of PBC by using a meta-analysis. Methods PubMed and the Chinese National Knowledge Infrastructure (CNKI) database were used to search correlative literatures, and the documents which were about the relationships between the polymorphisms of CTLA4 (rs231775, rs231725, rs3087243, and rs5742909) and PBC were collected as of June 2016. The strength of correlation based on odds ratios (ORs) and its 95% confidence intervals (95%CIs) was computed by STATA. Results Generally, in rs231775, a significant risk was found in G allele, the value of OR was 1.32, and its 95%CI was 1.19 to 1.47. The same situation was found in A allele of rs231725, the value of OR was 1.33, and its 95%CI was 1.22 to 1.45. As genotypic level, different genotypic models were also found to have obvious relevance with PBC in rs231775 and rs231725. No obvious connections were found in other SNPs. Conclusion This study indicated that the polymorphisms of rs231775 and rs231725 would be the risk factors of PBC.
Mercury in the Soil of Two Contrasting Watersheds in the Eastern United States

Soil represents the largest store of mercury (Hg) in terrestrial ecosystems, and further study of the factors associated with soil Hg storage is needed to address concerns about the magnitude and persistence of global environmental Hg bioaccumulation. To address this need, we compared total Hg and methyl Hg concentrations and stores in the soil of different landscapes in two watersheds in different geographic settings with similar and relatively high methyl Hg concentrations in surface waters and biota, Fishing Brook, Adirondack Mountains, New York, and McTier Creek, Coastal Plain, South Carolina. Median total Hg concentrations and stores in organic and mineral soil samples were three-fold greater at Fishing Brook than at McTier Creek. Similarly, median methyl Hg concentrations were about two-fold greater in Fishing Brook soil than in McTier Creek soil, but this difference was significant only for mineral soil samples, and methyl Hg stores were not significantly different among these watersheds. In contrast, the methyl Hg/total Hg ratio was significantly greater at McTier Creek suggesting greater climate-driven methylation efficiency in the Coastal Plain soil than that of the Adirondack Mountains. The Adirondack soil had eight-fold greater soil organic matter than that of the Coastal Plain, consistent with greater total Hg stores in the northern soil, but soil organic matter – total Hg relations differed among the sites. A strong linear relation was evident at McTier Creek (r2 = 0.68; p<0.001), but a linear relation at Fishing Brook was weak (r2 = 0.13; p<0.001) and highly variable across the soil organic matter content range, suggesting excess Hg binding capacity in the Adirondack soil. These results suggest greater total Hg turnover time in Adirondack soil than that of the Coastal Plain, and that future declines in stream water Hg concentrations driven by declines in atmospheric Hg deposition will be more gradual and prolonged in the Adirondacks.
Formulation Optimization and In Vivo Proof-of-Concept Study of Thermosensitive Liposomes Balanced by Phospholipid, Elastin-Like Polypeptide, and Cholesterol

One application of nanotechnology in medicine that is presently being developed involves a drug delivery system (DDS) employing nanoparticles to deliver drugs to diseased sites in the body avoiding damage of healthy tissue. Recently, the mild hyperthermia-triggered drug delivery combined with anticancer agent-loaded thermosensitive liposomes was widely investigated. In this study, thermosensitive liposomes (TSLs), composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG), cholesterol, and a fatty acid conjugated elastin-like polypeptide (ELP), were developed and optimized for triggered drug release, controlled by external heat stimuli. We introduced modified ELP, tunable for various biomedical purposes, to our thermosensitive liposome (e-TSL) to convey a high thermoresponsive property. We modulated thermosensitivity and stability by varying the ratios of e-TSL components, such as phospholipid, ELP, and cholesterol. Experimental data obtained in this study corresponded to results from a simulation study that demonstrated, through the calculation of the lateral diffusion coefficient, increased permeation of the lipid bilayer with higher ELP concentrations, and decreased permeation in the presence of cholesterol. Finally, we identified effective drug accumulation in tumor tissues and antitumor efficacy with our optimized e-TSL, while adjusting lag-times for systemic accumulation.
Human Cytomegalovirus Particles Treated with Specific Antibodies Induce Intrinsic and Adaptive but Not Innate Immune Responses

ABSTRACT Human cytomegalovirus (HCMV) persistently infects 40% to 100% of the human population worldwide. Experimental and clinical evidence indicates that humoral immunity to HCMV plays an important role in restricting virus dissemination and protecting the infected host from disease. Specific immunoglobulin preparations from pooled plasma of adults selected for high titers of HCMV antibodies have been used for the prevention of CMV disease in transplant recipients and pregnant women. Even though incubation of HCMV particles with these preparations leads to the neutralization of viral infectivity, it is still unclear whether the antibody-treated HCMV particles (referred to here as HCMV-Ab) enter the cells and modulate antiviral immune responses. Here we demonstrate that HCMV-Ab did enter macrophages. HCMV-Ab did not initiate the expression of immediate early antigens (IEAs) in macrophages, but they induced an antiviral state and rendered the cells less susceptible to HCMV infection upon challenge. Resistance to HCMV infection seemed to be due to the activation of intrinsic restriction factors and was independent of interferons. In contrast to actively infected cells, autologous NK cells did not degranulate against HCMV-Ab-treated macrophages, suggesting that these cells may not be eliminated by innate effector cells. Interestingly, HCMV-Ab-treated macrophages stimulated the proliferation of autologous adaptive CD4+ and CD8+ T cells. Our findings not only expand the current knowledge on virus-antibody immunity but may also be relevant for future vaccination strategies. IMPORTANCE Human cytomegalovirus (HCMV), a common herpesvirus, establishes benign but persistent infections in immunocompetent hosts. However, in subjects with an immature or dysfunctional immune system, HCMV is a major cause of morbidity and mortality. Passive immunization has been used in different clinical settings with variable clinical results. Intravenous hyperimmune globulin preparations (IVIg) are obtained from pooled adult human plasma selected for high anti-CMV antibody titers. While HCMV neutralization can be shown in vitro using different systems, data are lacking regarding the cross-influence of IVIg administration on the cellular immune responses. The aim of this study was to evaluate the effects of IVIg on distinct components of the immune response against HCMV, including antigen presentation by macrophages, degranulation of innate natural killer cells, and proliferation of adaptive CD4+ and CD8+ T cells.
Electronic Transport Properties of Trigonal Graphene Nanoribbon with Different Edge Termination

The electronic transport properties of trigonal graphene nanoribbon with different edge termination are studied with the first principle methods. It is found that edge termination plays an important role in electronic transport in these systems. The current of Fe-terminated nanoribbon increases more than two orders of magnitude compared with that of H-terminated systems. The reason of the current enhancement is attributed to the change of transmission spectra in the presence of different edge termination.
A Spin-on Dielectric Material for High Aspect Ratio Gap Fill

This communication describes the results of a potential spin-on glass (SOG) solution for narrow and high aspect ratio trench fill in both shallow trench isolation (STI) and premetal dielectric (PMD) applications. We have focused our development work on a hydrogen silsesquioxane (HSQ, (HSiO 3/2 )n) material, which offers the advantage of a carbon free gap fill solution. The main challenge for carbon-free SOG materials is to achieve material densification in the nano-scale gaps during thermal processing that of the gap filled material during the wet cleaning steps. This paper reports some approaches and findings on material densification in the nano-scale gaps and the results of subsequent wet etch tests.
Learning Filterbanks from Raw Speech for Phone Recognition

We train a bank of complex filters that operates on the raw waveform and is fed into a convolutional neural network for end-to-end phone recognition. These time-domain filterbanks (TD-filterbanks) are initialized as an approximation of mel-filterbanks, and then fine-tuned jointly with the remaining convolutional architecture. We perform phone recognition experiments on TIMIT and show that for several architectures, models trained on TD- filterbanks consistently outperform their counterparts trained on comparable mel-filterbanks. We get our best performance by learning all front-end steps, from pre-emphasis up to averaging. Finally, we observe that the filters at convergence have an asymmetric impulse response, and that some of them remain almost analytic.
Substrate recognition and mechanism revealed by ligand-bound polyphosphate kinase 2 structures

Significance Polyphosphate kinases (PPKs) are involved in many metabolic processes in bacteria, including pathogenic species. As these enzymes are not present in animals, they are a prime target for the development of novel antibiotics. The detailed knowledge of the mechanism of action and structure–function relationships of these enzymes is of utmost importance for the identification and design of new pharmaceutically active compounds and the rational improvement of lead structures. In addition, PPKs use inexpensive and stable polyphosphate as a phosphate donor and phosphorylate nucleoside 5′-mono- as well as 5′-diphosphates. This makes them of special interest for application in ATP regeneration systems, which can be efficiently coupled to ATP-consuming enzymes in environmentally friendly and sustainable biotechnological processes. Inorganic polyphosphate is a ubiquitous, linear biopolymer built of up to thousands of phosphate residues that are linked by energy-rich phosphoanhydride bonds. Polyphosphate kinases of the family 2 (PPK2) use polyphosphate to catalyze the reversible phosphorylation of nucleotide phosphates and are highly relevant as targets for new pharmaceutical compounds and as biocatalysts for cofactor regeneration. PPK2s can be classified based on their preference for nucleoside mono- or diphosphates or both. The detailed mechanism of PPK2s and the molecular basis for their substrate preference is unclear, which is mainly due to the lack of high-resolution structures with substrates or substrate analogs. Here, we report the structural analysis and comparison of a class I PPK2 (ADP-phosphorylating) and a class III PPK2 (AMP- and ADP-phosphorylating), both complexed with polyphosphate and/or nucleotide substrates. Together with complementary biochemical analyses, these define the molecular basis of nucleotide specificity and are consistent with a Mg2+ catalyzed in-line phosphoryl transfer mechanism. This mechanistic insight will guide the development of PPK2 inhibitors as potential antibacterials or genetically modified PPK2s that phosphorylate alternative substrates.
Quantitative analysis of gallstones in Libyan patients

Gallstone disease is one of the major surgical problems in the Libyan population; it is probably related to diet, especially excessive consumption of meat. The study was conducted to determine the composition of gallstones and their possible etiology in a Libyan population. The chemical composition of gallstones from 41 patients (six males and 35 females) was analyzed. The stones were classified into cholesterol, pigment, and mixed stones (MS). Cholesterol stones (CS) showed a significantly higher cholesterol content than pigment stones (PS) (p=0.0085) though not significantly higher than MS. Their phospholipid content and inorganic phosphates were higher than in the other types of stones and oxalate content was significantly elevated in comparison with MS (p=0.0471). In MS, the cholesterol, bile acids, and bilirubin were intermediate between cholesterol and PS, whereas triglycerides were significantly more than PS (p=0.0004). Bilirubin (0.0001) and bile acids (p=0.0009) were significantly higher than CS (p=0.0001). However, they contained the lowest amounts of sodium, potassium, magnesium, and oxalate. In PS, bilirubin (p=0.0001) was significantly higher than both groups. Bile acid content was significantly higher than CS (p=0.0001) but not significantly more than MS. They showed the highest values of calcium, sodium, potassium, magnesium, and chlorides compared to the other types of stones. High levels of cholesterol in stones and dyslipidemia associated with mixed as well as cholesterol gallstones suggest an etiological association and efforts to reduce dietary fat among the Libyan population may lead to decreased cholesterol and mixed gallstones.
Downregulation of neuroligin1 ameliorates postoperative pain through inhibiting neuroligin1/postsynaptic density 95-mediated synaptic targeting of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor GluA1 subunits in rat dorsal horns

Neuroligin1 is an important synaptic cell adhesion molecule that modulates the function of synapses through protein–protein interactions. Yet, it remains unclear whether the regulation of synaptic transmission in the spinal cord by neruoligin1 contributes to the development of postoperative pain. In a rat model of postoperative pain induced by plantar incision, we conducted Western blot study to examine changes in the expression of postsynaptic membrane of neuroligin1, postsynaptic density 95 (PSD-95), and α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor GluA1 and GluA2 subunits in the spinal cord dorsal horn after injury. The interaction between neuroligin1 and PSD-95 was further determined by using coimmunoprecipitation. Protein levels of neuroligin1 and GluA1, but not GluA2 and PSD-95, were significantly increased in the postsynaptic membrane of the ipsilateral dorsal horn at 3 h and 1 day after incision, as compared to that in control group (naïve). A greater amount of PSD-95 was coimmunoprecipitated with neuroligin1 at 3 h after incision than that in the control group. Intrathecal administration of small interfering RNAs (siRNAs) targeting neuroligin1 suppressed the expression of neuroligin1 in the spinal cord. Importantly, pretreatment with intrathecal neuroligin1 siRNA2497, but not scrambled siRNA or vehicle, prevented the upregulation of GluA1 expression at 3 h after incision, inhibited the enhanced neuroligin1/PSD-95 interaction, and attenuated postoperative pain. Together, current findings suggest that downregulation of spinal neuroligin1 expression may ameliorate postoperative pain through inhibiting neuroligin1/PSD-95 interaction and synaptic targeting of GluA1 subunit. Accordingly, spinal neuroligin1 may be a potential new target for postoperative pain treatment.
Connectivity Predicts deep brain stimulation outcome in Parkinson disease

The benefit of deep brain stimulation (DBS) for Parkinson disease (PD) may depend on connectivity between the stimulation site and other brain regions, but which regions and whether connectivity can predict outcome in patients remain unknown. Here, we identify the structural and functional connectivity profile of effective DBS to the subthalamic nucleus (STN) and test its ability to predict outcome in an independent cohort.
A Meta-analysis of the Association Between Physical Activity and Breast Cancer Mortality.

BACKGROUND There are conflicting data on the association between physical activity (PA) intensity and amount and prognosis of breast cancer. It is unknown whether increasing or decreasing PA is associated with all-cause mortality. OBJECTIVE The purpose of this study was to estimate the associations between PA and the risk of mortality. METHODS MEDLINE and EMBASE were used to find eligible studies published from January 1970 to March 2017 for this meta-analysis. We included 24 studies, with a total of 144 224 patients and follow-up periods ranging from 1.9 to 12.7 years. We categorized the amount of PA as low (<300 min/wk), moderate (300-500 min/wk), and high (>500 min/wk). RESULTS We found that high amounts of PA had an inverse relationship with breast-cancer-specific mortality and all-cause morality. Patients who decreased PA after diagnosis showed poorer all-cause mortality, whereas patients who increased PA postdiagnosis had a favorable association with all-cause mortality. Last, patients who met PA guidelines after diagnosis had a lower breast-cancer-specific mortality and all-cause mortality. CONCLUSION Physical activity may play a pivotal role in reducing the risk of death. Getting at least 300 min/wk of moderate-intensity PA will help improve the risk of breast cancer death. IMPLICATIONS FOR PRACTICE Participating in PA is an essential factor in breast cancer care that extends throughout the life span of cancer survivors. Higher levels of PA than current PA guidelines should be recommended to cancer patients.
Molecular landscape of acute promyelocytic leukemia at diagnosis and relapse

Acute promyelocytic leukemia (APL) occurs in about 5–30% of adult de novo AML and is characterized by the presence of the chromosomal translocation t(15;17)(q24;q21). The resulting PML-RARA chimeric gene involves the retinoic acid receptor alpha-(RARA) gene on chromosome 17 and the PML gene, a
E-commerce user behavior classification based on URL information from telecom DPI data

With the rapid development of mobile Internet, users turn to shopping online through e-commerce App. It is important to analyze user behavior such as browsing products, adding to cart, searching, and paying the bill. In this paper, we utilize the visiting information from DPI data of ISPs, and propose an e-commerce use behavior classification method only based on URL. In addition to N-gram features for URL, five schemes including Bi- and Tri-grams and combination words segmentation are proposed for feature extraction. Naive Bayesian, support vector machines, logistic regression, decision trees and random forests are used for multi-classification. Experimental results compare different feature extraction schemes with different models, which validate our proposed e-commerce user behavior classification method.
Pulmonary , gastrointestinal and urogenital pharmacology Effects of andrographolide on intrahepatic cholestasis induced by alpha-naphthylisothiocyanate in rats

Cholestasis is a cardinal manifestation of liver diseases but effective therapeutic approaches are limited. Therefore, alternative therapy for treating and preventing cholestatic liver diseases is necessary. Andrographolide, a promising anticancer drug derived from the medicinal plant Andrographis paniculata, has diverse pharmacological properties and multi-spectrum therapeutic applications. However, it is unknownwhether andrographolide has a hepatoprotective effect on intrahepatic cholestasis. The aims of this study were to investigate the protective effect and possible mechanisms of andrographolide in a rat model of acute intrahepatic cholestasis induced by alpha-naphthylisothiocyanate (ANIT). Andrographolide was administered intragastrically for four consecutive days, with a single intraperitoneal injection of ANIT on the second day. Liver injury was evaluated biochemically and histologically together with hepatic gene and protein expression analysis. Rats pretreated with andrographolide prior to ANIT injection demonstrated lower levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase, as well as bilirubin and bile acids as compared to rats treated with ANIT alone. Andrographolide also decreased the incidence and extent of periductular fibrosis and bile duct proliferation. Analysis of protein expression in livers from andrographolide-treated cholestatic rats revealed markedly decreased expression of alpha-smooth muscle actin and nuclear factor kappa-B (NF-κB). In conclusion, andrographolide has a potent protective property against ANIT-induced cholestatic liver injury. The mechanisms that underlie this protective effect are mediated through downregulation of NF-κB expression and inhibition of hepatic stellate cell activation. These findings suggest that andrographolide could be a promising therapeutic option in prevention and slowing down the progression of cholestatic liver diseases. & 2016 Elsevier B.V. All rights reserved.