Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploring the Potential of Hydrophilic Matrix Combined with Insoluble Film Coating: Preparation and Evaluation of Ambroxol Hydrochloride Extended Release Tablets

To explore the potential utility of combination of hydrophilic matrix with membrane-controlled technology, the present study prepared tablets of a water-soluble model drug (ambroxol hydrochloride), through process of direct compression and spray coating. Single-factor experiments were accomplished to optimize the formulation. In vivo pharmacokinetics was then performed to evaluate the necessity and feasibility of further development of this simple process and low-cost approach. Various release rates could be easily obtained by adjusting the viscosity and amount of hypromellose, pore-former ratios in coating dispersions and coating weight gains. Dissolution profiles of coated tablets displayed initial delay, followed by near zero-order kinetics. The pharmacokinetic study of different formulations showed that lag time became longer as the permeability of coating membrane decreased, which was consistent with the in vitro drug release trend. Besides, in vitro/in vivo correlation study indicated that coated tablets exhibited a good correlation between in vitro release and in vivo absorption. The results, therefore, demonstrated that barrier-membrane-coated matrix formulations were extremely promising for further application in industrialization and commercialization.
Nudging Urban Food Pantry Users in Utah Toward Healthier Choices

Purpose. To evaluate the impact of a nudge program on food pantry clients’ self-reported selection and use of healthy foods. Method. A convenience sample of clients of six urban food pantries in Utah were surveyed about their experience with the Thumbs Up for Healthy Choices nudge program. Chi-square tests were used to identify associations between demographic characteristics and self-reported program impact. Results. Ninety-four percent (n = 158) of respondents agreed that the program made it easier to make healthy choices. Sixty-five percent reported healthier diets since its implementation. Additionally, Hispanic respondents were more likely to report positive impacts than non-Hispanic respondents. Conclusions and Implications. Nudge programs are effective in increasing the selection of healthy foods among pantry clients in Utah. Impacts seemed to be particularly positive for Hispanic pantry users in Utah. Nutrition programs should consider implementing these low-cost strategies to improve dietary quality of pantry users.
Transglutaminase 2 mediates hypoxia-induced selective mRNA translation via polyamination of 4EBPs

This study highlights the role of transglutaminase 2 in selective mRNA translation of hypoxic cancer cells by polyamination-dependent modulation of 4EBPs, providing a target for cancer treatment. Hypoxia selectively enhances mRNA translation despite suppressed mammalian target of rapamycin complex 1 activity, contributing to gene expression reprogramming that promotes metastasis and survival of cancer cells. Little is known about how this paradoxical control of translation occurs. Here, we report a new pathway that links hypoxia to selective mRNA translation. Transglutaminase 2 (TG2) is a hypoxia-inducible factor 1–inducible enzyme that alters the activity of substrate proteins by polyamination or crosslinking. Under hypoxic conditions, TG2 polyaminated eukaryotic translation initiation factor 4E (eIF4E)-bound eukaryotic translation initiation factor 4E-binding proteins (4EBPs) at conserved glutamine residues. 4EBP1 polyamination enhances binding affinity for Raptor, thereby increasing phosphorylation of 4EBP1 and cap-dependent translation. Proteomic analyses of newly synthesized proteins in hypoxic cells revealed that TG2 activity preferentially enhanced the translation of a subset of mRNA containing G/C-rich 5′UTRs but not upstream ORF or terminal oligopyrimidine motifs. These results indicate that TG2 is a critical regulator in hypoxia-induced selective mRNA translation and provide a promising molecular target for the treatment of cancers.
Non-Thermalized Precursor-Mediated Dissociative Chemisorption at High Catalysis Temperatures.

Quasi-classical trajectory calculations and vibrational-state-selected beam-surface measurements of CH$_4$ chemisorption on Ir(111) reveal a non-thermal, hot-molecule mechanism for C-H bond activation. Low-energy vibrationally excited molecules trap in the physisorption well, and react before vibrational and translational energies accommodate with the surface. Reaction probability is strongly surface-temperature dependent and arises from the pivotal role of Ir atom thermal motion. In reactive trajectories, the mean outward Ir atom displacement largely exceeds that of the transition state geometry obtained through a full geometry optimization. The study also highlights a new way for (temporary) surface defects to impact high-temperature heterogeneous catalytic reactivity. Instead of reactants diffusing to and competing for geometrically localized lower barrier sites; transient, thermally activated surface atom displacements deliver low-barrier surface reaction geometries to the physisorbed reactants.
Retention forestry influences understory diversity and functional identity.

In recent decades, a paradigm shift in forest management and associated policies has led to greater emphasis on harvest practices that retain mature, overstory trees in forest stands that would otherwise be clearcut. While it is often assumed that the maintenance of compositional and structural complexity, such as that achieved through retention forestry approaches, will also mitigate negative impacts to functional diversity, empirical evidence of this relationship is sparse. We examined the effects of an aggregated retention system on taxonomic and functional diversity in a regenerating aspen-dominated forest. Sampling was conducted along transects arranged to capture the transition from harvested (regenerating) forest to mature, unharvested forest (both intact forest stands and 0.1 ha retention aggregates). We then assessed the magnitude and distance of edge effects on multiple indices of taxonomic and functional diversity as well as functional identity. Twelve years after harvest, the distance and magnitude of edge effects on functional and taxonomic diversity did not differ between the two unharvested patch sizes (intact vs. aggregate); however, intact forest exhibited greater resistance to edge effects and greater depth of edge influence into harvested areas for some traits compared to aggregates. Analyses relying on functional traits were generally applicable across sites within a highly variable forest type, and our results demonstrate the promise of using functional traits to assess management impacts on plant diversity across a landscape. Aggregates maintained some functional attributes associated with interior forest and influenced adjacent regeneration. However, trends in some traits (i.e. shade tolerance and seed mass), particularly in the seedling layer, suggest aggregates of this size provide primarily edge habitat.
Homozygous in‐frame variant of SCL6A3 causes dopamine transporter deficiency syndrome in a consanguineous family

The human dopamine transporter (hDAT) participates in dopamine homeostasis by clearing dopamine from the extracellular space using secondary active transport. Dysregulation of hDAT has been reported to be associated with different neuropsychiatric disorders. Dopamine transporter deficiency syndrome (DTDS) is a complex disease caused by defects in dopamine uptake within the synaptic cleft and patients manifest parkinsonian features. The extracellular loops are crucial for DAT activity and defects in these regions disturb dopamine transport. In the present study, a 3.5‐year‐old female in a consanguineous Iranian family with an initial diagnosis of gait imbalance and speech delay has been identified. We utilized whole‐exome sequencing (WES) to identify the possible genetic defect(s). WES identified a novel homozygous in‐frame indel variant, c. 1139_1150del; p.(Gly380_Lys384delinsGlu), in the SLC6A3 gene (NM_001044.4), as the most likely disease‐susceptibility variant. This variant is located in extracellular loop 4 (EL4) of the DAT protein. Our study highlights the role of extracellular loops and shows the EL4 of hDAT as a critical region for the protein activity. The identified variant in the EL4 region of DAT is predicted to compromise DAT function and may lead to DTDS in this case. However, complementary studies are required to confirm.
Knowledge and attitudes of secondary and higher secondary school teachers toward mental illness in Ahmedabad

Background: Teachers can be trained in early identification of possible mental illness and referral which is well-established in the west and lacking in India. Hence, we attempt to study the knowledge and attitudes of secondary school teachers toward mental illness and probable gender differences in these measures. Materials and Methods: Five hundred and twenty teachers from English medium schools of Ahmedabad city were assessed by a self-reported, predesigned and pretested 25 item questionnaire, the first 15 of which assessed their knowledge about mental illnesses and the remaining 10 pertained to negative attitudes. Results: 79.4% of teachers were 45 years or less, 77.5% were female teachers and 86.9% were married. 76% of teachers scored <7 out of 15 which points toward majority of them having inadequate knowledge. 63.6% scored 5 or more on the negative attitudes questionnaire, which points toward high prevalence of negative attitudes. Females had comparatively more knowledge than males about symptoms and management of mental illness, although there was no significant gender difference in the attitude toward mental illnesses. Conclusion: The knowledge of teachers about mental illness is insufficient, and they hold a lot of stigma against mentally ill as demonstrated by their low score in attitude.
A System Based-Approach to Examine Host Response during Infection with Influenza A Virus Subtype H7N9 in Human and Avian Cells

Although the influenza A virus H7N9 subtype circulates within several avian species, it can also infect humans with a severe disease outcome. To better understand the biology of the H7N9 virus we examined the host response to infection in avian and human cells. In this study we used the A/Anhui/1/2013 strain, which was isolated during the first wave of the H7N9 epidemic. The H7N9 virus-infected both human (Airway Epithelial cells) and avian (Chick Embryo Fibroblast) cells, and each infected host transcriptome was examined with bioinformatic tools and compared with other representative avian and human influenza A virus subtypes. The H7N9 virus induced higher expression changes (differentially regulated genes) in both cell lines, with more prominent changes observed in avian cells. Ortholog mapping of differentially expression genes identified significant enriched common and cell-type pathways during H7N9 infections. This data confirmed our previous findings that different influenza A virus subtypes have virus-specific replication characteristics and anti-virus signaling in human and avian cells. In addition, we reported for the first time, the new HIPPO signaling pathway in avian cells, which we hypothesized to play a vital role to maintain the antiviral state of H7N9 virus-infected avian cells. This could explain the absence of disease symptoms in avian species that tested positive for the presence of H7N9 virus.
Segregation distortion: Utilizing simulated genotyping data to evaluate statistical methods

Segregation distortion is the phenomenon in which genotypes deviate from expected Mendelian ratios in the progeny of a cross between two varieties or species. There is not currently a widely used consensus for the appropriate statistical test, or more specifically the multiple testing correction procedure, used to detect segregation distortion for high-density single-nucleotide polymorphism (SNP) data. Here we examine the efficacy of various multiple testing procedures, including chi-square test with no correction for multiple testing, false-discovery rate correction and Bonferroni correction using an in-silico simulation of a biparental mapping population. We find that the false discovery rate correction best approximates the traditional p-value threshold of 0.05 for high-density marker data. We also utilize this simulation to test the effect of segregation distortion on the genetic mapping process, specifically on the formation of linkage groups during marker clustering. Only extreme segregation distortion was found to effect genetic mapping. In addition, we utilize replicate empirical mapping populations of wheat varieties Avalon and Cadenza to assess how often segregation distortion conforms to the same pattern between closely related wheat varieties.
A high-fat diet during pregnancy impairs memory acquisition and increases leptin receptor expression in the hippocampus of rat offspring

ABSTRACT A high-fat diet (HFD) during pregnancy influences the neurodevelopment of progeny, particularly in the hippocampus, a brain region involved in cognitive processes. The hippocampus has high levels of leptin receptors (Ob-R) that participate in synaptic plasticity. This study examined the effect of maternal HFD during gestation on Ob-R expression in the CA1 and CA3 hippocampal regions, and its relationship with spatial learning and memory in the offspring. We used 48 rat pups: 24 from dams fed a balanced diet (BD, 6.2% fat) and 24 from those fed an HFD (42% fat) during pregnancy. We recorded weight gain and food intake in each pup every day beginning on postnatal day 3 (PND 3). Memory acquisition was assessed on PND 28 and memory retention on PND 42 in the Morris water maze (MWM). Then, 12 pups per group were selected randomly and subjected to bioimpedance spectroscopy. The remaining offspring was perfused to determine Ob-R expression levels in the CA1 and CA3 hippocampal regions. Interestingly, HFD pups had significantly higher weight gain, food intake, and fat mass than BD offspring. Interestingly, the HFD group showed poor memory performance, which correlated with changes in the Ob-R expression in both hippocampal regions. These data indicate that maternal exposure to HFD impacts neurodevelopmental and cognitive functions of the offspring.
Different MicroRNA Families Involved in Regulating High Temperature Stress Response during Cotton (Gossypium hirsutum L.) Anther Development

MicroRNAs (miRNAs) are small molecule RNAs widely involved in responses to plant abiotic stresses. We performed small RNA sequencing of cotton anthers at four developmental stages under normal and high temperature (NT and HT, respectively) conditions to investigate the stress response characteristics of miRNA to HT. A total of 77 miRNAs, including 33 known miRNAs and 44 novel miRNAs, were identified, and 41 and 28 miRNAs were differentially expressed under NT and HT stress conditions, respectively. The sporogenous cell proliferation (SCP), meiotic phase (MP), microspore release period (MRP), and pollen maturity (PM) stages had 10 (including 12 miRNAs), four (including six miRNAs), four (including five miRNAs), and seven (including 11 miRNAs) HT stress-responsive miRNA families, respectively, which were identified after removing the changes in genotype-specific miRNAs under NT condition. Seven miRNA families (miR2949, miR167, and miR160 at the SCP stage; miR156 and miR172 at the MP stage; miR156 at the MRP stage; and miR393 and miR3476 at the PM stage), which had expression abundance of more than 10% of the total expression abundance, served as the main regulators responding to HT stress with positive or negative regulation patterns. These miRNAs orchestrated the expression of the corresponding target genes and led to different responses in the HT-tolerant and the HT-sensitive lines. The results revealed that the HT stress response of miRNAs in cotton anthers were stage-specific and differed with the development of anthers. Our study may enhance the understanding of the response of miRNAs to HT stress in cotton anthers and may clarify the mechanism of plant tolerance to HT stress.
Free Fatty Acid Receptor 3 Differentially Contributes to Beta Cell Compensation Under High Fat Diet and Streptozotocin Stress.

The free fatty acid receptor 3 (FFA3) is a nutrient sensor of gut microbiota generated nutrients, the short chain fatty acids. Previously, we have shown that FFA3 is expressed in β cells and inhibits islet insulin secretion ex vivo. Here, we determined the physiological relevance of the above observation by challenging wildtype (WT) and FFA3 knockout (KO) male mice with, (a) hyperglycemia and monitoring insulin response via highly sensitive hyperglycemic clamps, (b) dietary high fat (HF), and (c) chemical induced diabetes. As expected, FFA3 KO mice exhibited significantly higher insulin secretion and glucose infusion rate in hyperglycemic clamps. Predictably, under metabolic stress induced by HF diet feeding, FFA3 KO mice exhibited less glucose intolerance compared to the WT mice. Moreover, similar islet architecture and β cell area in HF diet fed FFA3 KO and WT mice was observed. Upon challenge with streptozotocin (STZ), FFA3 KO mice initially exhibited a tendency for an accelerated incidence of diabetes compared to the WT mice. However, this difference was not maintained. Similar glycemia and β cell mass loss was observed in both genotypes 10 days post-STZ challenge. Higher resistance to STZ induced diabetes in WT mice could be due to higher basal islet autophagy. However, this difference was not protective as in response to STZ, similar autophagy induction was observed in both WT and FFA3 KO islets. These data demonstrate that FFA3 plays a role in modulating insulin secretion and β cell response to stressors. β cell FFA3 and autophagy link warrant further research.
hsa_circ_0000092 promotes hepatocellular carcinoma progression through up‐regulating HN1 expression by binding to microRNA‐338‐3p

Abstract Circular RNAs (circRNAs) have been identified in diverse cancers for their role in regulating multiple cellular processes by antagonizing microRNAs (miRNAs or miRs). However, the role of circRNA hsa_circ_0000092 in hepatocellular carcinoma (HCC) still remains enigmatic. Therefore, we aimed to investigate the specific mechanism of hsa_circ_0000092 in HCC. Differentially expressed circRNAs associated to HCC were initially analysed. The expression of hsa_circ_0000092, miR‐338‐3p and HN1 in HCC tissues and cell lines was examined. Next, the interaction among hsa_circ_0000092, miR‐338‐3p and HN1 was determined by dual‐luciferase reporter, RNA pull‐down and northern blot assays. Subsequently, a series of mimic, inhibitor or siRNA plasmids were delivered into HCC cells to validate the effects of hsa_circ_0000092, miR‐338‐3p and HN1 in controlling cell proliferation, migration, invasion and angiogenesis in vitro. Furthermore, the role of hsa_circ_0000092 in tumour growth of HCC in vivo was assessed with hsa_circ_0000092 depleted with siRNA. The hsa_circ_0000092/miR‐338‐3p/HN1 axis was predicted to participate in the development of HCC. hsa_circ_0000092 and HN1 were highly expressed while miR‐338‐3p was poorly expressed in HCC tissues and cell lines. hsa_circ_0000092 could competitively bind to miR‐338‐3p to up‐regulate HN1 expression. Moreover, depleted hsa_circ_0000092 or elevated miR‐338‐3p was shown to suppress HCC cell proliferation, migration, invasion and angiogenesis in vitro via down‐regulation of HN1. Furthermore, silencing hsa_circ_0000092 was demonstrated to suppress tumour growth in HCC in vivo. The results of this study suggested that hsa_circ_0000092 impaired miR‐338‐3p‐mediated HN1 inhibition to aggravate the development of HCC, indicating that hsa_circ_0000092 is a potential candidate marker and therapeutic target for HCC.
The R-Loop Atlas of Arabidopsis Development and Responses to Environmental Stimuli[OPEN]

This study provides the landscape of R-loops in Arabidopsis during development and stress responses and lays the groundwork for future investigation of the diverse functions of R-loops. R-loops are a common chromatin feature with essential functions in multiple cellular processes and diseases. However, little is known about the dynamic patterns of R-loops in a given organism. Here, using our recently developed genome-wide R-loop profiling method, we generated a comprehensive atlas quantifying the R-loop patterns of Arabidopsis (Arabidopsis thaliana) in 53 samples during development and during responses to environmental stimuli. The R-loop patterns were fairly stable in plants at the vegetative stage and in response to different light spectra and other environmental stimuli. Notably, the R-loops showed turnover during the plant life cycle, with patterns switching between generations. Importantly, R-loop dynamics was not strongly associated with RNA abundance, indicating that the mechanisms regulating R-loop formation and RNA accumulation are independent. We also observed enrichment of R-loops in transcription factor binding regions, suggesting that R-loops could function as potential cis-transcriptional regulators. This study provides an overview of R-loop dynamics in Arabidopsis during development and stress responses, highlights the unique dynamics of R-loops in the flowering plant Arabidopsis, and lays the groundwork for elucidating the functions of R-loops.
Effect of TRF1 rs3863242 polymorphism on telomere length in omethoate-exposed workers

Abstract Telomere length was found to be associated with omethoate exposure and polymorphisms in certain genes among occupational workers. However, whether the polymorphisms in telomere-binding protein genes influence telomere length remains unclear. To explore the correlation between telomere length and polymorphisms in telomere-binding protein genes, telomere length in peripheral blood leukocytes was determined by real-time quantitative polymerase chain reaction in 180 omethoate-exposed workers and 115 healthy controls. Polymorphisms in 10 pairs of alleles were detected using flight mass spectrometry or polymerase chain reaction–restriction fragment length polymorphism technique. The results showed that individuals with GG genotype in TRF1 rs3863242 had longer telomere lengths than those with AG + AA genotype in the control group (p = 0.005). The multiple regression analysis suggested that both omethoate exposure (b = 0.526, p < 0.001) and TRF1 rs3863242 GG (b = 0.220, p = 0.002) were related to a longer telomere length. In conclusion, GG genotype in TRF1 rs3863242 is linked to prolongation of telomere length, and individuals with GG genotype are recommended to strengthen health protection in a Chinese occupational omethoate-exposed population.