bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of an Artificial Neural Network to Identify the Factors Influencing Neurorehabilitation Outcomes of Patients with Ischemic Stroke Treated with Thrombolysis
Authors: Iosa Marco , Paolucci Stefano , Antonucci Gabriella , Ciancarelli Irene , Morone Giovanni
Published: February 2023

The administration of thrombolysis usually reduces the risk of death and the consequences of stroke in the acute phase. However, having received thrombolysis administration is not a prognostic factor for neurorehabilitation outcome in the subacute phase of stroke. It is conceivably due to the complex intertwining of many clinical factors. An artificial neural network (ANN) analysis could be helpful in identifying the prognostic factors of neurorehabilitation outcomes and assigning a weight to each of the factors considered. This study hypothesizes that the prognostic factors could be different between patients who received and those who did not receive thrombolytic treatment, even if thrombolysis is not a prognostic factor per se. In a sample of 862 patients with ischemic stroke, the tested ANN identified some common factors (such as disability at admission, age, unilateral spatial neglect), some factors with higher weight in patients who received thrombolysis (hypertension, epilepsy, aphasia, obesity), and some other factors with higher weight in the other patients (dysphagia, malnutrition, total arterial circulatory infarction). Despite the fact that thrombolysis is not an independent prognostic factor for neurorehabilitation, it seems to modify the relative importance of other clinical factors in predicting which patients will better respond to neurorehabilitation.
Novel Green Fluorescent Polyamines to Analyze ATP13A2 and ATP13A3 Activity in the Mammalian Polyamine Transport System
Authors: Houdou Marine , Jacobs Nathalie , Coene Jonathan , Azfar Mujahid , Vanhoutte Roeland , Van den Haute Chris , Eggermont Jan , Daniëls Veronique , Verhelst Steven H. L. , Vangheluwe Peter
Published: February 2023

Cells acquire polyamines putrescine (PUT), spermidine (SPD) and spermine (SPM) via the complementary actions of polyamine uptake and synthesis pathways. The endosomal P5B-type ATPases ATP13A2 and ATP13A3 emerge as major determinants of mammalian polyamine uptake. Our biochemical evidence shows that fluorescently labeled polyamines are genuine substrates of ATP13A2. They can be used to measure polyamine uptake in ATP13A2- and ATP13A3-dependent cell models resembling radiolabeled polyamine uptake. We further report that ATP13A3 enables faster and stronger cellular polyamine uptake than does ATP13A2. We also compared the uptake of new green fluorescent PUT, SPD and SPM analogs using different coupling strategies (amide, triazole or isothiocyanate) and fluorophores (symmetrical BODIPY, BODIPY-FL and FITC). ATP13A2 promotes the uptake of various SPD and SPM analogs, whereas ATP13A3 mainly stimulates the uptake of PUT and SPD conjugates. However, the polyamine linker and coupling position on the fluorophore impacts the transport capacity, whereas replacing the fluorophore affects polyamine selectivity. The highest uptake in ATP13A2 or ATP13A3 cells is observed with BODIPY-FL-amide conjugated to SPD, whereas BODIPY-PUT analogs are specifically taken up via ATP13A3. We found that P5B-type ATPase isoforms transport fluorescently labeled polyamine analogs with a distinct structure–activity relationship (SAR), suggesting that isoform-specific polyamine probes can be designed.
Spatio-Temporal Expression Pattern of CAKUT Candidate Genes DLG1 and KIF12 during Human Kidney Development
Authors: Veljačić Visković Daniela , Lozić Mirela , Vukoja Martina , Šoljić Violeta , Vukojević Katarina , Glavina Durdov Merica , Filipović Natalija , Lozić Bernarda
Published: February 2023

We aimed to investigate expression of the novel susceptibility genes for CAKUT, DLG1 and KIF12, proposed by a systematic in silico approach, in developing and postnatal healthy human kidneys to provide information about their spatiotemporal expression pattern. We analyzed expression of their protein products by immunohistochemistry and immunofluorescence and quantified relative mRNA levels by RT-qPCR. Statistically significant differences in expression patterns were observed between certain developmental stages. Strong expression of DLG1 was observed in the developing kidney, with a gradual decrease from the first phase of kidney development (Ph1) until the third phase (Ph3), when most nephrons are formed; at later stages, the highest expression was observed in the tubules. KIF12 was highly expressed in the developing structures, especially in Ph1, with a gradual decrease until the postnatal phase, which would indicate a significant role in nephrogenesis. Co-localization of DLG1 and KIF12 was pronounced in Ph1, especially on the apical side of the tubular epithelial cells. Thereafter, their expression gradually became weaker and was only visible as punctate staining in Ph4. The direct association of DLG1 with KIF12 as control genes of normal kidney development may reveal their new functional aspect in renal tubular epithelial cells.
The Mechanism of Enantioselective Neurosteroid Actions on GABAA Receptors
Authors: Tateiwa Hiroki , Chintala Satyanarayana M. , Chen Ziwei , Wang Lei , Amtashar Fatima , Bracamontes John , Germann Allison L. , Pierce Spencer R. , Covey Douglas F. , Akk Gustav , Evers Alex S.
Published: February 2023

The neurosteroid allopregnanolone (ALLO) and pregnanolone (PREG), are equally effective positive allosteric modulators (PAMs) of GABAA receptors. Interestingly, the PAM effects of ALLO are strongly enantioselective, whereas those of PREG are not. This study was aimed at determining the basis for this difference in enantioselectivity. The oocyte electrophysiology studies showed that ent-ALLO potentiates GABA-elicited currents in α1β3 GABAA receptors with lower potency and efficacy than ALLO, PREG or ent-PREG. The small PAM effect of ent-ALLO was prevented by the α1(Q242L) mutation in the intersubunit neurosteroid binding site between the β3 and α1 subunits. Consistent with this result, neurosteroid analogue photolabeling with mass spectrometric readout, showed that ent-ALLO binds weakly to the β3-α1 intersubunit binding site in comparison to ALLO, PREG and ent-PREG. Rigid body docking predicted that ent-ALLO binds in the intersubunit site with a preferred orientation 180° different than ALLO, PREG or ent-PREG, potentially explaining its weak binding and effect. Photolabeling studies did not identify differences between ALLO and ent-ALLO binding to the α1 or β3 intrasubunit binding sites that also mediate neurosteroid modulation of GABAA receptors. The results demonstrate that differential binding of ent-ALLO and ent-PREG to the β3-α1 intersubunit site accounts for the difference in enantioselectivity between ALLO and PREG.
The Application of Single-Cell RNA Sequencing in the Inflammatory Tumor Microenvironment
Authors: Zhao Jiayi , Shi Yiwei , Cao Guangwen
Published: February 2023

The initiation and progression of tumors are complex. The cancer evolution-development hypothesis holds that the dysregulation of immune balance is caused by the synergistic effect of immune genetic factors and environmental factors that stimulate and maintain non-resolving inflammation. Throughout the cancer development process, this inflammation creates a microenvironment for the evolution and development of cancer. Research on the inflammatory tumor microenvironment (TME) explains the initiation and progression of cancer and guides anti-cancer immunotherapy. Single-cell RNA sequencing (scRNA-seq) can detect the transcription levels of cells at the single-cell resolution level, reveal the heterogeneity and evolutionary trajectory of infiltrated immune cells and cancer cells, and provide insight into the composition and function of each cell group in the inflammatory TME. This paper summarizes the application of scRNA-seq in inflammatory TME.
Liver X Receptor Inverse Agonist GAC0001E5 Impedes Glutaminolysis and Disrupts Redox Homeostasis in Breast Cancer Cells
Authors: Premaratne Asitha , Ho Charles , Basu Shinjini , Khan Ashfia Fatima , Bawa-Khalfe Tasneem , Lin Chin-Yo
Published: February 2023

Liver X receptors (LXRs) are members of the nuclear receptor family of ligand-dependent transcription factors which regulate the expression of lipid and cholesterol metabolism genes. Moreover, LXRs and their ligands have been shown to inhibit tumor growth in a variety of cancers. We have previously identified the small molecule compound GAC0001E5 (1E5) as an LXR inverse agonist and a potent inhibitor of pancreatic cancer cells. Transcriptomic and metabolomic studies showed that 1E5 disrupts glutamine metabolism, an essential metabolic pathway commonly reprogrammed during malignant transformation, including in breast cancers. To determine the role of LXRs and potential application of 1E5 in breast cancer, we examined LXR expression in publicly available clinical samples, and found that LXR expression is elevated in breast tumors as compared to normal tissues. In luminal A, endocrine therapy-resistant, and triple-negative breast cancer cells, 1E5 exhibited LXR inverse agonist and “degrader” activity and strongly inhibited cell proliferation and colony formation. Treatments with 1E5 downregulated the transcription of key glutaminolysis genes, and, correspondingly, biochemical assays indicated that 1E5 lowered intracellular glutamate and glutathione levels and increased reactive oxygen species. These results indicate that novel LXR ligand 1E5 is an inhibitor of glutamine metabolism and redox homeostasis in breast cancers and suggest that modulating LXR activity and expression in tumor cells is a promising strategy for targeting metabolic reprogramming in breast cancer therapeutics.
Brain Metabolic Alterations in Seropositive Autoimmune Encephalitis: An 18F-FDG PET Study
Authors: Bergeret Sébastien , Birzu Cristina , Meneret Pierre , Giron Alain , Demeret Sophie , Marois Clemence , Cousyn Louis , Rozenblum Laura , Laurenge Alice , Alentorn Agusti , Navarro Vincent , Psimaras Dimitri , Kas Aurélie
Published: February 2023

Introduction: Autoimmune encephalitis (AE) diagnosis and follow-up remain challenging. Brain 18F-fluoro-deoxy-glucose positron emission tomography (FDG PET) has shown promising results in AE. Our aim was to investigate FDG PET alterations in AE, according to antibody subtype. Methods: We retrospectively included patients with available FDG PET and seropositive AE diagnosed in our center between 2015 and 2020. Brain PET Z-score maps (relative to age matched controls) were analyzed, considering metabolic changes significant if |Z-score| ≥ 2. Results: Forty-six patients were included (49.4 yrs [18; 81]): 13 with GAD autoantibodies, 11 with anti-LGI1, 9 with NMDAR, 5 with CASPR2, and 8 with other antibodies. Brain PET was abnormal in 98% of patients versus 53% for MRI. The most frequent abnormalities were medial temporal lobe (MTL) and/or striatum hypermetabolism (52% and 43% respectively), cortical hypometabolism (78%), and cerebellum abnormalities (70%). LGI1 AE tended to have more frequent MTL hypermetabolism. NMDAR AE was prone to widespread cortical hypometabolism. Fewer abnormalities were observed in GAD AE. Striatum hypermetabolism was more frequent in patients treated for less than 1 month (p = 0.014), suggesting a relation to disease activity. Conclusion: FDG PET could serve as an imaging biomarker for early diagnosis and follow-up in AE.
Uromodulin and Vesico-Ureteral Reflux: A Genetic Study
Authors: Maringhini Silvio , Cusumano Rosa , Corrado Ciro , Puccio Giuseppe , Pavone Giovanni , D’Alessandro Maria Michela , Sapia Maria Chiara , Devuyst Olivier , Abbate Serena
Published: February 2023

Vesicoureteral reflux (VUR) is associated with urinary tract infections (UTI) and renal scars. The kidney damage is correlated with the grade of reflux and the number of UTI, but other factors may also play a role. Uromodulin (UMOD) is a protein produced by kidney tubular cells, forming a matrix in the lumen. We evaluated whether the common variant rs4293393 in the UMOD gene was associated with febrile UTI (FUTI) and/or scars in a group of children with VUR. A total of 31 patients with primary VUR were enrolled. Renal scars were detected in 16 children; no scar was detected in 15 children. Genotype rs4293393 TC (TC) was present in 8 patients, 7 (88%) had scars; genotype rs4293393 TT (TT) was found in 23 patients, and 9 (39%) had scars. Among children with scars, those with TC compared with those with TT were younger (mean age 77 vs. 101 months), their reflux grade was comparable (3.7 vs. 3.9), and the number of FUTI was lower (2.9 vs. 3.7 per patient). Children with VUR carrying UMOD genotype rs4293393 TC seem more prone to developing renal scars, independent of FUTI.
Progress in Fluorescence Biosensing and Food Safety towards Point-of-Detection (PoD) System
Authors: Kakkar Saloni , Gupta Payal , Kumar Navin , Kant Krishna
Published: February 2023

The detection of pathogens in food substances is of crucial concern for public health and for the safety of the natural environment. Nanomaterials, with their high sensitivity and selectivity have an edge over conventional organic dyes in fluorescent-based detection methods. Advances in microfluidic technology in biosensors have taken place to meet the user criteria of sensitive, inexpensive, user-friendly, and quick detection. In this review, we have summarized the use of fluorescence-based nanomaterials and the latest research approaches towards integrated biosensors, including microsystems containing fluorescence-based detection, various model systems with nano materials, DNA probes, and antibodies. Paper-based lateral-flow test strips and microchips as well as the most-used trapping components are also reviewed, and the possibility of their performance in portable devices evaluated. We also present a current market-available portable system which was developed for food screening and highlight the future direction for the development of fluorescence-based systems for on-site detection and stratification of common foodborne pathogens.
Single Printing Step Prussian Blue Bulk-Modified Transducers for Oxidase-Based Biosensors
Authors: Vokhmyanina Darya , Daboss Elena , Sharapova Olesya , Mogilnikova Mariia , Karyakin Arkady
Published: February 2023

We report on hydrogen peroxide sensors made through a single printing step with carbon ink containing catalytically synthesized Prussian blue nanoparticles. Despite their reduced sensitivity, the resulting bulk-modified sensors displayed both a wider linear calibration range (5 × 10−7–1 × 10−3 M) and an approximately four times lower detection limit versus the surface-modified sensors due to the dramatically decreased noise resulting in, on average, a six times higher signal-to-noise ratio. The corresponding glucose and lactate biosensors demonstrated similar and even higher sensitivities compared to those of biosensors based on surface-modified transducers. The biosensors have been validated through analysis of human serum. The decreased time and cost for production of single printing step bulk-modified transducers, as well as their analytical performance characteristics, which are advantageous over conventional surface-modified ones, would be expected to enable their wide use in (bio)sensorics.
Fluholoscopy—Compact and Simple Platform Combining Fluorescence and Holographic Microscopy
Authors: Alonso David , Garcia Javier , Micó Vicente
Published: February 2023

The combination of different imaging modalities into single imaging platforms has a strong potential in biomedical sciences as it permits the analysis of complementary properties of the target sample. Here, we report on an extremely simple, cost-effective, and compact microscope platform for achieving simultaneous fluorescence and quantitative phase imaging modes with the capability of working in a single snapshot. It is based on the use of a single illumination wavelength to both excite the sample’s fluorescence and provide coherent illumination for phase imaging. After passing the microscope layout, the two imaging paths are separated using a bandpass filter, and the two imaging modes are simultaneously obtained using two digital cameras. We first present calibration and analysis of both fluorescence and phase imaging modalities working independently and, later on, experimental validation for the proposed common-path dual-mode imaging platform considering static (resolution test targets, fluorescent micro-beads, and water-suspended lab-made cultures) as well as dynamic (flowing fluorescent beads, human sperm cells, and live specimens from lab-made cultures) samples.
Challenging the Classical View: Recognition of Identity and Expression as Integrated Processes
Authors: Schwartz Emily , O’Nell Kathryn , Saxe Rebecca , Anzellotti Stefano
Published: February 2023

Recent neuroimaging evidence challenges the classical view that face identity and facial expression are processed by segregated neural pathways, showing that information about identity and expression are encoded within common brain regions. This article tests the hypothesis that integrated representations of identity and expression arise spontaneously within deep neural networks. A subset of the CelebA dataset is used to train a deep convolutional neural network (DCNN) to label face identity (chance = 0.06%, accuracy = 26.5%), and the FER2013 dataset is used to train a DCNN to label facial expression (chance = 14.2%, accuracy = 63.5%). The identity-trained and expression-trained networks each successfully transfer to labeling both face identity and facial expression on the Karolinska Directed Emotional Faces dataset. This study demonstrates that DCNNs trained to recognize face identity and DCNNs trained to recognize facial expression spontaneously develop representations of facial expression and face identity, respectively. Furthermore, a congruence coefficient analysis reveals that features distinguishing between identities and features distinguishing between expressions become increasingly orthogonal from layer to layer, suggesting that deep neural networks disentangle representational subspaces corresponding to different sources.
Immunotherapy in Melanoma: Recent Advances and Future Directions
Authors: Knight Andrew , Karapetyan Lilit , Kirkwood John M.
Published: February 2023

The use of immunotherapy in the treatment of advanced and high-risk melanoma has led to a striking improvement in outcomes. Although the incidence of melanoma has continued to rise, median survival has improved from approximately 6 months to nearly 6 years for patients with advanced inoperable stage IV disease. Recent understanding of the tumor microenvironment and its interplay with the immune system has led to the explosive development of novel immunotherapy treatments. Since the approval of the therapeutic cytokines interleukin-2 and interferon alfa-2 in the 1990s, the development of novel immune checkpoint inhibitors (ICIs), oncolytic virus therapy, and modulators of the tumor microenvironment have given way to a new era in melanoma treatment. Monoclonal antibodies directed at programmed cell death protein 1 receptor (PD-1) and its ligand (PDL-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and lymphocyte-activation gene 3 (LAG-3) have provided robust activation of the adaptive immune system, restoring immune surveillance leading to host tumor recognition and destruction. Multiple other immunomodulatory therapeutics are under investigation to overcome resistance to ICI therapy, including the toll-like receptor-9 (TLR-9) and 7/8 (TLR-7/8) agonists, stimulator of interferon genes (STING) agonists, and fecal microbiota transplantation. In this review, we focus on the recent advances in immunotherapy for the treatment of melanoma and provide an update on novel therapies currently under investigation.
Safety and Quality of Life in Women with Immediate Reconstruction with Polyurethane Implants after Neoadjuvant Chemotherapy: Outcomes from The Preq-20 Trial
Authors: Acea-Nebril Benigno , García-Novoa Alejandra , Cereijo-Garea Carmen , Conde Iglesias Carmen , Bouzón Alejandro Alberto , Díaz Carballada Carlota
Published: February 2023

Introduction: Various studies have evaluated the impact of neoadjuvant chemotherapy (NAC) on the complications of breast cancer surgery, most of which were retrospective and did not assess the variables related to postoperative risk factors. The aim of this study is to analyse the safety and satisfaction of women included in the PreQ-20 trial who underwent NAC and who underwent mastectomy and immediate reconstruction with prepectoral polyurethane implants. Material and Methods: The patients included in the study belong to the prospective study PreQ-20. The study group consisted of patients who underwent immediate reconstruction after primary systemic therapy. The control groups consisted of patients with immediate reconstruction and adjuvant chemotherapy (control group 1) and patients with an infiltrating carcinoma or in situ ductal carcinoma who did not require chemotherapy (control group 2). Results: The study included 157 women, 58 (36.9%) of whom underwent primary systemic therapy. The indication for genetic study was significantly greater for the study group (87.9%) than for control groups 1 (49.1%) or 2 (30.4%). Seventy-two (45.9%) of the patients underwent bilateral mastectomy (BM), a procedure that was performed significantly more frequently in the study group (69%) than in control groups 1 (30.2%) or 2 (34.8%). The incidence rate for BM after complete pathologic response was 78%. There were no statistically significant differences in the number of complications between the groups. Implant loss was significantly more frequent in control group 1 (13.2%) than in the study group (3.4%) and control group 2 (2.2%). Conclusions: Mastectomy with prepectoral polyurethane implant reconstruction in patients with neoadjuvant chemotherapy presented a similar incidence of complications compared with patients who underwent primary surgery. There is a high rate of BM in women with NAC.
Role of Patient-Reported Outcomes in Clinical Trials in Metastatic Colorectal Cancer: A Scoping Review
Authors: Maring Jan Gerard , Eijsink Job F. H. , Tichelaar Friso D. , Veluwenkamp-Worawutputtapong Pawida , Postma Maarten J. , Touw Daan J. , de Groot Jan Willem B.
Published: February 2023

Purpose: To perform a scoping review on the use of Patient-Reported Outcome Measures (PROMs) in randomized trials on systemic therapy in patients with metastatic colorectal cancer (mCRC) between 2010 and 2021. Methods: First, a search on clinicaltrials.gov was performed, looking for randomized trials in mCRC. The use of PROMs was analyzed quantitatively. Subsequently, we assessed the completeness of PROM reporting based on the CONSORT PRO extension in publications related to the selected trials acquired using Embase and PubMed. Results: A total of 46/176 trials were registered on clinicaltrials.gov used PROMs. All these trials used validated PROM instruments. The EORTC QLQ-C30 was most frequently used (37 times), followed by the EQ-5D (21 times) and the EORTC QLQ-CR29 (six times). A total of 56/176 registered trials were published. In 35% (n = 20), the results of the PROMs were available. Overall, 7/20 (35%) trials documented all items of the CONSORT PRO extension and quality of reporting according to the CONSORT PRO extension was higher than in the period 2004–2012. In 3/20 (15%) of the published trials, the results of PROMs were not discussed nor included in the positioning of the new treatment compared to the reference treatment. Conclusion: When PROMs are used, the quality of reporting on patient-reported outcomes is improving, but this must continue in order to optimize the translation of trial results to individual patient values.
miR-34a and IRE1A/XBP-1(S) Form a Double-Negative Feedback Loop to Regulate Hypoxia-Induced EMT, Metastasis, Chemo-Resistance and Autophagy
Authors: Bouznad Nassim , Rokavec Matjaz , Öner Meryem Gülfem , Hermeking Heiko
Published: February 2023

Tumor-associated hypoxia, i.e., decreased availability of oxygen, results in a poor clinical outcome since it promotes EMT, metastasis, and chemotherapy-resistance. We have previously identified p53 and its target miR-34a, as critical determinants of the effect of hypoxia on colorectal cancer (CRC). Here, we aimed to characterize mechanisms that contribute to the selective advantage of cells with loss of p53/miR-34a function in a hypoxic environment. Using in silico prediction, we identified XBP-1 and IRE1A as potential miR-34a targets. IRE1A and XBP-1 are central components of the unfolded protein response that is activated by ER stress, which is also induced in tumor cells as a response to harsh conditions surrounding tumors such as hypoxia and a limited supply of nutrients. Here we characterized the XBP-1(S) transcription factor and its regulator IRE1A as direct, conserved miR-34a targets in CRC cells. After hypoxia and DNA damage, IRE1A and XBP-1 were repressed by p53 in a miR-34a-dependent manner, whereas p53-deficient cells showed induction of IRE1A and XBP-1(S). Furthermore, miR-34a expression was directly suppressed by XBP-1(S). In p53-deficient CRC cells, hypoxia-induced EMT, migration, invasion, metastases formation, and resistance to 5-FU were dependent on IRE1A/XBP-1(S) activation. Hypoxia-induced autophagy was identified as an XBP-1(S)-dependent mediator of 5-FU resistance and was reversed by ectopic miR-34a expression. The HIF1A/IRE1A/XBP-1(S)/p53/miR-34a feedback loop described here represents a central regulator of the response to hypoxia and ER stress that maintains cellular homeostasis. In tumors, the inactivation of p53 and miR-34a may result in IRE1A/XPB-1(S)-mediated EMT and autophagy, which ultimately promotes metastasis and chemoresistance.
Kinetics of Plasma Cell-Free DNA under a Highly Standardized and Controlled Stress Induction
Authors: Herhaus Benedict , Neuberger Elmo , Juškevičiūtė Ema , Simon Perikles , Petrowski Katja
Published: February 2023

Psychological stress affects the immune system and activates peripheral inflammatory pathways. Circulating cell-free DNA (cfDNA) is associated with systemic inflammation, and recent research indicates that cfDNA is an inflammatory marker that is sensitive to psychological stress in humans. The present study investigated the effects of acute stress on the kinetics of cfDNA in a within-subjects design. Twenty-nine males (mean age: 24.34 ± 4.08 years) underwent both the Trier Social Stress Test (TSST) and a resting condition. Blood samples were collected at two time points before and at 9 time points up to 105 min after both conditions. The cfDNA immediately increased 2-fold after the TSST and returned to baseline levels after 30 min after the test, showing that a brief psychological stressor was sufficient to evoke a robust and rapid increase in cfDNA levels. No associations were detected between perceived stress, whereas subjects with higher basal cfDNA levels showed higher increases. The rapid cfDNA regulation might be attributed to the transient activation of immune cells caused by neuroendocrine-immune activation. Further research is required to evaluate the reliability of cfDNA as a marker of neuroendocrine-immune activation, which could be used for diagnostics purposes or monitoring of treatment progression.
The Dynamic Poly(A) Tail Acts as a Signal Hub in mRNA Metabolism
Authors: Zhang Guiying , Luo Haolin , Li Xinyi , Hu Zhangli , Wang Quan
Published: February 2023

In eukaryotes, mRNA metabolism requires a sophisticated signaling system. Recent studies have suggested that polyadenylate tail may play a vital role in such a system. The poly(A) tail used to be regarded as a common modification at the 3′ end of mRNA, but it is now known to be more than just that. It appears to act as a platform or hub that can be understood in two ways. On the one hand, polyadenylation and deadenylation machinery constantly regulates its dynamic activity; on the other hand, it exhibits the ability to recruit RNA-binding proteins and then interact with diverse factors to send various signals to regulate mRNA metabolism. In this paper, we outline the main complexes that regulate the dynamic activities of poly(A) tails, explain how these complexes participate polyadenylation/deadenylation process and summarize the diverse signals this hub emit. We are trying to make a point that the poly(A) tail can metaphorically act as a “flagman” who is supervised by polyadenylation and deadenylation and sends out signals to regulate the orderly functioning of mRNA metabolism.
Analyzing the Electrochemical Interaction of the Angiogenesis Inhibitor Batimastat by Surface-Enhanced Raman Spectroscopy
Authors: Pięta Ewa , Paluszkiewicz Czesława , Kwiatek Wojciech M. , López-Ramírez María Rosa
Published: February 2023

This is the first work to describe the vibrational properties of the anticancer drug batimastat (BB-94) as an inhibitor of extracellular matrix metalloproteinase with a broad spectrum of activity. In addition, the adsorption of this molecule onto a silver roughened electrode surface using surface-enhanced Raman spectroscopy (SERS) was studied. This research provides a complete account of the influence of applied electrode potential and excitation wavelengths at the molecule-metal interface. Although vibrational assignment becomes more difficult as the molecule size increases, we performed density functional theory (DFT) at the B3LYP/6-31G(d,p) level of theory to calculate molecular geometry in the equilibrium state and Raman frequencies to clarify the nature of vibrational modes. The greatest amplification of the SERS signal occurs for the electrode potential of −0.3 V for the 532 nm excitation line and shifts as moves to the near-infrared laser line at 785 nm. The conclusion is that the mercaptothiophene part and one of the amide groups interact with the metal surface. This results in a charge transfer resonant process in the SERS of this molecule, which has been found by analyzing the charge transfer SERS profiles. Finally, there is the possibility of the formation of different adsorption species or metal complexes on the surface that could contribute to the whole signal observed in the SERS spectra.
Affiliation to a Social Group as a Preventive Factor in Suicidal Behaviors in Children and Adolescents during the COVID-19 Pandemic
Authors: Grzejszczak Jagoda , Strzelecki Dominik , Gabryelska Agata , Kotlicka-Antczak Magdalena
Published: February 2023

Suicide is one of the most common causes of death in the population of children and adolescents. Available data show the continuous growth of this phenomenon and the ineffectiveness of prevention programs. Additionally, the COVID-19 pandemic significantly affected young people’s mental health, including an increased risk of suicidal behaviors due to limited direct contact with the school and peer groups in favor of the home environment. Therefore, the aim of this narrative review was to consider the risk factors and protective factors for suicidal behavior in the under-18 population, with a particular focus on the importance of belonging to a social group and building identification with it as a phenomenon protecting against suicidal behavior. Additionally, in this review, we evaluate how the COVID-19 pandemic affected these relationships. The PubMed database was used in the search with the following keywords: suicide, suicide behaviors, child and adolescent suicide behaviors, group affiliation, family affiliation, ethnicity, religious affiliation, and the COVID-19 pandemic, with articles published between 2002 and 2022 analyzed. Research conducted to date indicates that both sustained and stable family and peer relationships, as well as a sense of identification and belonging, noticeably reduce the risk of suicidal behavior. Ethnic or cultural affiliation seems to have been particularly important during the isolation in the home environment caused by the COVID-19 pandemic. Additionally, it has been shown that while in lockdown, contact through social media with individuals’ identification groups was associated with a reduced chance of emotional crises. Furthermore, regardless of cultural background, attachment to a particular group correlates with enhanced psychiatric state of children and adolescents. Thus, available data highlight the need for building and maintaining affiliations with suitable groups as a protective factor against suicidal behaviors.
A Cross-Sectional Investigation of Preadolescent Cardiometabolic Health: Associations with Fitness, Physical Activity, Sedentary Behavior, Nutrition, and Sleep
Authors: Castro Nicholas , Zieff Gabriel , Bates Lauren C. , Pagan Lassalle Patricia , Higgins Simon , Faulkner James , Lark Sally , Skidmore Paula , Hamlin Michael J. , Signal T. Leigh , Williams Michelle A. , Stoner Lee
Published: February 2023

Background: Cardiometabolic disease (CMD) risk often begins early in life. Healthy lifestyle behaviors can mitigate risk, but the optimal combination of behaviors has not been determined. This cross-sectional study simultaneously examined the associations between lifestyle factors (fitness, activity behaviors, and dietary patterns) and CMD risk in preadolescent children. Methods: 1480 New Zealand children aged 8–10 years were recruited. Participants included 316 preadolescents (50% female, age: 9.5 ± 1.1 years, BMI: 17.9 ± 3.3 kg/m2). Fitness (cardiorespiratory fitness [CRF], muscular fitness), activity behaviors (physical activity, sedentary, sleep), and dietary patterns were measured. Factor analysis was used to derive a CMD risk score from 13 variables (adiposity, peripheral and central hemodynamics, glycemic control, and blood lipids). Results: Only CRF (β = −0.45, p < 0.001) and sedentary time (β = 0.12, p = 0.019) were associated with the CMD risk score in the adjusted multivariable analysis. CRF was found to be nonlinear (VO2 max ≤ ≈42 mL/kg/min associated with higher CMD risk score), and thus a CRF polynomial term was added, which was also associated (β = 0.19, p < 0.001) with the CMD risk score. Significant associations were not found with sleep or dietary variables. Conclusion: The findings indicate that increasing CRF and decreasing sedentary behavior may be important public health targets in preadolescent children.
Influence of Perinatal Factors on Blood Tryptase and Fecal Calprotectin Levels in Newborns
Authors: Paysal Justine , Oris Charlotte , Troin Ugo , Limeri Pierre-Nicolas , Allard Jeanne , Tadrent Marie , Pereira Bruno , Merlin Etienne , Rochette Emmanuelle , Evrard Bertrand , Durif Julie , Sapin Vincent , Pons Maguelonne
Published: February 2023

Background: Blood tryptase and fecal calprotectin levels may serve as biomarkers of necrotizing enterocolitis. However, their interpretation may be hindered by the little-known effects of perinatal factors. The aim of this study was to compare the tryptase and calprotectin levels in newborns according to their term, trophicity, and sex. Method: One hundred and fifty-seven premature newborns and 157 full-term newborns were included. Blood tryptase and fecal calprotectin were assayed. Results: Blood tryptase levels were higher in premature than in full-term newborns (6.4 vs. 5.2 µg/L; p < 0.001). In situations of antenatal use of corticosteroids (p = 0.007) and non-exclusive use of human milk (p = 0.02), these levels were also higher. However, in multiple linear regression analyses, only prematurity significantly influenced tryptase levels. Fecal calprotectin levels were extremely wide-ranging and were much higher in female than in male newborns (300.5 vs. 110.5 µg/g; p < 0.001). Conclusions: The differences in tryptase levels according to term could be linked to early aggression of the still-immature digestive wall in premature newborns, in particular, by enteral feeding started early. The unexpected influence of sex on fecal calprotectin levels remains unexplained.
The Molecular and Histopathological Assessment of Inflammatory Status in Very and Extremely Premature Infants: A Prospective Study
Authors: Borțea Claudia Ioana , Enatescu Ileana , Pantea Manuela , Dima Mirabela , Iacob Emil Radu , Dumitru Catalin , Popescu Alin , Stoica Florina , Heredea Rodica Elena , Iacob Daniela
Published: February 2023

Prematurity comes with a varying range of complications, implying a high prevalence of complications and mortality and depending on the severity of prematurity and the sustained inflammation among these infants, which recently sparked an important scientific interest. The primary objective of this prospective study was to establish the degree of inflammation in very (VPIs) and extremely preterm infants (EPIs) in association with the histology findings of the umbilical cord (UC), while the secondary objective was to study the inflammatory markers in the neonates’ blood as predictors of fetal inflammatory response (FIR). A total of thirty neonates were analyzed, ten of them being born extremely premature (<28 weeks of gestation) and twenty very premature (28–32 weeks of gestation). The EPIs had considerably higher levels of IL-6 at birth than VPIs (638.2 pg/mL vs. 151.1 pg/mL). The CRP levels at delivery did not vary substantially across groups; however, after days, the EPIs had significantly higher CRP levels (11.0 mg/dL vs. 7.2 mg/dL). In contrast, the LDH was considerably higher in the extremely preterm infants at birth and four days after birth. Surprisingly, the proportions of infants with pathologically increased inflammatory markers did not differ between the EPIs and VPIs. The LDH increased considerably in both groups, although the CRP levels increased exclusively among the VPIs. The stage of inflammation in the UC did not vary substantially between the EPIs and VPIs. The majority of infants were identified with Stage 0 UC inflammation (40% in EPI vs. 55% in VPIs). There was a substantial correlation link between gestational age and newborn weight and a significant inverse correlation among gestational age and IL-6 and LDH levels. There was a strong negative association between weight and IL-6 (rho = −0.349) and LDH (rho = −0.261). The stage of the UC inflammation demonstrated a statistically significant direct connection with IL-6 (rho = 0.461) and LDH (rho = 0.293), but none with the CRP. Further studies involving a bigger population size of preterm newborns are required to validate the findings and analyze more inflammatory markers, while prediction models on inflammatory markers that are measured expectantly, before the onset of preterm labor, need to be created.
Antifouling Coatings Fabricated by Laser Cladding
Authors: Wang Shuwen , Chen Yang , Gu Chunxing , Sai Qingyi , Lei Tianyu , Williams John
Published: February 2023

Laser surface treatment is a very useful technology for the fabrication of functional surfaces. In this study, novel antifouling surfaces are fabricated by laser cladding of TC4 and Ni60 mixed materials in various mass ratios on the surfaces of 316L stainless steel substrates. Parametric studies are carried out to investigate the effects of the mixed powder mass ratios and laser cladding parameters on the antifouling performance of the laser clad coatings (LCCs). The antifouling mechanism of the LCCs is investigated by using the water contact angle/surface energy measurement, scanning electron microscope (SEM) surface observation, and phase composition analysis via XRD (X-ray diffractometer) testing. The experimental results show that the LCCs with Ni60/TC4 mass ratio of 3/7 has better antifouling performance in this study. The antifouling performance of the LCC decreases with the increase in laser scanning speed. Surface energy and surface topography have a significant effect on the antifouling performance of LCCs. In order to get the optimal antifouling performance of LCCs, the Ni60/TC4 mass ratio and laser cladding parameters should be optimized.
Tribological Properties and Cutting Performance of AlTiN Coatings with Various Geometric Structures
Authors: Li Bin , Xu Yuxiang , Rao Guoliang , Wang Qimin , Zheng Jun , Zhu Ruiyuan , Chen Yubo
Published: February 2023

The development of advanced machining techniques requires high-performance tool coatings. To improve the wear resistance and cutting performance of AlTiN coatings, a structure optimization strategy involving bias control and a nano-multilayer architecture strategy is presented. The investigated AlTiN coatings were deposited by cathodic arc evaporation and studied with regard to phase structure, hardness, adhesion, and tribological properties by a combination of X-ray diffraction, nanoindentation, scratch, and ball-on-disk friction tests. A high bias potential (up to −120 V) with enhanced adatom mobility suppressed the formation of the wurtzite structure AlN in AlTiN. In addition, the epitaxial growth of Al0.67Ti0.33N on Al0.5Ti0.5N in the AlTiN nano-multilayer could also promote the single-phase structure. The hardness of AlTiN-based coatings with a dominated cubic structure was 3–4 GPa higher than conventional ones. In addition, the interlayer interfaces in the Al0.67Ti0.33N/Al0.5Ti0.5N multilayer could deflect the cracks and thus improve the fracture toughness. As a consequence, the Al0.67Ti0.33N/Al0.5Ti0.5N multilayer with enhanced mechanical properties obtained the lowest wear rate of 1.1 × 10−5 mm3/N·m and the longest cutting lifetime of 25 min during dry turning the SUS304 stainless steel.
Two Crystal Forms of 4′-Methyl-2,4-dinitrodiphenylamine: Polymorphism Governed by Conformational Flexibility of a Supramolecular Synthon
Authors: Fedyanin Ivan V. , Samigullina Aida I.
Published: February 2023

Single crystals of two polymorphic forms of 4′-methyl-2,4-dinitrodiphenylamine were obtained by crystallization and characterized by X-ray diffraction analysis. One of the forms is non-centrosymmetric (space group P21212), while the second is centrosymmetric (space group P¯1) and contains two crystallographically independent molecules in the asymmetric unit. In both forms, the same supramolecular synthon, a dimer linked by bonding N-H···O, O···O, and C-H···O interactions were found. Despite nearly the same connectivity of the bonding interactions, the conformation of the supramolecular synthon is different, including its unavoidably different symmetry in two polymorphs. The comparison of the crystal packing of the orthorhombic polymorph with that of the related 2,4-dinitrodiphenylamine (space group P21/n) shows the quasi-isostructurality of the fragments, infinite π-stacks joined by weak non-directional intermolecular interactions. However, the fragments are linked by the supramolecular synthons via either a two-fold axis or an inversion center, which lead to only the partial isostructurality of the crystals.
Genetic Diversity of Oxytropis Species from the Center of the Genus Origin: Insight from Molecular Studies
Authors: Sandanov Denis V. , Kholina Alla B. , Kozyrenko Marina M. , Artyukova Elena V. , Wang Zhiheng
Published: February 2023

The genus Oxytropis (Fabaceae) was formed from the ancient species of Astragalus presumably approximately 5.6 Ma ago in Southern Siberia. Our study summarized data on the genetic diversity of 69 populations of 31 Oxytropis species in the center of origin of the genus based on the sequencing of plastid genome markers. Most of the populations (82.6%) are characterized by high gene diversity (0.600–1.000), which indicates a relatively stable state. Phylogenetic relationships between most Oxytropis species remain unresolved. Three genetic complexes and four phyletic lineages have been identified. Some species form weakly differentiated complexes, which is probably caused by their relatively recent divergence and the demography processes, as well as interspecific hybridization and polyploidy characteristic of Oxytropis species.
Expanding the Fossil Record of Soldier Fly Larvae—An Important Component of the Cretaceous Amber Forest
Authors: Amaral André P. , Gombos Denis , Haug Gideon T. , Haug Carolin , Gauweiler Joshua , Hörnig Marie K. , Haug Joachim T.
Published: February 2023

Larvae of soldier flies and their closest relatives (Diptera: Stratiomyomorpha) are important decomposers of organic material, including wood, that take part in carbon cycling. They also play a certain role in the modern-day animal and human food industry, representing economic value. Larvae of Stratiomyomorpha are considered to be rather rare in the fossil record. Indeed, only very few larvae have been reported so far. Here, we demonstrate that larvae of Stratiomyomorpha are in fact abundant in the Cretaceous, at least in Myanmar amber (about 100 million years old), based on more than 100 amber pieces containing larvae. The specimens could be differentiated into three morphotypes, two already described in a previous work, and a new one. For one morphotype, three larval stages could be distinguished by analysing the dimensions of the head capsules. A quantitative analysis of body shapes indicates a lower morphological diversity of the fossil sample in comparison to the extant fauna, but suggests that they might have had a different ecology in the past. It appears that the data set is not yet saturated, i.e., that more fossil larvae of this group, including different morphologies, are expected to be found.
First Short-Term Study of the Relationship between Native and Invasive Earthworms in the Zone of Soil Freezing in Western Siberia—Experiments in Mesocosms
Authors: Golovanova Elena V. , Kniazev Stanislav Yu. , Karaban Kamil , Babiy Kirill A. , Shekhovtsov Sergei V.
Published: February 2023

Earthworm invasions often reduce biodiversity and affect the ability of ecosystems to perform ecosystem functions. Over the past few decades, European lumbricid species have spread widely in natural habitats in Western Siberia, without completely displacing the native species. The aim of the present experiment is to study the survival, reproductive potential, vertical distribution, abundance, and biomass of Aporrectodea caliginosa and Lumbricus rubellus invasive species for the region and the native species Eisenia nordenskioldi and their influence on each other. For this purpose, winter and vegetation experiments were conducted in mesocosms simulating the real situation of invasions in the same communities on the same types of soils with the same amount and composition of litter. The authors found that the native species was significantly inferior to A. caliginosa in reproduction rate, number of offspring, and final biomass, but had an advantage over L. rubellus. The native species was positively influenced by the presence of A. caliginosa. In the experiment, there was a significant rejuvenation of the populations of the studied species, as well as an increase in abundance and relative mass under interaction conditions compared to mono variants. The native species had advantages over the invasive species in terms of winter survival. The natural volume of litter used in the experiment was insufficient for L. rubellus. According to the results of the experiment, it can be assumed that the spread of L. rubellus will continue to be limited to non-freezing biotopes rich in organic matter. A. caliginosa will spread in natural communities and agrocenoses of Western Siberia.