bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of changes in ecosystem capacity index and driving factors in the Loess Plateau under ecological engineering orientation
Authors: Yuan Li , Zhong yuan Mao , Bin Xu , Yu xuan Wan
Published: July 2024

Background

In recent decades, the Loess Plateau is one of the regions in China that urgently needs ecological governance due to the severe situation of soil erosion and land desertification. Due to the impact of climate change and human activities, the threat to the ecological space security of the Loess Plateau has intensified. This paper reveals the time lag effect of ecological engineering construction on the changes in the ecosystem service capacity index of the Loess Plateau, providing a scientific basis and decision-making reference for the sustainable development of the study area and improving the quality and management of ecological engineering construction, which is of great significance for building a solid ecological security barrier on the Loess Plateau.

Methods

Based on the hierarchical analysis method, quantitative indicator method, spatial correlation analysis method and two-way fixed effect model, this paper analyzes the temporal and spatial changes of the ecosystem service capacity index of the Loess Plateau under the background of ecological engineering implementation.

Results

The results showed that: 1) the vegetation coverage of the Loess Plateau increased with the increase of the area of ecological engineering construction, and showed a fluctuating growth distribution characteristic from southeast to northwest in space; 2) the water conservation capacity index, wind and sand fixation capacity index, biodiversity capacity index and comprehensive service capacity index of the Loess Plateau from 2000 to 2020 all showed exponential growth, which were highly coupled with the growth and change of vegetation coverage area in time and space; 3) the cold spots and hot spots of the ecosystem service capacity index of the Loess Plateau showed a step-by-step decrease of "hot in the south and cold in the north" in spatial distribution; the hot spots and sub-hot spots showed a reciprocating cycle from aggregation to fragmentation in time and space; the cold spots and sub-cold spots were mainly distributed in the northwest region. 4) The changes in the ecosystem service capacity index of the Loess Plateau were mainly affected by factors such as the cumulative project implementation area, urbanization rate and precipitation.

Conclusion

The construction of ecological engineering on the Loess Plateau has achieved remarkable results. The growth of vegetation coverage area and ecosystem service capacity index on the Loess Plateau from 2000 to 2020 has promoted the recovery of ecosystem functions. Therefore, we should actively promote the construction of ecological projects to provide scientific decision-making references for solving regional ecological security issues.
Comparative analysis of chloroplast genome and evolutionary history of Hemerocallis
Authors: Wu Jiang , Gao Yang , Wang Jinyao , Guo Aihua , Qin Nannan , Xing Guoming , Li Sen
Published: July 2024

Members of the genus Hemerocallis have significant value as ornamental, edible, and medicinal plants, particularly in China, where they have been utilized for thousands of years as both a vegetable and Traditional Chinese Medicine. Hemerocallis species exhibit strict control over flowering time, with individuals flowering either diurnally or nocturnally. However, our understanding of the evolutionary history of this genus, especially concerning important horticultural traits, remains limited. In this study, sequencing and assembly efforts were conducted on 73 samples within the Hemerocallis genus. All accessions were classified into two distinct groups based on their diurnal (daylilies) or nocturnal (nightlilies) flowering habits. Comparative analysis of the chloroplast genomes from these two groups identified fifteen variant hotspot regions, including fourteen SNPs and one deletion, which hold promise for the development of molecular markers for interspecific identification. Phylogenetic trees, generated through both maximum-likelihood and Bayesian inference methods using 76 shared protein-coding sequences, revealed that diurnal flowering evolved prior to nocturnal flowering. The divergence between the two groups is estimated to have occurred approximately 0.82 MYA (95% CI: 0.35–1.45 MYA). The ancestral state of Hemerocallis is hypothesized to have featured diurnal flowering with orange yellow petals. This study marks the first reconstruction of the evolutionary history and ancestral state of the genus Hemerocallis. The findings contribute significantly to our understanding of the adaptation and speciation history within the genus.
TACE plus lenvatinib and tislelizumab for intermediate-stage hepatocellular carcinoma beyond up-to-11 criteria: a multicenter cohort study
Authors: Chen Song , Shuangyan Tang , Shi Feng , Cai Hongjie , Wu Zhiqiang , Wang Liguang , Ma Ping , Zhou Yuanmin , Mai Qicong , Wang Fan , Lai Jiaming , Chen Xiaoming , Chen Huanwei , Guo Wenbo
Published: July 2024

Background

Intermediate-stage (BCLC-B) hepatocellular carcinoma (HCC) beyond the up-to-11 criteria represent a significant therapeutic challenge due to high and heterogeneous tumor burden. This study evaluated the effectiveness and safety of transarterial chemoembolization (TACE) in combination with lenvatinib and tislelizumab for these patients.

Methods

In this retrospective cohort study, patients with unresectable intermediate-stage HCC beyond the up-to-11 criteria were enrolled and divided into TACE monotherapy (T), TACE combined with lenvatinib (TL), or TACE plus lenvatinib and tislelizumab (TLT) group based on the first-line treatment, respectively. The primary endpoint was overall survival (OS). The secondary outcomes included progression-free survival (PFS), tumor response according to RESIST1.1 and modified RECIST, and adverse events (AEs).

Results

There were 38, 45, and 66 patients in the T, TL, and TLT groups, respectively. The TLT group exhibited significantly higher ORR and DCR than the other two groups, as assessed by either mRECIST or RECIST 1.1 (all P<0.05). Median PFS and OS were significantly longer in the TLT group compared with the T group (PFS: 8.5 vs. 4.4 months; OS: 31.5 vs. 18.5 months; all P<0.001) and TL group (PFS: 8.5 vs. 5.5 months; OS: 31.5 vs. 20.5 months; all P<0.05). The incidence of TRAEs was slightly higher in the TLT and TL groups than in the T group, while all the toxicities were tolerable. No treatment-related death occurred in all groups.

Conclusions

TACE combined with lenvatinib and tislelizumab significantly improved the survival benefit compared with TACE monotherapy and TACE plus lenvatinib in patients with intermediate-stage HCC beyond the up-to-11 criteria, with an acceptable safety profile.
Long-term investigation of spatial–temporal variations, risk assessments, and controlling factors of persistent organic pollutants (HCHs, DDTs, and PAHs) and heavy metals in coastal regions along the Chinese Bohai Sea
Authors: Su Yanting , Wang Wanguan , Su Yueyue , Wang Xiaoxuan , Zhao Haitao , Li Zhunjie , Yu You
Published: July 2024

Persistent organic pollutants (POPs) and heavy metals in marine systems have been given more and more attention due to their high toxicity and bioaccumulation capacity. After discharging into the marine systems, large proportions of POPs and heavy metals are likely to remain in coastal seas, causing serious contamination and high ecological risks. However, the lack of systematic studies restricts our understanding of POP and heavy metal cycling in coastal regions. Herein, the coastal regions along the Chinese Bohai Sea (an important fishing and typically polluted area) were chosen to establish a study model for investigating long-term spatial–temporal variations, risk assessments, and controlling factors of hexachlorocyclohexanes (HCHs), dichlorodiphenyltrichloroethanes (DDTs), polycyclic aromatic hydrocarbons (PAHs), and heavy metals in coastal regions. The results showed that concentrations of HCHs, DDTs, and PAHs in sediment, and contents of heavy metals in seawater and sediment were higher than those in other coastal regions during 2015–2018 and that concentrations of As and Cu in approximately 95% and 20% of sampled organisms exceeded maximum permissible levels recommended by China and the WHO, respectively. The significantly temporal variations in HCH and PAH concentrations were indicative of increasing POP pollution, and no significantly temporal variations in most heavy metal concentrations were found. Meanwhile, the higher concentrations of POPs and heavy metals were mainly located in estuaries and other nearshore areas. The geo-accumulation index (Igeo), potential ecological risk index (PERI), and provisional tolerable daily intake (PTDI) showed that As, Cd and Hg should be listed as the primary heavy metal pollutants in sediment; higher dietary risk was posed by As through seafood consumption; the dietary risks posed by HCHs, DDTs, and PAHs were lower. Finally, the results of multiple regression, Pearson’s, and cluster analyses indicated that anthropogenic activities (e.g., industrial and agricultural discharges, and riverine input) played important roles in controlling HCH, DDT, PAH, and heavy metal distributions in coastal regions along the Chinese Bohai Sea. The outcomes of this study are expected to shed new light on an improved understanding of POP and heavy metal cycling and provide a scientific basis for contamination control in coastal systems.
Effective debriefings in the clinical setting: a pilot study to test the impact of an evidence based debriefing app on anesthesia care providers’ performance
Authors: Seelandt Julia C , Schneider Jeannine , Kolbe Michaela , Grande Bastian
Published: July 2024

Background

Debriefing enhances team learning, performance, and patient safety. Despite its benefits, it’s underused. To address this, we developed an evidence-based debriefing app.

Methods

This pilot study, conducted at a Swiss hospital, evaluated team performance during two anesthesia inductions using the Team Performance Scale (TPS). Following the first induction, teams engaged with the Zurich Debriefing App, with debriefing sessions meticulously recorded for subsequent evaluation. To mitigate bias, raters underwent comprehensive TPS training. The debriefings were analyzed through the DE-CODE framework. We utilized paired t-tests to examine performance improvements and linear regressions to assess the impact of reflective statements on performance, moderated by psychological safety.

Results

Team performance significantly improved from the first to the second induction (t (9) = −2.512, p = 0.033). Senior physicians’ (n = 8) reflective statements predicted post-assessment TPS scores (R2 = 0.732, p = 0.061), while consultants (n = 7) and nurse anesthetists (n = 10) did not. Interaction analysis revealed no moderation effects, but a main effect indicated the significance of senior physicians’ reflective statements.

Conclusion

This pilot study confirms the efficacy of the evidence-based debriefing app in enhancing anesthesia team performance. Senior physicians’ reflective statements positively influenced performance; however, no moderation effects were observed. The study highlights the potential of debriefing apps to streamline and enhance team debriefing processes, with significant implications for improving clinical practice and patient safety. Further research is needed to validate these findings on a larger scale and optimize the integration of debriefing into routine clinical practice.
Multi-omics analysis of the biological mechanism of the pathogenesis of non-alcoholic fatty liver disease
Authors: Lin Jie , Zhang Ruyi , Liu Huaie , Zhu Yunzhen , Dong Ningling , Qu Qiu , Bi Hongyan , Zhang Lihua , Luo Ou , Sun Lei , Ma Mengjuan , You Jing
Published: July 2024

Background

Non-alcoholic fatty liver disease (NAFLD) is a type of liver metabolic syndrome. Employing multi-omics analyses encompassing the microbiome, metabolome and transcriptome is crucial for comprehensively elucidating the biological processes underlying NAFLD.

Methods

Hepatic tissue, blood and fecal samples were obtained from 9 NAFLD model mice and 8 normal control mice. Total fecal microbiota DNA was extracted, and 16S rRNA was amplified, to analyze alterations in the gut microbiota (GM) induced by NAFLD. Subsequently, diagnostic strains for NAFLD were screened, and their functional aspects were examined. Differential metabolites and differentially expressed genes were also screened, followed by enrichment analysis. Correlations between the differential microbiota and metabolites, as well as between the DEGs and differential metabolites were studied. A collinear network involving key genes-, microbiota-and metabolites was constructed.

Results

Ileibacterium and Ruminococcaceae, both belonging to Firmicutes; Olsenella, Duncaniella and Paramuribaculum from Bacteroidota; and Bifidobacterium, Coriobacteriaceae_UCG_002 and Olsenella from Actinobacteriota were identified as characteristic strains associated with NAFLD. Additionally, differentially expressed metabolites were predominantly enriched in tryptophan, linoleic acid and methylhistidine metabolism pathways. The functions of 2,510 differentially expressed genes were found to be associated with disease occurrence. Furthermore, a network comprising 8 key strains, 14 key genes and 83 key metabolites was constructed.

Conclusion

Through this study, we conducted a comprehensive analysis of NAFLD alterations, exploring the gut microbiota, genes and metabolites of the results offer insights into the speculated biological mechanisms underlying NAFLD.
Seasonal variations affect the ecosystem functioning and microbial assembly processes in plantation forest soils
Authors: Wang Min , Masoudi Abolfazl , Wang Can , Zhao Liqiang , Yang Jia , Yu Zhijun , Liu Jingze
Published: July 2024

While afforestation mitigates climate concerns, the impact of afforestation on ecological assembly processes and multiple soil functions (multifunctionality) in afforested areas remains unclear. The Xiong’an New Area plantation forests (Pinus and Sophora forests) in North China were selected to examine the effects of plantation types across four distinct seasons on soil microbiomes. Three functional categories (nutrient stocks, organic matter decomposition, and microbial functional genes) of multifunctionality and the average (net) multifunctionality were quantified. All these categories are directly related to soil functions. The results showed that net soil multifunctionality as a broad function did not change seasonally, unlike other narrow functional categories. Bacterial communities were deterministically (variable selection and homogenous selection) structured, whereas the stochastic process of dispersal limitation was mainly responsible for the assembly and turnover of fungal and protist communities. In Pinus forests, winter initiates a sudden shift from deterministic to stochastic processes in bacterial community assembly, accompanied by decreased Shannon diversity and heightened nutrient cycling (nutrient stocks and organic matter decomposition). This indicates the potential vulnerability of deterministic assembly to seasonal fluctuations, particularly in environments rich in nutrients. The results predicted that protist community composition was uniquely structured with C-related functional activities relative to bacterial and fungal β-diversity variations, which were mostly explained by seasonal variations. Our study highlighted the importance of the protist phagocytosis process on soil microbial interactions through the predicted impact of protist α-diversity on microbial cooccurrence network parameters. This association might be driven by the high abundance of protist consumers as the main predators of bacterial and fungal lineages in our sampling plots. Our findings reveal that the complexity of microbial co-occurrence interactions was considerably higher in spring, perhaps attributing thermal variability and increased resource availability within spring that foster microbial diversity and network complexity. This study contributes to local ecosystem prospects to model the behavior of soil biota seasonally and their implied effects on soil functioning and microbial assembly processes, which will benefit global-scale afforestation programs by promoting novel, precise, and rational plantation forests for future environmental sustainability and self-sufficiency.
Identification of a novel recombinant polerovirus and other emergent viruses and tombusvirus-like associated RNA species associated with carrot motley dwarf disease in the United States
Authors: Erickson Anna , Ter Horst Anneliek M. , Carlson Curtis R. , Falk Bryce W. , Kuo Yen-Wen
Published: July 2024

Carrot motley dwarf (CMD) is a viral disease complex caused by co-infection of the polerovirus carrot red leaf virus with the umbraviruses carrot mottle virus or carrot mottle mimic virus, and/or a tombusvirus like associated RNA (tlaRNA), which depend on co-infection with a helper polerovirus to gain aphid transmissibility. In 2020 and 2021 carrot samples from Washington, United States (U.S.), and parsley and cilantro samples from California, U.S., exhibiting typical symptoms of CMD were submitted for diagnosis. Initial RT-PCR diagnostic assays identified the typical CMD viruses in the carrot samples, however only the umbraviruses and tlaRNAs were detected in the parsley and cilantro samples; as such, these samples were retested with another RT-PCR assay for generic polerovirus detection. Unexpectedly, the poleroviruses Torilis crimson leaf virus (TorCLV) and fennel motley virus were identified. Subsequent RNA sequencing analysis was conducted to confirm these results and look for other emergent viruses. In addition to confirming the diagnostic results, the recently described polerovirus Foeniculum vulgare polerovirus, the umbraviruses Pastinaca umbravirus 1 and wild carrot mottle virus, and the tlaRNA Arracacha latent virus E associated RNA were identified, making this the first report of these viruses and tlaRNA in the U.S. Using phylogenetic and pairwise identity comparisons and RDP4 recombination analyses, we also identified a putative novel polerovirus, for which we propose the name parsley polerovirus, that appears to be a recombinant between carrot polerovirus 1, sharing 92% amino acid (aa) identity with the RNA dependent RNA polymerase in the 5′ gene block, and TorCLV, sharing >98% aa identity with the capsid protein in the 3 gene block. This work adds to the growing list of polerovirus species exhibiting recombination between the 5′ and 3′ gene blocks, and highlights the unique, variable, and dynamic associations that can occur in polerovirus, umbravirus, and tlaRNA disease complexes.
Epigenetic clocks and gliomas: unveiling the molecular interactions between aging and tumor development
Authors: Chen Shiliang , Jiang Yi , Wang Cong , Tong Shiyuan , He Yibo , Lu Wenqiang , Zhang Zhezhong
Published: July 2024

Gliomas, the most prevalent and aggressive primary brain tumors, represent a diverse group of malignancies originating from glial cells. These tumors account for significant brain tumor-related morbidity and mortality, with higher incidence rates in North America and Europe compared to Asia and Africa. Genetic predispositions and environmental factors, particularly ionizing radiation, critically impact glioma risk. Epigenetics, particularly DNA methylation, plays a pivotal role in glioma research, with IDH-mutant gliomas showing aberrant methylation patterns contributing to tumorigenesis. Epigenetic clocks, biomarkers based on DNA methylation patterns predicting biological age, have revealed significant insights into aging and tumor development. Recent studies demonstrate accelerated epigenetic aging in gliomas, correlating with increased cancer risk and poorer outcomes. This review explores the mechanisms of epigenetic clocks, their biological significance, and their application in glioma research. Furthermore, the clinical implications of epigenetic clocks in diagnosing, prognosticating, and treating gliomas are discussed. The integration of epigenetic clock data into personalized medicine approaches holds promise for enhancing therapeutic strategies and patient outcomes in glioma treatment.
Adaptation of the inferior temporal neurons and efficient visual processing
Authors: Yamane Yukako
Published: July 2024

Numerous studies examining the responses of individual neurons in the inferior temporal (IT) cortex have revealed their characteristics such as two-dimensional or three-dimensional shape tuning, objects, or category selectivity. While these basic selectivities have been studied assuming that their response to stimuli is relatively stable, physiological experiments have revealed that the responsiveness of IT neurons also depends on visual experience. The activity changes of IT neurons occur over various time ranges; among these, repetition suppression (RS), in particular, is robustly observed in IT neurons without any behavioral or task constraints. I observed a similar phenomenon in the ventral visual neurons in macaque monkeys while they engaged in free viewing and actively fixated on one consistent object multiple times. This observation indicates that the phenomenon also occurs in natural situations during which the subject actively views stimuli without forced fixation, suggesting that this phenomenon is an everyday occurrence and widespread across regions of the visual system, making it a default process for visual neurons. Such short-term activity modulation may be a key to understanding the visual system; however, the circuit mechanism and the biological significance of RS remain unclear. Thus, in this review, I summarize the observed modulation types in IT neurons and the known properties of RS. Subsequently, I discuss adaptation in vision, including concepts such as efficient and predictive coding, as well as the relationship between adaptation and psychophysical aftereffects. Finally, I discuss some conceptual implications of this phenomenon as well as the circuit mechanisms and the models that may explain adaptation as a fundamental aspect of visual processing.
Frontier and hotspot evolution in cerebrotendinous xanthomatosis: a bibliometric analysis from 1993 to 2023
Authors: Luo Fei , Ding Yali , Zhang Shanyun , Diao Juanjuan , Yuan Bin
Published: July 2024

Background

Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive disease associated with lipid metabolic disorders. Because of its clinical diversity and rarity, the diagnosis is often unclear. However, there is still a lack of reports on bibliometric analysis of CTX. The aim of this study was to assess the progress and research developments of CTX over the past three decades, identify emerging trends, and establish novel directions for future research.

Methods

The eligible literature were screened from the Web of Science Core Collection (WoSCC) database. The annual publication, countries, institutions, authors, journals, keywords and references were visually analyzed by Microsoft Excel 2019, CiteSpace 6.2.R4, VOSviewer 1.6.18 and online bibliometrics website (https://bibliometric.com/).

Results

A total of 561 publications from WoSCC were included in this study. The United States is the country with the largest number of publications, and Karolinska Institutet is the institution with the largest number of publications. Björkhem I. ranks as the most published and cited author in the last three decades. Journal of Lipid Research is the most widely published and cited journal. The strongest burst of keywords is “diagnosis.”

Conclusion

Unraveling the pathogenesis of CTX and improving its diagnosis and treatment continue to be critical challenges that require urgent attention. Future research endeavors will be centered on enhancing the efficiency and accuracy of early diagnosis and intervention.
Association between psychiatric disorders and intracranial aneurysms: evidence from Mendelian randomization analysis
Authors: Bao Sichen , Xing Zhenqiu , He Shengkai , Hu Xiaowei , Yang Jianjing , Zhou Bingqing
Published: July 2024

Objective

Several studies have explored the relationship between intracranial aneurysms and psychiatric disorders; nevertheless, the causal connection remains ambiguous. This study aimed to evaluate the causal link between intracranial aneurysms and specific psychiatric disorders.

Methods

A two-sample Mendelian randomization (MR) analysis was conducted utilizing aggregated genome-wide association study (GWAS) data from the International Stroke Genetics Association for Intracranial Aneurysms (IAs), unruptured Intracranial Aneurysm (uIA), and aneurysmal Subarachnoid Hemorrhage (aSAH). Psychiatric disorder data, encompassing Schizophrenia (SCZ), Bipolar Disorder (BD), and Panic Disorder (PD), were sourced from the Psychiatric Genomics Consortium (PGC), while Cognitive Impairment (CI) data, comprising Cognitive Function (CF) and Cognitive Performance (CP), were obtained from IEU OpenGWAS publications. Causal effects were evaluated using inverse variance weighted (IVW), MR-Egger, and weighted median methods, with the robustness of findings assessed via sensitivity analyses employing diverse methodological approaches.

Results

Our MR analysis indicated no discernible causal link between intracranial aneurysm (IA) and an elevated susceptibility to psychiatric disorders. However, among individuals with genetically predisposed unruptured intracranial aneurysms (uIA), there was a modest reduction in the risk of SCZ (IVW odds ratio [OR] = 0.95, 95% confidence interval [CI] 0.92–0.98, p = 0.0002). Similarly, IAs also exhibited a moderate reduction in SCZ risk (OR = 0.92, 95% CI 0.86–0.99, p = 0.02). Nevertheless, limited evidence was found to support a causal association between intracranial aneurysms and the risk of the other three psychiatric disorders.

Conclusion

Our findings furnish compelling evidence suggesting a causal influence of intracranial aneurysms on psychiatric disorders, specifically, both IAs and uIA exhibit a negative causal association with SCZ.
Understanding societal challenges: a NeurotechEU perspective
Authors: Schulz Daniela , Lillo-Navarro Carmen , Slors Marc , Hrabéczy Anett , Reuter Martin
Published: July 2024

Futuristic universities like The NeurotechEU and the technological innovations they provide will shape and serve society, but will also require support from society. Positive attitudes about neuro-technologies will increase their reach within society and may also impact policy-making, including funding decisions. However, the acceptability rates, especially of invasive neuro-technologies, are quite low and the majority of people are more worried than enthusiastic about them. The question therefore arises as to what neuro-technological advances should entail. In a rare effort to reach out to the public, we propose to conduct a trans-national survey with the goal to better understand the challenges of our NeurotechEU nations. We aim to compare and contrast our nations specifically with respect to their perspectives on neuro-technological advances, i.e., their needs for, interests in, access to, knowledge of and trust in neuro-technologies, and whether these should be regulated. To this end, we have developed the first version of a new tool—the Understanding Societal Challenges Questionnaire (USCQ)—which assesses all six of these dimensions (needs, interest, access, knowledge, trust, and policy-making) and is designed for administration across EU/AC countries. In addition to trans-national comparisons, we will also examine the links of our nations' perspectives on neuro-technological advances to demographic and personality variables, for example, education and socio-economic status, size of the residential area, the Big Five personality traits, religiosity, political standings, and more. We expect that this research will provide a deeper understanding of the challenges that our nations are facing as well as the similarities and differences between them, and will also help uncover the variables that predict positive and negative attitudes toward neuro-technological advances. By integrating this knowledge into the scientific process, The NeurotechEU may be able to develop neuro-technologies that people really care about, are ethical and regulated, and actually understood by the user.
Ab-initio molecular dynamics study of eutectic chloride salt: MgCl2–NaCl–KCl
Authors: De Stefanis Emily , Ramic Kemal , Vidal Judith , Zhao Youyang , Gallington Leighanne C. , Bedell Ryan , Liu Li (Emily)
Published: July 2024

Ionic liquid materials are viable candidates as a heat transfer fluid (HTF) in a wide range of applications, notably within concentrated solar power (CSP) technology and molten salt reactors (MSRs). For next-generation CSP and MSR technologies that strive for higher power generation efficiency, a HTF with wide liquid phase range and energy storage capabilities is crucial. Studies have shown that eutectic chloride salts exhibit thermal stability at high temperatures, high heat storage capacity, and are less expensive than nitrate and carbonate salts. However, the experimental data needed to fully evaluate the potential of eutectic chloride salts as a HTF contender are scarce and entail large uncertainties. Considering the high cost and potential hazards associated with the experimental methods used to determine the properties of ionic liquids, molecular modeling can be used as a viable alternative resource. In this study, the eutectic ternary chloride salt MgCl2–NaCl–KCl is modeled using ab-initio molecular dynamics simulations (AIMDs) in the liquid phase. Using the simulated data, the thermophysical and transport properties of eutectic chloride salt can be calculated: density, viscosity, heat capacity, diffusion coefficient, and ionic conductivity. For an initial model validation, experimental pair-distribution function data were obtained from X-ray total scattering techniques and compared to the theoretical pair-distribution function. Additionally, theoretical viscosity values are compared to experimental viscosity values for a similar system. The results provide a starting foundation for a MgCl2–NaCl–KCl model that can be extended to predict other fundamental properties.
Emerging biomarkers for non-invasive diagnosis and treatment of cancer: a systematic review
Authors: Zakari Suleiman , Niels Nguedia K. , Olagunju Grace V. , Nnaji Precious C. , Ogunniyi Oluwabusayo , Tebamifor Mercy , Israel Emmanuel N. , Atawodi Sunday E. , Ogunlana Olubanke Olujoke
Published: July 2024

Cancer remains a global health challenge, necessitating continuous advancements in diagnostic and treatment strategies. This review focuses on the utility of non-invasive biomarkers in cancer diagnosis and treatment, their role in early detection, disease monitoring, and personalized therapeutic interventions. Through a systematic review of the literature, we identified 45 relevant studies that highlight the potential of these biomarkers across various cancer types, such as breast, prostate, lung, and colorectal cancers. The non-invasive biomarkers discussed include liquid biopsies, epigenetic markers, non-coding RNAs, exosomal cargo, and metabolites. Notably, liquid biopsies, particularly those based on circulating tumour DNA (ctDNA), have emerged as the most promising method for early, non-invasive cancer detection due to their ability to provide comprehensive genetic and epigenetic information from easily accessible blood samples. This review demonstrates how non-invasive biomarkers can facilitate early cancer detection, accurate subtyping, and tailored treatment strategies, thereby improving patient outcomes. It underscores the transformative potential of non-invasive biomarkers in oncology, highlighting their application for enhancing early detection, survival rates, and treatment precision in cancer care.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023474749 PROSPERO, identifier CRD42023474749.
The immunoregulatory role of monocytes and thrombomodulin in myelodysplastic neoplasms
Authors: Janssen Luca L. G. , van Leeuwen-Kerkhoff Nathalie , Westers Theresia M. , de Gruijl Tanja D. , van de Loosdrecht Arjan A.
Published: July 2024

Myelodysplastic neoplasms (MDS) are clonal disorders of the myeloid lineage leading to peripheral blood cytopenias. Dysregulation of innate immunity is hypothesized to be a potent driver of MDS. A recent study revealed increased thrombomodulin (TM) expression on classical monocytes in MDS, which was associated with prolonged survival. TM is a receptor with immunoregulatory capacities, however, its exact role in MDS development remains to be elucidated. In this review we focus on normal monocyte biology and report on the involvement of monocytes in myeloid disease entities with a special focus on MDS. Furthermore, we delve into the current knowledge on TM and its function in monocytes in health and disease and explore the role of TM-expressing monocytes as driver, supporter or epiphenomenon in the MDS bone marrow environment.
Construction and validation of prognostic signatures related to mitochondria and macrophage polarization in gastric cancer
Authors: Zhang Yan , Cao Jian , Yuan Zhen , Zuo Hao , Yao Jiacong , Tu Xiaodie , Gu Xinhua
Published: July 2024

Background

Increasing evidence reveals the involvement of mitochondria and macrophage polarisation in tumourigenesis and progression. This study aimed to establish mitochondria and macrophage polarisation-associated molecular signatures to predict prognosis in gastric cancer (GC) by single-cell and transcriptional data.

Methods

Initially, candidate genes associated with mitochondria and macrophage polarisation were identified by differential expression analysis and weighted gene co-expression network analysis. Subsequently, candidate genes were incorporated in univariateCox analysis and LASSO to acquire prognostic genes in GC, and risk model was created. Furthermore, independent prognostic indicators were screened by combining risk score with clinical characteristics, and a nomogram was created to forecast survival in GC patients. Further, in single-cell data analysis, cell clusters and cell subpopulations were yielded, followed by the completion of pseudo-time analysis. Furthermore, a more comprehensive immunological analysis was executed to uncover the relationship between GC and immunological characteristics. Ultimately, expression level of prognostic genes was validated through public datasets and qRT-PCR.

Results

A risk model including six prognostic genes (GPX3, GJA1, VCAN, RGS2, LOX, and CTHRC1) associated with mitochondria and macrophage polarisation was developed, which was efficient in forecasting the survival of GC patients. The GC patients were categorized into high-/low-risk subgroups in accordance with median risk score, with the high-risk subgroup having lower survival rates. Afterwards, a nomogram incorporating risk score and age was generated, and it had significant predictive value for predicting GC survival with higher predictive accuracy than risk model. Immunological analyses revealed showed higher levels of M2 macrophage infiltration in high-risk subgroup and the strongest positive correlation between risk score and M2 macrophages. Besides, further analyses demonstrated a better outcome for immunotherapy in low-risk patients. In single-cell and pseudo-time analyses, stromal cells were identified as key cells, and a relatively complete developmental trajectory existed for stromal C1 in three subclasses. Ultimately, expression analysis revealed that the expression trend of RGS2, GJA1, GPX3, and VCAN was consistent with the results of the TCGA-GC dataset.

Conclusion

Our findings demonstrated that a novel prognostic model constructed in accordance with six prognostic genes might facilitate the improvement of personalised prognosis and treatment of GC patients.
A network meta-analysis of efficacy and safety for first-line and maintenance therapies in patients with unresectable colorectal liver metastases
Authors: Jiang Yunlin , Shao Taihang , Zhao Mingye , Xue Yahong , Zheng Xueping
Published: July 2024

Background: Evidence comparing the efficacy of different treatments for patients with unresectable colorectal liver metastases (CRLM) receiving first-line or maintenance therapy is sparse. We aimed to assess the efficacy and safety of these treatments, with a distinct focus on evaluating first-line and maintenance treatments separately.

Methods: We conducted Bayesian network meta-analyses, sourcing English-language randomized controlled trials (RCTs) published through July 2023 from databases including PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, and key conference proceedings. Phase Ⅱ or Ⅲ trials that assessed two or more therapeutic regimens were included. Primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), adverse events graded as 3 or above (SAE), and R0 liver resection rate. Hazards Ratios (HRs) and 95% confidence intervals (CI) were used as effect size for OS and PFS, Odds Ratios (ORs) and 95% CI were used for ORR, SAEs and R0 resection rate. Subgroup and sensitive analyses were conducted to analysis the model uncertainty (PROSPERO: CRD42023420498).

Results: 56 RCTs were included (50 for first-line treatment, six for maintenance therapies), with a total of 21,323 patients. Regarding first-line, for OS, the top three mechanisms were: local treatment + single-drug chemotherapy (SingleCT), Targeted therapy (TAR)+SingleCT, and TAR + multi-drug chemotherapy (MultiCT). Resection or ablation (R/A)+SingleCT, S1, and Cetuximab + intensified fluorouracil-based combination chemotherapy (ICTFU) were identified as the best treatments. For PFS, the top three mechanisms were: Immune therapy + TAR + MultiCT, multi-targeted therapy (MultiTAR), TAR + SingleCT. The top three treatments were: Atezolizumab + Bevacizumab + fluorouracil-based combination chemotherapy (CTFU), TAS-102+bevacizumab, Bevacizumab + ICTFU. Cetuximab + CTFU was the best choice for RAS/RAF wild-type patients. Regarding maintenance treatment, Bevacizumab + SingleCT and Adavosertib were the best options for OS and PFS, respectively. For safety, MultiCT was the safest, followed by local treatment + MultiCT, TAR + MultiCT caused the most SAEs. Bevacizumab plus chemotherapy was found to be the safest among all targeted combination therapies.

Conclusion: In first-line, local treatment or targeted therapsy plus chemotherapy are the best mechanisms. R/A + SingleCT or CTFU performed the best for OS, Atezolizumab + Bevacizumab + ICTFU was the best option regarding PFS. For RAS/RAF wild-type patients, Cetuximab + CTFU was the optimal option. Monotherapy may be preferred choice for maintenance treatment. Combination therapy resulted in more SAEs when compared to standard chemotherapy.
LSD1 inhibition by tranylcypromine hydrochloride reduces alkali burn-induced corneal neovascularization and ferroptosis by suppressing HIF-1α pathway
Authors: Deng Qian , Gao Yuelan , Wang Yujin , Mao Jiewen , Yan Yulin , Yang Zixian , Cong Yuyu , Yang Yanning , Wan Shanshan
Published: July 2024

Background

Corneal neovascularization (CNV) is a sight-threatening condition that necessitates epigenetic control. The role of lysine-specific demethylase 1 (LSD1) in CNV remains unclear, despite its established significance in tumor angiogenesis regulation.

Methods

An alkali burn-induced CNV mouse model was used in vivo. The effects of LSD1 inhibitor tranylcypromine hydrochloride (TCP) were examined through slit lamp, histological staining, and immunofluorescence. The expression of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were assessed in corneal tissues. Oxidative stress and ferrous ion expression during CNV were determined using 4-HNE, GPX4, and FerroOrange staining. In vitro, a hypoxia-reoxygenation (H/R) model was established using human umbilical vein endothelial cells (HUVECs) to study LSD1 or hypoxia-inducible factor (HIF-1α) knockdown and lentiviral overexpression of HIF-1α. The effects on HUVECs migration, invasion, and angiogenesis were evaluated through cell scratching assay, transwell migration assay and tube formation assay. The role of ferroptosis was investigated using ROS staining, FerroOrange staining, and key ferroptosis proteins. Further, The JAK2/STAT3 pathway’s involvement in CNV regulation was explored through in vivo experiments with subconjunctival injection of AG490.

Results

The results showed a substantial correlation between corneal damage and LSD1 levels. In addition, HIF-1α expression was also elevated after alkali burns, and subconjunctival injection of TCP reduced corneal inflammation and neovascularization. Corneal alkali burns increased ROS levels and reduced antioxidative stress indicators, accompanied by elevated ferrous ion levels, which were reversed by TCP injection. In vitro, TCP or siRNAs inhibited H/R-induced ferroptosis and angiogenesis in HUVECs by affecting specific protein expressions and MDA, SOD, and GSH levels. HIF-1α levels, associated with ROS production, ferroptosis, and angiogenesis, increased during H/R, but were reversed by TCP or siRNA administration. HIF-1α overexpression counteracted the effects of LSD1 inhibition. Additionally, AG490 injection effectively reduced HIF-1α and VEGFA expression in the CNV model.

Discussion

These findings suggest that LSD1 inhibition via the HIF-1α-driven pathway prevents angiogenesis, oxidative stress, and ferroptosis in corneal alkali burn-induced CNV, highlighting LSD1 as a potential therapeutic target.
Safety profiles of doxycycline, minocycline, and tigecycline in pediatric patients: a real-world pharmacovigilance analysis based on the FAERS database
Authors: Qiao Yanli , Chen Yechao , Wang Qiaoyun , Liu Jingrui , Guo Xiaohui , Gu Qiaoling , Ding Peng , Zhang Haixia , Mei Hongliang
Published: July 2024

Introduction

Recently, the rise of antibiotic resistance has prompted a reconsideration of tetracyclines. However, existing studies are inadequate in assessing the pediatric safety of this class of antibiotics. To address the gap, our study aims to comprehensively assess the safety of tetracyclines in children.

Methods

Adverse event (AE) reports from January 2005 to September 2023 were obtained from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, and reporting odds ratio (ROR) was performed to identify potential risk signals in children under 18 years old who were administered any of the three tetracyclines: doxycycline, minocycline, and tigecycline.

Results

A total of 1903 AE cases were included in our study: 782 for doxycycline, 981 for minocycline, and 140 for tigecycline. Doxycycline and tigecycline were predominantly associated with “general disorders and administration site conditions” and “gastrointestinal disorders,” while minocycline was more frequently linked to “skin and subcutaneous tissue disorders” and “gastrointestinal disorders.” Psychiatric risks predominantly included depression, suicidal ideation, and suicide attempt. In the category of skin and subcutaneous tissues, 30.88% of the minocycline-induced drug reaction with eosinophilia and systemic symptoms (DRESS) cases resulted in death, alongside a high occurrence of co-occurring AEs such as multiple organ dysfunction syndrome, Type 1 Diabetes Mellitus (T1DM), and autoimmune thyroiditis. As for the endocrine system, both doxycycline and minocycline were found to potentially increase the risk of thyroid dysfunction. For children under the age of 8, doxycycline was associated with tooth discoloration (N = 7, ROR = 20.11%, 95% CI: 9.48–42.67), although it remained unclear whether the discoloration was permanent.

Conclusion

Our findings indicated that for pediatric patients, the majority of results were in line with the prescribing information and previous studies, and minocycline tended to cause more frequent and severe AEs than doxycycline. However, it is noteworthy that exceptions were found for psychiatric disorders and thyroid dysfunction associated with doxycycline, which are not mentioned in its FDA prescribing information. Additionally, further safety studies on tigecycline are still needed for children. When prescribing tetracyclines to pediatric patients, a careful risk-benefit assessment is crucial.
Vitamin D/vitamin D receptor protects intestinal barrier against colitis by positively regulating Notch pathway
Authors: Li Yanni , Guo Yaoyu , Geng Chong , Song Shuailing , Yang Wenjuan , Li Xiao , Wang Chunhui
Published: July 2024

Objective

Vitamin D/Vitamin D receptor (VD/VDR) signaling and the Notch pathway are involved in intestinal barrier restoration in colitis; however, their relationship and underlying mechanism are largely unknown. Therefore, this study aimed to investigate the role and mechanism of VD/VDR and the Notch pathways in intestinal barrier protection.

Methods

Genetic Vdr knockout (VDR KO) and VD deficient (VDd) mice were established, and colitis was induced by feeding 2.5% dextran sodium sulfate (DSS) water. Mechanistic studies, including real-time PCR, immunofluorescence, Western blotting and dual-luciferase reporter assays, were performed on cultured Caco-2 cells and intestinal organoids.

Results

VD deficiency and VDR genetical KO increased the severity of DSS-induced colitis in mice, which presented a higher disease activity index score, increased intestinal permeability, and more severe intestinal histological damage than controls, accompanied by decreased and disrupted claudin-1 and claudin-3. Moreover, inhibition of Notch pathway by LY411,575 aggravated the severity of DSS-induced colitis and intestinal injury. In Caco-2 cells and intestinal organoids, the expression of Notch-1, N1ICD and Hes1 decreased upon downregulation or KO of VDR but increased upon paricalcitol (PAR, a VDR agonist) treatment. Meanwhile, PAR rescued claudin-1 and claudin-3 impairments that resulted from TNF-α exposure but failed to restore claudin-3 upon Notch inhibition. The dual-luciferase reporter assay further suggested that VD/VDR positively regulated the Notch signaling pathway by modulating Notch-1 transcription.

Conclusion

VD/VDR positively modulates Notch activation by promoting Notch-1 transcription to maintain intestinal tight junction integrity and barrier function. This highlights the VD/VDR-Notch pathway as a potential new therapeutic target for protecting the intestinal barrier against ulcerative colitis.
Typical everyday movements cause specific patterns in heart rate
Authors: Heidelbach Max J. , Cysarz Dirk , Edelhäuser Friedrich
Published: July 2024

Physical inactivity and sedentary behaviour are important risk factors for cardiovascular disease. Knowledge about the impact of everyday movements on cardiac autonomic regulation is sparse. This study aims to provide evidence that typical everyday movements show a clear impact on heart rate regulation. 40 healthy participants performed two everyday movements: (1) calmly kneeling down (“tie one’s shoes”) and standing up again and (2) raising the arms to the horizontal (“expressive yawning”). Both movements elicited reproducible pattern in the sequence of heart periods. Local minima and local maxima appeared in the transient period of approx. 30 s. The regulatory response for ergometer cycling, which was used as control, did not show a pattern formation. Calmly performed everyday movements are able to elicit rich cardiac regulatory responses including specific patterns in heart rate. These newly described patterns have multiple implications for clinical and rehabilitative medicine, basic research, digital health data processing, and public health. If carried out regularly these regulatory responses may help to mitigate the burden of physical inactivity and enrich cardiovascular regulation.