bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Pleistocene River-Fed Paleocoast in Western Umbria (Central Italy): Facies Analysis and Coastal Models
Authors: Bizzarri Roberto , Baldanza Angela
Published: June 2023

Pliocene (?)—early Pleistocene shallow marine deposits, varying from gravel to sand to clay, characterize the southernmost sector of the Valdichiana Basin, between Orte and Città della Pieve, across Tuscany, Umbria and Latium (Central Italy). Facies associations, referring to the evolution of a river-fed coast, with a sensible facies heteropy, and a sub-environment articulation, both across and alongshore, have been recently described. Although the main part of the territory responds to a wave-dominated coastal model, a clear fluvial sediment origin and the presence of localized river mouths have also been documented. Nearshore is mainly represented by interbedded sand and gravel beachface to upper shoreface deposits, in which both a mouth bar organization and a lateral distribution of gravel beaches are recognizable. Sediment origins largely depend ondebris flow processes, related to small alluvial fans/fan deltas. In constrained areas, debris flow and current continental deposits occur, referring to coalescent alluvial fans, organized as a smoothly seaward-dipping piedmont band, drained by shallow braided channels. This roughly organized fluvial system feeds a coastal area, with a fandeltabuild-up. The as-described fan delta and beach systems are characterized by a smooth seaward morphology, according to models resembling, on a coast-transverse profile, the shelf-type fan delta. Although the proposed models differ from each other’s, with respect tothe shelf-type one, this is mainly on a lateral facies distribution.
Sea Caves and Other Landforms of the Coastal Scenery on Gozo Island (Malta): Inventory and New Data on Their Formation
Authors: Furlani Stefano , Antonioli Fabrizio , Colica Emanuele , D’Amico Sebastiano , Devoto Stefano , Grego Pietro , Gambin Timmy
Published: June 2023

Sea caves are a type of cave formed primarily by the wave action of the sea. The coastal scenery of the Gozitan coast is very interesting in that sea caves and other coastal landforms, such as sea arches, develop at the sea level. We mapped seventy-nine semi-submerged sea caves opening at the sea level, five completely submerged sea caves, seven sea arches, one sea stack, and one shelter around the coast of Gozo, mainly in the Western and Eastern parts of the island, due to favorable lithological and topographical conditions. Additionally, we surveyed the topography of the emerged part of nine sea caves using the iPhone build-in LiDAR sensor, and eight sea caves in the submerged part using SCUBA equipment. This inventory represents the most detailed example of a database of coastal caves and related forms in the Mediterranean, mainly sourced from a swimming survey along the entire island. Thanks to the combination of outputs of the above-water emerged and submerged surveys, we defined three types of semi-submerged sea caves: (i) box caves, (ii) joint caves, and (iii) complex caves. Moreover, we added a cave-like landform above the sea level on calcarenites called shelter, or a little extended notch deeply carved into the cliff. The shape mainly depends on the structural and lithological setting of sea cliffs. In the Western sector of the island, we also discovered the only sea cave in Gozo, measuring 122 m in length and 10 m in width, with its floor developing above the mean sea level. This cave base is of interest due to rounded landforms related to marine erosion. In the innermost part of the cave, there is also a beach with rounded pebble at an elevation of about 7 m asl. Considering the tectonic stability of the island, it could be possibly related to the MIS 5.5 highstand.
The Value of Age-Friendly Public Health Systems in the Age-Friendly Ecosystem
Authors: Wolfe Megan , Gracia J. Nadine
Published: June 2023

The United States population is living longer and healthier than ever. This enables our communities—and our society—to continue to benefit from our knowledge, experience, and energy as we age. The public health system is foundational for increasing life expectancy, and now it has the opportunity to further support older adult health and well-being. Trust for America’s Health (TFAH), in partnership with The John A. Hartford Foundation, launched the age-friendly public health systems initiative in 2017 with the goal of raising awareness within the public health sector of its many potential roles in healthy aging. TFAH has worked with state and local departments of health to build capacity and expertise in older adult health and has provided guidance and technical assistance to expand this work across the U.S. TFAH now envisions a public health system that has healthy aging as a core function. This paper aims to describe why the public health sector should adopt healthy aging policies and practices, how this is being operationalized at the state and local levels, and the value of age-friendly public health systems within the age-friendly ecosystem.
“Komai Nisan Dare, Akwai Wani Online”: Social Media and the Emergence of Hausa Neoproverbs
Authors: Adamu Abdalla Uba
Published: June 2023

This paper interrogates the changing paradigm in the evolution of traditional African proverbs in the postcolonial setting in which Hausa youth create proverbs centered around the power of both social media and their technologies. In this context, the notion of colonized subjects, cowering under the glare of English linguistic imperialism, is challenged by the Hausa youth through newly fabricated social media proverbs that acknowledge English terms, but use social media platforms to convey what I call ‘Hausa technofolk’ philosophy. This provides insight into how contemporary African youth force a new narrative in the notion of coloniality.
The Effect of Physical Exercise during COVID-19 Lockdown
Authors: Ricci Pasquale , Pallocci Margherita , Treglia Michele , Ricci Serafino , Ferrara Rosaria , Zanovello Claudia , Passalacqua Pierluigi , Damato Felice Marco
Published: June 2023

The COVID-19 pandemic has exerted an effect on the general population that went over every expectation. To explore the effect of physical exercise (PE) during the national lockdown in Italy, a survey was drawn up and administered to a sample composed of 208 subjects. The questionnaire comprised 81 multiple-choice items, including sociodemographic data, health-related questions, and assessment of physical exercise, satisfaction with life, depression, and personality. The purpose of this study is to explore the role of physical exercise during the outbreak following the present hypothesis: first, if a link exists between the time spent on physical exercise during the lockdown and the perceived health condition, depressive and somatic symptomatology, and life satisfaction; second, to find associations among the SF-12 component summaries and the other psychological outcomes; and finally, to explore how physical and psychological variables are predictive of PCS-12 and MCS-12. The results showed that both vigorous and moderate physical exercise was strongly correlated with psychological variables, with statistically significant negative correlations found between age and physical exercise. Additionally, significant positive correlations were observed between physical exercise and mental health indices, such as MCS-12 and SWLS, whereas negative correlations were found with BDI, PCS-12, and SOM-H. The correlation analysis also revealed that physical and individual mental health summaries were associated with psychological outcomes, with statistically significant negative correlations found between PCS-12 and MCS, PCS-12 and SOM-H, and MCS-12 and BDI scores. Regression analysis showed that physical activities and psychological status both had a direct influence on perceived mental and physical well-being during the lockdown, accounting for 56.7% and 35.5% of the variance, respectively. The p-values for the significant correlations ranged from <0.05 to <0.01. Overall, these findings highlight the importance of physical exercise and psychological well-being in maintaining good health during the pandemic.
Factors Related to Oral Problems in Patients with Prolonged Disorders of Consciousness in Long-Term Care: A Cross-Sectional Study
Authors: Yoshimi Kanako , Nakagawa Kazuharu , Yamaguchi Kohei , Nakane Ayako , Hayashi Masaharu , Miyata Rie , Chiba Yumi , Tohara Haruka
Published: June 2023

Factors influencing oral problems, such as malocclusion and oral motor dysfunction, in patients with prolonged disorders of consciousness (DOC) remain unclear. This study aimed to clarify the relationship between oral problems and physical function, communication, respiration, and oral intake status, as well as related factors in patients with DOC receiving long-term care at home. A cross-sectional study was conducted in October 2018; 127 patients who developed DOC > 5 years ago were analyzed. The differences between patients with and without oral problems were examined, and a binomial logistic regression analysis was performed to examine factors associated with oral problems, with the presence of oral problems as the dependent variable, and age, the number of years since onset, drooling, oral intake status, and the presence of a family dentist as explanatory variables. A post hoc power analysis of the binomial logistic regression analysis for oral problems (odds ratio: 2.05, alpha value: 0.05, incidence of oral problems: 0.80, and total sample size: 127) demonstrated an observed power of 93.09%. Oral intake status (p = 0.010) and the number of years since onset (p = 0.046) were significantly related to oral problems. Preventive oral management and rehabilitation from the early stage after onset may be effective for oral problems in patients with DOC.
Teledermatology Evaluation and Feedback Systems: A Tool for Improving Care
Authors: Gatica José Luis , Aragón-Caqueo Diego , Aedo Gabriel , Fuenzalida Héctor , Loubies Rodrigo , Aedo Sócrates , Carrasco María Francisca , Sabando Vezna , Cunill Carolina , Letelier María José
Published: June 2023

Chile is a country where teledermatology has been growing exponentially since the implementation of a single national asynchronous teledermatology platform for the public system in December 2018. To ensure the quality of care in teledermatology systems, it is crucial to evaluate the fulfillment of basic specifiers such as ICD-Diagnosis, therapeutic suggestions, and diagnostic suggestions, among others. This article aims to evaluate the teledermatology system of the Chilean public health service by analyzing 243 randomly extracted consultations, representative of the 20,716 electronic consultations performed during 2020. Compliance with basic specifiers is evaluated. From these, fulfillment of core teledermatology functions, such as diagnostic and therapeutic suggestions, is observed in most consultations. There are statistically significant relationships between the patient’s destination (primary health center [PHC] or face-to-face referral), pharmacological prescription, coverage of the drug prescribed by the public system, and the education received by the consulting physician. If the consultation is resolved in the PHC, there is a higher chance for pharmacological prescription, prescribing mostly drugs that are covered by the government. This is less likely to occur when patients are referred for face-to-face evaluation. A targeted evaluation of education, pharmacological prescriptions, and their applicability is key to improving the quality of teledermatology systems.
Methods of Primary Clinical Prevention of Dental Caries in the Adult Patient: An Integrative Review
Authors: Veiga Nélio , Figueiredo Ricardo , Correia Patrícia , Lopes Pedro , Couto Patrícia , Fernandes Gustavo Vicentis Oliveira
Published: June 2023

Aim: Preventive approaches to oral health diseases, mainly dental caries, require individual and collective policies. Thus, this review was conducted to identify the primary prevention methods of dental caries in adults to improve oral health at the clinical and community levels. Methods: This review followed the PICO strategy with the research question: “What are the methods of primary prevention of dental caries, in adults, for improving and maintaining oral health integrating clinical and community-based strategies?” Electronic screening was carried out by two independent reviewers in five databases (MedLine/PubMed, SciELO, Web of Science, Cochrane Library, and LILACS) to find relevant publications between 2015–2022. We applied eligibility criteria for selection of the articles. The following MeSH terms were used: “Primary Prevention”; “Adult”; “Oral Health”; “Dental Caries”; “Fluorides, Topical”; “Fluoride Varnishes”; “Pit and Fissure Sealants”; “Preventive Dentistry”. Although the term “Prevention strategy” is not a MeSH descriptor, several correlated terms appeared and were used in the search engines: “Preventative Care”, “Disease Prevention, Primary”, and “Prevention, Primary”. The tool provided by the JBI organization (Joanna Briggs Institute) was used to assess the quality of the included studies. Results: Nine studies were included. Overall, it was found that the main primary prevention methods applied in dentistry in adults are the application of pit and fissure sealants, topical application of fluoride performed in the dental clinic, use of fluoridated toothpaste, mouthwash with chlorhexidine at home, use of xylitol, the recommendation for regular appointments with the dentist, and the need to inform patients about the saliva buffer capacity and adoption of a non-cariogenic diet. For that purpose, preventive policies should be taken to prevent dental caries. These include three major challenges: providing the adult population with more knowledge regarding their oral health, empowering patients through adopting healthy lifestyles, and developing new preventive strategies and awareness campaigns aimed at the adult population to promote proper oral health habits. Conclusions: A small number of studies were found whose participants were adult patients. There was some consistency regarding primary prevention methods in our studies. However, good quality randomized control studies are still required to define the best intervention strategies for adult caries prevention.
Causes for Medical Errors in Obstetrics and Gynaecology
Authors: Klemann Désirée , Rijkx Maud , Mertens Helen , van Merode Frits , Klein Dorthe
Published: June 2023

Background: Quality strategies, interventions, and frameworks have been developed to facilitate a better understanding of healthcare systems. Reporting adverse events is one of these strategies. Gynaecology and obstetrics are one of the specialties with many adverse events. To understand the main causes of medical errors in gynaecology and obstetrics and how they could be prevented, we conducted this systematic review. Methods: This systematic review was performed in compliance with the Prisma 2020 guidelines. We searched several databases for relevant studies (Jan 2010–May 2023). Studies were included if they indicated the presence of any potential risk factor at the hospital level for medical errors or adverse events in gynaecology or obstetrics. Results: We included 26 articles in the quantitative analysis of this review. Most of these (n = 12) are cross-sectional studies; eight are case–control studies, and six are cohort studies. One of the most frequently reported contributing factors is delay in healthcare. In addition, the availability of products and trained staff, team training, and communication are often reported to contribute to near-misses/maternal deaths. Conclusions: All risk factors that were found in our review imply several categories of contributing factors regarding: (1) delay of care, (2) coordination and management of care, and (3) scarcity of supply, personnel, and knowledge.
The Impact of a Psychoeducational Group Program on the Mental Well-Being of Unit-Based Nurse Leaders: A Randomized Controlled Trial
Authors: Sawyer Amanda T. , Tao Hong , Bailey Amanda K.
Published: June 2023

This randomized controlled trial examined the impact of a psychoeducational group program on the mental well-being of unit-based nurse leaders, specifically nurse managers and assistant nurse managers. The program was developed around the themes of resilience, insight, self-compassion, and empowerment to fight burnout and enhance purposeful adaptive coping to reduce distress and improve mental wellbeing. The sample included 77 unit-based nurse leaders. Outcomes included post-traumatic growth, resilience, insight, self-compassion, empowerment, perceived stress, burnout, and job satisfaction. Paired samples t-tests and repeated measures ANOVA tests were conducted to compare outcomes at baseline to the follow-up timepoints of endpoint, one-month follow-up, three-month follow-up, and six-month follow-up. The intervention group participants showed significant improvement in post-traumatic growth between baseline and all follow-up timepoints compared to the waitlist control group. Among intervention group participants, there were also significant improvements in self-reflection and insight, self-compassion, psychological empowerment, and compassion satisfaction, as well as significant reductions in perceived stress, burnout, and secondary traumatic stress. This study extends existing evidence that this psychoeducational group program can be an effective intervention for improving and protecting mental wellbeing. Among nurse leaders, it can reduce stress and burnout and improve post-traumatic growth, self-reflection and insight, self-compassion, psychological empowerment, and compassion satisfaction.
Development, Implementation and Evaluation of an Acute Care Physical Therapy ‘Float’ Placement during the COVID-19 Pandemic: A Case Report
Authors: Dhir Jasdeep , Connell Amy , McCaughan Magda , Hatzoglou Diana , Ajami Daana , Fursman Andrea , Wojkowski Sarah , Kho Michelle E.
Published: June 2023

Clinical education is a mandatory component of physical therapy curricula globally. COVID-19 disrupted clinical education, jeopardizing students’ abilities to meet graduation requirements. The objective of this case report is to outline the development, implementation and evaluation of a multiple clinical instructor (CI), multiple unit, acute care float clinical placement for a final year, entry-level physical therapy student and offer implementation recommendations. This placement included an eight-week, multiple CI (one primary, four supporting), multiple (five) unit clinical placement which was developed between St. Joseph’s Healthcare and the McMaster University Masters of Science (Physiotherapy) Program between 10 August and 2 October 2020. Student evaluations and reflections by the student and CIs were collected and analyzed using interpretive description. Analysis from the reflections revealed six themes: (1) CI and student attributes; (2) increased feasibility; (3) varied exposure; (4) central communication and resources; (5) organization; and (6) managing expectations. An acute care clinical experience is required for students in Canadian entry-to-practice physical therapy programs. Due to COVID-19, placement opportunities were limited. The float placement allowed clinicians to offer supervision despite staff re-deployment and increased organizational and work–life pressures during the pandemic. This model provides an approach to extenuating circumstances and may also increase acute care placements during non-pandemic times for physical therapy and other similarly structured healthcare professions.
The Spatial Effect of Accessibility to Public Service Facilities on Housing Prices: Highlighting the Housing Equity
Authors: Yu Peiheng , Yung Esther H. K. , Chan Edwin H. W. , Zhang Shujin , Wang Siqiang , Chen Yiyun
Published: June 2023

Understanding how public service accessibility is related to housing prices is crucial to housing equity, yet the heterogeneous capitalisation effect remains unknown. This study aims to investigate the spatial effect of public service accessibility on housing prices in rapidly urbanising regions. Here, we propose a novel methodological framework that integrates the hedonic price model, geographical detector model and the spatial association detector model to understand housing equity issues. The rapidly rising housing prices, vastly transformed urban planning and heterogeneous land use patterns make the urban centre of Wuhan a typical case study. High-value units of public service accessibility are concentrated in built-up areas, while low-value units are located at the urban fringe. The results indicate that larger public services have more significant clustering effects than smaller ones. Recreational, medical, educational and financial facilities all have capitalisation effects on housing prices. Both the geographical detector model and the spatial association detector model could identify the drivers of housing prices, but the explanatory power of the latter is greater and could enhance the validity and reliability of the findings. We further find that the explanatory power of the driving factors on housing prices obtained from the spatial association detector model is greater than that of the geographical detector model. Based on the spatial association detector model, the main drivers of public service facilities are accessibility to restaurants and bars and accessibility to ATMs. In addition, there are bivariate or nonlinear enhancement effects between each pair of driving factors. This approach provides significant insights for urban environmental development planning and local real estate planning.
Research on Spatial Patterns and Mechanisms of Live Streaming Commerce in China Based on Geolocation Data
Authors: Zhu Yiwen , Zhang Xumin , Yan Simin , Zou Lin
Published: June 2023

Live streaming commerce (LSC) effectively combines the traditional real economy and e-commerce. Based on more than half a million unique GIS data values on LSC activities sourced via Taobao (Alibaba), we traced the spatial distribution of different players along the supply chain and further highlighted the intermediary role of streamers in developing the inter-regional industry. This study guides industrial planning in a diversified regional context, especially in economically peripheral regions. Our results show the following outcomes: (1) in contrast to dispersed suppliers, streamers and consumers are highly clustered. This trend proves that streamers are rooted in a specific urban context while playing the role of an intermediary in inter-regional supply chains, effectively extending geographic interactivity between suppliers and (potential) customers. (2) LSC primarily promotes regional light industry, especially in economically peripheral and rural areas, and provides opportunities for rapid development in cities with skilled handicraft providers. (3) China’s LSC streams have a pyramid structure, and the top group is highly clustered in metropolitan regions, such as the Yangtze River Delta (YRD) and the Pearl River Delta (PRD). This clustering makes it easier for streamers to work with large, well-known brands. The bottom group is mainly in charge of expanding the supply chain within the region and relies more on the local industrial base. It is diversified due to the different types of businesses or products. Ultimately, we draw attention to adaptive spatial planning and resource allocation in the context of the economic and geographic reforms brought by this growing industry, and discuss the policy implications based on the relationships between the supply of and demand for live streamers from a broader regional perspective.
High VEGF Concentrations Accelerate Human Trabecular Meshwork Fibrosis in a TAZ-Dependent Manner
Authors: Sung Mi Sun , Kim So Young , Eom Gwang Hyeon , Park Sang Woo
Published: June 2023

We aimed to investigate the effects of different concentrations of vascular endothelial growth factor (VEGF) on the extracellular matrix (ECM) and fibrotic proteins in human trabecular meshwork (TM) cells. We also explored how the Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) signaling pathway modulates VEGF-induced fibrosis. We determined cross-linked actin network (CLAN) formation using TM cells. Changes in fibrotic and ECM protein expression were determined. High VEGF concentrations (10 and 30 ng/mL) increased TAZ and decreased p-TAZ/TAZ expression in TM cells. Western blotting and real-time PCR revealed no YAP expression changes. Fibrotic and ECM protein expression decreased at low VEGF concentrations (1 and 10 ρg/mL) and significantly increased at high VEGF concentrations (10 and 30 ng/mL). CLAN formation increased in TM cells treated with high VEGF concentrations. Moreover, TAZ inhibition by verteporfin (1 μM) rescued TM cells from high-VEGF-concentration-induced fibrosis. Low VEGF concentrations reduced fibrotic changes, whereas high VEGF concentrations accelerated fibrosis and CLAN formations in TM cells in a TAZ-dependent manner. These findings reflect the dose-dependent influences of VEGF on TM cells. Moreover, TAZ inhibition might be a therapeutic target for VEGF-induced TM dysfunction.
Conformations and Physicochemical Properties of Biological Ligands in Various Environments
Authors: Le Questel Jean-Yves
Published: June 2023

An accurate description of the conformational behavior of drug-like molecules is often a prerequisite for a comprehensive understanding of their behavior, in particular in the targeted receptor surroundings [...]
Enhancing the Catalytic Activity of Thermo-Asparaginase from Thermococcus sibiricus by a Double Mesophilic-like Mutation in the Substrate-Binding Region
Authors: Dumina Maria , Zhdanov Dmitry , Zhgun Alexander , Pokrovskaya Marina , Aleksandrova Svetlana , Veselovsky Alexander , El’darov Michael
Published: June 2023

L-asparaginases (L-ASNases) of microbial origin are the mainstay of blood cancer treatment. Numerous attempts have been performed for genetic improvement of the main properties of these enzymes. The substrate-binding Ser residue is highly conserved in L-ASNases regardless of their origin or type. However, the residues adjacent to the substrate-binding Ser differ between mesophilic and thermophilic L-ASNases. Based on our suggestion that the triad, including substrate-binding Ser, either GSQ for meso-ASNase or DST for thermo-ASNase, is tuned for efficient substrate binding, we constructed a double mutant of thermophilic L-ASNase from Thermococcus sibiricus (TsA) with a mesophilic-like GSQ combination. In this study, the conjoint substitution of two residues adjacent to the substrate-binding Ser55 resulted in a significant increase in the activity of the double mutant, reaching 240% of the wild-type enzyme activity at the optimum temperature of 90 °C. The mesophilic-like GSQ combination in the rigid structure of the thermophilic L-ASNase appears to be more efficient in balancing substrate binding and conformational flexibility of the enzyme. Along with increased activity, the TsA D54G/T56Q double mutant exhibited enhanced cytotoxic activity against cancer cell lines with IC90 values from 2.8- to 7.4-fold lower than that of the wild-type enzyme.
Skeletal Muscle-Specific Bis Depletion Leads to Muscle Dysfunction and Early Death Accompanied by Impairment in Protein Quality Control
Authors: Jung Soon-Young , Riew Tae-Ryong , Yun Hye Hyeon , Lim Ji Hee , Hwang Ji-Won , Jung Sung Won , Kim Hong Lim , Lee Jae-Seon , Lee Mun-Yong , Lee Jeong-Hwa
Published: June 2023

Bcl-2-interacting cell death suppressor (BIS), also called BAG3, plays a role in physiological functions such as anti-apoptosis, cell proliferation, autophagy, and senescence. Whole-body Bis-knockout (KO) mice exhibit early lethality accompanied by abnormalities in cardiac and skeletal muscles, suggesting the critical role of BIS in these muscles. In this study, we generated skeletal muscle-specific Bis-knockout (Bis-SMKO) mice for the first time. Bis-SMKO mice exhibit growth retardation, kyphosis, a lack of peripheral fat, and respiratory failure, ultimately leading to early death. Regenerating fibers and increased intensity in cleaved PARP1 immunostaining were observed in the diaphragm of Bis-SMKO mice, indicating considerable muscle degeneration. Through electron microscopy analysis, we observed myofibrillar disruption, degenerated mitochondria, and autophagic vacuoles in the Bis-SMKO diaphragm. Specifically, autophagy was impaired, and heat shock proteins (HSPs), such as HSPB5 and HSP70, and z-disk proteins, including filamin C and desmin, accumulated in Bis-SMKO skeletal muscles. We also found metabolic impairments, including decreased ATP levels and lactate dehydrogenase (LDH) and creatine kinase (CK) activities in the diaphragm of Bis-SMKO mice. Our findings highlight that BIS is critical for protein homeostasis and energy metabolism in skeletal muscles, suggesting that Bis-SMKO mice could be used as a therapeutic strategy for myopathies and to elucidate the molecular function of BIS in skeletal muscle physiology.
Genome-Wide Identification and Characterization of the Msr Gene Family in Alfalfa under Abiotic Stress
Authors: Zhao Xianglong , Han Xiao , Lu Xuran , Yang Haoyue , Wang Zeng-Yu , Chai Maofeng
Published: June 2023

Alfalfa (Medicago sativa) is an important leguminous forage, known as the “The Queen of Forages”. Abiotic stress seriously limits the growth and development of alfalfa, and improving the yield and quality has become an important research area. However, little is known about the Msr (methionine sulfoxide reductase) gene family in alfalfa. In this study, 15 Msr genes were identified through examining the genome of the alfalfa “Xinjiang DaYe”. The MsMsr genes differ in gene structure and conserved protein motifs. Many cis-acting regulatory elements related to the stress response were found in the promoter regions of these genes. In addition, a transcriptional analysis and qRT-PCR (quantitative reverse transcription PCR) showed that MsMsr genes show expression changes in response to abiotic stress in various tissues. Overall, our results suggest that MsMsr genes play an important role in the response to abiotic stress for alfalfa.
The Natriuretic Peptide System: A Single Entity, Pleiotropic Effects
Authors: Della Corte Vittoriano , Pacinella Gaetano , Todaro Federica , Pecoraro Rosaria , Tuttolomondo Antonino
Published: June 2023

In the modern scientific landscape, natriuretic peptides are a complex and interesting network of molecules playing pleiotropic effects on many organs and tissues, ensuring the maintenance of homeostasis mainly in the cardiovascular system and regulating the water–salt balance. The characterization of their receptors, the understanding of the molecular mechanisms through which they exert their action, and the discovery of new peptides in the last period have made it possible to increasingly feature the physiological and pathophysiological role of the members of this family, also allowing to hypothesize the possible settings for using these molecules for therapeutic purposes. This literature review traces the history of the discovery and characterization of the key players among the natriuretic peptides, the scientific trials performed to ascertain their physiological role, and the applications of this knowledge in the clinical field, leaving a glimpse of new and exciting possibilities for their use in the treatment of diseases.
TROAP Promotes the Proliferation, Migration, and Metastasis of Kidney Renal Clear Cell Carcinoma with the Help of STAT3
Authors: Wang Jun , Wan Hongyuan , Mi Yuanyuan , Wu Sheng , Li Jie , Zhu Lijie
Published: June 2023

Kidney renal clear cell carcinoma (KIRC) is a subtype of renal cell carcinoma that threatens human health. The mechanism by which the trophinin-associated protein (TROAP)–an important oncogenic factor–functions in KIRC has not been studied. This study investigated the specific mechanism by which TROAP functions in KIRC. TROAP expression in KIRC was analyzed using the RNAseq dataset from the Cancer Genome Atlas (TCGA) online database. The Mann–Whitney U test was used to analyze the expression of this gene from clinical data. The Kaplan–Meier method was used for the survival analysis of KIRC. The expression level of TROAP mRNA in the cells was detected using qRT-PCR. The proliferation, migration, apoptosis, and cell cycle of KIRC were detected using Celigo, MTT, wound healing, cell invasion assay, and flow cytometry. A mouse subcutaneous xenograft experiment was designed to demonstrate the effect of TROAP expression on KIRC growth in vivo. To further investigate the regulatory mechanism of TROAP, we performed co-immunoprecipitation (CO-IP) and shotgun liquid chromatography–tandem mass spectrometry (LC-MS). TCGA-related bioinformatics analysis showed that TROAP was significantly overexpressed in KIRC tissues and was related to higher T and pathological stages, and a poor prognosis. The inhibition of TROAP expression significantly reduced the proliferation of KIRC, affected the cell cycle, promoted cell apoptosis, and reduced cell migration and invasion. The subcutaneous xenograft experiments showed that the size and weight of the tumors in mice were significantly reduced after TROAP-knockdown. CO-IP and post-mass spectrometry bioinformatics analyses revealed that TROAP may combine with signal transducer and activator of transcription 3 (STAT3) to achieve tumor progression in KIRC; this was verified by functional recovery experiments. TROAP may regulate KIRC proliferation, migration, and metastasis by binding to STAT3.
Regulation of Vicia faba L. Response and Its Effect on Megoura crassicauda Reproduction under Zinc Stress
Authors: Wan Si-Jing , Si Hui-Ru , Wang Xian-Zhong , Chao Lei , Ma Wu , Sun Si-Si , Tang Bin , Tan Xiao-Ling , Wang Shigui
Published: June 2023

The heavy metal zinc (Zn) is known to be transmitted in the food chain; however, the effect of Zn stress on beans and herbivorous insects is largely unclear. This study aimed to investigate the resistance of broad bean plants to Zn stress and the consequent changes in their physiological and biochemical metabolism by simulating heavy metal pollution in soil. Simultaneously, the effects of aphid progeny treated with different Zn concentrations on the expression of carbohydrate and related genes were analyzed. The results showed that Zn had no effect on the germination rate of broad beans, but other effects mainly manifested as follows. (1) Chlorophyll content decreased. (2) The total soluble sugar and Zn content in stems and leaves increased with increasing Zn content. (3) The proline content first increased and then decreased with increasing Zn content. (4) The height of the seedlings indicates that low concentrations promote growth and high concentrations inhibit growth. In addition, only the first-generation fecundity decreased significantly when aphids fed on heavy metal broad beans. Continuous high Zn levels increase the trehalose content of aphid F1 and F2, while F3 decreases. These results can not only provide a theoretical basis for exploring the impact of soil heavy metal pollution on ecosystems but also preliminarily evaluate the possibility of broad beans as a means of pollution remediation.
Nutritional Biochemistry
Authors: Hsia Shih Min
Published: June 2023

Nutritional biochemistry involves a wide range of fields, and many studies on nutritional biochemistry have focused not only on uncovering the relationship between diet and disease but also on revealing the importance of nutritional intake in the development of cancer [...]
Liver Fibrosis Resolution: From Molecular Mechanisms to Therapeutic Opportunities
Authors: Pei Qiying , Yi Qian , Tang Liling
Published: June 2023

The liver is a critical system for metabolism in human beings, which plays an essential role in an abundance of physiological processes and is vulnerable to endogenous or exogenous injuries. After the damage to the liver, a type of aberrant wound healing response known as liver fibrosis may happen, which can result in an excessive accumulation of extracellular matrix (ECM) and then cause cirrhosis or hepatocellular carcinoma (HCC), seriously endangering human health and causing a great economic burden. However, few effective anti-fibrotic medications are clinically available to treat liver fibrosis. The most efficient approach to liver fibrosis prevention and treatment currently is to eliminate its causes, but this approach’s efficiency is too slow, or some causes cannot be fully eliminated, which causes liver fibrosis to worsen. In cases of advanced fibrosis, the only available treatment is liver transplantation. Therefore, new treatments or therapeutic agents need to be explored to stop the further development of early liver fibrosis or to reverse the fibrosis process to achieve liver fibrosis resolution. Understanding the mechanisms that lead to the development of liver fibrosis is necessary to find new therapeutic targets and drugs. The complex process of liver fibrosis is regulated by a variety of cells and cytokines, among which hepatic stellate cells (HSCs) are the essential cells, and their continued activation will lead to further progression of liver fibrosis. It has been found that inhibiting HSC activation, or inducing apoptosis, and inactivating activated hepatic stellate cells (aHSCs) can reverse fibrosis and thus achieve liver fibrosis regression. Hence, this review will concentrate on how HSCs become activated during liver fibrosis, including intercellular interactions and related signaling pathways, as well as targeting HSCs or liver fibrosis signaling pathways to achieve the resolution of liver fibrosis. Finally, new therapeutic compounds targeting liver fibrosis are summarized to provide more options for the therapy of liver fibrosis.
Differential Analysis of Three Copper-Based Nanomaterials with Different Morphologies to Suppress Alternaria alternata and Safety Evaluation
Authors: Yuan Zitong , Li Yiwei , He Yuke , Qian Kun , Zhang Yongqiang
Published: June 2023

The overuse of copper-based fertilizers and pesticides over the last few decades has resulted in detrimental risks to our environment. Nano-enabled agrichemicals with a high effective utilization ratio have shown great potential for maintaining or minimizing environmental issues in agriculture. Copper-based nanomaterials (Cu-based NMs) serve as a promising alternative to fungicides. Three types of Cu-based NMs with different morphologies were analyzed for their different antifungal effects on Alternaria alternata in this current study. Compared to commercial copper hydroxide water power (Cu(OH)2 WP), all tested Cu-based NMs, including cuprous oxide nanoparticles (Cu2O NPs), copper nanorods (Cu NRs) and copper nanowires (Cu NWs), especially Cu2O NPs and Cu NWs, showed higher antifungal activity against Alternaria alternata. Its EC50 were 104.24 and 89.40 mg L−1, respectively, achieving comparable activity using a dose approximately 1.6 and 1.9-fold lower. Cu-based NMs could introduce the downregulation of melanin production and soluble protein content. In contrast to trends in antifungal activity, Cu2O NPs showed the strongest power in regulating melanin production and protein content and similarly exhibited the highest acute toxicity to adult zebrafish compared to other Cu-based NMs. These results demonstrate that Cu-based NMs could offer great potential in plant disease management strategies.
The Combination of a Human Biomimetic Liver Microphysiology System with BIOLOGXsym, a Quantitative Systems Toxicology (QST) Modeling Platform for Macromolecules, Provides Mechanistic Understanding of Tocilizumab- and GGF2-Induced Liver Injury
Authors: Beaudoin James J. , Clemens Lara , Miedel Mark T. , Gough Albert , Zaidi Fatima , Ramamoorthy Priya , Wong Kari E. , Sarangarajan Rangaprasad , Battista Christina , Shoda Lisl K. M. , Siler Scott Q. , Taylor D. Lansing , Howell Brett A. , Vernetti Lawrence A. , Yang Kyunghee
Published: June 2023

Biologics address a range of unmet clinical needs, but the occurrence of biologics-induced liver injury remains a major challenge. Development of cimaglermin alfa (GGF2) was terminated due to transient elevations in serum aminotransferases and total bilirubin. Tocilizumab has been reported to induce transient aminotransferase elevations, requiring frequent monitoring. To evaluate the clinical risk of biologics-induced liver injury, a novel quantitative systems toxicology modeling platform, BIOLOGXsym™, representing relevant liver biochemistry and the mechanistic effects of biologics on liver pathophysiology, was developed in conjunction with clinically relevant data from a human biomimetic liver microphysiology system. Phenotypic and mechanistic toxicity data and metabolomics analysis from the Liver Acinus Microphysiology System showed that tocilizumab and GGF2 increased high mobility group box 1, indicating hepatic injury and stress. Tocilizumab exposure was associated with increased oxidative stress and extracellular/tissue remodeling, and GGF2 decreased bile acid secretion. BIOLOGXsym simulations, leveraging the in vivo exposure predicted by physiologically-based pharmacokinetic modeling and mechanistic toxicity data from the Liver Acinus Microphysiology System, reproduced the clinically observed liver signals of tocilizumab and GGF2, demonstrating that mechanistic toxicity data from microphysiology systems can be successfully integrated into a quantitative systems toxicology model to identify liabilities of biologics-induced liver injury and provide mechanistic insights into observed liver safety signals.
GABA-Positive Astrogliosis in Sleep-Promoting Areas Associated with Sleep Disturbance in 5XFAD Mice
Authors: Drew Victor James , Park Mincheol , Kim Tae
Published: June 2023

Sleep disturbances, a debilitating symptom of Alzheimer’s disease (AD), are associated with neuropathological changes. However, the relationship between these disturbances and regional neuron and astrocyte pathologies remains unclear. This study examined whether sleep disturbances in AD result from pathological changes in sleep-promoting brain areas. Male 5XFAD mice underwent electroencephalography (EEG) recordings at 3, 6, and 10 months, followed by an immunohistochemical analysis of three brain regions associated with sleep promotion. The findings showed that 5XFAD mice demonstrated reduced duration and bout counts of nonrapid eye movement (NREM) sleep by 6 months and reduced duration and bout counts of rapid eye movement (REM) sleep by 10 months. Additionally, peak theta EEG power frequency during REM sleep decreased by 10 months. Sleep disturbances correlated with the total number of GFAP-positive astrocytes and the ratio of GFAP- and GABA-positive astrocytes across all three sleep-associated regions corresponding to their roles in sleep promotion. The presence of GABRD in sleep-promoting neurons indicated their susceptibility to inhibition by extrasynaptic GABA. This study reveals that neurotoxic reactive astrogliosis in NREM and REM sleep-promoting areas is linked to sleep disturbances in 5XFAD mice, which suggests a potential target for the treatment of sleep disorders in AD.
SPINK2 Protein Expression Is an Independent Adverse Prognostic Marker in AML and Is Potentially Implicated in the Regulation of Ferroptosis and Immune Response
Authors: Pitts Herbert Augustus , Cheng Chi-Keung , Cheung Joyce Sin , Sun Murphy Ka-Hei , Yung Yuk-Lin , Chan Hoi-Yun , Wong Raymond S. M. , Yip Sze-Fai , Lau Ka-Ngai , Wong Wai Shan , Raghupathy Radha , Chan Natalie P. H. , Ng Margaret H. L.
Published: June 2023

There is an urgent need for the identification as well as clinicopathological and functional characterization of potent prognostic biomarkers and therapeutic targets in acute myeloid leukemia (AML). Using immunohistochemistry and next-generation sequencing, we investigated the protein expression as well as clinicopathological and prognostic associations of serine protease inhibitor Kazal type 2 (SPINK2) in AML and examined its potential biological functions. High SPINK2 protein expression was an independent adverse biomarker for survival and an indicator of elevated therapy resistance and relapse risk. SPINK2 expression was associated with AML with an NPM1 mutation and an intermediate risk by cytogenetics and European LeukemiaNet (ELN) 2022 criteria. Furthermore, SPINK2 expression could refine the ELN2022prognostic stratification. Functionally, an RNA sequencing analysis uncovered a potential link of SPINK2 with ferroptosis and immune response. SPINK2 regulated the expression of certain P53 targets and ferroptosis-related genes, including SLC7A11 and STEAP3, and affected cystine uptake, intracellular iron levels and sensitivity to erastin, a specific ferroptosis inducer. Furthermore, SPINK2 inhibition consistently increased the expression of ALCAM, an immune response enhancer and promoter of T-cell activity. Additionally, we identified a potential small-molecule inhibitor of SPINK2, which requires further characterization. In summary, high SPINK2 protein expression was a potent adverse prognostic marker in AML and might represent a druggable target.
Effects of Tip Leakage Vortex Cavitation on Flow Field under Cavitation Instability
Authors: Yoon Youngkuk , Song Seung Jin
Published: June 2023

Cavitation instabilities can induce axial and circumferential vibrations, as well as noise in turbopump inducers. Therefore, the purpose of the present study is to investigate the mechanism of cavitation instability. The flow field near the two-bladed inducer leading edge under alternate blade cavitation was experimentally investigated using particle image velocimetry (PIV). It was found that the tip leakage vortex cavitation draws the flow toward its region of collapse and induces a negative change in the incidence to the adjacent blade. Moreover, this blade-to-blade interaction was identified as the main cause of alternate blade cavitation. Furthermore, it was demonstrated that this blade-to-blade interaction is strongest when the cavity collapse occurs in the inducer throat area, where the leading edge of the following blade is located.
Benchmarking Thermodynamic Models for Optimization of PSA Oxygen Generators
Authors: Carty Michael L. , Bilodeau Stephane
Published: June 2023

In this review, the authors conducted benchmarks for three thermodynamic models to analyze PSA-based medical oxygen concentrator (MOC) systems to allow for optimization and operational flexibility. PSA oxygen generator plants are good medical-grade oxygen sources, a crucial tool in healthcare from the primary to the tertiary level. However, they must be designed accordingly and properly operated, considering key design goals such as improving adsorbent productivity, improving oxygen recovery, and innovating to reduce unit size and weight. The importance of mapping the performance of various design and operating requirements or designs themselves on outlet product specifications and production effectiveness is outlined. Emphasizing optimal PSA design and operation, the authors suggest considering simulation-based optimization frameworks or high-fidelity modeling for the optimal layout and operation conditions of adsorption-based MOC systems. Notwithstanding, a simplified first-principles-based model with additional assumptions and simplifications generates a large volume of scenarios faster. Therefore, it represents a good approach for a feasibility study dealing with many options and designs or even the real-time monitoring of PSA operating conditions. All this paved the way for efficient translation into machine learning models and even deep learning networks that might be better suited to simulate the complex PSA process. The conclusion outlines that PSA-based plants can be flexible and effective units using any of the three models when properly optimized.