bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-layered Network Analysis of Osteoking in the Treatment of Osteoporosis: Unraveling Mechanisms from Gene Expression to Molecular Docking
Authors: Chen He , Ying Jun , Xie Xianjie , Huang Boyun , Lin Pengcheng
Published: March 2024

This study aimed to elucidate the therapeutic mechanisms of Osteoking in the treatment of osteoporosis through a comprehensive analysis of potential targets, active ingredients, and associated pathways.

Method

The study employed an integrated approach to understand the molecular mechanisms underlying Osteoking’s treatment of osteoporosis. The construction of the protein-protein interaction network involved analyzing data from GENEMANIA and STRING databases. KEGG enrichment analysis was performed to identify enriched pathways, focusing on the cAMP signaling and PI3K-AKT signaling pathways. Active ingredients, disease targets, and osteoporosis-related pathways were integrated into a comprehensive network diagram using Cytoscape.

Result

The Gene Expression Omnibus (GEO) database was employed to identify osteoporosis-related gene targets, revealing 3,578 downregulated and 1,204 upregulated genes. Simultaneously, Osteoking’s active ingredients and potential targets were investigated using the Traditional Chinese Medicine Integrated Database (ETCM). A protein-protein interaction network and KEGG pathway enrichment analysis were constructed, highlighting potential targets for Osteoking’s therapeutic effects on osteoporosis. The study also conducted molecular docking analysis, revealing the strong binding capacities of Kaempferol with key disease targets. The results suggest that Osteoking, particularly its active component Kaempferol, holds promise as a potential intervention for osteoporosis, providing insights for further exploration and development of osteoporosis treatments

Conclusions

In conclusion, despite some limitations, this study provides valuable information for the treatment of osteoporosis. Future research should make further progress by continually expanding data sources, conducting in-depth experimental validations, and broadening the scope of targets to better understand and address this common skeletal disorder.

Funding

This work was supported by the Scientific Foundation of Fuzhou Municipal Health Commission (2021-S-wp3).
Myosin A and F-Actin play a critical role in mitochondrial dynamics and inheritance inToxoplasma gondii
Authors: Souza Rodolpho Ornitz Oliveira , Yang Chunlin , Arrizabalaga Gustavo
Published: March 2024

The single mitochondrion of the obligate intracellular parasiteToxoplasma gondiiis highly dynamic. Toxoplasma’s mitochondrion changes morphology as the parasite moves from the intracellular to the extracellular environment and during division. Toxoplasma’s mitochondrial dynamic is dependent on an outer mitochondrion membrane-associated protein LMF1 and its interaction with IMC10, a protein localized at the inner membrane complex (IMC). In the absence of either LMF1 or IMC10, parasites have defective mitochondrial morphology and inheritance defects. As little is known about mitochondrial inheritance inToxoplasma, we have used the LMF1/IMC10 tethering complex as an entry point to dissect the machinery behind this process. Using a yeast two-hybrid screen, we previously identified Myosin A (MyoA) as a putative interactor of LMF1. Although MyoA is known to be located at the parasite’s pellicle, we now show through ultrastructure expansion microscopy (U-ExM) that this protein accumulates around the mitochondrion in the late stages of parasite division. Parasites lacking MyoA show defective mitochondrial morphology and a delay in mitochondrion delivery to the daughter parasite buds during division, indicating that this protein is involved in organellar inheritance. Disruption of the parasite’s actin network also affects mitochondrion morphology. We also show that parasite-extracted mitochondrion vesicles interact with actin filaments. Interestingly, mitochondrion vesicles extracted out of parasites lacking LMF1 pulled down less actin, showing that LMF1 might be important for mitochondrion and actin interaction. Accordingly, we are showing for the first time that actin and Myosin A are important forToxoplasmamitochondrial morphology and inheritance.
Excitonic enhancement of cavity-mediated interactions in a two-band Hubbard model
Authors: Wang Xiao , Jaksch Dieter , Schlawin Frank
Published: March 2024

We study cavity-mediated interactions that are generated in a two-dimensional two-band Hubbard model coupled to an optical cavity, when it is driven in-gap by a strong laser. Starting from a Floquet description of the driven system, we derive effective low-energy Hamiltonians by projecting out the high-energy degrees of freedom and treating intrinsic interactions on a mean-field level. We then investigate how the emergence of high-energy Frenkel excitons from the electronic interband coupling, which form near the upper electronic band, affects the interactions as well as the laser-induced Floquet renormalization of the electronic band structure. Cavity-mediated interactions are enhanced strongly when the light couples to an excitonic transition. Additionally, the interaction as well as the Floquet renormalization are strongly broadened in reciprocal space, which could further boost the impact of cavity-mediated interactions on the driven-dissipative steady state.

Published by the American Physical Society
2024
Accessing the gravitational form factors of the nucleon and nuclei through a massive graviton
Authors: Hatta Yoshitaka
Published: March 2024

In contrast to the electromagnetic form factors of the nucleon and nuclei that have been extensively studied in electron scattering, there is no known way to directly measure the gravitational form factors (GFFs), the off-forward hadronic matrix element of the QCD energy-momentum tensor. I suggest exploring the possibility to access the GFFs of the proton and nuclei in conjunction with massive graviton searches at future TeV-scale lepton-ion colliders.

Published by the American Physical Society
2024
Interactions and Migration Rescuing Ecological Diversity
Authors: Garcia Lorenzana Giulia , Altieri Ada , Biroli Giulio
Published: March 2024

How diversity is maintained in natural ecosystems is a long-standing question in Theoretical Ecology. By studying a system that combines ecological dynamics, heterogeneous interactions, and spatial structure, we uncover a new mechanism for the survival of diversity-rich ecosystems in the presence of demographic fluctuations. For a single species, one finds a continuous phase transition between an extinction and a survival state, that falls into the universality class of Directed Percolation. Here we show that the case of many species with heterogeneous interactions is different and richer. By merging theory and simulations, we demonstrate that with sufficiently strong demographic noise, the system exhibits behavior akin to the single-species case, undergoing a continuous transition. Conversely, at low demographic noise, we observe unique features indicative of the ecosystem's complexity. The combined effects of the heterogeneity in the interaction network and migration enable the community to thrive, even in situations where demographic noise would lead to the extinction of isolated species. The emergence of mutualism induces the development of global bistability, accompanied by sudden tipping points. We present a way to predict the catastrophic shift from high diversity to extinction by probing responses to perturbations as an early warning signal.

Published by the American Physical Society
2024
The green library revolution: a catalyst for climate change action
Authors: Ajani Yusuf Ayodeji , Tella Adeyinka , Enakrire Rexwhite Tega
Published: March 2024

Purpose

Libraries are currently undergoing a significant transformation, emerging as dynamic advocates for environmental sustainability, surpassing their conventional roles as mere repositories of knowledge. In today’s world, dominated by the growing climate crisis, these evolving institutions are poised to play a pivotal role in addressing climate change. However, they confront a range of challenges, including the need to establish sustainable operations, provide accessible climate information, engage diverse audiences and uphold ethical standards.

Design/methodology/approach

The research methodology used for this study involves an extensive review of literature. The authors analyze existing studies concerning green libraries and their role as catalysts for climate change action globally. This analysis draws from a variety of scholarly sources, encompassing articles, books and reports, to provide a comprehensive overview of the subject.

Findings

The findings indicate that despite the aforementioned challenges, libraries in developed countries worldwide have demonstrated noteworthy success through initiatives such as green building projects, community engagement programs, collaborative partnerships, expansion of digital resources, innovative climate literacy initiatives and a commitment to ethical stewardship. These achievements serve as a source of inspiration, fostering hope and spurring action as libraries empower communities to embrace environmental stewardship. They showcase the potential of libraries as catalysts for positive environmental change.

Originality/value

The originality and value of this research lie in its insights into the potential of green libraries initiative as a catalyst for climate change action. Ultimately, this study opens the door to untold literary exploration, revolutionizing the art of green library capacity in the ever-evolving technological landscape. To augment their impact, libraries are encouraged to broaden the scope of their climate education initiatives, expand their digital resources, cultivate strategic collaborations, prioritize ethical responsibility and implement thorough evaluation and communication practices.
Debt, economic growth and threshold effects: Evidence from developing countries
Authors: Ibañez Martín María María , Rojas Mara Leticia , Dabús Carlos
Published: March 2024

Purpose

Most empirical papers on threshold effects between debt and growth focus on developed countries or a mix of developing and developed economies, often using public debt. Evidence for developing economies is inconclusive, as is the analysis of other threshold effects such as those probably caused by the level of relative development or the repayment capacity. The objective of this study was to examine threshold effects for developing economies, including external and total debt, and identify them in the debt-growth relation considering three determinants: debt itself, initial real Gross Domestic Product (GDP) per capita and debt to exports ratio.

Design/methodology/approach

We used a panel threshold regression model (PTRM) and a dynamic panel threshold model (DPTM) for a sample of 47 developing countries from 1970 to 2019.

Findings

We found (1) no evidence of threshold effects applying total debt as a threshold variable; (2) one critical value for external debt of 42.32% (using PTRM) and 67.11% (using DPTM), above which this factor is detrimental to growth; (3) two turning points for initial GDP as a threshold variable, where total and external debt positively affects growth at a very low initial GDP, it becomes nonsignificant between critical values, and it negatively influences growth above the second threshold; (4) one critical value for external debt to exports using PTRM and DPTM, below which external debt positively affects growth and negatively above it.

Originality/value

The outcome suggests that only poorer economies can leverage credits. The level of the threshold for the debt to exports ratio is higher than that found in previous literature, implying that the external restriction could be less relevant in recent periods. However, the threshold for the external debt-to-GDP ratio is lower compared to previous evidence.
Leveraging artificial intelligence in firm-generated online customer communities: a framework and future research agenda
Authors: Marti Candice L. , Liu Huimin , Kour Gurpreet , Bilgihan Anil , Xu Yu
Published: March 2024

Purpose

In an era where complex technological advances increasingly govern service delivery, it is incumbent on service firms to pioneer innovative strategies to sustain customer engagement and cultivate loyalty. This conceptual paper examines the transformative potential of artificial intelligence (AI) in the realm of online customer communities, with a particular focus on its creation, management and enhancement facets. The authors explore how AI can revolutionize the dynamics of customer interaction, feedback mechanisms and overall engagement within the service industry.

Design/methodology/approach

This conceptual paper draws from marketing and management literature focusing on customer communities and AI in service and customer engagement contexts with a robust future research agenda.

Findings

A classification of online customer community engagement is provided along with a conceptual framework to guide our understanding of the integration of AI into online customer communities.

Originality/value

This exploration underscores the imperative for service firms to embrace AI-driven approaches to online customer community management, not only as a means to optimize their operations but as a vital strategy to stay competitive in the ever-evolving digital landscape. This paper examines the novel combination of AI with online customer communities and provides the framework in the form of an input-process-output (IPO) model for future research into this integration.
The end of tourism? Contemplations of collapse
Authors: Higgins-Desbiolles Freya
Published: March 2024

Purpose

This viewpoint engages with Jem Bendell’s deep adaptation framework which was developed as a response to the threat of collapse. Proponents of deep adaptation argue that societal collapse is either likely, inevitable or already underway. The deep adaptation framework is employed as a tool to contemplate the necessary adaptation of tourism development and planning in a context of polycrisis leading to collapse.

Design/methodology/approach

This is a conceptual viewpoint article that is built on deductive analysis of recent events, reports and scientific findings. It employs the deep adaptation framework to analyse possible alternative tourism futures in the face of the threat of collapse.

Findings

Bendell’s framework included four aspects of response to the recognition of the threat of collapse: resilience, relinquishment, restoration and reconciliation. In this work, the deep adaptation framework is employed to analyse what a deep adaptation approach to tourism might offer for efforts in securing optimal social and ecological outcomes. Findings highlight damaging activities that we should relinquish, more resilient approaches that communities could encourage and restorative practices such as rewilding and pluriversal economies as protective measures. This work recommends a precautionary approach to transform tourism education, research and practice in order to secure better tourism futures.

Originality/value

This work is novel in engaging with the threat of future collapse and in using the deep adaptation framework to consider alternative tourism futures.
Assessment of working capital management efficiency – a two-stage slack-based measure of data envelopment analysis
Authors: Seth Himanshu , Deepak Deepak , Ruparel Namita , Chadha Saurabh , Agarwal Shivi
Published: March 2024

Purpose

This study aims to assess the efficiency of managing working capital in 1,388 Indian manufacturing firms from 2008 to 2019 and investigate the effects of firm-specific and macro-level determinants on working capital management (WCM) efficiency.

Design/methodology/approach

The current study accommodates a slack-based measure (SBM) in data envelopment analysis (DEA) for computing WCM efficiency. Further, we implement a panel data fixed-effects model that controls for heterogeneity across firms in determining the relationships of selected variables with WCM efficiency.

Findings

The results highlight that manufacturing firms operate at around 50 percent efficiency, which is constant throughout the study period. Furthermore, among the selected variables, yield, earnings, age, size, ability to create internal resources, interest rate and gross domestic product (GDP) significantly affect WCM efficiency.

Originality/value

Instead of the traditional models used for assessing efficiency, the SBM-DEA model is unit-invariant and monotone for slacks, implying that it can handle zero and negative data, which overcomes the incapability of prior DEA models. Hence, this provides accurate efficiency scores for robust analysis. Additionally, this paper provides a holistic working capital model recognizing firm-specific and macro-level determinants for a more explicit estimation of the relationship between WCM efficiency and the selected determinants.
Woody semi‐natural habitats modulate the effects of field size and functional crop diversity on farmland birds
Authors: Frank Claudia , Hertzog Lionel , Klimek Sebastian , Schwieder Marcel , Tetteh Gideon Okpoti , Böhner Hannah G. S. , Röder Norbert , Levers Christian , Katzenberger Jakob , Kreft Holger , Kamp Johannes
Published: March 2024

Agricultural intensification has simplified landscape composition and configuration, which has led to biodiversity declines. Increasing landscape‐wide crop heterogeneity can promote farmland biodiversity. However, knowledge is still lacking on how the effects of configurational and compositional crop heterogeneity (i.e. field size and crop diversity) are modulated by the amount of semi‐natural habitats in the landscape, especially across large scales.

We tested how mean field size and functional crop diversity affect farmland bird diversity and abundance over three consecutive years, and how these effects are modulated by the amount of small woody features (SWF) in the landscape. We related data from a national bird monitoring scheme to field‐level information from a novel, high‐resolution remote sensing‐based crop type map.

Smaller field sizes and higher functional crop diversity were not generally associated with a higher diversity or abundance of farmland birds. Associations varied with species' breeding habitat preferences and were modulated by the amount of SWF.

In landscapes with a low SWF amount, species diversity and the abundance of species breeding in field edges or shrubs were negatively associated with increasing field size. However, where the amount of SWF was high, larger field size was associated with higher species diversity and abundance of field and shrub breeders. Diversity increased with higher functional crop diversity, as did the abundance of non‐field breeders in landscapes with a medium to high SWF amount. Field size tended to have a stronger effect on bird diversity and abundance than functional crop diversity.

Policy implications: National and EU agricultural policies should adopt a landscape perspective by considering the amount of semi‐natural habitats when designing biodiversity‐enhancing measures that target field size and functional crop diversity. In landscapes with low SWF amount, decreasing field sizes may be particularly effective to promote farmland bird diversity and the abundance of non‐field breeders. In landscapes with a medium to high SWF amount, increasing functional crop diversity is likely more effective than reducing field sizes. Field and shrub breeders may be promoted by maintaining landscapes with large fields, only if these offer a high SWF amount, low agronomic yield potential and low productivity.
Expectations and experiences of a dance programme for autistic children: A qualitative study of parents, teachers and therapists
Authors: Golding Ali , Ambrose Zoe , Lara Joanne , Malamateniou Christina , Green Dido
Published: March 2024

This study explores the expectations of dance therapists/practitioners and parents and teachers of autistic children engaging in a developmental dance programme. Information gathered will support development of an evaluation tool aligned with the International Classification of Functioning Disability and Health (ICF) Core Sets for autism spectrum disorders (ASD). A qualitative study included a convenience cohort of teachers (n = 6), parents (n = 2) of children with ASD and therapists (n = 3). Three role specific focus groups were undertaken considering potential benefits and challenges of the programme. Content and thematic analysis was undertaken using NVivo12. Findings reflected four positive themes relating to behaviour, skills, social interaction and environmental supports. Therapists, teachers and parents focused differently on stereotypical and restricted behaviours, environmental supports and habits and routines respectively. These themes also emerged as challenges (to implement/achieve); with parents identifying more emotional and behavioural restrictions. A fourth challenge theme of transferability of skills emerged from teachers and therapists. Items mapped against 28 ICF Core Sets (across the lifespan) and six to ICF categories, with creativity and imagination mismatched. Findings highlight need for a specific outcome measure for dance and/or movement programmes for autistic individuals that captures meaningful functions across ICF domains for differing stakeholders.
Diagnostic challenge and survival analysis of pulmonary oligometastases and primary lung cancer in breast cancer patients
Authors: Mai Siyao , Liu Haiqing , Zeng Hong , Cheng Ziliang , Huang Jingwen , Shi Guangzi , Li Yong , Wu Zhuo
Published: March 2024

Background

The aim of this study was to compare breast cancer patients with pulmonary oligometastases (POM) and primary lung cancer (PLC) and to assess whether there were differences in clinical features, CT features, and survival outcomes between the two groups.

Methods

From January 2010 to December 2021, the clinical records of 437 with malignant pulmonary nodules who had breast cancer patients were reviewed. POM was identified in 45 patients and PLC in 43 patients after the initial detection of pulmonary nodules. The clinicopathological characteristics, CT appearance of pulmonary nodules, and survival of the two groups were compared.

Results

Stage II to IV breast tumors (p < 0.001), high pathological grade of breast cancer (p = 0.001), low proportion of luminal‐type breast cancer (p = 0.003), and the higher serum CYFRA 21‐1 level (p = 0.046) were the clinical characteristics of pulmonary nodules suggestive of POM rather than PLC. The CT features of lung nodules indicative of PLC rather than POM were the subsolid component (p < 0.001), lobulation (p = 0.010), air bronchogram (p < 0.001) and pleural indentation (p = 0.004). Ten‐year survival rate for PLC was 93.2%, which was higher compared with 57.8% in those with POM (p = 0.001).

Conclusions

Elevated serum CYFRA 21‐1 levels and late‐stage breast cancer may be beneficial for the diagnosis of POM. CT imaging appearances of the subsolid component, lobulation, air bronchogram, and pleural indentation increase the likelihood of PLC. Breast cancer patients with PLC presented better survival with attentive monitoring than those with POM.
Prospective validity evidence for the abbreviated emergency medicine Copenhagen Burnout Inventory
Authors: Reisdorff Earl J. , Johnston Mary M. , Lall Michelle D. , Lu Dave W. , Bilimoria Karl Y. , Barton Melissa A.
Published: March 2024

Background

Prior research has provided retrospective validity evidence for an abbreviated Copenhagen Burnout Inventory (CBI) to measure burnout among emergency medicine (EM) residents. We sought to provide additional validity and reliability evidence for the two‐factor, six‐item abbreviated CBI.

Methods

This cross‐sectional study used data from the abbreviated CBI that was administered following the 2022 American Board of Emergency Medicine In‐training Examination. Confirmatory factor analysis (CFA) was performed and the prevalence of burnout among EM residents was determined.

Results

Of the 8918 eligible residents, 7465 (83.7%) completed the abbreviated CBI. CFA confirmed the previously developed model of two factors using six items answered with a 1‐ to 5‐point Likert scale. The internal factor was derived from personal and work‐related burnout and the external factor was related to caring for patients. The reliability was determined using Cronbach's alpha (0.87). The overall prevalence of burnout was 49.4%; the lowest prevalence was at the EM1 level (43.1%) and the highest was at the EM2 level (53.8%).

Conclusions

CFA of the abbreviated CBI demonstrated good reliability and model fit. The two‐factor, six‐item survey instrument identified an increase in the prevalence of burnout among EM residents that coincided with working in the COVID‐19 environment. The abbreviated CBI has sufficient reliability and validity evidence to encourage its broader use.
Are larger termite mounds more resistant to fire? A study of two southern African termites (Isoptera: Termitidae)
Authors: de la Fontaine Benjamin , Edwards Shelley
Published: March 2024

Termites are resistant to fire, a common disturbance in the world's savannas, but most explanations for how termites resist fire are speculative. Some researchers have suggested that the mounds of some termite species can serve as a structural defence against direct fire mortality. Because mound structure is related to thermoregulation, and larger mounds have more stable internal temperatures, larger mounds may confer greater fire resistance. Fire also causes indirect mortality to termites by removing food sources, which may give an advantage to larger mounds as they have superior food provisioning and storage ability. Using natural fires, we measured mound size and colony survival of two southern African termite species (Trinervitermes trinervoides and Amitermes sp.) in plots recently burnt (<4 months after fire), recovering from fire (1–2 years after fire), or unburnt (>3 years after fire). Burn status and mound size were each significant factors in colony survival. Recent fire was associated with the lowest survival, and larger mounds with greater survival. There is some evidence that larger mounds are generally more resistant to fire, especially the long term, indirect effects, but sample sizes were not adequate to confirm this.
Avian colouration in a polluted world: a meta‐analysis
Authors: Janas Katarzyna , Gudowska Agnieszka , Drobniak Szymon M.
Published: March 2024

Brilliant, diverse colour ornaments of birds were one of the crucial cues that led Darwin to the idea of sexual selection. Although avian colouration plays many functions, including concealment, thermoregulation, or advertisement as a distasteful prey, a quality‐signalling role in sexual selection has attracted most research attention. Sexually selected ornaments are thought to be more susceptible to external stressors than naturally selected traits, and as such, they might be used as a test for environmental quality. For this reason, the last two decades have seen numerous studies on the impact of anthropogenic pollution on the expression of various avian colour traits. Herein, we provide the first meta‐analytical summary of these results and examine whether there is an interaction between the mechanism of colour production (carotenoid‐based, melanin‐based and structural) and the type of anthropogenic factor (categorised as heavy metals, persistent organic pollutants, urbanisation, or other). Following the assumption of heightened condition dependence of ornaments under sexual selection, we also expected the magnitude of effect sizes to be higher in males. The overall effect size was close to significance and negative, supporting a general detrimental impact of anthropogenic pollutants on avian colouration. In contrast to expectations, there was no interaction between pollution types and colour‐producing mechanisms. Yet there were significant differences in sensitivity between colour‐producing mechanisms, with carotenoid‐based colouration being the most affected by anthropogenic environmental disturbances. Moreover, we observed no significant tendency towards heightened sensitivity in males. We identified a publication gap on structural colouration, which, compared to pigment‐based colouration, remains markedly understudied and should thus be prioritised in future research. Finally, we call for the unification of methods used in colour quantification in ecological research to ensure comparability of results among studies.
How barriers become invisible: Children are less sensitive to constraints that are stable over time
Authors: Amemiya Jamie , Heyman Gail D. , Walker Caren M.
Published: March 2024

When making inferences about the mental lives of others (e.g., others’ preferences), it is critical to consider the extent to which the choices we observe are constrained. Prior research on the development of this tendency indicates a contradictory pattern: Children show remarkable sensitivity to constraints in traditional experimental paradigms, yet often fail to consider real‐world constraints and privilege inherent causes instead. We propose that one explanation for this discrepancy may be that real‐world constraints are often stable over time and lose their salience. The present research tested whether children (N = 133, 5‐ to 12‐year‐old mostly US children; 55% female, 45% male) become less sensitive to an actor's constraints after first observing two constrained actors (Stable condition) versus after first observing two actors in contexts with greater choice (Not Stable condition). We crossed the stability of the constraint with the type of constraint: either the constraint was deterministic such that there was only one option available (No Other Option constraint) or, in line with many real‐world constraints, the constraint was probabilistic such that there was another option, but it was difficult to access (Hard to Access constraint). Results indicated that children in the Stable condition became less sensitive to the probabilistic Hard to Access constraint across trials. Notably, we also found that children's sensitivity to constraints was enhanced in the Not Stable condition regardless of whether the constraint was probabilistic or deterministic. We discuss implications for children's sensitivity to real‐world constraints.

Research Highlights

This research addresses the apparent contradiction that children are sensitive to constraints in experimental paradigms but are often insensitive to constraints in the real world.

One explanation for this discrepancy is that constraints in the real world tend to be stable over time and may lose their salience.

When probabilistic constraints (i.e., when a second option is available but hard to access) are stable, children become de‐sensitized to constraints across trials.

First observing contexts with greater choice increases children's sensitivity to both probabilistic and deterministic constraints.
Effects of drought stress on the functional traits and rhizosphere microbial community structure of Cyperus esculentus
Authors: Liu Binshuo , Hu Yunhang , Li Ming , Xue Honghai , Wang Ying , Li Zhonghe
Published: March 2024

Drought is a major factor limiting plant growth. Plants cope with stress via morphophysiological responses. Rhizosphere‐related bacteria, fungi and other microorganisms can help plants cope with drought via various mechanisms. We conducted a pot experiment on Cyperus esculentus wherein we subjected it to various drought levels and analyzed the functional traits of its aboveground and belowground organs. High‐throughput sequencing was used to study the structure and diversity of the microbial community in the rhizosphere. Drought stress substantially lowered the densities of the leaves, stems, roots and seeds relative to the untreated control. Drought stress inhibited the growth and reduced the yield of C. esculentus. The leaves and seeds have higher water content and are more sensitive to drought stress than the roots. With the aggravation of drought stress, the plant height of C. esculentus decreased significantly, the root:shoot ratio increased and the specific leaf weight had no significant difference. Change in shoot height was the most evident response of C. esculentus to drought stress. Plants under drought stress reduced their leaf area and assumed a specific leaf weight to maintain photosynthetic performance. Rhizosphere fungi were more sensitive to drought stress than rhizosphere bacteria. Drought stress increased the relative abundances of Bacteroidetes, Verrucomicrobia, Patescibacteria, Actinobacteria and Nitrospirae. Drought‐stressed C. esculentus maintained their photosynthetic performance by reducing shoot height and leaf area while assuming a stable specific leaf weight. Drought stress exerted a significantly stronger negative impact on rhizosphere fungi than rhizosphere bacteria. The results clarified the response strategies of functional traits and rhizosphere microorganisms of C. esculentus to drought stress.
Defining success in haemophilia care – Are we doing it right?
Authors: Srivastava Alok
Published: March 2024

Introduction

Transformational advances have occurred in the management of haemophilia in the last decade leading to much better outcomes. However, a detailed and critical examination of its assessment and reporting show gaps in many aspects. These are discussed in this review.

Methods

The relevant literature related to different aspects of management of haemophilia was reviewed to identify gaps which need to be addressed. These include detection and diagnosis of haemophilia, documentation and reporting of joint bleeding, its management and methods of reporting in clinical trials and practice, aspects of personalizing care as well as access to therapeutic products and the need for and organization of comprehensive care.

Results

Current diagnostic approaches have more than doubled the identified number of persons with haemophilia (PWH) over the last 25 years but still constitute only ∼30% of the expected number. Joint bleeding is the primary indicator of disease severity and treatment efficacy, but there is lack of consistency and standardization in the way it is recorded and reported. Its continued use as an efficacy measure of modern treatments which maintain steady state factor levels or equivalence of >5% will lack sensitivity. The treatment of acute haemarthrosis has focussed on haemostasis and pain control, ignoring the role of inflammation in joint damage. Phenotypic heterogeneity of severe haemophilia has recognized clinical and laboratory variations based on haemostasis but not differences in local response to blood in the joint. At the organizational level, IU/capita provides a relevant measure of access to therapeutic products when the detection rate is ∼100% but is fallaciously low when detection rates are very low. With highly effective modern therapies for haemophilia and nearly no bleeding, the concept of comprehensive care team will need modifications.

Conclusion

As haemophilia care advances, a deeper dive is needed into the details of various aspects its management to ensure consistency and contemporary relevance.
Effects of freeze–thaw cycles on the physicochemical and in vitro digestibility of starch in pre‐fermented frozen raw dough
Authors: Zhang Haifeng , Yin Li , Wang Qiuyu , Wang Yun , Su Jiamin , Li Chunmei , Zhou Xiaoyan
Published: March 2024

In this study, pre‐fermented frozen raw dough (PFRD) was subjected to freeze–thaw cycling (FTC) to explore the deterioration mechanism of PFRD, after which the physical quality, chemical properties and in vitro digestion characteristics of starch in the dough were analysed. The results showed that after the 5th FTC, the surface area of the dough and starch exhibited obvious depression deformation, and the damaged starch content increased by 38.21%. The random mechanical damage caused by ice crystals also had no significant regularity in the water retention and the short‐range order of starch. Moreover, the breakdown of the double helix structure of starch led to the dissolution of amylose, and the expansion and gelatinization enthalpy increased. In addition, the in vitro digestion results showed that freeze–thaw cycle twice increased the digestibility of the starch, and the hydrolysis rate reached 75.16%, Therefore, the effects of FTC twice on the starch of PFRD are controllable. This study provides a theoretical basis for the development of prefabricated frozen starch food industry technology in the future.
Post‐translational modifications in diabetic cardiomyopathy
Authors: Li Zhi , Chen Jie , Huang Hailong , Zhan Qianru , Wang Fengzhi , Chen Zihan , Lu Xinwei , Sun Guozhe
Published: March 2024

The increasing attention towards diabetic cardiomyopathy as a distinctive complication of diabetes mellitus has highlighted the need for standardized diagnostic criteria and targeted treatment approaches in clinical practice. Ongoing research is gradually unravelling the pathogenesis of diabetic cardiomyopathy, with a particular emphasis on investigating various post‐translational modifications. These modifications dynamically regulate protein function in response to changes in the internal and external environment, and their disturbance of homeostasis holds significant relevance for the development of chronic ailments. This review provides a comprehensive overview of the common post‐translational modifications involved in the initiation and progression of diabetic cardiomyopathy, including O‐GlcNAcylation, phosphorylation, methylation, acetylation and ubiquitination. Additionally, the review discusses drug development strategies for targeting key post‐translational modification targets, such as agonists, inhibitors and PROTAC (proteolysis targeting chimaera) technology that targets E3 ubiquitin ligases.
CD40 stimulation via CD40 ligand enhances adenovirus‐mediated tumour immunogenicity including ‘find‐me’, ‘eat‐me’, and ‘kill‐me’ signalling
Authors: Naseri Sedigheh , Cordova Mariela Mejia , Wenthe Jessica , Lövgren Tanja , Eriksson Emma , Loskog Angelica , Ullenhag Gustav J.
Published: March 2024

Immunostimulatory gene therapy using oncolytic viruses is currently evaluated as a promising therapy for cancer aiming to induce anti‐tumour immunity. Here, we investigate the capacity of oncolytic adenoviruses (LOAd) and their transgenes to induce immunogenicity in the infected tumour cells. Oncolysis and death‐related markers were assessed after infection of eight human solid cancer cell lines with different LOAd viruses expressing a trimerized, membrane‐bound (TMZ)‐CD40L, TMZ‐CD40L and 41BBL, or no transgenes. The viruses induced transgene expression post infection before they were killed by oncolysis. Death receptors TRAIL‐R1, TRAIL‐R2 and Fas as well as immunogenic cell death marker calreticulin were upregulated in cell lines post infection. Similarly, caspase 3/7 activity was increased in most cell lines. Interestingly, in CD40+ cell lines there was a significant effect of the TMZ‐CD40L‐encoding viruses indicating activation of the CD40‐mediated apoptosis pathway. Further, these cell lines showed a significant increase of calreticulin, and TRAIL receptor 1 and 2 post infection. However, LOAd viruses induced PD‐L1 upregulation which may hamper anti‐tumour immune responses. In conclusion, LOAd infection increased the immunogenicity of infected tumour cells and this was potentiated by CD40 stimulation. Due to the simultaneous PD‐L1 increase, LOAd viruses may benefit from combination with antibodies blocking PD1/PD‐L1.
Microglia orchestrate synaptic and neuronal stripping: Implication in neuropsychiatric lupus
Authors: Zhou Yishan , Chen Liang , Zheng Xiulan , Fang Qijun , Qian Yunzhi , Xu Tianshu , Liang Jun , Zhang Huajun , Han Xiaojuan , Sun Lingyun
Published: March 2024

Systemic lupus erythematosus (SLE), a multifactorial autoimmune disease, can affect the brain and cause neuropsychiatric dysfunction, also named neuropsychiatric lupus (NPSLE). Microglial activation is observed in NPSLE patients. However, the mechanisms regulating microglia‐mediated neurotoxicity in NPSLE remain elusive. Here, we showed that M1‐like proinflammatory cytokine levels were increased in the cerebrospinal fluid (CSF) of SLE patients, especially those with neuropsychiatric symptoms. We also demonstrated that MRL/lpr lupus mice developed anxiety‐like behaviours and cognitive deficits in the early and active phases of lupus, respectively. An increase in microglial number was associated with upregulation of proinflammatory cytokines in the MRL/lpr mouse brain. RNA sequencing revealed that genes associated with phagocytosis and M1 polarization were upregulated in microglia from lupus mice. Functionally, activated microglia induced synaptic stripping in vivo and promoted neuronal death in vitro. Finally, tofacitinib ameliorated neuropsychiatric disorders in MRL/lpr mice, as evidenced by reductions in microglial number and synaptic/neuronal loss and alleviation of behavioural abnormalities. Thus, our results indicated that classically activated (M1) microglia play a crucial role in NPSLE pathogenesis. Minocycline and tofacitinib were found to alleviate NPSLE by inhibiting micrglial activation, providing a promising therapeutic strategy.
Borax induces ferroptosis of glioblastoma by targeting HSPA5/NRF2/GPx4/GSH pathways
Authors: Tuncer Cengiz , Hacioglu Ceyhan
Published: March 2024

Glioblastoma multiforme (GBM) is a highly aggressive and lethal form of primary brain tumour. Borax has been demonstrated to exhibit anti‐cancer activity through cell death pathways. However, the specific impact of borax on ferroptosis in GBM is not well‐established, and the underlying regulatory mechanisms remain unclear. Initially, the effective concentration of borax on cell viability and proliferation in U251 and A172 cells was determined. Subsequently, the effects of borax on the wound healing were analysed. Nuclear factor erythroid 2‐related factor 2 (NRF2), glutathione peroxidase 4 (GPx4), glutathione (GSH), HSP70 protein 5 (HSPA5), malondialdehyde (MDA) levels and caspase‐3/7 activity were determined in borax‐treated and untreated cells. Finally, the protein expression levels of HSPA5, NRF2 and GPx4 were analysed. Borax suppressed cell viability and proliferation in U251 and A172 cells in a concentration‐ and time‐dependent manner. In addition, borax treatment decreased GPx4, GSH, HSPA5 and NRF2 levels in U251 and A172 cells while increasing MDA levels and caspase‐3/7 activity. Moreover, borax reduced mRNA and protein levels of HSPA5, NRF2 and GPx4 in U251 and A172 cells. Consequently, borax may induce ferroptosis in GBM cells and regulate the associated regulatory mechanisms targeting NRF2 and HSPA5 pathways. This knowledge may contribute to the development of novel therapeutic approaches targeting ferroptosis in GBM and potentially improve patient outcomes.
The value proposition for geriatrics
Authors: Ouslander Joseph G. , Rackman A. Sasha , Russell William
Published: March 2024

In response to some of the challenges that have been articlulated about the future of Geriatrics, we describe a more positive view and value proposition for the field. Health professionals with specific training in Geriatrics are a natural fit for a variety of roles in value‐based care (VBC) programs and health systems. These roles include serving as educators for primary care health professionals and specialists in person‐centered care of older adults, serving as consultants on geriatric conditions and syndromes in a co‐management model of care, becoming effective leaders in VBC programs and health systems, and conducting quality improvement initiatives to build on the evidence‐base for the management of common conditions in the older population. We further recommend that VBC programs and systems support Centers of Excellence or Institutes to implement these strategies within and Age‐Friendly, learning system approach.
Chronic social defeat stress induces the down‐regulation of the Nedd4L‐GLT‐1 ubiquitination pathway in the prefrontal cortex of mice
Authors: Kosuge Aika , Kunisawa Kazuo , Iida Tsubasa , Wulaer Bolati , Kawai Tomoki , Tanabe Moeka , Saito Kuniaki , Nabeshima Toshitaka , Mouri Akihiro
Published: March 2024

Stressful life events contribute to the onset of major depressive disorder (MDD). We recently demonstrated abnormalities in ubiquitination in the pathophysiology of MDD. However, the underlying molecular mechanisms remain unclear. We investigated the involvement of the ubiquitination system‐mediated glutamatergic dysfunction in social impairment induced by chronic social defeat stress (CSDS). Adult C57BL/6J mice were exposed to aggressor ICR male mice for 10 consecutive days. Social impairment was induced by CSDS in the social interaction test 1 days after the last stress exposure. In terms of brain microdialysis, CSDS reduced depolarization‐evoked glutamate release in the prefrontal cortex (PFC), which was reversed by a glutamate transporter 1 (GLT‐1) inhibitor. Interestingly, the expression of ubiquitinated, but not total GLT‐1, was decreased in the PFC of mice exposed to CSDS. The expression of neural precursor cells expressing developmentally downregulated gene 4‐like (Nedd4L: E3 ligase for GLT‐1), and ubiquitin‐conjugating enzyme E2D2 (Ube2d2: E2 ubiquitin‐conjugating enzyme for Nedd4L) was also reduced in CSDS mice. Furthermore, the downregulation of the Nedd4L‐GLT‐1 ubiquitination pathway decreased SIT ratio, but up‐regulation increased it even in non‐CSDS mice. Taken together, the decrease in GLT‐1 ubiquitination may reduce the release of extracellular glutamate induced by high‐potassium stimulation, which may lead to social impairment, while we could not find differences in GLT‐1 ubiquitination between susceptible and resistant CSDS mice. In conclusion, GLT‐1 ubiquitination could play a crucial role in the pathophysiology of MDD and is an attractive target for the development of novel antidepressants.

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Endogenous property rights, credit market, and economic development
Authors: Bose Niloy , Cothren Richard , Sedaghatkish Nazanin
Published: March 2024

Empirical evidence suggests that credit markets can catalyze property rights reforms. We illustrate this in a theoretical framework where a borrower must expend costly effort to protect output from predation. We consider two possible equilibrium loan contracts. In the first, lenders leave the decision to protect output to borrowers. In the second, lenders set the standard of property protection as a precondition for lending. The second contracting regime results in a higher level of property rights enforcement. Significantly, the level of economic development determines the equilibrium contracting form and vice versa. Based on this analysis, we jointly determine the evolution of property rights and economic development. The analysis also sheds light on the environments that lead an economy to a low development trap with a poor quality of property rights institutions.