bluuebunny/crossref_metadata_2025 huggingface dataset:
Indigenous and decolonial futures: Indigenous Protected and Conserved Areas as potential pathways of reconciliation
Authors: Townsend Justine , Roth Robin
Published: December 2023

Crown governments, the conservation sector, academics, and some Indigenous governments, communities, and organizations are framing Indigenous Protected and Conserved Areas (IPCAs)—a newly recognized form of Indigenous-led conservation in Canada—as advancing reconciliation with Indigenous Peoples. Yet it is often unclear what is being, or could be, reconciled through IPCAs. While highly diverse, IPCAs are advanced by Indigenous Nations, governments, and communities who protect them, with or without partners, according to their Indigenous knowledge, legal, and governance systems. IPCAs may be expressions of “generative refusal,” visions of Indigenous futures, and commitments to uphold responsibilities to the lands, waters, and past and future generations. IPCAs refuse settler colonial ontologies including the expectation of ongoing white settler privilege, which relies on the continued appropriation of lands and resources. By examining the practical, relational, and systemic challenges Indigenous Nations advancing IPCAs encounter, we discuss opportunities for Crown governments and the conservation sector to cultivate decolonial responses. Indigenous Nations advancing IPCAs may face challenges with resource extraction, laws and legislation, financing, relationships and capacity, and jurisdiction and governance. We contend that IPCAs could be pathways of reconciliation if Crown governments and the conservation sector support IPCAs in ways consistent with the recommendations of Indigenous leaders. This requires dismantling the roadblocks arising from settler ontologies and institutions that impede IPCA establishment and ongoing stewardship. Thus, not only could Indigenous futures be advanced, we might also cultivate decolonial futures in which all peoples and species can thrive.
Bioinformatics-led discovery of liver-specific genes and macrophage infiltration in acute liver injury
Authors: Cao Zhiwen , Lu Peipei , Li Li , Geng Qi , Lin Lin , Yan Lan , Zhang Lulu , Shi Changqi , Li Li , Zhao Ning , He Xiaojuan , Tan Yong , Lu Cheng
Published: December 2023

Background

Acute liver injury (ALI) is an important global health concern, primarily caused by widespread hepatocyte cell death, coupled with a complex immune response and a lack of effective remedies. This study explores the underlying mechanisms, immune infiltration patterns, and potential targets for intervention and treatment ALI.

Methods

The datasets of acetaminophen (APAP), carbon tetrachloride (CCl4), and lipopolysaccharide (LPS)-induced ALI were obtained from the GEO database. Differentially expressed genes (DEGs) were individually identified using the limma packages. Functional enrichment analysis was performed using KEGG, GO, and GSEA methods. The overlapping genes were extracted from the three datasets, and hub genes were identified using MCODE and CytoHubba algorithms. Additionally, PPI networks were constructed based on the String database. Immune cell infiltration analysis was conducted using ImmuCellAI, and the correlation between hub genes and immune cells was determined using the Spearman method. The relationship between hub genes, immune cells, and biochemical indicators of liver function (ALT, AST) was validated using APAP and triptolide (TP) -induced ALI mouse models.

Results

Functional enrichment analysis indicated that all three ALI models were enriched in pathways linked to fatty acid metabolism, drug metabolism, inflammatory response, and immune regulation. Immune analysis revealed a significant rise in macrophage infiltration. A total of 79 overlapping genes were obtained, and 10 hub genes were identified that were consistent with the results of the biological information analysis after screening and validation. Among them, Clec4n, Ms4a6d, and Lilrb4 exhibited strong associations with macrophage infiltration and ALI.
The regulatory effect of growth differentiation factor 11 on different cells
Authors: Shao Yingchun , Liu Ting , Wen Xiaobo , Zhang Renshuai , Liu Xinlin , Xing Dongming
Published: December 2023

Growth differentiation factor 11 (GDF11) is one of the important factors in the pathophysiological process of animals. It is widely expressed in many tissues and organs of animals, showing its wide biological activity and potential application value. Previous research has demonstrated that GDF11 has a therapeutic effect on various diseases, such as anti-myocardial aging and anti-tumor. This has not only sparked intense interest and enthusiasm among academics but also spurred some for-profit businesses to attempt to develop GDF11 as a medication for regenerative medicine or anti-aging application. Currently, Sotatercept, a GDF11 antibody drug, is in the marketing application stage, and HS-235 and rGDF11 are in the preclinical research stage. Therefore, we believe that figuring out which cells GDF11 acts on and its current problems should be an important issue in the scientific and commercial communities. Only through extensive, comprehensive research and discussion can we better understand the role and potential of GDF11, while avoiding unnecessary risks and misinformation. In this review, we aimed to summarize the role of GDF11 in different cells and its current controversies and challenges, providing an important reference for us to deeply understand the function of GDF11 and formulate more effective treatment strategies in the future.
Chronic jet lag alters gut microbiome and mycobiome and promotes the progression of MAFLD in HFHFD-fed mice
Authors: Zheng Ruoyi , Xiang Xingwei , Shi Ying , Qiu Anqi , Luo Xin , Xie Junyan , Russell Ryan , Zhang Dongmei
Published: December 2023

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide. Circadian disruptors, such as chronic jet lag (CJ), may be new risk factors for MAFLD development. However, the roles of CJ on MAFLD are insufficiently understood, with mechanisms remaining elusive. Studies suggest a link between gut microbiome dysbiosis and MAFLD, but most of the studies are mainly focused on gut bacteria, ignoring other components of gut microbes, such as gut fungi (mycobiome), and few studies have addressed the rhythm of the gut fungi. This study explored the effects of CJ on MAFLD and its related microbiotic and mycobiotic mechanisms in mice fed a high fat and high fructose diet (HFHFD). Forty-eight C57BL6J male mice were divided into four groups: mice on a normal diet exposed to a normal circadian cycle (ND-NC), mice on a normal diet subjected to CJ (ND-CJ), mice on a HFHFD exposed to a normal circadian cycle (HFHFD-NC), and mice on a HFHFD subjected to CJ (HFHFD-CJ). After 16 weeks, the composition and rhythm of microbiota and mycobiome in colon contents were compared among groups. The results showed that CJ exacerbated hepatic steatohepatitis in the HFHFD-fed mice. Compared with HFHFD-NC mice, HFHFD-CJ mice had increases in Aspergillus, Blumeria and lower abundances of Akkermansia, Lactococcus, Prevotella, Clostridium, Bifidobacterium, Wickerhamomyces, and Saccharomycopsis genera. The fungi-bacterial interaction network became more complex after HFHFD and/or CJ interventions. The study revealed that CJ altered the composition and structure of the gut bacteria and fungi, disrupted the rhythmic oscillation of the gut microbiota and mycobiome, affected interactions among the gut microbiome, and promoted the progression of MAFLD in HFHFD mice.
The effects of temperature on prevalence of facultative insect heritable symbionts across spatial and seasonal scales
Authors: Martins Marcos , César Cássia Siqueira , Cogni Rodrigo
Published: December 2023

Facultative inheritable endosymbionts are common and diverse in insects and are often found at intermediate frequencies in insect host populations. The literature assessing the relationship between environment and facultative endosymbiont frequency in natural host populations points to temperature as a major component shaping the interaction. However, a synthesis describing its patterns and mechanistic basis is lacking. This mini-review aims to bridge this gap by, following an evolutionary model, hypothesizing that temperature increases endosymbiont frequencies by modulating key phenotypes mediating the interaction. Field studies mainly present positive correlations between temperature and endosymbiont frequency at spatial and seasonal scales; and unexpectedly, temperature is predominantly negatively correlated with the key phenotypes. Higher temperatures generally reduce the efficiency of maternal transmission, reproductive parasitism, endosymbiont influence on host fitness and the ability to protect against natural enemies. From the endosymbiont perspective alone, higher temperatures reduce titer and both high and low temperatures modulate their ability to promote host physiological acclimation and behavior. It is necessary to promote research programs that integrate field and laboratory approaches to pinpoint which processes are responsible for the temperature correlated patterns of endosymbiont prevalence in natural populations.
MicroRNA as potential biomarker for severity, progression, and therapeutic monitoring in animal models of limb-girdle muscular dystrophy: a systematic review
Authors: Oliveira Mayala Thayrine de Jesus Santos , da Silva Santana Talita Araújo Barbosa , Costa Marcela Câmara Machado , Borges Grasiely Faccin , de Miranda Felipe Silva , Slaibi-Filho José , Luiz Wilson Barros , Campos Luciene Cristina Gastalho
Published: December 2023

Limb-girdle muscular dystrophies (LGMD) constitute a heterogeneous group of neuromuscular disorders in which there are alterations in proteins responsible for the preservation of muscle architecture and function, leading to proximal and progressive muscle weakness. There is, however, significant phenotypic and genotypic variation, as well as difficulty in establishing biomarkers that help to define pathogenic mechanisms and assess disease severity and progression. In this field, there is special attention to microRNAs, small non-coding RNA molecules related to the regulation of gene expression and, consequently, the production of proteins. Thus, this research aimed to verify the correlation between the expression of microRNAs and the severity, progression, and therapeutic response of LGMD animal models. A search was carried out in the PubMed, Embase, Scopus, ScienceDirect, Cochrane, and SciELO databases, with articles in English and without a time limit. The PRISMA 2020 checklist was used, and the protocol of this review was submitted to PROSPERO. The bibliographic survey of the 434 records found that 5 original articles met the inclusion criteria. The studies explored myomicroRNAs or miRNA panels with gene expression analysis. The analysis demonstrates that miR-1, 133a, and 206 are differentially expressed in serum and muscle. They change according to the degree of inflammation, fibrosis, muscle regeneration, and progression of the dystrophic process. MicroRNAs are up-regulated in dystrophic muscles, which are reversed after treatment in a dose-dependent manner. The present study inferred that miRs are essential in severity, progression, and therapeutic response in LGMD models and may be a useful biomarker in clinical research and prognosis. However, the practical application of these findings should be further explored.
Biomarkers associated with the pathogenesis of Alzheimer’s disease
Authors: Wang Hui , Sun Mengli , Li Wenhui , Liu Xing , Zhu Mengfan , Qin Hua
Published: December 2023

Alzheimer’s disease (AD) is a progressive degenerative neurological illness with insidious onset. Due to the complexity of the pathogenesis of AD and different pathological changes, the clinical phenotypes of dementia are diverse, and these pathological changes also interact with each other. Therefore, it is of great significance to search for biomarkers that can diagnose these pathological changes to improve the ability to monitor the course of disease and treat the disease. The pathological mechanism hypothesis with high recognition of AD mainly includes the accumulation of β-amyloid (Aβ) around neurons and hyperphosphorylation of tau protein, which results in the development of neuronal fiber tangles (NFTs) and mitochondrial dysfunction. AD is an irreversible disease; currently, there is no clinical cure or delay in the disease process of drugs, and there is a lack of effective early clinical diagnosis methods. AD patients, often in the dementia stages and moderate cognitive impairment, will seek medical treatment. Biomarkers can help diagnose the presence or absence of specific diseases and their pathological processes, so early screening and diagnosis are crucial for the prevention and therapy of AD in clinical practice. β-amyloid deposition (A), tau pathology (T), and neurodegeneration/neuronal damage (N), also known as the AT (N) biomarkers system, are widely validated core humoral markers for the diagnosis of AD. In this paper, the pathogenesis of AD related to AT (N) and the current research status of cerebrospinal fluid (CSF) and blood related biomarkers were reviewed. At the same time, the limitations of humoral markers in the diagnosis of AD were also discussed, and the future development of humoral markers for AD was prospected. In addition, the contents related to mitochondrial dysfunction, prion virology and intestinal microbiome related to AD are also described, so as to understand the pathogenesis of AD in many aspects and dimensions, so as to evaluate the pathological changes related to AD more comprehensively and accurately.
Astrocytes control hippocampal synaptic plasticity through the vesicular-dependent release of D-serine
Authors: Abreu Daniela Sofia , Gomes Joana I. , Ribeiro Filipa F. , Diógenes Maria J. , Sebastião Ana M. , Vaz Sandra H.
Published: December 2023

Astrocytes, the most abundant glial cells in the central nervous system (CNS), sense synaptic activity and respond through the release of gliotransmitters, a process mediated by intracellular Ca2+ level changes and SNARE-dependent mechanisms. Ionotropic N-methyl-D-aspartate (NMDA) receptors, which are activated by glutamate along with D-serine or glycine, play a crucial role in learning, memory, and synaptic plasticity. However, the precise impact of astrocyte-released D-serine on neuronal modulation remains insufficiently characterized. To address this, we have used the dominant negative SNARE (dnSNARE) mouse model, which selectively inhibits SNARE-dependent exocytosis from astrocytes. We recorded field excitatory postsynaptic potentials (fEPSPs) in CA3-CA1 synapses within hippocampal slices obtained from dnSNARE mice and wild-type (Wt) littermates. Our results demonstrate that hippocampal θ-burst long-term potentiation (LTP), a critical form of synaptic plasticity, is impaired in hippocampal slices from dnSNARE mice. Notably, this LTP impairment was rescued upon incubation with D-serine. To further investigate the involvement of astrocytes in D-serine-mediated mechanisms of LTP maintenance, we perfused hippocampal slices with L-serine – a substrate used by both neurons and astrocytes for D-serine production. The enhancement in LTP observed in dnSNARE mice was exclusively associated with D-serine presence, with no effects evident in the presence of L-serine. Additionally, both D- and L-serine reduced basal synaptic strength in the hippocampal slices of both Wt and dnSNARE mice. These results provide compelling evidence that distinct processes underlie the modulation of basal synaptic transmission and LTP through D-serine. Our findings underscore the pivotal contribution of astrocytes in D-serine-mediated processes that govern LTP establishment and basal transmission. This study not only provides essential insights into the intricate interplay between neurons and astrocytes but also emphasizes their collective role in shaping hippocampal synaptic function.
The flow of axonal information among hippocampal sub-regions 2: patterned stimulation sharpens routing of information transmission
Authors: Lassers Samuel Brandon , Vakilna Yash S. , Tang William C. , Brewer Gregory J.
Published: December 2023

The sub-regions of the hippocampal formation are essential for episodic learning and memory formation, yet the spike dynamics of each region contributing to this function are poorly understood, in part because of a lack of access to the inter-regional communicating axons. Here, we reconstructed hippocampal networks confined to four subcompartments in 2D cultures on a multi-electrode array that monitors individual communicating axons. In our novel device, somal, and axonal activity was measured simultaneously with the ability to ascertain the direction and speed of information transmission. Each sub-region and inter-regional axons had unique power-law spiking dynamics, indicating differences in computational functions, with abundant axonal feedback. After stimulation, spiking, and burst rates decreased in all sub-regions, spikes per burst generally decreased, intraburst spike rates increased, and burst duration decreased, which were specific for each sub-region. These changes in spiking dynamics post-stimulation were found to occupy a narrow range, consistent with the maintenance of the network at a critical state. Functional connections between the sub-region neurons and communicating axons in our device revealed homeostatic network routing strategies post-stimulation in which spontaneous feedback activity was selectively decreased and balanced by decreased feed-forward activity. Post-stimulation, the number of functional connections per array decreased, but the reliability of those connections increased. The networks maintained a balance in spiking and bursting dynamics in response to stimulation and sharpened network routing. These plastic characteristics of the network revealed the dynamic architecture of hippocampal computations in response to stimulation by selective routing on a spatiotemporal scale in single axons.
Research trends and hotspots of post-stroke dysphagia rehabilitation: a bibliometric study and visualization analysis
Authors: He Yuanyuan , Tan Xuezeng , Kang Huiqi , Wang Huan , Xie Yuyao , Zheng Dongxiang , Li Chen
Published: December 2023

Background

Post-stroke dysphagia (PSD) is one of the most prevalent stroke sequelae, affecting stroke patients’ prognosis, rehabilitation results, and quality of life while posing a significant cost burden. Although studies have been undertaken to characterize the pathophysiology, epidemiology, and risk factors of post-stroke dysphagia, there is still a paucity of research trends and hotspots on this subject. The purpose of this study was to create a visual knowledge map based on bibliometric analysis that identifies research hotspots and predicts future research trends.

Methods

We searched the Web of Science Core Collection for material on PSD rehabilitation research from its inception until July 27, 2023. We used CiteSpace, VOSviewer, and Bibliometrix R software packages to evaluate the annual number of publications, nations, institutions, journals, authors, references, and keywords to describe present research hotspots and prospective research orientations.

Results

This analysis comprised 1,097 articles from 3,706 institutions, 374 journals, and 239 countries or regions. The United States had the most publications (215 articles), and it is the most influential country on the subject. “Dysphagia” was the most published journal (100 articles) and the most referenced journal (4,606 citations). Highly cited references focused on the pathophysiology and neuroplasticity mechanisms of PSD, therapeutic modalities, rehabilitation tactics, and complications prevention. There was a strong correlation between the terms “validity” and “noninvasive,” which were the strongest terms in PSD rehabilitation research. The most significant words in PSD rehabilitation research were “validity” and “noninvasive brain stimulation,” which are considered two of the most relevant hotspots in the field.

Conclusion

We reviewed the research in the field of PSD rehabilitation using bibliometrics to identify research hotspots and cutting-edge trends in the field, primarily including the pathogenesis and neurological plasticity mechanisms of PSD, complications, swallowing screening and assessment methods, and swallowing rehabilitation modalities, and this paper can provide in the follow-up research in the field of PSD rehabilitation. The results of this study can provide insightful data for subsequent studies in the field of PSD rehabilitation.
Children with developmental coordination disorder have less variable motor unit firing rate characteristics across contractions compared to typically developing children
Authors: Esselaar Maaike , Parr Johnny V. V. , Wood Greg , Hodson-Tole Emma
Published: December 2023

Introduction

Understanding the nuances of neuromuscular control is crucial in unravelling the complexities of developmental coordination disorder (DCD), which has been associated with differences in skeletal muscle activity, implying that children with DCD employ distinct strategies for muscle control. However, force generation and control are dependent on both recruitment of motor units and their firing rates and these fine details of motor function have yet to be studied in DCD. The purpose of this study was therefore to compare motor unit characteristics in a small muscle of the hand during low level, handgrip contractions in typically developing (TD) children and children with DCD.

Methods

Eighteen children (9 TD vs. 9 DCD) completed a series of manual handgrip contractions at 10 ± 5% of their maximum voluntary contraction. High density surface electromyography was used to record excitation of the first dorsal interosseus muscle. Recorded signals were subsequently decomposed into individual motor unit action potential trains. Motor unit characteristics (firing rate, inter-pulse interval, and action potential amplitude) were analysed for contractions that had a coefficient variation of <10%.

Results and Discussion

This study found few differences in average motor unit characteristics (number of motor units: TD 20.24 ± 9.73, DCD 27.32 ± 14.00; firing rate: TD 7.74 ± 2.16 p.p.s., DCD 7.86 ± 2.39 p.p.s.; inter-pulse interval: TD 199.72 ± 84.24 ms, DCD 207.12 ± 103 ms) when force steadiness was controlled for, despite the DCD group being significantly older (10.89 ± 0.78 years) than the TD group (9.44 ± 1.67 years). However, differences were found in the variability of motor unit firing statistics, with the children with DCD surprisingly showing less variability across contractions (standard deviation of coefficient of variation of inter-pulse interval: TD 0.38 ± 0.12, DCD 0.28 ± 0.11). This may suggest a more fixed strategy to stabilise force between contractions used by children with DCD. However, as variability of motor unit firing has not been considered in previous studies of children further work is required to better understand the role of variability in motor unit firing during manual grasping tasks, in all children.
Practical considerations of diffusion-weighted MRS with ultra-strong diffusion gradients
Authors: Davies-Jenkins Christopher W. , Döring André , Fasano Fabrizio , Kleban Elena , Mueller Lars , Evans C. John , Afzali Maryam , Jones Derek K. , Ronen Itamar , Branzoli Francesca , Tax Chantal M. W.
Published: December 2023

Introduction

Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) offers improved cellular specificity to microstructure—compared to water-based methods alone—but spatial resolution and SNR is severely reduced and slow-diffusing metabolites necessitate higher b-values to accurately characterize their diffusion properties. Ultra-strong gradients allow access to higher b-values per-unit time, higher SNR for a given b-value, and shorter diffusion times, but introduce additional challenges such as eddy-current artefacts, gradient non-uniformity, and mechanical vibrations.

Methods

In this work, we present initial DW-MRS data acquired on a 3T Siemens Connectom scanner equipped with ultra-strong (300 mT/m) gradients. We explore the practical issues associated with this manner of acquisition, the steps that may be taken to mitigate their impact on the data, and the potential benefits of ultra-strong gradients for DW-MRS. An in-house DW-PRESS sequence and data processing pipeline were developed to mitigate the impact of these confounds. The interaction of TE, b-value, and maximum gradient amplitude was investigated using simulations and pilot data, whereby maximum gradient amplitude was restricted. Furthermore, two DW-MRS voxels in grey and white matter were acquired using ultra-strong gradients and high b-values.

Results

Simulations suggest T2-based SNR gains that are experimentally confirmed. Ultra-strong gradient acquisitions exhibit similar artefact profiles to those of lower gradient amplitude, suggesting adequate performance of artefact mitigation strategies. Gradient field non-uniformity influenced ADC estimates by up to 4% when left uncorrected. ADC and Kurtosis estimates for tNAA, tCho, and tCr align with previously published literature.

Discussion

In conclusion, we successfully implemented acquisition and data processing strategies for ultra-strong gradient DW-MRS and results indicate that confounding effects of the strong gradient system can be ameliorated, while achieving shorter diffusion times and improved metabolite SNR.
CLEC12A sensitizes differentially responsive breast cancer cells to the anti-cancer effects of artemisinin by repressing autophagy and inflammation
Authors: Chatterjee Ranodeep , Shukla Aditya , Chakrabarti Kausiki , Chatterji Urmi
Published: December 2023

Background

Enhanced inflammatory responses promote tumor progression by activating toll-like receptors (TLRs), which in turn are inhibited by C-type lectin like receptors (CTLRs), like CLEC12A. Although the presence of CLEC12A in acute myeloid leukemia is well established, its role in non-hematopoietic tumors is still obscure. In hematopoietic tumors, CLEC12A mostly inhibits TLRs and modulates inflammatory responses via NF-κB signaling. In this study, the fate of tumor progression was determined by modulating CLEC12A using artemisinin (ART), a FDA-approved anti-malarial drug, known for its anti-cancer and immunomodulatory properties with minimal adverse effects on normal cells.

Method

Effects of ART were primarily determined on hematological factors and primary metastatic organs, such as lungs, kidney and liver in normal and tumor-bearing BALB/c mice. Tumor-bearing mice were treated with different concentrations of ART and expressions of CLEC12A and associated downstream components were determined. CLEC12A was overexpressed in MDA-MB-231 and 4T1 cells, and the effects of ART were analyzed in the overexpressed cells. Silencing TLR4 using vivo morpholino was performed to elucidate its role in tumor progression in response to ART. Finally, CLEC12A modulation by ART was evaluated in the resident cancer stem cell (CSC) population.

Results

ART did not alter physiology of normal mice, in contrast to tumor-bearing mice, where ART led to tumor regression. In addition, ART reduced expression of CLEC12A. Expectedly, TLR4 expression increased, but surprisingly, that of NF-κB (RelA) and JNK/pJNK decreased, along with reduced inflammation, reduced autophagy and increased apoptosis. All the above observations reverted on overexpression of CLEC12A in MDA-MB-231 and 4T1 cells. Inhibition of TLR4, however, indicated no change in the expressions of CLEC12A, NF-κB, or apoptotic markers. The effect of ART showed a similar trend in the CSC population as in cancer cells.

Conclusion

This study, for the first time, confirmed a differential role of CLEC12A in non-hematopoietic tumor and cancer stem cells in response to ART. Subsequent interaction and modulation of CLEC12A with ART induced tumor cell death and abrogation of CSCs, confirming a more comprehensive tumor therapy with reduced risk of recurrence. Therefore, ART may be repurposed as an effective drug for cancer treatment in future.
A real-world disproportionality analysis of mepolizumab based on the FDA adverse event reporting system
Authors: Li Huqun , Wang Chongshu , Deng Aiping , Guo Cuilian
Published: December 2023

Background: Mepolizumab has been approved by the FDA for add-on maintenance treatment of severe asthma with an eosinophilic phenotype. Real-world studies on mepolizumab-associated adverse events are limited. The present study aimed to explore mepolizumab-related adverse events based on the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Methods: A disproportionality analysis was performed to assess the safety profile of mepolizumab based on the reports from the FAERS database between October 2015 and December 2022. Demographic information, the time to onset, the safety of long-term mepolizumab exposure as well as safety in pediatric patients were also investigated.

Results: A total of 736 significant preferred terms (PTs) were identified among the 13,497 mepolizumab-associated adverse events (AEs) reports collected from the FAERS database. The frequently reported AEs including dyspnea, fatigue, and headache were in line with drug instruction and previous studies. Unexpected significant AEs such as cough, malaise, and chest discomfort were also identified. Most AEs occurred within the first month after mepolizumab initiation. Pneumonia and wheezing were frequently reported in patients with long-term mepolizumab exposure as well as in the pediatric population.

Conclusion: Our results were consistent with the observations in previous clinical and real-world studies. New and unexpected AE signals of mepolizumab were also identified. Close attention should be paid to the long-term safety of mepolizumab as well as safety in the pediatric population. Prospective studies are required for optimal use of mepolizumab.
Berberine-microbiota interplay: orchestrating gut health through modulation of the gut microbiota and metabolic transformation into bioactive metabolites
Authors: Dehau Tessa , Cherlet Marc , Croubels Siska , Van De Vliet Michiel , Goossens Evy , Van Immerseel Filip
Published: December 2023

Berberine is an isoquinoline alkaloid found in plants. It presents a wide range of pharmacological activities, including anti-inflammatory and antioxidant properties, despite a low oral bioavailability. Growing evidence suggests that the gut microbiota is the target of berberine, and that the microbiota metabolizes berberine to active metabolites, although little evidence exists in the specific species involved in its therapeutic effects. This study was performed to detail the bidirectional interactions of berberine with the broiler chicken gut microbiota, including the regulation of gut microbiota composition and metabolism by berberine and metabolization of berberine by the gut microbiota, and how they contribute to berberine-mediated effects on gut health. As previous evidence showed that high concentrations of berberine may induce dysbiosis, low (0.1 g/kg feed), middle (0.5 g/kg feed) and high (1 g/kg feed) doses were here investigated. Low and middle doses of in-feed berberine stimulated potent beneficial bacteria from the Lachnospiraceae family in the large intestine of chickens, while middle and high doses tended to increase villus length in the small intestine. Plasma levels of the berberine-derived metabolites berberrubine, thalifendine and demethyleneberberine were positively correlated with the villus length of chickens. Berberrubine and thalifendine were the main metabolites of berberine in the caecum, and they were produced in vitro by the caecal microbiota, confirming their microbial origin. We show that members of the genus Blautia could demethylate berberine into mainly thalifendine, and that this reaction may stimulate the production of short-chain fatty acids (SCFAs) acetate and butyrate, via acetogenesis and cross-feeding respectively. We hypothesize that acetogens such as Blautia spp. are key bacteria in the metabolization of berberine, and that berberrubine, thalifendine and SCFAs play a significant role in the biological effect of berberine.
In search of biomarkers for low back pain: can traction therapy effectiveness be prognosed by surface electromyography or blood parameters?
Authors: Ratajczak Marzena , Waszak Małgorzata , Śliwicka Ewa , Wendt Michał , Skrypnik Damian , Zieliński Jacek , Krutki Piotr
Published: December 2023

Background: Lumbar traction therapy is a common method to reduce low back pain (LBP) but is not always effective. The search for biomarkers that would prognose the effectiveness of LBP management is one priority for improving patients’ quality of life.

Objectives: 1) To determine the phenotype of patients benefiting most from lumbar traction therapy. 2) To correlate systemic and electromyographic biomarkers with pain and pain-related disability.

Methods: Data on muscle bioelectrical activity (surface electromyography [SEMG]) in the flexion-extension task, the concentrations of twelve systemic biochemical factors, LBP intensity (Visual Analog Scale), the Oswestry Disability Index, and the Roland–Morris Disability Questionnaire (RMDQ) were collected before and 72 h after 20 sessions of lumbar traction therapy. Patients were divided into responders and nonresponders based on the criterion of a 50% reduction in maximal pain.

Results: The responders had lower maximal muscle bioactivity in the extension phase on the left side (p < 0.01) and higher flexion-extension ratios on both sides of the body in the SEMG (left: p < 0.05; right: p < 0.01), and higher adipsin, interleukin-2, interleukin-4, and interleukin-10 concentrations (p < 0.05) than nonresponders. Patients with higher interleukin-4 concentrations before therapy achieved greater reductions in maximal pain in the sitting position, bioelectrical muscle activity in flexion, and flexion-relaxation ratio on the left side of the body. Changes in adipsin and interleukin-4 concentrations correlated with changes in LBP intensity (r = 0.68; r = −0.77). Changes in stem cell growth factor and interleukin-17A correlated with changes in RMDQ (R = 0.53) and bioelectrical muscle activity in extension (left: R = −0.67; right: R = −0.76), respectively.

Conclusion: Responders to traction therapy had SEMG indices of less favorable muscle activity in the flexion-extension task and elevated indices of inflammation before the study. For the first time, interleukin-4 was indicated as a potential biomarker for prognosing post-therapy changes in pain intensity and muscle activity.
Biocontrol potential of Pseudomonas protegens ML15 against Botrytis cinerea causing gray mold on postharvest tomato (Solanum lycopersicum var. cerasiforme)
Authors: Ajijah Nur , Fiodor Angelika , Dziurzynski Mikolaj , Stasiuk Robert , Pawlowska Julia , Dziewit Lukasz , Pranaw Kumar
Published: December 2023

Gray mold, caused by Botrytis cinerea is a major cause of post-harvest rot of fresh fruits and vegetables. The utilization of selected microorganisms as biocontrol agents is a promising alternative to effectively control gray mold on tomatoes. The current study was conducted to explore potential biocontrol mechanisms of the Pseudomonas strain to control infections on post-harvest tomatoes. Among the 8 tested bacterial isolates, Pseudomonas protegens ML15 demonstrated antagonistic activity to Botrytis cinerea. Moreover, P. protegens ML15 exhibited the production of siderophores, hydrogen cyanide, ammonia, exopolysaccharides, lipase, biosurfactant, 2,4-diacetylphloroglucinol, and several other antifungal compounds, such as 1-tetradecanol, cyclododecane, 2,4-di-tert-butylphenol, and 2-methyl-1-hexadecanol. A comprehensive genomic analysis of P. protegens ML15 unravels 18 distinct genetic regions with the potential for biosynthesizing secondary metabolites, known for their pivotal role in biocontrol responses against plant pathogens. In vivo, experiments showed that both culture suspension and cell-free supernatant of P. protegens ML15 significantly reduced fungal growth (53.0 ± 0.63%) and mitigated disease development (52.8 ± 1.5%) in cherry tomatoes at four days post-B. cinerea inoculation. During the infection, the application of P. protegens ML15 resulted in the augmentation of total antioxidant, phenolic content, and ascorbic acids content. Thus, our results suggested that P. protegens ML15’s role as a biocontrol agent against B. cinerea-induced postharvest tomato decay achieved through the secretion of antifungal substances, induction of tomato defense responses, and inhibition of mycelial growth of B. cinerea. These findings provide a significant contribution to the ongoing search for alternative, eco-friendly methods of controlling gray mold in fresh products. The utilization of P. protegens ML15 as a biocontrol agent could help to reduce the reliance on chemical fungicides and promote sustainable agriculture practices.
Advancing understanding of Ficus carica: a comprehensive genomic analysis reveals evolutionary patterns and metabolic pathway insights
Authors: Bao Yuting , He Miaohua , Zhang Chenji , Jiang Sirong , Zhao Long , Ye Zhengwen , Sun Qian , Xia Zhiqiang , Zou Meiling
Published: December 2023

Ficus carica L. (dioecious), the most significant commercial species in the genus Ficus, which has been cultivated for more than 11,000 years and was one of the first species to be domesticated. Herein, we reported the most comprehensive F. carica genome currently. The contig N50 of the Orphan fig was 9.78 Mb, and genome size was 366.34 Mb with 13 chromosomes. Based on the high-quality genome, we discovered that F. carica diverged from Ficus microcarpa ~34 MYA, and a WGD event took place about 2─3 MYA. Throughout the evolutionary history of F. carica, chromosomes 2, 8, and 10 had experienced chromosome recombination, while chromosome 3 saw a fusion and fission. It is worth proposing that the chromosome 9 experienced both inversion and translocation, which facilitated the emergence of the F. carica as a new species. And the selections of F. carica for the genes of recombination chromosomal fragment are compatible with their goal of domestication. In addition, we found that the F. carica has the FhAG2 gene, but there are structural deletions and positional jumps. This gene is thought to replace the one needed for female common type F. carica to be pollinated. Subsequently, we conducted genomic, transcriptomic, and metabolomic analysis to demonstrate significant differences in the expression of CHS among different varieties of F. carica. The CHS playing an important role in the anthocyanin metabolism pathway of F. carica. Moreover, the CHS gene of F. carica has a different evolutionary trend compared to other Ficus species. These high-quality genome assembly, transcriptomic, and metabolomic resources further enrich F. carica genomics and provide insights for studying the chromosomes evolution, sexual system, and color characteristics of Ficus.
HPLC method for quantifying verbascoside in Stizophyllum perforatum and assessment of verbascoside acute toxicity and antileishmanial activity
Authors: Alves Osvaine Junior Alvarenga , Ozelin Saulo Duarte , Magalhães Larissa Fernandes , Candido Ana Carolina Bolela Bovo , Gimenez Valéria Maria Melleiro , Silva Márcio Luís Andrade e , Cunha Wilson Roberto , Januário Ana Helena , Tavares Denise Crispim , Magalhães Lizandra Guidi , Pauletti Patricia Mendonça
Published: December 2023

We report the chemical composition of the crude leaf extracts obtained from Stizophyllum perforatum (Cham.) Miers (Bignoniaceae), a simple high-performance liquid chromatography–diode array detection (HPLC-DAD) method based on mangiferin as an internal standard to quantify verbascoside, and the verbascoside acute oral toxicity and antileishmanial activity. HPLC–high-resolution mass spectrometry–DAD (HPLC–HRMS–DAD) analyses of the crude ethanol S. perforatum leaf extracts (CE-1 and CE-2) revealed that verbascoside was the major constituent in both extracts. CE-1 was purified, and verbascoside and casticin, among other compounds, were isolated. The developed HPLC-DAD method was validated and met the required standards. Investigation of the CE-2 acute toxicity indicated a lethal dose (LD50) greater than 2,000 mg/kg of body weight. Both CE-1 and CE-2 exhibited antileishmanial activity. The isolated compounds, verbascoside and casticin, also displayed antileishmanial activity with effective concentrations (IC50) of 6.23 and 24.20 µM against promastigote forms and 3.71 and 18.97 µM against amastigote forms of Leishmania amazonensis, respectively, but they were not cytotoxic to J774A.1 macrophages. Scanning electron microscopy of the L. amazonensis promastigotes showed that the parasites became more rounded and that their plasma membrane was altered in the presence of verbascoside. Additionally, transmission electron microscopy demonstrated that vacuoles emerged, lipids accumulated, kinetoplast size increased, and interstitial extravasation occurred in L. amazonensis promastigotes exposed to verbascoside. These findings suggest that S. perforatum is a promising candidate for further in vivo investigations against L. amazonensis.
Intra- and inter-specific reproductive barriers in the tomato clade
Authors: Moreels Pauline , Bigot Servane , Defalque Corentin , Correa Francisco , Martinez Juan-Pablo , Lutts Stanley , Quinet Muriel
Published: December 2023

Tomato (Solanum lycopersicum L.) domestication and later introduction into Europe resulted in a genetic bottleneck that reduced genetic variation. Crosses with other wild tomato species from the Lycopersicon clade can be used to increase genetic diversity and improve important agronomic traits such as stress tolerance. However, many species in the Lycopersicon clade have intraspecific and interspecific incompatibility, such as gametophytic self-incompatibility and unilateral incompatibility. In this review, we provide an overview of the known incompatibility barriers in Lycopersicon. We begin by addressing the general mechanisms self-incompatibility, as well as more specific mechanisms in the Rosaceae, Papaveraceae, and Solanaceae. Incompatibility in the Lycopersicon clade is discussed, including loss of self-incompatibility, species exhibiting only self-incompatibility and species presenting both self-compatibility and self-incompatibility. We summarize unilateral incompatibility in general and specifically in Lycopersicon, with details on the ’self-compatible x self-incompatible’ rule, implications of self-incompatibility in unilateral incompatibility and self-incompatibility-independent pathways of unilateral incompatibility. Finally, we discuss advances in the understanding of compatibility barriers and their implications for tomato breeding.
Prevalence of sexual dysfunction and its association with psychological symptoms in drug-naive major depressive disorder patients in West China
Authors: Jiang Fugui , Liu Zenghui , Wu Xianglong , Tan Arui , Qin Xiaohong , Su Rong Cheng , Li Hui , Wang Huan , Xiao Jun , Zhou Bo
Published: December 2023

Background

Sexual dysfunction is commonly observed in individuals with Major Depressive Disorder (MDD), along with various psychological symptoms such as anxiety, somatic complaints, interpersonal sensitivity, and obsessive-compulsive tendencies. However, there is a research gap in understanding the impact of these psychological symptoms on sexual functioning in MDD. Furthermore, there is limited data on the incidence of sexual dysfunction among drug-naive MDD patients in West China. This study aims to determine the prevalence of sexual dysfunction in this patient population and explore its association with other psychological indicators.

Methods

We conducted a retrospective analysis of patient data from October 2020 to September 2022 using propensity score matching. A focused group of 165 males and 490 females was selected from a total of 1941 MDD patients. This allowed for a comparative analysis of demographic data, as well as scores from the Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), and Symptom Checklist-90 (SCL-90), the Arizona Sexual Experience Scale (ASEX).

Results

Our findings reveal that 46.2% of drug-naive MDD patients experienced sexual dysfunction. Notably, there was a higher prevalence of sexual dysfunction among female patients (50.3%) compared to males (37.5%). MDD patients without sexual dysfunction consistently exhibited higher SDS scores than those with sexual dysfunction (p < 0.01), There were no statistically significant differences between male and female MDD patients with or without concomitant sexual dysfunction in terms of Somatic complaints, Obsessive-compulsive, Interpersonal sensitivity, Anxiety, Phobic anxiety, Paranoid ideation, Psychoticism and Diet/sleep difficulties (p > 0.05). In addition, male MDD patients with sexual dysfunction showed a emerging trend towards elevated Hostility scores on the SCL-90 (p = 0.058), male MDD patients with sexual dysfunction showed an increasing trend in hostility scores on the SCL-90, whereas female MDD patients with sexual dysfunction did not show such a trend.

Conclusion

The study highlights a significant gender difference in the prevalence of sexual dysfunction among MDD patients, with females being more susceptible than males. There is a positive correlation between the severity of depression and sexual dysfunction in both genders. Interestingly, male MDD patients demonstrated a potential protective effect of hostility against sexual dysfunction, which was not observed in female patients.
Relationship between sleep quality and subjective well-being: resilience as a mediator and belief in a just world as a moderator
Authors: Su Peng , He Mu
Published: December 2023

Background/Purpose

Sleep quality significantly impacts subjective well-being, yet its underlying mechanisms remain largely unknown from a scholarly perspective. Existing research has inadequately addressed the relationship between sleep quality and the subjective well-being of College students. This study primarily investigates the influence of sleep quality on the subjective well-being of College students and explores the mediating role of resilience and the moderating role of belief in a just world.

Methods

The study sample comprises 3349 enrolled College students. Measures include the Pittsburgh Sleep Quality Index, the Subjective Well-being Scale, resilience scale, and belief in a just world scale. A moderated mediation model is employed to verify the mediating role of resilience and the moderating role of belief in a just world.

Results

(1) Sleep quality among College students is significantly positively correlated with resilience, belief in a just world, and subjective well-being. (2) Sleep quality positively predicts subjective well-being among College students. Resilience among College students serves as a mediator between sleep quality and subjective well-being, while belief in a just world moderates the influence of resilience on subjective well-being.

Conclusion

The results suggest that sleep quality can directly enhance the subjective well-being of College students and can also indirectly affect it through resilience. Additionally, belief in a just world can enhance the promoting effect of resilience on the subjective well-being of College students. These findings may contribute to understanding the impact of sleep quality on the subjective well-being of College students and its pathways. These research findings can serve as a reference for improving the subjective well-being of College students.