bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural Products Induce Different Anti-Tumor Immune Responses in Murine Models of 4T1 Mammary Carcinoma and B16-F10 Melanoma
Authors: Lasso Paola , Rojas Laura , Arévalo Cindy , Urueña Claudia , Murillo Natalia , Fiorentino Susana
Published: November 2023

Natural products obtained from Petiveria alliacea (Anamu-SC) and Caesalpinia spinosa (P2Et) have been used for cancer treatment, but the mechanisms by which they exert their antitumor activity appear to be different. In the present work, we show that the Anamu-SC extract reduces tumor growth in the 4T1 murine mammary carcinoma model but not in the B16-F10 melanoma model, unlike the standardized P2Et extract. Both extracts decreased the levels of interleukin-10 (IL-10) in the B16-F10 model, but only P2Et increased the levels of tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ). Likewise, co-treatment of P2Et and doxorubicin (Dox) significantly reduced tumor size by 70% compared to the control group, but co-treatment of Anamu-SC with Dox had no additive effect. Analysis of intratumoral immune infiltrates showed that Anamu-SC decreased CD4+ T cell frequency more than P2Et but increased CD8+ T cell frequency more significantly. Both extracts reduced intratumoral monocytic myeloid-derived suppressor-like cell (M-MDSC-LC) migration, but the effect was lost when co-treated with doxorubicin. The use of P2Et alone or in co-treatment with Anamu-SC reduced the frequency of regulatory T cells and increased the CD8+/Treg ratio. In addition, Anamu-SC reduced glucose consumption in tumor cells, but this apparently has no effect on IFNγ- and TNFα-producing T cells, although it did reduce the frequency of IL-2-producing T cells. The efficacy of these herbal preparations is increasingly clear, as is the specificity conditioned by tumor heterogeneity as well as the different chemical complexity of each preparation. Although these results contribute to the understanding of specificity and its future benefits, they also underline the fact that the development of each of these standardized extracts called polymolecular drugs must follow a rigorous path to elucidate their biological activity.
Transluminal Pillars—Their Origin and Role in the Remodelling of the Zebrafish Caudal Vein Plexus
Authors: Röss Helena , Aaldijk Dea , Vladymyrov Mykhailo , Odriozola Adolfo , Djonov Valentin
Published: November 2023

Intussusceptive pillars, regarded as a hallmark of intussusceptive angiogenesis, have been described in developing vasculature of many organs and organisms. The aim of this study was to resolve the question about pillar formation and their further maturation employing zebrafish caudal vein plexus (CVP). The CVP development was monitored by in vivo confocal microscopy in high spatio-temporal resolution using the transgenic zebrafish model Fli1a:eGPF//Gata1:dsRed. We tracked back the formation of pillars (diameter ≤ 4 µm) and intercapillary meshes (diameter > 4 µm) and analysed their morphology and behaviour. Transluminal pillars in the CVP arose via a combination of sprouting, lumen expansion, and/or the creation of intraluminal folds, and those mechanisms were not associated directly with blood flow. The follow-up of pillars indicated that one-third of them disappeared between 28 and 48 h post fertilisation (hpf), and of the remaining ones, only 1/17 changed their cross-section area by >50%. The majority of the bigger meshes (39/62) increased their cross-section area by >50%. Plexus simplification and the establishment of hierarchy were dominated by the dynamics of intercapillary meshes, which formed mainly via sprouting angiogenesis. These meshes were observed to grow, reshape, and merge with each other. Our observations suggested an alternative view on intussusceptive angiogenesis in the CVP.
Loss of Uncoupling Protein 1 Expression in the Subcutaneous Adipose Tissue Predicts Childhood Obesity
Authors: Gyurina Katalin , Yarmak Mariia , Sasi-Szabó László , Molnár Sarolta , Méhes Gábor , Röszer Tamás
Published: November 2023

Stimulation of thermogenesis by inducing uncoupling protein 1 (UCP1) expression in adipocytes is thought to promote weight loss by increasing energy expenditure, and it is postulated that the human newborn has thermogenic subcutaneous fat depots. However, it remains unclear whether a relevant number of UCP1-expressing (UCP1+) adipocytes exist in the early postnatal life. Here we studied the distribution of UCP1 and the expression of thermogenic genes in the subcutaneous adipose tissues of the human fetus, infant and child. We show that the deep layer of human fetal and neonatal subcutaneous fat, particularly the abdominal wall, is rich in UCP1+ adipocytes. These adipocytes develop in the late third trimester and persist throughout childhood, expressing a panel of genes linked to mitochondrial biogenesis and thermogenesis. During the early childhood adiposity rebound—a critical phase that determines obesity risk later in life—the absence of adipose tissue UCP1 expression in children with normal body mass index (BMI) correlates with an obesity-associated gene expression signature. Finally, UCP1 expression is negatively correlated with BMI z-score and adipocyte size in infants and children. Overall, our results show that the absence of UCP1 expression in adipose tissue is an early indicator of adipose tissue expansion in children.
Conformational Analysis of 1,5-Diaryl-3-Oxo-1,4-Pentadiene Derivatives: A Nuclear Overhauser Effect Spectroscopy Investigation
Authors: Belov Konstantin , Brel Valery , Sobornova Valentina , Fedorova Irina , Khodov Ilya
Published: November 2023

1,5-Diaryl-3-Oxo-1,4-Pentadiene derivatives are intriguing organic compounds with a unique structure featuring a pentadiene core, aryl groups, and a ketone group. This study investigates the influence of fluorine atoms on the conformational features of these derivatives in deuterated chloroform (CDCl3) solution. Through nuclear magnetic resonance (NMR) spectroscopy and quantum chemical calculations, we discerned variations in interatomic distances and established predominant conformer proportions. The findings suggest that the non-fluorinated entity exhibits a uniform distribution across various conformer groups. The introduction of a fluorine atom induces substantial alterations, resulting in the predominance of a specific conformer group. This structural insight may hold the key to their diverse anticancer activities, previously reported in the literature.
Ceruloplasmin Reduces the Lactoferrin/Oleic Acid Antitumor Complex-Mediated Release of Heme-Containing Proteins from Blood Cells
Authors: Elizarova Anna Yu. , Sokolov Alexey V. , Vasilyev Vadim B.
Published: November 2023

Our previous study showed that not only bovine lactoferrin (LF), the protein of milk and neutrophils, but also the human species forms complexes with oleic acid (OA) that inhibit tumor growth. Repeated injections of human LF in complex with OA (LF/8OA) to hepatoma-carrying mice decelerated tumor growth and increased animals’ longevity. However, whether the effect of the LF/8OA complex is directed exclusively against malignant cells was not studied. Hence, its effect on normal blood cells was assayed, along with its possible modulation of ceruloplasmin (CP), the preferred partner of LF among plasma proteins. The complex LF/8OA (6 μM) caused hemolysis, unlike LF alone or BSA/8OA (250 μM). The activation of neutrophils with exocytosis of myeloperoxidase (MPO), a potent oxidant, was induced by 1 μM LF/8OA, whereas BSA/8OA had a similar effect at a concentration increased by an order. The egress of heme-containing proteins, i.e., MPO and hemoglobin, from blood cells affected by LF/8OA was followed by a pronounced oxidative/halogenating stress. CP, which is the natural inhibitor of MPO, added at a concentration of 2 mol per 1 mol of LF/8OA abrogated its cytotoxic effect. It seems likely that CP can be used effectively in regulating the LF/8OA complex’s antitumor activity.
Nature-Derived Polysaccharide-Based Composite Hydrogels for Promoting Wound Healing
Authors: Lee Hyerin , Jung Yerim , Lee Nayeon , Lee Inhye , Lee Jin Hyun
Published: November 2023

Numerous innovative advancements in dressing technology for wound healing have emerged. Among the various types of wound dressings available, hydrogel dressings, structured with a three-dimensional network and composed of predominantly hydrophilic components, are widely used for wound care due to their remarkable capacity to absorb abundant wound exudate, maintain a moisture environment, provide soothing and cooling effects, and mimic the extracellular matrix. Composite hydrogel dressings, one of the evolved dressings, address the limitations of traditional hydrogel dressings by incorporating additional components, including particles, fibers, fabrics, or foams, within the hydrogels, effectively promoting wound treatment and healing. The added elements enhance the features or add specific functionalities of the dressings, such as sensitivity to external factors, adhesiveness, mechanical strength, control over the release of therapeutic agents, antioxidant and antimicrobial properties, and tissue regeneration behavior. They can be categorized as natural or synthetic based on the origin of the main components of the hydrogel network. This review focuses on recent research on developing natural polysaccharide-based composite hydrogel wound dressings. It explores their preparation and composition, the reinforcement materials integrated into hydrogels, and therapeutic agents. Furthermore, it discusses their features and the specific types of wounds where applied.
Synthesis and Characterization of a New Class of Chromene-Azo Sulfonamide Hybrids as Promising Anticancer Candidates with the Exploration of Their EGFR, hCAII, and MMP-2 Inhibitors Based on Molecular Docking Assays
Authors: Alblewi Fawzia F. , Alsehli Mosa H. , Hritani Zainab M. , Eskandrani Areej , Alsaedi Wael H. , Alawad Majed O. , Elhenawy Ahmed A. , Ahmed Hanaa Y. , El-Gaby Mohamed S. A. , Afifi Tarek H. , Okasha Rawda M.
Published: November 2023

In this study, novel selective antitumor compounds were synthesized based on their fundamental pharmacophoric prerequisites associated with EGFR inhibitors. A molecular hybridization approach was employed to design and prepare a range of 4H-chromene-3-carboxylates 7a–g, 8, and 11a–e derivatives, each incorporating a sulfonamide moiety. The structures of these hybrid molecules were verified using comprehensive analytical and spectroscopic techniques. During the assessment of the newly synthesized compounds for their anticancer properties against three tumor cell lines (HepG-2, MCF-7, and HCT-116), compounds 7f and 7g displayed remarkable antitumor activity against all tested cell lines, outperforming the reference drug Cisplatin in terms of efficacy. Consequently, these promising candidates were selected for further investigation of their anti-EGFR, hCAII, and MMP-2 potential, which exhibited remarkable effectiveness against EGFR and MMP2 when compared to Sorafenib. Additionally, docking investigations regarding the EGFR binding site were implemented for the targeted derivatives in order to attain better comprehension with respect to the pattern in which binding mechanics occur between the investigated molecules and the active site, which illustrated a higher binding efficacy in comparison with Sorafenib.
Molecular Dynamics and Docking Simulations of Homologous RsmE Methyltransferases Hints at a General Mechanism for Substrate Release upon Uridine Methylation on 16S rRNA
Authors: Hernández-Cid Aaron , Lozano-Aponte Jorge , Scior Thomas
Published: November 2023

In this study, molecular dynamics (MD) and docking simulations were carried out on the crystal structure of Neisseria Gonorrhoeae RsmE aiming at free energy of binding estimation (ΔGbinding) of the methyl transfer substrate S-adenosylmethionine (SAM), as well as its homocysteine precursor S-adenosylhomocysteine (SAH). The mechanistic insight gained was generalized in view of existing homology to two other crystal structures of RsmE from Escherichia coli and Aquifex aeolicus. As a proof of concept, the crystal poses of SAM and SAH were reproduced reflecting a more general pattern of molecular interaction for bacterial RsmEs. Our results suggest that a distinct set of conserved residues on loop segments between β12, α6, and Met169 are interacting with SAM and SAH across these bacterial methyltransferases. Comparing molecular movements over time (MD trajectories) between Neisseria gonorrhoeae RsmE alone or in the presence of SAH revealed a hitherto unknown gatekeeper mechanism by two isoleucine residues, Ile171 and Ile219. The proposed gating allows switching from an open to a closed state, mimicking a double latch lock. Additionally, two key residues, Arg221 and Thr222, were identified to assist the exit mechanism of SAH, which could not be observed in the crystal structures. To the best of our knowledge, this study describes for the first time a general catalytic mechanism of bacterial RsmE on theoretical ground.
Integrative Metabolomic and Transcriptomic Landscape during Akebia trifoliata Fruit Ripening and Cracking
Authors: Jiang Yongli , Du Yanlin , Chen Chongyang , Wang Danfeng , Zhong Yu , Deng Yun
Published: November 2023

Akebia trifoliata fruit is prone to crack after ripening, but little is known about the mechanism underlying the cracking process. This study integrated transcriptomic and metabolomic data, revealing significant changes in 398 metabolites and 8414 genes during ripening and cracking, mainly impacting cell-wall metabolism. Multi-omics joint analysis indicated that genes related to polygalacturonase, pectate lyase, α-amylase, and glycogen phosphorylase were up-regulated after cracking, degrading cell wall and starch. Concurrently, diminished photosynthetic metabolism and heightened phenylpropanoid metabolism suggested alterations in cuticle structure, potentially impacting cell-wall robustness. Numerous auxin and abscisic acid signaling-related genes were expressed, and we assume that they contributed to the promoting peel growth. These alterations collectively might compromise peel strength and elevate expanding pressure, potentially leading to A. trifoliata cracking. Transcription factors, predominantly ethylene response factors and helix-loop-helix family members, appeared to regulate these metabolic shifts. These findings provide valuable insights into A. trifoliata cracking mechanisms; however, direct experimental validation of these assumptions is necessary to strengthen these conclusions and expedite their commercial utilization.
History of Parkinson’s Disease-Associated Gene, Parkin: Research over a Quarter Century in Quest of Finding the Physiological Substrate
Authors: Kitada Tohru , Ardah Mustafa T. , Haque M. Emdadul
Published: November 2023

Parkin, the gene responsible for hereditary Parkinson’s disease (PD) called “Autosomal Recessive Juvenile Parkinsonism (AR-JP)” was discovered a quarter of a century ago. Owing to its huge gene structure and unique protein functions, parkin has become a subject of interest to those involved in PD research and researchers and clinicians in various fields and is being vigorously studied worldwide in relation to its nature and disease. The gene structure was registered under the gene name “parkin” in the GenBank in 1997. In 1998, deletion and point mutations in the parkin gene were reported, thereby demonstrating parkin is the causative gene for hereditary PD. Although 25 years have passed since the gene’s discovery and many researchers have worked tirelessly to elucidate the function of the Parkin protein and the mechanism of its role against neuronal cell death and pathogenesis remain unknown, which raises a major question concerning the current leading hypothesis. In this review, we present the results of related research on the parkin gene in chronological order and discuss unresolved problems concerning its function and pathology as well as new trends in the research conducted to solve them. The relationship between parkin and tumorigenesis has also been addressed from the perspective of Parkin’s redox molecule.
Repair of Small-Area Delamination in Carbon Fiber-Reinforced Polymer through Small Drilled Hole and Carbon Nanotubes-Reinforced Resin Pre-Coating Technique
Authors: Han Gang , Hu Xiaozhi
Published: November 2023

This study explores the potential for repairing small, isolated delamination areas in carbon fiber-reinforced polymer (CFRP), while preserving the integrity of the composite structures. A small drilled hole at the center of the delamination section served as a channel for the epoxy infill of the sharp delamination cracks. The pressureless infill repair was achieved through the capillary action of an acetone-diluted resin pre-coating (RPC) solution (without hardener) with CNT reinforcement, comprising 89 m/m% acetone, 10 m/m% resin, and 1 m/m% CNT. This acetone-rich resin pre-coating (RPC) solution is easily prepared and applied to the drilled hole area. Curing of the CNT-toughened resin infill was induced by filling the small drilled hole with a resin–hardener mixture toughened by CNT/aramid pulp. The effectiveness of the delamination repair was compared for curing periods of two weeks and three months. The flexural strength measurements indicated that a restoration level of 77% was achieved in this study, while the optimum 100% restoration was achieved using the same technique for edge delamination repairs.
Advanced Age May Not Be an Absolute Contraindication for Radical Nephroureterectomy in Patients with Upper Tract Urothelial Carcinoma: A Single-Center Case Series and a Systematic Review with Meta-Analyses
Authors: Ye Jianjun , Wu Qiyou , Liao Xinyang , Zheng Lei , Wei Qiang , Bao Yige
Published: November 2023

Objective: This study aims to investigate whether advanced age is an absolute contraindication for radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) through a single-center case series and a systematic review with meta-analysis. Materials and methods: In the single-center case series, 588 UTUC patients who underwent RNU between May 2003 and June 2019 in West China Hospital were enrolled, and cancer-specific survival (CSS) was the primary outcome of interest. In the systematic review with meta-analysis, PubMed, Scopus, Embase, and Cochrane databases were systematically searched for related articles for further analysis. The endpoints for meta-analyses were overall survival (OS) and CSS. Results: The single-center case series included 57 (9.7%) octogenarians. The CSS of octogenarians after RNU was comparable to that of younger people. Advanced age (≥80) was not an independent risk factor for poor CSS (HR, 1.08; 95% CI, 0.48, 2.40). In a systematic review with meta-analysis, the cut-off value of advanced age is 70, and the results showed that advanced age was associated with inferior OS (pooled HR, 1.55; 95% CI, 1.29, 2.01) and CSS (pooled HR, 1.37; 95% CI, 1.08, 1.65). However, the subgroup analysis of countries found no positive correlation between advanced age and CSS (pooled HR, 1.33; 95% CI 0.92, 1.74) in Chinese. Conclusions: Advanced age may no longer be an absolute contraindication for RNU. RNU can be safely and effectively performed on UTUC patients of advanced age after a comprehensive presurgical evaluation.
Optimized Refeeding vs. Standard Care in Malnourished Older Hospitalized Patients: A Prospective, Non-Randomized Cluster-Controlled Study in Geriatric Acute Care
Authors: Pourhassan Maryam , Daubert Diana , Laurentius Thea , Wirth Rainer
Published: November 2023

Malnutrition is a prevalent geriatric syndrome with adverse health outcomes. This study aimed to assess the effectiveness of an optimized protocol for treatment of malnutrition in older hospitalized patients. We conducted a prospective, non-randomized cluster-controlled study with 156 malnourished patients in the intervention and 73 in the control group, determined using the Mini Nutritional Assessment-Short-Form. The intervention group received individualized nutritional care, including electrolyte and micronutrients monitoring, while the control received standard care. We primarily focused on complications such as infections, falls, unplanned hospital readmissions, and mortality, and secondarily focused on functional status and mobility improvements. Post-discharge follow-ups occurred at 3 and 6 months. Our findings demonstrated that the intervention group (age 82.3 ± 7.5 y, 69% female), exhibited greater previous weight loss (11.5 kg vs. 4.7 kg), more cognitive impairment and a longer hospital stay (19 days vs. 15 days). Binary logistic regression showed no difference in primary endpoint outcomes between groups during hospitalization. At 3- and 6-month follow-ups, the control group exhibited fewer adverse outcomes, particularly falls and readmissions. Both groups showed in-hospital functional improvements, but only controls maintained post-discharge mobility gains. The study concludes that the nutritional intervention did not outperform standard care, potentially due to study limitations and high-quality standard care in control group geriatric departments.
Prevalence and Antimicrobial Resistance Patterns of Hospital Acquired Infections through the COVID-19 Pandemic: Real-Word Data from a Tertiary Urological Centre
Authors: Gavi Filippo , Fiori Barbara , Gandi Carlo , Campetella Marco , Bientinesi Riccardo , Marino Filippo , Fettucciari Daniele , Rossi Francesco , Moretto Stefano , Murri Rita , Pierconti Francesco , Racioppi Marco , Sacco Emilio
Published: November 2023

Background: Antimicrobial resistance (AMR) remains a significant public health concern, closely linked to antibiotic overuse. During the COVID-19 pandemic, broad-spectrum antibiotics were frequently administered, potentially exacerbating AMR. This study aimed to assess AMR patterns in our urology department before and after the pandemic. Methods: The study encompassed patients admitted to our urology department from January 2016 to December 2022, with confirmed urinary tract infection, bloodstream infection, or wound infection based on positive culture results. Descriptive statistics, including mean, frequency, and percentage, summarized the data. Trends were analyzed using the Joinpoint Regression program. Results: A total of 506 patients were included. Escherichia coli and Klebsiella pneumoniae displayed resistance rates of 65% and 62% to ciprofloxacin, respectively. K. pneumoniae showed resistance rates of 41% to piperacillin tazobactam and 3rd generation cephalosporins (3GC). Carbapenem resistance was observed in 38% of K. pneumoniae isolates. Additionally, 26% of E. coli, 26% of K. pneumoniae, and 59% of Proteus mirabilis isolates were ESBL-positive. Among gram+, 72% of Staphylococcus aureus isolates were MRSA, and 23% of Enterococcus faecium isolates were VRE. Trends in antimicrobial susceptibility patterns over the 7-year study period revealed a statistically significant decrease in E. coli resistance to amoxicillin-clavulanic acid (APC: −5.85; C.I. 95% p < 0.05) and a statistically significant increase in K. pneumoniae resistance to 3GC (APC: 9.93; CI (−19.9–14.4 95% p < 0.05). There were no statistically significant differences in AMR incidence pre- and post-COVID-19. Conclusion: The COVID-19 pandemic did not appear to influence the AMR incidence in our urology department. However, the overall prevalence of AMR and MDROs in our department remains high compared to European AMR.
Microvesicles Are Associated with Early Veno Venous ECMO Circuit Change during Severe ARDS: A Prospective Observational Pilot Study
Authors: Guervilly Christophe , Bousquet Giovanni , Arnaud Laurent , Gragueb-Chatti Ines , Daviet Florence , Adda Mélanie , Forel Jean-Marie , Dignat-George Françoise , Papazian Laurent , Roch Antoine , Lacroix Romaric , Hraiech Sami
Published: November 2023

Background: Veno venous Extra Corporeal Membrane Oxygenation (vvECMO) is associated with frequent hematological ECMO-related complications needing ECMO circuit change. Microvesicles (MVs) interplay during the thrombosis-fibrinolysis process. The main objective of the study was to identify subpopulations of MVs associated with indications of early vvECMO circuit change. Methods: This is a prospective observational monocenter cohort study. Blood gas was sampled on the ECMO circuit after the membrane oxygenator to measure the PO2 post oxy at inclusion, day 3, day 7 and the day of ECMO circuit removal. Blood samples for MV analysis were collected at inclusion, day 3, day 7 and the day of ECMO circuit removal. MV subpopulations were identified by flow cytometry. Results: Nineteen patients were investigated. Seven patients (37%) needed an ECMO circuit change for hemolysis (n = 4), a pump thrombosis with fibrinolysis (n = 1), persistent thrombocytopenia with bleeding (n = 1) and a decrease of O2 transfer (n = 1). Levels of leukocyte and endothelial MVs were significantly higher at inclusion for patients who thereafter had an ECMO circuit change (p = 0.01 and p = 0.001). The areas under the received operating characteristics curves for LeuMVs and EndoMVs sampled the day of cannulation and the need for ECMO circuit change were 0.84 and 0.92, respectively. PO2 post oxy did not significantly change except for in one patient during the ECMO run. Conclusions: Our pilot study supports the potential interest of subpopulations of microvesicles early associated with hematological ECMO-related complications. Our results warrant further studies.
Expression of p53, p63, p16, Ki67, Cyclin D, Bcl-2, and CD31 Markers in Actinic Keratosis, In Situ Squamous Cell Carcinoma and Normal Sun-Exposed Skin of Elderly Patients
Authors: Balcere Alise , Sperga Māris , Čēma Ingrīda , Lauskis Gunārs , Zolovs Maksims , Rone Kupfere Māra , Krūmiņa Angelika
Published: November 2023

Background: Age and cumulative exposure to ultraviolet (UV) light are primary contributors to skin cancer development. Regulatory proteins within the cell cycle are essential for the homeostasis of squamous epithelium. Methods: This study assessed the expression of immunohistochemical markers p53, p63, p16, Ki67, Cyclin D, Bcl-2, and CD31 in keratinocyte intraepithelial neoplasia (actinic keratosis and squamous cell carcinoma in situ) compared to normal skin. The objective was to distinguish disease-specific changes from those attributable to ageing and sun exposure in elderly skin. Results. Analysis included 22 actinic keratoses (AK), 7 in situ squamous cell carcinomas (SCC), and 8 normal skin biopsies. The mean age was 78.1 years for the AK/SCC group and 73.8 years for controls, with no significant age difference noted between the groups. The AK/SCC group exhibited a higher occurrence of amorphous masses, higher intensity of p53, lower Bcl-2 expression in the epidermis, higher Bcl-2 expression in the dermis, and higher CD31 expression in the dermis, all of which were statistically significant (p < 0.05). Conclusions: The study identifies distinct differences in the presence of amorphous masses and the expression levels of p53, Bcl-2, and CD31 between sun-exposed skin and in situ cutaneous squamous cell carcinomas, including actinic keratoses.
Recessive SERPING1 Variant Leads to Kinin–Kallikrein System Control Failure in a Consanguineous Brazilian Family with Hereditary Angioedema
Authors: Maia Luana Sella Motta , Burger Bettina , Ghannam Arije , Nunes Fernanda Leonel , Ferriani Mariana Paes Leme , Dias Marina Mendonça , Arruda Luisa Karla , Drouet Christian , Cichon Sven
Published: November 2023

Background: Hereditary angioedema (HAE) is a severe and potentially life-threatening disease. The most common forms are caused by variants in SERPING1, resulting in C1-inhibitor (C1-INH) deficiency (HAE-C1-INH). C1-INH is a serine protease inhibitor (SERPIN) that regulates multiple proteases pathways, including the kallikrein–kinin system (KKS) and its complement. In HAE-C1-INH patients, C1-INH deficiencies affect KKS control, resulting in the development of kallikrein activity in plasma and the subsequent release of bradykinin (BK). While the overwhelming majority of disease-causing SERPING1 variants are dominant, very few recessive variants have been described. We present a large Brazilian HAE-C1-INH family with a recessive form of HAE-C1-INH. Methods: Blood samples of family members were investigated for protein levels of C1-INH, C4, C1q, and C1-INH function. The SERPING1 gene was sequenced. Results: In two severely affected sisters, we identified a homozygous missense variant in SERPING1 (NM_000062.3:c.964G>A;p.Val322Met). Fourteen family members were asymptomatic heterozygous carriers of the variant. Data regarding C1-INH function in the plasma showed that homozygous p.Val322Met strongly impacts C1-INH function to inhibit C1s and kallikrein (PKa). When heterozygously expressed, it affects the C1-INH control of C1s more than that of PKa. Conclusions: These studies of the variant’s effects on the structure–function relationship reinforce prior observations suggesting that C1-INH deficiency is a conformational disease.
Structural Characterization of Composites Based on Butadiene Rubber and Expanded Perlite
Authors: Edres Nada , Buniyat-zadeh Irada , Turp Sinan Mehmet , Soylak Mustafa , Aliyeva Solmaz , Binnetova Nurlana , Guliyeva Naila , Mammadyarova Sevinj , Alosmanov Rasim
Published: November 2023

The article presents a method for obtaining new composites using the well-known mineral expanded perlite (EP), and the industrial polymer butadiene rubber (BR). For the design of composites, a joint oxidative chlorophosphorylation reaction of BR and EP (as well as BR and modified EP) was carried out, and the modifications resulting from these reactions were further hydrolyzed. The structure and morphology of the obtained samples were characterized in detail using Fourier transform infrared spectroscopy, ultraviolet-visible spectroscopy, X-ray powder diffraction, as well as scanning electron microscopy, and energy-dispersive X-ray analysis. EP and BR were separately modified with a similar reaction and characterized for data interpretation.
Extended Analysis of Raman Spectra Using Artificial Intelligence Techniques for Colorectal Abnormality Classification
Authors: Kalatzis Dimitris , Spyratou Ellas , Karnachoriti Maria , Kouri Maria Anthi , Stathopoulos Ioannis , Danias Nikolaos , Arkadopoulos Nikolaos , Orfanoudakis Spyros , Seimenis Ioannis , Kontos Athanassios G. , Efstathopoulos Efstathios P.
Published: November 2023

Raman spectroscopy (RS) techniques are attracting attention in the medical field as a promising tool for real-time biochemical analyses. The integration of artificial intelligence (AI) algorithms with RS has greatly enhanced its ability to accurately classify spectral data in vivo. This combination has opened up new possibilities for precise and efficient analysis in medical applications. In this study, healthy and cancerous specimens from 22 patients who underwent open colorectal surgery were collected. By using these spectral data, we investigate an optimal preprocessing pipeline for statistical analysis using AI techniques. This exploration entails proposing preprocessing methods and algorithms to enhance classification outcomes. The research encompasses a thorough ablation study comparing machine learning and deep learning algorithms toward the advancement of the clinical applicability of RS. The results indicate substantial accuracy improvements using techniques like baseline correction, L2 normalization, filtering, and PCA, yielding an overall accuracy enhancement of 15.8%. In comparing various algorithms, machine learning models, such as XGBoost and Random Forest, demonstrate effectiveness in classifying both normal and abnormal tissues. Similarly, deep learning models, such as 1D-Resnet and particularly the 1D-CNN model, exhibit superior performance in classifying abnormal cases. This research contributes valuable insights into the integration of AI in medical diagnostics and expands the potential of RS methods for achieving accurate malignancy classification.
Comprehensive Investigation of Hastelloy C-22 Powder Weld Overlay on SA 240 Type 316L Using Laser Beam Welding for Enhanced Performance
Authors: Mehta Manish V. , Chaudhari Mrunalkumar D. , Chaudhari Rakesh , Khanna Sakshum , Vora Jaykumar
Published: November 2023

This article presents a comprehensive study on the application of Hastelloy C-22 powder weld overlay on SA 240 Type 316L austenitic stainless steel using the laser beam welding process. This novel combination of materials and processes was investigated for the first time, focusing on its potential utility for various industrial applications. Various testing techniques, including visual testing, hardness testing, bend testing, chemical composition analysis using optical spectroscopy, corrosion resistance assessment through the potentiodynamic polarization technique, and macro- and microstructural observation, were employed to evaluate the performance of the weld overlay. The research findings had several significant outcomes. Notably, precise control and minimal alloy mixing were achieved, as evidenced by the dilution at a remarkable height of 0.5 mm from the base metal. The laser welding process resulted in a minimal heat-affected zone and a fine columnar interdendritic microstructure, with average primary and secondary arm spacing values of 3.981 µm and 2.289 µm, respectively. Rigorous visual and bend testing confirmed the integrity of the sound welds in the overlay. Moreover, the high-quality finish of the weld overlay eliminated the need for extensive machining and finishing processes, resulting in cost reductions. This study also demonstrated primary and secondary inter-laminar spacing, leading to improved overall structural integrity. Additionally, the weld overlay exhibited excellent hardness characteristics. The current work contributes to the advancement of welding processes and provides practical solutions to enhance efficiency, cost-effectiveness, and structural performance in relevant industrial applications.
New Steps to Deep-Water Hydrate Long-Term Mining by Formation Stabilization
Authors: Lin Dong , Bu Yuhuan , Xiang Changyou , Lu Chang , Liu Huajie , Guo Shenglai
Published: November 2023

The decomposition of hydrates can cause serious sand production and collapse problems, hindering the long-term effective production of hydrates. This study proposes a theory for framework reconstruction and reinforcement for deep-water hydrate layers based on grouting fracturing technology and chemical sand control principles. The setting liquid was injected via fracturing and grouting to form several cracks with a certain depth and width. The setting liquid remains in the fracture and solidifies to form a “reconstruction body.” Simultaneously, the setting liquid permeates and diffuses from the cracks to the surrounding hydrate layer, bonding with the sediment and forming a gradient solidification zone to achieve solidification and reinforcement of the hydrate layer. To achieve effective production of hydrates, the reconstruction body must consider internal reinforcement, sand control, and good permeability. The parameters of the reconstruction body were designed based on the geological characteristics of hydrate formation in a certain area. In order to effectively support the hydrate layer, the reconstruction body was designed with a 24 h compressive strength of at least 3.20 MPa and a long-term compressive strength of at least 17.70 MPa. To ensure that the permeability characteristics of the reconstructed body meet production needs, the permeability of the reconstructed body must be greater than that of the hydrate layer. The maximum concentrated pore size of the skeleton reconstruction body is designed to be 9 μm based on the particle characteristics of shale sand in hydrate reservoirs. This study provides a new approach to solving sand production and collapse.
Single-Stage Peninsular-Shaped Lateral Tongue Flap for Personalized Reconstruction of Various Small- to Moderate-Sized Intraoral Defects: A Retrospective Case Series with Tongue Function Evaluation Using the Functional Intraoral Glasgow Scale
Authors: Cho Wonseok , Jang Eun-A , Kim Kyu-Nam
Published: November 2023

Herein, we present our experience using a single-stage peninsular-shaped lateral tongue flap (pLTF) to cover various intraoral defects and confirm the versatile utility and effective application of pLTF in intraoral defect reconstruction. This study included eight cases (six males and two females; average age 60.3 ± 16.9 years) of intraoral defect reconstruction performed by a single surgeon between August 2020 and May 2023 using the single-stage pLTF technique. Electronic medical records and photographs of the patients were collected and analyzed. The functional intraoral Glasgow scale (FIGS) was used to evaluate preoperative and postoperative tongue function. Defect sizes ranged from 3 cm × 3 cm to 4 cm × 6 cm. Notably, all defects were successfully covered with pLTFs, and the flap sizes ranged between 3 cm × 4.5 cm and 4.5 cm × 7.5 cm. The flaps completely survived without any postoperative complications. At follow-up (average, 9.87 ± 2.74 months), no patient had tumor recurrence or significant tongue functional deficits. The mean preoperative and postoperative FIGS were 14.75 ± 0.46 and 14.00 ± 0.92, respectively (p = 0.059). Thus, the single-stage pLTF technique is a good reconstructive modality for various small to moderate intraoral defect coverage in selected cases for personalized intraoral reconstruction.
COVID-19 “Nightmare”: Perceived Stress, Emotional Distress, and Burnout Syndrome among Medical Staff after One Year of the COVID-19 Pandemic
Authors: Ruta Maria Victoria , Alexescu Teodora , Todea Doina Adina , Motoc Nicoleta Stefania , Necrelescu Octavia Luiza , Campean Andrada Urda , Toma Claudia , Crisan Catalina Angela , Man Milena Adina
Published: November 2023

(1) After one year of treating patients with SARS-CoV-2 infection, physical exhaustion is added to emotional stress and burnout syndrome. (2) By applying specific questionnaires, we evaluated healthcare workers who handled patients infected with SARS-CoV-2in terms of disease perception, perceived stress, emotional distress, and burnout syndrome after one year of the COVID-19 pandemic and compared them with staff who did not handle infected patients. (3) A total of 165 persons were evaluated, with 79 working in the COVID-19 department and 86 working in the non-COVID-19 department. No statistically significant differences were found in the perceived stress scores, emotional distress (functional or dysfunctional), and disease perception among the COVID-19 and non-COVID-19 groups. Also, we did not find any differences between the COVID-19 and non-COVID-19 departments concerning their total Maslach scores—50 in the COVID-19 department and 51 in the non-COVID-19 department, p = 0480—so a moderate level of burnout in the two groups. The only statistical difference was in the Maslach depersonalization scores, which were higher among COVID-19 workers (p = 0.024). (4) In our center, there was no statistically significant difference in perceived stress or emotional distress. The level of burnout syndrome seems to be the same among the two groups, regardless if they worked withCOVID-19-infected patients or not.
Heterogeneity of Adhesive Joint Properties
Authors: Anasiewicz Kamil , Kuczmaszewski Józef
Published: November 2023

This paper presents the results of a study of adhesive joints, focused on the heterogeneity of the properties of the adhesive material in the adhesive joint. The main objective of the study was to determine potential differences in the material properties of adhesive joints made with selected structural adhesives. Due to the impact of the joined material on the adhesive during the curing of the joint as well as the impact of phenomena occurring during the curing of the adhesive, the properties of the adhesive joint may vary along the thickness of the joint. Determining the differences in material properties over the thickness of the adhesive bond is important for more accurate prediction of adhesive bond strength in FEM simulations. In order to observe changes in the material properties of bonds, nanoindentation tests have been carried out on eight adhesive joint bonds made with common structural adhesives used to join sheets of aluminium alloy or corrosion-resistant steel. Basing on the achieved test results, load/unload curves were developed for imprints at characteristic spots of the joints. Distinct differences in the achieved average force value were observed for imprints located in the wall-adjacent zone and in the centre of the adhesive joint; this can be interpreted as areas of the joint with different material structures of higher or lower density of imperfections or porosities. Differences in the load/unload curves for ‘rigid’ and ‘flexible’ adhesives were analysed. The summary includes a conclusion that an adhesive joint is characterised by heterogeneous properties along its thickness.
Formulating Geopolymer Mortars through Construction and Demolition Waste (CDW) Recycling: A Comprehensive Case Study
Authors: Manzi Stefania , Baldazzi Luca , Saccani Andrea
Published: November 2023

The overall amount of construction and demolition waste (CDW) is steadily increasing due to urbanization-related phenomena in metropolitan cities. Only a small fraction is recycled to produce new concrete, a practice that would avoid the exploitation of natural aggregates. Furthermore, the Portland cement production process causes the release of high values of CO2 emissions into the atmosphere, increasing the global warming potential. For these reasons, materials alternative to ordinary Portland cement (OPC) are becoming more and more widespread, such as alkali-activated materials, which, when used with recycled aggregates, could become environmentally friendly substitutes for traditional concrete. During this study, various mix designs were formulated for alkali-activated metakaolin mortars containing recycled concrete aggregates. Their properties in the fresh and hardened states were analyzed. The main problem encountered was the presence of the adhered mortar layer on the recycled concrete aggregate. This layer not only caused a detrimental effect deriving from the increase in open porosity but also activated competitive reactions which partially compromised the alkali activation of metakaolin. All these phenomena deteriorated the final compressive strength of the composites containing recycled aggregates, which after 28 days, was around 20 MPa for samples with 12.5% of replacement of natural aggregate and 15 MPa for those with 25% of replacement, corresponding to a reduction of 35% and 50% compared to the standard sample without replacement, respectively.
Data-Driven Prediction and Uncertainty Quantification of Process Parameters for Directed Energy Deposition
Authors: Hermann Florian , Michalowski Andreas , Brünnette Tim , Reimann Peter , Vogt Sabrina , Graf Thomas
Published: November 2023

Laser-based directed energy deposition using metal powder (DED-LB/M) offers great potential for a flexible production mainly defined by software. To exploit this potential, knowledge of the process parameters required to achieve a specific track geometry is essential. Existing analytical, numerical, and machine-learning approaches, however, are not yet able to predict the process parameters in a satisfactory way. A trial-&-error approach is therefore usually applied to find the best process parameters. This paper presents a novel user-centric decision-making workflow, in which several combinations of process parameters that are most likely to yield the desired track geometry are proposed to the user. For this purpose, a Gaussian Process Regression (GPR) model, which has the advantage of including uncertainty quantification (UQ), was trained with experimental data to predict the geometry of single DED tracks based on the process parameters. The inherent UQ of the GPR together with the expert knowledge of the user can subsequently be leveraged for the inverse question of finding the best sets of process parameters by minimizing the expected squared deviation between target and actual track geometry. The GPR was trained and validated with a total of 379 cross sections of single tracks and the benefit of the workflow is demonstrated by two exemplary use cases.
Advances in Emerging Catalytic Materials for the Conversion of Carbon Dioxide
Authors: Sun Bingyue , Wang Bingquan , Wang Rui
Published: November 2023

The use of fossil fuels leads to significant CO2 emissions, thus highlighting the importance for investigating the utilization of CO2 for generating high-value chemical products toward achieving the dual-carbon goal. CO2 can be efficiently used in synthesizing valuable organic compounds through C-C, C-O, C-H, and C-N bond construction, with reduction technologies effectively converting CO2 to organic carbon sources. Therefore, the research in developing environmentally friendly catalysts for efficient and renewable CO2 conversion holds great importance. New materials for catalytic conversion include zeolites, activated carbon, graphene, metal-organic frameworks (MOFs), covalent organic frameworks (COFs), ionic liquids, semiconducting photocatalysts, single-atom catalysts (SACs), and dendritic mesoporous silica nanoparticles (DMSNs). The proper research and use of these materials can aid in the quest to reduce carbon emissions and mitigate climate change. This Review focuses on the utilization of single-atom catalysts (SACs), ionic liquids (ILs), dendritic mesoporous silica nanoparticles (DMSNs), and carbene-metal catalytic systems in CO2 conversion. The potential for new materials in catalyzing the conversion of CO2 is examined by analyzing various common chemical carbon sequestration methods, ultimately providing possible research directions for effective solutions to climate and environmental pollution problems. On the basis of the high reaction rate and high treatment efficiency of the catalyst for the catalytic conversion of CO2, the Review focuses on the simpler and more economical synthesis method of the catalyst itself and the wider application prospects.
Effects of Ion-Releasing Materials on Dentine: Analysis of Microhardness, Appearance, and Chemical Composition
Authors: Šalinović Ivan , Schwendicke Falk , Askar Haitham , Yassine Jamila , Miletić Ivana
Published: November 2023

The aim of this study was to compare the potential of standard ion-releasing materials to repair demineralized lesions with recently introduced alkasite and glass hybrid materials. Glass ionomer (GC Fuji TRIAGE), two glass hybrids (EQUIA Forte HT, Riva SC), calcium silicate cement (Biodentine) and an alkasite (Cention Forte) were tested. A total of 72 human third molars were used for sample preparation; on the dentine surface, a class-I cavity was prepared, and one half was covered with nail varnish. The teeth were subjected to a demineralization protocol, filled with the examined materials, and cut in half. The evaluation included a dentine microhardness assessment (n = 10) and SEM/EDS analysis (n = 2). The results were analyzed using SPSS 22.0 statistical software and compared using an analysis of variance and Scheffe post-hoc test. The statistical significance level was set to 0.05. Mean microhardness values (HV0.1) after 14 and 28 days were, respectively: EQUIA Forte HT (26.7 ± 1.45 and 37.74 ± 1.56), Riva Self Cure (19.66 ± 1.02 and 29.58 ± 1.18), Cention Forte (19.01 ± 1.24 and 27.93 ± 1.33), Biodentine (23.35 ± 1.23 and 29.92 ± 1.02), GC Fuji TRIAGE (25.94 ± 1.35 and 33.87 ± 5.57) and control group (15.57 ± 0.68 and 15.64 ± 0.82). The results were significantly different between most groups (p < 0.001). SEM/EDS revealed varying patterns, material deposits and distinct elemental variations. To conclude, all materials increased microhardness and affected the dentine surface appearance and chemical composition; EQUIA Forte HT demonstrated the most pronounced effects.