bluuebunny/crossref_metadata_2025 huggingface dataset:
Flt3L therapy increases the abundance of Treg-promoting CCR7+ cDCs in preclinical cancer models
Authors: Clappaert Emile J. , Kancheva Daliya , Brughmans Jan , Debraekeleer Ayla , Bardet Pauline M. R. , Elkrim Yvon , Lacroix Dagmar , Živalj Maida , Hamouda Ahmed E.I. , Van Ginderachter Jo A. , Deschoemaeker Sofie , Laoui Damya
Published: August 2023

Conventional dendritic cells (cDCs) are at the forefront of activating the immune system to mount an anti-tumor immune response. Flt3L is a cytokine required for DC development that can increase DC abundance in the tumor when administered therapeutically. However, the impact of Flt3L on the phenotype of distinct cDC subsets in the tumor microenvironment is still largely undetermined. Here, using multi-omic single-cell analysis, we show that Flt3L therapy increases all cDC subsets in orthotopic E0771 and TS/A breast cancer and LLC lung cancer models, but this did not result in a reduction of tumor growth in any of the models. Interestingly, a CD81+migcDC1 population, likely developing from cDC1, was induced upon Flt3L treatment in E0771 tumors as well as in TS/A breast and LLC lung tumors. This CD81+migcDC1 subset is characterized by the expression of both canonical cDC1 markers as well as migratory cDC activation and regulatory markers and displayed a Treg-inducing potential. To shift the cDC phenotype towards a T-cell stimulatory phenotype, CD40 agonist therapy was administered to E0771 tumor-bearing mice in combination with Flt3L. However, while αCD40 reduced tumor growth, Flt3L failed to improve the therapeutic response to αCD40 therapy. Interestingly, Flt3L+αCD40 combination therapy increased the abundance of Treg-promoting CD81+migcDC1. Nonetheless, while Treg-depletion and αCD40 therapy were synergistic, the addition of Flt3L to this combination did not result in any added benefit. Overall, these results indicate that merely increasing cDCs in the tumor by Flt3L treatment cannot improve anti-tumor responses and therefore might not be beneficial for the treatment of cancer, though could still be of use to increase cDC numbers for autologous DC-therapy.
Deciphering the crosstalk of immune dysregulation between COVID-19 and idiopathic inflammatory myopathy
Authors: Zhang Zhao , Tao Weidong , Cheng Debin , Qin Marong , Fu Jun , Liu Dong
Published: August 2023

Background

The coronavirus disease (COVID-19) pandemic is a serious threat to public health worldwide. Growing evidence reveals that there are certain links between COVID-19 and autoimmune diseases; in particular, COVID-19 and idiopathic inflammatory myopathies (IIM) have been observed to be clinically comorbid. Hence, this study aimed to elucidate the molecular mechanisms of COVID-19 and IIM from a genomic perspective.

Methods

We obtained transcriptome data of patients with COVID-19 and IIM separately from the GEO database and identified common differentially expressed genes (DEGs) by intersection. We then performed functional enrichment, PPI, machine learning, gene expression regulatory network, and immune infiltration analyses of co-expressed genes.

Results

A total of 91 common genes were identified between COVID-19 and IIM. Functional enrichment analysis revealed that these genes were mainly involved in immune dysregulation, response to external stimuli, and MAPK signaling pathways. The MCODE algorithm recognized two densely linked clusters in the common genes, which were related to inflammatory factors and interferon signaling. Subsequently, three key genes (CDKN1A, IFI27, and STAB1) were screened using machine learning to predict the occurrence of COVID-19 related IIM. These key genes exhibited excellent diagnostic performance in both training and validation cohorts. Moreover, we created TF-gene and miRNA-gene networks to reveal the regulation of key genes. Finally, we estimated the relationship between key genes and immune cell infiltration, of which IFI27 was positively associated with M1 macrophages.

Conclusion

Our work revealed common molecular mechanisms, core genes, potential targets, and therapeutic approaches for COVID-19 and IIM from a genomic perspective. This provides new ideas for the diagnosis and treatment of COVID-19 related IIM in the future.
A comprehensive rhythmicity analysis of host proteins and immune factors involved in malaria pathogenesis to decipher the importance of host circadian clock in malaria
Authors: Rankawat Sourbh , Kundal Kavita , Chakraborty Shreyayukta , Kumar Rahul , Ray Sandipan
Published: August 2023

Background

Circadian rhythms broadly impact human health by regulating our daily physiological and metabolic processes. The circadian clocks substantially regulate our immune responses and susceptibility to infections. Malaria parasites have intrinsic molecular oscillations and coordinate their infection cycle with host rhythms. Considering the cyclical nature of malaria, a clear understanding of the circadian regulations in malaria pathogenesis and host responses is of immense importance.

Methods

We have thoroughly investigated the transcript level rhythmic patterns in blood proteins altered in falciparum and vivax malaria and malaria-related immune factors in mice, baboons, and humans by analyzing datasets from published literature and comprehensive databases. Using the Metascape and DAVID platforms, we analyzed Gene Ontology terms and physiological pathways associated with the rhythmic malaria-associated host immune factors.

Results

We observed that almost 50% of the malaria-associated host immune factors are rhythmic in mice and humans. Overlapping rhythmic genes identified in mice, baboons, and humans, exhibited enrichment (Q < 0.05, fold-enrichment > 5) of multiple physiological pathways essential for host immune and defense response, including cytokine production, leukocyte activation, cellular defense, and response, regulation of kinase activity, B-cell receptor signaling pathway, and cellular response to cytokine stimulus.

Conclusions

Our analysis indicates a robust circadian regulation on multiple interconnected host response pathways and immunological networks in malaria, evident from numerous rhythmic genes involved in those pathways. Host immune rhythms play a vital role in the temporal regulation of host-parasite interactions and defense machinery in malaria.
Zilucoplan, a macrocyclic peptide inhibitor of human complement component 5, uses a dual mode of action to prevent terminal complement pathway activation
Authors: Tang Guo-Qing , Tang Yalan , Dhamnaskar Ketki , Hoarty Michelle D. , Vyasamneni Rohit , Vadysirisack Douangsone D. , Ma Zhong , Zhu Nanqun , Wang Jian-Guo , Bu Charlie , Cong Bestine , Palmer Elizabeth , Duda Petra W. , Sayegh Camil , Ricardo Alonso
Published: August 2023

Introduction

The complement system is a key component of the innate immune system, and its aberrant activation underlies the pathophysiology of various diseases. Zilucoplan is a macrocyclic peptide that binds and inhibits the cleavage/activation of human complement component 5 (C5). We present in vitro and ex vivo data on the mechanism of action of zilucoplan for the inhibition of C5 activation, including two clinically relevant C5 polymorphisms at R885.

Methods

The interaction of zilucoplan with C5, including for clinical C5 R885 variants, was investigated using surface plasmon resonance (SPR), hemolysis assays, and ELISA. The interference of C5b6 formation by zilucoplan was investigated by native gel analysis and hemolysis assay. The permeability of zilucoplan in a reconstituted basement membrane was assessed by the partition of zilucoplan on Matrigel-coated transwell chambers.

Results

Zilucoplan specifically bound human complement C5 with high affinity, competitively inhibited the binding of C5 to C3b, and blocked C5 cleavage by C5 convertases and the assembly of the cytolytic membrane attack complex (MAC, or C5b9). Zilucoplan fully prevented the in vitro activation of C5 clinical variants at R885 that have been previously reported to respond poorly to eculizumab treatment. Zilucoplan was further demonstrated to interfere with the formation of C5b6 and inhibit red blood cell (RBC) hemolysis induced by plasmin-mediated non-canonical C5 activation. Zilucoplan demonstrated greater permeability than a monoclonal C5 antibody in a reconstituted basement membrane model, providing a rationale for the rapid onset of action of zilucoplan observed in clinical studies.

Conclusion

Our findings demonstrate that zilucoplan uses a dual mode of action to potently inhibit the activation of C5 and terminal complement pathway including wild-type and clinical R885 variants that do not respond to eculizumab treatment. These data may be relevant to the clinically demonstrated benefits of zilucoplan.
Evolution and expression of the duck TRIM gene repertoire
Authors: Campbell Lee K. , Peery Rhiannon M. , Magor Katharine E.
Published: August 2023

Tripartite motif (TRIM) proteins are involved in development, innate immunity, and viral restriction. TRIM gene repertoires vary between species, likely due to diversification caused by selective pressures from pathogens; however, this has not been explored in birds. We mined a de novo assembled transcriptome for the TRIM gene repertoire of the domestic mallard duck (Anas platyrhynchos), a reservoir host of influenza A viruses. We found 57 TRIM genes in the duck, which represent all 12 subfamilies based on their C-terminal domains. Members of the C-IV subfamily with C-terminal PRY-SPRY domains are known to augment immune responses in mammals. We compared C-IV TRIM proteins between reptiles, birds, and mammals and show that many C-IV subfamily members have arisen independently in these lineages. A comparison of the MHC-linked C-IV TRIM genes reveals expansions in birds and reptiles. The TRIM25 locus with related innate receptor modifiers is adjacent to the MHC in reptile and marsupial genomes, suggesting the ancestral organization. Within the avian lineage, both the MHC and TRIM25 loci have undergone significant TRIM gene reorganizations and divergence, both hallmarks of pathogen-driven selection. To assess the expression of TRIM genes, we aligned RNA-seq reads from duck tissues. C-IV TRIMs had high relative expression in immune relevant sites such as the lung, spleen, kidney, and intestine, and low expression in immune privileged sites such as in the brain or gonads. Gene loss and gain in the evolution of the TRIM repertoire in birds suggests candidate immune genes and potential targets of viral subversion.
Megakaryocyte NLRP3 hyperactivation induces mild anemia and potentiates inflammatory response in mice
Authors: Bourne Joshua H. , Campos Joana , Hopkin Sophie J. , Whitworth Katharine , Palis James , Senis Yotis A. , Rayes Julie , Iqbal Asif J. , Brill Alexander
Published: August 2023

Background

The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome has been described in both immune cells and platelets, but its role in the megakaryocyte (MK) lineage remains elusive.

Objective

The aim of this study was to explore the role of NLRP3 inflammasome in megakaryocytes and platelets.

Methods

We generated Nlrp3A350V/+/Gp1ba-CreKI/+ mice carrying a mutation genetically similar to the one observed in human Muckle–Wells syndrome, which leads to hyperactivity of NLRP3 specifically in MK and platelets.

Results

Platelets from the mutant mice expressed elevated levels of both precursor and active form of caspase-1, suggesting hyperactivity of NLRP3 inflammasome. Nlrp3A350V/+/Gp1ba-CreKI/+ mice developed normally and had normal platelet counts. Expression of major platelet receptors, platelet aggregation, platelet deposition on collagen under shear, and deep vein thrombosis were unchanged. Nlrp3A350V/+/Gp1ba-CreKI/+ mice had mild anemia, reduced Ter119+ cells in the bone marrow, and splenomegaly. A mild increase in MK TGF-β1 might be involved in the anemic phenotype. Intraperitoneal injection of zymosan in Nlrp3A350V/+/Gp1ba-CreKI/+ mice induced increased neutrophil egression and elevated levels of a set of proinflammatory cytokines, alongside IL-10 and G-CSF, in the peritoneal fluid as compared with control animals.

Conclusion

MK/platelet NLRP3 inflammasome promotes the acute inflammatory response and its hyperactivation in mice leads to mild anemia and increased extramedullary erythropoiesis.
The marine diatom Thalassiosira rotula: chemical profile and antioxidant activity of hydroalcoholic extracts
Authors: Frleta Matas Roberta , Popović Marijana , Čagalj Martina , Šimat Vida
Published: August 2023

The cosmopolitan centric diatom Thalassiosira rotula produces compounds in its natural habitat that can inhibit copepod reproduction. Moreover, it has been reported to possess compounds with therapeutic effects beneficial for health care. In this experiment, the extraction yield, total phenolic content (TPC), antioxidant activity by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability, ferric reducing/antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC), and chemical profile by gas chromatography-mass spectrometry (GC-MS) analyses of T. rotula were investigated. Extractions were performed with 50% and 70% ethanol. A higher extraction yield [0.21 ± 0.01 g extract/g dry weight (DW) diatom] was observed for 70% ethanol. In addition, higher TPC (5.80 ± 0.32 mg gallic acid equivalents (GAE)/g DW diatom) and antioxidant activity [DPPH inhibition of 17.53% ± 0.56%, FRAP of 766.67 ± 34.69 µM Trolox equivalents (TE), and ORAC of 58.87 ± 2.03 µM TE] were observed for this extract. Myristic acid, palmitelaidic acid, palmitic acid, eicosapentaenoic acid, 24-methylenecholesterol, and docosapentaenoic acid were identified as dominant compounds in both extracts, while extraction in 70% ethanol yielded a higher content of fatty acids such as myristic acid, eicosapentaenoic acid, docosapentaenoic acid, and sterol 24-methylenecholesterol. Thus, it can be concluded that extraction of T. rotula with 70% ethanol improves antioxidant activity and provides a higher yield of compounds such as polyunsaturated fatty acids and sterols. Therefore, the species T. rotula could be considered a sustainable source of essential fatty acids and other bioactive compounds for further applications.
Damage localization method using ultrasonic lamb waves and Wav2Vec2.0 neural network
Authors: Qian Lubin , Liu Sihao , Fan Guopeng , Liu Xinlong , Zhang Hui , Mei Yaohua , Xing Yuhui , Wang Zhiqiang
Published: August 2023

In this paper, a Wav2Vec2.0 neural network based on an attention mechanism is proposed to locate defects in array ultrasonic testing signals. This method does not require knowledge of the a priori condition of the sample sound velocity or the feature extraction of ultrasonic scattering signals. First, an array piezoelectric ultrasonic testing system is used to detect a signal through hole defects at different positions in the plate structure. Then, three different neural networks—1D-CNN, Muti-Transformer, and Wav2Vec2.0—are used to locate the defects in the collected ultrasonic testing data. The performance of the network is verified with the data set collected through finite element simulation and the experimental system, and the identification accuracy and the calculation efficiency of different networks are compared and analyzed. To provide a solution for the poor balance of the experimental data set and the weak noise resistance of the simulation data set, a data set expansion method based on time domain transformation technology is proposed. The research results show that, the positioning accuracy of the Wav2Vec2.0 neural network proposed in this article is 98.46%, and the positioning accuracy is superior to Muti Transformer and ID-CNN.
Dysregulated cross-talk between alveolar epithelial cells and stromal cells in idiopathic pulmonary fibrosis reduces epithelial regenerative capacity
Authors: Wisman Marissa , Nizamoglu Mehmet , Noordhoek Jacobien A. , Timens Wim , Burgess Janette K. , Heijink Irene H.
Published: August 2023

In idiopathic pulmonary fibrosis (IPF) constant epithelial micro-injury and aberrant interactions within the stromal micro-environment lead to abnormal alveolar repair and fibrosis. We hypothesized that alveolar epithelial regenerative responses in IPF are impaired due to disturbed crosstalk between epithelial cells and their stromal niche. We established organoid cultures from unfractionated suspensions and isolated EpCAM+ cells from distal lung tissue of patients with and without IPF. We observed significantly more organoids being formed from unfractionated suspensions compared to isolated EpCAM+ cell cultures, indicating the presence of supportive cells in the unfractionated suspensions. Importantly, lower organoid numbers were observed in unfractionated cultures from IPF lungs compared to non-IPF lungs. This difference was not found when comparing organoid formation from isolated EpCAM+ cells alone between IPF and non-IPF groups, suggesting that crosstalk between the supportive population and epithelial cells is impaired in lungs from IPF patients. Additionally, organoids grown from IPF lung-derived cells were larger in size compared to those from non-IPF lungs in both unfractionated and EpCAM+ cultures, indicating an intrinsic abnormality in epithelial progenitors from IPF lungs. Together, our observations suggest that dysregulated crosstalk between alveolar progenitor cells and the stromal niche affects the regenerative capacity, potentially contributing to alveolar impairment in IPF.
Genetic and geographic influence on phenotypic variation in European sarcoidosis patients
Authors: Freitag-Wolf Sandra , Schupp Jonas C. , Frye Björn C. , Fischer Annegret , Anwar Raihanatul , Kieszko Robert , Mihailović-Vučinić Violeta , Milanowski Janusz , Jovanovic Dragana , Zissel Gernot , Bargagli Elena , Rottoli Paola , Bumbacea Dragos , Jonkers René , Ho Ling-Pei , Gaede Karoline I. , Dubaniewicz Anna , Marshall Ben G. , Günther Andreas , Petrek Martin , Keane Michael P. , Haraldsdottir Sigridur O. , Bonella Francesco , Grah Christian , Peroš-Golubičić Tatjana , Kadija Zamir , Pabst Stefan , Grohé Christian , Strausz János , Safrankova Martina , Millar Ann , Homolka Jiří , Wuyts Wim A. , Spencer Lisa G. , Pfeifer Michael , Valeyre Dominique , Poletti Venerino , Wirtz Hubertus , Prasse Antje , Schreiber Stefan , Dempfle Astrid , Müller-Quernheim Joachim
Published: August 2023

Introduction

Sarcoidosis is a highly variable disease in terms of organ involvement, type of onset and course. Associations of genetic polymorphisms with sarcoidosis phenotypes have been observed and suggest genetic signatures.

Methods

After obtaining a positive vote of the competent ethics committee we genotyped 1909 patients of the deeply phenotyped Genetic-Phenotype Relationship in Sarcoidosis (GenPhenReSa) cohort of 31 European centers in 12 countries with 116 potentially disease-relevant single-nucleotide polymorphisms (SNPs). Using a meta-analysis, we investigated the association of relevant phenotypes (acute vs. sub-acute onset, phenotypes of organ involvement, specific organ involvements, and specific symptoms) with genetic markers. Subgroups were built on the basis of geographical, clinical and hospital provision considerations.

Results

In the meta-analysis of the full cohort, there was no significant genetic association with any considered phenotype after correcting for multiple testing. In the largest sub-cohort (Serbia), we confirmed the known association of acute onset with TNF and reported a new association of acute onset an HLA polymorphism. Multi-locus models with sets of three SNPs in different genes showed strong associations with the acute onset phenotype in Serbia and Lublin (Poland) demonstrating potential region-specific genetic links with clinical features, including recently described phenotypes of organ involvement.

Discussion

The observed associations between genetic variants and sarcoidosis phenotypes in subgroups suggest that gene–environment-interactions may influence the clinical phenotype. In addition, we show that two different sets of genetic variants are permissive for the same phenotype of acute disease only in two geographic subcohorts pointing to interactions of genetic signatures with different local environmental factors. Our results represent an important step towards understanding the genetic architecture of sarcoidosis.
Visualization of the entire process of rice spikelet infection by Ustilaginoidea virens through nondestructive inoculation
Authors: Hu Xianfeng , Wang Jian , Zhang Yubo , Wu Xiaomao , Li Rongyu , Li Ming
Published: August 2023

Introduction

Rice false smut caused by Ustilaginoidea virens, is a destructive fungal disease encountered in many rice-producing areas worldwide. To determine the process by which U. virens infects rice spikelets in the field.

Methods

The green fluorescent protein-labeled U. virens was used as an inoculum to conduct artificial inoculation on rice at the booting stage via non-destructive panicle sheath instillation inoculation.

Results

The results showed that the conidia of U. virens germinated on the surface of rice glumes and produced hyphae, which clustered at the mouth of rice glumes and entered the glumes through the gap between the palea and lemma. The conidia of U. virens colonized in rice floral organs, which led to pollen abortion of rice. U. virens wrapped the whole rice floral organ, and the floral organ-hyphae complex gradually expanded to open the glumes to form a rice false smut ball, which was two to three times larger than that observed in normal rice.

Discussion

Panicle sheath instillation inoculation was shown to be a non-destructive inoculation method that could simulate the natural infection of U. virens in the field. The entire infection process of U. virens was visualized, providing a theoretical reference for formulating strategies to control rice false smut in the field.
Genetic analysis of acute intermittent porphyria caused by novel classical splicing variant in the insertion region of 29-residue specific to human HMBS protein
Authors: Liang Lei , Meng Haixia , Wu Haotian , Zhao Jianrong
Published: August 2023

Background: Acute intermittent porphyria (AIP; OMIM#176000) is a genetic disorder that is caused by mutations in the hydroxymethylbilane synthetase (HMBS) gene. This gene encodes the third enzyme in the heme biosynthesis pathway. Human HMBS (hHMBS) contains a 29-residue insert (residues 296-324) at the interface between domains 1 and 3. The function of this insert is currently unknown. In this study, a previously unidentified classical Splicing variant was discovered in the HMBS gene of a female AIP patient from China. The variant was validated through comparison with the patient’s husband and daughter.

Methods: Peripheral blood samples were obtained from the patient, the patient’s husband, and their daughter. Gene expression was analyzed using whole exon sequencing and Sanger sequencing. To validate alternative splicing, RNA was extracted from the patient’s peripheral blood and reverse transcribed into cDNA. Aberrant splicing caused by variants was predicted using I-TASSER and PyMOL software to simulate protein structures. Finally, molecular dynamics of the proteins were simulated using the AMBER14sb software.

Results: The patient and her daughter have a classical Splicing variant c.912 + 1G>C of the HMBS gene. This variant was not found in the patient’s husband and has not been previously reported in scientific literature. Analysis of the patient’s peripheral blood transcripts revealed that c.912 + 1G>C retained intron 13 and resulted in an exon 13 skipping. Further analysis through homology modelling and molecular dynamics showed that this variant alters the secondary structure of the HMBS protein, leading to functional differences.

Conclusion: This research has discovered a new classical Splicing variant c.912 + 1G>C in the HMBS gene that has been identified as pathogenic. This finding not only expands the molecular heterogeneity of AIP but also provides crucial information for genetic diagnosis.
Association of sleep disorders with clinical symptoms and age in Chinese older adult patients with and without cognitive decline
Authors: Mei Xi , Zhao Zheng , Qiu Zhengfa , Wang Juan , Yu Haihang , Zheng Chengying
Published: August 2023

Objective

To investigate correlation between cognitive function, age, and sleep disturbances.

Methods

This retrospective clinical study enrolled 78 patients with sleep disorders who were divided into three groups: a group of 24 patients with sleep disorders accompanied by cognitive decline (SD-CD); 54 patients with sleep disorders and no cognitive decline (SD-nCD) was divided into two groups, one of 30 patients aged between 60 and 70 years and another of 24 patients aged >70 years. Polysomnography was used to record patients’ sleep indicators throughout night; these included total sleep duration, sleep efficiency (SE), sleep latency, sleep structure and percentage of N1, N2, and N3 stages, rapid eye movement (REM) stage, as well as apnea hypopnea index (AHI), and oxygen saturation (OS). Analysis of variance (ANOVA) for continuous variables and chi-square test for categorical variables were used to analyze variables between different groups. Pearson’s correlation was used to analyze correlation between sleep parameters and mini-mental state examination (MMSE). Blood samples were used to determine their Aβ, Aβ40, Aβ42, total tau, phosphorylated tau protein (ptau), ptau181, ptau217, the inflammatory factor IL-1β, vitamin B12 (VB12), and melatonin levels.

Results

In the SD-CD group, there was a significant decrease in SE and an increase in N1 stage sleep in older patients and a significant increase in AHI, REM stage AHI, and non-REM stage AHI. In patients with SD-nCD, the minimum OS, minimum OS in the REM period, and minimum OS in the non-REM period were significantly reduced. OS was significantly correlated with cognitive level, as evaluated by the MMSE. The addition of sleep parameters can significantly improve the accuracy of dementia diagnosis. Dementia biomarkers of Aβ and tau proteins in blood showed cognition-related differences, while ptau181 was associated with both cognition and age-related differences. Regression models revealed that age was related to higher levels of cognitive decline before (β = −0.43, P < 0.001) and after (β = −0.38, P < 0.001) adjustment of gender, BMI, and education level. There was a significant mediation effect of relationship between aging and cognitive function by sleep efficiency and N1 stage sleep.

Conclusion

Sleep disorders and low OS are associated with a higher incidence of cognitive decline and dementia.
Retinal astrocyte morphology predicts integration of vascular and neuronal architecture
Authors: Holden Joseph M. , Wareham Lauren K. , Calkins David J.
Published: August 2023

Astrocytes are important regulators of blood flow and play a key role in the response to injury and disease in the central nervous system (CNS). Despite having an understanding that structural changes to these cells have consequences for local neurovascular physiology, individual astrocyte morphology remains largely unexplored in the retina. Here, we used MORF3 mice to capture full membranous morphology for over fifteen hundred individual astrocytes in the mouse retina, a highly metabolically active component of the CNS. We demonstrate that retinal astrocytes have been misrepresented as stellate in morphology due to marker use like GFAP and S100β which underestimates cell complexity. We also find that astrocytes contain recurring morphological motifs which are predictive of the underlying neurovascular architecture of the inner retina and suggestive of function. These motifs predict fine sampling and integration of retinal ganglion cell electrical activity with consequences for blood flow regulation. Additionally, our data shows that astrocytes participate in neurovascular interactions to a much greater degree than currently reported. 100% of cells contact the vasculature through one of three mutually exclusive classes of connections. Similarly, 100% of cells contact some neuronal element, be it an RGC axon or soma. Finally, we report that astrocyte morphology depends on retinal eccentricity, with cells appearing compressed near the nerve head and in the periphery. These results reveal a large degree of astrocyte morphological complexity that informs their contribution to neurovascular coupling in the retina.
Not your usual neurodegenerative disease: a case report of neuronal intranuclear inclusion disease with unconventional imaging patterns
Authors: Xu Luyao , Zhang Hongxia , Yuan Hanye , Xie Liwen , Zhang Junliang , Liang Zhigang
Published: August 2023

Background

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative illness with characteristic brain magnetic resonance imaging (MRI) manifestations: diffuse symmetric white-matter hyperintensities in lateral cerebral ventricle areas in fluid-attenuated inversion recovery (FLAIR) and high-intensity signals along the corticomedullary junction of the frontal–parietal–temporal lobes in diffusion weighted imaging (DWI). Here, we report a case of adult-onset NIID who was misdiagnosed with Susac syndrome (SS) due to unusual corpus callosum imaging findings.

Case presentation

A 39-year-old man presented with chronic headache, blurred vision, tinnitus, and numbness in the hands as initial symptoms, accompanied by cognitive slowing and decreased memory. Brain MRI revealed round hypointense lesions on T1-weighted imaging (T1WI) and hyperintense lesions on T2WI/FLAIR/DWI in the genu and splenium of the corpus callosum. An initial diagnosis of SS was made based on the presence of the SS-typical symptoms and SS-characteristic radiology changes. Furthermore, the patient’s symptoms improved upon completion of a combined pharmacotherapy plan. However, no significant changes were evident 18 months after the brain MRI scan. Eventually, the patient was then diagnosed with NIID based on a skin biopsy and detection of expanded GGC (guanine, guanine, cytosine) repeats in the NOTCH2NLC gene.

Conclusion

The present NIID case in which there was simultaneous onset of altered nervous and visual system functioning and atypical imaging findings, the atypical imaging findings may reflect an initial change of NIID leukoencephalopathy.
Association between green tea and coffee consumption and body iron storage in Japanese men and women: a cross-sectional study from the J-MICC Study Saga
Authors: Nanri Hinako , Hara Megumi , Nishida Yuichiro , Shimanoe Chisato , Iwasaka Chiharu , Higaki Yasuki , Tanaka Keitaro
Published: August 2023

Purpose

This study examined the association between daily green tea and coffee consumption and body iron stores among Japanese middle-aged and older adults.

Methods

This cross-sectional study used data obtained from 2005 to 2007. A total of 10,435 participants were recruited for this study. The participants completed a validated, self-administered food frequency questionnaire on green tea and coffee consumption. A multivariate linear regression analysis was conducted to assess the relationship between green tea and coffee consumption and serum ferritin levels. Additionally, logistic regression analysis was performed to ascertain whether excessive consumption of these beverages was linked to iron deficiency.

Results

We observed that higher green tea and coffee consumption was associated with lower ferritin levels in men and postmenopausal women, even after adjusting for covariates (all P for trends <0.05). Among premenopausal women, we found an inverse association between green tea consumption and serum ferritin levels, while no significant association was observed for coffee consumption after adjusting for covariates (green tea, P for trend <0.05; coffee, P for trend = 0.08). Notably, the association between these beverages and iron deficiency was found only in postmenopausal women; the odds ratios (95% confidence intervals) for iron deficiency associated with almost None, <1 cup/day, 1–2 cups/day, and ≥ 3 cups/day were 1.00 (reference), 0.78 (0.26–2.49), 1.29 (0.49–3.39), and 1.59 (0.63–4.04) (P for trend = 0.05), respectively, for green tea and 1.00, 1.32 (0.64–2.73), 1.46 (0.68–3.13), and 2.20 (1.06–4.55) (P for trend <0.01), respectively, for coffee.

Conclusion

Higher green tea and coffee consumption was associated with lower serum ferritin levels in men and postmenopausal women. In premenopausal women, consumption of green tea, but not coffee, was associated with lower serum ferritin levels. However, postmenopausal women who ≥3 cups of coffee demonstrated a higher prevalence of iron deficiency compared to those who consumed almost none.
The incidence and mortality of lung cancer in China: a trend analysis and comparison with G20 based on the Global Burden of Disease Study 2019
Authors: Long Jianhai , Zhai Mimi , Jiang Qin , Li Jiyang , Xu Cixian , Chen Duo
Published: August 2023

Background

Lung cancer is a significant health concern in China. There is limited available data of its burden and trends. This study aims to evaluate the trends of lung cancer across different age groups and genders in China and the Group of Twenty (G20) countries, explore the risk factors, and predict the future trends over a 20-year period.

Methods

The data were obtained from the GBD study 2019. The number of cases, age standardized rate (ASR), and average annual percentage changes (AAPC) were used to estimate the trend in lung cancer by age, gender, region and risk factor. The trend of lung cancer was predicted by autoregressive integrated moving average (ARIMA) model by the “xtarimau” command. The joinpoint regression analysis was conducted to identify periods with the highest changes in incidence and mortality. Additionally, the relationship between AAPCs and socio-demographic index (SDI) was explored.

Results

From 1990 to 2019, both the incidence and mortality of lung cancer in China and G20 significantly increased, with China experiencing a higher rate of increase. The years with the highest increase in incidence of lung cancer in China were 1998-2004 and 2007-2010. Among the G20 countries, the AAPC in incidence and mortality of lung cancer in the Republic of Korea was the highest, followed closely by China. Although India exhibited similarities, its AAPC in lung cancer incidence and mortality rates was lower than that of China. The prediction showed that the incidence in China will continue to increase. In terms of risk factors, smoking was the leading attributable cause of mortality in all countries, followed by occupational risk and ambient particulate matter pollution. Notably, smoking in China exhibited the largest increase among the G20 countries, with ambient particulate matter pollution ranking second.

Conclusion

Lung cancer is a serious public health concern in China, with smoking and environmental particulate pollution identified as the most important risk factors. The incidence and mortality rates are expected to continue to increase, which places higher demands on China’s lung cancer prevention and control strategies. It is urgent to tailor intervention measures targeting smoking and environmental pollution to contain the burden of lung cancer.
Combination effects of herbal and western medicines on osteoporosis in rheumatoid arthritis: systematic review and meta-analysis
Authors: Kwon Do Young , Gu Ji Hyang , Oh Minseok , Lee Eun-Jung
Published: August 2023

Purpose: This study aimed to comprehensively review the effect of combining herbal medicine (HM) with Western Medicine (WM) compared to WM alone on bone mineral density (BMD) improvement for osteoporosis in patients with rheumatoid arthritis (RA).

Methods: Randomized controlled trials (RCTs) were searched using 10 databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Nation Information by NII. We selected studies that used BMD as an evaluation index and administered HM treatment for osteoporosis in patients with RA. Subsequently, a meta-analysis was conducted using BMD as a continuous variable using RevMan version 5.4.

Results: Eighteen RCTs that met the eligibility criteria of this study were selected. The total number of study participants was 1,491 (481 men and 1,010 women). The mean age of participants was 52.4 ± 7.4 years, and the mean morbidity period of RA was 6.8 ± 1.3 years. In all studies, disease-modifying anti-rheumatic drugs (DMARDs; 16 RCTs) or bisphosphonates (two RCTs) were used as WM co-intervention with HMs (17 types of HM, 18 RCTs). Overall, the combination of HM and WM improved the BMD score, producing better results than WM alone. In particular, when HM was used in combination with DMARDs, which were used in most studies, BMD improved by 0.04 g/cm2 (95% confidence interval [CI]: 0.03–0.05, p < 0.001, I2 = 19%) in the lumbar spine and 0.03 g/cm2 (95% CI: 0.02–0.03, p < 0.001, I2 = 0%) in the femoral neck compared to the DMARDs alone group after treatment. In addition to BMD, bone markers and inflammatory indicators evaluated by each RCT showed significant improvement after HM plus WM treatment. In the analysis of frequently prescribed HMs, the BMD after treatment was higher by 0.04 g/cm2 (95% CI: 0.03–0.04, p < 0.001, I2 = 45%) in the Xianlinggubao-capsule plus methotrexate (MTX) group and by 0.02 g/cm2 (95% CI: 0.00–0.03, p = 0.04, I2 = 0) in the Hanbikang-tang plus MTX group compared to the MTX alone group.

Conclusion: This systematic review cautiously provides evidence for the combined therapeutic effect of HM and WM for osteoporosis in patients with RA. However, well-designed, large-scale clinical trials are necessary before recommending this combination therapy for osteoporosis in patients with RA.

Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=331854], identifier [CRD42022331854].
Microplastics in agriculture – a potential novel mechanism for the delivery of human pathogens onto crops
Authors: Quilliam Richard S. , Pow Chloe J. , Shilla Dativa J. , Mwesiga James J. , Shilla Daniel A. , Woodford Luke
Published: August 2023

Mulching with plastic sheeting, the use of plastic carriers in seed coatings, and irrigation with wastewater or contaminated surface water have resulted in plastics, and microplastics, becoming ubiquitous in agricultural soils. Once in the environment, plastic surfaces quickly become colonised by microbial biofilm comprised of a diverse microbial community. This so-called ‘plastisphere’ community can also include human pathogens, particularly if the plastic has been exposed to faecal contamination (e.g., from wastewater or organic manures and livestock faeces). The plastisphere is hypothesised to facilitate the survival and dissemination of pathogens, and therefore plastics in agricultural systems could play a significant role in transferring human pathogens to crops, particularly as microplastics adhering to ready to eat crops are difficult to remove by washing. In this paper we critically discuss the pathways for human pathogens associated with microplastics to interact with crop leaves and roots, and the potential for the transfer, adherence, and uptake of human pathogens from the plastisphere to plants. Globally, the concentration of plastics in agricultural soils are increasing, therefore, quantifying the potential for the plastisphere to transfer human pathogens into the food chain needs to be treated as a priority.
Evidence that a common arbuscular mycorrhizal network alleviates phosphate shortage in interconnected walnut sapling and maize plants
Authors: Mortier Emma , Mounier Arnaud , Kreplak Jonathan , Martin-Laurent Fabrice , Recorbet Ghislaine , Lamotte Olivier
Published: August 2023

Under agroforestry practices, inter-specific facilitation between tree rows and cultivated alleys occurs when plants increase the growth of their neighbors especially under nutrient limitation. Owing to a coarse root architecture limiting soil inorganic phosphate (Pi) uptake, walnut trees (Juglans spp.) exhibit dependency on soil-borne symbiotic arbuscular mycorrhizal fungi that extend extra-radical hyphae beyond the root Pi depletion zone. To investigate the benefits of mycorrhizal walnuts in alley cropping, we experimentally simulated an agroforestry system in which walnut rootstocks RX1 (J. regia x J. microcarpa) were connected or not by a common mycelial network (CMN) to maize plants grown under two contrasting Pi levels. Mycorrhizal colonization parameters showed that the inoculum reservoir formed by inoculated walnut donor saplings allowed the mycorrhization of maize recipient roots. Relative to non-mycorrhizal plants and whatever the Pi supply, CMN enabled walnut saplings to access maize Pi fertilization residues according to significant increases in biomass, stem diameter, and expression of JrPHT1;1 and JrPHT1;2, two mycorrhiza-inducible phosphate transporter candidates here identified by phylogenic inference of orthologs. In the lowest Pi supply, stem height, leaf Pi concentration, and biomass of RX1 were significantly higher than in non-mycorrhizal controls, showing that mycorrhizal connections between walnut and maize roots alleviated Pi deficiency in the mycorrhizal RX1 donor plant. Under Pi limitation, maize recipient plants also benefited from mycorrhization relative to controls, as inferred from larger stem diameter and height, biomass, leaf number, N content, and Pi concentration. Mycorrhization-induced Pi uptake generated a higher carbon cost for donor walnut plants than for maize plants by increasing walnut plant photosynthesis to provide the AM fungus with carbon assimilate. Here, we show that CMN alleviates Pi deficiency in co-cultivated walnut and maize plants, and may therefore contribute to limit the use of chemical P fertilizers in agroforestry systems.
Comprehensive identification and characterization of lncRNAs and circRNAs reveal potential brown planthopper-responsive ceRNA networks in rice
Authors: Wu Yan , Zha Wenjun , Qiu Dongfeng , Guo Jianping , Liu Gang , Li Changyan , Wu Bian , Li Sanhe , Chen Junxiao , Hu Liang , Shi Shaojie , Zhou Lei , Zhang Zaijun , Du Bo , You Aiqing
Published: August 2023

Brown planthopper (Nilaparvata lugens Stål, BPH) is one of the most destructive pests of rice. Non-coding RNA plays an important regulatory role in various biological processes. However, comprehensive identification and characterization of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in BPH-infested rice have not been performed. Here, we performed a genome-wide analysis of lncRNAs and circRNAs in BPH6-transgenic (resistant, BPH6G) and Nipponbare (susceptible, NIP) rice plants before and after BPH feeding (early and late stage) via deep RNA-sequencing. A total of 310 lncRNAs and 129 circRNAs were found to be differentially expressed. To reveal the different responses of resistant and susceptible rice to BPH herbivory, the potential functions of these lncRNAs and circRNAs as competitive endogenous RNAs (ceRNAs) were predicted and investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Dual-luciferase reporter assays revealed that miR1846c and miR530 were targeted by the lncRNAs XLOC_042442 and XLOC_028297, respectively. In responsive to BPH infestation, 39 lncRNAs and 21 circRNAs were predicted to combine with 133 common miRNAs and compete for miRNA binding sites with 834 mRNAs. These mRNAs predictably participated in cell wall organization or biogenesis, developmental growth, single-organism cellular process, and the response to stress. This study comprehensively identified and characterized lncRNAs and circRNAs, and integrated their potential ceRNA functions, to reveal the rice BPH-resistance network. These results lay a foundation for further study on the functions of lncRNAs and circRNAs in the rice-BPH interaction, and enriched our understanding of the BPH-resistance response in rice.
Weight change across adulthood in relation to the risk of depression
Authors: Wang Tao , Dai Bingqin , Shi Huanchen , Li Huawei , Fan Kexin , Zhang Dongfeng , Zhou Yunping
Published: August 2023

Background

Studies examining weight change patterns and depression are scarce and report inconsistent findings. This study—aimed to elucidate the association between weight change patterns and the risk of depression in a large, representative sample of US adults.

Methods

Data from the National Health and Nutrition Examination Survey (NHANES) 2005–2018 was analyzed. Five weight change groups were categorized: stable normal, weight loss, weight gain, maximum overweight, and stable obesity. Depression was ascertained using the validated Patient Health Questionnaire (PHQ-9) and depression was defined as PHQ score ≥ 10.

Results

A total of 17,556 participants were included. Compared with participants who maintained normal weight, stable obesity participants had increased risks of depression across adulthood from age 25 years to 10 years before the survey (OR = 1.61, 95% CI =1.23 to 2.11), in the 10 years period before the survey (OR = 2.15, 95% CI =1.71 to 2.70), and from age 25 years to survey (OR = 1.88, 95% CI =1.44 to 2.44). Weight gain was associated with an increased risk of depression from age 25 years to 10 years before the survey (OR = 1.71, 95% CI = 1.41 to 2.04), in the 10 years period before the survey (OR = 1.73, 95% CI = 1.35 to 2.21), and for the period from age 25 years to survey (OR = 1.83, 95% CI = 1.49 to 2.24). In the stratified analyses, we found statistically significant interactions with sex.

Conclusion

Our study suggested that stable obesity and weight gain across adulthood were associated with increased risks of depression.
Effects of carbohydrate drinks ingestion on executive function in athletes: a systematic review and meta-analysis
Authors: Yang Jingye , Han Qi , Liu Qi , Li Tieying , Shao Yongcong , Sui Xuemei , Wang Qirong
Published: August 2023

Background

Carbohydrates are often used as boosters for endurance and high-intensity exercise. However, it is unclear whether carbohydrate drinks intake before or during exercise can affect specific domains of cognitive function, such as Executive Function (EF).

Methods

Following the guidance of PRISMA 2020, we searched six major databases including PubMed, WOS, SPORTDiscus, Cochrane, Embase, and Scopus. Outcomes were presented in the form of Reaction Time (RT), Accuracy (ACC), and Scores (Score) for performing EF tests. Effect sizes were calculated from the test results of EF and expressed as standardized mean differences (SMDs). After analyzing the overall results, we performed subgroup analyses based on the athletes’ program characteristics.

Results

After retrieving a total of 5,355 articles, ten randomized controlled trials (RCTs) were identified and included in this review. The overall results showed that the intake of carbohydrate drinks before or during exercise did not have a significant effect on the reduction of EF after exercise (ACC (−0.05 [−0.27, 0.18]); RT (−0.18 [−0.45, 0.09]); Score (0.24 [−0.20, 0.68])). The subgroup analyses based on open skill sports and close skill sports also showed invalid results, but the results of RT ended up with different preference (ACC of open skill sports athletes (−0.10 [−0.34, 0.14]); RT of open skill athletes (−0.27 [−0.60, 0.07]); RT of close skill athletes (0.29 [−0.24, 0.82])).

Conclusion

The intake of 6–12% of single or mixed carbohydrates before or during exercise was not significantly effective in reducing the decline in EF after exercise. Our findings may have been influenced by the type of intervention, dose, mode of administration, or individual variability of the included subjects.