bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Synthetic Jet Flow Control Technique for Modulating Turbulent Jet Noise
Authors: Murillo-Rincón Jairo , Duque-Daza Carlos
Published: March 2023

The use of a synthetic jet as the flow control technique to modulate a turbulent incompressible round jet was explored and assessed by numerical simulations. The flow response was characterised in terms of turbulent statistics and acoustic response in the far-field. A quasi-Direct Numerical Simulation (qDNS) strategy was used to predict the turbulent effects. The Ffowcs-Williams and Hawkings (FWH) acoustic analogy was employed to compute the far-field acoustic response. An amplification effect of the instabilities induced by the control jet was observed for some of the parameters explored. It was observed that the control technique allows controlling the axial distribution of the production and dissipation of turbulent kinetic energy, but with respect to the acoustic aspects, the appearance of a greater number of noise sources was observed, which in the far-field, resulted in an increase from 1 to 20 dB of the equivalent noise for the different operating parameters of the control technique studied.
An Underutilized Food “Miwu”: Diet History, Nutritional Evaluations, and Countermeasures for Industrial Development
Authors: Zou Jinpeng , Wang Jiayi , Hou Kai , Wang Fang , Su Shiwen , Xue Wenjing , Wu Wei , Yang Ni , Du Xuan
Published: March 2023

About 10 major crops basically feed the world. In fact, there are still a large number of plants that have not been fully explored and utilized because they have been ignored by the market and research. The expansion of food sources in various countries plays an important role in maintaining food security and nutrition security in the world. Miwu is the aerial part of the medicinal plant Rhizoma Chuanxiong belonging to a traditional local characteristic food raw material. Its edible value is still little known. Through textual research, component determination, literature survey, field research, and SWOT analysis, this paper has a comprehensive understanding of Miwu’s diet history, chemical components, safety risks, and industrial development status. It is found that Miwu has been eaten for 800 years, is rich in nutrients and active ingredients, and has no acute toxicity. In addition, the current industrial development of Miwu has significant advantages and many challenges. To sum up, Miwu is a potentially underutilized food raw material. This paper also provides countermeasures for the industrialized development of Miwu, which will provide a milestone reference for the future utilization and development of Miwu.
Effect of Heating under Different Vacuum Levels on Physicochemical and Oxidative Properties of Beef Sirloin
Authors: Kim Ah-Na , Lee Kyo-Yeon , Park Chae Eun , Choi Sung-Gil
Published: March 2023

The physicochemical and oxidative properties of beef sirloin slices heated under atmospheric (101.33 kPa, a vacuum percent of 0%, control) and vacuum (50.8 kPa, 50% and 7.2 Pa, 99.99%) conditions by using an airtight vacuum container were compared. Heating at a higher vacuum level resulted in the lowest pH and cooking loss compared with the other conditions (p < 0.05). The beef in vacuum groups was less hard, chewy, and gummy than the control group, without any significant differences between the vacuum groups. More structural shrinkage and lower browning were observed in the meat heated at higher vacuum levels. Similarly, higher vacuum levels suppressed increases in the lightness (L*), redness (a*), and total color difference (E*) of the surface after heating. The thiobarbituric acid (TBA) values, a sensitive indicator of meat oxidation due to heating, were only influenced by the vacuum conditions. Consequently, applying a vacuum effectively prevents the degradation in the meat’s physicochemical and oxidative properties during heating. The findings are useful for the sous-vide industry because they scientifically demonstrate how vacuum pressure affects the physicochemical and oxidative properties of the meat by using a specially designed airtight vacuum container.
Prevention of Fungal Contamination in Semi-Hard Cheeses by Whey–Gelatin Film Incorporated with Levilactobacillus brevis SJC120
Authors: Silva Sofia P. M. , Teixeira José A. , Silva Célia C. G.
Published: March 2023

Cheese whey fermented by lactic acid bacteria (LAB) was used to develop an edible film with antifungal properties. Five LAB strains isolated from artisanal cheeses were screened for antifungal activity and incorporated into a whey–gelatin film. Of the strains tested, Levilactobacillus brevis SJC120 showed the strongest activity against five filamentous fungi isolated from cheese and cheese-making environment, at both 10 °C and 20 °C. The cell-free supernatant from L. brevis inhibited fungal growth by more than 80%. Incorporation of bacterial cells into the film did not alter the moisture content, water vapor permeability, or mechanical and optical properties. The whey–gelatin film was also able to maintain the viability of L. brevis cells at 107 log CFU/g after 30 days at 10 °C. In cheeses wrapped with L. brevis film, the size of fungal colonies decreased by 55% to 76%. Furthermore, no significant differences (p > 0.05) were observed in cheese proteolysis or in the moisture, fat, and protein content of the cheese wrapped with films. The results showed that whey–gelatin film with L. brevis SJC120 can reduce the contamination of cheese with filamentous fungi and could be used as an alternative to conventional cheese preservation and packaging.
Metabolomic Characteristics of Cecum Contents in High-Fat-Diet-Induced Obese Mice Intervened with Different Fibers
Authors: Zhang Qian , Cheng Jinhua , Jiang Xiaole , Tang Junni , Zhu Chenglin , Chen Hong , Laghi Luca
Published: March 2023

The aim of this study was to demonstrate the effect of single or mixed fibers (arabinoxylan, β-glucan, xyloglucan, and inulin) on the metabolome of cecum content in mice with obesity caused by a high-fat diet. Twenty-eight six-week-old male mice were divided randomly into seven groups (n = 4/group), including a normal-diet group (CON), a high-fat-diet group (HFD), and groups with the same high-fat diet but supplemented with arabinoxylan (HFAX), arabinoxylan + β-glucan (HFAβ), arabinoxylan + xyloglucan (HFAG), xyloglucan (HFXG), and xyloglucan + inulin (HFXI). A total of 66 molecules were identified and quantified in cecum content by proton nuclear magnetic resonance (1 H-NMR). The metabolomic profiles combined with statistical analysis revealed compounds distinguishing the control group from those supplemented with fibers. In detail, a high-fat diet could significantly elevate the concentrations of acetone and methionine (p < 0.05) while decreasing the levels of methanol, arabinose, acetate, and 3-hydroxyphenylacetate (p < 0.05) in the cecum contents of mice. Compared to HFD, the supplementation caused higher levels of fumarate and hypoxanthine (p < 0.05) and lower levels of phenylacetate, acetate, fucose, formate, proline, betaine, and trimethylamine N-oxide (TMAO) (p < 0.05). An enrichment analysis highlighted that the pathways mainly altered were amino sugar metabolism, aspartate metabolism, and arginine and proline metabolism. In conclusion, non-starch polysaccharide (NSP) supplementation could change the metabolomic profiles of cecum contents in obese mice as a result of a high-fat diet. Moreover, mixed NSPs exhibited more beneficial effects than singular form on gut metabolism.
The Mechanism Underlying the Amylose-Zein Complexation Process and the Stability of the Molecular Conformation of Amylose-Zein Complexes in Water Based on Molecular Dynamics Simulation
Authors: Wang Chaofan , Ji Na , Dai Lei , Qin Yang , Shi Rui , Xiong Liu , Sun Qingjie
Published: March 2023

The aim of this study was to employ molecular dynamics simulations to elucidate the mechanism involved in amylose–zein complexation and the stability of the molecular conformation of amylose–zein complexes in water at the atomic and molecular levels. The average root mean square deviation and radius of gyration were lower for amylose–zein complexes (1.11 nm and 1 nm, respectively) than for amylose (2.13 nm and 1.2 nm, respectively), suggesting a significantly higher conformational stability for amylose–zein complexes than for amylose in water. The results of radial distribution function, solvent-accessible surface area, and intramolecular and intermolecular hydrogen bonds revealed that the amylose–zein interaction inhibited water permeation into the amylose cavity, leading to enhanced conformational stabilities of the V-type helical structure of amylose and the amylose–zein complexes. Furthermore, the amylose in amylose–zein complexes displayed the thermodynamically stable 4C1 conformation. These findings can provide theoretical guidance in terms of the application of protein on starch processing aiming to improve the physicochemical and functional properties of starch (such as swelling capacity, pasting properties, and digestibility) for developing novel low-digestibility starch–protein products.
Behaviour of Escherichia coli O157:H7 and Listeria monocytogenes in Normal and DFD Beef of an Autochthonous Portuguese Breed
Authors: Saraiva Cristina , Saraiva Sónia , Patarata Luis , da Conceição Fontes Maria , Martins Conceição
Published: March 2023

This study was carried out to identify the behaviour of Escherichia coli O157:H7 and of Listeria monocytogenes inoculated in Maronesa breed beef with different ultimate pH (pHu) (Normal and DFD), and stored at two different temperatures (4 and 9 °C), during 28 days post mortem (pm). The main objective was to illustrate the problematic feature of dealing with beef showing high pHu and stored at mild abusive temperatures (9 °C). Beef steaks (ms. longissimus dorsi) were inoculated with low levels (2–3 log CFU/g) of those both pathogens and packed in air, vacuum and three gaseous mixtures with decreasing O2 and increasing CO2 concentrations (MAP70/20, MAP50/40 and MAP30/60). At 4 °C, the growth of E. coli O157:H7 presented the same pattern on Normal and DFD meat. On the contrary, the growth of L. monocytogenes was higher in DFD meat, revealing the effect of the pHu and its psychotropic character. At abusive temperatures, both pathogens grew, achieving high levels in DFD meat. In these cases, the MAP with the highest CO2 concentration (60%) was revealed to be more effective against the development of E. coli O157:H7, therefore, not exceeding levels of 5 log CFU/g at the end of storage, while in L. monocytogenes, it reaches 8 log CFU/g under the same conditions.
Exploring the Role of Infodemics in People’s Incompliance with Preventive Measures during the COVID-19 in Conflict Settings (Mixed Method Study)
Authors: Al-Aghbari Ahmed Asa’ad , Hassan Ola El Hajj , Dar Iang Maureen , Jahn Albrecht , Horstick Olaf , Dureab Fekri
Published: March 2023

The evolving availability of health information on social media, regardless of its credibility, raises several questions about its impact on our health decisions and social behaviors, especially during health crises and in conflict settings where compliance with preventive measures and health guidelines is already a challenge due to socioeconomic factors. For these reasons, we assessed compliance with preventive measures and investigated the role of infodemic in people’s non-compliance with COVID-19 containment measures in Yemen. To this purpose and to triangulate our data collection, we executed a mixed method approach in which raw aggregated data were taken and analyzed from multiple sources (COVID-19 Government Response Tracker and Google COVID-19 Community Mobility Reports), then complemented and verified with In-depth interviews. Our results showed that the population in Yemen had relatively complied with the governmental containment measures at the beginning of the pandemic. However, containment measures were not supported by daily COVID-19 reports due to low transparency, which, together with misinformation and lack of access to reliable sources, has caused the population not to believe in COVID-19 and even practice social pressure on those who showed some compliance with the WHO guidelines. Those results indicate the importance of adopting an infodemic management approach in response to future outbreaks, particularly in conflict settings.
Back Pain: Pathophysiology, Diagnosis, and Treatment
Authors: Vanaclocha Vicente
Published: March 2023

Although back pain is one of the most common medical conditions [...]
An Optimised Region-Growing Algorithm for Extraction of the Loess Shoulder-Line from DEMs
Authors: Liu Zihan , Zhang Hongming , Dong Liang , Sun Zhitong , Wu Shufang , Zhang Biao , Yuan Linlin , Wang Zhenfei , Jia Qimeng
Published: March 2023

The positive and negative terrains (P–N terrains) of the Loess Plateau of China are important geographical topography elements for measuring the degree of surface erosion and distinguishing the types of landforms. Loess shoulder-lines are an important terrain feature in the Loess Plateau and are often used as a criterion for distinguishing P–N terrains. The extraction of shoulder lines is important for predicting erosion and recognising a gully head. However, existing extraction algorithms for loess shoulder-lines in areas with insignificant slopes need to be improved. This study proposes a regional fusion (RF) method that integrates the slope variation-based method and region-growing algorithm to extract loess shoulder-lines based on a Digital Elevation Model (DEM) at a spatial resolution of 5 m. The RF method introduces different terrain factors into the growth standards of the region-growing algorithm to extract loess-shoulder lines. First, we employed a slope-variation-based method to build the initial set of loess shoulder-lines and used the difference between the smoothed and real DEMs to extract the initial set for the N terrain. Second, the region-growing algorithm with improved growth standards was used to generate a complete area of the candidate region of the loess shoulder-lines and the N terrain, which were fused to generate and integrate contours to eliminate the discontinuity. Finally, loess shoulder-lines were identified by detecting the edge of the integrated contour, with results exhibiting congregate points or spurs, eliminated via a hit-or-miss transform to optimise the final results. Validation of the experimental area of loess ridges and hills in Shaanxi Province showed that the accuracy of the RF method based on the Euclidean distance offset percentage within a 10-m deviation range reached 96.9% compared to the manual digitalisation method. Based on the mean absolute error and standard absolute deviation values, compared with Zhou’s improved snake model and the bidirectional DEM relief-shading methods, the proposed RF method extracted the loess shoulder-lines highly accurately.
Systematic Review and Meta-Analysis of the Impact of Bariatric Surgery on Future Cancer Risk
Authors: Wilson Robert B. , Lathigara Dhruvi , Kaushal Devesh
Published: March 2023

The study aimed to perform a systematic review and meta-analysis of the evidence for the prevention of future cancers following bariatric surgery. A systematic literature search of the Cochrane Library, Embase, Scopus, Web of Science and PubMed databases (2007–2023), Google Scholar and grey literature was conducted. A meta-analysis was performed using the inverse variance method and random effects model. Thirty-two studies involving patients with obesity who received bariatric surgery and control patients who were managed with conventional treatment were included. The meta-analysis suggested bariatric surgery was associated with a reduced overall incidence of cancer (RR 0.62, 95% CI 0.46–0.84, p < 0.002), obesity-related cancer (RR 0.59, 95% CI 0.39–0.90, p = 0.01) and cancer-associated mortality (RR 0.51, 95% CI 0.42–0.62, p < 0.00001). In specific cancers, bariatric surgery was associated with reduction in the future incidence of hepatocellular carcinoma (RR 0.35, 95% CI 0.22–0.55, p < 0.00001), colorectal cancer (RR 0.63, CI 0.50–0.81, p = 0.0002), pancreatic cancer (RR 0.52, 95% CI 0.29–0.93, p = 0.03) and gallbladder cancer (RR 0.41, 95% CI 0.18–0.96, p = 0.04), as well as female specific cancers, including breast cancer (RR 0.56, 95% CI 0.44–0.71, p < 0.00001), endometrial cancer (RR 0.38, 95% CI 0.26–0.55, p < 0.00001) and ovarian cancer (RR 0.45, 95% CI 0.31–0.64, p < 0.0001). There was no significant reduction in the incidence of oesophageal, gastric, thyroid, kidney, prostate cancer or multiple myeloma after bariatric surgery as compared to patients with morbid obesity who did not have bariatric surgery. Obesity-associated carcinogenesis is closely related to metabolic syndrome; visceral adipose dysfunction; aromatase activity and detrimental cytokine, adipokine and exosomal miRNA release. Bariatric surgery results in long-term weight loss in morbidly obese patients and improves metabolic syndrome. Bariatric surgery may decrease future overall cancer incidence and mortality, including the incidence of seven obesity-related cancers.
Uptake of Tropheryma whipplei by Intestinal Epithelia
Authors: Friebel Julian , Schinnerling Katina , Weigt Kathleen , Heldt Claudia , Fromm Anja , Bojarski Christian , Siegmund Britta , Epple Hans-Jörg , Kikhney Judith , Moter Annette , Schneider Thomas , Schulzke Jörg D. , Moos Verena , Schumann Michael
Published: March 2023

Background: Tropheryma whipplei (TW) can cause different pathologies, e.g., Whipple’s disease and transient gastroenteritis. The mechanism by which the bacteria pass the intestinal epithelial barrier, and the mechanism of TW-induced gastroenteritis are currently unknown. Methods: Using ex vivo disease models comprising human duodenal mucosa exposed to TW in Ussing chambers, various intestinal epithelial cell (IEC) cultures exposed to TW and a macrophage/IEC coculture model served to characterize endocytic uptake mechanisms and barrier function. Results: TW exposed ex vivo to human small intestinal mucosae is capable of autonomously entering IECs, thereby invading the mucosa. Using dominant-negative mutants, TW uptake was shown to be dynamin- and caveolin-dependent but independent of clathrin-mediated endocytosis. Complementary inhibitor experiments suggested a role for the activation of the Ras/Rac1 pathway and actin polymerization. TW-invaded IECs underwent apoptosis, thereby causing an epithelial barrier defect, and were subsequently subject to phagocytosis by macrophages. Conclusions: TW enters epithelia via an actin-, dynamin-, caveolin-, and Ras-Rac1-dependent endocytosis mechanism and consecutively causes IEC apoptosis primarily in IECs invaded by multiple TW bacteria. This results in a barrier leak. Moreover, we propose that TW-packed IECs can be subject to phagocytic uptake by macrophages, thereby opening a potential entry point of TW into intestinal macrophages.
Histological and Histomorphometric Evaluation of Implanted Photodynamic Active Biomaterials for Periodontal Bone Regeneration in an Animal Study
Authors: Sigusch Bernd , Kranz Stefan , von Hohenberg Andreas Clemm , Wehle Sabine , Guellmar André , Steen Dorika , Berg Albrecht , Rabe Ute , Heyder Markus , Reise Markus
Published: March 2023

Recently, our group developed two different polymeric biomaterials with photodynamic antimicrobial surface activity for periodontal bone regeneration. The aim of the present study was to analyze the biocompatibility and osseointegration of these materials in vivo. Two biomaterials based on urethane dimethacrylate (BioM1) and tri-armed oligoester-urethane methacrylate (BioM2) that additionally contained ß-tricalcium phosphate and the photosensitizer mTHPC (meso-tetra(hydroxyphenyl)chlorin) were implanted in non-critical size bone defects in the femur (n = 16) and tibia (n = 8) of eight female domestic sheep. Bone specimens were harvested and histomorphometrically analyzed after 12 months. BioM1 degraded to a lower extent which resulted in a mean remnant square size of 17.4 mm², while 12.2 mm² was estimated for BioM2 (p = 0.007). For BioM1, a total percentage of new formed bone by 30.3% was found which was significant higher compared to BioM2 (8.4%, p < 0.001). Furthermore, BioM1 was afflicted by significant lower soft tissue formation (3.3%) as compared to BioM2 (29.5%). Additionally, a bone-to-biomaterial ratio of 81.9% was detected for BioM1, while 8.5% was recorded for BioM2. Implantation of BioM2 caused accumulation of inflammatory cells and led to fibrous encapsulation. BioM1 (photosensitizer-armed urethane dimethacrylate) showed favorable regenerative characteristics and can be recommended for further studies.
Activation of TRPV1-Expressing Renal Sensory Nerves of Rats with N-Oleoyldopamine Attenuates High-Fat-Diet-Induced Impairment of Renal Function
Authors: Yu Shuang-Quan , Ma Shuangtao , Wang Donna H.
Published: March 2023

Enhanced renal sympathetic nerve activity (RSNA) contributes to obesity-induced renal disease, while the role of afferent renal nerve activity (ARNA) is not fully understood. The present study tested the hypothesis that activating the transient receptor potential vanilloid 1 (TRPV1) channel in afferent renal nerves suppresses RSNA and prevents renal dysfunction and hypertension in obese rats. N-oleoyldopamine (OLDA, 1 ng/kg, daily) was administrated intrathecally (T8-L3) via an indwelled catheter to chronically activate, TRPV1-positive afferent renal nerves in rats fed a chow diet or high-fat diet (HFD) for 8 weeks. HFD intake significantly increased the body weight, impaired glucose and insulin tolerance, decreased creatinine clearance, and elevated systolic blood pressure in rats compared with the levels of the chow-fed rats (all p < 0.05). An intrathecal OLDA treatment for 8 weeks did not affect the fasting glucose level, glucose tolerance, and insulin tolerance in rats fed either chow or HFD. As expected, the chronic OLDA treatment significantly increased the levels of plasma calcitonin gene-related peptide and substance P and ARNA in the HFD-fed rats (all p < 0.05). Interestingly, the OLDA treatment decreased the urinary norepinephrine level and RSNA in rats fed HFD (both p < 0.05). Importantly, the OLDA treatment attenuated HFD-induced decreases in creatinine clearance and urinary Na+ excretion and increases in the plasma urea level, urinary albumin level, and systolic blood pressure at the end of an 8-week treatment (all p < 0.05). Taken together, the intrathecal administration of OLDA ameliorates the enhancement of RSNA, renal dysfunction, and hypertension in obese rats. These findings shed light on the roles of TRPV1-positive renal afferent nerves in obesity-related renal dysfunction and hypertension.
Metabolite Profiling of the Gut–Renal–Cerebral Axis Reveals a Particular Pattern in Early Diabetic Kidney Disease in T2DM Patients
Authors: Balint Lavinia , Socaciu Carmen , Socaciu Andreea Iulia , Vlad Adrian , Gadalean Florica , Bob Flaviu , Milas Oana , Cretu Octavian Marius , Suteanu-Simulescu Anca , Glavan Mihaela , Ienciu Silvia , Mogos Maria , Jianu Dragos Catalin , Petrica Ligia
Published: March 2023

Type 2 diabetes mellitus (T2DM) represents an important microvascular disease concerning the kidney and the brain. Gut dysbiosis and microbiota-derived metabolites may be in relation with early pathophysiological changes in diabetic kidney disease (DKD). The aim of the study was to find new potential gut-derived biomarkers involved in the pathogenesis of early DKD, with a focus on the complex interconnection of these biomarkers with podocyte injury, proximal tubule dysfunction, renal and cerebrovascular endothelial dysfunction. The study design consisted of metabolite profiling of serum and urine of 90 T2DM patients (subgroups P1-normoalbuminuria, P2-microalbuminuria, P3-macroalbuminuria) and 20 healthy controls (group C), based on ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry analysis (UHPLC-QTOF-ESI+-MS). By multivariate and univariate analyses of serum and urine, which included Partial Least Squares Discriminant Analysis (PLSDA), Variable Importance Plots (VIP), Random Forest scores, One Way ANOVA and Biomarker analysis, there were discovered metabolites belonging to nitrogen metabolic pathway and retinoic acid signaling pathway which differentiate P1 group from P2, P3, C groups. Tyrosine, phenylalanine, indoxyl sulfate, serotonin sulfate, and all-trans retinoic acid express the metabolic fingerprint of P1 group vs. P2, P3, C groups, revealing a particular pattern in early DKD in T2DM patients.
Molecular Mechanism of Chronic Viral and Non-Viral Liver Diseases
Authors: Kanda Tatsuo
Published: March 2023

In this Special Issue, “Molecular Mechanism of Chronic Viral and Non-viral Liver Diseases”, invaluable articles have been published [...]
Enzymatic Synthesis of 2-Chloropurine Arabinonucleosides with Chiral Amino Acid Amides at the C6 Position and an Evaluation of Antiproliferative Activity In Vitro
Authors: Eletskaya Barbara Z. , Berzina Maria Ya. , Fateev Ilya V. , Kayushin Alexei L. , Dorofeeva Elena V. , Lutonina Olga I. , Zorina Ekaterina A. , Antonov Konstantin V. , Paramonov Alexander S. , Muzyka Inessa S. , Zhukova Olga S. , Kiselevskiy Mikhail V. , Miroshnikov Anatoly I. , Esipov Roman S. , Konstantinova Irina D.
Published: March 2023

A number of purine arabinosides containing chiral amino acid amides at the C6 position of the purine were synthesized using a transglycosylation reaction with recombinant E. coli nucleoside phosphorylases. Arsenolysis of 2-chloropurine ribosides with chiral amino acid amides at C6 was used for the enzymatic synthesis, and the reaction equilibrium shifted towards the synthesis of arabinonucleosides. The synthesized nucleosides were shown to be resistant to the action of E. coli adenosine deaminase. The antiproliferative activity of the synthesized nucleosides was studied on human acute myeloid leukemia cell line U937. Among all the compounds, the serine derivative exhibited an activity level (IC50 = 16 μM) close to that of Nelarabine (IC50 = 3 μM) and was evaluated as active.
Association between Hepatocellular Carcinoma Recurrence and Graft Size in Living Donor Liver Transplantation: A Systematic Review
Authors: Parente Alessandro , Cho Hwui-Dong , Kim Ki-Hun , Schlegel Andrea
Published: March 2023

The aim of this work was to assess the association between graft-to-recipient weight ratio (GRWR) in adult-to-adult living donor liver transplantation (LDLT) and hepatocellular carcinoma (HCC) recurrence. A search of the MEDLINE and EMBASE databases was performed until December 2022 for studies comparing different GRWRs in the prognosis of HCC recipients in LDLT. Data were pooled to evaluate 1- and 3-year survival rates. We identified three studies, including a total of 782 patients (168 GRWR < 0.8 vs. 614 GRWR ≥ 0.8%). The pooled overall survival was 85% and 77% at one year and 90% and 83% at three years for GRWR < 0.8 and GRWR ≥ 0.8, respectively. The largest series found that, in patients within Milan criteria, the GRWR was not associated with lower oncological outcomes. However, patients with HCC outside the Milan criteria with a GRWR < 0.8% had lower survival and higher tumor recurrence rates. The GRWR < 0.8% appears to be associated with lower survival rates in HCC recipients, particularly for candidates with tumors outside established HCC criteria. Although the data are scarce, the results of this study suggest that considering the individual GRWR not only as risk factor for small-for-size-syndrome but also as contributor to HCC recurrence in patients undergoing LDLT would be beneficial. Novel perfusion technologies and pharmacological interventions may contribute to improving outcomes.
On the Utmost Importance of the Basis Set Choice for the Calculations of the Relativistic Corrections to NMR Shielding Constants
Authors: Rusakova Irina L. , Rusakov Yuriy Yu.
Published: March 2023

The investigation of the sensitivity of the relativistic corrections to the NMR shielding constants (σ) to the configuration of angular spaces of the basis sets used on the atoms of interest was carried out within the four-component density functional theory (DFT). Both types of relativistic effects were considered, namely the so-called heavy atom on light atom and heavy atom on heavy atom effects, though the main attention was paid to the former. As a main result, it was found that the dependence of the relativistic corrections to σ of light nuclei (exemplified here by 1H and 13C) located in close vicinity to a heavy atom (exemplified here by In, Sn, Sb, Te, and I) on the basis set used on the light spectator atom was very much in common with that of the Fermi-contact contribution to the corresponding nonrelativistic spin-spin coupling constant (J). In general, it has been shown that the nonrelativistic J-oriented and σ-oriented basis sets, artificially saturated in the tight s-region, provided much better accuracy than the standard nonrelativistic σ-oriented basis sets when calculating the relativistic corrections to the NMR shielding constants of light nuclei at the relativistic four-component level of the DFT theory.
An Acidic Heteropolysaccharide Isolated from Pueraria lobata and Its Bioactivities
Authors: Zhao Shifan , Xue Hualei , Tao Yijiong , Chen Kai , Li Xiao , Wang Mi
Published: March 2023

A novel water-soluble acidic heteropolysaccharide, called PPL-1, was purified from Pueraria lobata. PPL-1 had an average molecular weight of 35 Kad, and it was composed of glucose, arabinose, galactose and galacturonic acid (6.3:0.8:0.8:2.1). In accordance with methylation and nuclear magnetic resonance analyses, PPL-1 primarily consisted of (1→2)-linked α-Araf, (1→4)-linked α-Glcp, (1→)-linked β-Glcp, (1→6)-linked α-Glcp, (1→3,6)-linked α-Galp, (1→)-linked β-GalpA and (1→4)-linked α-GalpA. In terms of bioactivities, PPL-1 exhibited remarkable scavenging ability towards DPPH (1,1-Diphenyl-2-picrylhydrazyl) radicals and moderate activity by enhancing the proliferation rate of RAW 264.7 cells by approximately 30% along with the secretion of NO. This work demonstrates that PPL-1 can be a potential source of immunoenhancers and antioxidants.
Sigma-2 Receptors—From Basic Biology to Therapeutic Target: A Focus on Age-Related Degenerative Diseases
Authors: Lizama Britney N. , Kahle Jennifer , Catalano Susan M. , Caggiano Anthony O. , Grundman Michael , Hamby Mary E.
Published: March 2023

There is a large unmet medical need to develop disease-modifying treatment options for individuals with age-related degenerative diseases of the central nervous system. The sigma-2 receptor (S2R), encoded by TMEM97, is expressed in brain and retinal cells, and regulates cell functions via its co-receptor progesterone receptor membrane component 1 (PGRMC1), and through other protein–protein interactions. Studies describing functions of S2R involve the manipulation of expression or pharmacological modulation using exogenous small-molecule ligands. These studies demonstrate that S2R modulates key pathways involved in age-related diseases including autophagy, trafficking, oxidative stress, and amyloid-β and α-synuclein toxicity. Furthermore, S2R modulation can ameliorate functional deficits in cell-based and animal models of disease. This review summarizes the current evidence-based understanding of S2R biology and function, and its potential as a therapeutic target for age-related degenerative diseases of the central nervous system, including Alzheimer’s disease, α-synucleinopathies, and dry age-related macular degeneration.
A Novel Multi-Observation System to Study the Effects of Anterior Ocular Inflammation in Zinn’s Zonule Using One Specimen
Authors: Takahashi Akira , Arima Takeshi , Toda Etsuko , Kobayakawa Shinichiro , Shimizu Akira , Takahashi Hiroshi
Published: March 2023

Zinn’s zonule is a fragile and thin tissue, and little is known about its pathogenesis. The aim of this study was to develop an experimental setup for a comprehensive analysis of Zinn’s zonule. Rats were divided into two groups: a control group (n = 4) and an alkali injury group (n = 4). Seven days after injury, the eyes were enucleated, the anterior eye was dissected and embedded in gelatin, and macroscopic observations were made. The gelatin specimens were then embedded in paraffin and observed in detail by low-vacuum scanning electron microscopy, immunofluorescence, and quantitative reverse transcription polymerase chain reaction (RT-qPCR). The results show qualitative changes in Zinn’s zonules in both macroscopic and microscopic observations. In addition, macrophage infiltration and increased matrix metalloproteinase 2 (MMP2) expression were observed in the injured group, consistent with the RT-qPCR results. The experimental system in this study allowed us to capture the morphological and molecular biological changes of Zinn’s zonule and to gain insight into its pathogenesis. In conclusion, this study presents a new experimental setup for the comprehensive analysis of the rat Zinn’s zonule. The results suggest that this system can be used in the future to study and analyze a variety of paraffin-embedded tissues and specimens.
NUSAP1 Binds ILF2 to Modulate R-Loop Accumulation and DNA Damage in Prostate Cancer
Authors: Chiu Chun-Lung , Li Caiyun G. , Verschueren Erik , Wen Ru M. , Zhang Dalin , Gordon Catherine A. , Zhao Hongjuan , Giaccia Amato J. , Brooks James D.
Published: March 2023

Increased expression of NUSAP1 has been identified as a robust prognostic biomarker in prostate cancer and other malignancies. We have previously shown that NUSAP1 is positively regulated by E2F1 and promotes cancer invasion and metastasis. To further understand the biological function of NUSAP1, we used affinity purification and mass spectrometry proteomic analysis to identify NUSAP1 interactors. We identified 85 unique proteins in the NUSAP1 interactome, including ILF2, DHX9, and other RNA-binding proteins. Using proteomic approaches, we uncovered a function for NUSAP1 in maintaining R-loops and in DNA damage response through its interaction with ILF2. Co-immunoprecipitation and colocalization using confocal microscopy verified the interactions of NUSAP1 with ILF2 and DHX9, and RNA/DNA hybrids. We showed that the microtubule and charged helical domains of NUSAP1 were necessary for the protein-protein interactions. Depletion of ILF2 alone further increased camptothecin-induced R-loop accumulation and DNA damage, and NUSAP1 depletion abolished this effect. In human prostate adenocarcinoma, NUSAP1 and ILF2 mRNA expression levels are positively correlated, elevated, and associated with poor clinical outcomes. Our study identifies a novel role for NUSAP1 in regulating R-loop formation and accumulation in response to DNA damage through its interactions with ILF2 and hence provides a potential therapeutic target.
Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro
Authors: Navarrete-Meneses María del Pilar , Salas-Labadía Consuelo , Juárez-Velázquez María del Rocío , Moreno-Lorenzana Dafné , Gómez-Chávez Fernando , Olaya-Vargas Alberto , Pérez-Vera Patricia
Published: March 2023

The evidence supporting the biological plausibility of the association of permethrin and malathion with hematological cancer is limited and contradictory; thus, further studies are needed. This study aimed to investigate whether in vitro exposure to 0.1 μM permethrin and malathion at 0, 24, 48 and 72 h after cell culture initiation induced changes in the gene expression and DNA methylation in mononuclear cells from bone marrow and peripheral blood (BMMCs, PBMCs). Both pesticides induced several gene expression modifications in both tissues. Through gene ontology analysis, we found that permethrin deregulates ion channels in PBMCs and BMMCs and that malathion alters genes coding proteins with nucleic acid binding capacity, which was also observed in PBMCs exposed to permethrin. Additionally, we found that both insecticides deregulate genes coding proteins with chemotaxis functions, ion channels, and cytokines. Several genes deregulated in this study are potentially associated with cancer onset and development, and some of them have been reported to be deregulated in hematological cancer. We found that permethrin does not induce DNA hypermethylation but can induce hypomethylation, and that malathion generated both types of events. Our results suggest that these pesticides have the potential to modify gene expression through changes in promoter DNA methylation and potentially through other mechanisms that should be investigated.
Current Bioinformatics Tools to Optimize CRISPR/Cas9 Experiments to Reduce Off-Target Effects
Authors: Naeem Muhammad , Alkhnbashi Omer S.
Published: March 2023

The CRISPR-Cas system has evolved into a cutting-edge technology that has transformed the field of biological sciences through precise genetic manipulation. CRISPR/Cas9 nuclease is evolving into a revolutionizing method to edit any gene of any species with desirable outcomes. The swift advancement of CRISPR-Cas technology is reflected in an ever-expanding ecosystem of bioinformatics tools designed to make CRISPR/Cas9 experiments easier. To assist researchers with efficient guide RNA designs with fewer off-target effects, nuclease target site selection, and experimental validation, bioinformaticians have built and developed a comprehensive set of tools. In this article, we will review the various computational tools available for the assessment of off-target effects, as well as the quantification of nuclease activity and specificity, including web-based search tools and experimental methods, and we will describe how these tools can be optimized for gene knock-out (KO) and gene knock-in (KI) for model organisms. We also discuss future directions in precision genome editing and its applications, as well as challenges in target selection, particularly in predicting off-target effects.
Tceal7 Regulates Skeletal Muscle Development through Its Interaction with Cdk1
Authors: Xiong Zhenzhen , Wang Mengni , Wu Jianhua , Shi Xiaozhong
Published: March 2023

We have previously reported Tceal7 as a muscle-specific gene that represses myoblast proliferation and promotes myogenic differentiation. The regulatory mechanism of Tceal7 gene expression has been well clarified recently. However, the underlying mechanism of Tceal7 function in skeletal muscle development remains to be elucidated. In the present study, we have generated an MCK 6.5 kb-HA-Tceal7 transgenic model. The transgenic mice are born normally, while they have displayed defects in the growth of body weight and skeletal muscle myofiber during postnatal development. Although four RxL motifs have been identified in the Tceal7 protein sequence, we have not detected any direct protein-protein interaction between Tceal7 and Cyclin A2, Cyclin B1, Cylin D1, or Cyclin E1. Further analysis has revealed the interaction between Tceal7 and Cdk1 instead of Cdk2, Cdk4, or Cdk6. Transgenic overexpression of Tceal7 reduces phosphorylation of 4E-BP1 Ser65, p70S6K1 Thr389, and Cdk substrates in skeletal muscle. In summary, these studies have revealed a novel mechanism of Tceal7 in skeletal muscle development.
Comparative Transcriptomic Analysis Reveals the Functionally Segmented Intestine in Tunicate Ascidian
Authors: Zhang Wei , Jiang An , Yu Haiyan , Dong Bo
Published: March 2023

The vertebrate intestinal system consists of separate segments that remarkably differ in morphology and function. However, the origin of intestinal segmentation remains unclear. In this study, we investigated the segmentation of the intestine in a tunicate ascidian species, Ciona savignyi, by performing RNA sequencing. The gene expression profiles showed that the whole intestine was separated into three segments. Digestion, ion transport and signal transduction, and immune-related pathway genes were enriched in the proximal, middle, and distal parts of the intestine, respectively, implying that digestion, absorption, and immune function appear to be regional specializations in the ascidian intestine. We further performed a multi−species comparison analysis and found that the Ciona intestine showed a similar gene expression pattern to vertebrates, indicating tunicates and vertebrates might share the conserved intestinal functions. Intriguingly, vertebrate pancreatic homologous genes were expressed in the digestive segment of the Ciona intestine, suggesting that the proximal intestine might play the part of pancreatic functions in C. savignyi. Our results demonstrate that the tunicate intestine can be functionally separated into three distinct segments, which are comparable to the corresponding regions of the vertebrate intestinal system, offering insights into the functional evolution of the digestive system in chordates.
Mouse Models with SGLT2 Mutations: Toward Understanding the Role of SGLT2 beyond Glucose Reabsorption
Authors: Unno Keiko , Taguchi Kyoko , Takagi Yoshiichi , Hase Tadashi , Meguro Shinichi , Nakamura Yoriyuki
Published: March 2023

The sodium–glucose cotransporter 2 (SGLT2) mainly carries out glucose reabsorption in the kidney. Familial renal glycosuria, which is a mutation of SGLT2, is known to excrete glucose in the urine, but blood glucose levels are almost normal. Therefore, SGLT2 inhibitors are attracting attention as a new therapeutic drug for diabetes, which is increasing worldwide. In fact, SGLT2 inhibitors not only suppress hyperglycemia but also reduce renal, heart, and cardiovascular diseases. However, whether long-term SGLT2 inhibition is completely harmless requires further investigation. In this context, mice with mutations in SGLT2 have been generated and detailed studies are being conducted, e.g., the SGLT2−/− mouse, Sweet Pee mouse, Jimbee mouse, and SAMP10-ΔSglt2 mouse. Biological changes associated with SGLT2 mutations have been reported in these model mice, suggesting that SGLT2 is not only responsible for sugar reabsorption but is also related to other functions, such as bone metabolism, longevity, and cognitive functions. In this review, we present the characteristics of these mutant mice. Moreover, because the relationship between diabetes and Alzheimer’s disease has been discussed, we examined the relationship between changes in glucose homeostasis and the amyloid precursor protein in SGLT2 mutant mice.
Plumbagin Exhibits Genotoxicity and Induces G2/M Cell Cycle Arrest via ROS-Mediated Oxidative Stress and Activation of ATM-p53 Signaling Pathway in Hepatocellular Cells
Authors: Liu Huan , Zhang Wenchao , Jin Lijie , Liu Shasha , Liang Liying , Wei Yanfei
Published: March 2023

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone, PLB), a naturally occurring naphthoquinone mainly isolated from the plant Plumbago zeylanica L., has been proven to possess anticancer activities towards multiple types of cancer. Although there has been an increasing amount of research regarding its anticancer effects, the association between oxidative stress, genotoxicity and the cell cycle arrest induced by PLB still remains unclear. Therefore, it is important to investigate their potential connections and the involvement of DNA damage and the ataxia telangiectasia mutated protein (ATM)-p53 signaling pathway in PLB’s anticancer mechanism. The present study showed that PLB exposure significantly reduced HCC cell viability and colony formation. In addition, PLB-induced G2/M cell cycle arrest, oxidative stress, and DNA damage was detected, which could be almost blocked by NAC pretreatment. PLB could trigger a DNA damage response by activating cell cycle checkpoints such as ATM, checkpoint kinase 1 (Chk1), checkpoint kinase 2 (Chk2) and p53. Meanwhile, the key modulator of the G2/M transition factor, Cell Division Cycle 25C (cdc25C), was significantly downregulated in an ROS-dependent manner. Furthermore, pretreatment with ATM and p53 inhibitors (KU55933 and Pifithrin-α) could reduce the occurrence of G2/M cell cycle arrest by inhibiting the activation of the ATM-p53 pathway. Taken together, these results indicate that ROS-mediated oxidative stress plays a key role in PLB-induced G2/M cell cycle arrest mediated by the ATM-p53 pathway.
Learning in the Single-Cell Organism Physarum polycephalum: Effect of Propofol
Authors: Kippenberger Stefan , Pipa Gordon , Steinhorst Katja , Zöller Nadja , Kleemann Johannes , Özistanbullu Deniz , Kaufmann Roland , Scheller Bertram
Published: March 2023

Propofol belongs to a class of molecules that are known to block learning and memory in mammals, including rodents and humans. Interestingly, learning and memory are not tied to the presence of a nervous system. There are several lines of evidence indicating that single-celled organisms also have the capacity for learning and memory which may be considered as basal intelligence. Here, we introduce a new experimental model for testing the learning ability of Physarum polycephalum, a model organism frequently used to study single-celled “intelligence”. In this study, the impact of propofol on Physarum’s “intelligence” was tested. The model consists of a labyrinth of subsequent bifurcations in which food (oat flakes soaked with coconut oil-derived medium chain triglycerides [MCT] and soybean oil-derived long chain triglycerides [LCT]) or propofol in MCT/LCT) is placed in one of each Y-branch. In this setting, it was tested whether Physarum memorized the rewarding branch. We saw that Physarum was a quick learner when capturing the first bifurcations of the maze; thereafter, the effect decreased, perhaps due to reaching a state of satiety. In contrast, when oat flakes were soaked with propofol, Physarum’s preference for oat flakes declined significantly. Several possible actions, including the blocking of gamma-aminobutyric acid (GABA) receptor signaling, are suggested to account for this behavior, many of which can be tested in our new model.
Secondary Reporting of G6PD Deficiency on Newborn Screening
Authors: Hoang Stephanie C. , Blumenschein Pamela , Lilley Margaret , Olshaski Larissa , Bruce Aisha , Wright Nicola A. M. , Ridsdale Ross , Christian Susan
Published: March 2023

In April 2019, the Alberta Newborn Screening Program expanded to include screening for classic galactosemia using a two-tier screening approach. This approach secondarily identifies infants with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The goals of this study were (i) to evaluate the performance of a two-tier galactosemia screening protocol, (ii) to explore the impact on and acceptability to families of reporting G6PD deficiency as a secondary finding, and (iii) assess the communication and follow-up process for positive G6PD deficiency screening results. The two-tiered galactosemia approach increased the positive predictive value (PPV) for galactosemia from 8% to 79%. An additional 119 positive newborn screen results were reported for G6PD deficiency with a PPV of 92%. The results show that there may be utility in reporting G6PD deficiency results. Most parents who participated in the study reported having some residual worry around the unexpected diagnosis; however, all thought it was helpful to know of their child’s diagnosis of G6PD deficiency. Finally, the communication process for reporting G6PD deficiency newborn screen results was determined to result in appropriate follow up of infants.