bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Hypertrophic Scar Fibroblast-Derived Exosomes on Keratinocytes of Normal Human Skin
Authors: Cui Hui Song , Joo So Young , Lee Seung Yeol , Cho Yoon Soo , Kim Dong Hyun , Seo Cheong Hoon
Published: March 2023

Epidermal keratinocytes are highly activated, hyper-proliferated, and abnormally differentiated in the post-burn hypertrophic scar (HTS); however, the effects of scar fibroblasts (SFs) on keratinocytes through cell–cell interaction in HTS remain unknown. Here, we investigated the effects of HTSF-derived exosomes on the proliferation and differentiation of normal human keratinocytes (NHKs) compared with normal fibroblasts (NFs) and their possible mechanism to provide a reference for clinical intervention of HTS. Fibroblasts were isolated and cultured from HTS and normal skin. Both HTSF-exosomes and NF-exosomes were extracted via a column-based method from the cell culture supernatant. NHKs were treated for 24 or 48 h with 100 μg/mL of cell-derived exosomes. The expression of proliferation markers (Ki-67 and keratin 14), activation markers (keratins 6, 16, and 17), differentiation markers (keratins 1 and 10), apoptosis factors (Bax, Bcl2, caspase 14, and ASK1), proliferation/differentiation regulators (p21 and p27), and epithelial–mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, and vimentin) was investigated. Compared with NF-exosomes, HTSF-exosomes altered the molecular pattern of proliferation, activation, differentiation, and apoptosis, proliferation/differentiation regulators of NHKs, and EMT markers differently. In conclusion, our findings indicate that HTSF-derived exosomes may play a role in the epidermal pathological development of HTS.
Accurate Prediction of Transcriptional Activity of Single Missense Variants in HIV Tat with Deep Learning
Authors: Derbel Houssemeddine , Giacoletto Christopher J. , Benjamin Ronald , Chen Gordon , Schiller Martin R. , Liu Qian
Published: March 2023

Tat is an essential gene for increasing the transcription of all HIV genes, and affects HIV replication, HIV exit from latency, and AIDS progression. The Tat gene frequently mutates in vivo and produces variants with diverse activities, contributing to HIV viral heterogeneity as well as drug-resistant clones. Thus, identifying the transcriptional activities of Tat variants will help to better understand AIDS pathology and treatment. We recently reported the missense mutation landscape of all single amino acid Tat variants. In these experiments, a fraction of double missense alleles exhibited intragenic epistasis. However, it is too time-consuming and costly to determine the effect of the variants for all double mutant alleles through experiments. Therefore, we propose a combined GigaAssay/deep learning approach. As a first step to determine activity landscapes for complex variants, we evaluated a deep learning framework using previously reported GigaAssay experiments to predict how transcription activity is affected by Tat variants with single missense substitutions. Our approach achieved a 0.94 Pearson correlation coefficient when comparing the predicted to experimental activities. This hybrid approach can be extensible to more complex Tat alleles for a better understanding of the genetic control of HIV genome transcription.
Intra-Airway Treatment with Synthetic Lipoxin A4 and Resolvin E2 Mitigates Neonatal Asthma Triggered by Maternal Exposure to Environmental Particles
Authors: Ramar Mohankumar , Yano Naohiro , Fedulov Alexey V.
Published: March 2023

Particulate matter in the air exacerbates airway inflammation (AI) in asthma; moreover, prenatal exposure to concentrated urban air particles (CAPs) and diesel exhaust particles (DEPs) predisposes the offspring to asthma and worsens the resolution of AI in response to allergens. We previously tested the hypothesis that such exposure impairs the pathways of specialized proresolving mediators that are critical for resolution and found declined Lipoxin A4 (LxA4) and Resolvin E2 (RvE2) levels in the “at-risk” pups of exposed mothers. Here, we hypothesized that supplementation with synthetic LxA4 or RvE2 via the airway can ameliorate AI after allergen exposure, which has not been tested in models with environmental toxicant triggers. BALB/c newborns with an asthma predisposition resultant from prenatal exposure to CAPs and DEPs were treated once daily for 3 days with 750 ng/mouse of LxA4 or 300 ng/mouse of RvE2 through intranasal instillation, and they were tested with the intentionally low-dose ovalbumin protocol that elicits asthma in the offspring of particle-exposed mothers but not control mothers, mimicking the enigmatic maternal transmission of asthma seen in humans. LxA4 and RvE2 ameliorated the asthma phenotype and improved AI resolution, which was seen as declining airway eosinophilia, lung tissue infiltration, and proallergic cytokine levels.
Impact of Pesticide Residues on the Gut-Microbiota–Blood–Brain Barrier Axis: A Narrative Review
Authors: Abou Diwan Maria , Lahimer Marwa , Bach Véronique , Gosselet Fabien , Khorsi-Cauet Hafida , Candela Pietra
Published: March 2023

Accumulating evidence indicates that chronic exposure to a low level of pesticides found in diet affects the human gut-microbiota–blood–brain barrier (BBB) axis. This axis describes the physiological and bidirectional connection between the microbiota, the intestinal barrier (IB), and the BBB. Preclinical observations reported a gut microbial alteration induced by pesticides, also known as dysbiosis, a condition associated not only with gastrointestinal disorders but also with diseases affecting other distal organs, such as the BBB. However, the interplay between pesticides, microbiota, the IB, and the BBB is still not fully explored. In this review, we first consider the similarities/differences between these two physiological barriers and the different pathways that link the gut microbiota and the BBB to better understand the dialogue between bacteria and the brain. We then discuss the effects of chronic oral pesticide exposure on the gut-microbiota-BBB axis and raise awareness of the danger of chronic exposure, especially during the perinatal period (pregnant women and offspring).
Polymer Translocation and Nanopore Sequencing: A Review of Advances and Challenges
Authors: Singh Swarn Lata , Chauhan Keerti , Bharadwaj Atul S. , Kishore Vimal , Laux Peter , Luch Andreas , Singh Ajay Vikram
Published: March 2023

Various biological processes involve the translocation of macromolecules across nanopores; these pores are basically protein channels embedded in membranes. Understanding the mechanism of translocation is crucial to a range of technological applications, including DNA sequencing, single molecule detection, and controlled drug delivery. In this spirit, numerous efforts have been made to develop polymer translocation-based sequencing devices, these efforts include findings and insights from theoretical modeling, simulations, and experimental studies. As much as the past and ongoing studies have added to the knowledge, the practical realization of low-cost, high-throughput sequencing devices, however, has still not been realized. There are challenges, the foremost of which is controlling the speed of translocation at the single monomer level, which remain to be addressed in order to use polymer translocation-based methods for sensing applications. In this article, we review the recent studies aimed at developing control over the dynamics of polymer translocation through nanopores.
Interplay of Vitamin D and SIRT1 in Tissue-Specific Metabolism—Potential Roles in Prevention and Treatment of Non-Communicable Diseases Including Cancer
Authors: Nemeth Zsuzsanna , Patonai Attila , Simon-Szabó Laura , Takács István
Published: March 2023

The importance of the prevention and control of non-communicable diseases, including obesity, metabolic syndrome, type 2 diabetes, cardiovascular diseases, and cancer, is increasing as a requirement of the aging population in developed countries and the sustainability of healthcare. Similarly, the 2013–2030 action plan of the WHO for the prevention and control of non-communicable diseases seeks these achievements. Adequate lifestyle changes, alone or with the necessary treatments, could reduce the risk of mortality or the deterioration of quality of life. In our recent work, we summarized the role of two central factors, i.e., appropriate levels of vitamin D and SIRT1, which are connected to adequate lifestyles with beneficial effects on the prevention and control of non-communicable diseases. Both of these factors have received increased attention in relation to the COVID-19 pandemic as they both take part in regulation of the main metabolic processes, i.e., lipid/glucose/energy homeostasis, oxidative stress, redox balance, and cell fate, as well as in the healthy regulation of the immune system. Vitamin D and SIRT1 have direct and indirect influence of the regulation of transcription and epigenetic changes and are related to cytoplasmic signaling pathways such as PLC/DAG/IP3/PKC/MAPK, MEK/Erk, insulin/mTOR/cell growth, proliferation; leptin/PI3K-Akt-mTORC1, Akt/NFĸB/COX-2, NFĸB/TNFα, IL-6, IL-8, IL-1β, and AMPK/PGC-1α/GLUT4, among others. Through their proper regulation, they maintain normal body weight, lipid profile, insulin secretion and sensitivity, balance between the pro- and anti-inflammatory processes under normal conditions and infections, maintain endothelial health; balance cell differentiation, proliferation, and fate; and balance the circadian rhythm of the cellular metabolism. The role of these two molecules is interconnected in the molecular network, and they regulate each other in several layers of the homeostasis of energy and the cellular metabolism. Both have a central role in the maintenance of healthy and balanced immune regulation and redox reactions; therefore, they could constitute promising targets either for prevention or as complementary therapies to achieve a better quality of life, at any age, for healthy people and patients under chronic conditions.
Characterization of the Protein Corona of Three Chairside Hemoderivatives on Melt Electrowritten Polycaprolactone Scaffolds
Authors: Fernandez-Medina T. , Vaquette C. , Gomez-Cerezo M. N. , Ivanovski S.
Published: March 2023

In tissue engineering, the relationship between a biomaterial surface and the host’s immune response during wound healing is crucial for tissue regeneration. Despite hemoderivative functionalization of biomaterials becoming a common tissue-engineering strategy for enhanced regeneration, the characteristics of the protein–biomaterial interface have not been fully elucidated. This study characterized the interface formed by the adsorbed proteins from various hemoderivatives with pristine and calcium phosphate (CaP)-coated polycaprolactone (PCL) melt electrowritten scaffolds. PCL scaffolds were fabricated by using melt electrospinning writing (MEW). Three hemoderivatives (pure platelet-rich plasma (P-PRP), leucocyte platelet-rich plasma (L-PRP) and injectable platelet-rich fibrin (i-PRF)) and total blood PLASMA (control) were prepared from ovine blood. Hemoderivatives were characterized via SEM/EDX, cross-linking assay, weight loss, pH and protein quantification. The interface between PCL/CaP and hemoderivative was examined via FTIR, XPS and electrophoresis. i-PRF/PCL-CaP (1653 cm−1), PLASMA/PCL-CaP (1652 cm−1) and i-PRF/PCL (1651 cm−1) demonstrated a strong signal at the Amide I region. PLASMA and i-PRF presented similar N1s spectra, with most of the nitrogen involved in N-C=O bonds (≈400 eV). i-PRF resulted in higher adsorption of low molecular weight (LMW) proteins at 60 min, while PLASMA exhibited the lowest adsorption. L-PRP and P-PRP had a similar pattern of protein adsorption. The characteristics of biomaterial interfaces can be customized, thus creating a specific hemoderivative-defined layer on the PCL surface. i-PRF demonstrated a predominant adsorption of LMW proteins. Further investigation of hemoderivative functionalized biomaterials is required to identify the differential protein corona composition, and the resultant immune response and regenerative capacity.
pilE G-Quadruplex Is Recognized and Preferentially Bound but Not Processed by the MutL Endonuclease from Neisseria gonorrhoeae Mismatch Repair Pathway
Authors: Savitskaya Viktoriia Yu. , Strekalovskikh Vadim V. , Snyga Viktoriia G. , Monakhova Mayya V. , Arutyunyan Alexander M. , Dolinnaya Nina G. , Kubareva Elena A.
Published: March 2023

The human pathogen Neisseria gonorrhoeae uses a homologous recombination to undergo antigenic variation and avoid an immune response. The surface protein pilin (PilE) is one of the targets for antigenic variation that can be regulated by N. gonorrhoeae mismatch repair (MMR) and a G-quadruplex (G4) located upstream of the pilE promoter. Using bioinformatics tools, we found a correlation between pilE variability and deletion of DNA regions encoding ngMutS or ngMutL proteins, the main participants in N. gonorrhoeae methyl-independent MMR. To understand whether the G4 structure could affect the ngMutL-mediated regulation of pilin antigenic variation, we designed several synthetic pilE G4-containing oligonucleotides, differing in length, and related DNA duplexes. Using CD measurements and biochemical approaches, we have showed that (i) ngMutL preferentially binds to pilE G4 compared to DNA duplex, although the latter is a cognate substrate for ngMutL endonuclease, (ii) protein binding affinity decreases with shortening of quadruplex-containing and duplex ligands, (iii) the G4 structure inhibits ngMutL-induced DNA nicking and modulates cleavage positions; the enzyme does not cleave DNA within G4, but is able to bypass this noncanonical structure. Thus, pilE G4 may regulate the efficiency of pilin antigenic variation by quadruplex binding to ngMutL and suppression of homologous recombination.
Inhibitory Effects of 3-Cyclopropylmethoxy-4-(difluoromethoxy) Benzoic Acid on TGF-β1-Induced Epithelial–Mesenchymal Transformation of In Vitro and Bleomycin-Induced Pulmonary Fibrosis In Vivo
Authors: Sun Tianxiao , Li Haihua , Zhang Yan , Xiong Guixin , Liang Yuerun , Lu Fang , Zheng Rong , Zou Qi , Hao Jiejie
Published: March 2023

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by lung inflammation and excessive deposition of extracellular matrix components. Transforming growth factor-β1 (TGF-β1) induced epithelial–mesenchymal transformation of type 2 lung epithelial cells leads to excessive extracellular matrix deposition, which plays an important role in fibrosis. Our objective was to evaluate the effects of 3-cyclopropylmethoxy-4-(difluoromethoxy) benzoic acid (DGM) on pulmonary fibrosis and aimed to determine whether EMT plays a key role in the pathogenesis of pulmonary fibrosis and whether EMT can be used as a therapeutic target for DGM therapy to reduce IPF. Firstly, stimulation of in vitro cultured A549 cells to construct EMTs with TGF-β1. DGM treatment inhibited the expression of proteins such as α-SMA, vimentin, and collagen Ⅰ and increased the expression of E-cadherin. Accordingly, Smad2/3 phosphorylation levels were significantly reduced by DGM treatment. Secondly, models of tracheal instillation of bleomycin and DGM were used to treat rats to demonstrate their therapeutic effects, such as improving lung function, reducing lung inflammation and fibrosis, reducing collagen deposition, and reducing the expression of E-cadherin. In conclusion, DGM attenuates TGF-β1-induced EMT in A549 cells and bleomycin-induced pulmonary fibrosis in rats.
Mutation at the Site of Hydroxylation in the Ribosomal Protein uL15 (RPL27a) Causes Specific Changes in the Repertoire of mRNAs Translated in Mammalian Cells
Authors: Zolotenkova Elizaveta A. , Gopanenko Alexander V. , Tupikin Alexey E. , Kabilov Marsel R. , Malygin Alexey A.
Published: March 2023

Ribosomal protein uL15 (RPL27a) carries a specific modification, hydroxylation, at the His39 residue, which neighbors the CCA terminus of the E-site-bound tRNA at the mammalian ribosome. Under hypoxia, the level of hydroxylation of this protein decreases. We transiently transfected HEK293T cells with constructs expressing wild-type uL15 or mutated uL15 (His39Ala) incapable of hydroxylation, and demonstrated that ribosomes containing both proteins are competent in translation. By applying RNA-seq to the total cellular and polysome-associated mRNAs, we identified differentially expressed genes (DEGs) in cells containing exogenous uL15 or its mutant form. Analyzing mRNA features of up- and down-regulated DEGs, we found an increase in the level of more abundant mRNAs and shorter CDSs in cells with uL15 mutant for both translated and total cellular mRNAs. The level of longer and rarer mRNAs, on the contrary, decreased. Our data show how ribosome heterogeneity can change the composition of the translatome and transcriptome, depending on the properties of the translated mRNAs.
The Arabidopsis Deubiquitylase OTU5 Suppresses Flowering by Histone Modification-Mediated Activation of the Major Flowering Repressors FLC, MAF4, and MAF5
Authors: Radjacommare Ramalingam , Lin Shih-Yun , Usharani Raju , Lin Wen-Dar , Jauh Guang-Yuh , Schmidt Wolfgang , Fu Hongyong
Published: March 2023

Distinct phylogeny and substrate specificities suggest that 12 Arabidopsis Ovarian Tumor domain-containing (OTU) deubiquitinases participate in conserved or plant-specific functions. The otu5-1 null mutant displayed a pleiotropic phenotype, including early flowering, mimicking that of mutants harboring defects in subunits (e.g., ARP6) of the SWR1 complex (SWR1c) involved in histone H2A.Z deposition. Transcriptome and RT-qPCR analyses suggest that downregulated FLC and MAF4-5 are responsible for the early flowering of otu5-1. qChIP analyses revealed a reduction and increase in activating and repressive histone marks, respectively, on FLC and MAF4-5 in otu5-1. Subcellular fractionation, GFP-fusion expression, and MNase treatment of chromatin showed that OTU5 is nucleus-enriched and chromatin-associated. Moreover, OTU5 was found to be associated with FLC and MAF4-5. The OTU5-associated protein complex(es) appears to be distinct from SWR1c, as the molecular weights of OTU5 complex(es) were unaltered in arp6-1 plants. Furthermore, the otu5-1 arp6-1 double mutant exhibited synergistic phenotypes, and H2A.Z levels on FLC/MAF4-5 were reduced in arp6-1 but not otu5-1. Our results support the proposition that Arabidopsis OTU5, acting independently of SWR1c, suppresses flowering by activating FLC and MAF4-5 through histone modification. Double-mutant analyses also indicate that OTU5 acts independently of the HUB1-mediated pathway, but it is partially required for FLC-mediated flowering suppression in autonomous pathway mutants and FRIGIDA-Col.
Influence of MMR, MGMT Promotor Methylation and Protein Expression on Overall and Progression-Free Survival in Primary Glioblastoma Patients Treated with Temozolomide
Authors: Brawanski Konstantin R. , Sprung Susanne , Freyschlag Christian F. , Hoeftberger Romana , Ströbel Thomas , Haybaeck Johannes , Thomé Claudius , Manzl Claudia , Birkl-Toeglhofer Anna M.
Published: March 2023

Glioblastoma is the most common malignant brain tumor in adults. Standard treatment includes tumor resection, radio-chemotherapy and adjuvant chemotherapy with temozolomide (TMZ). TMZ methylates DNA, whereas O6-methylguanine DNA methyltransferase (MGMT) counteracts TMZ effects by removing the intended proteasomal degradation signal. Non-functional MGMT mediates the mismatch repair (MMR) system, leading to apoptosis after futile repair attempts. This study investigated the associations between MGMT promoter methylation, MGMT and MMR protein expression, and their effect on overall survival (OS) and progression-free survival (PFS) in patients with glioblastoma. MGMT promoter methylation was assessed in 42 treatment-naïve patients with glioblastoma WHO grade IV by pyrosequencing. MGMT and MMR protein expression was analyzed using immunohistochemistry. MGMT promoter methylation was present in 52%, whereas patients <70 years of age revealed a significantly longer OS using a log-rank test and a significance threshold of p ≤ 0.05. MGMT protein expression and methylation status showed no correlation. MMR protein expression was present in all patients independent of MGMT status and did not influence OS and PFS. Overall, MGMT promoter methylation implicates an improved OS in patients with glioblastoma aged <70 years. In the elderly, the extent of surgery has an impact on OS rather than the MGMT promoter methylation or protein expression.
BmCBP Catalyzes the Acetylation of BmApoLp-II Protein and Regulates Its Stability in Silkworm, Bombyx mori
Authors: Chen Yanmei , Lv Jiao , Zu Guowei , Yang Fan , Geng Jiasheng , You Zhengying , Jiang Caiying , Sheng Qing , Nie Zuoming
Published: March 2023

Acetylation is an important and reversible post-translational modification (PTM) of protein, which is involved in many cellular physiological processes. In previous studies, lots of nutrient storage proteins were found to be highly acetylated in silkworms, and acetylation can improve the stability of these proteins. However, the related acetyltransferase was not involved. In the present work, a Bombyx mori nutrient storage protein, apolipophorin II (BmApoLp-II), was further confirmed to be acetylated, and the acetylation could improve its protein expression. Furthermore, RNAi and Co-IP showed that the acetyltransferase BmCBP was found to catalyze the acetylation modification of BmApoLp-II, and thus affect its protein expression. Meanwhile, it was proved that acetylation could improve the stability of the BmApoLp-II protein by completing its ubiquitination. These results lay a foundation for further study on the mechanism of regulating nutrition storage and hydrolysis utilization of storage proteins by BmCBP and the acetylation in the silkworm Bombyx mori.
Convolutional Neural Network-Based Low-Powered Wearable Smart Device for Gait Abnormality Detection
Authors: Shakya Sanjeev , Taparugssanagorn Attaphongse , Silpasuwanchai Chaklam
Published: March 2023

Gait analysis is a powerful technique that detects and identifies foot disorders and walking irregularities, including pronation, supination, and unstable foot movements. Early detection can help prevent injuries, correct walking posture, and avoid the need for surgery or cortisone injections. Traditional gait analysis methods are expensive and only available in laboratory settings, but new wearable technologies such as AI and IoT-based devices, smart shoes, and insoles have the potential to make gait analysis more accessible, especially for people who cannot easily access specialized facilities. This research proposes a novel approach using IoT, edge computing, and tiny machine learning (TinyML) to predict gait patterns using a microcontroller-based device worn on a shoe. The device uses an inertial measurement unit (IMU) sensor and a TinyML model on an advanced RISC machines (ARM) chip to classify and predict abnormal gait patterns, providing a more accessible, cost-effective, and portable way to conduct gait analysis.
Strategies for Safe Implantation and Effective Performance of Single-Chamber and Dual-Chamber Leadless Pacemakers
Authors: Tong Fei , Sun Zhijun
Published: March 2023

Leadless pacemakers (LPMs) have emerged as an alternative to conventional transvenous pacemakers to eliminate the complications associated with leads and subcutaneous pockets. However, LPMs still present with complications, such as cardiac perforation, dislodgment, vascular complications, infection, and tricuspid valve regurgitation. Furthermore, the efficacy of the leadless VDD LPMs is influenced by the unachievable 100% atrioventricular synchrony. In this article, we review the available data on the strategy selection, including appropriate patient selection, procedure techniques, device design, and post-implant programming, to minimize the complication rate and maximize the efficacy, and we summarize the clinical settings in which a choice must be made between VVI LPMs, VDD LPMs, or conventional transvenous pacemakers. In addition, we provide an outlook for the technology for the realization of true dual-chamber leadless and battery-less pacemakers.
Diagnostic Utility of Serum Leucine-Rich α-2-Glycoprotein 1 for Acute Appendicitis in Children
Authors: Tintor Goran , Jukić Miro , Šupe-Domić Daniela , Jerončić Ana , Pogorelić Zenon
Published: March 2023

Purpose: The aim of this study is to assess the diagnostic utility of serum leucine-rich α-2-glycoprotein 1 (LRG1) in pediatric patients with acute abdominal pain, admitted to the emergency surgical unit, in order to make a prompt and accurate diagnosis of acute appendicitis. Patients and methods: Pediatric patients older than 5 years of age who presented to the emergency department from 15 October 2021 to 30 June 2022 with acute abdominal pain and suspected acute appendicitis were prospectively recruited in the study. Demographic and clinical data, as well as operative and postoperative data, were recorded. A total of 92 patients were equally distributed into two groups: children with acute appendicitis who underwent laparoscopic appendectomy and non-appendicitis patients, presenting with non-specific abdominal pain. LRG1 levels were determined using a commercially available LRG1 enzyme-linked immunosorbent assay (ELISA) kit. Serum LRG1 levels, as well as other inflammatory markers (white blood cell count (WBC), C-reactive protein (CRP) and absolute neutrophil count) were compared between groups. Results: The median level of LRG1 in serum was significantly higher in the group of children with pathohistologically confirmed acute appendicitis than in the control group, at 350.3 µg/mL (interquartile range (IQR) 165.2–560.3) and 25.7 µg/mL (IQR 14.7–36.8) (p < 0.001), respectively. Receiver operating characteristic area under the curve for LRG1 from serum was 1.0 (95% CI 0.96–1.00; p < 0.001) and the value of >69.1 µg/mL was found to perfectly separate acute appendicitis cases from controls. Additionally, as expected, each of the examined laboratory inflammatory markers provided a significantly higher values in the acute appendicitis group compared to the control group: WBC 14.6 × 109/L (IQR 12.7, 18.7) vs. 7.0 × 109/L (IQR 5.4, 9.0) (p < 0.001), CRP 16.3 mg/dL (IQR 6.9, 50.4) vs. 2.2 mg/dL (IQR 2, 2) (p < 0.001) and absolute neutrophil count 84.6% (IQR 79.5, 89.0) vs. 59.5% (IQR 51.5, 68.6) (p < 0.001). Conclusions: LRG1 in the serum was found to be a promising novel biomarker, with excellent differentiation of acute appendicitis from non-appendicitis cases in children presenting with non-specific abdominal pain.
Clinical Course and Severity of COVID-19 in 940 Infants with and without Comorbidities Hospitalized in 2020 and 2021: The Results of the National Multicenter Database SARSTer-PED
Authors: Pawłowska Małgorzata , Pokorska-Śpiewak Maria , Talarek Ewa , Mania Anna , Hasiec Barbara , Żwirek-Pytka Elżbieta , Stankiewicz Magdalena , Stani Martyna , Frańczak-Chmura Paulina , Szenborn Leszek , Zaleska Izabela , Chruszcz Joanna , Majda-Stanisławska Ewa , Dryja Urszula , Gąsiorowska Kamila , Figlerowicz Magdalena , Mazur-Melewska Katarzyna , Faltin Kamil , Ciechanowski Przemysław , Peregrym Michał , Łasecka-Zadrożna Joanna , Rudnicki Józef , Szczepańska Barbara , Pałyga-Bysiecka Ilona , Rogowska Ewelina , Hudobska-Nawrot Dagmara , Domańska-Granek Katarzyna , Sybilski Adam , Kucharek Izabela , Franczak Justyna , Sobolewska-Pilarczyk Małgorzata , Kuchar Ernest , Wronowski Michał , Paryż Maria , Kalicki Bolesław , Toczyłowski Kacper , Sulik Artur , Niedźwiecka Sławomira , Flisiak Robert , Marczyńska Magdalena
Published: March 2023

This study aimed to analyze the differences in severity and clinical characteristics of COVID-19 in infants hospitalized in Poland in 2021, when the dominance of variants of concern (VOCs) alpha and delta was reported, compared to 2020, when original (wild) SARS-CoV-2 was dominant (III–IV vs. I–II waves of the pandemic, respectively). In addition, the influence of the presence of comorbidities on the clinical course of COVID-19 in infants was studied. This multicenter study, based on the pediatric part of the national SARSTer database (SARSTer-PED), included 940 infants with COVID-19 diagnosed between March 1, 2020, and December 31, 2021, from 13 Polish inpatient centers. An electronic questionnaire, which addressed epidemiological and clinical data, was used. The number of hospitalized infants was significantly higher in 2021 than in 2020 (651 vs. 289, respectively). The analysis showed similar lengths of infant hospitalization in 2020 and 2021, but significantly more children were hospitalized for more than 7 days in 2020 (p < 0.009). In both analyzed periods, the most common route of infection for infants was household contact. There was an increase in the percentage of comorbidities, especially prematurity, in children hospitalized in 2021 compared to 2020. Among the clinical manifestations, fever was predominant among children hospitalized in 2021 and 2020. Cough, runny nose, and loss of appetite were significantly more frequently observed in 2021 (p < 0.0001). Severe and critical conditions were significantly more common among children with comorbidities. More infants were hospitalized during the period of VOCs dominance, especially the delta variant, compared to the period of wild strain dominance, even though indications for hospitalization did not include asymptomatic patients during that period. The course of COVID-19 was mostly mild, characterized mainly by fever and respiratory symptoms. Comorbidities, particularly from the cardiovascular system and prematurity, were associated with a more severe course of the disease in infants.
Causal Link between Inflammatory Bowel Disease and Fistula: Evidence from Mendelian Randomization Study
Authors: Tan Zongbiao , Zhu Shijie , Liu Chuan , Meng Yang , Li Jiao , Zhang Jixiang , Dong Weiguo
Published: March 2023

Background: Previous observational studies have found that fistulas are common in Crohn’s disease (CD) and less common in ulcerative colitis (UC). However, some patients have a fistula before diagnosis. Based on retrospective analysis, it was not possible to determine whether there was a bi-directional causal relationship between inflammatory bowel disease (IBD) and fistulas. Methods: Data were extracted from the open GWAS database; 25,042 cases and 34,915 controls were included for IBD, and 6926 cases and 30,228 controls were included for fistula. Two-sample Mendelian randomization and multivariable Mendelian randomization were used in combination to determine the causal relationship between IBD and fistula. Results: Forward MR showed that IBD increased the risk of colonic or urogenital fistula (FISTULA) (OR: 1.09, 95% CI: 1.05 to 1.13, p = 1.22 × 10−6), mainly associated with fissure and fistula of the anal and rectal regions (FISSANAL) (OR:1.10, 95% CI:1.06 to 1.14, p = 6.12 × 10−8), but not with fistulas involving the female genital tract (FEMGENFISTUL) (OR:0.97, 95% CI: 0.85 to 1.11, p = 0.669). Furthermore, both UC and CD increased the risk of FISTULA. However, after adjusting by MVMR, only CD increased the risk of FISTULA (OR: 1.06, 95% CI: 1.02 to 1.11, p = 0.004), and UC did not increase the risk of FISTULA (OR: 1.01, 95% CI: 0.95 to 1.06, p = 0.838). Reverse MR showed that fistulas did not increase the risk of IBD. Conclusion: Our study confirms it is CD, rather than UC, that casually leads to an increased risk of fistula, but fistulas do not increase the risk of IBD.
Magnetic Nanoscalpel for the Effective Treatment of Ascites Tumors
Authors: Zamay Tatiana , Zamay Sergey , Luzan Natalia , Fedotovskaya Victoriya , Masyugin Albert , Zelenov Fyodor , Koshmanova Anastasia , Nikolaeva Elena , Kirichenko Daria , Veprintsev Dmitry , Kolovskaya Olga , Shchugoreva Irina , Zamay Galina , Lapin Ivan , Lukyanenko Anna , Borus Andrey , Sukhachev Alexander , Volochaev Mikhail , Lukyanenko Kirill , Shabanov Alexandr , Zabluda Vladimir , Zhizhchenko Alexey , Kuchmizhak Aleksandr , Sokolov Alexey , Narodov Andrey , Prokopenko Vladimir , Galeev Rinat , Svetlichnyi Valery , Kichkailo Anna
Published: March 2023

One of the promising novel methods for radical tumor resection at a single-cell level is magneto-mechanical microsurgery (MMM) with magnetic nano- or microdisks modified with cancer-recognizing molecules. A low-frequency alternating magnetic field (AMF) remotely drives and controls the procedure. Here, we present characterization and application of magnetic nanodisks (MNDs) as a surgical instrument (“smart nanoscalpel”) at a single-cell level. MNDs with a quasi-dipole three-layer structure (Au/Ni/Au) and DNA aptamer AS42 (AS42-MNDs) on the surface converted magnetic moment into mechanical and destroyed tumor cells. The effectiveness of MMM was analyzed on Ehrlich ascites carcinoma (EAC) cells in vitro and in vivo using sine and square-shaped AMF with frequencies from 1 to 50 Hz with 0.1 to 1 duty-cycle parameters. MMM with the “Nanoscalpel” in a sine-shaped 20 Hz AMF, a rectangular-shaped 10 Hz AMF, and a 0.5 duty cycle was the most effective. A sine-shaped field caused apoptosis, whereas a rectangular-shaped field caused necrosis. Four sessions of MMM with AS42-MNDs significantly reduced the number of cells in the tumor. In contrast, ascites tumors continued to grow in groups of mice and mice treated with MNDs with nonspecific oligonucleotide NO-MND. Thus, applying a “smart nanoscalpel” is practical for the microsurgery of malignant neoplasms.
Elevated Temperature, Nitrate and Diesel Oil Enhance the Distribution of the Opportunistic Pathogens Scedosporium spp.
Authors: Rainer Johannes , Eggertsberger Marlene
Published: March 2023

Scedosporium infections mainly occur after aspiration of contaminated water or inoculation with polluted environmental materials. Scedosporium spp. have been isolated from anthropogenic environments frequently. To understand their propagation and routes of infection, possible reservoirs of Scedosporium spp. should be explored. In this study, the impact of temperature, diesel and nitrate on Scedosporium populations in soil is described. Soil was treated with diesel and KNO3 and incubated for nine weeks at 18 and 25 °C. Isolation of Scedosporium strains was done using SceSel+. For the identification of 600 isolated strains, RFLP and rDNA sequencing were used. Scedosporium apiospermum, S. aurantiacum, S. boydii and S. dehoogii were isolated at the beginning and/or the end of incubation. Temperature alone had a minor effect on the Scedosporium population. The combination of 25 °C and nitrate resulted in higher Scedosporium numbers. Treatment with 10 g diesel/kg soil and incubation at 25 °C resulted in even higher abundance, and favored S. apiospermum and S. dehoogii. The results of this study show that diesel-polluted soils favor dispersal of Scedosporium strains, especially S. apiospermum and S. dehoogii. Higher temperature force the effect of supplementations.
Susceptibility to Colorectal Cancer Based on HSD17B4 rs721673 and rs721675 Polymorphisms and Alcohol Intake among Taiwan Biobank Participants: A Retrospective Case Control Study Using the Nationwide Claims Data
Authors: Lin Tzu-Chiao , Chuang Min-Hua , Hsiung Chia-Ni , Chang Pi-Kai , Sun Chien-An , Yang Tsan , Chou Yu-Ching , Hu Je-Ming , Hsu Chih-Hsiung
Published: March 2023

Colorectal cancer (CRC) is a major public health issue, and there are limited studies on the association between 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4) polymorphism and CRC. We used two national databases from Taiwan to examine whether HSD17B4 rs721673, rs721675, and alcohol intake were independently and interactively correlated with CRC development. We linked the Taiwan Biobank (TWB) participants’ health and lifestyle information and genotypic data from 2012 to 2018 to the National Health Insurance Database (NHIRD) to confirm their medical records. We performed a genome-wide association study (GWAS) using data from 145 new incident CRC cases and matched 1316 healthy, non-CRC individuals. We calculated the odds ratios (OR) and 95% confidence intervals (CI) for CRC based on multiple logistic regression analyses. HSD17B4 rs721673 and rs721675 on chromosome 5 were significantly and positively correlated with CRC (rs721673 A > G, aOR = 2.62, p = 2.90 × 10−8; rs721675 A > T, aOR = 2.61, p = 1.01 × 10−6). Within the high-risk genotypes, significantly higher ORs were observed among the alcohol intake group. Our results demonstrated that the rs721673 and rs721675 risk genotypes of HSD17B4 might increase the risk of CRC development in Taiwanese adults, especially those with alcohol consumption habits.
The Digital Platform, Enterprise Digital Transformation, and Enterprise Performance of Cross-Border E-Commerce—From the Perspective of Digital Transformation and Data Elements
Authors: Yang Yunpeng , Chen Nan , Chen Hongmin
Published: March 2023

The digital trade ecosystem’s development relies on the growth of cross-border e-commerce platforms. To ensure the continued growth of China’s digital trade, it is crucial to consider the service capabilities of digital platforms and the digital transformation capabilities of cross-border e-commerce firms. This study explores the impact of these factors on the performance of cross-border e-commerce companies, with digital transformation capability acting as a mediator. Empirical research reveals that the service capability of digital platforms is composed of supply chain communication and cost control abilities, which partially mediate the relationship between digital platform serviceability and cross-border e-commerce enterprise performance. Moreover, both the service capabilities of digital platforms and the digital transformation capabilities of cross-border e-commerce companies have a positive and significant impact on enterprise performance.
Spatiotemporal Relationship between Ecological Restoration Space and Ecosystem Services in the Yellow River Basin, China
Authors: Zhang Yuhang , Hu Zhenqi , Han Jiazheng , Liu Xizhao , Feng Zhanjie , Zhang Xi
Published: March 2023

Ecological restoration is an important implement to avoid land degradation and improve the sustainability of ecosystems. As a spatial definition of ecological restoration, ecological restoration space (ERS) is recognized to have a positive impact on the environment. However, its spatiotemporal pattern and magnitude of contribution to ecosystem services (ESs) remain uncertain. In this study, an ecological restoration trajectories model was developed to investigate the spatiotemporal pattern and evolution of ERS. The InVEST model and geographically weighted regression were used to evaluate the dynamic relationship between ERS and crucial ESs. Results demonstrated that from 1990 to 2015, the cumulative area of ERS in the Yellow River Basin (YRB) was 184,197.05 km2, with Inner Mongolia, Qinghai, and Shaanxi having the largest distribution. The change in geographical center of three subcategories, forest restoration space (FRS), grassland restoration space (GRS), and shrub restoration space (SRS), showed a pronounced geographical migration. Meanwhile, the distribution of ERS significantly improved the conditions of habitat quality (HQ), carbon storage (CS), and soil conservation (SC) on 75.48%, 71.86%, and 56.75% of the grids, respectively. This study provides a scientific foundation for the ecosystem conservation and land management of the YRB.
Quantifying the Contribution of Rural Residents’ Participation in the Cultural Tourism Industry to Improve the Soil Erosion Control Effect in Ecologically Fragile Areas: A Case Study in the Shaanxi–Gansu–Ningxia Border Region, China
Authors: He Yilun , Zhan Shaowen , Aziz Noshaba
Published: March 2023

Previous studies have paid little attention to the causal effect and mechanism between rural residents’ participation in the cultural tourism industry and the effect of soil erosion control. To analyze this phenomenon empirically, this study employs the propensity scores matching (PSM) method and the mediating effect model to explore the impact and mechanism of rural residents’ participation in the cultural tourism industry on the effect of soil erosion control in ecologically fragile areas. Using data gathered from 572 rural households from the Shaanxi, Gansu and Ningxia border region, China, the results show that: (1) Compared with non-participation, residents’ participation in the cultural tourism industry positively influences the soil erosion control effect; if the residents participating in the cultural tourism industry did not participate, the soil erosion control effect would decrease to 2.715–2.844. (2) Considering the heterogeneity of residents’ endowments and attributes of soil erosion technology, the effect of water erosion control is also heterogeneous. (3) Mechanism analysis confirms that residents’ participation in the cultural tourism industry mainly affects soil erosion control through increased non-agricultural income, optimal allocation of labor, and improved environmental protection awareness. Finally, some valuable and promotable policy implications are put forward.
Species Enriched Grass–Clover Pastures Show Distinct Carabid Assemblages and Enhance Endangered Species of Carabid Beetles (Coleoptera: Carabidae) Compared to Continuous Maize
Authors: Beye Henriette , Taube Friedhelm , Donath Tobias W. , Schulz Jan , Hasler Mario , Diekötter Tim
Published: March 2023

There is an urgent global need for the ecological intensification of agricultural systems to reduce negative impacts on the environment while meeting the rising demand for agricultural products. Enriching grasslands with floral species is a tool to promote diversity and the associated services at higher trophic levels, and ultimately, to enhance the agricultural landscape matrix. Here, we studied an organic pastures-based dairy production system with plant species enhanced grass–clover pastures with respect to the effect on the activity density, functional traits, carabid assemblages, and species richness of carabid beetles. To understand the effect of land management on carabid beetles, we studied two types of grass–clover pastures with low and relatively high plant diversities in an integrated crop–livestock rotational grazing system (ICLS). As a comparison, organic permanent grasslands and conventionally managed maize were studied. We installed pitfall traps for three weeks in early summer, and for two weeks in autumn. In total, 11,347 carabid beetles of 66 species were caught. Grass–clover pastures did not differ in activity density, functional traits, habitat guilds, or species richness, but conventional maize did show a higher activity density in autumn and a higher proportion of eurytopic species and mobile species compared to grass–clover pastures. On grass–clover pastures, we found more endangered species, Carabus beetles, and a distinct carabid assemblage compared to maize. However, we attribute the lack of an effect of increased plant diversity of the grass–clover pastures on carabid species richness and functional traits to the intensive grazing regime, which resulted in the compositional and structural homogeneity of vegetation. Still, the presence of specialized and endangered species indicated the potential for organically managed grass–clover pastures to promote dispersal through an otherwise depleted and fragmented agricultural landscape. By increasing crop diversity in ICLS, more resources for foraging and nesting are created; therefore, organically managed grass–clover pastures add to the multi-functionality of agricultural landscapes.
Precipitation Forecasting and Monitoring in Degraded Land: A Study Case in Zaghouan
Authors: Weslati Okba , Bouaziz Moncef , Serbaji Mohamed-Moncef
Published: March 2023

The study aimed to forecast and monitor drought over degraded land based on monthly precipitation using the Seasonal Autoregressive Integrated Moving Average (SARIMA) approach. Several statistical parameters to select the most appropriate model were applied. The results indicate that the SARIMA (1,1,1) (0,1,1)12 is the most suitable for 1981 to 2019 CHIRPS time-series data. The combination of precipitation data and this approved model will subsequently be applied to compute, assess, and predict the severity of drought in the study area. The forecasting performance of the generated SARIMA model was evaluated according to the mean absolute percentage error (15%), which indicated that the proposed model showed high performance in forecasting drought. The forecasting trends showed adequate results, fitting well with the historical tendencies of drought events.
Prospective Analysis of B Lymphocyte Subtypes, before and after Initiation of Dialysis, in Patients with End-Stage Renal Disease
Authors: Daikidou Dimitra-Vasilia , Lioulios Georgios , Sampani Erasmia , Xochelli Aliki , Nikolaidou Vasiliki , Moysidou Eleni , Christodoulou Michalis , Iosifidou Artemis , Iosifidou Myrto , Briza Dimitria , Papagianni Aikaterini , Fylaktou Asimina , Stangou Maria
Published: March 2023

End-stage renal disease (ESRD) is followed by alterations in adaptive immunity. The aim of this study was to evaluate B lymphocyte subtypes in ESRD patients before and after hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Patients and Methods. CD5, CD27, BAFF, IgM and annexin were evaluated by flow cytometry on CD19+ cells in ESRD patients (n = 40), at time of initiating HD or CAPD (T0) and 6 months later (T6). Results. A significant reduction in ESRD-T0 compared to controls was noticed for CD19+, 70.8 (46.5) vs. 171 (249), p < 0.0001, CD19+CD5−, 68.6 (43) vs. 168.9 (106), p < 0.0001, CD19+CD27−, 31.2 (22.1) vs. 59.7 (88.4), p < 0.0001, CD19+CD27+, 42.1 (63.6) vs. 84.3 (78.1), p = 0.002, CD19+BAFF+, 59.7 (37.8) vs. 127.9 (123.7), p < 0.0001 and CD19+IgM+ cells, 48.9 (42.8) vs. 112.5 (81.7) (K/μL), p < 0.0001. The ratio of early/late apoptotic B lymphocytes was reduced (16.8 (10.9) vs. 110 (25.4), p = 0.03). CD19+CD5+ cells were the only cell type with an increased proportion in ESRD-T0 patients (2.7 (3.7) vs. 0.6 (1.1), p < 0.0001). After 6 months on CAPD or HD, CD19+CD27−(%) and early apoptotic lymphocytes were reduced further. The HD patients also showed a significant increase in late apoptotic lymphocytes, from 1.2 (5.7) to 4.2 (7.2) K/mL, p = 0.02. Conclusions. B cells and most of their subtypes were significantly reduced in ESRD-T0 patients compared to controls, the only exception being CD19+CD5+ cells. Apoptotic changes were prominent in ESRD-T0 patients and were exacerbated by HD.