bluuebunny/crossref_metadata_2025 huggingface dataset:
Integration of transcriptome and metabolome analyses reveals key lodging-resistance-related genes and metabolic pathways in maize
Authors: Liu Lei , Liu Songtao , Lu Haibo , Tian Zaimin , Zhao Haichao , Wei Dong , Wang Shuo , Huang Zhihong
Published: October 2022

Stalk lodging, or breakage of the stalk at or below the ear, is one of the vital factors causing substantial yield losses in maize (Zea mays. L). Lodging affects maize plants’ physiological and molecular processes, eventually impacting plant growth and productivity. Despite this known fact, few researchers have investigated the genetic architecture underlying lodging in maize. Herein, through integrated transcriptome, metabolome, and phenotypic analyses of stalks of three diverse hybrid cultivars (highly resistant JNK738, mildly resistant JNK728, and lowly resistant XY335) at the tasseling (10 days to silking, 10 DTS) stage, we identified key genes and metabolic pathways modulating lodging resistance in maize. Based on the RNA-Seq analysis, a total of 10093 differentially expressed genes (DEGs) were identified from the comparison of the three varieties in pairs. Additionally, key lodging resistance–related metabolic pathways were obtained by KEGG enrichment analysis, and the DEGs were found predominantly enriched in phenylpropanoid and secondary metabolites biosynthesis pathways in the L_vs._H and M_vs._H comparison groups. Moreover, K-means analysis clustered the DEGs into clear and distinct expression profiles for each cultivar, with several functional and regulatory genes involved in the cell wall assembly, lignin biosynthetic process and hormone metabolic process being identified in the special clusters related to lodging resistance. Subsequently, integrating metabolome and transcriptome analyses revealed nine key lignin-associated metabolites that showed different expression trends in the three hybrid cultivars, among which L-phenylalanine and p-coumaric acid were regarded as differentially changed metabolites (DCMs). These two DCMs belonged to phenylalanine metabolism and biosynthesis pathways and were also supported by the RNA-Seq data. Furthermore, plant hormone signal transduction pathway–related genes encoding auxin, abscisic acid, jasmonates, and salicylic acid were differentially expressed in the three comparisons of lodging resistance, indicating these DEGs were valuable potential targets for improving maize lodging resistance. Finally, comparative physiological and qRT-PCR analyses results supported our transcriptome-based findings. Our research not only provides a preliminary theoretical basis and experimental ideas for an in-depth study of the regulatory networks involved in maize lodging resistance regulation but also opens up new avenues for molecular maize stalk lodging resistance breeding.
Endometrial cancer prognosis prediction using correlation models based on CDK family genes
Authors: Gu Xianhua , Shen Honghong , Bai Wenqi , Xiang Zheng , Li Xinwei , Zhang Rong , Shi Fan , Li Huiyuan , Zhu Guangzheng , Guo Suyang
Published: October 2022

Cyclin-dependent kinases (CDKs) play an important role in cell division. Given that abnormal cell proliferation caused by dysregulation of cell division is one of the major causes of endometrial cancer (EC), it is important to elucidate the role of CDK family genes in the diagnosis and prognosis of EC. In this study, The Cancer Genome Atlas (TCGA) database was used to analyze the frequency of copy number variations and somatic mutations in 26 CDK family genes. Subsequently, the expression of these genes in EC was assessed, and their relationship with overall survival (OS) was examined via Kaplan–Meier analysis to assess their prognostic significance. A prognostic model based on seven CDK genes was constructed using Lasso and Cox regression, and the predictive performance of the model was analyzed using Kaplan–Meier analysis and column line plots. The correlation between CDK genes and immune cells was also examined. Patients with EC in the high-risk group had a poorer prognosis. The results of qRT-PCR and immunohistochemical analyses validated that CDK16 is highly expressed in EC tissues. Patients with EC with high CDK16 expression had worse 10-year OS than patients with low CDK16 expression. These findings suggest that the prognostic model constructed based on CDK genes can help to develop individualized and targeted treatment strategies for patients with EC.
Bioinformatics analysis to screen for genes related to myocardial infarction
Authors: Yang Liting , Pan Xuyang , Zhang Ying , Zhao Dongsheng , Wang Liang , Yuan Guoliang , Zhou Changgao , Li Tao , Li Wei
Published: October 2022

Myocardial infarction (MI) is an acute and persistent myocardial ischemia caused by coronary artery disease. This study screened potential genes related to MI. Three gene expression datasets related to MI were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened using the MetaDE package. Afterward, the modules and genes closely related to MI were screened and a gene co-expression network was constructed. A support vector machine (SVM) classification model was then constructed based on the GSE61145 dataset using the e1071 package in R. A total of 98 DEGs were identified in the MI samples. Next, three modules associated with MI were screened and an SVM classification model involving seven genes was constructed. Among them, BCL6, CEACAM8, and CUGBP2 showed co-interactions in the gene co-expression network. Therefore, ACOX1, BCL6, CEACAM8, and CUGBP2, in addition to GPX7, might be feature genes related to MI.
Cumulative evidence for associations between genetic variants in interleukin 17 family gene and risk of human diseases
Authors: Liu Tianyu , Yang Lei , Lv Xiaolong , Zuo Chunjian , Jia Chenhao , Yang Zelin , Fan Chongqi , Chen Huanwen
Published: October 2022

Background

Genetic association studies have elucidated the link of variants in the interleukin 17 (IL-17) family genes with susceptibility to human diseases, yet have obtained controversial outcomes. Therefore, we sought to update comprehensive synopsis of variants in the IL-17 family genes with susceptibility to human diseases.

Methods

Our study screened the Pubmed and Web of Science to enroll eligible articles and performed a meta-analysis, then graded the cumulative evidence of significant association using Venice criteria and false-positive report probability test, and finally assessed the function of variants with strong evidence.

Results

Seven variants in IL-17 family genes had significant relationships with susceptibility to 18 human diseases identified by meta-analyses. Strong evidence was assigned to 4 variants (IL-17A rs2275913, IL-17A rs8193037, IL-17F rs1889570, IL-17F rs763780) with susceptibility to 6 human diseases (lung and cervical cancer, spondyloarthritis, asthma, multiple sclerosis, rheumatoid arthritis), moderate to 2 variants with risk of 5 diseases, weak to 5 variants with risk of 10 diseases. Bioinformatics analysis suggested that the variants with strong evidence might fall in putative functional regions. Additionally, positive relationships for 5 variants with risk of 4 diseases (based on two datasets) and 14 variants with risk of 21 diseases (based on one dataset) were considered noteworthy.

Conclusions

This study offers updated and comprehensive clues that variants in the IL-17 family genes are significantly linked with susceptibility to cervical, lung cancer, asthma, multiple sclerosis, rheumatoid arthritis and spondyloarthritis, and elucidates the crucial role of the IL-17 regions in the genetic predisposition to cancer or noncancerous diseases.
Combining single-cell sequencing data to construct a prognostic signature to predict survival, immune microenvironment, and immunotherapy response in gastric cancer patients
Authors: Hu Bo , Meng Yan , Qu Chao , Wang Bing-Yan , Xiu Dian-Rong
Published: October 2022

Background and objective

Gastric cancer (GC) represents a major factor inducing global cancer-associated deaths, but specific biomarkers and therapeutic targets for GC are lacking at present. Therefore, the present work focused on developing an immune-related genetic signature at the single-cell level for categorizing GC cases and predicting patient prognostic outcome, immune status as well as treatment response.

Methods

Single-cell RNA-sequencing (scRNA-seq) data were combined with bulk RNA-seq data in GC patients for subsequent analyses. Differences in overall survival (OS), genomic alterations, immune status, together with estimated immunotherapeutic outcomes were measured between different groups.

Results

Nine cell types were identified by analyzing scRNA-seq data from GC patients, and marker genes of immune cells were also selected for subsequent analysis. In addition, an immune-related signature was established to predict OS while validating the prediction power for GC patients. Afterwards, a nomogram with high accuracy was constructed for improving our constructed signature’s clinical utility. The low-risk group was featured by high tumor mutation burden (TMB), increased immune activation, and microsatellite instability-high (MSI-H), which were related to the prolonged OS and used in immunotherapy. By contrast, high-risk group was associated with microsatellite stability (MSS), low TMB and immunosuppression, which might be more suitable for targeted therapy. Meanwhile, the risk score generated by our signature was markedly related to the cancer stem cell (CSC) index. In addition, the immunotherapeutic response prediction accuracy of our signature was validated in an external dataset IMvigor210 cohort.

Conclusion

A signature was constructed according to scRNA-seq data analysis. The signature-screened low- and high-risk patients had different prognoses, immune statuses and enriched functions and pathways. Such results shed more lights on immune status of GC, prognosis assessment, and development of efficient immunotherapeutic treatments.
The clinical value of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and D-dimer-to-fibrinogen ratio for predicting pneumonia and poor outcomes in patients with acute intracerebral hemorrhage
Authors: Luo Sai , Yang Wen-Song , Shen Yi-Qing , Chen Ping , Zhang Shu-Qiang , Jia Zhen , Li Qi , Zhao Jian-Ting , Xie Peng
Published: October 2022

Background

This study aimed to investigate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and D-dimer-to-fibrinogen ratio (DFR) as predictors of pneumonia and poor outcomes in patients with acute intracerebral hemorrhage (ICH).

Methods

We retrospectively examined patients with acute ICH treated in our institution from May 2018 to July 2020. Patient characteristics, laboratory testing data, radiologic imaging data, and 90-day outcomes were recorded and analyzed.

Results

Among the 329 patients included for analysis, 183 (55.6%) developed pneumonia. Systolic blood pressure, initial hematoma volume, D-dimer concentration, NLR, PLR, DFR, and white blood cell, platelet, neutrophil, and lymphocyte counts at admission were significantly higher in patients who developed pneumonia than in those who did not; however, the Glasgow coma scale (GCS) score at admission was significantly lower in pneumonia patients compared with non-pneumonia patients (all P <0.05). Multivariate logistic regression showed that the NLR and PLR were independent predictors of pneumonia, and the NLR and DFR were independent predictors of poor 90-day outcomes (modified Rankin scale score 4–6).

Conclusion

The NLR and PLR were independent predictors of pneumonia and the NLR and DFR were independent predictors of poor 90-day outcomes. The NLR, PLR, and DFR can provide prognostic information about acute ICH patients.
Improved diagnostic performance of CASPAR criteria with integration of ultrasound
Authors: Geng Yan , Song Zhibo , Zhang Xiaohui , Deng Xuerong , Wang Yu , Zhang Zhuoli
Published: October 2022

Background

The difficulty in determining synovitis, tenosynovitis, or enthesitis by physical examination (PE) has limited the diagnostic capability of CASPAR for psoriatic arthritis (PsA). Therefore, we aimed to evaluate the diagnostic utility of CASPAR with the integration of ultrasound (US).

Methods

Patients with a hint of PsA were enrolled. Besides routine PE for tender or swollen joints, enthesitis, and dactylitis, US was performed to evaluate peripheral joints, entheses, and tendons. The additional value of the US to the CASPAR criteria was analyzed.

Results

A total of 326 consecutive patients with 164 PsA and 162 non-PsA were enrolled. A total of 162 non-PsA patients consisted of 58 cases of psoriasis (PsO), 27 osteoarthritis with PsO/family history of PsO, five fibromyalgia with PsO, 69 sero-negative rheumatoid arthritis, and three undifferentiated arthritis. Significantly higher frequencies of tenosynovitis and enthesitis on US and new bone formation on X-rays were found in PsA vs. non-PsA patients (59.1% vs. 13.0%; 63.4% vs. 14.2%; 62.2% vs. 8.0%, p <0.01 for all). Logistic regression analysis showed that dactylitis (OR = 12.0, p <0.01), family history of PsO/PsA (OR = 3.1, p <0.05), nail involvement (OR = 3.5, p = 0.01), new bone formation on X-ray (OR = 14.8, p <0.01), tenosynovitis on US (OR = 21.3, p <0.01), and enthesitis on US (OR = 21.7, p <0.01) were independent risk factors for PsA. By combining US tenosynovitis and/or enthesitis, the diagnostic utility of CASPAR criteria was improved, with superior specificity (91.4% vs. 84.0%) and similar sensitivity (95.7% vs. 94.5%). Replacing X-ray by US or adding US, the CASPAR criteria showed comparable sensitivity and specificity for PsA diagnosis. The diagnostic accuracy was 89.3% for CASPAR criteria based on PE, 93.6% for CASPAR added with US, and 93.3% for CASPAR with US replacing X-ray.

Conclusion

The diagnostic utility of the CASPAR was improved by integrating tenosynovitis and/or enthesitis when using US. US provides additional value for PsA recognition.
The immune response as a therapeutic target in non-alcoholic fatty liver disease
Authors: Ortiz-López Nicolás , Fuenzalida Catalina , Dufeu María Soledad , Pinto-León Araceli , Escobar Alejandro , Poniachik Jaime , Roblero Juan Pablo , Valenzuela-Pérez Lucía , Beltrán Caroll J.
Published: October 2022

Non-alcoholic fatty liver disease (NAFLD) is a complex and heterogeneous disorder considered a liver-damaging manifestation of metabolic syndrome. Its prevalence has increased in the last decades due to modern-day lifestyle factors associated with overweight and obesity, making it a relevant public health problem worldwide. The clinical progression of NAFLD is associated with advanced forms of liver injury such as fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). As such, diverse pharmacological strategies have been implemented over the last few years, principally focused on metabolic pathways involved in NAFLD progression. However, a variable response rate has been observed in NAFLD patients, which is explained by the interindividual heterogeneity of susceptibility to liver damage. In this scenario, it is necessary to search for different therapeutic approaches. It is worth noting that chronic low-grade inflammation constitutes a central mechanism in the pathogenesis and progression of NAFLD, associated with abnormal composition of the intestinal microbiota, increased lymphocyte activation in the intestine and immune effector mechanisms in liver. This review aims to discuss the current knowledge about the role of the immune response in NAFLD development. We have focused mainly on the impact of altered gut-liver-microbiota axis communication on immune cell activation in the intestinal mucosa and the role of subsequent lymphocyte homing to the liver in NAFLD development. We further discuss novel clinical trials that addressed the control of the liver and intestinal immune response to complement current NAFLD therapies.
Mouse Ocilrp2/Clec2i negatively regulates LPS-mediated IL-6 production by blocking Dap12-Syk interaction in macrophage
Authors: Cao Mingya , Ma Lina , Yan Chenyang , Wang Han , Ran Mengzhe , Chen Ying , Wang Xiao , Liang Xiaonan , Chai Lihui , Li Xia
Published: October 2022

C-type lectin Ocilrp2/Clec2i is widely expressed in dendritic cells, lymphokine-activated killer cells and activated T cells. Previous studies have shown that Ocilrp2 is an important regulator in the activation of T cells and NK cells. However, the role of Ocilrp2 in the inflammatory responses by activated macrophages is currently unknown. This study investigated the expression of inflammatory cytokines in LPS-induced macrophages from primary peritoneal macrophages silenced by specific siRNA target Ocilrp2. Ocilrp2 was significantly downregulated in macrophages via NF-κB and pathways upon LPS stimuli or VSV infection. Silencing Ocilrp2 resulted in the increased expression of IL-6 in LPS-stimulated peritoneal macrophages and mice. Moreover, IL-6 expression was reduced in LPS-induced Ocilrp2 over-expressing iBMDM cells. Furthermore, we found that Ocilrp2-related Syk activation is responsible for expressing inflammatory cytokines in LPS-stimulated macrophages. Silencing Ocilrp2 significantly promotes the binding of Syk to Dap12. Altogether, we identified the Ocilrp2 as a critical role in the TLR4 signaling pathway and inflammatory macrophages’ immune regulation, and added mechanistic insights into the crosstalk between TLR and Syk signaling.
Mobilization of CD11b+/Ly6chi monocytes causes multi organ dysfunction syndrome in acute pancreatitis
Authors: Wilden Anika , Glaubitz Juliane , Otto Oliver , Biedenweg Doreen , Nauck Matthias , Mack Matthias , Ribback Silvia , Bröker Barbara M. , Rheinbaben Sabrina Freiin von , Lerch Markus M. , Aghdassi Ali Alexander , Weiss Frank Ulrich , Sendler Matthias
Published: October 2022

Objective

Acute pancreatitis (AP) is an inflammatory disorder, the severe form of which is burdened with multi-organ dysfunction and high mortality. The pathogenesis of life –threatening organ complications, such as respiratory and renal failure, is unknown.

Design

Organ dysfunction was investigated in a mouse model of AP. The influence of monocytes and neutrophils on multi organ dysfunction syndrome (MODS) was investigated in vivo by antibody depletion. Using real-time-fluorescence and deformability-cytometry (RT-DC) analysis we determined the mechanical properties of neutrophils and monocytes during AP. Furthermore, blood samples of pancreatitis patients were used to characterize severity-dependent chemokine profiles according to the revised Atlanta classification.

Results

Similar to AP in humans, severe disease in the mouse model associates with organ dysfunction mainly of lung and kidney, which is triggered by a mobilisation of Ly6g-/CD11b+/Ly6c hi monocytes, but not of Ly6g+/CD11b+ neutrophils. Monocyte depletion by anti-CCR2 antibody treatment ameliorated lung function (oxygen consumption) without interfering with the systemic immune response. RT-DC analysis of circulation monocytes showed a significant increase in cell size during SAP, but without a compensatory increase in elasticity. Patient chemokine profiles show a correlation of AP severity with monocyte attracting chemokines like MCP-1 or MIG and with leukocyte mobilisation.

Conclusion

In AP, the physical properties of mobilized monocytes, especially their large size, result in an obstruction of the fine capillary systems of the lung and of the kidney glomeruli. A selective depletion of monocytes may represent a treatment strategy for pancreatitis as well as for other inflammation-related disorders.
Assessment of Posidonia oceanica traits along a temperature gradient in the Mediterranean Sea shows impacts of marine warming and heat waves
Authors: Stipcich Patrizia , Apostolaki Eugenia T. , Chartosia Niki , Efthymiadis Pavlos Theofilos , Jimenez Carlos E. , La Manna Gabriella , Pansini Arianna , Principato Elena , Resaikos Vasilis , Ceccherelli Giulia
Published: October 2022

Global warming and Marine Heat Waves (MHWs) are having large-scale impacts on the seagrasses and their effects on the Mediterranean endemic Posidonia oceanica need to be properly defined. This research aimed to sharpen the knowledge on P. oceanica response to the warming by correlating the shoot morphology and the productivity of the seagrass to temperature conditions and MHW occurrence. Two correlative studies, along a Mediterranean temperature range (sites at the same latitude), were conducted: one explored the associations of summer 2021 Sea Surface Temperature (SST) and MHWs on P. oceanica morphology and the other used a reconstruction technique (lepidochronological analysis) to relate past temperature conditions and MHW occurrence to proxies of seagrass productivity for the corresponding periods. The results showed that the mean summer temperature affected the P. oceanica leaf necrosis and that MHWs occurrence changed the morphology of the plant by lowering the leaf area and increasing leaf necrosis. Interesting results were also found relating the past thermal environment, since rhizome biomass has been negatively affected by the number of MHWs and rhizome length by the temperature range. This research provides fundamental insights about P. oceanica changes linked to warming and MHWs, identifying the potential plant indicators assisting future experimental and modelling studies. To the best of our knowledge, this is the first time a reconstruction technique is used to evaluate the effects of past MHWs on the morphology and productivity of a plant species.
Quantifying errors in wind and wave measurements from a compact, low-cost wave buoy
Authors: Beckman Jesse N. , Long Joseph W.
Published: October 2022

A yearlong wind and wave dataset derived from a cost-effective GPS wave buoy (Spotter) is compared to waves obtained from an accelerometer wave buoy (Datawell) and winds obtained from a collocated meteorological buoy. Overall, there was a strong correlation in bulk wave parameters obtained from the Spotter buoy and the Datawell buoy (RMSE of 0.06 m, 0.27 s, and 21.89° for significant wave height, mean wave period, and peak wave direction, respectively). Similarly, the bulk characteristics compared well when separating the directional wave spectra into sea and swell components with more scatter in mean wave periods for lower frequencies. Measurements of mean directional spread from the Spotter buoy were 7.51° larger than the Datawell, spreading more wave energy across different directions outside the peak direction. Additional analysis indicates that the increased directional spreading arises from a bias in the a1 and b1 spectral moments. Using the equilibrium frequency range of the wave energy spectrum, the Spotter buoy can derive wind speed and direction. This study found the Spotter buoy can report wind speed and direction with reasonable accuracy but underestimates wind speeds less than 4 m/s and greater than 8 m/s and was less accurate reporting wind directions oriented offshore. A comparison with a Spotter buoy in deeper water revealed the Spotter buoy further offshore was most accurate in reporting wind directions indicating this proxy-based measurement of wind speed and wind direction may be significantly influenced by fetch and local geography (e.g., large-scale cuspate coastlines).
Do we miss rare adverse events induced by COVID-19 vaccination?
Authors: Mohseni Afshar Zeinab , Tavakoli Pirzaman Ali , Liang Jackson J. , Sharma Akanksha , Pirzadeh Marzieh , Babazadeh Arefeh , Hashemi Erfan , Deravi Niloofar , Abdi Sadaf , Allahgholipour Amirreza , Hosseinzadeh Rezvan , Vaziri Zahra , Sio Terence T. , Sullman Mark J. M. , Barary Mohammad , Ebrahimpour Soheil
Published: October 2022

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused many complications, the invention of coronavirus disease 2019 (COVID-19) vaccines has also brought about several adverse events, from common side effects to unexpected and rare ones. Common vaccine-related adverse reactions manifest locally or systematically following any vaccine, including COVID-19 vaccines. Specific side effects, known as adverse events of particular interest (AESI), are unusual and need more evaluation. Here, we discuss some of the most critical rare adverse events of COVID-19 vaccines.
Critical evaluation of asthma biomarkers in clinical practice
Authors: Guida Giuseppe , Bagnasco Diego , Carriero Vitina , Bertolini Francesca , Ricciardolo Fabio Luigi Massimo , Nicola Stefania , Brussino Luisa , Nappi Emanuele , Paoletti Giovanni , Canonica Giorgio Walter , Heffler Enrico
Published: October 2022

The advent of personalized medicine has revolutionized the whole approach to the management of asthma, representing the essential basis for future developments. The cornerstones of personalized medicine are the highest precision in diagnosis, individualized prediction of disease evolution, and patient-tailored treatment. To this aim, enormous efforts have been established to discover biomarkers able to predict patients' phenotypes according to clinical, functional, and bio-humoral traits. Biomarkers are objectively measured characteristics used as indicators of biological or pathogenic processes or clinical responses to specific therapeutic interventions. The diagnosis of type-2 asthma, prediction of response to type-2 targeted treatments, and evaluation of the risk of exacerbation and lung function impairment have been associated with biomarkers detectable either in peripheral blood or in airway samples. The surrogate nature of serum biomarkers, set up to be less invasive than sputum analysis or bronchial biopsies, has shown several limits concerning their clinical applicability. Routinely used biomarkers, like peripheral eosinophilia, total IgE, or exhaled nitric oxide, result, even when combined, to be not completely satisfactory in segregating different type-2 asthma phenotypes, particularly in the context of severe asthma where the choice among different biologics is compelling. Moreover, the type-2 low fraction of patients is not only an orphan of biological treatments but is at risk of being misdiagnosed due to the low negative predictive value of type-2 high biomarkers. Sputum inflammatory cell analysis, considered the highest specific biomarker in discriminating eosinophilic inflammation in asthma, and therefore elected as the gold standard in clinical trials and research models, demonstrated many limits in clinical applicability. Many factors may influence the measure of these biomarkers, such as corticosteroid intake, comorbidities, and environmental exposures or habits. Not least, biomarkers variability over time is a confounding factor leading to wrong clinical choices. In this narrative review, we try to explore many aspects concerning the role of routinely used biomarkers in asthma, applying a critical view over the “state of the art” and contemporarily offering an overview of the most recent evidence in this field.
Do microbes have a memory? History-dependent behavior in the adaptation to variable environments
Authors: Vermeersch Lieselotte , Cool Lloyd , Gorkovskiy Anton , Voordeckers Karin , Wenseleers Tom , Verstrepen Kevin J.
Published: October 2022

Microbes are constantly confronted with changes and challenges in their environment. A proper response to these environmental cues is needed for optimal cellular functioning and fitness. Interestingly, past exposure to environmental cues can accelerate or boost the response when this condition returns, even in daughter cells that have not directly encountered the initial cue. Moreover, this behavior is mostly epigenetic and often goes hand in hand with strong heterogeneity in the strength and speed of the response between isogenic cells of the same population, which might function as a bet-hedging strategy. In this review, we discuss examples of history-dependent behavior (HDB) or “memory,” with a specific focus on HDB in fluctuating environments. In most examples discussed, the lag time before the response to an environmental change is used as an experimentally measurable proxy for HDB. We highlight different mechanisms already implicated in HDB, and by using HDB in fluctuating carbon conditions as a case study, we showcase how the metabolic state of a cell can be a key determining factor for HDB. Finally, we consider possible evolutionary causes and consequences of such HDB.
Therapeutic effects of oral administration of lytic Salmonella phages in a mouse model of non-typhoidal salmonellosis
Authors: Sukjoi Chutikarn , Buddhasiri Songphon , Tantibhadrasapa Arishabhas , Kaewsakhorn Thattawan , Phothaworn Preeda , Nale Janet Y. , Lopez-Garcia Angela V. , AbuOun Manal , Anjum Muna F. , Malik Danish J. , Galyov Edouard E. , Clokie Martha R. J. , Korbsrisate Sunee , Thiennimitr Parameth
Published: October 2022

Acute non-typhoidal salmonellosis (NTS) caused by a Gram-negative bacteriumSalmonella entericaserovar Typhimurium (S.Tm) is one of the most common bacterial foodborne diseases worldwide. Bacteriophages (phages) can specifically target and lyse their host bacteria, including the multidrug-resistant strains, without collateral damage to other bacteria in the community. However, the therapeutic use ofSalmonellaphagesin vivois still poorly investigated.Salmonellaphages ST-W77 and SE-W109 have previously been shown by our group to be useful for biocontrol properties. Here, we tested whether phages ST-W77 and SE-W109 can reduceSalmonellainvasion into cultured human cells and confer a therapeutic benefit for acute NTS in a mammalian host. Human colonocytes, T84 cells, were treated with phages ST-W77, SE-W109, and its combination for 5 min beforeS.Tm infection. Gentamicin protection assays demonstrated that ST-W77 and SE-W109 significantly reducedS.Tm invasion and inflammatory response in human colonocytes. Next, streptomycin-pretreated mice were orally infected withS.Tm (108CFU/mouse) and treated with a single or a combination of ST-W77 and SE-W109 (1010PFU/mouse for 4 days) by oral feeding. Our data showed that phage-treated mice had lowerS.Tm numbers and tissue inflammation compared to the untreated mice. Our study also revealed that ST-W77 and SE-W109 persist in the mouse gut lumen, but not in systemic sites. Together, these data suggested thatSalmonellaphages ST-W77 and SE-W109 could be further developed as an alternative approach for treating an acute NTS in mammalian hosts.
Heart fatty acid-binding protein is associated with phosphorylated tau and longitudinal cognitive changes
Authors: Fu Yan , Wang Zuo-Teng , Huang Liang-Yu , Tan Chen-Chen , Cao Xi-Peng , Tan Lan
Published: October 2022

Background

Perturbation of lipid metabolism is associated with Alzheimer’s disease (AD). Heart fatty acid-binding protein (HFABP) is an adipokine playing an important role in lipid metabolism regulation.

Materials and methods

Two datasets separately enrolled 303 and 197 participants. First, we examine the associations of cerebrospinal fluid (CSF) HFABP levels with cognitive measures [including Mini-Mental State Examination (MMSE), Clinical Dementia Rating sum of boxes (CDRSB), and the cognitive section of Alzheimer’s Disease Assessment Scale] and AD biomarkers (CSF amyloid beta and tau levels). Second, we examine the longitudinal associations of baseline CSF HFABP levels and the variability of HFABP with cognitive measures and AD biomarkers. Structural equation models explored the mediation effects of AD pathologies on cognition.

Results

We found a significant relationship between CSF HFABP level and P-tau (dataset 1: β = 2.04, p < 0.001; dataset 2: β = 1.51, p < 0.001). We found significant associations of CSF HFABP with longitudinal cognitive measures (dataset 1: ADAS13, β = 0.09, p = 0.008; CDRSB, β = 0.10, p = 0.003; MMSE, β = −0.15, p < 0.001; dataset 2: ADAS13, β = 0.07, p = 0.004; CDRSB, β = 0.07, p = 0.005; MMSE, β = −0.09, p < 0.001) in longitudinal analysis. The variability of HFABP was associated with CSF P-tau (dataset 2: β = 3.62, p = 0.003). Structural equation modeling indicated that tau pathology mediated the relationship between HFABP and cognition.

Conclusion

Our findings demonstrated that HFABP was significantly associated with longitudinal cognitive changes, which might be partially mediated by tau pathology.
A flexible Python-based touchscreen chamber for operant conditioning reveals improved visual perception of cardinal orientations in mice
Authors: Wiesbrock Christopher , Musall Simon , Kampa Björn M.
Published: October 2022

Natural scenes are composed of a wide range of edge angles and spatial frequencies, with a strong overrepresentation of vertical and horizontal edges. Correspondingly, many mammalian species are much better at discriminating these cardinal orientations compared to obliques. A potential reason for this increased performance could be an increased number of neurons in the visual cortex that are tuned to cardinal orientations, which is likely to be an adaptation to the natural scene statistics. Such biased angular tuning has recently been shown in the mouse primary visual cortex. However, it is still unknown if mice also show a perceptual dominance of cardinal orientations. Here, we describe the design of a novel custom-built touchscreen chamber that allows testing natural scene perception and orientation discrimination performance by applying different task designs. Using this chamber, we applied an iterative convergence towards orientation discrimination thresholds for cardinal or oblique orientations in different cohorts of mice. Surprisingly, the expert discrimination performance was similar for both groups but showed large inter-individual differences in performance and training time. To study the discrimination of cardinal and oblique stimuli in the same mice, we, therefore, applied, a different training regime where mice learned to discriminate cardinal and oblique gratings in parallel. Parallel training revealed a higher task performance for cardinal orientations in an early phase of the training. The performance for both orientations became similar after prolonged training, suggesting that learning permits equally high perceptual tuning towards oblique stimuli. In summary, our custom-built touchscreen chamber offers a flexible tool to test natural visual perception in rodents and revealed a training-induced increase in the perception of oblique gratings. The touchscreen chamber is entirely open-source, easy to build, and freely available to the scientific community to conduct visual or multimodal behavioral studies. It is also based on the FAIR principles for data management and sharing and could therefore serve as a catalyst for testing the perception of complex and natural visual stimuli across behavioral labs.
Efficacy prediction of acupuncture treatment for migraine without aura based on multimodal MRI: A study protocol
Authors: Cheng Shirui , Zhang Xinyue , Zheng Huabin , Jiang Nannan , Zhou Jun , Li Xinling , Fang Yu , Huang Xiaopeng , Liang Jingtao , Yin Tao , Liang Fanrong , Zeng Fang , Li Zhengjie
Published: October 2022

Introduction

Acupuncture is an effective and safe therapy for patients with migraine without aura (MwoA), but only 41–59% of patients show improvement with this treatment. Screening positive responders to acupuncture treatment for MwoA can ensure that healthcare resources can be appropriately targeted to specific patients who would most benefit. The objective of this study is to determine whether the structure and functional activity in certain brain regions can predict analgesia response in patients with MwoA who receive acupuncture treatment.

Methods and analysis

A total of 72 patients with MwoA and 72 healthy controls (HCs) will be enrolled in this study. Resting-state structural and functional magnetic resonance imaging (MRI) data will be collected from each participant at baseline. Patients with MwoA will undergo 12 sessions of acupuncture treatment for 8 weeks, twice per week in the first 4 weeks and once per week for the last 4 weeks. The follow-up will be 12 weeks. The number of days with migraine, frequency of migraine attacks, and average visual analog scale scores will be recorded in detail at weeks 0, 4, 8, 12, and 16 and at the end of follow-up (week 20). The positive response rate will be calculated as the proportion of patients with ≥50% reduction in the number of migraine days during follow-up compared with baseline. Machine learning methods will be applied to classify patients with MwoA and HCs and predict patients with response or non-response to acupuncture treatment based on multimodal MRI parameters, such as gray matter volume, regional homogeneity, amplitude of low-frequency fluctuation, fractional anisotropy, and mean diffusivity.

Discussion

This study aims to establish brain structural and functional characteristics that can identify patients with MwoA who will derive analgesia benefits from acupuncture treatment.

Trial registration number

http://www.chictr.org.cn/showproj.aspx?proj=65443, identifier: ChiCTR2100042915.
Shear wave elastography combined with electromyography to assess the effect of botulinum toxin on spastic dystonia following stroke: A pilot study
Authors: Campanella William , Corazza Angelo , Puce Luca , Privitera Laura , Pedrini Riccardo , Mori Laura , Boccuni Leonardo , Turtulici Giovanni , Trompetto Carlo , Marinelli Lucio
Published: October 2022

Background

Shear wave elastography (SWE) is a method for carrying out a quantitative assessment of the mechanical properties of soft tissues in terms of stiffness. In stroke survivors, the paretic muscles may develop hypertonia due to both neural-mediated mechanisms and structural alterations with consequent muscular fibrous-fatty remodeling.

Methods

Fourteen adult patients with spastic dystonia following stroke were recruited. Muscle hypertonia was assessed using the modified Ashworth scale (MAS). Muscle activation was measured by surface electromyography (sEMG) with the selected muscle in shortened (spastic dystonia) and stretched (dynamic stretch reflex) positions. SWE was performed on a selected paretic muscle and on the contralateral non-paretic one to calculate shear wave velocities (SWV) along and across muscular fibers. The modified Heckmatt scale (MHS) pattern was also determined. All evaluations were performed shortly before BoNT-A injections (T0) and one month later (T1).

Results

All SWV on paretic muscles were higher than contralateral non-paretic ones (p < 0.01). After BoNT-A injection, a significant reduction in MAS (p = 0.0018), spastic dystonia (p = 0.0043), and longitudinal SWE measurements, both in shortened (p = 0.001) and in stretched muscular conditions (p = 0.0029), was observed. No significant changes in SWV on non-paretic muscles were observed. Higher SWV resulted along the direction of muscular fibers vs. across them (p = 0.001). No changes resulted from the MHS evaluations after BoNT-A. There was a positive correlation between MHS scores and SWV values while the muscle was in the shortened position, but not with spastic dystonia recorded by sEMG.

Conclusions

This is the first study evaluating the effect of BoNT-A on muscle hypertonia following stroke, assessed by both SWE and sEMG. These findings support SWE as a useful method to disclose intrinsic muscular remodeling, independently of the effect of spastic dystonia, in particular, while muscles were assessed in a neutral position. SWE measurements of muscle stiffness cannot tell apart neural-mediated and intrinsic muscle hypertonia. Interestingly, when sEMG activity is very limited, as in spastic muscles kept in a shortened position, SWE can provide a measurement of stiffness due almost completely to intrinsic muscle changes. Alongside sEMG, SWE could aid clinicians in the assessment of responses to treatments.
The therapeutic effect and targets of cellulose polysaccharide on coronary heart disease (CHD) and the construction of a prognostic signature based on network pharmacology
Authors: Liu Lang , Zhang Yundi , Du Yuxin , Li Haoyue , Wang Mingzhao , Lv Jianfeng
Published: October 2022

Cellulose is the first rich biological polysaccharide in nature and has many excellent properties, so it is being developed as a variety of drug carriers. Moreover, applications in drug delivery, biosensors/bioanalysis, immobilization of enzymes and cells, stem cell therapy, and skin tissue repair are also highlighted by many studies. Coronary heart disease, as one of the diseases with the highest incidence, is urgent to enhance the survival outcome and life quality of patients with coronary heart disease, whereas the mechanism of cellulose's interaction with the human body remains unclear. However, the mechanism of cellulose's interaction with the human body remains unclear. We obtained 92 genes associated with cellulose and coronary heart disease through the intersection of different databases. Ten key genes were identified: HRAS, STAT3, HSP90AA1, FGF2, VEGFA, CXCR4, TERT, IL2, BCL2L1, and CDK1. Molecular docking of the 10 genes revealed their association with their respective receptors. Analysis by KEGG and GO has discovered that these related targets were more enriched in metabolic- and activation-related functions, which further confirmed that cellulose polysaccharides can also interact with cardiovascular diseases as molecules. In the end, we screened out six key genes that were more associated with the prognosis (CDK1, HSP90AA1, CXCR4, IL2, VEGFA, and TERT) and constructed a signature, which has a good predictive effect and has significant statistical significance. Our study is the first study to explore the interaction targets of cellulose and CHD and to construct a prognostic model. Our findings provide insights for future molecular design, drug development, and clinical trials.
Global publication trends and research hotspots of curcumin application in tumor: A 20-year bibliometric approach
Authors: Zhang Jun , Huang Yanran , Xu Jingtao , Zhao Runhan , Xiong Chuang , Habu Jiwa , Wang Yuping , Luo Xiaoji
Published: October 2022

Malignant tumor is a disease caused by the imbalance of cell growth and proliferation mechanism, which seriously threatens human health and life safety. However, side effects and drug resistance are the key factors that limit the efficacy of anti-tumor drugs. Therefore, it is urgent and necessary to explore and unearth natural, safe and effective chemosensitizers in tumor researches. Curcumin is the main active ingredient in Curcuma, which has anti-inflammatory, anti-inflammatory and anti-oxidation effects, and has inhibitory effects on a variety of cancers. Bibliometric analysis is a scientific and quantitative method to assess the published articles, which can help researchers to find the development trends and the research hotspots of a specific research field, providing the development of future research for researchers. This study searched the Web Science Core Collection (woscc) for publications related to curcumin and tumors from January 1, 2001 to December 31, 2021. The specific characteristics of 1707 publications were analyzed by using Microsoft Excel software, CiteSpace, Vosviewer and online analysis platform of literature metrology. China had the largest number of published articles, with 579 publications. Aggarwal BB’s articles total citations and average citations were the most. PLoS One had the largest number of publications, with 32 publications. The current research focuses on “nanoparticles”, “delivery”, “micells” and “doxorubicin”. At present, nano based drug delivery system to improve the bioavailability of curcumin and thus to treat tumors will be the focus of future research.
Experimental study of camptothecin combined with drug-eluting bead transarterial chemoembolization in the rabbit VX2 liver tumor model
Authors: Meng Fanguang , Li Yuyao , Liu Qian , Sun Liwei , Wang Hankang , Li Xiaodong , Li Guijie , Chen Feng
Published: October 2022

Drug-eluting bead transarterial chemoembolization (DEB-TACE) has been widely used in the treatment of liver cancer; however, the utilization rate of chemotherapeutic drugs after embolization is low. Chemotherapy resistance mediated by high nuclear factor E2-related factor 2 (NRF2) expression limits DEB-TACE efficacy. Camptothecin (CPT), an NRF2 inhibitor, exerts chemosensitizing effects. We designed a controlled experiment to determine the efficacy and feasibility of DEB-TACE combined with CPT for the treatment of rabbit VX2 hepatoma. DEB-TACE activated NRF2 expression in the tumor region. NRF2 activation could be inhibited by the combined use of CPT. After DEB-TACE alone, the tumor necrosis was incomplete, there were still highly active tumor residues, and the apparent diffusion coefficient (ADC) value, which was negatively correlated with tumor activity observed by magnetic resonance imaging, remained low. After DEB-TACE combined with CPT, the relative necrosis of the tumor was more complete, the ADC value was higher, and the ADC change was greater. The single application of CPT did not result in evident liver function and physical burden to the rabbits. The combined use of CPT and DEB-TACE did not significantly increase DEB-TACE imaging of liver function and body. In conclusion, CPT can also inhibit high NRF2 expression after DEB-TACE treatment. Combining CPT with DEB-TACE can improve the sensitivity of DEB-TACE in the treatment of VX2 tumors, improve the therapeutic effect, and has no evident toxic and side effects. This study explored the methods for enhancing the efficacy of DEB-TACE in liver cancer from a new perspective and performed model experiments, which provided a theoretical basis for future clinical treatment.
CUP-syndrome: Inguinal high grade serous ovarian carcinoma lymph node metastases with unknown primary origin – a case report and literature review
Authors: Restaino Stefano , Mauro Jessica , Zermano Silvia , Pellecchia Giulia , Mariuzzi Laura , Orsaria Maria , Titone Francesca , Biasioli Anna , Della Martina Monica , Andreetta Claudia , Poletto Elena , Arcieri Martina , Buda Alessandro , Driul Lorenza , Vizzielli Giuseppe
Published: October 2022

Objective

High-grade serous ovarian carcinoma (HGSC) often presents lymph node involvement. According to the paths of lymphatic drainage, the most common site of nodal metastasis is in the aortic area. However, pelvic lymph nodes are also involved and inguinal metastases are less frequent.

Methods

Our report concerns the case of a 78-year-old woman with an inguinal lymph node relapse of HGSC, with the prior positivity of a right inguinal lymph node, after the primary surgery. Ovaries and tubes were negative on histological examination. A comprehensive search of the literature published from January 2000 to October 2021 was conducted on PubMed and Scopus. The papers were selected following the PRISMA guidelines. Nine retrospective studies were evaluated.

Results

Overall, 67 studies were included in the initial search. Applying the screening criteria, 36 articles were considered eligible for full-text reading of which, after applying the exclusion criteria, 9 studies were selected for the final analysis and included in the systematic review. No studies were included for a quantitative analysis. We divided the results according to the relapse location: loco-regional, abdominal, and extra-abdominal recurrence.

Conclusions

Inguinal node metastasis is a rare but not unusual occurrence in HGSC. A reasonable level of suspicion should be maintained in patients with inguinal adenopathy and high CA125 values, especially in women with a history of gynecologic surgery, even in the absence of negative imaging for an ovarian origin.