Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of EjSPL3, EjSPL4, EjSPL5, and EjSPL9 in Regulating Flowering in Loquat (Eriobotrya japonica Lindl.)

The age pathway is important for regulating flower bud initiation in flowering plants. The major regulators in this pathway are miR156 and SPL transcription factors. To date, SPL genes have been identified in many species of plants. Loquat, as a woody fruit tree of Rosaceae, is unique in flowering time as it blooms in winter. However, the study of its SPL homologous genes on the regulation mechanism of flowering time is still limited. In this study, four SPL homologs—EjSPL3, EjSPL4, EjSPL5, and EjSPL9—are cloned from loquat, and phylogenetic analysis showed that they share a high sequence similarity with the homologues from other plants, including a highly conserved SQUAMOSA promoter binding protein (SBP)-box domain. EjSPL3, EjSPL4, EjSPL5 are localized in the cytoplasm and nucleus, and EjSPL9 is localized only in the nucleus. EjSPL4, EjSPL5, and EjSPL9 can significantly activate the promoters of EjSOC1-1, EjLFY-1, and EjAP1-1; overexpression of EjSPL3, EjSPL4, EjSPL5, and EjSPL9 in wild-type Arabidopsis thaliana can promote flowering obviously, and downstream flowering genes expression were upregulated. Our work indicated that the EjSPL3, EjSPL4, EjSPL5, and EjSPL9 transcription factors are speculated to likely participate in flower bud differentiation and other developmental processes in loquat. These findings are helpful to analyze the flowering regulation mechanism of loquat and provide reference for the study of the flowering mechanism of other woody fruit trees.
Nanoformulated Zoledronic Acid Boosts the Vδ2 T Cell Immunotherapeutic Potential in Colorectal Cancer

Aminobisphosphonates, such as zoledronic acid (ZA), have shown potential in the treatment of different malignancies, including colorectal carcinoma (CRC). Yet, their clinical exploitation is limited by their high bone affinity and modest bioavailability. Here, ZA is encapsulated into the aqueous core of spherical polymeric nanoparticles (SPNs), whose size and architecture resemble that of biological vesicles. On Vδ2 T cells, derived from the peripheral blood of healthy donors and CRC patients, ZA-SPNs induce proliferation and trigger activation up to three orders of magnitude more efficiently than soluble ZA. These activated Vδ2 T cells kill CRC cells and tumor spheroids, and are able to migrate toward CRC cells in a microfluidic system. Notably, ZA-SPNs can also stimulate the proliferation of Vδ2 T cells from the tumor-infiltrating lymphocytes of CRC patients and boost their cytotoxic activity against patients’ autologous tumor organoids. These data represent a first step toward the use of nanoformulated ZA for immunotherapy in CRC patients.
Functional Characterization of a Venom Protein Calreticulin in the Ectoparasitoid Pachycrepoideus vindemiae

Venom proteins act in the immunological interactions between parasitoids and their host insects. The effect of venom proteins on host immunity is not fully understood in pupal parasitoids. We identified the functions of a venom protein, calreticulin (PvCRT), in the pupal ectoparasitoid Pachycrepoideus vindemiae. Here, we report that PvCRT features a signal peptide and two conserved “calreticulin” domains. Multiple sequence alignments show that PvCRT shares 83.54% amino acid identity with CRT from both Pteromalus puparum and Nasonia vitripennis, which infers a close relationship among these three species. Using qPCR analysis, we found a lower expression level of PvCRT (0.27-fold) in the venom apparatus compared to the corresponding carcass. Immunohistochemical localization revealed that PvCRT was ubiquitously expressed in venom gland. The expression of the PvCRT gene in Drosophila transgenic lines via the UAS/Gal4 binary expression system reduced the self-encapsulation phenotype of tu(1)Sz1 mutants. Additionally, studies on humoral immunity indicate that PvCRT does not affect the antimicrobial immune responses of the host. This work on an ectoparasitoid will increase our understanding of venom–mediated host-parasitoid interactions.
Targeting fibrinogen‐like protein 1 is a novel therapeutic strategy to combat obesity

Fibrinogen‐like‐protein 1 (FGL1) is a novel hepatokine that plays an important role in hepatic steatosis and insulin resistance. Although FGL1 expression can be detected in adipose tissues, the functions of FGL1 in adipose tissues are still unknown. In this study, 356 participants with (body mass index (BMI) ≥25 kg/m2; n = 134) or without obesity (BMI <25 kg/m2; n = 222) were recruited, and we found that the plasma FGL1 concentrations were significantly higher in obese group than those of in the normal weight group, and were positively correlated with age, BMI, waist circumference, fat content, plasma glucose at 2 hours during an oral glucose tolerance test, and the insulin sensitivity index. In univariate analyses, BMI, waist circumference, total fat, visceral fat, and subcutaneous fat areas were positively correlated with FGL1 levels. After adjusting for age and gender, obesity indices, including the BMI and different fat areas, remained significantly associated with FGL1 levels. In order to investigate the causal relationship between FGL1 and obesity, animal and cell models were used. Overexpression of FGL1 in epididymal adipose tissue by lentiviral vector encoding FGL1 increased the fat pad size, whereas FGL1‐knockdown by lentiviral vector encoding short‐hairpin RNA targeted to FGL1 decreased high‐fat diet‐induced adiposity. In addition, 3T3‐L1 adipocytes were used to clarify the possible mechanism of FGL1‐induced adipogenesis. FGL1 induced adipogenesis through an ERK1/2‐C/EBPβ‐dependent pathway in 3T3‐L1 adipocytes. These findings highlight the pathophysiological role of FGL1 in obesity, and FGL1 might be a novel therapeutic target to combat obesity.
X-ray diffraction from strongly bent crystals and spectroscopy of X-ray free-electron laser pulses

A strongly bent crystal diffracts kinematically when the bending radius is small compared with the critical radius given by the ratio of the extinction length to the Darwin width of the reflection. Under these conditions, the spectral resolution of the X-ray free-electron laser pulse is limited by the crystal thickness and can be better than under dynamical diffraction conditions.
[Association of mobile phone overuse with sleep disorder and unhealthy eating behaviors in college students of a medical university in Guangzhou].

OBJECTIVE To investigate the association of mobile phone use with sleep disorder and unhealthy eating behavior among college students of a medical university in Guangzhou. METHODS Mobile Phone Involvement Questionnaire (MPIQ), Pittsburgh Sleep Quality Index (PSQI) and the Three Factor Eating Questionnaire Revised 21 Item (TFEQ-R21) were used to survey 2122 undergraduates of the medical university. One-sample t test, One-way ANOVA and multiple linear regression analysis were used to analyze the data. RESULTS Age, body mass index (BMI), phone use before sleep, phone use frequency, sleep quality (assessed by total PSQI score) and the dimension scores of TFEQ-R21 for uncontrolled eating, cognitive restraint, and emotional eating were all significantly correlated with the total score of MPIQ (P < 0.05). Phone use before sleep, high frequency of mobile phone use, poor sleep quality and emotional eating were associated with high MPIQ scores, while lower cognitive restraint and emotional eating tendency were correlated with lower scores of MPIQ. Bivariate analysis revealed that age (r=0.088, P < 0.001), BMI (r=0.055, P < 0.05), PSQI scores (r=0.204, P < 0.001), TFEQ-UE scores (r=0.199, P < 0.001), TFEQ-CR scores (r=-0.076, P < 0.001), TFEQ-EE scores (r=0.170, P < 0.001), phone use before sleep (r=0.429, P < 0.001), and phone use frequency (r=0.316, P < 0.001) were all significantly correlated with MPIQ scores; multiple linear regression analysis showed that model 4 incorporating the scores of TFEQ-UE, TFEQ-CR, and TFEQ-EE explained up to 21.8% of the main effect (adjusted R2= 21.5%). CONCLUSIONS Mobile phone overuse is associated with poor sleep quality and unhealthy eating behaviors, and education and interventions for mobile phone use is essential among college students.
Genes Involved in the HPA Axis and the Symptom Cluster of Fatigue, Depressive Symptoms, and Anxiety in Women With Breast Cancer During 18 Months of Adjuvant Therapy

This study aimed to (1) identify subgroups of women with breast cancer with the psychological symptom cluster (fatigue, depressive symptoms, and anxiety) during the first 18 months of adjuvant therapy and (2) explore associations between demographic and clinical characteristics and variations in genetic polymorphisms related to hypothalamic–pituitary–adrenal (HPA) axis function and predicted symptom trajectory subgroup membership. We obtained symptom data at 4 time points from baseline to 18 months of adjuvant therapy among 292 postmenopausal women with breast cancer. Genetic data were collected in a subgroup at baseline (N = 184). Group-based multitrajectory modeling was used to classify women into subgroups with similar psychological symptom cluster trajectories. Binary logistic regression was used to explore the associations between each genotypic and phenotypic predictor and predicted subgroup membership. Two distinct symptom subgroups (low and high) were identified based on the trajectories of the symptom cluster of fatigue, depressive symptoms, and anxiety over the first 18 months of adjuvant therapy. Women who were younger, less educated, and who received chemotherapy had greater likelihood of being in the high-symptom subgroup. Variation in genes regulating the HPA axis (FKBP5 rs9394309 [odds ratio (OR) = 3.98, p = . 015], NR3C2 rs5525 [OR = 2.54, p = . 036], and CRHR1 rs12944712 [OR = 3.99, p = . 021]) was associated with membership in the high-symptom subgroup. These results may help to identify women with breast cancer who are at increased risk for psychological symptoms, facilitating the development of individualized and preemptive interventions to better manage these symptoms during adjuvant therapy.
Biodegradable polymer-coated thin strut sirolimus-eluting stent versus durable polymer-coated everolimus-eluting stent in the diabetic population

Background The number of patients with diabetes mellitus (DM) presenting with coronary artery disease is increasing and accounts for more than 30% of patients undergoing percutaneous coronary interventions (PCI). The biodegradable polymer drug-eluting stents were developed to improve vascular healing. It was sought herein, to determine 1-year clinical follow-up in patients with DM treated with the thin strut biodegradable polymer-coated sirolimus-eluting stent (BP-SES) versus durable coating everolimus-eluting stent (DP-EES). Methods Patients were retrospectively analyzed with DM were treated with either a BP-SES (ALEX™, Balton, Poland, n = 670) or a DP-EES (XIENCE™, Abbott, USA, n = 884) with available 1 year clinical follow-up using propensity score matching. Outcomes included target vessel revascularization (TVR) as efficacy outcome and all-cause death, myocardial infarction, and definite/probable stent thrombosis as safety outcomes. Results After propensity score matching 527 patients treated with BP-SES and 527 patients treated with DP-EES were selected. Procedural and clinical characteristics were similar between both groups. In-hospital mortality was 3.23% in BP-SES vs. 2.09% in DP-EES group (p = 0.25). One-year follow-up demonstrated comparable efficacy outcome TVR (BP-SES 6.64% vs. DP-EES 5.88%; p = 0.611), as well as similar safety outcomes of all-cause death (BP-SES 10.06% vs. DP-EES 7.59%; p = 0.158), myocardial infarction (BP-SES 7.959% vs. DP-EES 6.83%; p = 0.813), and definite/probable stent thrombosis (BP-SES 1.14% vs. DP-EES 0.76%; p = 0.525). Conclusions The thin-strut biodegradable polymer coated, sirolimus-eluting stent demonstrated comparable clinical outcomes at 1-year after implantation to DP-EES. These data support the relative safety and efficacy of BP-SES in diabetic patients undergoing PCI.
Spatial Distribution of (R)-salbutamol in Rat Brain Following Nasal and Intravenous Administration Using DESI-MS

Recent studies have shown that β2-Adrenoreceptor is a regulator of the a-synuclein gene driving risk of Parkinson’s disease. The β2-AR agonist (R)-salbutamol, eutomer of rac-salbutamol, may hold therapeutic potential for Parkinson’s disease (PD) following nasal administration. In this study, we use desorption electrospray ionization mass spectrometry (DESI-MS) to analyze spatial distribution of (R)-salbutamol in rat brain following nasal and intravenous administration. Here, we report that (R)-salbutamol efficiently deliver to the brain and had more drug dosage exposure in rat’s brain through nasal route administration than that of intravenous route administration. In conclusion, administering (R)-salbutamol through nasal route of administration may hold advantages in improving spatial distribution and increased exposure of drug in brain.
Detection of lentiviral suicide gene therapy in C6 rat glioma using hyperpolarised [1‐13C]pyruvate

Hyperpolarised [1‐13C]pyruvate MRI has shown promise in monitoring therapeutic efficacy in a number of cancers including glioma. In this study, we assessed the pyruvate response to the lentiviral suicide gene therapy of herpes simplex virus‐1 thymidine kinase with the prodrug ganciclovir (HSV‐TK/GCV) in C6 rat glioma and compared it with traditional MR therapy markers. Female Wistar rats were inoculated with 106 C6 glioma cells. Treated animals received intratumoural lentiviral HSV‐TK gene transfers on days 7 and 8 followed by 2‐week GCV therapy starting on day 10. Animals were repeatedly imaged during therapy using volumetric MRI, diffusion and relaxation mapping, as well as metabolic [1‐13C]pyruvate MRS imaging. Survival (measured as time before animals reached a humane endpoint and were euthanised) was assessed up to day 30 posttherapy. HSV‐TK/GCV gene therapy lengthened the median survival time from 12 to 25 days. This was accompanied by an apparent tumour growth arrest, but no changes in diffusion or relaxation parameters in treated animals. The metabolic response was more evident in the case‐by‐case analysis than in the group‐level analysis. Treated animals also showed a 37 ± 15% decrease (P < 0.05, n = 5) in lactate‐to‐pyruvate ratio between therapy weeks, whereas a 44 ± 18% increase (P < 0.05, n = 6) was observed in control animals. Hyperpolarised [1‐13C]pyruvate MRI can offer complementary metabolic information to traditional MR methods to give a more comprehensive picture of the slowly developing gene therapy response. This may benefit the detection of the successful therapy response in patients.
Efficacy and Safety of Switching to Dolutegravir/Lamivudine Fixed-Dose 2-Drug Regimen vs Continuing a Tenofovir Alafenamide–Based 3- or 4-Drug Regimen for Maintenance of Virologic Suppression in Adults Living With Human Immunodeficiency Virus Type 1: Phase 3, Randomized, Noninferiority TANGO Study

Abstract Background The 2-drug regimen dolutegravir (DTG) + lamivudine (3TC) is indicated for treatment-naive adults with human immunodeficiency virus type 1 (HIV-1). We present efficacy and safety of switching to DTG/3TC in virologically suppressed individuals. Methods TANGO is an open-label, multicenter, phase 3 study that randomized adults (1:1, stratified by baseline third agent class) with HIV-1 RNA <50 copies/mL to switch to once-daily fixed-dose DTG/3TC or remain on a tenofovir alafenamide (TAF)–based regimen. The primary end point was proportion of participants with HIV-1 RNA ≥50 copies/mL at week 48 (US Food and Drug Administration Snapshot algorithm) in the intention-to-treat–exposed population (4% noninferiority margin). Results 743 adults were enrolled; 741 received ≥1 dose of study drug (DTG/3TC, N = 369; TAF-based regimen, N = 372). At week 48, proportion of participants with HIV-1 RNA ≥50 copies/mL receiving DTG/3TC was 0.3% (1/369) vs 0.5% (2/372) with a TAF-based regimen (adjusted treatment difference [95% confidence interval], −0.3 [−1.2 to .7]), meeting noninferiority criteria. No participants receiving DTG/3TC and 1 receiving a TAF-based regimen met confirmed virologic withdrawal criteria, with no emergent resistance at failure. Drug-related grade ≥2 adverse events and withdrawals due to adverse events occurred in 17 (4.6%) and 13 (3.5%) participants with DTG/3TC and 3 (0.8%) and 2 (0.5%) with a TAF-based regimen, respectively. Conclusions DTG/3TC was noninferior in maintaining virologic suppression vs a TAF-based regimen at week 48, with no virologic failure or emergent resistance reported with DTG/3TC, supporting it as a simplification strategy for virologically suppressed people with HIV-1. Clinical Trials Registration NCT03446573.
iLncRNAdis-FB: Identify lncRNA-Disease Associations by Fusing Biological Feature Blocks Through Deep Neural Network

Identification of lncRNA-disease associations is not only important for exploring the disease mechanism, but will also facilitate the molecular targeting drug discovery. Fusing multiple biological information is able to generate a more comprehensive view of lncRNA-disease association feature. However, the existing fusion strategies in this field fail to remove the noisy and irrelevant information from each data source. As a result, their predictive performance is still too low to be applied to real world applications. In this regard, a novel computational predictor called iLncRNAdis-FB is proposed based on the Convolution Neural Network (CNN) to integrate different data sources by using the feature blocks in a supervised manner. The lncRNA similarity matrix and disease similarity matrix are constructed, based on which the three-dimensional feature blocks are generated. These feature blocks are then fed into CNN to train the model so as to predict unknown lncRNA-disease associations. Experimental results show that iLncRNAdis-FB achieves better performance compared with other state-of-the-art predictors. Furthermore, a web server of iLncRNAdis-FB has been established at http://bliulab.net/iLncRNAdis-FB/, by which users can submit lncRNA sequences to detect their potential associated diseases.
Memristive and CMOS Devices for Neuromorphic Computing

Neuromorphic computing has emerged as one of the most promising paradigms to overcome the limitations of von Neumann architecture of conventional digital processors. The aim of neuromorphic computing is to faithfully reproduce the computing processes in the human brain, thus paralleling its outstanding energy efficiency and compactness. Toward this goal, however, some major challenges have to be faced. Since the brain processes information by high-density neural networks with ultra-low power consumption, novel device concepts combining high scalability, low-power operation, and advanced computing functionality must be developed. This work provides an overview of the most promising device concepts in neuromorphic computing including complementary metal-oxide semiconductor (CMOS) and memristive technologies. First, the physics and operation of CMOS-based floating-gate memory devices in artificial neural networks will be addressed. Then, several memristive concepts will be reviewed and discussed for applications in deep neural network and spiking neural network architectures. Finally, the main technology challenges and perspectives of neuromorphic computing will be discussed.
Using Sensory Cues to Optimise the Satiety Value of a Reduced-Calorie Product Labelled ‘Healthier Choice’

Reformulation strategies to reduce the energy density of commonly consumed foods and beverages are intended to support weight management, but expectations generated by labelling these as ‘healthier’ alternatives can have unintended effects on the product’s sensory evaluations and consumption behaviours. We compared the impact of four different strategies for presenting a lower-calorie beverage to consumers on product perceptions, short-term appetite and energy intake. Participants (N = 112) consumed higher- (211 kcal/portion) and lower-calorie (98 kcal/portion) fixed-portion soymilks in the morning across two test days, with the lower-calorie version presented in one of four contexts varying in label information and sensory quality: (1) sensory-matched/unlabelled, (2) sensory-matched/labelled, (3) sensory-reduced (less sweet and creamy)/labelled, and (4) sensory-enhanced (sweeter and creamier)/labelled. The label was Singapore’s Healthier Choice Symbol, which also highlighted that the soymilk was lower calorie. Changes in reported appetite, ad libitum lunch intake, and self-reported intake for the rest of the text day were recorded. Results indicated that total energy intake was consistently lower on the days the lower calorie beverages were consumed, regardless of how they were presented. However, the ‘healthier choice’ label increased hunger prior to lunch and reduced the soymilks’ perceived thickness and sweetness compared to the same unlabelled version. Increasing the product’s sensory intensity successfully maintained liking, experienced sensory quality and appetite. Results suggest that food companies wanting to explicitly label product reformulations could combine messages of ‘lower calorie’ and ‘healthier choice’ with appropriate taste and texture enhancements to maintain acceptance and avoid negative effects on appetite.
Aging aggravates intervertebral disc degeneration by regulating transcription factors toward chondrogenesis

Osterix is a critical transcription factor of mesenchymal stem cell fate, where its loss or loss of Wnt signaling diverts differentiation to a chondrocytic lineage. Intervertebral disc (IVD) degeneration activates the differentiation of prehypertrophic chondrocyte‐like cells and inactivates Wnt signaling, but its interactive role with osterix is unclear. First, compared to young‐adult (5 mo), mechanical compression of old (18 mo) IVD induced greater IVD degeneration. Aging (5 vs 12 mo) and/or compression reduced the transcription of osterix and notochordal marker T by 40‐75%. Compression elevated the transcription of hypertrophic chondrocyte marker MMP13 and pre‐osterix transcription factor RUNX2, but less so in 12 mo IVD. Next, using an Ai9/td reporter and immunohistochemical staining, annulus fibrosus and nucleus pulposus cells of young‐adult IVD expressed osterix, but aging and compression reduced its expression. Lastly, in vivo LRP5‐deficiency in osterix‐expressing cells inactivated Wnt signaling in the nucleus pulposus by 95%, degenerated the IVD to levels similar to aging and compression, reduced the biomechanical properties by 45‐70%, and reduced the transcription of osterix, notochordal markers and chondrocytic markers by 60‐80%. Overall, these data indicate that age‐related inactivation of Wnt signaling in osterix‐expressing cells may limit regeneration by depleting the progenitors and attenuating the expansion of chondrocyte‐like cells.
Synthesis of Monolayer MoSe2 with Controlled Nucleation via Reverse-Flow Chemical Vapor Deposition

Two-dimensional (2D) layered semiconductor materials, such as transition metal dichalcogenides (TMDCs), have attracted considerable interests because of their intriguing optical and electronic properties. Controlled growth of TMDC crystals with large grain size and atomically smooth surface is indeed desirable but remains challenging due to excessive nucleation. Here, we have synthesized high-quality monolayer, bilayer MoSe2 triangular crystals, and continuous thin films with controlled nucleation density via reverse-flow chemical vapor deposition (CVD). High crystallinity and good saturated absorption performance of MoSe2 have been systematically investigated and carefully demonstrated. Optimized nucleation and uniform morphology could be achieved via fine-tuning reverse-flow switching time, growth time and temperature, with corresponding growth kinetics proposed. Our work opens up a new approach for controllable synthesis of monolayer TMDC crystals with high yield and reliability, which promote surface/interface engineering of 2D semiconductors towards van der Waals heterostructure device applications.