bluuebunny/crossref_metadata_2025 huggingface dataset:
Reviewing the Tradeoffs between Sunburn Mitigation and Red Color Development in Apple under a Changing Climate
Authors: Willsea Noah , Blanco Victor , Rajagopalan Kirti , Campbell Thiago , Howe Orlando , Kalcsits Lee
Published: April 2023

Orchard systems have drastically changed over the last three decades to high-density plantings that prioritize light interception that is evenly distributed throughout the entire canopy. These conditions allow the production of fruit with a high red color that meets consumer demands for uniformly colored fruit without external disorders. However, these systems also expose a higher proportion of fruit to full-sunlight conditions. In many semi-arid apple production regions, summer temperatures often exceed thresholds for the development of fruit sunburn, which can lead to >10% fruit losses in some regions and some years. To combat this, growers and researchers use sunburn mitigation strategies such as shade netting and evaporative cooling, which bring a different set of potential fruit quality impacts. Often, there is a tradeoff between red color development and fruit sunburn, particularly for strategies that affect light intensity reaching the fruit surface. In this paper, we review agronomic and environmental factors leading to reductions in red color and increases in sunburn incidence, along with advancements in management practices that help mitigate these issues. Furthermore, we also identify gaps in knowledge on the influence climate change might have on the viability of some practices that either enhance red color or limit sunburn for apple orchards in semi-arid environments. There is a need for cost-effective management strategies that reduce losses to sunburn but do not inhibit red color development in bicolor apple cultivars.
Comparing Spanish-Style and Natural Fermentation Methods to Valorise Carolea, Nocellara Messinese and Leccino as Table Olives
Authors: Timpanaro Nicolina , Rutigliano Chiara A. C. , Benincasa Cinzia , Foti Paola , Mangiameli Solidea , Nicoletti Rosa , Muzzalupo Innocenzo , Romeo Flora V.
Published: April 2023

This paper presents the results of the transformation into table olives of drupes belonging to three Italian cultivars: Carolea, Leccino and Nocellara Messinese, widely used for virgin olive oil production, by using the two most common methods to produce fermented table olives: the Spanish-style method (SS) and the natural fermentation (NF). The most suitable drupes as table olives due to their flesh-to-pit ratio and high-weight fruits were Nocellara Messinese olives. From the results obtained, it was highlighted that fermentation must be improved by using a selected starter culture that can drive the fermentation by rapid acidification. In fact, the long time required by NF results in a lower pH close to the hygienic safety limit but not low enough to be considered as a stable product, while the fast fermentation obtained by treating the olives with lye solution resulted in pH values that were too high. The sugar content in all table olives was almost null, and the sensory evaluation showed that SS olives were less bitter than NF olives. Moreover, NF olive-flesh samples showed a higher amount of healthy phenolic compounds than SS olives, whose phenolic content was drastically affected by the alkaline treatment and the successive washing steps.
Self-Reported Chronic Back Pain and Current Depression in Brazil: A National Level Study
Authors: Norris Ryan J. , Oancea S. Cristina , Nucci Luciana B.
Published: April 2023

There is limited literature investigating the association between chronic back pain (CBP) and depression in Brazil. This study evaluates the association between CBP, CBP-related physical limitations (CBP-RPL), and self-reported current depression (SRCD), in a nationally representative sample of Brazilian adults. The data for this cross-sectional study came from the 2019 Brazilian National Health Survey (n = 71,535). The Personal Health Questionnaire depression scale (PHQ-8) was used to measure the SRCD outcome. The exposures of interest were self-reported CBP and CBP-RPL (none, slight, moderate, and high limitation). Multivariable weighted and adjusted logistic regression models were used to investigate these associations. The weighted prevalence of SRCD among CBP was 39.5%. There was a significant weighted and adjusted association between CBP and SRCD (weighted and adjusted odds ratio (WAOR) 2.69 (95% CI: 2.45–2.94). The WAOR of SRCD among individuals with high, moderate, and slight levels of physical limitation was significantly greater than for those without physical limitation due to CBP. Among Brazilian adults with high levels of CBP-RPL, there was over a five-fold increased risk of SRCD compared to those without CBP-RPL. These results are important for increasing awareness of the link between CBP and SRCD and for informing health services policies.
Protein Supplementation in a Prehabilitation Program in Patients Undergoing Surgery for Endometrial Cancer
Authors: Sole-Sedeno Josep M. , Miralpeix Ester , Muns Maria-Dolors , Rodriguez-Cosmen Cristina , Fabrego Berta , Kanjou Nadwa , Medina Francesc-Xavier , Mancebo Gemma
Published: April 2023

Enhanced recovery after surgery (ERAS) and prehabilitation programs are multidisciplinary care pathways to reduce stress response and improve perioperative outcomes, which also include nutritional interventions. The aim of this study is to assess the impact of protein supplementation with 20 mg per day before surgery in a prehabilitation program in postoperative serum albumin, prealbumin, and total proteins in endometrial cancer patients undergoing laparoscopic surgery. Methods: A prospective study including patients who underwent laparoscopy for endometrial cancer was conducted. Three groups were identified according to ERAS and prehabilitation implementation (preERAS, ERAS, and Prehab). The primary outcome was levels of serum albumin, prealbumin, and total protein 24–48 h after surgery. Results: A total of 185 patients were included: 57 in the preERAS group, 60 in the ERAS group, and 68 in the Prehab group. There were no basal differences in serum albumin, prealbumin, or total protein between the three groups. After surgery, regardless of the nutritional intervention, the decrease in the values was also similar. Moreover, values in the Prehab group just before surgery were lower than the initial ones, despite the protein supplementation. Conclusions: Supplementation with 20 mg of protein per day does not impact serum protein levels in a prehabilitation program. Supplementations with higher quantities should be studied.
Stepping into the Void: Lessons Learned from Civil Society Organizations during COVID-19 in Rio de Janeiro
Authors: Curty Pereira Rodrigo , Elliott Susan J. , Llaguno Cárdenas Pablo
Published: April 2023

Brazil experienced some of the highest rates of COVID-19 globally. This was complicated by the fact that 35 million of its citizens have limited access to water, a primary resource necessary to stem the spread of infectious diseases. In many cases, civil society organizations (CSOs) stepped into this void left by responsible authorities. This paper explores how CSOs in Rio de Janeiro helped populations struggling with access to water, sanitation, and hygiene (WASH) during the pandemic, and what coping strategies are transferable to similar contexts. In-depth interviews (n = 15) were conducted with CSO representatives in the metropolitan region of Rio de Janeiro. Thematic analysis of the interviews revealed that COVID-19 exacerbated pre-existing social inequities among vulnerable populations, undermining their ability to protect their health. CSOs provided emergency relief aid but faced the counterproductive actions of public authorities who promoted a narrative that diminished the risks of COVID-19 and the importance of non-pharmacological interventions. CSOs fought this narrative by promoting sensitization among vulnerable populations and partnering with other stakeholders in networks of solidarity, playing a vital role in the distribution of health-promoting services. These strategies are transferrable to other contexts where state narratives oppose public health understandings, particularly for extremely vulnerable populations.
REM Sleep Impairment May Underlie Sleep-Driven Modulations of Tinnitus in Sleep Intermittent Tinnitus Subjects: A Controlled Study
Authors: Guillard Robin , Korczowski Louis , Léger Damien , Congedo Marco , Londero Alain
Published: April 2023

(1) Background: Poor sleep and fragmented sleep are associated with several chronic conditions. Tinnitus is an auditory symptom that often negatively combines with poor sleep and has been associated with sleep impairment and sleep apnea. The relationship between tinnitus psychoacoustic characteristics and sleep is still poorly explored, notably for a particular subgroup of patients, for whom the perceived loudness of their tinnitus is highly modulated by sleep. (2) Methods: For this observational prospective study, 30 subjects with tinnitus were recruited, including 15 “sleep intermittent tinnitus” subjects, who had reported significant modulations of tinnitus loudness related to night sleep and naps, and a control group of 15 subjects displaying constant non-sleep-modulated tinnitus. The control group had matching age, gender, self-reported hearing loss grade and tinnitus impact on quality of life with the study group. All patients underwent a polysomnography (PSG) assessment for one complete night and then were asked to fill in a case report form, as well as a report of tinnitus loudness before and after the PSG. (3) Results: “Sleep Intermittent tinnitus” subjects had less Stage 3 sleep (p < 0.01), less Rapid-Eye Movement (REM) Sleep (p < 0.05) and more Stage 2 sleep (p < 0.05) in proportion and duration than subjects from the control group. In addition, in the “sleep Intermittent tinnitus” sample, a correlation was found between REM sleep duration and tinnitus overnight modulation (p < 0.05), as well as tinnitus impact on quality of life (p < 0.05). These correlations were not present in the control group. (4) Conclusions: This study suggests that among the tinnitus population, patients displaying sleep-modulated tinnitus have deteriorated sleep quality. Furthermore, REM sleep characteristics may play a role in overnight tinnitus modulation. Potential pathophysiological explanations accounting for this observation are hypothesized and discussed.
Fear of COVID-19, Mental Health and Resilient Coping in Young Adult Male Inmates: A Portuguese Cross-Sectional Study
Authors: Mendes Rute , Baccon Wanessa Cristina , Laranjeira Carlos
Published: April 2023

Inmates are highly exposed to mental and physical disorders. Therefore, periodic screening of their mental health and other health risks is required. This study aims to investigate the perceived fear of COVID-19 and the psychological impact of the pandemic in a sample of young adult male inmates. An institutional-based quantitative cross-sectional study design was performed. Data collection took place from July to September 2022 at a juvenile prison in the central region of Portugal. Data were collected using questionnaires on demographic and health characteristics; fear of COVID-19; depression, anxiety and stress levels; and resilient coping. The sample included 60 male inmates imprisoned for over 2 years. Stress was the most common symptom among inmates (75%), followed by anxiety (38.3%) and depression (36.7%). The mean score on the Fear of COVID-19 Scale was 17.38 ± 4.80, indicating relatively low fear levels. Low resilient scores were found in 38 participants (63.3%). Participants reported moderately high ranges of 3.62 ± 0.87 regarding mental health perception, 3.73 ± 0.95 for physical health perception, and 3.27 ± 0.82 for global health concerning the previous month. The Pearson correlation matrix indicated significant and moderate to strong correlations between fear of COVID-19 and mental health-related variables (p < 0.001). The predicting factors of fear of COVID-19 were identified by deploying a multiple linear regression model. We found four predictors: age, perception of mental health, and overall levels of anxiety and stress (R2 = 0.497). Fear of a given scenario or factor may shift with time. Therefore, long-term research is needed to evaluate whether fear of COVID-19 is adaptive or long-reactive in victims. Our study can assist policymakers, mental health and public health experts, and others in recognizing and managing pandemic-related fears and mental health symptoms.
Demonstrating the Feasibility of an Economic Empowerment and Health Promotion Intervention among Low-Income Women Affected by HIV in New York City
Authors: Filippone Prema L. , Hernandez Trejo Yajaira , Witte Susan S.
Published: April 2023

Women of color in the U.S. face systematic exclusion from the labor market, work protections, and employer-based benefits. Women’s economic vulnerability increases their susceptibility to health-related issues, including HIV transmission and substance use, which are work-restricting disabilities, by constraining their capacity to effectively reduce risk. The Women’s Economic Empowerment pilot examined the feasibility of a structural intervention, implemented at a neighborhood agency, combining both health promotion and economic empowerment components as a pathway to accessing an urban job market for low-income women with work-restricting disabilities, including living with HIV. Ten women clients from a partner agency in New York completed four health promotion sessions, six financial literacy sessions, and a concurrent opportunity to match savings; some also followed with up to 24 vocational rehabilitation sessions. Interviews captured self-reported data on health promotion and financial outcomes at pre-/post-intervention and 3-month follow-up. Qualitative analysis of recorded group sessions and field notes demonstrate that women express improved HVI/STI knowledge and problem-solving strategies for risk reduction, a shared optimism for the future due to group participation, enhanced social support through relationship-building, a heightened sense of empowerment regarding financial decision making, and a desire to re-engage in the labor force. Findings suggest an empowering approach to re-engage women impacted by poverty, unemployment, and disabilities, including living with HIV, into the workforce may be implemented in a community setting.
Feasibility and Acceptability of an Online Mindfulness-Based Intervention for Stress Reduction and Psychological Wellbeing of University Students in Pakistan: A Pilot Randomized Controlled Trial
Authors: Sarfraz Anum , Siddiqui Salma , Galante Julieta , Sikander Siham
Published: April 2023

The rise in mental health concerns of university students is causing a serious hinderance to their wellbeing, impeding their functioning. The socio-economic and political friction in low- and middle-income countries adds to their vulnerability and calls for a cost-effective indigenous intervention. Consequently, this study aimed to inform a large definitive trial by assessing the feasibility and acceptability of a randomized controlled trial (RCT) design evaluating a culturally adapted online Mindfulness Training Course (MTC) used to improve stress and wellbeing among Pakistani university students. A two-arm pilot randomized controlled trial was conducted. University students (n = 156) were randomly assigned to either the MTC group (n = 80) or Wait-list (WL) control group (n = 76) and completed baseline and post-intervention self-report measures for mindfulness, stress and psychological wellbeing. Additionally, semi-structured interviews were conducted with consenting MTC group participants (n = 18) to explore their views about MTC, employing reflexive thematic analysis. Of 80 participants randomized to the MTC group, 32 completed the course, whereas, from the 156 randomized participants, 102 completed assessment surveys. Feasibility and acceptability indicators showed high recruitment, compliance, and adherence to MTC, with practical steps for randomization and online data collection. Further results showed higher levels of mindfulness and psychological wellbeing and lowered stress levels in the MTC group compared to the control group. The attrition and dropout rates were high; however, the feedback from participants who completed the MTC was highly positive and encouraging. In conclusion, if the trial proceeds with increased outreach in a large-scale RCT, the recruitment might be revised to reduce attrition rates. Further recommendations are discussed.
Implementation of Patient-Centered Care by Athletic Training Students during Clinical Experiences: A Report from the Association of Athletic Training Education Research Network
Authors: Cavallario Julie M. , Van Lunen Bonnie L. , Walker Stacy E. , Bay R. Curtis , Welch Bacon Cailee E.
Published: April 2023

Patient-centered care (PCC) is a core competency that should be required by all healthcare education programs, but little is known about its implementation in athletic training clinical experiences. Therefore, we examined characteristics of patient encounters documented by athletic training students implementing PCC behaviors. A multisite panel design was used to recruit 363 students from twelve professional athletic training programs (five undergraduate, seven graduate). Over 1.5 years, clinical experience patient encounter data were logged in E*Value Case Logs, including student role during the encounter, length of encounter, and clinical site. Generalized estimating equations models characterized the likelihood students included PCC behaviors in 30,522 encounters. Discussing patient goals was associated with student role (χ2(2) = 40.6, p < 0.001) and length of encounter (χ2(4) = 67.6, p < 0.001). Using patient-reported outcome measures was associated with student role (χ2(2) = 21.6, p < 0.001), length of encounter (χ2(4) = 34.5, p < 0.001), and clinical site (χ2(3) = 17.3, p = 0.001). Implementing clinician-rated outcome measures was affected by length of encounter (χ2(4) = 27.9, p < 0.001) and clinical site (χ2(3) = 8.6, p = 0.04). PCC behaviors were largely associated with student role and length of encounters; clinical site had less impact. Athletic training educators should emphasize progressive autonomous supervision with preceptors and encourage students to facilitate slightly longer patient visits, when possible, to incorporate more PCC behaviors.
Psycho-Social Correlates of Cyberbullying among Polish Adolescents
Authors: Rębisz Sławomir , Jasińska-Maciążek Aleksandra , Grygiel Paweł , Dolata Roman
Published: April 2023

Cyberbullying has recently attracted attention due to its increasing prevalence and serious consequences for both victims and perpetrators. The objective of this population-based study was to examine the determinants of a person becoming a perpetrator of cyberbullying, including personal resources (emotional self-regulation, self-esteem, internal locus of control, optimism), social skills (prosocial behavior, assertiveness, cognitive empathy, cooperation), peer relationships (peer support, threats from peers, peer rejection, dislike of peers), and problematic Internet use (excessive Internet use, impulsive reactions to Internet deprivation). Participants (N = 541) were students at elementary schools (age 14–15) in Ostroleka, a city in central-eastern Poland. Two-part regression was used to explore protective/risk factors of the likelihood of an individual using cyberviolence (dichotomous part: involvement in violence) and how often it is used (continuous part: frequency of cyberbullying). The results showed that the emotional component is crucial to cyberbullying, as indicated by the importance of emotional self-control, which reduces the frequency of cyberbullying. Other important factors are assertiveness, impulsive response to limited Internet access (which increases the likelihood of engaging in cyberbullying) and fear of peers (which reduces its frequency). In turn, the importance of pro-sociality (which inhibits engagement) and peer support (which promotes engagement) points to the second important component of cyberbullying—that is, group mechanisms. At the same time, the results indicate that while the importance of Internet addiction as a risk factor for cyberbullying should not be underestimated, the amount of time spent online cannot be seen as the source of the problem. The study leads to the conclusion that effective interventions targeting cyberbullying should focus on the development of more adaptive styles of coping with emotions.
Environmental Monitoring of Legionella in Hospitals in the Campania Region: A 5-Year Study
Authors: Lombardi Annalisa , Borriello Tonia , De Rosa Elvira , Di Duca Fabiana , Sorrentino Michele , Torre Ida , Montuori Paolo , Trama Ugo , Pennino Francesca
Published: April 2023

Legionella is a pathogen that colonizes soils, freshwater, and building water systems. People who are most affected are those with immunodeficiencies, so it is necessary to monitor its presence in hospitals. The purpose of this study was to evaluate the presence of Legionella in water samples collected from hospitals in the Campania region, Southern Italy. A total of 3365 water samples were collected from January 2018 to December 2022 twice a year in hospital wards from taps and showers, tank bottoms, and air-treatment units. Microbiological analysis was conducted in accordance with the UNI EN ISO 11731:2017, and the correlations between the presence of Legionella and water temperature and residual chlorine were investigated. In total, 708 samples (21.0%) tested positive. The most represented species was L. pneumophila 2–14 (70.9%). The serogroups isolated were 1 (27.7%), 6 (24.5%), 8 (23.3%), 3 (18.9%), 5 (3.1%), and 10 (1.1%). Non-pneumophila Legionella spp. represented 1.4% of the total. Regarding temperature, the majority of Legionella positive samples were found in the temperature range of 26.0–40.9 °C. An influence of residual chlorine on the presence of the bacterium was observed, confirming that chlorine disinfection is effective for controlling contamination. The positivity for serogroups other than serogroup 1 suggested the need to continue environmental monitoring of Legionella and to focus on the clinical diagnosis of other serogroups.
Systematic Study of Solid-State Fluorescence and Molecular Packing of Methoxy-trans-Stilbene Derivatives, Exploration of Weak Intermolecular Interactions Based on Hirshfeld Surface Analysis
Authors: Piekuś-Słomka Natalia , Małecka Magdalena , Wierzchowski Marcin , Kupcewicz Bogumiła
Published: April 2023

In recent years, fluorescent compounds that emit efficiently in the solid state have become particularly interesting, especially those that are easily prepared and inexpensive. Hence, exploring the photophysical properties of stilbene derivatives, supported by a detailed analysis of molecular packing obtained from single-crystal X-ray diffraction data, is a relevant area of research. A complete understanding of the interactions to determine the molecular packing in the crystal lattice and their effect on the material’s physicochemical properties is essential to tune various properties effectively. In the present study, we examined a series of methoxy-trans-stilbene analogs with substitution pattern-dependent fluorescence lifetimes between 0.82 and 3.46 ns and a moderate-to-high fluorescence quantum yield of 0.07–0.69. The relationships between the solid-state fluorescence properties and the structure of studied compounds based on X-ray analysis were investigated. As a result, the QSPR model was developed using PLSR (Partial Least Squares Regression). Decomposition of the Hirshfeld surfaces (calculated based on the arrangement of molecules in the crystal lattice) revealed the various types of weak intermolecular interactions that occurred in the crystal lattice. The obtained data, in combination with global reactivity descriptors calculated using HOMO and LUMO energy values, were used as explanatory variables. The developed model was characterized by good validation metrics (RMSECAL = 0.017, RMSECV = 0.029, R2CAL = 0.989, and R2CV = 0.968) and indicated that the solid-state fluorescence quantum yield of methoxy-trans-stilbene derivatives was mainly dependent on weak intermolecular C…C contacts corresponding to π-π stacking and C…O/O…C interactions. To a lesser extent and inversely proportional, the fluorescence quantum yield was affected by the interactions of the type O…H/H…O and H…H and the electrophilicity of the molecule.
Proteomic and Metabolic Analysis of Pinus halepensis Mill. Embryonal Masses Induced under Heat Stress
Authors: Pereira Cátia , Castander-Olarieta Ander , Montalbán Itziar A. , Mendes Vera M. , Correia Sandra , Pedrosa Ana , Manadas Bruno , Moncaleán Paloma , Canhoto Jorge
Published: April 2023

Understanding the physiological and molecular adjustments occurring during tree stress response is of great importance for forest management and breeding programs. Somatic embryogenesis has been used as a model system to analyze various processes occurring during embryo development, including stress response mechanisms. In addition, “priming” plants with heat stress during somatic embryogenesis seems to favor the acquisition of plant resilience to extreme temperature conditions. In this sense, Pinus halepensis somatic embryogenesis was induced under different heat stress treatments (40 °C for 4 h, 50 °C for 30 min, and 60 °C for 5 min) and its effects on the proteome and the relative concentration of soluble sugars, sugar alcohols and amino acids of the embryonal masses obtained were assessed. Heat severely affected the production of proteins, and 27 proteins related to heat stress response were identified; the majority of the proteins with increased amounts in embryonal masses induced at higher temperatures consisted of enzymes involved in the regulation of metabolism (glycolysis, the tricarboxylic acid cycle, amino acid biosynthesis and flavonoids formation), DNA binding, cell division, transcription regulation and the life-cycle of proteins. Finally, significant differences in the concentrations of sucrose and amino acids, such as glutamine, glycine and cysteine, were found.
Celiac Disease Is a Risk Factor for Mature T and NK Cell Lymphoma: A Mendelian Randomization Study
Authors: Martín-Masot Rafael , Herrador-López Marta , Navas-López Víctor Manuel , Carmona Francisco David , Nestares Teresa , Bossini-Castillo Lara
Published: April 2023

Celiac disease (CeD) is an immune-mediated disorder triggered by gluten ingestion that damages the small intestine. Although CeD has been associated with a higher risk for cancer, the role of CeD as a risk factor for specific malignancies, such as enteropathy-associated T-cell lymphoma (EATL), remains controversial. Using two-sample Mendelian randomization (2SMR) methods and the summarized results of large genome-wide association studies from public repositories, we addressed the causal relationship between CeD and eight different malignancies. Eleven non-HLA SNPs were selected as instrumental variables (IVs), and causality estimates were obtained using four 2SMR methods: random-effects inverse variance-weighted, weighted median estimation, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO). We identified a significant causal relationship between CeD and mature T/NK cell lymphomas. Under a multivariate Mendelian randomization model, we observed that the causal effect of CeD was not dependent on other known lymphoma risk factors. We found that the most instrumental IV was located in the TAGAP locus, suggesting that aberrant T cell activation might be relevant in the T/NK cell malignization process. Our findings provide new insights into the connection between immune imbalance and the development of severe comorbidities, such as EATL, in patients with CeD.
SiNF-YC2 Regulates Early Maturity and Salt Tolerance in Setaria italica
Authors: Niu Jiahong , Guan Yanan , Yu Xiao , Wang Runfeng , Qin Ling , Chen Erying , Yang Yanbing , Zhang Huawen , Wang Hailian , Li Feifei
Published: April 2023

Early maturity is an important agronomic trait in most crops, because it can solve the problem of planting in stubble for multiple cropping as well as make full use of light and temperature resources in alpine regions, thereby avoiding damage from low temperatures in the early growth period and early frost damage in the late growth period to improve crop yield and quality. The expression of genes that determine flowering affects flowering time, which directly affects crop maturity and indirectly affects crop yield and quality. Therefore, it is important to analyze the regulatory network of flowering for the cultivation of early-maturing varieties. Foxtail millet (Setaria italica) is a reserve crop for future extreme weather and is also a model crop for functional gene research in C4 crops. However, there are few reports on the molecular mechanism regulating flowering in foxtail millet. A putative candidate gene, SiNF-YC2, was isolated based on quantitative trait loci (QTL) mapping analysis. Bioinformatics analysis showed that SiNF-YC2 has a conserved HAP5 domain, which indicates that it is a member of the NF-YC transcription factor family. The promoter of SiNF-YC2 contains light-response-, hormone-, and stress-resistance-related elements. The expression of SiNF-YC2 was sensitive to the photoperiod and was related to the regulation of biological rhythm. Expression also varied in different tissues and in response to drought and salt stress. In a yeast two-hybrid assay, SiNF-YC2 interacted with SiCO in the nucleus. Functional analysis suggested that SiNF-YC2 promotes flowering and improves resistance to salt stress.
Lipid-Independent Regulation of PLIN5 via IL-6 through the JAK/STAT3 Axis in Hep3B Cells
Authors: Krizanac Marinela , Mass Sanchez Paola Berenice , Schröder Sarah K. , Weiskirchen Ralf , Asimakopoulos Anastasia
Published: April 2023

Perilipin 5 (PLIN5) is a lipid droplet coat protein that is highly expressed in oxidative tissues such as those of muscles, the heart and the liver. PLIN5 expression is regulated by a family of peroxisome proliferator-activated receptors (PPARs) and modulated by the cellular lipid status. So far, research has focused on the role of PLIN5 in the context of non-alcoholic fatty liver disease (NAFLD) and specifically in lipid droplet formation and lipolysis, where PLIN5 serves as a regulator of lipid metabolism. In addition, there are only limited studies connecting PLIN5 to hepatocellular carcinoma (HCC), where PLIN5 expression is proven to be upregulated in hepatic tissue. Considering that HCC development is highly driven by cytokines present throughout NAFLD development and in the tumor microenvironment, we here explore the possible regulation of PLIN5 by cytokines known to be involved in HCC and NAFLD progression. We demonstrate that PLIN5 expression is strongly induced by interleukin-6 (IL-6) in a dose- and time-dependent manner in Hep3B cells. Moreover, IL-6-dependent PLIN5 upregulation is mediated by the JAK/STAT3 signaling pathway, which can be blocked by transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α). Furthermore, IL-6-mediated PLIN5 upregulation changes when IL-6 trans-signaling is stimulated through the addition of soluble IL-6R. In sum, this study sheds light on lipid-independent regulation of PLIN5 expression in the liver, making PLIN5 a crucial target for NAFLD-induced HCC.
Effects of Glutamine, Curcumin and Fish Bioactive Peptides Alone or in Combination on Intestinal Permeability in a Chronic-Restraint Stress Model
Authors: Langlois Ludovic D. , Oddoux Sarah , Aublé Kanhia , Violette Paul , Déchelotte Pierre , Noël Antoine , Coëffier Moïse
Published: April 2023

Irritable bowel syndrome (IBS), a multifactorial intestinal disorder, is often associated with a disruption in intestinal permeability as well as an increased expression of pro-inflammatory markers. The aim of this study was to first test the impact of treatment with glutamine (Gln), a food supplement containing natural curcumin extracts and polyunsaturated n-3 fatty acids (Cur); bioactive peptides from a fish protein hydrolysate (Ga); and a probiotic mixture containing Bacillus coagulans, Lactobacillus acidophilus, Lactobacillus gasseri and Lactobacillus helveticus. These compounds were tested alone on a stress-based IBS model, the chronic-restraint stress model (CRS). The combination of Gln, Cur and Ga (GCG) was also tested. Eight-week-old C57Bl/6 male mice were exposed to restraint stress for two hours every day for four days and received different compounds every day one week before and during the CRS procedure. Plasma corticosterone levels were measured as a marker of stress, and colonic permeability was evaluated ex vivo in Ussing chambers. Changes in the gene expression of tight junction proteins (occludin, claudin-1 and ZO 1) and inflammatory cytokines (IL1β, TNFα, CXCL1 and IL10) were assessed using RT-qPCR. The CRS model led to an increase in plasma corticosterone and an increase in colonic permeability compared with unstressed animals. No change in plasma corticosterone concentrations was observed in response to CRS with the different treatments (Gln, Cur, Ga or GCG). Stressed animals treated with Gln, Cur and Ga alone and in combination showed a decrease in colonic permeability when compared to the CRS group, while the probiotic mixture resulted in an opposite response. The Ga treatment induced an increase in the expression of the anti-inflammatory cytokine IL-10, and the GCG treatment was able to decrease the expression of CXCL1, suggesting the synergistic effect of the combined mixture. In conclusion, this study demonstrated that a combined administration of glutamine, a food supplement containing curcumin and polyunsaturated n-3 fatty acids, and bioactive peptides from a fish hydrolysate was able to reduce colonic hyperpermeability and reduce the inflammatory marker CXCL1 in a stress-based model of IBS and could be of interest to patients suffering from IBS.
Heat Treatment Enhances the Neuroprotective Effects of Crude Ginseng Saponin by Increasing Minor Ginsenosides
Authors: Ji Yun-Jeong , Kim Hyung Don , Lee Eun Suk , Jang Gwi Yeong , Seong Hyun-A
Published: April 2023

Ginsenoside is the primary active substance of ginseng and has many pharmacological effects, such as anti-cancer, immune, regulating sugar and lipid metabolism, and antioxidant effects. It also protects the nervous and cardiovascular systems. This study analyzes the effects of thermal processing on the bioactivities of crude ginseng saponin. Heat treatment increased the contents of minor ginsenosides in crude saponins, such as Rg3, and heat-treated crude ginseng saponin (HGS) had better neuroprotective effects than non-treated crude saponin (NGS). HGS reduced glutamate-induced apoptosis and reactive oxygen species generation in pheochromocytoma 12 (PC12) cells, significantly more than NGS. HGS protected PC12 cells against glutamate-induced oxidative stress by upregulating Nrf2-mediated antioxidant signaling and downregulating MAPK-mediated apoptotic signaling. HGS has the potential for the prevention and treatment of neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease.
H19 Sperm Methylation in Male Infertility: A Systematic Review and Meta-Analysis
Authors: Cannarella Rossella , Crafa Andrea , Barbagallo Federica , Lundy Scott D. , La Vignera Sandro , Condorelli Rosita A. , Calogero Aldo E.
Published: April 2023

This systematic review and meta-analysis summarize the difference in the methylation of the H19 gene in patients with abnormal versus normal conventional sperm parameters. It also evaluates the effects of age and sperm concentration on H19 methylation in spermatozoa using meta-regression analysis. It was performed according to the MOOSE guidelines for meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The quality of the evidence reported in the studies included was assessed using the Cambridge Quality Checklists. A total of 11 articles met our inclusion criteria. Quantitative analysis showed that H19 methylation levels were significantly lower in the group of infertile patients than in fertile controls. The reduction in methylation was much more pronounced in patients with oligozoospermia (alone or associated with other sperm parameter abnormalities) and in those with recurrent pregnancy loss. Meta-regression analysis showed the results to be independent of both patient age and sperm concentration. Therefore, the H19 methylation pattern should be evaluated among couples accessing assisted reproductive techniques (ART), in order to gain prognostic information on ART outcome and offspring health.
Investigation of the Compatibility between Warheads and Peptidomimetic Sequences of Protease Inhibitors—A Comprehensive Reactivity and Selectivity Study
Authors: Müller Patrick , Meta Mergim , Meidner Jan Laurenz , Schwickert Marvin , Meyr Jessica , Schwickert Kevin , Kersten Christian , Zimmer Collin , Hammerschmidt Stefan Josef , Frey Ariane , Lahu Albin , de la Hoz-Rodríguez Sergio , Agost-Beltrán Laura , Rodríguez Santiago , Diemer Kira , Neumann Wilhelm , Gonzàlez Florenci V. , Engels Bernd , Schirmeister Tanja
Published: April 2023

Covalent peptidomimetic protease inhibitors have gained a lot of attention in drug development in recent years. They are designed to covalently bind the catalytically active amino acids through electrophilic groups called warheads. Covalent inhibition has an advantage in terms of pharmacodynamic properties but can also bear toxicity risks due to non-selective off-target protein binding. Therefore, the right combination of a reactive warhead with a well-suited peptidomimetic sequence is of great importance. Herein, the selectivities of well-known warheads combined with peptidomimetic sequences suited for five different proteases were investigated, highlighting the impact of both structure parts (warhead and peptidomimetic sequence) for affinity and selectivity. Molecular docking gave insights into the predicted binding modes of the inhibitors inside the binding pockets of the different enzymes. Moreover, the warheads were investigated by NMR and LC-MS reactivity assays against serine/threonine and cysteine nucleophile models, as well as by quantum mechanics simulations.
Nanomechanical Characterization of Ovarian Cancer Cell Lines as a Marker of Response to 2c Treatment
Authors: Tierno Domenico , Azzalini Eros , Farra Rossella , Drioli Sara , Felluga Fulvia , Lazzarino Marco , Grassi Gabriele , Dapas Barbara , Bonin Serena
Published: April 2023

Epithelial ovarian cancers (EOCs) are a heterogeneous group of tumors with different molecular and clinical features. In past decades, few improvements have been achieved in terms of EOC management and treatment efficacy, such that the 5-year survival rate of patients remained almost unchanged. A better characterization of EOCs’ heterogeneity is needed to identify cancer vulnerabilities, stratify patients and adopt proper therapies. The mechanical features of malignant cells are emerging as new biomarkers of cancer invasiveness and drug resistance that can further improve our knowledge of EOC biology and allow the identification of new molecular targets. In this study, we determined the inter and intra-mechanical heterogeneity of eight ovarian cancer cell lines and their association with tumor invasiveness and resistance to an anti-tumoral drug with cytoskeleton depolymerization activity (2c).
Resistance to TOP-1 Inhibitors: Good Old Drugs Still Can Surprise Us
Authors: Kumar Santosh , Sherman Michael Y.
Published: April 2023

Irinotecan (SN-38) is a potent and broad-spectrum anticancer drug that targets DNA topoisomerase I (Top1). It exerts its cytotoxic effects by binding to the Top1-DNA complex and preventing the re-ligation of the DNA strand, leading to the formation of lethal DNA breaks. Following the initial response to irinotecan, secondary resistance is acquired relatively rapidly, compromising its efficacy. There are several mechanisms contributing to the resistance, which affect the irinotecan metabolism or the target protein. In addition, we have demonstrated a major resistance mechanism associated with the elimination of hundreds of thousands of Top1 binding sites on DNA that can arise from the repair of prior Top1-dependent DNA cleavages. Here, we outline the major mechanisms of irinotecan resistance and highlight recent advancements in the field. We discuss the impact of resistance mechanisms on clinical outcomes and the potential strategies to overcome resistance to irinotecan. The elucidation of the underlying mechanisms of irinotecan resistance can provide valuable insights for the development of effective therapeutic strategies.
Copper- and Silver-Containing Heterometallic Iodobismuthates: Features of Thermochromic Behavior
Authors: Shentseva Irina A. , Usoltsev Andrey N. , Korobeynikov Nikita A. , Sukhikh Taisiya S. , Shayapov Vladimir R. , Sokolov Maxim N. , Adonin Sergey A.
Published: April 2023

Nine heterometallic iodobismuthates with the general formula Cat2{[Bi2M2I10}] (M = Cu(I), Ag(I), Cat = organic cation) were synthesized. According to X-ray diffraction data, their crystal structures consisted of {Bi2I10} units interconnected with Cu(I) or Ag(I) atoms through I-bridging ligands, forming one-dimensional polymers. The compounds are thermally stable up to 200 °C. Optical band gaps (Eg), estimated at room temperature via diffuse reflectance measurements, range from 1.81 to 2.03 eV. Thermally induced changes in optical behavior (thermochromism) for compounds 1–9 were recorded, and general correlations were established. The thermal dependence of Eg appears to be close to linear for all studied compounds.
Exploring the Metabolic Differences between Cisplatin- and UV Light-Induced Apoptotic Bodies in HK-2 Cells by an Untargeted Metabolomics Approach
Authors: Bernardo-Bermejo Samuel , Sánchez-López Elena , Castro-Puyana María , Fernández-Martínez Ana , Lucio-Cazaña Francisco , Marina María
Published: April 2023

Among the extracellular vesicles, apoptotic bodies (ABs) are only formed during the apoptosis and perform a relevant role in the pathogenesis of different diseases. Recently, it has been demonstrated that ABs from human renal proximal tubular HK-2 cells, either induced by cisplatin or by UV light, can lead to further apoptotic death in naïve HK-2 cells. Thus, the aim of this work was to carry out a non-targeted metabolomic approach to study if the apoptotic stimulus (cisplatin or UV light) affects in a different way the metabolites involved in the propagation of apoptosis. Both ABs and their extracellular fluid were analyzed using a reverse-phase liquid chromatography-mass spectrometry setup. Principal components analysis showed a tight clustering of each experimental group and partial least square discriminant analysis was used to assess the metabolic differences existing between these groups. Considering the variable importance in the projection values, molecular features were selected and some of them could be identified either unequivocally or tentatively. The resulting pathways indicated that there are significant, stimulus-specific differences in metabolites abundancies that may propagate apoptosis to healthy proximal tubular cells; thus, we hypothesize that the share in apoptosis of these metabolites might vary depending on the apoptotic stimulus.
Developmental Stage-Dependent Changes in Mitochondrial Function in the Brain of Offspring Following Prenatal Maternal Immune Activation
Authors: Cieślik Magdalena , Zawadzka Aleksandra , Czapski Grzegorz A. , Wilkaniec Anna , Adamczyk Agata
Published: April 2023

Maternal immune activation (MIA) is an important risk factor for neurodevelopmental disorders such as autism. The aim of the current study was to investigate the development-dependent changes in the mitochondrial function of MIA-exposed offspring, which may contribute to autism-like deficits. MIA was evoked by the single intraperitoneal administration of lipopolysaccharide to pregnant rats at gestation day 9.5, and several aspects of mitochondrial function in fetuses and in the brains of seven-day-old pups and adolescent offspring were analyzed along with oxidative stress parameters measurement. It was found that MIA significantly increased the activity of NADPH oxidase (NOX), an enzyme generating reactive oxygen species (ROS) in the fetuses and in the brain of seven-day-old pups, but not in the adolescent offspring. Although a lower mitochondrial membrane potential accompanied by a decreased ATP level was already observed in the fetuses and in the brain of seven-day-old pups, persistent alterations of ROS, mitochondrial membrane depolarization, and lower ATP generation with concomitant electron transport chain complexes downregulation were observed only in the adolescent offspring. We suggest that ROS observed in infancy are most likely of a NOX activity origin, whereas in adolescence, ROS are produced by damaged mitochondria. The accumulation of dysfunctional mitochondria leads to the intense release of free radicals that trigger oxidative stress and neuroinflammation, resulting in an interlinked vicious cascade.
Transcriptome Analysis of Roots from Wheat (Triticum aestivum L.) Varieties in Response to Drought Stress
Authors: Xi Wei , Hao Chenyang , Li Tian , Wang Huajun , Zhang Xueyong
Published: April 2023

Under climate change, drought is one of the most limiting factors that influences wheat (Triticum aestivum L.) production. Exploring stress-related genes is vital for wheat breeding. To identify genes related to the drought tolerance response, two common wheat cultivars, Zhengmai 366 (ZM366) and Chuanmai 42 (CM42), were selected based on their obvious difference in root length under 15% PEG-6000 treatment. The root length of the ZM366 cultivar was significantly longer than that of CM42. Stress-related genes were identified by RNA-seq in samples treated with 15% PEG-6000 for 7 days. In total, 11,083 differentially expressed genes (DEGs) and numerous single nucleotide polymorphisms (SNPs) and insertions/deletions (InDels) were identified. GO enrichment analysis revealed that the upregulated genes were mainly related to the response to water, acidic chemicals, oxygen-containing compounds, inorganic substances, and abiotic stimuli. Among the DEGs, the expression levels of 16 genes in ZM366 were higher than those in CM42 after the 15% PEG-6000 treatment based on RT-qPCR. Furthermore, EMS-induced mutants in Kronos (T. turgidum L.) of 4 representative DEGs possessed longer roots than the WT after the 15% PEG-6000 treatment. Altogether, the drought stress genes identified in this study represent useful gene resources for wheat breeding.
Preliminary Study on the Effect of a Single High-Energy Electromagnetic Pulse on Morphology and Free Radical Generation in Human Mesenchymal Stem Cells
Authors: Czwartos Joanna , Dobosz Bernadeta , Kasprzycka Wiktoria , Osuchowska Paulina Natalia , Stępińska Małgorzata , Trafny Elżbieta Anna , Starzyński Jacek , Mierczyk Zygmunt
Published: April 2023

The effect of nanosecond electromagnetic pulses on human health, and especially on forming free radicals in human cells, is the subject of continuous research and ongoing discussion. This work presents a preliminary study on the effect of a single high-energy electromagnetic pulse on morphology, viability, and free radical generation in human mesenchymal stem cells (hMSC). The cells were exposed to a single electromagnetic pulse with an electric field magnitude of ~1 MV/m and a pulse duration of ~120 ns generated from a 600 kV Marx generator. The cell viability and morphology at 2 h and 24 h after exposure were examined using confocal fluorescent microscopy and scanning electron microscopy (SEM), respectively. The number of free radicals was investigated with electron paramagnetic resonance (EPR). The microscopic observations and EPR measurements showed that the exposure to the high-energy electromagnetic pulse influenced neither the number of free radicals generated nor the morphology of hMSC in vitro compared to control samples.