Miracle-dz/UniFAR-FTUs huggingface dataset:
EMT-Induced Gemcitabine Resistance in Pancreatic Cancer Involves the Functional Loss of Equilibrative Nucleoside Transporter 1

Epithelial–mesenchymal transition (EMT) in cancer cells drives cancer chemoresistance, yet the molecular events of EMT that underpin the acquisition of chemoresistance are poorly understood. Here, we demonstrate a loss of gemcitabine chemosensitivity facilitated by human equilibrative nucleoside transporter 1 (ENT1) during EMT in pancreatic cancer and identify that cadherin switching from the epithelial (E) to neuronal (N) type, a hallmark of EMT, contributes to this loss. Our findings demonstrate that N-cadherin decreases ENT1 expression, membrane localization, and gemcitabine transport, while E-cadherin augments each of these. Besides E- and N-cadherin, another epithelial cell adhesion molecule, EpCAM, played a more prominent role in determining ENT1 membrane localization. Forced expression of EpCAM opposed cadherin switching with restored ENT1 expression, membrane localization, and gemcitabine transport in EMT-committed pancreatic cancer cells. In gemcitabine-treated mice, EpCAM-positive tumors had high ENT1 expression and reduced metastasis, whereas tumors with N-cadherin expression resisted gemcitabine treatment and formed extensive secondary metastatic nodules. Tissue microarray profiling and multiplexed IHC analysis of pancreatic cancer patient-derived primary tumors revealed EpCAM and ENT1 cell surface coexpression is favored, and ENT1 plasma membrane expression positively predicted median overall survival times in patients treated with adjuvant gemcitabine. Together, our findings identify ENT1 as an inadvertent target of EMT signaling mediated by cadherin switching and provide a mechanism by which mesenchymal pancreatic cancer cells evade gemcitabine therapy during EMT.
Fine-Scale Patterns of Genetic Structure in the Host Plant Chamaecrista fasciculata (Fabaceae) and Its Nodulating Rhizobia Symbionts

In natural plant populations, a fine-scale spatial genetic structure (SGS) can result from limited gene flow, selection pressures or spatial autocorrelation. However, limited gene flow is considered the predominant determinant in the establishment of SGS. With limited dispersal ability of bacterial cells in soil and host influence on their variety and abundance, spatial autocorrelation of bacterial communities associated with plants is expected. For this study, we collected genetic data from legume host plants, Chamaecrista fasciculata, their Bradyrhizobium symbionts and rhizosphere free-living bacteria at a small spatial scale to evaluate the extent to which symbiotic partners will have similar SGS and to understand how plant hosts choose among nodulating symbionts. We found SGS across all sampled plants for both the host plants and nodulating rhizobia, suggesting that both organisms are influenced by similar mechanisms structuring genetic diversity or shared habitat preferences by both plants and microbes. We also found that plant genetic identity and geographic distance might serve as predictors of nodulating rhizobia genetic identity. Bradyrhizobium elkanii was the only type of rhizobia found in nodules, which suggests some level of selection by the host plant.
Pectobacterium atrosepticum KDPG aldolase, Eda, participates in the Entner–Doudoroff pathway and independently inhibits expression of virulence determinants

Abstract Pectobacterium carotovorum has an incomplete Entner–Doudoroff (ED) pathway, including enzyme 2‐keto‐3‐deoxy‐6‐phosphogluconate aldolase (Eda) but lacking phosphogluconate dehydratase (Edd), while P. atrosepticum (Pba) has a complete pathway. To understand the role of the ED pathway in Pectobacterium infection, mutants of these two key enzymes, Δeda and Δedd, were constructed in Pba SCRI1039. Δeda exhibited significant decreased virulence on potato tubers and colonization in planta and was greatly attenuated in pectinase activity and the ability to use pectin breakdown products, including polygalacturonic acid (PGA) and galacturonic acid. These reduced phenotypes were restored following complementation with an external vector expressing eda. Quantitative reverse transcription PCR analysis revealed that expression of the pectinase genes pelA, pelC, pehN, pelW, and pmeB in Δeda cultured in pyruvate, with or without PGA, was significantly reduced compared to the wild type, while genes for virulence regulators (kdgR, hexR, hexA, and rsmA) remained unchanged. However, Δedd showed similar phenotypes to the wild type. To our knowledge, this is the first demonstration that disruption of eda has a feedback effect on inhibiting pectin degradation and that Eda is involved in building the arsenal of pectinases needed during infection by Pectobacterium.
Acceleration of Carbon Fixation in Chilling-Sensitive Banana under Mild and Moderate Chilling Stresses

Banana is one of the most important food and fruit crops in the world and its growth is ceasing at 10–17 °C. However, the mechanisms determining the tolerance of banana to mild (>15 °C) and moderate chilling (10–15 °C) are elusive. Furthermore, the biochemical controls over the photosynthesis in tropical plant species at low temperatures above 10 °C is not well understood. The purpose of this research was to reveal the response of chilling-sensitive banana to mild (16 °C) and moderate chilling stress (10 °C) at the molecular (transcripts, proteins) and physiological levels. The results showed different transcriptome responses between mild and moderate chilling stresses, especially in pathways of plant hormone signal transduction, ABC transporters, ubiquinone, and other terpenoid-quinone biosynthesis. Interestingly, functions related to carbon fixation were assigned preferentially to upregulated genes/proteins, while photosynthesis and photosynthesis-antenna proteins were downregulated at 10 °C, as revealed by both digital gene expression and proteomic analysis. These results were confirmed by qPCR and immunofluorescence labeling methods. Conclusion: Banana responded to the mild chilling stress dramatically at the molecular level. To compensate for the decreased photosynthesis efficiency caused by mild and moderate chilling stresses, banana accelerated its carbon fixation, mainly through upregulation of phosphoenolpyruvate carboxylases.
The Effect of Resistance Training on the Function after Hip Replacement: A Meta-analysis of Randomized Controlled Trials

Abstract Introduction The efficacy of resistance training for hip replacement remains controversial. We conducted a systematic review and meta-analysis to explore the influence of resistance training on functional recovery for hip replacement. Methods We searched PubMed, EMbase, Web of Science, EBSCO, and Cochrane Library databases through April 2018 for randomized controlled trials (RCTs) assessing the effect of resistance training on hip replacement. Results Five RCTs involving 251 patients are included in the meta-analysis. Overall, compared with the control group for post-hip replacement patients, resistance training can significantly improve hip-related quality of life (standard mean difference [SMD] = 0.35; 95% CI = 0.02 to 0.68; p = 0.04), symptoms (SMD = 0.41; 95% CI = 0.08 to 0.74; p = 0.02), sports and recreation (SMD = 0.41; 95% CI = 0.08 to 0.75; p = 0.01), and reduce pain scores (SMD = 0.41; 95% CI = 0.08 to 0.74; p = 0.02), but has no remarkable impact on activities of daily living function (SMD = 0.48; 95% CI = 0 to 0.96; p = 0.05), sit to stand (SMD = 0.17; 95% CI = − 0.25 to 0.59; p = 0.44), stair climb performance (SMD = 0.06; 95% CI = − 0.36 to 0.48; p = 0.77), and leg extension power (SMD = 0.42; 95% CI = − 0.17 to 1.01; p = 0.17). Conclusions Resistance training is associated with significantly improved hip-related quality of life, symptoms, and sports and recreation, and decreased pain scores in post-hip replacement patients.
Genetic Diversity of the Noncoding Control Region of the Novel Human Polyomaviruses

The genomes of polyomaviruses are characterized by their tripartite organization with an early region, a late region and a noncoding control region (NCCR). The early region encodes proteins involved in replication and transcription of the viral genome, while expression of the late region generates the capsid proteins. Transcription regulatory sequences for expression of the early and late genes, as well as the origin of replication are encompassed in the NCCR. Cell tropism of polyomaviruses not only depends on the appropriate receptors on the host cell, but cell-specific expression of the viral genes is also governed by the NCCR. Thus far, 15 polyomaviruses have been isolated from humans, though it remains to be established whether all of them are genuine human polyomaviruses (HPyVs). The sequences of the NCCR of these HPyVs show high genetic variability and have been best studied in the human polyomaviruses BK and JC. Rearranged NCCRs in BKPyV and JCPyV, the first HPyVs to be discovered approximately 30 years ago, have been associated with the pathogenic properties of these viruses in nephropathy and progressive multifocal leukoencephalopathy, respectively. Since 2007, thirteen novel PyVs have been isolated from humans: KIPyV, WUPyV, MCPyV, HPyV6, HPyV7, TSPyV, HPyV9, HPyV10, STLPyV, HPyV12, NJPyV, LIPyV and QPyV. This review describes all NCCR variants of the new HPyVs that have been reported in the literature and discusses the possible consequences of NCCR diversity in terms of promoter strength, putative transcription factor binding sites and possible association with diseases.
Développement de procédés plasma pour l'élaboration et la caractérisation du silicium photovoltaïque : dépôt de couches minces épitaxiées de silicium par PECVD : mesure de la pureté du silicium à l'état solide ( 20°C) et liquide (1414°C) par LIBS

Aujourd’hui, le principal facteur limitant le photovoltaique est le prix eleve du kWh produit par les modules PV. Pour faire face a cette difficulte, les recherches actuelles se concentrent autour de plusieurs leviers et solutions alternatives : la reduction du cout energetique avec notamment la reduction du cout de la matiere premiere, qui consiste en la diminution de l’epaisseur des wafers de silicium, ou encore l’elaboration de cellules en couches minces de silicium. Ce dernier procede a pour but de s’affranchir de l’etape de sciage des blocs de silicium, necessaire pour la realisation de plaquette photovoltaique de faible epaisseur. C’est cette derniere approche qui nous a conduits a proposer un procede d’elaboration de couches minces a l’aide d’un plasma et du chauffage du substrat. Par ailleurs, quel que soit le procede choisi pour atteindre la cristallinite et la purete exigees pour le grade solaire, il est necessaire de disposer de technique analytique multielementaire pour controler l’evolution de la purete en fonction des parametres. La LIBS que nous avons developpee au laboratoire offre l’opportunite de repondre a ces attentes : tres basses limites de detection tout en permettant un suivi en ligne du silicium a l’etat solide ou en fusion.
Methanol bioeconomy: promotion of rice crop yield in paddy fields with microbial cells prepared from natural gas‐derived C1 compound

Methylotrophs, which can utilize methanol as a sole carbon source, are promising microorganisms to be exploited in a methanol‐based bioeconomy, in which a variety of useful compounds are biotechnologically produced from natural gas‐derived methanol. Pink‐pigmented facultative methylotrophs (PPFMs) are common plant phyllospheric bacteria and are known to enhance seedling growth and total biomass of various plants. However, improvement of crop yield by inoculation of PPFMs at the field level has not been well investigated. We herein describe improvement of crop yield of several rice cultivars by foliar spraying of PPFMs. After selection of PPFM strains and rice cultivars by the in vitro seedling growth test, we further conducted paddy field experiments. The crop yield of the sake‐brewing rice Oryza sativa cultivar Hakutsurunishiki was reproducibly improved in a commercial paddy field for over a 5‐year period. A one‐time foliar spray of PPFM cells (living or killed) or a cell wall polysaccharide fraction, after the heading date, acted in the phyllosphere and effectively improved crop yield. Our results show that the established process with PPFMs is feasible for improvement of food production in the methanol bioeconomy.
Radiosensitivity of Cancer Stem Cells Has Potential Predictive Value for Individual Responses to Radiotherapy in Locally Advanced Rectal Cancer

Simple Summary Radiotherapy is often used as a neo-adjuvant treatment in locally advanced rectal cancer. While treatment generally induces an improvement in the outcome, some patients show resistance to treatment for reasons that still have to be elucidated. In this work, we report an in vitro and in vivo model based on patient-derived cancer stem cells. This model is able to predict individual responses to radiotherapy. The results indicate that cells found to be radiation-sensitive in vitro generated radiation-sensitive tumor xenografts upon subcutaneous implantation. Analogously, cancer stem cells (CSCs) that did not respond to in vitro radiation treatment generated radiation-resistant tumor xenografts. Moreover, radioresistant CSCs were generally isolated via biopsies of patients with poor responses to neo-adjuvant radiotherapy. This suggests that a cell-based in vitro test may itself be sufficient to predict outcomes in donor patients. Abstract Neo-adjuvant radiotherapy is frequently employed in the therapeutic management of locally advanced rectal cancer (LARC). Radiotherapy can both reduce local recurrence and improve the success of surgical procedures by reducing tumor mass size. However, some patients show a poor response to treatment, which results in primary resistance or relapse after apparent curative surgery. In this work, we report in vitro and in vivo models based on patient-derived cancer stem cells (CSCs); these models are able to predict individual responses to radiotherapy in LARC. CSCs isolated from colorectal cancer biopsies were subjected to in vitro irradiation with the same clinical protocol used for LARC patients. Animal models, generated by CSC xenotransplantation, were also obtained and treated with the same radiotherapy protocol. The results indicate that CSCs isolated from rectal cancer needle biopsies possess an intrinsic grade of sensitivity to treatment, which is also maintained in the animal model. Notably, the specific CSCs’ in vitro and in vivo sensitivity values correspond to patients’ responses to radiotherapy. This evidence suggests that an in vitro radiotherapy response predictivity assay could support clinical decisions for the management of LARC patients, thus avoiding radiation toxicity to resistant patients and reducing the treatment costs.
Development of the Chinese, Malay and Tamil translations of the Positive Mental Health Instrument: Cross-cultural adaptation, validity and internal consistency

This study describes the development and validation of Chinese, Malay and Tamil translations of the Positive Mental Health Instrument (PMHI) in a general population sample in Singapore. Translations were performed using two independent forward translations followed by expert panel discussions and tested for content, construct and language appropriateness using focus group discussions. The final translated tools were field-tested among 220 residents per language using self-administered questionnaires comprising the translated PMHI and other validity measures. Missing data, floor and ceiling effects, confirmatory factor analysis (CFA), internal consistency, item response theory differential item functioning (IRT-DIF) and criterion validity were assessed. A total of 10 PMHI-Chinese items, 26 PMHI-Malay items and six response categories and six PMHI-Tamil items were modified based on expert panel and focus group discussions. PMHI had low missing data and showed negative but acceptable skewness (<2) and kurtosis (<7) for all translations, except for the PMHI-Malay “spirituality” subscale (skewness: -2.8; kurtosis: 12.5). CFA showed that all three PMHI translations fulfilled the original six-factor-higher-order structure (RMSEA = 0.05, CFI = 0.962, TLI = 0.96). Cronbach’s alpha coefficients for total PMHI were 0.958, 0.954, 0.945 and 0.949 in the overall sample and the Chinese, Malay and Tamil translations, respectively. The three translations of the PMHI showed expected and significant positive (r = 0.116 to 0.663) and negative correlations (r = −0.137 to −0.574) with established measures. The findings show that the Chinese, Malay and Tamil translations of the PMHI have high internal consistency and validity in this multi-ethnic population.
Photodynamic cancer therapy: role of Ag- and Au-based hybrid nano-photosensitizers

Abstract The utilization of photodynamic therapy (PDT) has been rapidly increasing due to its advantage as an effective treatment modality for cancer. The organic photosensitizers employed for PDT have some disadvantages, including high toxicity, non-selectivity toward tumors and poor absorption of light. The low light penetration into the tumor sites resulting from low wavelength of absorption and long-term skin photosensitivity. Hence, the attention toward non-toxic inorganic photosensitizers like noble metal nanoparticles (NPs) has been increasing nowadays. In bioscience, NPs are replacing organic dyes since they have photostability and non-toxicity. Generally, nanomaterials can easily form compounds with other substances as well as organic materials and the modified NPs surface enhances the chemical activity. Among the metal NPs, noble metals, especially gold and silver are attractive because of their size and shape-dependent unique optoelectronic properties. The coating of inorganic/organic materials on top of the noble metal makes the NPs bio-compatible and less toxic. Furthermore, Ag- and Au-based inorganic/organic complex NPs could offer a new possibility because of their unique structures. Meanwhile, the coating of inorganic/organic complex NPs protects the noble metals and stabilizes them against chemical corrosion and enhances the production of reactive oxygen species. Thus, in this review, we have highlighted the role of Ag- and Au-based inorganic/organic hybrid nano-photosensitizers in photodynamic therapy. Communicated by Ramaswamy H. Sarma
Cognitive Impairment in Older Adults and Therapeutic Strategies

Cognitive impairment and its severe form dementia are increasingly prevalent in older adults and loom as a public health disaster unless effective interventions are developed. Cognitive impairment is a convergent trait caused by damage from an idiosyncratic mix of four prevalent diseases (Alzheimer disease; vascular brain injury; Lewy body diseases, such as Parkinson disease and dementia with Lewy bodies; and limbic-predominant age-related transactive response DNA-binding protein 43 encephalopathy) that is counterbalanced by individually varying resilience, which is comprised of reserve and compensation. Brain regional damage from each of these four prevalent diseases is generated by the net effect of injury and (mal)adaptive response and is accompanied by characteristic lesions. Existing therapeutics enhance resilience, whereas most agents under development target mechanisms of damage with only suppression of vascular brain injury yet to show therapeutic promise. We hope to anticipate future tailored interventions that target mechanisms of damage and thereby avert the oncoming surge of cognitive impairment and dementia in older adults. Significance Statement Brain regional damage is generated by the net effect of injury and (mal)adaptive response. The extent to which signs and symptoms of such damage occur is influenced by an underlying resilience comprising reserve and compensation. Finding tailored interventions that target specific mechanisms of damage likely yields the most effective therapies.
Nature and Light Dependence of Bulk Recombination in Co-Pi-Catalyzed BiVO4 Photoanodes

BiVO4 is considered to be a promising photoanode material for solar water splitting applications. Its performance is limited by two main factors: slow water oxidation kinetics and poor charge separation. We confirm recent reports that cobalt phosphate (Co-Pi) is an efficient water oxidation catalyst for BiVO4 and report an AM1.5 photocurrent of 1.7 mA/cm2 at 1.23 V vs RHE for 100 nm spray-deposited, compact, and undoped BiVO4 films with an optimized Co-Pi film thickness of 30 nm. The charge separation of these films depends strongly on light intensity, ranging from 90% at low light intensities to less than 20% at intensities corresponding to 1 sun. These observations indicate that the charge separation efficiency in BiVO4 is limited by poor electron transport and not by the presence of bulk defect states, interface traps, or the presence of a Schottky junction at the back-contact.
An exploratory clinical trial on acceptance and commitment therapy as an adjunct to psychoeducational relaxation therapy for chronic pain

Abstract Objective: The aim of this study was to compare the clinical efficacy of two differently-designed psychological interventions for chronic pain. Design: 138 patients presenting chronic pain were randomly assigned to one of two experimental conditions: (1) Psychoeducational relaxation therapy (PRT, n = 84) or (2) PRT followed by acceptance and commitment therapy (PRT + ACT, n = 54). Main outcome measures: Pain intensity, quality of life (SF-36), anxiety and depression (HADS), stress (PSS), pain catastrophizing (PCS), chronic pain acceptance (CPAQ), and psychological inflexibility (PIPS) were assessed at three time-points: before therapy (T1); at the end of the therapy (T2); and 3- months after the end of the therapy (T3). Results: In T2, the PRT intervention showed more significant improvements in the measures of mental quality of life [F (1,92) = 7.478, P < . 05] and depression [F (1, 92) = 5.804, P < . 05] compared to the PRT + ACT intervention. The experimental groups did not differ in their outcome measures at T3. Conclusion: PRT appears to be an effective solution in the psychological care of chronic pain. The effectiveness of this type of intervention seems to have been underestimated. The addition of ACT sessions did not significantly impact the results, indicating that both designs of interventions are effective in the short term.
Aircraft Control Method Based on Deep Reinforcement Learning

To address the failure of precise overload tracking and anti-interference caused by the difficulty of accurate modeling of a complex aircraft, the controller designing method based on deep reinforcement learning is studied. This paper trained the control network based on the Proximal Policy Optimization (PPO), studied the tracking control problem of the aircraft, and accurately tracked the typical command signals. Fixed-point simulation of the aircraft is performed, with results showing that, in presence of aircraft model parameter variation and external disturbance, the controller based on deep reinforcement learning can achieve accurate tracking of overload commands.