Miracle-dz/UniFAR-FTUs huggingface dataset:
A lncRNA survey finds increases in neuroprotective LINC‐PINT in Parkinson’s disease substantia nigra

Recent reports highlight regulatory functions of long noncoding RNAs (lncRNAs) in neurodegeneration and aging, but biomedical implications remain limited. Here, we report an rRNA‐depletion‐based long RNA‐Sequencing Resource of 65 substantia nigra, amygdala, and medial temporal gyrus samples from Parkinson's disease (PD) and matched control brains. Using a lncRNA‐focused analysis approach to identify functionally important transcripts, we discovered and prioritized many lncRNAs dysregulated in PD. Those included pronounced elevation of the P53‐induced noncoding transcript LINC‐PINT in the substantia nigra of PD patients, as well as in additional models of oxidative stress and PD. Intriguingly, we found that LINC‐PINT is a primarily neuronal transcript which showed conspicuous increases in maturing primary culture neurons. LINC‐PINT also accumulated in several brain regions of Alzheimer's and Huntington's disease patients and decreased with healthy brain aging, suggesting a general role in aging and neurodegeneration for this lncRNA. RNAi‐mediated depletion of LINC‐PINT exacerbated the death of cultured N2A and SH‐SY5Y cells exposed to oxidative stress, highlighting a previously undiscovered neuroprotective role for this tumor‐inducible lncRNA in the brains of patients with neurodegenerative disorders.
The physician manager. Practice management education in the 21st century.

: Are physicians prepared to operate competitively for the 21st century? Not according to a recent survey completed by the Society of Physicians in Administration's (SPA) membership. In fact, as far back as the 1980s, physician surveys indicated that third-year physician residents and recent graduates felt their training in practice management was inadequate. Understanding practice management issues would improve a physician's chances for success. According to the SPA survey, however, most medical schools and residency training programs don't offer courses in management.
Potential insertion complications with cochlear implant electrodes

Objectives: The aim of this discussion paper and literature review was to estimate the incidence of a variety of complications associated with the surgical placement of cochlear implant (CI) electrode arrays and to discuss the implications and management of sub-optimal electrode placement. Results: A review of the peer-reviewed literature suggests that the incidence of incomplete electrode insertion and kinking is more prevalent in straight arrays and not more than about 2% in CI recipients with normal cochlear anatomy/patency. Incidence of tip fold-over is greater with perimodiolar arrays but also occurs with straight arrays and is typically less than 5%. Conversely, electrode migration is more common with straight arrays, and high rates (up to 46%) have been reported in some studies. Scalar translocations have also been reported for both perimodiolar and straight arrays. Higher rates have been reported for stylet-based perimodiolar electrodes inserted via cochleostomy (up to 56%), but with much lower rates (<10%) with both sheath-based perimodiolar arrays and lateral wall arrays. Electrode positioning complications represent a significant proportion of perioperative CI complications and compromise the level of benefit from the device. Careful surgical planning and appropriate pre- and intraoperative imaging can reduce the likelihood and impact of electrode positioning complications. There is also evidence that newer array designs are less prone to certain complications, particularly scalar translocation. Conclusions: It is important that implanting surgeons are aware of the impact of sub-optimal electrode placement and the steps that can be taken to avoid, identify and manage such complications.
Correlating imaging parameters with molecular data: An integrated approach to improve the management of breast cancer patients

The goal of this review is to provide an overview of the studies aimed at integrating imaging parameters with molecular biomarkers for improving breast cancer patient’s diagnosis and prognosis. The use of diagnostic imaging to extract quantitative parameters related to the morphology, metabolism, and functionality of tumors, as well as their correlation with cancer tissue biomarkers is an emerging research topic. Thanks to the development of imaging biobanks and the technological tools required for extraction of imaging parameters including radiomic features, it is possible to integrate imaging markers with genetic data. This new field of study represents the evolution of radiology–pathology correlation from an anatomic–histologic level to a genetic level, which paves new interesting perspectives for breast cancer management.
Disassembling 2D van der Waals crystals into macroscopic monolayers and reassembling into artificial lattices

Larger monolayers with gold tapes Although the exfoliation of monolayers of materials such as transition metal dichalcogenides produces high-quality electronic materials with low defect densities, the size of the monolayers is limited to the micrometer scale. Liu et al. modified this method by creating atomically flat gold layers on polymer supports. The strong van der Waals adhesion of the gold layer allowed monolayers to be exfoliated on the centimeter scale. Multilayers could be reassembled to artificial structures, such as a MoSe2/WSe2 single-crystal bilayer with a twist angle chosen to quench intralayer exciton formation. Science, this issue p. 903 A polymer-supported atomically flat gold tape exfoliated centimeter-scale monolayers of transition metal dichalcogenides. Two-dimensional materials from layered van der Waals (vdW) crystals hold great promise for electronic, optoelectronic, and quantum devices, but technological implementation will be hampered by the lack of high-throughput techniques for exfoliating single-crystal monolayers with sufficient size and high quality. Here, we report a facile method to disassemble vdW single crystals layer by layer into monolayers with near-unity yield and with dimensions limited only by bulk crystal sizes. The macroscopic monolayers are comparable in quality to microscopic monolayers from conventional Scotch tape exfoliation. The monolayers can be assembled into macroscopic artificial structures, including transition metal dichalcogenide multilayers with broken inversion symmetry and substantially enhanced nonlinear optical response. This approach takes us one step closer to mass production of macroscopic monolayers and bulk-like artificial materials with controllable properties.
Autonomous Dam Surveillance Robot System Based on Multi-Sensor Fusion †

Dams are important engineering facilities in the water conservancy industry. They have many functions, such as flood control, electric power generation, irrigation, water supply, shipping, etc. Therefore, their long-term safety is crucial to operational stability. Because of the complexity of the dam environment, robots with various kinds of sensors are a good choice to replace humans to perform a surveillance job. In this paper, an autonomous system design is proposed for dam ground surveillance robots, which includes general solution, electromechanical layout, sensors scheme, and navigation method. A strong and agile skid-steered mobile robot body platform is designed and created, which can be controlled accurately based on an MCU and an onboard IMU. A novel low-cost LiDAR is adopted for odometry estimation. To realize more robust localization results, two Kalman filter loops are used with the robot kinematic model to fuse wheel encoder, IMU, LiDAR odometry, and a low-cost GNSS receiver data. Besides, a recognition network based on YOLO v3 is deployed to realize real-time recognition of cracks and people during surveillance. As a system, by connecting the robot, the cloud server and the users with IOT technology, the proposed solution could be more robust and practical.
Marketing to Children in Supermarkets: An Opportunity for Public Policy to Improve Children’s Diets

Public health experts worldwide are calling for a reduction of the marketing of nutrient-poor food and beverages to children. However, industry self-regulation and most government policies do not address in-store marketing, including shelf placement and retail promotions. This paper reports two U.S.-based studies examining the prevalence and potential impact of in-store marketing for nutrient-poor child-targeted products. Study 1 compares the in-store marketing of children’s breakfast cereals with the marketing of other (family/adult) cereals, including shelf space allocation and placement, special displays and promotions, using a national audit of U.S. supermarkets. Child-targeted cereals received more shelf space, middle- and lower-shelf placements, special displays, and promotions compared with other cereals. Study 2 compares the proportion of product sales associated with in-store displays and promotions for child-targeted versus other fruit drinks/juices, using syndicated sales data. A higher proportion of child-targeted drink sales were associated with displays and promotions than sales of other drinks. In both categories, the results were due primarily to major company products. Although in-store marketing of child-targeted products likely appeals to both children and parents, these practices encourage children’s consumption of nutrient-poor food and drinks. If companies will not voluntarily address in-store marketing to children, government policy options are available to limit the marketing of unhealthy foods in the supermarket.
CUX1 and IκBζ (NFKBIZ) mediate the synergistic inflammatory response to TNF and IL-17A in stromal fibroblasts

Significance Rheumatoid arthritis is characterized by elevated levels of inflammatory cytokines including TNF and IL-17A. Synovial fibroblasts produce inflammatory factors such as IL-6 in response to TNF, and the addition of IL-17A synergistically amplifies this response. We profiled the transcriptomic response of synovial fibroblasts to TNF and different IL-17A dosages over time, and defined a set of genes induced by the addition of IL-17A. We found that CUX1 and IκBζ (NFKBIZ) mediate leukocyte recruitment by regulating production of multiple cytokines and chemokines. We show that gene targets of CUX1 are elevated in synovial tissue from individuals with rheumatoid arthritis relative to controls. While many studies have focused on leukocytes, our results highlight CUX1 and IκBζ as key regulators of inflammation in synovial fibroblasts. The role of stromal fibroblasts in chronic inflammation is unfolding. In rheumatoid arthritis, leukocyte-derived cytokines TNF and IL-17A work together, activating fibroblasts to become a dominant source of the hallmark cytokine IL-6. However, IL-17A alone has minimal effect on fibroblasts. To identify key mediators of the synergistic response to TNF and IL-17A in human synovial fibroblasts, we performed time series, dose–response, and gene-silencing transcriptomics experiments. Here we show that in combination with TNF, IL-17A selectively induces a specific set of genes mediated by factors including cut-like homeobox 1 (CUX1) and IκBζ (NFKBIZ). In the promoters of CXCL1, CXCL2, and CXCL3, we found a putative CUX1–NF-κB binding motif not found elsewhere in the genome. CUX1 and NF-κB p65 mediate transcription of these genes independent of LIFR, STAT3, STAT4, and ELF3. Transcription of NFKBIZ, encoding the atypical IκB factor IκBζ, is IL-17A dose-dependent, and IκBζ only mediates the transcriptional response to TNF and IL-17A, but not to TNF alone. In fibroblasts, IL-17A response depends on CUX1 and IκBζ to engage the NF-κB complex to produce chemoattractants for neutrophil and monocyte recruitment.
Direct and indirect effects of temperature and precipitation on alpine seed banks in the Tibetan Plateau.

Plant community responses to global environmental change focus primarily on aboveground vegetation, however, the important role of the seed bank is frequently neglected. Specifically, the direct and indirect effects of changes in temperature and precipitation on seed banks remain poorly understood, yet seed banks provide a vital source of ecosystem resilience to global environmental change. We used a structural equation model to explore the direct and indirect effects of temperature and precipitation, and other biotic and abiotic factors, on soil seed bank community composition using 1026 soil seed bank samples from 57 sites along an elevation gradient that served as a space-for-time substitution for changing climate in the Tibetan Plateau. Seed bank richness was negatively correlated with both precipitation and temperature, but neither climate factor affected seed bank density. Temperature was also negatively correlated with vegetation species richness, which was positively correlated with seed bank richness and density. Both precipitation and temperature were positively correlated with soil total N, and total N was negatively correlated with vegetation richness. Both precipitation and temperature were negatively correlated with soil pH, and soil pH was negatively correlated with vegetation richness, but positively correlated with seed bank richness and density. Increasing precipitation and temperature would decrease seed bank diversity through direct effects as well as indirectly by decreasing vegetation diversity. Soil pH and total N emerged as the most important soil abiotic factors for seed bank diversity. Increasing precipitation and temperature under climate change may increase the extinction risk of some species in the seed bank by altering bet-hedging and risk-spreading strategies, which will degrade natural restoration ability and ultimately ecosystem resilience. This research is important because it identifies the potential underlying mechanistic basis of climate change impacts on seed banks through effects of aboveground vegetation and belowground biotic and abiotic factors.
Hippocampal and parahippocampal volumes vary by sex and traumatic life events in children

Background Childhood trauma is reliably associated with smaller hippocampal volume in adults; however, this finding has not been shown in children, and even less is known about how sex and trauma interact to affect limbic structural development in children. Methods Typically developing children aged 9 to 15 years who completed a trauma history questionnaire and structural T1-weighted MRI were included in this study (n = 172; 85 female, 87 male). All children who reported 4 or more traumas (n = 36) composed the high trauma group, and all children who reported 3 or fewer traumas (n = 136) composed the low trauma group. Using multivariate analysis of covariance, we compared FreeSurfer-derived structural MRI volumes (normalized by total intracranial volume) of the amygdalar, hippocampal and parahippocampal regions by sex and trauma level, controlling for age and study site. Results We found a significant sex × trauma interaction, such that girls with high trauma had greater volumes than boys with high trauma. Follow-up analyses indicated significantly increased volumes for girls and generally decreased volumes for boys, specifically in the hippocampal and parahippocampalregions for the high trauma group; we observed no sex differences in the low trauma group. We noted no interaction effect for the amygdalae. Limitations We assessed a community sample and did not include a clinical sample. We did not collect data about the ages at which children experienced trauma. Conclusion Results revealed that psychological trauma affects brain development differently in girls and boys. These findings need to be followed longitudinally to elucidate how structural differences progress and contribute to well-known sex disparities in psychopathology.
On the evolution of protein–adenine binding

Significance How proteins evolved to recognize and bind their ligands is a key mystery in protein function evolution. To explore this mystery, we study how proteins bind adenine, an ancient fragment. We characterize physicochemical patterns of protein–adenine interactions and link these to proteins’ evolutionary origins. In conflict with previous findings, we see that all of adenine’s hydrogen donors and acceptors have been used to bind proteins, and that adenine binding is likely to have emerged multiple times in evolution. To identify adenine-binding sites of shared origin, we use “themes”: short amino acid segments suggested to constitute evolutionary building blocks. We detect specific themes that are engaged in adenine binding; the detection of these in a protein’s sequence might reveal its function. Proteins’ interactions with ancient ligands may reveal how molecular recognition emerged and evolved. We explore how proteins recognize adenine: a planar rigid fragment found in the most common and ancient ligands. We have developed a computational pipeline that extracts protein–adenine complexes from the Protein Data Bank, structurally superimposes their adenine fragments, and detects the hydrogen bonds mediating the interaction. Our analysis extends the known motifs of protein–adenine interactions in the Watson–Crick edge of adenine and shows that all of adenine’s edges may contribute to molecular recognition. We further show that, on the proteins' side, binding is often mediated by specific amino acid segments (“themes”) that recur across different proteins, such that different proteins use the same themes when binding the same adenine-containing ligands. We identify numerous proteins that feature these themes and are thus likely to bind adenine-containing ligands. Our analysis suggests that adenine binding has emerged multiple times in evolution.
Achyranthis radix Extract-Loaded Eye Drop Formulation Development and Novel Evaluation Method for Dry Eye Treatment

Recently, Achyranthis radix extract has been studied as a therapeutic agent for dry eye disease that occurs from fine dust. The aim of this study was the development of Achyranthis radix extract-loaded eye drop formulations using lubricants, generally used for artificial tear eye drops. Ecdysterone was used as a marker compound for Achyranthis radix extract and 1% Achyranthis radix extract solution contained 14.37 ± 0.04 μg/mL of ecdysterone. Before formulation studies, a new method was performed to evaluate pigmentation, which might be caused by eye drops of herbal extract. A comparative study of the water retention ability of each formulation and ability to prevent the death of conjunctival epithelial cells in dry conditions was conducted. Moreover, treatment of Achyranthis radix extract (USL) eye drop formulation exhibited a significant inhibitory effect on inflammation in a concentration-dependent manner. The long-term and accelerated stability tests showed that lubricants could contribute to the stability of herbal extracts in solution. In conclusion, hyaluronic acid showed a good effect on the development of eye drop formulation using Achyranthis radix extracts for treating dry eye disease.
Nrf2 Activation Enhances Muscular MCT1 Expression and Hypoxic Exercise Capacity

ABSTRACT Introduction Skeletal muscle is the major producing and metabolizing site of lactic acid. A family of monocarboxylate transporter (MCT) proteins, especially MCT1 and MCT4, are involved in the lactate–pyruvate exchange and metabolism. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal coordinator of antioxidant response and energy metabolism, and has been reported to associate with the physiological functions of the skeletal muscle. Methods In this study, C57BL/6 J mice were administrated with an Nrf2 activator, sulforaphane (SFN) before taking incremental treadmill exercise to exhaustion under hypoxia; then the effects of SFN on exercise endurance and molecular/biochemical makers of the skeletal muscle were evaluated. Results The results indicated that SFN pretreatment enhanced the exercise endurance under hypoxia. SFN not only increased the expressions of antioxidant genes and activity of antioxidant enzymes, but also significantly increased the mRNA and protein levels of MCT1 and CD147, but not MCT4. Moreover, the expressions of LDH-B and LDH activity of converting lactate into pyruvate, as well as citrate synthase activity were significantly higher, whereas the LDH activity of converting pyruvate into lactate and blood lactate level were remarkably lower in the SFN-exercise mice than those of the phosphate-buffered saline–exercise group. Furthermore, Atf3Δzip2 (the alternatively spliced isoform of activating transcription factor-3) mRNA was increased by the exercise and further potentiated by SFN. Conclusion These results show, for the first time, that SFN increases MCT1 expression in the skeletal muscle under acute hypoxic exercise and suggest that Nrf2 activation is a promising strategy to enhance exercise performance under hypoxia.
Cleavage and degradation of EDEM1 promotes coxsackievirus B3 replication via ATF6a‐mediated unfolded protein response signalling

Our previous study of coxsackievirus B3 (CVB3)‐induced unfolded protein responses (UPR) found that overexpression of ATF6a enhances CVB3 VP1 capsid protein production and increases viral particle formation. These findings implicate that ATF6a signalling benefits CVB3 replication. However, the mechanism by which ATF6a signalling is transduced to promote virus replication is unclear. In this study, using a Tet‐On inducible ATF6a HeLa cell line, we found that ATF6a signalling downregulated the protein expression of the endoplasmic reticulum (ER) degradation‐enhancing α‐mannosidase‐like protein 1 (EDEM1), resulting in accumulation of CVB3 VP1 protein; in contrast, expression of a dominant negative ATF6a had the opposite effect. Furthermore, we found that EDEM1 was cleaved by both CVB3 protease 3C and virus‐activated caspase and subsequently degraded via the ubiquitin‐proteasome pathway. However, overexpression of EDEM1 caused VP1 degradation, likely via a glycosylation‐independent and ubiquitin‐lysosome pathway. Finally, we demonstrated that CRISPR/Cas9‐mediated knockout of EDEM1 increased VP1 accumulation and thus CVB3 replication. This is the first study to report the ER protein quality control of non‐enveloped RNA virus and reveals a novel mechanism by which CVB3 evades host ER quality control pathways through cleavage and degradation of the UPR target gene EDEM1, to ultimately benefit its own replication.
Circulating myokine levels in different stages of glucose intolerance

Abstract Type 2 diabetes is the fastest growing metabolic disease in the world. Recently, muscle is considered an endocrine organ which secretes various peptides that play an important role in insulin resistance and metabolic syndrome. We assessed 4 different myokines, irisin, interleukin-13 (IL-13), follistatin-related protein-1 (FSTL-1), and fractalkine, in normal, prediabetes, and diabetes patients. A total of 126 participants who visited Gangnam Severance Hospital were enrolled and divided into normal, prediabetes, and diabetes groups based on oral glucose tolerance test and hemoglobin a1c. A cross-sectional study was conducted to measure and compare serum levels of irisin, IL-13, FSTL-1, and fractalkine among the groups. Irisin level showed a tendency to increase in prediabetes group compared to normal group (P < .1) but showed a significant decrease when comparing diabetes from prediabetes group (P < .001). IL-13 decreased in diabetes group compared to prediabetes and normal group (P < .001, P < .05, respectively). FSTL-1 of diabetes group was lower than that of prediabetes group (P < .05), and fractalkine was higher in diabetes group compared to that of prediabetes and normal group (P < .01, P < .01, respectively). Irisin, IL-13, and FSTL-1 levels were reduced in diabetes group compared to normal or prediabetes group while fractalkine showed a progressive increase from normal to diabetes group. Further studies are warranted to study the roles of various myokine in diabetes through a larger prospective study.