bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Trifocal and Microsurgical Testicular Sperm Extraction Enhances Sperm Retrieval Rate in Low-Chance Retrieval Non-Obstructive Azoospermia
Authors: Falcone Marco , Boeri Luca , Timpano Massimiliano , Cirigliano Lorenzo , Preto Mirko , Russo Giorgio I. , Peretti Federica , Ferro Ilaria , Plamadeala Natalia , Gontero Paolo
Published: July 2022

Background: Low-chance retrieval non-obstructive azoospermic (NOA) patients are a subpopulation of NOA patients. The objective of this study is to compare the surgical outcome of microsurgical-assisted testicular sperm extraction (M-TeSE) and combined trifocal/M-TeSE in low-chance retrieval NOA patients. Material and Methods: A single-center retrospective analysis of NOA patients who underwent testicular sperm extraction was performed. Low-chance retrieval NOA (testicular volume < 10 cc and FSH > 12.4 UI/L) was set as the inclusion criteria. Re-do TeSE procedures were excluded from the current analysis. Data were extrapolated from clinical records and operative notes. We compared data from patients who underwent classic M-TeSE (group A) with that from patients submitted to combined trifocal/M-TeSE (group B). Sperm retrieval rate (SRr) was the primary outcome of the study. Surgical outcomes and postoperative complications were evaluated. A multivariate analysis was conducted to investigate predictive factors for positive SR. Results: Overall, 80 patients (60 patients in Group A and 20 patients in Group B) fulfilled the inclusion criteria. The average (SD) age was 35 (8.2) years. The average preoperative FSH was 27.5 (13) UI/L. The average testicular volume was 6.3 (3) cc on the left side and 6.8 (2.5) cc on the right. Groups were similar in terms of preoperative parameters. The overall SRr was 28%. Patients in group B had higher SRr than those in group A (29.4% vs. 26.9%, p < 0.03). We identified a significant association between testicular histopathology and positive SR (hypospermatogenesis 100%, spermatogenic arrest 32%, and Sertoli cell-only syndrome 22%). The histopathology report was the only significant predicting factor for SR in the multivariate analysis. Conclusion: The combined trifocal and M-TeSE approach is safe and may represent a valuable approach to enhance the SRr in low-chance retrieval NOA. The histopathology report is confirmed to be the only valuable predicting factor for a positive SR.
Development and Validation of the Open Matrices Item Bank
Authors: Koch Marco , Spinath Frank M. , Greiff Samuel , Becker Nicolas
Published: July 2022

Figural matrices tasks are one of the most prominent item formats used in intelligence tests, and their relevance for the assessment of cognitive abilities is unquestionable. However, despite endeavors of the open science movement to make scientific research accessible on all levels, there is a lack of royalty-free figural matrices tests. The Open Matrices Item Bank (OMIB) closes this gap by providing free and unlimited access (GPLv3 license) to a large set of empirically validated figural matrices items. We developed a set of 220 figural matrices based on well-established construction principles commonly used in matrices tests and administered them to a sample of N = 2572 applicants to medical schools. The results of item response models and reliability analyses demonstrate the excellent psychometric properties of the items. In the discussion, we elucidate how researchers can already use the OMIB to gain access to high-quality matrices tests for their studies. Furthermore, we provide perspectives for features that could additionally improve the utility of the OMIB.
Fast Finite-Time Path-Following Control of Unmanned Surface Vehicles with Sideslip Compensation and Time-Varying Disturbances
Authors: He Zhiping , Wang Guofeng , Fan Yunsheng , Qiao Shuanghu
Published: July 2022

This paper studies the fast finite-time path following of underactuated unmanned surface vehicles (USV) with sideslip compensation, time-varying disturbances and input saturation. In the guidance module, the fast finite-time predictor-based line-of-sight (FFTPLOS) is proposed to overcome the large guidance angle and high-frequency oscillation and eliminate the sideslip angle with finite time. Then, the robust finite-time feedback control is applied to keep the vehicle following the desired path in the control module, where the reduced-order extended state observers (ROESO) are applied to deal with time-varying disturbances. Additionally, fast finite-time auxiliary dynamic systems with smoothly switching functions (FFTADS-SSF) achieve the saturation constraints on actuators with low consumption. The stability analysis proves that the guidance-control system of USVs is uniformly ultimately bounded stable within finite time. The effectiveness and performance of this proposed scheme are superior to the comparison schemes.
Endocrine-Disrupting Effects of Bisphenol A on the Cardiovascular System: A Review
Authors: Fonseca Maria , Lorigo Margarida , Cairrao Elisa
Published: July 2022

Currently, the plastic monomer and plasticizer bisphenol A (BPA) is one of the most widely used chemicals. BPA is present in polycarbonate plastics and epoxy resins, commonly used in food storage and industrial or medical products. However, the use of this synthetic compound is a growing concern, as BPA is an endocrine-disrupting compound and can bind mainly to estrogen receptors, interfering with different functions at the cardiovascular level. Several studies have investigated the disruptive effects of BPA; however, its cardiotoxicity remains unclear. Therefore, this review’s purpose is to address the most recent studies on the implications of BPA on the cardiovascular system. Our findings suggest that BPA impairs cardiac excitability through intracellular mechanisms, involving the inhibition of the main ion channels, changes in Ca2+ handling, the induction of oxidative stress, and epigenetic modifications. Our data support that BPA exposure increases the risk of developing cardiovascular diseases (CVDs) including atherosclerosis and its risk factors such as hypertension and diabetes. Furthermore, BPA exposure is also particularly harmful in pregnancy, promoting the development of hypertensive disorders during pregnancy. In summary, BPA exposure compromises human health, promoting the development and progression of CVDs and risk factors. Further studies are needed to clarify the human health effects of BPA-induced cardiotoxicity.
Detection of Patients with Congenital and Often Concealed Long-QT Syndrome by Novel Deep Learning Models
Authors: Doldi Florian , Plagwitz Lucas , Hoffmann Lea Philine , Rath Benjamin , Frommeyer Gerrit , Reinke Florian , Leitz Patrick , Büscher Antonius , Güner Fatih , Brix Tobias , Wegner Felix Konrad , Willy Kevin , Hanel Yvonne , Dittmann Sven , Haverkamp Wilhelm , Schulze-Bahr Eric , Varghese Julian , Eckardt Lars
Published: July 2022

Introduction: The long-QT syndrome (LQTS) is the most common ion channelopathy, typically presenting with a prolonged QT interval and clinical symptoms such as syncope or sudden cardiac death. Patients may present with a concealed phenotype making the diagnosis challenging. Correctly diagnosing at-risk patients is pivotal to starting early preventive treatment. Objective: Identification of congenital and often concealed LQTS by utilizing novel deep learning network architectures, which are specifically designed for multichannel time series and therefore particularly suitable for ECG data. Design and Results: A retrospective artificial intelligence (AI)-based analysis was performed using a 12-lead ECG of genetically confirmed LQTS (n = 124), including 41 patients with a concealed LQTS (33%), and validated against a control cohort (n = 161 of patients) without known LQTS or without QT-prolonging drug treatment but any other cardiovascular disease. The performance of a fully convolutional network (FCN) used in prior studies was compared with a different, novel convolutional neural network model (XceptionTime). We found that the XceptionTime model was able to achieve a higher balanced accuracy score (91.8%) than the associated FCN metric (83.6%), indicating improved prediction possibilities of novel AI architectures. The predictive accuracy prevailed independently of age and QTc parameters. Conclusions: In this study, the XceptionTime model outperformed the FCN model for LQTS patients with even better results than in prior studies. Even when a patient cohort with cardiovascular comorbidities is used. AI-based ECG analysis is a promising step for correct LQTS patient identification, especially if common diagnostic measures might be misleading.
Land Change Science and the STEPLand Framework: An Assessment of Its Progress
Authors: Serra Pere , Salvati Luca
Published: July 2022

This contribution assesses a new term that is proposed to be established within Land Change Science: Spatio-TEmporal Patterns of Land (‘STEPLand’). It refers to a specific workflow for analyzing land-use/land cover (LUC) patterns, identifying and modeling driving forces of LUC changes, assessing socio-environmental consequences, and contributing to defining future scenarios of land transformations. In this article, we define this framework based on a comprehensive meta-analysis of 250 selected articles published in international scientific journals from 2000 to 2019. The empirical results demonstrate that STEPLand is a consolidated protocol applied globally, and the large diversity of journals, disciplines, and countries involved shows that it is becoming ubiquitous. In this paper, the main characteristics of STEPLand are provided and discussed, demonstrating that the operational procedure can facilitate the interaction among researchers from different fields, and communication between researchers and policy makers.
A Typology of Nature-Based Solutions for Sustainable Development: An Analysis of Form, Function, Nomenclature, and Associated Applications
Authors: Anderson Vidya , Gough William A.
Published: July 2022

This study presents a typology of nature-based solutions (NbS), addressing the need for a standardized source of definitions and nomenclature, and to facilitate communication in this interdisciplinary field of theory and practice. Growing usage of the umbrella phrase ‘nature-based solutions’ has led to a broad inclusion of terms. With the diversity of terminology used, the full potential of NbS may be lost in the confusion of misapplied terms. Standardization and definition of commonly used nature-based nomenclature are necessary to facilitate communication in this rapidly expanding field. Through objective systemization of applications, functions, and benefits, NbS can be embraced as a standard intervention to address societal challenges and support achievement of the UN SDGs.
Comment on Boitrelle et al. The Sixth Edition of the WHO Manual for Human Semen Analysis: A Critical Review and SWOT Analysis. Life 2021, 11, 1368
Authors: Pallotti Francesco , Lombardo Francesco , Paoli Donatella
Published: July 2022

We wish to congratulate Boitrelle and colleagues for their comprehensive critical review on the Sixth Edition of the WHO Laboratory Manual for Human semen examination [...]
In Vitro Skin Co-Delivery and Antibacterial Properties of Chitosan-Based Microparticles Containing Ascorbic Acid and Nicotinamide
Authors: Di Filippo Leonardo Delello , Duarte Jonatas Lobato , Roque-Borda Cesar Augusto , Pavan Fernando Rogério , Meneguin Andreia Bagliotti , Chorilli Marlus , Melero Ana , Guillot Antonio José , Spagnol Caroline Magnani , Correa Marcos Antônio
Published: July 2022

Vitamins are widely found in nature, for example, in plants and fruits. Ascorbic acid and nicotinamide are examples of these compounds that have potent antioxidant properties, besides stimulating collagen production and depigmenting properties that protect the skin from premature aging. To overcome the skin barrier and reduce the instability of antioxidant compounds, alternative systems have been developed to facilitate the delivery of antioxidants, making them efficiently available to the tissue for an extended time without causing damage or toxicity. The objective of this study was to obtain chitosan biodegradable microparticles containing ascorbic acid and nicotinamide for topical delivery. The microparticles were obtained by spray drying and characterized chemically by means of scanning electron microscopy, infrared spectroscopy, X-ray diffraction, and differential exploratory calorimetry. The drugs were successfully encapsulated and the microparticles showed positive zeta potential. In vitro release assays showed a sustained release profile. The evaluation of ex vivo skin permeation and retention demonstrated low permeation and adequate retention of the compounds in the epidermis/dermis, suggesting the efficient delivery from the obtained microparticles. Antibacterial assays have shown that microparticles can inhibit the growth of microorganisms in a time- and dose-dependent manner, corroborating their use in cosmetic products for application on the skin.
Elastohydrodynamic Lubrication of Compliant Circular Contacts near Glass-Transition Temperature
Authors: Krupka Jiri , Dockal Krystof , Krupka Ivan , Hartl Martin
Published: July 2022

Lubrication of polymer materials nowadays represents a subject of interest in many engineering applications, such as bearings or gears, to utilize them in the areas where conventional metal materials have so far dominated. However, material properties of polymers are strongly dependent on temperature that delimits a lubrication process and leads to manifestations of viscoelastic behavior of polymers. An understanding of mechanisms, which are responsible for formation of film thickness near the glass-transition temperature, is necessary to prevent initialization of failure modes and to increase the durability of polymer engineering components. Optical chromatic interferometry was applied to investigate development of film thickness and changes in contact geometry of compliant circular contacts operated in the elastohydrodynamic lubrication regime (EHL). Film thickness was compared with soft EHL prediction models, differences in contact geometry were assessed and their contribution to film thickness development were evaluated. Qualitatively good agreement of experimental results of central film thickness and soft EHL predictions was observed; however, minimum film thickness shows significant discrepancies. Outcomes and findings confirm the operation of the compliant circular contact in Isoviscous-elastic regime of EHL and the main influence of temperature and load to thermomechanical response of amorphous polymer PMMA.
On the Convergence of the Damped Additive Schwarz Methods and the Subdomain Coloring
Authors: Badea Lori
Published: July 2022

In this paper, we consider that the subdomains of the domain decomposition are colored such that the subdomains with the same color do not intersect and introduce and analyze the convergence of a damped additive Schwarz method related to such a subdomain coloring for the resolution of variational inequalities and equations. In this damped method, a single damping value is associated with all the subdomains having the same color. We first make this analysis both for variational inequalities and, as a special case, for equations in an abstract framework. By introducing an assumption on the decomposition of the convex set of the variational inequality, we theoretically analyze in a reflexive Banach space the convergence of the damped additive Schwarz method. The introduced assumption contains a constant C0, and we explicitly write the expression of the convergence rates, depending on the number of colors and the constant C0, and find the values of the damping constants which minimize them. For problems in the finite element spaces, we write the constant C0 as a function of the overlap parameter of the domain decomposition and the number of colors of the subdomains. We show that, for a fixed overlap parameter, the convergence rate, as a function of the number of subdomains has an upper limit which depends only on the number of the colors of the subdomains. Obviously, this limit is independent of the total number of subdomains. Numerical results are in agreement with the theoretical ones. They have been performed for an elasto-plastic problem to verify the theoretical predictions concerning the choice of the damping parameter, the dependence of the convergence on the overlap parameter and on the number of subdomains.
Combined Anterior Cruciate Ligament and Anterolateral Ligament Reconstruction Using a Single Achilles Tendon Allograft: A Technical Note
Authors: Lee Chul-Soo , Han Seung-Beom , Jang Ki-Mo
Published: July 2022

Clinical outcomes after anterior cruciate ligament reconstruction (ACLR) have improved remarkably. However, residual rotational instability of the knee joint remains a major concern. The anterolateral ligament (ALL) has recently gained interest as a secondary stabilizer of knee joint rotatory instability, and this has led to the attempt of ALL reconstruction (ALLR) in combination with ACLR to restore rotational stability in patients with anterior cruciate ligament (ACL) injury. Although several techniques for ALLR have recently been introduced, the ideal graft type and surgical technique for combined ACLR and ALLR are yet to be established. This technical note therefore aimed at introducing a novel surgical procedure involving the use of a single Achilles tendon allograft as a relatively simple and minimally invasive procedure for combined ALL and ACL reconstruction.
Persistence of Metabolomic Changes in Patients during Post-COVID Phase: A Prospective, Observational Study
Authors: Liptak Peter , Baranovicova Eva , Rosolanka Robert , Simekova Katarina , Bobcakova Anna , Vysehradsky Robert , Duricek Martin , Dankova Zuzana , Kapinova Andrea , Dvorska Dana , Halasova Erika , Banovcin Peter
Published: July 2022

Several relatively recently published studies have shown changes in plasma metabolites in various viral diseases such as Zika, Dengue, RSV or SARS-CoV-1. The aim of this study was to analyze the metabolome profile of patients during acute COVID-19 approximately one month after the acute infection and to compare these results with healthy (SARS-CoV-2-negative) controls. The metabolome analysis was performed by NMR spectroscopy from the peripheral blood of patients and controls. The blood samples were collected on 3 different occasions (at admission, during hospitalization and on control visit after discharge from the hospital). When comparing sample groups (based on the date of acquisition) to controls, there is an indicative shift in metabolomics features based on the time passed after the first sample was taken towards controls. Based on the random forest algorithm, there is a strong discriminatory predictive value between controls and different sample groups (AUC equals 1 for controls versus samples taken at admission, Mathew correlation coefficient equals 1). Significant metabolomic changes persist in patients more than a month after acute SARS-CoV-2 infection. The random forest algorithm shows very strong discrimination (almost ideal) when comparing metabolite levels of patients in two various stages of disease and during the recovery period compared to SARS-CoV-2-negative controls.
Development of a Novel Peptide Nucleic Acid Probe for the Detection of Legionella spp. in Water Samples
Authors: Nácher-Vázquez Montserrat , Barbosa Ana , Armelim Inês , Azevedo Andreia Sofia , Almeida Gonçalo Nieto , Pizarro Cristina , Azevedo Nuno Filipe , Almeida Carina , Cerqueira Laura
Published: July 2022

Legionella are opportunistic intracellular pathogens that are found throughout the environment. The Legionella contamination of water systems represents a serious social problem that can lead to severe diseases, which can manifest as both Pontiac fever and Legionnaires’ disease (LD) infections. Fluorescence in situ hybridization using nucleic acid mimic probes (NAM-FISH) is a powerful and versatile technique for bacterial detection. By optimizing a peptide nucleic acid (PNA) sequence based on fluorescently selective binding to specific bacterial rRNA sequences, we established a new PNA-FISH method that has been successfully designed for the specific detection of the genus Legionella. The LEG22 PNA probe has shown great theoretical performance, presenting 99.9% specificity and 96.9% sensitivity. We also demonstrated that the PNA-FISH approach presents a good signal-to-noise ratio when applied in artificially contaminated water samples directly on filtration membranes or after cells elution. For water samples with higher turbidity (from cooling tower water systems), there is still the need for further method optimization in order to detect cellular contents and to overcome interferents’ autofluorescence, which hinders probe signal visualization. Nevertheless, this work shows that the PNA-FISH approach could be a promising alternative for the rapid (3–4 h) and accurate detection of Legionella.
Formulation and Optimization of Alogliptin-Loaded Polymeric Nanoparticles: In Vitro to In Vivo Assessment
Authors: Mohanty Dibyalochan , Gilani Sadaf Jamal , Zafar Ameeduzzafar , Imam Syed Sarim , Kumar Ladi Alik , Ahmed Mohammed Muqtader , Jahangir Mohammed Asadullah , Bakshi Vasudha , Ahmad Wasim , Eltayib Eyman Mohamed
Published: July 2022

The nano-drug delivery system has gained greater acceptability for poorly soluble drugs. Alogliptin (ALG) is a FDA-approved oral anti-hyperglycemic drug that inhibits dipeptidyl peptidase-4. The present study is designed to prepare polymeric ALG nanoparticles (NPs) for the management of diabetes. ALG-NPs were prepared using the nanoprecipitation method and further optimized by Box–Behnken experimental design (BBD). The formulation was optimized by varying the independent variables Eudragit RSPO (A), Tween 20 (B), and sonication time (C), and the effects on the hydrodynamic diameter (Y1) and entrapment efficiency (Y2) were evaluated. The optimized ALG-NPs were further evaluated for in vitro release, intestinal permeation, and pharmacokinetic and anti-diabetic activity. The prepared ALG-NPs show a hydrodynamic diameter of between 272.34 nm and 482.87 nm, and an entrapment efficiency of between 64.43 and 95.21%. The in vitro release data of ALG-NPs reveals a prolonged release pattern (84.52 ± 4.1%) in 24 h. The permeation study results show a 2.35-fold higher permeation flux than pure ALG. ALG-NPs exhibit a significantly (p < 0.05) higher pharmacokinetic profile than pure ALG. They also significantly (p < 0.05) reduce the blood sugar levels as compared to pure ALG. The findings of the study support the application of ALG-entrapped Eudragit RSPO nanoparticles as an alternative carrier for the improvement of therapeutic activity.
Potential Role of Quercetin in Polycystic Ovary Syndrome and Its Complications: A Review
Authors: Chen Tong , Jia Fan , Yu Yue , Zhang Wufan , Wang Chaoying , Zhu Shiqin , Zhang Nana , Liu Xinmin
Published: July 2022

Polycystic ovary syndrome (PCOS) is a common multisystem disease with reproductive, metabolic and psychological abnormalities. It is characterized by a high prevalence rate in women of childbearing age and highly heterogeneous clinical manifestations, which seriously harm women’s physical and mental health. Quercetin (QUR) is a natural compound of flavonoids found in a variety of foods and medicinal plants. It can intervene with the pathologic process of PCOS from multiple targets and channels and has few adverse reactions. It is mentioned in this review that QUR can improve ovulation disorder, relieve Insulin resistance (IR), reduce androgen, regulate lipid metabolism, regulate gut microbiota and improve vascular endothelial function, which is of great significance in the treatment of PCOS.
Doxorubicin-Based Hybrid Compounds as Potential Anticancer Agents: A Review
Authors: Peter Sijongesonke , Alven Sibusiso , Maseko Rejoice Bethusile , Aderibigbe Blessing Atim
Published: July 2022

The scarcity of novel and effective therapeutics for the treatment of cancer is a pressing and alarming issue that needs to be prioritized. The number of cancer cases and deaths are increasing at a rapid rate worldwide. Doxorubicin, an anticancer agent, is currently used to treat several types of cancer. It disrupts myriad processes such as histone eviction, ceramide overproduction, DNA-adduct formation, reactive oxygen species generation, Ca2+, and iron hemostasis regulation. However, its use is limited by factors such as drug resistance, toxicity, and congestive heart failure reported in some patients. The combination of doxorubicin with other chemotherapeutic agents has been reported as an effective treatment option for cancer with few side effects. Thus, the hybridization of doxorubicin and other chemotherapeutic drugs is regarded as a promising approach that can lead to effective anticancer agents. This review gives an update on hybrid compounds containing the scaffolds of doxorubicin and its derivatives with potent chemotherapeutic effects.
Effect of Moringa oleifera Leaf Extract on Excision Wound Infections in Rats: Antioxidant, Antimicrobial, and Gene Expression Analysis
Authors: Al-Ghanayem Abdullah A. , Alhussaini Mohammed Sanad , Asad Mohammed , Joseph Babu
Published: July 2022

The present study investigated the wound healing activity of Moringa oleifera leaf extract on an infected excision wound model in rats. Infection was induced using methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa. An investigation was also done to study the effect of Moringa extract on the vascular endothelial growth factor (VEGF) and transforming growth factor-beta 1 (TGF-β1) gene expression in vitro using human keratinocytes (HaCaT). The methanol extract of M. oleifera leaves was analyzed for the presence of phytochemicals by LCMS. The antimicrobial activity of the extract was also determined. Wound contraction, days for epithelization, antioxidant enzyme activities, epidermal height, angiogenesis, and collagen deposition were studied. M. oleifera showed an antimicrobial effect and significantly improved wound contraction, reduced epithelization period, increased antioxidant enzymes activity, and reduced capillary density. Effect of the extract was less in wounds infected with P. aeruginosa when compared to MRSA. The VEGF and TGF-β1 gene expression was increased by M. oleifera.
Screening of Big Pharma’s Library against Various in-house Biological Targets
Authors: Knez Damijan , Gobec Stanislav , Hrast Martina
Published: July 2022

Open innovation initiatives provide opportunities for collaboration and sharing of knowledge and experience between industry, academia, and government institutions. Through open innovation, Merck is offering a Mini Library of 80 carefully selected compounds from previous research and development projects to a broader scientific community for testing in academic drug discovery projects. These compounds are predominantly drug-like and cover a broad range of molecular targets. They could potentially interact with other enzymes, receptors, transporters, and ion channels of interest. The Mini Library was tested on seven in-house enzymes (bacterial MurA, MurC ligase, and DdlB enzyme, human MAO-A/B, human BChE, and murine AChE), and several hits were identified. A follow-up series of structural analogues provided by Merck gave a more detailed insight into the accessibility and the quality of the hit compounds. For example, sartan derivatives were moderate inhibitors of MurC, whereas bisarylureas were potent, selective, nanomolar inhibitors of hMAO-B. Importantly, 3-n-butyl-substituted indoles were identified as low nanomolar selective inhibitors of hBChE. All in all, the hit derivatives provide new starting points for the further exploration of the chemical space of high-quality enzyme inhibitors.
Tuning Immobilized Commercial Lipase Preparations Features by Simple Treatment with Metallic Phosphate Salts
Authors: Guimarães José R. , Carballares Diego , Tardioli Paulo W. , Rocha-Martin Javier , Fernandez-Lafuente Roberto
Published: July 2022

Four commercial immobilized lipases biocatalysts have been submitted to modifications with different metal (zinc, cobalt or copper) phosphates to check the effects of this modification on enzyme features. The lipase preparations were Lipozyme®TL (TLL-IM) (lipase from Thermomyces lanuginose), Lipozyme®435 (L435) (lipase B from Candida antarctica), Lipozyme®RM (RML-IM), and LipuraSelect (LS-IM) (both from lipase from Rhizomucor miehei). The modifications greatly altered enzyme specificity, increasing the activity versus some substrates (e.g., TLL-IM modified with zinc phosphate in hydrolysis of triacetin) while decreasing the activity versus other substrates (the same preparation in activity versus R- or S- methyl mandelate). Enantiospecificity was also drastically altered after these modifications, e.g., LS-IM increased the activity versus the R isomer while decreasing the activity versus the S isomer when treated with copper phosphate. Regarding the enzyme stability, it was significantly improved using octyl-agarose-lipases. Using all these commercial biocatalysts, no significant positive effects were found; in fact, a decrease in enzyme stability was usually detected. The results point towards the possibility of a battery of biocatalysts, including many different metal phosphates and immobilization protocols, being a good opportunity to tune enzyme features, increasing the possibilities of having biocatalysts that may be suitable for a specific process.
Prediction of pH Value of Aqueous Acidic and Basic Deep Eutectic Solvent Using COSMO-RS σ Profiles’ Molecular Descriptors
Authors: Panić Manuela , Radović Mia , Cvjetko Bubalo Marina , Radošević Kristina , Rogošić Marko , Coutinho João A. P. , Radojčić Redovniković Ivana , Jurinjak Tušek Ana
Published: July 2022

The aim of this work was to develop a simple and easy-to-apply model to predict the pH values of deep eutectic solvents (DESs) over a wide range of pH values that can be used in daily work. For this purpose, the pH values of 38 different DESs were measured (ranging from 0.36 to 9.31) and mathematically interpreted. To develop mathematical models, DESs were first numerically described using σ profiles generated with the COSMOtherm software. After the DESs’ description, the following models were used: (i) multiple linear regression (MLR), (ii) piecewise linear regression (PLR), and (iii) artificial neural networks (ANNs) to link the experimental values with the descriptors. Both PLR and ANN were found to be applicable to predict the pH values of DESs with a very high goodness of fit (R2independent validation > 0.8600). Due to the good mathematical correlation of the experimental and predicted values, the σ profile generated with COSMOtherm could be used as a DES molecular descriptor for the prediction of their pH values.
In Situ Identification of Unknown Crystals in Acute Kidney Injury Using Raman Spectroscopy
Authors: Yu Youjia , Jiang Qiaoyan , Wan Hua , Li Rong , Sun Yang , Zhang Zhiwei , Mao Zhengsheng , Cao Yue , Chen Feng
Published: July 2022

Raman spectroscopy is a well-established and powerful tool for in situ biomolecular evaluation. Type 2 crystal nephropathies are characterized by the deposition of crystalline materials in the tubular lumen, resulting in rapid onset of acute kidney injury without specific symptoms. Timely crystal identification is essential for its diagnosis, mechanism exploration and therapy, but remains challenging. This study aims to develop a Raman spectroscopy-based method to assist pathological diagnosis of type 2 crystal nephropathies. Unknown crystals in renal tissue slides from a victim suffered extensive burn injury were detected by Raman spectroscopy, and the inclusion of crystals was determined by comparing Raman data with established database. Multiple crystals were scanned to verify the reproducibility of crystal in situ. Raman data of 20 random crystals were obtained, and the distribution and uniformity of substances in crystals were investigated by Raman imaging. A mouse model was established to mimic the crystal nephropathy to verify the availability of Raman spectroscopy in frozen biopsy. All crystals on the human slides were identified to be calcium oxalate dihydrate, and the distribution and content of calcium oxalate dihydrate on a single crystal were uneven. Raman spectroscopy was further validated to be available in identification of calcium oxalate dihydrate crystals in the biopsy specimens. Here, a Raman spectroscopy-based method for in situ identification of unknown crystals in both paraffin-embedded tissues and biopsy specimens was established, providing an effective and promising method to analyze unknown crystals in tissues and assist the precise pathological diagnosis in both clinical and forensic medicine.
Alginate Oligosaccharides Ameliorate DSS-Induced Colitis through Modulation of AMPK/NF-κB Pathway and Intestinal Microbiota
Authors: Zhang Yue , Guo Congcong , Li Yanru , Han Xianlei , Luo Xuegang , Chen Liehuan , Zhang Tongcun , Wang Nan , Wang Weiming
Published: July 2022

Alginate oligosaccharides (AOS) are shown to have various biological activities of great value to medicine, food, and agriculture. However, little information is available about their beneficial effects and mechanisms on ulcerative colitis. In this study, AOS with a polymerization degree between 2 and 4 were found to possess anti-inflammatory effects in vitro and in vivo. AOS could decrease the levels of nitric oxide (NO), IL-1β, IL-6, and TNFα, and upregulate the levels of IL-10 in both RAW 264.7 and bone-marrow-derived macrophage (BMDM) cells under lipopolysaccharide (LPS) stimulation. Additionally, oral AOS administration could significantly prevent bodyweight loss, colonic shortening, and rectal bleeding in dextran sodium sulfate (DSS)-induced colitis mice. AOS pretreatment could also reduce disease activity index scores and histopathologic scores and downregulate proinflammatory cytokine levels. Importantly, AOS administration could reverse DSS-induced AMPK deactivation and NF-κB activation in colonic tissues, as evidenced by enhanced AMPK phosphorylation and p65 phosphorylation inhibition. AOS could also upregulate AMPK phosphorylation and inhibit NF-κB activation in vitro. Moreover, 16S rRNA gene sequencing of gut microbiota indicated that supplemental doses of AOS could affect overall gut microbiota structure to a varying extent and specifically change the abundance of some bacteria. Medium-dose AOS could be superior to low- or high-dose AOS in maintaining remission in DSS-induced colitis mice. In conclusion, AOS can play a protective role in colitis through modulation of gut microbiota and the AMPK/NF-kB pathway.
Investigation of the Renal Protective Effect of Combined Dietary Polyphenols in Streptozotocin-Induced Diabetic Aged Rats
Authors: Chtourou Yassine , Morjen Maram , Ammar Rahma , Mhiri Rania , Jemaà Mohamed , ELBini-Dhouib Ines , Fetoui Hamadi , Srairi-Abid Najet , Marrakchi Naziha , Jebali Jed
Published: July 2022

Natural polyphenols are widely reported to have a large range of pharmacological properties, especially antioxidant activities and free radical scavenging capacities. In this study, we investigate the effects of naringin, chlorogenic acid, and quercetin mixtures (NCQ) on renal fibrosis in streptozotocin (STZ)-induced diabetic aged rats and its underlying mechanisms for ten consecutive weeks. The oxidative defense system in the kidneys of treated rats was found to be improved. Several biomarkers were investigated including the blood urea nitrogen, creatinine, and uric acid. Moreover, antioxidant parameters were evaluated and we found that superoxide dismutase, catalase, glutathione peroxidase, Na+-K+-ATPase activities, the nitric oxide production, the protein carbonyl, the advanced oxidation protein products, lipid peroxidation, and reduced glutathione levels were all significantly balanced and close to control values. In addition, NCQ restored renal injuries and fibrosis as assessed by histological method and molecular biology investigation of the matrix metalloproteinase, the transforming growth factor-beta TGF-β, the tumor necrosis factor TNFα, and p53 expression. Our study proposes the NCQ combination as potential plant-derived bioactive compounds to prevent diabetic nephropathy.
Nutritional Support with Omega-3 Fatty Acids in Burn Patients: A Systematic Review with Meta-Analysis of Randomized Controlled Trials
Authors: Siritientong Tippawan , Thet Daylia , Buangbon Maneechat , Nokehoon Pawinee , Leelakanok Nattawut , Methaneethorn Janthima , Angspatt Apichai , Meevassana Jiraroch
Published: July 2022

Background: In burn patients, the profound effect of nutritional support on improved wound healing and a reduced rate of hospitalization and mortality has been documented. Fish oil as a primary source of omega-3 fatty acids in nutritional support may attenuate the inflammatory response and enhance immune function; however, unclear effects on the improvement of clinical outcomes in burn patients remain. Methods: The systematic literature review was conducted by searching the electronic databases: Cochrane Library, PubMed, ScienceDirect, and Scopus to assess the randomized controlled trials of nutritional support with omega-3 fatty acids compared to control diets in patients that presented with burns from any causes. Results: Seven trials were included in this meta-analysis. We found no significant differences in length of stay (LOS) (p = 0.59), mortality (p = 0.86), ventilation days (p = 0.16), gastrointestinal complications—e.g., constipation and diarrhea (p = 0.73)—or infectious complications—e.g., pneumonia and sepsis (p = 0.22)—between the omega-3-fatty-acid-receiving group and the control/other diets group. Conclusions: We did not find a benefit of omega-3 support in reducing the various complications, mortality and LOS in burn patients. Further studies are necessary to find the effect of nutritional support with omega-3 fatty acids over low-fat diets in this population.
High-Fat or High-Carbohydrate Meal—Does It Affect the Metabolism of Men with Excess Body Weight?
Authors: Ostrowska Lucyna , Smarkusz-Zarzecka Joanna , Muszyńska Anna , Adamska-Patruno Edyta , Górska Maria , Krętowski Adam
Published: July 2022

Excessive adipose tissue in the body may lead to adverse health effects, carbohydrate and lipid metabolism disorders, and cardiovascular diseases. The aim of this study was to analyze the effect of a standardized high-fat meal (HF) on changes in energy expenditure and changes in the oxidation of energy substrates as well as the concentration of glucose, insulin, triglycerides and homocysteine in blood serum in relation to a standardized high-carbohydrate (non-fat, HC) meal in men with different nutritional status. In this study, 26 men (aged 19–60) without carbohydrate disorders (study group GS = 13 overweight/obese; control group GC = 13 normal body weight) were examined. It was observed that following a high-fat or high-carbohydrate meal, men with excessive body weight metabolized the main nutrients differently than men with normal body weight, and postprandial insulin secretion was also different (even without any significant differences in glucose concentrations). Overweight/obesity, which is in itself a risk factor for cardiovascular disease, contributes to an increase in the concentration of other risk factors, such as the concentration of homocysteine and triglycerides, which is referred to as cardiometabolic risk. Consumption of a high-fat meal increased the number of potential risk factors for cardiovascular disease (homocysteine and triglycerides) compared to a high-carbohydrate meal.
Renoprotective Effect of Pediococcus acidilactici GKA4 on Cisplatin-Induced Acute Kidney Injury by Mitigating Inflammation and Oxidative Stress and Regulating the MAPK, AMPK/SIRT1/NF-κB, and PI3K/AKT Pathways
Authors: Lin Wen-Hsin , Jiang Wen-Ping , Chen Chin-Chu , Lee Li-Ya , Tsai You-Shan , Chien Liang-Hsuan , Chou Ya-Ni , Deng Jeng-Shyan , Huang Guan-Jhong
Published: July 2022

Acute kidney injury (AKI) describes a sudden loss of kidney function and is associated with a high mortality. Pediococcus acidilactici is a potent producer of bacteriocin and inhibits the growth of pathogens during fermentation and food storage; it has been used in the food industry for many years. In this study, the potential of P. acidilactici GKA4 (GKA4) to ameliorate AKI was investigated using a cisplatin-induced animal model. First, mice were given oral GKA4 for ten days and intraperitoneally injected with cisplatin on the seventh day to create an AKI mode. GKA4 attenuated renal histopathological alterations, serum biomarkers, the levels of inflammatory mediators, and lipid oxidation in cisplatin-induced nephrotoxicity. Moreover, GKA4 significantly decreased the expression of inflammation-related proteins and mitogen-activated protein kinase (MAPK) in kidney tissues. Eventually, GKA4 also increased the levels of related antioxidant enzymes and pathways. Consistently, sirtuin 1 (SIRT1) upregulated the level of autophagy-related proteins (LC3B, p62, and Beclin1). Further studies are needed to check our results and advance our knowledge of the mechanism whereby PI3K inhibition (wortmannin) reverses the effect of GKA4 on cisplatin-treated AKI. Taken together, GKA4 provides a therapeutic target with promising clinical potential after cisplatin treatment by reducing oxidative stress and inflammation via the MAPK, AMP-activated protein kinase (AMPK)/SIRT1/nuclear factor kappa B (NF-κB), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) axes.
Association between Early Life Famine Exposure and Metabolic Syndrome in Adulthood
Authors: Yao Fan , Zhao Liyun , Yang Yuxiang , Piao Wei , Fang Hongyun , Ju Lahong , Guo Qiya , Yu Dongmei
Published: July 2022

To analyze the relationship between famine exposure at different stages of early life and the risk of developing metabolic syndrome (MetS) in adulthood, 11,865 study participants from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance Program were enrolled and then divided into a non-exposed group, fetal exposure group, early childhood exposure group, middle childhood exposure group and late childhood exposure group according to their birth time and famine exposure. MetS was defined by the NCEP ATP III criteria. Using logistic regression to explore the association between famine exposure at different stages of early life and the increased risk of developing MetS in adulthood. After adjusting other factors, compared with the non-exposure group, famine exposure during the fetal period (OR = 1.23, 95% CI = 1.00–1.51), early childhood (OR = 1.44, 95% CI = 1.11–1.87), middle childhood (OR = 1.50, 95% CI = 1.13–1.99) and late childhood (OR = 1.67, 95% CI = 1.21–2.30) had a higher risk of developing MetS in adulthood. Stratified analysis found an association between early life famine exposure and the increased risk of MetS in adulthood in females, overweight or obese participants and those who lived in areas of severe famine, in city areas and in southern China. Compared with the non-exposed group, the fetal, early childhood, middle childhood and late childhood famine-exposed groups are more likely to suffer from MetS in adulthood, especially the subjects who are females, overweight or obese and had lived in severe famine areas, city areas and southern China.
Aspects of Antiviral Strategies Based on Different Phototherapy Approaches: Hit by the Light
Authors: Kunstek Hannah , Vreken Fanny , Keita Aminata , Hamblin Michael R. , Dumarçay Florence , Varbanov Mihayl
Published: July 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which caused the COVID-19 pandemic spreading around the world from late 2019, served as a ruthless reminder of the threat viruses pose to global public health. The synthesis of new antiviral drugs, as well as repurposing existing products, is a long-term ongoing process which has challenged the scientific community. One solution could be an effective, accessible, and rapidly available antiviral treatment based on phototherapy (PT). PT has been used to treat several diseases, and relies on the absorption of light by endogenous molecules or exogenous photosensitizers (PS). PT has often been used in cancer treatment and prophylaxis, and as a complement to established chemotherapy and immunotherapy in combined therapeutic strategy. Besides significant applications in anticancer treatment, studies have demonstrated the beneficial impact of PT on respiratory, systemic, emerging, and oncogenic viral infections. The aim of this review was to highlight the potential of PT to combat viral infections by summarizing current progress in photodynamic, photothermal, and photoacoustic approaches. Attention is drawn to the virucidal effect of PT on systemic viruses such as the human immunodeficiency virus and human herpes viruses, including the causative agent of Kaposi sarcoma, human herpes virus (HHV8). PT has good potential for disinfection in anti-norovirus research and against pandemic viruses like SARS-CoV-2.
Predictiveness of the Human-CYP3A4-Transgenic Mouse Model (Cyp3aXAV) for Human Drug Exposure of CYP3A4-Metabolized Drugs
Authors: Damoiseaux David , Li Wenlong , Martínez-Chávez Alejandra , Beijnen Jos H. , Schinkel Alfred H. , Huitema Alwin D. R. , Dorlo Thomas P. C.
Published: July 2022

The extrapolation of drug exposure between species remains a challenging step in drug development, contributing to the low success rate of drug approval. As a consequence, extrapolation of toxicology from animal models to humans to evaluate safe, first-in-human (FIH) doses requires high safety margins. We hypothesized that a human-CYP3A4-expressing transgenic (Cyp3aXAV) mouse is a more predictive model for human drug exposure of CYP3A4-metabolized small-molecule drugs. Population pharmacokinetic models based on wild-type (WT) and Cyp3aXAV mouse pharmacokinetic data of oral lorlatinib, brigatinib, ribociclib and fisogatinib were allometrically scaled and compared to human exposure. Extrapolation of the Cyp3aXAV mouse model closely predicted the observed human exposure for lorlatinib and brigatinib with a 1.1-fold and 1.0-fold difference, respectively, compared to a 2.1-fold and 1.9-fold deviation for WT-based extrapolations of lorlatinib and brigatinib, respectively. For ribociclib, the extrapolated WT mouse model gave better predictions with a 1.0-fold deviation compared to a 0.3-fold deviation for the extrapolated Cyp3aXAV mouse model. Due to the lack of a human population pharmacokinetic model for fisogatinib, only median maximum concentration ratios were calculated, resulting in ratios of 1.0 and 0.6 for WT and Cyp3aXAV mice extrapolations, respectively. The more accurate predictions of human exposure in preclinical research based on the Cyp3aXAV mouse model can ultimately result in FIH doses associated with improved safety and efficacy and in higher success rates in drug development.