bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Avoidance and Social Adjustment in Chinese Preschool Migrant Children: The Moderating Role of Household Chaos and Gender
Authors: Zhu Jingjing , Yin Xiaoqi , Wang Guangheng , Jiang Yaoqin , Li Yan
Published: December 2022

The present study explored the moderating role of household chaos and gender in the relation between social avoidance and social adjustment among Chinese preschool migrant children. Participants were 148 children (82 boys, Mage = 62.63 months, SD = 0.05) from two kindergartens, Shanghai, People’s Republic of China. Multi-source assessments included: (1) mother ratings of children’s social avoidance; (2) mother ratings of families’ household chaos; (3) teacher ratings of children’s prosocial behavior, peer exclusion, interpersonal skills, and internalizing problems. Results showed that social avoidance significantly predicted peer exclusion among Chinese migrant preschoolers. Moreover, household chaos moderated the relationship between social avoidance and social adjustment. Specifically, at higher levels of household chaos, social avoidance was negatively associated with interpersonal skills. In contrast, social avoidance was not associated with interpersonal skills at a lower level of household chaos. In addition, social avoidance was positively associated with peer exclusion among boys but not girls. The current findings inform us of the importance of reducing household chaos to buffer the negative adjustment among socially avoidant young children who migrated from rural to urban China. The findings also highlight the need to pay particular attention to migrant socially avoidant boys’ development in early childhood and the importance of considering the meaning and implication of social avoidance for migrant preschoolers in Chinese culture.
Effect of Watering down Environmental Regulation on Residents’ Health in China: A Quasi-Natural Experiment of Local Officials’ Promotion Motivation
Authors: Chen Xiaojia , Chen Yue , Li Yuanfen , Xu Wei
Published: December 2022

Environmental performance is increasingly important in promoting officials, whose pursuit of promotions and related behavior may affect the health of residents in their jurisdictions. In this study, we spatially matched Chinese river water quality monitoring station data, enterprise pollution emission data, and resident health data and quantified how Chinese officials pursuing promotions based on environmental performance affected resident health using a regression discontinuity design and difference-in-difference with interaction terms design strategy. The results show that the upstream–downstream disparity of environmental governance and pollutant emissions affects the residents’ health, medical treatment behavior, and medical expenditure. Furthermore, we identified the causal relationship between official promotion and upstream–downstream disparity and estimated the marginal effect of promotion on residents’ health. The study suggests that local officials limit the pollution emissions of enterprises in the upstream river to achieve environmental performance and relax the pollution restrictions of firms in the downstream river to achieve economic performance, such that the health of residents near the river is differentially affected.
Are We Ready to Implement Circadian Hygiene Interventions and Programs?
Authors: Moreno Claudia R. C. , Raad Rose , Gusmão Waléria D. P. , Luz Cristina S. , Silva Victor M. , Prestes Renilda M. , Saraiva Susy P. , Lemos Lucia C. , Vasconcelos Suleima P. , Nehme Patrícia X. S. A. , Louzada Fernando M. , Marqueze Elaine C.
Published: December 2022

Circadian hygiene, a concept not to be confused with the notion of public or social hygiene, should be discussed among experts and society. Light–dark cycles and other possible synchronizers of the human circadian timing system affect ways of life, including sleeping, eating, working and physical activity. Some of these behaviors have also been investigated individually as synchronizers (e.g., eating times). Therefore, the knowledge held today about circadian rhythms, and their implications for health, allows future perspectives in this field to be mapped. The present article summarizes the latest knowledge on factors influencing circadian rhythms to discuss a perspective for the future of health promotion based on circadian hygiene. However, it is important to highlight that circadian hygiene is the product of an imbrication of individual and societal involvement. First, it is important to adopt practices and devise public health policies in line with circadian hygiene. Second, individual healthy habits require internal rhythms to be examined. Last, the research agenda on circadian hygiene can be developed on a public as well as individual level, raising the question as to how much society is willing to embrace this change.
Portuguese Version of the Ageing Attitudes Questionnaire (AAQ): Validation of the Psychometric Properties
Authors: Pedroso de Lima Margarida , Martins Paulo , Gonzalez António-José
Published: December 2022

The Ageing Attitudes Questionnaire—AAQ was validated for the Portuguese population to understand the importance of attitudes towards old age and their impact on the subjective well-being of older adults. A sample of 400 subjects (from 18 to 93 years) answered a socio-demographic questionnaire, and the AAQ, composed of three subscales (psychosocial losses, physical change, and psychological growth). The CFA confirmed the tri-factorial structure with very good adjustment of the model to the data, with the Cronbach alpha of the total scale scoring 0.84 and ranging from 0.65 to 0.77 for each factor. A total of nine items were omitted for poor factor loadings (<0.50), namely in factor 1 items 9-17-20, in factor 2 items 7 and 24 and, finally, in factor 3 we omitted items 4-18-19-21. Notwithstanding, three items below the criteria were maintained, as they conceptually fit into the factor. Of the final 15 AAQ items, 5 belong to the Psychosocial Loss Factor, 6 to Physical Change Factor, and 4 to Psychosocial Growth Factor. This tree factor model explained 50.1% of the total variance. In conclusion, this study supports that AAQ has acceptable validity, confirming the composite reliability and the discriminant validity, but not the convergent validity. Through multi-group analysis, the invariance of the scale was confirmed. This validation is of pivotal importance once it allows measuring attitudes towards ageing in the Portuguese population, thus facilitating the prevention of ageism and the promotion of well-being across the lifespan.
Artificial Intelligence in the Management of Rotator Cuff Tears
Authors: Familiari Filippo , Galasso Olimpio , Massazza Federica , Mercurio Michele , Fox Henry , Srikumaran Uma , Gasparini Giorgio
Published: December 2022

Technological innovation is a key component of orthopedic surgery. Artificial intelligence (AI), which describes the ability of computers to process massive data and “learn” from it to produce outputs that mirror human cognition and problem solving, may become an important tool for orthopedic surgeons in the future. AI may be able to improve decision making, both clinically and surgically, via integrating additional data-driven problem solving into practice. The aim of this article will be to review the current applications of AI in the management of rotator cuff tears. The article will discuss various stages of the clinical course: predictive models and prognosis, diagnosis, intraoperative applications, and postoperative care and rehabilitation. Throughout the article, which is a review in terms of study design, we will introduce the concept of AI in rotator cuff tears and provide examples of how these tools can impact clinical practice and patient care. Though many advancements in AI have been made regarding evaluating rotator cuff tears—particularly in the realm of diagnostic imaging—further advancements are required before they become a regular facet of daily clinical practice.
Human Monkeypox—A Global Public Health Emergency
Authors: Zardi Enrico Maria , Chello Camilla
Published: December 2022

Monkeypox, a viral zoonosis caused by an Orthopoxvirus, is clinically characterized by fever, headache, lymphadenopathy, myalgia, rash and burdened by some complications that can be severe and life threatening. Monkeypox, endemic in some central and west African countries, in tropical areas near equator, rose to the headlines following its recent outbreak in non-endemic countries of Europe and the USA. Thus, the World Health Organization, worried about the growing dimension of the problem, declared monkeypox a global public health emergency. Now, after months of careful observation, the western scientific research is drawing conclusion that African endemic countries represent a reserve pool able to feed, through travelers and sexual networks, the outbreak in non-endemic countries in which high-risk communities such as gay and bisexual men are the most affected. Prevention through vaccination and early diagnosis are the core to breaking the chain of diffusion of this epidemic. Particular attention should be paid to avoid the spread from endemic countries, also implementing the economic investments in their public health system. Information campaigns and assistance to high-risk classes in non-endemic countries are important priorities, however, assuming that specific treatments for this disease are still tentative.
Barriers and Attitudes of Primary Healthcare Physicians to Insulin Initiation and Intensification in Saudi Arabia
Authors: Alhagawy Ali Jaber , Yafei Saeed , Hummadi Abdulrahman , Abutaleb Raed , Hakamy Mohammed , Alzughbi Turki , Gharawi Nabeel , Moafa Manal , Mokali Asma , Alhiqwy Ibrahim , Altherwi Mousa
Published: December 2022

Saudi Arabia is a country with high prevalence of diabetes, uncontrolled diabetes, and diabetes-related complications. Poor glycemic control is multifactorial and could be explained in part by physician and patient reluctance toward insulin or insulin inertia. This study aimed to address physician barriers toward insulin therapy in primary care settings. It included 288 physicians from 168 primary healthcare centers (PHC) in the Jazan region of Saudi Arabia. Participants responded to questionnaire investigating physicians’ attitude and barriers to insulin initiation and intensification in PHCs. In physician opinion, the most common barriers among their patients were fear of injection, lack of patient education, fear of hypoglycemia, and difficult administration. Physicians were reluctant to initiate insulin for T2D patients mostly due to patient non-adherence to blood sugar measurement, non-adherence to appointment or treatment, elderly patients, or due to patient refusal. Physicians’ fear of hypoglycemia, lack of staff for patient education, and lack of updated knowledge were the primary clinician-related barriers. Exaggerated fears of insulin side effects, patient non-adherence, limited staff for patient’s education, patient refusal, and inadequate consultation time were the main barriers to insulin acceptance and prescription.
Computational Prediction of Resistance Induced Alanine-Mutation in ATP Site of Epidermal Growth Factor Receptor
Authors: Amelia Tasia , Setiawan Aderian Novito , Kartasasmita Rahmana Emran , Ohwada Tomohiko , Tjahjono Daryono Hadi
Published: December 2022

Epidermal growth factor receptor (EGFR) resistance to tyrosine kinase inhibitors can cause low survival rates in mutation-positive non-small cell lung cancer patients. It is necessary to predict new mutations in the development of more potent EGFR inhibitors since classical and rare mutations observed were known to affect the effectiveness of the therapy. Therefore, this research aimed to perform alanine mutagenesis scanning on ATP binding site residues without COSMIC data, followed by molecular dynamic simulations to determine their molecular interactions with ATP and erlotinib compared to wild-type complexes. Based on the result, eight mutations were found to cause changes in the binding energy of the ATP analogue to become more negative. These included G779A, Q791A, L792A, R841A, N842A, V843A, I853A, and D855A, which were predicted to enhance the affinity of ATP and reduce the binding ability of inhibitors with the same interaction site. Erlotinib showed more positive energy among G779A, Q791A, I853A, and D855A, due to their weaker binding energy than ATP. These four mutations could be anticipated in the development of the next inhibitor to overcome the incidence of resistance in lung cancer patients.
METTL3 Regulates the Inflammatory Response in CPB2 Toxin-Exposed IPEC-J2 Cells through the TLR2/NF-κB Signaling Pathway
Authors: Zhang Juanli , Yang Jiaojiao , Gao Xiaoli , Huang Xiaoyu , Luo Ruirui , Yang Qiaoli , Yan Zunqiang , Wang Pengfei , Wang Wei , Xie Kaihui , Li Jie , Zhang Bo , Gun Shuangbao
Published: December 2022

Clostridium perfringens beta2 (CPB2) toxin is one of the main pathogenic toxins produced by Clostridium perfringens, which causes intestinal diseases in animals and humans. The N6-methyladenosine (m6A) modification is the most common reversible modification in eukaryotic disease processes. Methyltransferase-like 3 (METTL3) regulates immunity and inflammatory responses induced by the bacterial infections in animals. However, METTL3′s involvement in CPB2-treated intestinal porcine epithelial cell line-J2 (IPEC-J2) remains unclear. In the current study, we used methylated RNA immunoprecipitation-quantitative polymerase chain reaction, Western blotting and immunofluorescence assay to determine the role of METTL3 in CPB2-exposed IPEC-J2 cells. The findings revealed that m6A and METTL3 levels were increased in CPB2 treated IPEC-J2 cells. Functionally, METTL3 overexpression promoted the release of inflammatory factors, increased cytotoxicity, decreased cell viability and disrupted tight junctions between cells, while the knockdown of METTL3 reversed these results. Furthermore, METTL3 was involved in the inflammatory response of IPEC-J2 cells by activating the TLR2/NF-κB signaling pathway through regulating TLR2 m6A levels. In conclusion, METTL3 overexpression triggered the TLR2/NF-κB signaling pathway and promoted CPB2-induced inflammatory responses in IPEC-J2 cells. These findings may provide a new strategy for the prevention and treatment of diarrhea caused by Clostridium perfringens.
SARS-CoV-2 Spike Protein Mutation at Cysteine-488 Impairs Its Golgi Localization and Intracellular S1/S2 Processing
Authors: Yamamoto Yuichiro , Inoue Tetsuya , Inoue Miyu , Murae Mana , Fukasawa Masayoshi , Kaneko Mika K. , Kato Yukinari , Noguchi Kohji
Published: December 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds to the cellular receptor—angiotensin-converting enzyme-2 (ACE2) as the first step in viral cell entry. SARS-CoV-2 spike protein expression in the ACE2-expressing cell surface induces cell–cell membrane fusion, thus forming syncytia. To exert its fusogenic activity, the spike protein is typically processed at a specific site (the S1/S2 site) by cellular proteases such as furin. The C488 residue, located at the spike–ACE2 interacting surface, is critical for the fusogenic and infectious roles of the SARS-CoV-2 spike protein. We have demonstrated that the C488 residue of the spike protein is involved in subcellular targeting and S1/S2 processing. C488 mutant spike localization to the Golgi apparatus and cell surface were impaired. Consequently, the S1/S2 processing of the spike protein, probed by anti-Ser-686-cleaved spike antibody, markedly decreased in C488 mutant spike proteins. Moreover, brefeldin-A-mediated endoplasmic-reticulum-to-Golgi traffic suppression also suppressed spike protein S1/S2 processing. As brefeldin A treatment and C488 mutation inhibited S1/S2 processing and syncytia formation, the C488 residue of spike protein is required for functional spike protein processing.
Current Scenario of Exogenously Induced RNAi for Lepidopteran Agricultural Pest Control: From dsRNA Design to Topical Application
Authors: Lucena-Leandro Vívian S. , Abreu Emanuel F. A. , Vidal Leonardo A. , Torres Caroline R. , Junqueira Camila I. C. V. F. , Dantas Juliana , Albuquerque Érika V. S.
Published: December 2022

Invasive insects cost the global economy around USD 70 billion per year. Moreover, increasing agricultural insect pests raise concerns about global food security constraining and infestation rising after climate changes. Current agricultural pest management largely relies on plant breeding—with or without transgenes—and chemical pesticides. Both approaches face serious technological obsolescence in the field due to plant resistance breakdown or development of insecticide resistance. The need for new modes of action (MoA) for managing crop health is growing each year, driven by market demands to reduce economic losses and by consumer demand for phytosanitary measures. The disabling of pest genes through sequence-specific expression silencing is a promising tool in the development of environmentally-friendly and safe biopesticides. The specificity conferred by long dsRNA-base solutions helps minimize effects on off-target genes in the insect pest genome and the target gene in non-target organisms (NTOs). In this review, we summarize the status of gene silencing by RNA interference (RNAi) for agricultural control. More specifically, we focus on the engineering, development and application of gene silencing to control Lepidoptera through non-transforming dsRNA technologies. Despite some delivery and stability drawbacks of topical applications, we reviewed works showing convincing proof-of-concept results that point to innovative solutions. Considerations about the regulation of the ongoing research on dsRNA-based pesticides to produce commercialized products for exogenous application are discussed. Academic and industry initiatives have revealed a worthy effort to control Lepidoptera pests with this new mode of action, which provides more sustainable and reliable technologies for field management. New data on the genomics of this taxon may contribute to a future customized target gene portfolio. As a case study, we illustrate how dsRNA and associated methodologies could be applied to control an important lepidopteran coffee pest.
Dorsolateral Prefrontal Cortex Glutamate/Gamma-Aminobutyric Acid (GABA) Alterations in Clinical High Risk and First-Episode Schizophrenia: A Preliminary 7-T Magnetic Resonance Spectroscopy Imaging Study
Authors: Mayeli Ahmad , Sonnenschein Susan F. , Yushmanov Victor E. , Wilson James D. , Blazer Annie , Foran William , Perica Maria , Calabro Finnegan J. , Luna Beatriz , Hetherington Hoby P. , Sarpal Deepak K. , Ferrarelli Fabio
Published: December 2022

Converging lines of evidence suggest that an imbalance between excitation and inhibition is present in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia (SCZ). Gamma-aminobutyric-acid (GABA) and, to a lesser extent, glutamate (Glu) abnormalities were reported in the DLPFC of SCZ patients, especially on the right hemisphere, by post-mortem studies. However, in vivo evidence of GABA, Glu, and Glu/GABA DLPFC abnormalities, particularly on the right side and the early stages of illness, is limited. In this preliminary study, we utilized 7-Tesla magnetic resonance spectroscopic imaging (MRSI) to investigate bilateral Glu/Creatine (Cre), GABA/Cre, and Glu/GABA in the DLPFC of sixteen first episode schizophrenia (FES), seventeen clinical high risk (CHR), and twenty-six healthy comparison (HC) subjects. FES and CHR had abnormal GABA/Cre and Glu/GABA in the right DLPFC (rDLPFC) compared with HC participants, while no differences were observed in the left DLPFC (lDLPFC) among the three groups. Furthermore, HC had higher Glu/GABA in rDLPFC compared to lDLPFC (R > L), whereas the opposite relationship (R < L) was observed in the DLPFC Glu/GABA of FES patients. Altogether, these findings indicate that GABA/Cre and Glu/GABA DLPFC alterations are present before illness manifestation and worsen in FES patients, thus representing a putative early pathophysiological biomarker for SCZ and related psychotic disorders.
In-Silico Functional Metabolic Pathways Associated to Chlamydia trachomatis Genital Infection
Authors: Filardo Simone , Di Pietro Marisa , De Angelis Marta , Brandolino Gabriella , Porpora Maria Grazia , Sessa Rosa
Published: December 2022

The advent of high-throughput technologies, such as 16s rDNA sequencing, has significantly contributed to expanding our knowledge of the microbiota composition of the genital tract during infections such as Chlamydia trachomatis. The growing body of metagenomic data can be further exploited to provide a functional characterization of microbial communities via several powerful computational approaches. Therefore, in this study, we investigated the predicted metabolic pathways of the cervicovaginal microbiota associated with C. trachomatis genital infection in relation to the different Community State Types (CSTs), via PICRUSt2 analysis. Our results showed a more rich and diverse mix of predicted metabolic pathways in women with a CST-IV microbiota as compared to all the other CSTs, independently from infection status. C. trachomatis genital infection further modified the metabolic profiles in women with a CST-IV microbiota and was characterized by increased prevalence of the pathways for the biosynthesis of precursor metabolites and energy, biogenic amino-acids, nucleotides, and tetrahydrofolate. Overall, predicted metabolic pathways might represent the starting point for more precisely designed future metabolomic studies, aiming to investigate the actual metabolic pathways characterizing C. trachomatis genital infection in the cervicovaginal microenvironment.
A Dietary Oxysterol, 7-Ketocholesterol, Exacerbates Imiquimod-Induced Psoriasis-like Dermatitis in Steatohepatitic Mice
Authors: Saga Ayami , Koseki Masahiro , Kanno Kotaro , Chang Jiuyang , Higo Tomoaki , Okuzaki Daisuke , Okada Takeshi , Inui Hiroyasu , Asaji Masumi , Tanaka Katsunao , Omatsu Takashi , Nishihara Sae , Zhu Yinghong , Ito Kaori , Hattori Hiroaki , Ichi Ikuyo , Kamada Yoshihiro , Ono Masafumi , Saibara Toshiji , Ohama Tohru , Hikoso Shungo , Nishida Makoto , Yamashita Shizuya , Sakata Yasushi
Published: December 2022

Patients with psoriasis are at a higher risk of developing nonalcoholic fatty liver disease. We previously identified an oxidized derivative of cholesterol, 7-ketocholesterol (7KC), in diet-induced steatohepatitic mice. Here, we investigated whether 7KC exacerbates psoriasis-like dermatitis by accelerating steatohepatitis in mice. A high-fat/high-cholesterol/high-sucrose/bile salt diet (nonalcoholic steatohepatitis (NASH) diet) with or without 0.0125% 7KC was fed to C57BL/6 mice (7KC or control group) for three weeks to induce steatohepatitis. A 5% imiquimod cream was then applied to the ears and dorsal skin for four days to induce psoriasis-like dermatitis. Hepatic lipid accumulation and inflammatory cell infiltration were exacerbated in the 7KC group compared with the control group after three weeks. Serum tumor necrosis factor-α (TNF-α) levels were also elevated in the 7KC group (108.5 ± 9.8 vs. 83.1 ± 13.1 pg/mL, p < 0.005). Imiquimod cream increased the psoriasis area severity index (PASI) score in mice in the 7KC group (9.14 ± 0.75 vs. 5.17 ± 1.17, p < 0.0001). Additionally, Tnfa, Il23a, Il17a, and Il22 mRNA levels in the dorsal lesion were significantly upregulated. Finally, Th17 cell differentiation and the TNF signaling pathway were enhanced in the dorsal lesions and liver of mice in the 7KC group. These data suggest that steatohepatitis and psoriasis are linked by a potent, diet-related factor.
Selective CB2 Receptor Agonist, HU-308, Reduces Systemic Inflammation in Endotoxin Model of Pneumonia-Induced Acute Lung Injury
Authors: Hall Stefan , Faridi Sufyan , Trivedi Purvi , Sultana Saki , Ray Bithika , Myers Tanya , Euodia Irene , Vlatten David , Castonguay Mathieu , Zhou Juan , Kelly Melanie , Lehmann Christian
Published: December 2022

Acute respiratory distress syndrome (ARDS) and sepsis are risk factors contributing to mortality in patients with pneumonia. In ARDS, also termed acute lung injury (ALI), pulmonary immune responses lead to excessive pro-inflammatory cytokine release and aberrant alveolar neutrophil infiltration. Systemic spread of cytokines is associated with systemic complications including sepsis, multi-organ failure, and death. Thus, dampening pro-inflammatory cytokine release is a viable strategy to improve outcome. Activation of cannabinoid type II receptor (CB2) has been shown to reduce cytokine release in various in vivo and in vitro studies. Herein, we investigated the effect of HU-308, a specific CB2 agonist, on systemic and pulmonary inflammation in a model of pneumonia-induced ALI. C57Bl/6 mice received intranasal endotoxin or saline, followed by intravenous HU-308, dexamethasone, or vehicle. ALI was scored by histology and plasma levels of select inflammatory mediators were assessed by Luminex assay. Intravital microscopy (IVM) was performed to assess leukocyte adhesion and capillary perfusion in intestinal and pulmonary microcirculation. HU-308 and dexamethasone attenuated LPS-induced cytokine release and intestinal microcirculatory impairment. HU-308 modestly reduced ALI score, while dexamethasone abolished it. These results suggest administration of HU-308 can reduce systemic inflammation without suppressing pulmonary immune response in pneumonia-induced ALI and systemic inflammation.
The Utility of Novel Kidney Injury Biomarkers in Early Detection of CSA-AKI
Authors: Udzik Jakub , Waszczyk Aleksandra , Wojciechowska-Koszko Iwona , Kwiatkowski Paweł , Roszkowska Paulina , Rogulska Karolina , Safranow Krzysztof , Biskupski Andrzej , Kwiatkowski Sebastian , Kwiatkowska Ewa
Published: December 2022

Cardiac surgery-associated acute kidney injury (CSA-AKI) is one of the most common complications of cardiac surgery procedures. In this study, the authors attempt to provide new data regarding the application of novel kidney injury biomarkers in the early diagnostics of CSA-AKI. 128 adult patients undergoing elective cardiac surgery procedures with the use of cardiopulmonary by-pass (CPB) were enrolled in this study. Novel kidney injury biomarkers were marked in the plasma and urine 6 h after weaning from the CPB. A significant difference in the postoperative biomarkers’ concentration between the AKI and no-AKI group was found, regarding plasma IL-8, plasma TNF-α and urine NGAL, normalized for creatinine excretion (NGAL/Cr). These were also independent predictors of CSA-AKI. An independent risk factor for CSA-AKI proved to be preoperative CKD. Plasma IL-8 and TNF-α, as well as urine NGAL/Cr, are independent early indicators of CSA-AKI and pose a promising alternative for creatinine measurements. The cut-off points for these biomarkers proposed in this investigation should be confronted with more data and revised to achieve a suitable diagnostic value.
Exacerbation of Cisplatin Cellular Toxicity by Regulation of the Human Organic Cation Transporter 2 through Angiotensin II
Authors: Kantauskaite Marta , Hucke Anna , Snieder Beatrice , Ciarimboli Giuliano
Published: December 2022

Cisplatin (CDDP) is an efficient chemotherapeutic drug, whose use is associated with the development of serious undesired toxicities, such as nephrotoxicity. The human organic cation transporter 2 (hOCT2), which is highly expressed in the basolateral membrane domain of renal proximal tubules seems to play an important role in the development of CDDP nephrotoxicity. The role of angiotensin II (AII) signaling by binding to the AII receptor type 1 (AT1R) in the development and/or progression of CDDP nephrotoxicity is debated. Therefore, in this work, the regulation of hOCT2 activity by AII and its role in the development of CDDP cellular toxicity was investigated. To do this, hOCT2 was overexpressed by viral transduction in Madin–Darby Canine Kidney (MDCK) cells which were cultivated on a filter. This approach allows the separation of an apical and a basolateral membrane domain, which are easily accessible for experimentation. In this system, hOCT2 was mainly localized on the basolateral plasma membrane domain of the cells. The transporter was functional since a specific uptake of the fluorescent organic cation 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP+) with an affinity (Km) of 35 µM was only detectable by the addition of ASP+ to the basolateral compartment of hOCT2 expressing MDCK (hOCT2-MDCK) cells. Similarly, CDDP toxicity was evident mainly by CDDP addition to the basolateral compartment of hOCT2-MDCK cells cultivated on a filter. The addition of 1 nM AII stimulated hOCT2 function via PKC activation and worsened CDDP cytotoxicity via binding to AT1R. Therefore, the AII signaling pathway may be implicated in the development and/or progression of CDDP nephrotoxicity. This signaling pathway may be a target for protective interventions for example by blocking AT1R in the kidneys. However, it should be further investigated whether these findings obtained in a cell culture system may have translational relevance for the clinical situation. For toxicity experiments, a 100 µM CDDP concentration was used, which is high but allows us to identify clearly toxic effects due to hOCT2. In summary, down-regulation of hOCT2 activity by the inhibition of the AII signaling pathway may protect against CDDP nephrotoxicity.
New Strategies Protecting from Ischemia/Reperfusion
Authors: Hauet Thierry , Pisani Didier F.
Published: December 2022

This Special Issue aims to highlight new avenues in the management of Ischemia/Reperfusion (I/R) injury [...]
PKR-Mediated Phosphorylation of eIF2a and CHK1 Is Associated with Doxorubicin-Mediated Apoptosis in HCC1143 Triple-Negative Breast Cancer Cells
Authors: Lee Sol , Jee Ha-Yeon , Lee Yoon-Gyeong , Shin Jong-Il , Jeon Yong-Joon , Kim Ji-Beom , Seo Hye-eun , Lee Ji-Yeon , Lee Kyungho
Published: December 2022

Triple-negative breast cancer is more aggressive than other types of breast cancer. Protein kinase R (PKR), which is activated by dsRNA, is known to play a role in doxorubicin-mediated apoptosis; however, its role in DNA damage-mediated apoptosis is not well understood. In this study, we investigated the roles of PKR and its downstream players in doxorubicin-treated HCC1143 triple-negative breast cancer cells. Doxorubicin treatment induces DNA damage and apoptosis. Interestingly, doxorubicin treatment induced the phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) via PKR, whereas the inhibition of PKR with inhibitor C16 reduced eIF2α phosphorylation. Under these conditions, doxorubicin-mediated DNA fragmentation, cell death, and poly(ADP ribose) polymerase and caspase 7 levels were recovered. In addition, phosphorylation of checkpoint kinase 1 (CHK1), which is known to be involved in doxorubicin-mediated DNA damage, was increased by doxorubicin treatment, but blocked by PKR inhibition. Protein translation was downregulated by doxorubicin treatment and upregulated by blocking PKR phosphorylation. These results suggest that PKR activation induces apoptosis by increasing the phosphorylation of eIF2α and CHK1 and decreasing the global protein translation in doxorubicin-treated HCC1143 triple-negative breast cancer cells.
A Golgi-Located Transmembrane Nine Protein Gene TMN11 Functions in Manganese/Cadmium Homeostasis and Regulates Growth and Seed Development in Rice
Authors: Li He , Li Chao , Liu Xuesong , Yang Zhimin
Published: December 2022

Metal transporters play crucial roles in plant nutrition, development, and metal homeostasis. To date, several multi-proteins have been identified for metal transport across the plasma membrane and tonoplast. Nevertheless, Golgi endomembrane metal carriers and their mechanisms are less documented. In this study, we identified a new transmembrane nine (TMN) family gene, TMN11, which encodes a Mn transport protein that was localized to the cis-Golgi endomembrane in rice. OsTMN11 contains a typically conserved long luminal N-terminal domain and nine transmembrane domains. OsTMN11 was ubiquitously expressed over the lifespan of rice and strongly upregulated in young rice under excess Mn(II)/Cd(II) stress. Ectopic expression of OsTMN11 in an Mn-sensitive pmr1 mutant (PMR1 is a Golgi-resident Mn exporter) yeast (Saccharomyces cerevisiae) restored the defective phenotype and transported excess Mn out of the cells. As ScPMR1 mediates cellular Mn efflux via a vesicle-secretory pathway, the results suggest that OsTMN11 functions in a similar manner. OsTMN11 knockdown (by RNAi) compromised the growth of young rice, manifested as shorter plant height, reduced biomass, and chlorosis under excessive Mn and Cd conditions. Two lifelong field trials with rice cropped in either normal Mn supply conditions or in Cd-contaminated farmland demonstrated that knockdown of OsTMN11 impaired the capacity of seed development (including panicle, spikelet fertility, seed length, grain weight, etc.). The mature RNAi plants contained less Mn but accumulated Cd in grains and rice straw, confirming that OsTMN11 plays a fundamental role in metal homeostasis associated with rice growth and development even under normal Mn supply conditions.
Comprehensive Investigation of Parameters Influencing Fluorescence Lifetime Imaging Microscopy in Frequency- and Time-Domain Illustrated by Phasor Plot Analysis
Authors: Kellerer Thomas , Janusch Janko , Freymüller Christian , Rühm Adrian , Sroka Ronald , Hellerer Thomas
Published: December 2022

Having access to fluorescence lifetime, researchers can reveal in-depth details about the microenvironment as well as the physico-chemical state of the molecule under investigation. However, the high number of influencing factors might be an explanation for the strongly deviating values of fluorescent lifetimes for the same fluorophore reported in the literature. This could be the reason for the impression that inconsistent results are obtained depending on which detection and excitation scheme is used. To clarify this controversy, the two most common techniques for measuring fluorescence lifetimes in the time-domain and in the frequency-domain were implemented in one single microscopy setup and applied to a variety of fluorophores under different environmental conditions such as pH-value, temperature, solvent polarity, etc., along with distinct state forms that depend, for example, on the concentration. From a vast amount of measurement results, both setup- and sample-dependent parameters were extracted and represented using a single display form, the phasor-plot. The measurements showed consistent results between the two techniques and revealed which of the tested parameters has the strongest influence on the fluorescence lifetime. In addition, quantitative guidance as to which technique is most suitable for which research task and how to perform the experiment properly to obtain consistent fluorescence lifetimes is discussed.
Combined Micellar Liquid Chromatography Technique and QSARs Modeling in Predicting the Blood–Brain Barrier Permeation of Heterocyclic Drug-like Compounds
Authors: Janicka Małgorzata , Śliwińska Anna , Sztanke Małgorzata , Sztanke Krzysztof
Published: December 2022

The quantitative structure–activity relationship (QSAR) methodology was used to predict the blood–brain permeability (log BB) for 65 synthetic heterocyclic compounds tested as promising drug candidates. The compounds were characterized by different descriptors: lipophilicity, parachor, polarizability, molecular weight, number of hydrogen bond acceptors, number of rotatable bonds, and polar surface area. Lipophilic properties of the compounds were evaluated experimentally by micellar liquid chromatography (MLC). In the experiments, sodium dodecyl sulfate (SDS) as the effluent component and the ODS-2 column were used. Using multiple linear regression and leave-one-out cross-validation, we derived the statistically significant and highly predictive quantitative structure–activity relationship models. Thus, this study provides valuable information on the expected properties of the substances that can be used as a support tool in the design of new therapeutic agents.
Donor Genetic Predisposition to High Interleukin-10 Production Appears Protective against Acute Graft-Versus-Host Disease
Authors: Tripathi Gaurav , Khanolkar Rutvij A. , Faridi Rehan M. , Kalra Amit , Dharmani-Khan Poonam , Shabani-Rad Meer-Taher , Berka Noureddine , Daly Andrew , Storek Jan , Khan Faisal M.
Published: December 2022

The persistence of graft-versus-host disease (GVHD) as the principal complication of allogeneic hematopoietic cell transplantation (HCT) demonstrates that HLA matching alone is insufficient to prevent alloreactivity. We performed molecular and functional characterization of 22 candidate cytokine genes for their potential to improve matching in 315 myeloablative, 10/10 HLA-matched donor–recipient pairs. Recipients of a graft carrying the -1082GG IL10 gene promoter region variant had a three-fold lower incidence of grade II–IV acute GVHD compared to IL10-1082AA graft recipients (SHR = 0.25, p = 0.005). This was most evident in matched unrelated donor (MUD) transplants, where the greatest alloreactivity is expected. IL10-1082GG transplants did not experience an increased incidence of relapse, and, consequently, overall survival was two-fold higher in IL10-1082GG MUD transplants (HR = 0.17, p = 0.023). Longitudinal post-transplant measurements demonstrated that -1082GG is a high-IL10-producing and -expressing genotype with attenuated CD8+ T-cell reconstitution. High post-transplant donor chimerism in T- and myeloid-cells (>95%) confirmed a predominant donor, rather than recipient, genotype effect on immune function and aGVHD. To date, this is the first study to report corroborating genome-to-cellular evidence for a non-HLA donor immunogenetic variant that appears to be protective against GVHD. The incorporation of IL10 variants in donor selection criteria and clinical-management decisions has the potential to improve patient outcomes.
Impact of Saccharomyces cerevisiae on the Field of Single-Molecule Biophysics
Authors: Ball David A. , Jalloh Binta , Karpova Tatiana S.
Published: December 2022

Cellular functions depend on the dynamic assembly of protein regulator complexes at specific cellular locations. Single Molecule Tracking (SMT) is a method of choice for the biochemical characterization of protein dynamics in vitro and in vivo. SMT follows individual molecules in live cells and provides direct information about their behavior. SMT was successfully applied to mammalian models. However, mammalian cells provide a complex environment where protein mobility depends on numerous factors that are difficult to control experimentally. Therefore, yeast cells, which are unicellular and well-studied with a small and completely sequenced genome, provide an attractive alternative for SMT. The simplicity of organization, ease of genetic manipulation, and tolerance to gene fusions all make yeast a great model for quantifying the kinetics of major enzymes, membrane proteins, and nuclear and cellular bodies. However, very few researchers apply SMT techniques to yeast. Our goal is to promote SMT in yeast to a wider research community. Our review serves a dual purpose. We explain how SMT is conducted in yeast cells, and we discuss the latest insights from yeast SMT while putting them in perspective with SMT of higher eukaryotes.
Genome-Wide Association Analysis of Senescence-Related Traits in Maize
Authors: Yannam Venkata Rami Reddy , Caicedo Marlon , Malvar Rosa Ana , Ordás Bernardo
Published: December 2022

Senescence is a programmed process that involves the destruction of the photosynthesis apparatus and the relocation of nutrients to the grain. Identifying senescence-associated genes is essential to adapting varieties for the duration of the cultivation cycle. A genome-wide association study (GWAS) was performed using 400 inbred maize lines with 156,164 SNPs to study the genetic architecture of senescence-related traits and their relationship with agronomic traits. We estimated the timing of senescence to be 45 days after anthesis in the whole plant and specifically in the husks. A list of genes identified in a previous RNAseq experiment as involved in senescence (core senescence genes) was used to propose candidate genes in the vicinity of the significant SNPs. Forty-six QTLs of moderate to high effect were found for senescence traits, including specific QTLs for husk senescence. The allele that delayed senescence primarily increased grain yield and moisture. Seven and one significant SNPs were found in the coding and promoter regions of eight core senescence genes, respectively. These genes could be potential candidates for generating a new variation by genome editing for functional analysis and breeding purposes, particularly Zm00001d014796, which could be responsible for a QTL of senescence found in multiple studies.
Spinal Irisin Gene Delivery Attenuates Burn Injury-Induced Muscle Atrophy by Promoting Axonal Myelination and Innervation of Neuromuscular Junctions
Authors: Wu Sheng-Hua , Lu I-Cheng , Yang Shih-Ming , Hsieh Chia-Fang , Chai Chee-Yin , Tai Ming-Hong , Huang Shu-Hung
Published: December 2022

Muscle loss and weakness after a burn injury are typically the consequences of neuronal dysregulation and metabolic change. Hypermetabolism has been noted to cause muscle atrophy. However, the mechanism underlying the development of burn-induced motor neuropathy and its contribution to muscle atrophy warrant elucidation. Current therapeutic interventions for burn-induced motor neuropathy demonstrate moderate efficacy and have side effects, which limit their usage. We previously used a third-degree burn injury rodent model and found that irisin—an exercise-induced myokine—exerts a protective effect against burn injury-induced sensory and motor neuropathy by attenuating neuronal damage in the spinal cord. In the current study, spinal irisin gene delivery was noted to attenuate burn injury-induced sciatic nerve demyelination and reduction of neuromuscular junction innervation. Spinal overexpression of irisin leads to myelination rehabilitation and muscular innervation through the modulation of brain-derived neurotrophic factor and glial-cell-line-derived neurotrophic factor expression along the sciatic nerve to the muscle tissues and thereby modulates the Akt/mTOR pathway and metabolic derangement and prevents muscle atrophy.
Stability of Hydroxo/Oxo/Fluoro Zirconates vs. Hafniates—A DFT Study
Authors: Anders Jennifer , Göritz Fabian , Loges Anselm , John Timm , Paulus Beate
Published: December 2022

We performed density functional theory (DFT) calculations on binary and ternary oxo/fluoro crystals of the geochemical twin pair zirconium and hafnium to evaluate and compare their stabilities. This is the first DFT study on bulk ZrF4 or HfF4, as well as on a hypothetical ZrOF2 or HfOF2 bulk crystal. For α-MO2, β-MF4 and MOF2, we have found significantly higher cohesive energies for the respective hafnium species. This suggests a considerable gap in affinity toward fluorine and oxygen between the twin pair in the solid state. In agreement with experimental findings, this gap is slightly more pronounced for fluorine. This study is also the first to evaluate the theoretical, endothermic mono-hydroxylation of the respective fluorides or oxyfluorides to model the difference in affinity toward fluoride versus hydroxide. For these, we could also find a slight energetic preference for the hafnium compound.
Population Parameters and Feeding Preference of Spodoptera litura (Lepidoptera: Noctuidae) on Different Asparagus officinalis Tissues
Authors: Ye Li-Min , Di Xue-Yuan , Yan Bin , Liu Jian-Feng , Wang Xiu-Qin , Yang Mao-Fa
Published: December 2022

Spodoptera litura is an important pest that seriously affects Asparagus officinalis production. To clarify the population characteristics and feeding preference of S. litura on different asparagus tissues, asparagus stems and leaves were selected as the research objects, related studies were conducted by constructing the life table and the feeding preference experiment. The results showed that S. litura could complete its development and reproduction normally on asparagus stems or leaves. Although the adult longevity and fecundity of S. litura on the two types of tissues were not significantly different, the development duration of larvae and pupae, and total preoviposition period on leaves were significantly longer than those raised on stems. The intrinsic rate of increase and finite rate of increase were 0.186 d−1 and 1.204 d−1 on stems, which were significantly higher than those fed on leaves (0.161 d−1 and 1.175 d−1). The mean generation time on stems (32.88 d) was significantly lower than on leaves (36.88 d). It indicated that stems were more suitable for its population growth. In the feeding preference, the third and fifth instar larvae preferred to feed on leaves, and other instar larvae (except for the sixth instar of 2.5 h) had no significant difference. These results will provide a theoretical reference for further research and forecasting and integrated control.
Using XGBoost Regression to Analyze the Importance of Input Features Applied to an Artificial Intelligence Model for the Biomass Gasification System
Authors: Wen Hung-Ta , Wu Hom-Yu , Liao Kuo-Chien
Published: December 2022

Recently, artificial intelligence models have been developed to simulate the biomass gasification systems. The extant research models use different input features, such as carbon, hydrogen, nitrogen, sulfur, oxygen, and moisture content, in addition to ash, reaction temperature, volatile matter (VM), a lower heating value (LHV), and equivalence ratio (ER). The importance of these input features applied to artificial intelligence models are analyzed in this study; further, the XGBoost regression model was used to simulate a biomass gasification system and investigate its performance. The top-four features, according to the results are ER, VM, LHV, and carbon content. The coefficient of determination (R2) was highest (0.96) when all eleven input features noted above were selected. Further, the model performance using the top-three features produced a R2 value of 0.93. Thus, the XGBoost model performance was validated again and observed to outperform those of previous studies with a lower mean-squared error of 1.55. The comparison error for the hydrogen gas composition produced from the gasification at a temperature of 900 °C and ER = 0.4 was 0.07%.
Titanium and Tantalum Used as Functional Gradient Interlayer to Join Tungsten and Eurofer97
Authors: Richou Marianne , Chu Isabelle , Darut Geoffrey , Maestracci Raphael , Ramaniraka Manda , Meillot Erick
Published: December 2022

For the DEMO reactor, tungsten is considered as an armor material. Eurofer97 is planned to be used as a structural material for the first wall and in the divertor region, especially for the shielding liner component. To date, several joining solutions between W and Eurofer97 have been developed (copper brazing, W and Eurofer97 functional gradient material (FGM), etc.). Each existing joining solution has its own advantages (joining material, improved manufacturing process). In the present study, the choice of the joining material is driven, among other constraints, by a desire to minimize the thermal stresses at the materials’ interface. In this regard, FGM represents a promising solution. Another constraint that is taken into account in this study concerns the manufacturing process involved, which should be an improved industrial process. The present study proposes a joining solution, based on FGM, which, additionally to the advantages of the existing solutions, could reduce the long-term activation of the joining material. The development of a joining solution via Ti and Ta as materials constituting the FGM (Ti/Ta FGM) is presented in this paper. Due to the achieved density and the composition’s accuracy, the cold spray process is shown to be adapted for the Ti/Ta FGM’s manufacturing. Based on the feedback on the experience of joining between W, W/Cu FGM and CuCrZr, the final joining between W, Ti/Ta FGM and Eurofer97 is achieved using hot isostatic pressing, followed by a thermal treatment to recover Eurofer97’s mechanical properties, resulting in good joining quality.