bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring potential causal genes for mouth ulcers: A Mendelian randomization and transcriptome- wide association analysis
Authors: Shi Mengru , Wang Tianqi , Xie Qi , Meng Xiaofei , Shi Jiamin , Zhu Yining , Zhang Xinchun , Xia Juan , Xie Weili , Chen Xiaobing
Published: January 2023

In this study, we explored genes that were pleiotropically associated with mouth ulcers. We adopted the summary data-based Mendelian randomization (SMR) method which estimated the pleiotropic effect of gene expression on mouth ulcers. We performed separate SMR analysis using GTEx and CAGE eQTL data. We also conducted transcriptome-wide association study (TWAS) to explore genes whose cis-regulated expression levels were associated mouth ulcers. Using GTEx eQTL data, the SMR identified 70 probes, with CCR1 (ENSG00000163823.3, PSMR=9.20×10–17), PPP5C (ENSG00000011485.10, PSMR=6.86×10–16) and HLA-DRB5 (ENSG00000198502.5, PSMR=1.54×10–15) being the top three genes. Using the CAGE eQTL data, our SMR analysis identified 137 probes tagging 111 unique genes with CCR3 (ILMN_1763322, PSMR=7.76×10–41), CCR1 (ILMN_1678833, PSMR=3.89×10–38) and CA425595 (ILMN_1725170, PSMR=4.15×10–19) being the top three genes. TWAS analysis identified 181 significant genes whose expression was associated with mouth ulcers, 58 of which were also identified by SMR analysis using GTEx eQTL data and 39 by the SMR analysis using CAGE eQTL data. Our findings highlight the important roles of genes in the CCR family and the HLA complex in the pathogenesis of mouth ulcers. More studies are needed to explore the underlying mechanisms in the etiology of mouth ulcers.
Combined application of zinc oxide and iron nanoparticles enhanced Red Sails Lettuce growth and antioxidants enzymes activities while reducing the chromium uptake by plants grown in a Cr-contaminated soil
Authors: Sameer Alisha , Rabia Sara , Khan Aamir Amanat Ali , Hussain Afzal , Ali Basharat , Zaheer Muhammad Saqlain , Ali Habib , Sheteiwy Mohamed S. , Ali Shafaqat
Published: January 2023

Soils contaminated with chromium (Cr) have become a major ecological concern. Chromium poses serious health issues when become the part of our food chain. So, the key objective of the present experiment was to evaluate the impact of foliar applied zinc oxide nanoparticles (ZnO NPs) as varying levels (0, 25, 50, 100 mg L-1) as well as iron nanoparticles (Fe NPs) as varying levels (0, 5, 10, 20 mg L-1) on lettuce growth, biomass, photosynthetic process as well as essential nutrients and Cr uptake by lettuce plants under Cr stress. Foliar spray of ZnO and Fe NPs was applied as foliar spray and plants harvesting was done at maturity. Our results depicted that foliar application of ZnO NPs and Fe NPs improved the growth, photosynthesis, antioxidants enzymes activities and reduced the oxidative damage in lettuce plants by stimulating the antioxidative defense machinery. Additionally, application of ZnO and Fe NPs resulted in enhancement of Zn and Fe fortification in Red Sails Lettuce, respectively. Moreover, Zn and Fe NPs enhanced the uptake of the essential nutrients while limiting the Cr uptake by lettuce plants and Cr concentration in lettuce leaves was under the threshold limit for Cr.
Ultra-low Ag Loadings for CO2 Reduction via Tailored Molecular Electrocatalysts
Authors: Apfel Ulf-Peter , Pellumbi Kevinjeorjios , Krisch Dominik , Sun He , Sanden Sebastian , Hoof Lucas , Puring Kai junge , Siegmund Daniel , Schöfberger Wolfgang , Messing Leonard
Published: January 2023

Decreasing the catalytic loading and complexity of electrocatalysts for the reduction of CO2 is a critical necessity towards globally generating carbon-negative synthons. This effort therefore calls for the development of not only more active catalysts per employed g but also for more financially sound ones. Notably, molecular electrocatalysts allow for tuning the electronic and geometric environment around single-atom catalytic centers. Nevertheless, synthetic complexity, cost and electrochemical instability still hamper their large-scale implementation. With industrial application in mind, we herein present a holistic design approach starting from different Ag(I) N,N´-bis(arylimino)acenaphtene complexes to sophisticated architectures of electrolyzer components. Performed in industrially applicable cells at 60°C, this approach allows us to reach catalytic activity for CO formation close to 1 A cm-2, while achieving the highest mass activity reported for CO at 100.000 A gAg-1, accompanied by cost decreases up to a factor of 80 against the current heterogeneous standards. This study thus represents an unprecedented example to show the applicability of homogenous catalysts under industrially relevant conditions.
Usefulness of Non-invasive Assessment of Liver Fibrosis on Serum and Transient Elastography Markers in Pediatric Autoimmune Hepatitis
Authors: ALVARENGA Lucas Rocha , HESSEL Gabriel , PEREIRA Tiago Sevá , BELLOMO-BRANDÃO Maria Ângela
Published: January 2023

BACKGROUND
Liver biopsy is an invasive method to assess liver fibrosis in chronic liver diseases and, therefore, non-invasive methods are becoming common in daily practice. There is a lack of pediatric clinical trials using non-invasive markers. The aim of the study is to evaluate the correlation of non-invasive markers of liver fibrosis in pediatric Autoimmune Hepatitis (AIH) with Transient Liver Elastography (TLE).
METHODS
A cross-sectional study was done in a cohort of AIH pediatric patients at a tertiary care center between May 2016 and February 2020. Twenty-eight patients (between 3 and 20 years of age) with AIH were enrolled, all of them on immunosuppressive treatment and biochemical remission. They had undergone TLE (FibroScan®) and biochemical tests. Patients were divided into 2 groups: (1) ≥ F2 (TLE ≥ 6.45 kPa) and (2) < F2 (TLE < 6.45 kPa). The comparison between groups 1 and 2 was performed using Mann-Whitney test for quantitative variables and Fisher's exact test for categorical variables. The correlation between TE, APRI, FIB-4 and Platelet Count was assessed using Spearman coefficient (Rs) and the level of significance adopted for the study was 5%.
RESULTS
Twenty-eight pediatric patients with AIH were enrolled, 21 female and 22 AIH-1; 20 patients in group 1 and 8 in group 2. A statistically significant difference was found between the two groups on APRI and FIB-4 results (p = 0.0306 and p = 0.0055, respectively). When TLE (in kPa values) was compared with the other markers, there was a significant correlation with APRI and FIB-4 (Rs = 0.67 and 0.78, respectively; p <0.01) as well as with Platelet Count (Rs = - 0.68; p <0.01).
CONCLUSIONS
APRI, FIB-4 and Platelet Count showed positive correlation with TLE to predict liver fibrosis in pediatric AIH.
Effects of Ascophyllum Nodosum and Soil Amendments on the Development of Maize Seedlings Cultivated Under Acid Oxisol
Authors: Trindade Polyanna Ribeiro , Mooney Sacha J , Rodrigues Carlos Ribeiro , Castoldi Gustavo , Veneziano Vitor Martins , Atkinson Brian , Sturrock Craig J , Chagas Marcos Gustavo Kemmerich , Alves Guyanlukia Brito , Rodrigues Arthur Almeira , Filho Sebastião Carvalho Vasconcelos
Published: January 2023

Introduction
Maize (Zea mays L.) plays a fundamental role in Brazilian agriculture, and it is mostly cultivated in Brazilian Savannah areas, under high Al content and acidic pH.
Aims
The aim of this work was to evaluate the effects of soil amendments and A. nodosum extract on the initial development of the root system and nitrogen use efficiency of maize under aluminum toxicity.
Methods
The effects of lime and gypsum in combination with seed treatment + foliar application of Ascophyllum nodosum on shoot and root growth, plant nutrition and photosynthesis of 14-day-old maize seedlings were tested in two experiments. The experimental design was randomized 4x2 factorial, with the following treatments: lime (L), gypsum (G), lime + gypsum (LG) and control (C), cultivated with and without seed treatment and foliar application of the Ascophyllum nodosum.
Results
The treatments with A. nodosum extract led to an increase in the root area in the treatments with lime, and to a smaller transport of aluminum to the shoot of the plants. The lime and gypsum treatments were efficient in minimizing the deleterious effects of aluminum toxicity, even with their short-term application in sandy clay loam medium textured soil, providing better photochemical activity, better use efficiency of nutrients, better rooting and, consequently, higher dry weight of shoot and root.
Conclusions
The results show that the use of A. nodosum and soil amendments in acidic soils lead to promising physiological and morphological improvement, and by consequence, may influence in crop production.
Classifying knowledge on climate change induced landslides in retrospect and prospect: A state-of-the-art review
Authors: Sharma Aastha , Sajjad Haroon , . Roshani , Rahaman Md Hibjur
Published: January 2023

The frequency and intensity of landslides have increased due to variability in precipitation and temperature across the globe. Assessment of landslide risk is essential for devising effective mitigation and making societies resilient. Through an in-depth literature review from 1996 to 2021, this study carried out descriptive, thematic, and mechanism analyses of the current literature to identify the gaps in the literature and suggest a way forward. Findings revealed a steady increase in the publication of landslide studies over the years. Most of the studies were conducted on a regional scale. Modeling, landslides, climate change, multi-hazards, and vulnerability figured as the prominent keywords in the reviewed articles. Slope, precipitation, land use/land cover, proximity to coastal areas, risk, and adaptation strategies were found as the dominant thematic variables. A large number of reviewed articles utilized statistical models. Uncertainty in landslide-climate modeling, lack of advanced and interactive models for predicting landslide susceptibility; and less attention to environmental and economic vulnerability were identified as the major research gaps. Effective early warning systems, timely forecasting for landslides and effective risk assessment are also scant in the existing literature. The current study proposed a comprehensive future framework for landslide risk assessment and implies timely and appropriate landslide mitigation based on climate scenario data, deterministic models, and policy beliefs. Strengthening preventive actions, preparedness as an early warning system, immediate response mechanism, landslide adaptation behavior, socio-economic vulnerability, and decision support systems are suggested for future research.
Depletion of TAFIB Gene Inhibits Ribosome Biosynthesis and Proliferation of Gastric Tumor through Enhancing c-MYC mRNA Degradation
Authors: chen hangfei , Zhang Feng
Published: January 2023

With population growth and aging, the number of new cases about Stomach adenocarcinoma (STAD) is expected to continue to increase in the future. Increased ribosome biosynthesis (RiBi), a hallmark of many cancers for over 100 years, as a result of an emerging target for cancer therapy. The first key step of RiBi, the transcription of RNA polymerase I (Pol I) into the precursor ribosomal RNA (pre-rRNA), needs a Pol I specific Pre-initiation Complex (PIC) for accurate recruitment. Mammalian PIC of Pol I includes selectivity factor 1 (SL1), RRN3 and upstream binding factor (UBF), of which SL1 is essential and can stabilize the PIC structure. TAF1B, TBP-associated factor 1B, is one of the component subunits of SL1. TAF1B is required for Pre-initiation Complex of RNA polymerase I, but its function in cancers is not fully understood. In this study, when we knocked down TAF1B gene in STAD ,we found that the transcription and content of c-MYC decreased, which was associated with RPL 5, RPL 11 and RISC.
Artificial neural network prediction and comparative evaluation of pharmaceutical important flavones and antioxidant compositions in Teucrium polium callus culture elicited with methyl jasmonate and TiO2 nanoparticles
Authors: Tabarifard Mahshid , Cheniany Monireh , Khalilian-movahhed Mohammad
Published: January 2023

The present research study evaluated the effects of four concentrations of Benzylaminopurine (BAP) in combination with three concentrations of Naphthalene acetic acid (NAA), as well as methyl jasmonate and nano-sized TiO2 elicitors on callus induction, pharmaceutical important flavones and antioxidant compositions in leaf-derived calli of Teucrium polium. The feed-forward Artificial Neural Network (ANN) model, as well, was applied to predict the effects of hormones and elicitors on phenolic compounds production. The best callus induction was obtained with basal media fortified with 1.5 mg L− 1 BAP plus 0.5 mg L− 1 NAA, followed by 1.5 mg L− 1 BAP. Based on biochemical features (the total content of phenols, Ortho-diphenols, flavonoid, flavone, and rosmarinic acid), the extraction has substantially by elicitation raised in comparison to control, with the maximum ones in calli elicited with methyl jasmonate (50 µM). The exception was phenolic acids possessed much greater content in 10 mg L− 1 nano TiO2-treated calli. The high antioxidant activities (IC50 2.066 ± 0.24 µg mL− 1 and 383.79 ± 33.60 mg Fe+ 2 100 g− 1 DW) with approximate 2- and 1.5-fold increases compared to control, was observed in hydromethanolic extracts of calli elicited by 50 µM methyl jasmonate on an MS medium containing 1.5 mg L− 1 BAP plus 0.5 mg L− 1 NAA. Likewise, the highest contents of anti-genotoxic flavones apigenin and luteolin were measured at pretreatment of callus with 50 µM methyl jasmonate on the media supplemented with 1 mg L− 1 BAP (180.67 ± 2.52 and 201.11 ± 3.63 µg 100 g− 1 extract, respectively) and 1.5 mg L− 1 BAP plus 0.5 mg L− 1 NAA (206.01 ± 7 and 256.22 ± 2.1 µg 100 g− 1 extract, respectively). ANN with hyperbolic-tangent (10-1-3) activation function, R2 0.99, SSE 0.01, and RE 0.001 showed a strong correlation between ANN model outputs and the experimental amounts of polyphenols, Ortho-diphenols, and phenolic acids. The results support that methyl jasmonate elicitation could more trigger and increase the pharmaceutical phenolic compositions in T. polium callus cultures as compared with nano-sized TiO2 treatment. Meanwhile, the ANN model could successfully interconnect the output parameters (phenolic metabolites) to input variables (hormone and elicitor).
Profiling of circulating serum exosomal microRNAs in elderly patients with infectious stress hyperglycaemia
Authors: Zeng Kejing , He haozhe , Lv zhenjing , Lei Ming , wu weikun , sun hao , Wong Gordon , Kwok YatSze , Tian Junzhang , xu gugen
Published: January 2023

Early diagnosis of hospitalized elderly patients with infectious stress hyperglycaemia (ISH) is clinically important, as without timely prevention and effective treatment, it is likely to deteriorate into septic shock, which significantly worsen patients’ survival rate. Systematic screening of specific biomarkers of serum small extracellular vesicles (sEVs) from ISH patient has not yet been reported. In this study, serum sEVs were derived from 10 elderly patients with ISH and 5 control patients with disease-match without hyperlycemia (non-ISH). RNA sequencing identified a total number of 49 sEVs enriched fraction derived miRNAs with differential expression between ISH and control group. Of which, top 22 miRNAs ranked by sensitivity × specificity were chosen for further research. Moreover,7 out of 22 miRNAs that related to glucose metabolism or immune disorder, were picked up for further validation in an independent cohort consisting of 52 participants (31 ISH and 21 non-ISH). A validation analysis revealed that 3 miRNAs (hsa-miR-21-5p，hsa-miR-335-5p，hsa-miR-28-3p) were statistically up-regulated in exosomes from ISH patients. In the validation cohort and discovery cohort, the AUC of 3 individual miRNAs ranged from 0.73 to 0.88. A logistic model combining three miRNAs achieved an AUC of 0.96. Besides,sEV‐miRNA‐based signatures effectively characterized patients’ poor clinical outcome. Survival curve analysis showed that miR-335-5p, miR-28-3p but not miR-21-5p, were significantly closely related to mortality, and the combination of the three could also predict patients outcome.(P<0.05).This study depicted the circulating exosomal miRNAs change in ISH patient and which could be used as a promising biomarker to detect ISH at an early stage, and predict patients clinical outcome.
Short-range DNA translocation initiates long-range 1-dimensional DNA diffusion by the Type III restriction enzyme EcoP15I
Authors: Goese Martin , Magill Emma , Diffin Fiona , Rawson Tara , Nagy Zsofia , Seidel Ralf , Szczelkun Mark
Published: January 2023

Cleavage of bacteriophage DNA by the Type III Restriction-Modification enzymes requires long-range interaction between DNA sites. This is facilitated by 1-dimensional diffusion (“DNA sliding”) initiated by ATP hydrolysis catalysed by a superfamily 2 helicase-like ATPase. Here we combined ultrafast twist measurements based on plasmonic DNA origami nano-rotors with stopped-flow fluorescence and gel-based assays to examine the role(s) for ATP hydrolysis. Our data shows that the helicase-like domain plays multiple roles. Firstly, stabilising initial DNA-interactions alongside the methyltransferase subunits. Secondly, causing environmental changes in the flipped adenine base following hydrolysis of the first ATP. And thirdly, remodelling nucleoprotein interactions via constrained translocation of a ~5-20 bp dsDNA loop. Initiation of DNA sliding requires 10-15 bp DNA downstream of the motor, corresponding to the site of nuclease domain binding. Our data unifies previous contradictory communication models for Type III enzymes.
Analyzing the Environment of International Health Regulations Capacities in Lebanon: Protracted Crises, Economic Meltdown and Refugee Waves
Authors: Hassan Maya , Jamal Diana , El-Jardali Fadi
Published: January 2023

Background: Lebanon ratified the International Health Regulations IHR (2005) in 2007, and since then, it has been facing complex political deadlocks, financial deterioration, and infectious disease emergencies. Little is known about implementing IHR (2005) capacities in the Lebanese context. We aimed to understand the milestones of IHR capacities implementation, and the challenges of maintaining these capacities and explore the barriers refugees impose on the development of Lebanon's capacities.
Methods: We used a mixed-method design. The study combined the use of secondary data analysis of the 2020 SPAR submissions and qualitative design using semi-structured interviews with key informants. Semi-structured interviews were conducted with nine key informants. The analysis of the data generated was based on thematic analysis.
Results: In 2020, Lebanon had levels of 4 (≤ 80%) in the prevention, detection, response, enabling functions, and operational readiness capacities. The country scored more than its neighboring countries, Syria, and Jordan, which have similar contexts of economic crises, emergencies, and refugee waves. Despite this high level of commitment to meeting IHR (2005) capacities, the qualitative findings demonstrated several gaps in IHR (2005) implementation as resources shortage, governance, and political and economic challenges. The study also showed contradictory results regarding the impact of refugees on IHR (2005) capacities implementation. Some key informants agreed that the Syrian crisis had a positive impact, while others suggested the opposite. Whether refugees interfere with IHR development is still an area that needs further investigation.
Conclusion: The study shows that urgent interventions are needed to strengthen the implementation of the IHR capacities in Lebanon and crisis-stuck countries. The study recommends 1) reconsidering the weight given to IHR (2005) capacities; 2) promoting governance to strengthen IHR compliance; 3) integrating refugees and displaced persons in IHR (2005) framework and its assessment tools; 4) strengthening the multisectoral coordination mechanisms; 5) mobilizing and advancing the capacities of human resources at the central and sub-national levels; 6) ensuring sustainable financing; 7) acknowledging risk mapping as a pre-requisite to a successful response; 8) strengthening research on IHR (2005) implementation in Lebanon, and; 9) reinforcing risk communication strategies constantly.
Loss of Dead end1 induces testicular teratomas from primordial germ cells that failed to undergo sexual differentiation in embryonic testes
Authors: Imai Atsuki , Matsuda Kazuya , Niimi Yuki , Suzuki Atsushi
Published: January 2023

Spontaneous testicular teratomas (STTs) are tumours comprising a diverse array of cell and tissue types, which are derived from pluripotent stem-like cells called embryonal carcinoma cells (ECCs). Although mouse ECCs originate from primordial germ cells (PGCs) in embryonic testes, the molecular basis underlying ECC development remains unclear. This study shows that the conditional deletion of mouse Dead end1 (Dnd1) from migrating PGCs leads to STT development. InDnd1-conditional knockout (Dnd1-cKO) embryos, PGCs colonise the embryonic testes but fail to undergo sexual differentiation; subsequently, ECCs develop from a portion of the PGCs. Transcriptomic analyses reveal that PGCs not only fail to undergo sexual differentiation but are also prone to transformation into ECCs by upregulating the expression of ECC-specific genes in the testes ofDnd1-cKO embryos. Thus, our results clarify the role ofDnd1in developing STTs and developmental process of ECC from PGC, providing novel insights into pathogenic mechanisms of STTs.
Functions of scented nectar in fly-pollinated Fritillaria camtschatcensis (Liliaceae)
Authors: Li Junnan , Inui Yoko , Mochizuki Ko , Takeda Kazuya , Sakai Shoko , Kawakita Atushi
Published: January 2023

Volatile compounds in nectar have various functions, but we still know little about the distribution and functions of scented floral nectar. Here, we report functions of scented nectar in Fritillaria camtschatcensis. In Japan, F. camtschatcensis comprises two varieties, var. keisukei (hereafter, alpine type) and var. camtschatcensis (hereafter, lowland type), both of which secrete a large amount of scented nectar and attract flies as pollinators. We investigated sugar concentration of the nectar using high-performance liquid chromatography (HPLC) and studied the volatile chemical composition of the nectar using gas chromatography-mass spectrometry (GC-MS). We then conducted a bioassay using a synthetic mixture of components of the nectar scent of the lowland type to test if the nectar scent contributes to pollinator attraction. The HPLC analysis showed that substantial amounts of glucose and fructose occur in the nectar of the alpine type. The nectar of the lowland type also contained glucose, albeit at low concentration. The volatile compounds in the nectars were substantially different between the two types: the volatiles of the lowland type consisted of four aliphatic acids, whereas acetophenone was the main compound in the alpine type. The bioassay revealed that the nectar scent of the lowland type is sufficient to attract flies, including the pollinator species. This study showed that the nectar of F. camtschatcensis functions as both a reward and attractant for the pollinators, and indicates that flower nectar is much more diverse in terms of chemical composition and function than commonly thought.
Preliminary study of fetal HQ in cardiac structure and systolic function of fetal Coarctation of the aorta
Authors: Yang Jiaojiao , Tan Fang , Shen Yuqin , Zhao Yuan , Li Yanfeihai , Fan Sihan , Ji Xueqin , Xia Yan
Published: January 2023

Objective

To use fetal HQ software to carry out quantitative analysis of the 4-chamber view (4-CV) and left and right ventricle of fetuses with Coarctation of aortic(CoA) and normal fetuses, and to explore the application value of this software in evaluating the cardiac structure and systolic function of fetuses with CoA.

Methods

fetal HQ software was used to quantitatively analyze the GSI, 24-segment SI of left and right ventricles, fractional area change (FAC) left and right ventricular area, and longitudinal contractility in 53 normal singleton fetuses and 16 fetuses with CoA, 24-segment transverse width fractional shortenin FS .p < 0.05 was considered significant.

Results

Compared with the two groups of fetuses, the global spherical index (GSI) was significantly different (P < 0.05), and the left ventricle 18–24 segment spherical index was significantly different (P < 0.05); the right ventricle 8-11segmental spherical index was significant differences (P < 0.05); there were significant differences in left ventricular fraction area change and longitudinal strain in the CoA group (P < 0.05); there were no significant differences in right ventricular fraction area change and longitudinal strain in the CoA group (P > 0.05); the fetal left ventricular 24-segment transverse width fractional shortening FS in the CoA group was significantly different in segments 1–12 (P＜0.05);the FS 1–4 segments were significantly different (P < 0.05).

Conclusion

fetal HQ technique can quickly and easily obtain the spherical index and systolic function parameters of fetal heart, and provides a new method for quantitative analysis of fetal heart structure and systolic function with CoA.
A 2D ferroelectric vortex lattice in twisted BaTiO3 freestanding layers
Authors: Santamaria Jacobo , Sanchez-Santolino Gabriel , Rouco Victor , Zamora Victor , J. Fabian Cuellar , Leon Carlos , Puebla Sergio , Munuera Carmen , Mompean Federico , García-Hernández Mar , Castellanos-Gomez Andres , Aramberri Hugo , Íñiguez Jorge
Published: January 2023

The wealth of complex polar topologies [1- 6] recently found in nanoscale ferroelectrics result from a delicate balance between the materials’ intrinsic tendency to develop a homogeneous polarization and the electric and mechanic boundary conditions imposed upon them. Ferroelectric–dielectric interfaces are model systems where polarization curling originates from open circuit-like electric boundary conditions, to avoid the build-up of polarization charges through the formation of flux-closure [7-11] domains that evolve into vortex-like structures at the nanoscale [12-14]. Interestingly, while ferroelectricity is known to couple strongly to strain (both homogeneous [15] and inhomogeneous [16, 17]), the effect of mechanical constraints [18] on thin film nanoscale ferroelectrics has been comparatively less explored because of the relative paucity of strain patterns that can be implemented experimentally. Here we show that the stacking of freestanding ferroelectric perovskite layers with controlled twist angles opens an unprecedented opportunity to tailor these topological nanostructures in a way determined by the lateral strain modulation associated to the twisting. Interestingly, we find that a peculiar pattern of polarization vortices emerges from a so far unreported reciprocal converse flexoelectric coupling of polarization gradients to strain, with an estimated magnitude that is typical of ferroelectric perovskites. This finding opens exciting opportunities to create two-dimensional high density vortex crystals that would allow us to explore novel physical effects and functionalities.
Structure-based drug repurposing to inhibit the replication-associated essential protein DnaG of Mycobacterium tuberculosis.
Authors: Ali Waseem , Jamal Salma , Gangwar Rishabh , Ahmed Faraz , Agarwal Meetu , Sheikh Javaid Ahmad , Grover Sonam
Published: January 2023

Background: Mycobacterium tuberculosis (M.tb), the etiological agent of Tuberculosis (TB), is the second leading cause of mortality after COVID-19, with a global death toll of 1.5 million in 2020. The escalating cases of drug-resistant TB are further worsening the current situation and making TB treatment extremely challenging. Thus, it is crucial to look for new anti-TB drugs with novel mechanisms of action and high efficacy. The DnaG of M.tb replication machinery is an essential protein for pathogen survival. Also, its imperative primase activity and lack of structural homology to human proteins, make it a possible target for drug development.
Methods: In this presented study, using a computational structure-based drug repurposing approach, Food and drug administration (FDA) approved drugs were virtually screened against M.tb DnaG to identify potential inhibitors. Five drugs viz. Caspofungin, Doxorubicin, Mitoxantrone, Vapreotide, and Zanamivir showed higher molecular docking scores. Further RMSD, RMSF, Rg, SASA, H-bond, and PCA analysis of these drugs and DnaG complexes.
Alamar Blue Assay further evaluated the anti-TB activity of these drugs in vitro using H37Ra and H37Rv M.tb strains.
Results: The top results for DnaG binding included several FDA-approved drugs, out of which five were selected and subjected to Molecular dynamic simulation and displayed their high binding affinity, stable interaction, more compactness, and reduced atomic motion. The minimum inhibitory concentration of Doxorubicin, Mitoxantrone, and Vapreotide were detected in the range of 0.19-25 µg/ml for both H37Ra, and H37Rv, respectively.
Conclusions: Our findings from the study present potential repurposed drug candidates that target DnaG and inhibit M.tb survival. Thorough investigations of these compounds may lead to the discovery of new anti-TB therapeutics.
The expression and clinical significance of C1orf106 in low-grade serous ovarian cancer
Authors: Song Feifei , Chen Xiaojing , Zhou Caiyun , Cheng Xiaodong
Published: January 2023

Background
Low-grade serous ovarian cancer is a rare subtype of ovarian cancer and lack of large-scale systematic studies worldwide.This study is aimed to select the target gene and figure out the expression and clinical significance of it in low-grade serous ovarian cancer.
Methods and Results
The mRNA data was downloaded from the Gene Expression Omnibus (GEO), then the differentially expressed genes (DEGs) between cancer and normal tissue were screened out by R software. Under comprehensive consideration, C1orf106 was chosen as our target gene based on the significant |logFC|, known molecular function and research innovation. Immunohistochemistry and qRT-PCR both showed that C1orf106 was highly expressed in tumor tissue. Contacted with clinical information, high-expression of C1orf106 was associated with lower Body Mass Index (< 25kg/m2) and no residual lesion. Kaplan-Meier analysis showed that high-expression of C1orf106 was associated with better overall survival, but may not be correlated with progression-free survival. COX regression model indicated that C1orf106 was one of the prognostic factor for low-grade serous ovarian cancer, but not independently.
Conclusion
C1orf106 was highly expressed in low-grade serous ovarian cancer. High expression of C1orf106 indicated a better overall survival. Therefore, C1orf106 may be one of the biomarkers with diagnostic and prognostic value in low-grade serous ovarian cancer, but the precise mechanism still needs further research.
Autologous HER2-specific CAR T-cells after lymphodepletion for advanced sarcoma
Authors: Hegde Meenakshi , Navai Shoba , DeRenzo Christpher , Joseph Sujith , Sanber Khaled , Wu Meng-Fen , Janeway Katherine , Gad Ahmed , Campbell Matthew , Mullikin Dolores , Nawas Zeid , Robertson Catherine , Matthew Pretty , Zhang Huimin , Mehta Birju , Shree Ankita , Gerken Claudia , Kalra Mamta , Chakraborty Rikhia , Thakar Sachin , Dakhova Olga , Salsman Vita , Grilley Bambi , Lapteva Natasha , Gee Adrian , Dotti Gianpietro , Tao Wang , Hicks John , Brenner Malcolm , Heslop Helen , Wels Winfried , Gottschalk Stephen , Ahmed Nabil
Published: January 2023

Purpose
To determine the maximum tolerated dose (MTD) of autologous chimeric antigen receptor T cells (HER2-CART) after lymphodepletion and to describe the cellular kinetics, safety, feasibility of repeat treatment cycles, and antitumor activity of HER2-CART in patients with advanced sarcoma.
Patients and Methods
On this phase I study, 13 patients with progressive, metastatic HER2+ sarcoma were treated in 14 enrollments; one patient who achieved complete remission was re-enrolled because of disease recurrence. Lymphodepletion consisted of fludarabine (Flu) 25 mg/m2/dose x 5 days with or without cyclophosphamide (Cy) 30 mg/kg/dose x 2 days. The dose cohorts evaluated include 1x108 total T-cells/m2 after Flu (cohort A); 1x108 total T-cells/m2 after Flu/Cy (cohort B) and 1x108 CAR-positive T-cells/m2 after Flu/Cy (cohort C). The evaluation of safety was the primary endpoint. Secondary outcomes included assessment of cellular kinetics and antitumor activity.
Results
All study participants received at least one infusion of HER2-CART after lymphodepletion and were included in the analysis (median age 14 years; range 4-55 years). Seven received multiple HER2-CART infusions. CART expansion was observed after all but two of 21 total infusions given after lymphodepletion. Nine of 12 (75%) patients in cohorts A and B developed grade 1-2 CRS. Two patients in cohort C experienced dose limiting toxicity (DLT) with grade 3-4 CRS. All patients recovered from treatment-related adverse events during study follow-up. Median OS was 8.2 months (95% CI, 4.4-17 months). Antitumor activity was observed at the MTD (cohort B), with 1-year OS and PFS of 62.5% (95% CI, 22.9%-86.1%) and 33.3% (95% CI, 7.8-62.3%), respectively. Three patients remain alive, with one in long-term remission at the sixth year of follow-up. While infused CART products did not exhibit a distinct immunophenotype by sarcoma histology, we observed different trends in expression of immune checkpoints when compared by disease and by treatment response.
Conclusion and Relevance: Autologous HER2-CART can be infused safely after lymphodepletion in patients with progressive sarcoma, and the preliminary evidence of antitumor activity observed supports testing their efficacy in a phase II trial.
Trial Registration: ClinicalTrials.gov identifier: NCT00902044
Design of a new four-dimensional chaotic system and its application to color image encryption
Authors: Yan Shaohui , Li Lin , Zhao Weilong , Gu Binxian
Published: January 2023

In this paper, a new four-dimensional chaotic system is constructed. Then, the dynamics of the phase diagram, Lyapunov exponent, bifurcation, and complexity of the system are investigated, the simulation circuit of the system is designed and the trajectory simulation of the system is implemented using a Field Programmable Gate Array (FPGA). National Institute of Standards and Technology (NIST) tests have verified the randomness of the output of the chaotic sequence by the system. Finally, a new color image encryption algorithm is designed based on this system. In the proposed algorithm, the plaintext information is used to generate the initial value of the system through a hashing algorithm, and the plaintext information is applied to the algorithm, reflecting the idea of algorithmic adaption. The bit-plane decomposition row dislocation breaks the strong correlation between pixels, and finally, the DNA encoding is combined with the diffusion method to complete the complete encryption process. Multiple security analysis methods show that the scheme has a good encryption effect.
Sacubitril/valsartan Ameliorates Cardiac Function and Ventricular Remodeling in CHF Rats via the Inhibition of the Tryptophan/Kynurenine Metabolism and inflammation
Authors: gan jiali , Wang Yuli , Deng Yun , Zhang Jiaqi , Wang Shuangcui , Jiang Xijuan , Guo Maojuan , Song Lili
Published: January 2023

Purpose
Sacubitril/valsartan has been highly recognized as a treatment for Chronic Heart Failure (CHF). Its potential cardioprotective benefits and mechanisms, however, remain to be explored. Metabolomics can be used to identify the metabolic characteristics and related markers, as well as the influence of drugs, thereby opening up new mechanism for sacubitril/valsartan therapy in CHF disease.
Methods
The ligation of left anterior descending and exhaustive swimming were used to induce a rat model of CHF after myocardial infarction. A four-week pharmacological intervention was undertaken with sacubitril/valsartan (2.3 mg/d, n = 9) or 0.9% saline (2 ml/d, n = 9). The efficacy was appraised with echocardiography, serum NT-proBNP, and histopathologica. UPLC-Q/TOF-MS combined with multivariate statistical analysis approach were used to analyze the effect of sacubitril/valsartan on CHF rats. RT-qPCR and western blot were performed to investigate the tryptophan/kynurenine metabolism pathway.
Results
The results showed that the basal cardiac functions of LVEF and LVFS were increased, while the serum NT-proBNP and collagen volume fraction decreased in CHF rats with sacubitril/valsartan. The result of metabolomics demonstrated that sacubitril/valsartan regulated the expression of kynurenine et.al 8 metabolomic biomarkers in CHF rats serum, and it contributed to the cardioprotective effects through tryptophan metabolism pathway. In addition, it was confirmed that the mRNA and protein expression of the indoleamine 2,3-dioxygenase (IDO), the first rate-limiting enzyme of tryptophan metabolism, in the myocardial tissue of CHF rats, were down-regulated by sacubitril/valsartan, which was the same with the IL-1β, IFN-γ, TNF-α, COX-2, and IL-6 mRNA expression, and IL-1β, IFN-γ, and TNF-α expression in serum.
Conclusion
Sacubitril/valsartan can ameliorate cardiac function and ventricular remodeling in CHF rats, at least in part through inhibiting the tryptoph
The effect of reappraisal on the emotional regulation of shame in young adults with ASD and typical peers
Authors: Gaziel-Guttman Meyrav , Anaki David , Mashal Nira
Published: January 2023

Background
Previous findings show that young adults with ASD experience shame in social interactions. These feelings, if poorly mishandled and regulated in a maladaptive manner, may interfere with their attempts to engage with their typical peers and build lasting relationships. One strategy that has been identified to improve shame regulation is cognitive reappraisal. The current study examined the effect of reappraising shame-arousing scenarios on the shame feelings of young adults with ASD and typical young adults.
Methods
Thirty-three Caucasian young adults diagnosed with ASD and 38 typical participants were shown shame-arousing pictures. They were instructed to imagine themselves as the primary character in each social shame scenario and to rate their feelings on a proud-to-shame rating scale. Then, they were trained on how to reappraise shame-arousing pictures less negatively. Finally, participants viewed different social shame photos, reappraised each, and rated their feelings. They stated aloud the new interpretation they came up with for each picture. The reported narratives were recorded on audiotape for later analysis. All participants were given questionnaires and cognitive tasks to assess ASD symptoms, non-verbal intelligence, and verbal abilities.
Results
We found a significant shame reduction after reappraising the images in both groups. However, qualitative analysis of these narratives revealed that the participants with ASD used significantly fewer narratives of positive social interactions. Instead, they provided more neutral and unrealistic descriptions than their typical peers.
Limitations:
Shame induction was manipulated, and ecological validity (as well as long-term effects of reappraisal) is yet to be determined. Participants provided their narratives only in the post-reappraisal stage, and additional measures of reappraisal manipulation are recommended.
Conclusions
These findings highlight shame-regulation abilities in individuals with ASD while pointing to their unique contents. Therefore, we recommend that clinical interventions of emotion regulation in ASD emphasize generating positive reappraisals of social situations.
Spectrum of Neurological Manifestations in Pediatric Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) Linked to COVID-19
Authors: Mahmoud Nagwa M. Sabry , Khalil Ahmed F. M. , Raheem Moustafa M. Abdel
Published: January 2023

Background
Since December 2019, Covid-19 has resulted in high morbidity and mortality worldwide. MIS-C associated with SARS-CoV-2 infection led to serious and life-threatening illness in children causing severe multisystem inflammation. It presented with new neurological symptoms involving both the central and peripheral nervous systems. The aim is to evaluate the neurological manifestations in pediatric patients with MIS-C associated to COVID-19.
Aim
To evaluate the neurological manifestations in Pediatric Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) associated to COVID-19.
Methods
This cross section study included patients who were admitted to Pediatric Intensive Care Unit (PICU) isolation unit at Minia University Hospital during the period from December 2020 to April 2022. The study included a total of 303 patients who were classified in to 3 groups; Group (I) (MIS-C, PCR positive), Group (II) (MIS-C, PCR negative), and Group (III) (Non-MIS-C, PCR positive).
Results
The respiratory, cardiovascular, hematologic and gastrointestinal symptoms were significantly greater among Group (II). Convulsions, DCL, Headache, and Weakness were significantly more demonstrated in Group (I) (19 (31.7%), 17 (28.3%), 17 (28.3%), and 15 (25.0%), respectively). While, drowsiness was significantly more demonstrated in Group (II) (41 (21.9%)). Lymphocytes (%) showed significant lower values in Group (I) and Group (II) (Mean ± SD is 18.9 ± 1.8(, compared to Group (III) (Mean ± SD is 21.4 ± 1.8), p-value < 0.01. D-dimer, CRP and S. Ferritin levels were significantly increased among Group (I) while albumin levels were significantly decreased in Group (I). Troponin levels were significantly increased in patients of Group (II). The majority of patients in the three studied groups showed abnormal Chest CT findings in the form of ground glass opacities (CO-RADS III). The percentage of non-survived patients was significantly increased in Group (I).
Conclusion
Pediatric patients with MIS-C and associated to COVID-19 presenting with neurological, respiratory, cardiovascular, gastrointestinal, and hematologic symptoms. The neurological manifestations could include convulsions, DCL, headache, and weakness.
Integrative Identification of Angiogenesis-Related Genes for Predicting Immune Interaction and Prognosis in LUAD
Authors: Yu Weijie , Miao Zhoulin , Ainiwaer Julaiti , Qiao Bingzhang , Jumai Kawuli , Sheyhidin Ilyar
Published: January 2023

Background
Tumor microenvironment is characterized by angiogenesis. A tumor's microenvironment (TME) and its interactions with immunotherapy influence immunotherapy's effectiveness. In the study of Lung adenocarcinoma (LUAD), there is currently no clear link between multiple angiogenesis genes and clinical results, immune cell infiltration, and immunotherapy.
Methods
Clinical information and corresponding Gene expression were downloaded from the GEO and TCGA. Thirty-six angiogenesis-related genes (ARGs) were comprehensively evaluated, and correlations between angiogenesis and patterns of transcription and prognosis. The immune difference shows different functions and Infiltration in the sub-cluster. KEGG pathway and GO enrichment analyses were conducted based on distinct clusters. ARG_score was established to quantify the angiogenic subtype of each patient. Finally, we assessed their value in predicting prognosis and treatment response in the different risk groups.
Results
The mutations of ARGs in LUAD specimens were discussed at the genetic level. We identified two distinct molecular subtypes and observed that ARG mutations were associated with clinical characteristics, prognosis, and TME of patients. Next, an ARG_score predicting overall survival (OS) was established, confirming its robust predictive power for patients with LUAD. Moreover, a highly reliable Nomogram was created. Low risk score demonstrated better OS. In addition, the ARG_score was shown to be significantly correlated with cancer stem cell index and drug sensitivity. FSTL3 is considered potential target gene.
Conclusion
In general, we were the first to characterize the prognosis of ARGs in patients with LUAD. Angiogenesis may play an essential role in the development of LUAD. This characterization may assist in clarifying the features of angiogenesis in TME and enable the exploration of more cost-effective immunotherapy strategies.
A new (n+1)-dimensional generalized Kadomtsev-Petviashvili equation: Integrability characteristics and localized solutions
Authors: Xu Gui-Qiong , Wazwaz Abdul-Majid
Published: January 2023

In this paper, an integrable generalization of the Kadomtsev-Petviashvili (KP) equation in arbitrary spatial dimension is proposed. Firstly, the singularity manifold analysis is performed to prove that the (n+1)-dimensional KP equation with general form is Painleve integrable. Secondly, combining the truncated Painleve expansion and binary Bell polynomial approach, the integrable characteristics of the (n+1)-dimensional KP equation are derived systematically, including N-soliton solution, bilinear Backlund transformation, the associated Lax pair as well as infinite conservation laws. Moreover, various types of localized solutions can be constructed starting from the N-soliton solutions. The abundant interactions including overtaking solitons, head-on solitons, one-order lump, two-order lump, breather, breather-soliton mixed solutions are analyzed by some graphs.
Overcoming lattice mismatch for heterostructures
Authors: Chan Wen Kiat , Yu Zhongzheng , Zhou Donglei , Ye Junzhi , Tew Alasdair , Turnhout Lars van , Rao Akshay , Tan Timothy
Published: January 2023

The formation of core-shell heterostructures allows direct contact for more efficient energy transfer and requires exquisite lattice match. Lattice mismatch is one of the most challenging obstacles for combining two components with different phases. In this work, we develop a strategy to successfully overcome the limitation of lattice mismatch for the first time andgrow α-phase lead halide perovskites (LHPs) onto β-phase lanthanide nanoparticles (LnNPs) by seeding ultrasmall sub-5 nm LnNPs. This LnNP@LHP heterostructure enables more efficient two-way energy transfer within the heterostructures. Downconversion and upconversion emissions can be achieved under ultraviolet and near-infrared excitation, respectively. In addition, LHP has a high tolerance for defects and will passivate LnNPs for enhanced fluorescent performance. We identify and prove that size instead of phase is critical to overcome the lattice mismatch. Our strategy has uncovered fresh insights into the key factor of direct epitaxial growth for heterostructures and we believe the current synthesis strategy for high-quality heterostructures will have strong application potential in optoelectronics, anticounterfeiting and light detection etc.