bluuebunny/crossref_metadata_2025 huggingface dataset:
Host transcriptome and microbiome interactions in Holstein cattle under heat stress condition
Authors: Czech Bartosz , Wang Yachun , Wang Kai , Luo Hanpeng , Hu Lirong , Szyda Joanna
Published: November 2022

Climate change affects animal physiology. In particular, rising ambient temperatures reduce animal vitality due to heat stress and this can be observed at various levels which included genome, transcriptome, and microbiome. In a previous study, microbiota highly associated with changes in cattle physiology, which included rectal temperature, drooling score and respiratory score, were identified under heat stress conditions. In the present study, genes differentially expressed between individuals were selected representing different additive genetic effects toward the heat stress response in cattle in their production condition. Moreover, a correlation network analysis was performed to identify interactions between the transcriptome and microbiome for 71 Chinese Holstein cows sequenced for mRNA from blood samples and for 16S rRNA genes from fecal samples. Bioinformatics analysis was performed comprising: i) clustering and classification of 16S rRNA sequence reads, ii) mapping cows' transcripts to the reference genome and their expression quantification, and iii) statistical analysis of both data types—including differential gene expression analysis and gene set enrichment analysis. A weighted co-expression network analysis was carried out to assess changes in the association between gene expression and microbiota abundance as well as to find hub genes/microbiota responsible for the regulation of gene expression under heat stress. Results showed 1,851 differentially expressed genes were found that were shared by three heat stress phenotypes. These genes were predominantly associated with the cytokine-cytokine receptor interaction pathway. The interaction analysis revealed three modules of genes and microbiota associated with rectal temperature with which two hubs of those modules were bacterial species, demonstrating the importance of the microbiome in the regulation of gene expression during heat stress. Genes and microbiota from the significant modules can be used as biomarkers of heat stress in cattle.
2-hydroxyisobutyric acid (2-HIBA) modulates ageing and fat deposition in Caenorhabditis elegans
Authors: Schifano Emily , Conta Giorgia , Preziosi Adele , Ferrante Carino , Batignani Giovanni , Mancini Patrizia , Tomassini Alberta , Sciubba Fabio , Scopigno Tullio , Uccelletti Daniela , Miccheli Alfredo
Published: November 2022

High levels of 2-hydroxyisobutyric acid (2-HIBA) were found in urines of patients with obesity and hepatic steatosis, suggesting a potential involvement of this metabolite in clinical conditions. The gut microbial origin of 2-HIBA was hypothesized, however its actual origin and role in biological processes are still not clear. We investigated how treatment with 2-HIBA affected the physiology of the model organism Caenorhabditis elegans, in both standard and high-glucose diet (HGD) growth conditions, by targeted transcriptomic and metabolomic analyses, Coherent Anti-Stokes Raman Scattering (CARS) and two-photon fluorescence microscopy. In standard conditions, 2-HIBA resulted particularly effective to extend the lifespan, delay ageing processes and stimulate the oxidative stress resistance in wild type nematodes through the activation of insulin/IGF-1 signaling (IIS) and p38 MAPK pathways and, consequently, through a reduction of ROS levels. Moreover, variations of lipid accumulation observed in treated worms correlated with transcriptional levels of fatty acid synthesis genes and with the involvement of peptide transporter PEP-2. In HGD conditions, the effect of 2-HIBA on C. elegans resulted in a reduction of the lipid droplets deposition, accordingly with an increase of acs-2 gene transcription, involved in β-oxidation processes. In addition, the pro-longevity effect appeared to be correlated to higher levels of tryptophan, which may play a role in restoring the decreased viability observed in the HGD untreated nematodes.
Early-start antiplatelet therapy after operation in patients with spontaneous intracerebral hemorrhage and high risk of ischemic events (E-start): Protocol for a multi-centered, prospective, open-label, blinded endpoint randomized controlled trial
Authors: Wang Kaiwen , Mo Shaohua , Liu Qingyuan , Pu Jun , Huang Xiaobin , Kang Dezhi , Lin Fixin , Zou Dewei , Sun Xinguo , Ren Jinrui , Tong Xianzeng , Li Jiangan , Salman Rustam Al-Shahi , Wang Nuochuan , Guo Shuaiwei , Liu Yang , Zhang Yanan , Li Xiong , Wu Jun , Wang Shuo
Published: November 2022

Background

For severe spontaneous intracerebral hemorrhage (sSICH) patients with high risk of ischemic events, the incidence of postoperative major cardiovascular/cerebrovascular and peripheral vascular events (MACCPE) is notable. Although antiplatelet therapy is a potential way to benefit these patients, the severe hemorrhagic complications, e.g., intracranial re-hemorrhage, is a barrier for early starting antiplatelet therapy.

Objectives

This randomized controlled trial aims to identify the benefit and safety of early starting antiplatelet therapy after operation for sSICH patients with high risk of ischemic events.

Methods

This study is a multicenter, prospective, randomized, open-label, blinded-endpoint trial. We will enroll 250 sSICH patients with a high risk of ischemic events (including cerebral infarcts, transient ischemic attack, myocardial infarction, pulmonary embolism, and deep venous thrombosis). The participants will be randomized in a 1:1 manner to early-start group (start antiplatelet therapy at 3 days after operation) and normal-start group (start antiplatelet therapy at 30 days after operation). The early-start group will receive aspirin 100 mg daily. The control group will not receive antithrombotic therapy until 30 days after operation. The efficacy endpoint is the incidence of MACCPE, and the safety endpoint is the incidence of intracranial re-hemorrhage.

Discussion

The Early-Start antiplatelet therapy after operation in patients with spontaneous intracerebral hemorrhage trial (E-start) is the first randomized trial about early start antiplatelet therapy for operated sSICH patients with a high risk of ischemic events. This study will provide a new strategy and evidence for postoperative management in the future.

Clinical trial registration

ClinicalTrials.gov, identifier NCT04820972; Available at: https://clinicaltrials.gov/ct2/show/NCT04820972?term=NCT04820972&draw=2&rank=1.

Chinese Clinical Trial Registry, identifier ChiCTR2100044560; Available at: http://www.chictr.org.cn/showproj.aspx?proj=123277.
Discovery and validation of Ferroptosis-related molecular patterns and immune characteristics in Alzheimer’s disease
Authors: He Yi-Jie , Cong Lin , Liang Song-Lan , Ma Xu , Tian Jia-Nan , Li Hui , Wu Yun
Published: November 2022

Background

To date, the pathogenesis of Alzheimer’s disease is still not fully elucidated. Much evidence suggests that Ferroptosis plays a crucial role in the pathogenesis of AD, but little is known about its molecular immunological mechanisms. Therefore, this study aims to comprehensively analyse and explore the molecular mechanisms and immunological features of Ferroptosis-related genes in the pathogenesis of AD.

Materials and methods

We obtained the brain tissue dataset for AD from the GEO database and downloaded the Ferroptosis-related gene set from FerrDb for analysis. The most relevant Hub genes for AD were obtained using two machine learning algorithms (Least absolute shrinkage and selection operator (LASSO) and multiple support vector machine recursive feature elimination (mSVM-RFE)). The study of the Hub gene was divided into two parts. In the first part, AD patients were genotyped by unsupervised cluster analysis, and the different clusters’ immune characteristics were analysed. A PCA approach was used to quantify the FRGscore. In the second part: we elucidate the biological functions involved in the Hub genes and their role in the immune microenvironment by integrating algorithms (GSEA, GSVA and CIBERSORT). Analysis of Hub gene-based drug regulatory networks and mRNA-miRNA-lncRNA regulatory networks using Cytoscape. Hub genes were further analysed using logistic regression models.

Results

Based on two machine learning algorithms, we obtained a total of 10 Hub genes. Unsupervised clustering successfully identified two different clusters, and immune infiltration analysis showed a significantly higher degree of immune infiltration in type A than in type B, indicating that type A may be at the peak of AD neuroinflammation. Secondly, a Hub gene-based Gene-Drug regulatory network and a ceRNA regulatory network were successfully constructed. Finally, a logistic regression algorithm-based AD diagnosis model and Nomogram diagram were developed.

Conclusion

Our study provides new insights into the role of Ferroptosis-related molecular patterns and immune mechanisms in AD, as well as providing a theoretical basis for the addition of diagnostic markers for AD.
Estimated EEG functional connectivity and aperiodic component induced by vagal nerve stimulation in patients with drug-resistant epilepsy
Authors: Coa Roberta , La Cava Simone Maurizio , Baldazzi Giulia , Polizzi Lorenzo , Pinna Giovanni , Conti Carlo , Defazio Giovanni , Pani Danilo , Puligheddu Monica
Published: November 2022

Background

Vagal nerve stimulation (VNS) improves seizure frequency and quality of life in patients with drug-resistant epilepsy (DRE), although the exact mechanism is not fully understood. Previous studies have evaluated the effect of VNS on functional connectivity using the phase lag index (PLI), but none has analyzed its effect on EEG aperiodic parameters (offset and exponent), which are highly conserved and related to physiological functions.

Objective

This study aimed to evaluate the effect of VNS on PLI and aperiodic parameters and infer whether these changes correlate with clinical responses in subjects with DRE.

Materials and methods

PLI, exponent, and offset were derived for each epoch (and each frequency band for PLI), on scalp-derived 64-channel EEG traces of 10 subjects with DRE, recorded before and 1 year after VNS. PLI, exponent, and offset were compared before and after VNS for each patient on a global basis, individual scalp regions, and channels and separately in responders and non-responders. A correlation analysis was performed between global changes in PLI and aperiodic parameters and clinical response.

Results

PLI (global and regional) decreased after VNS for gamma and delta bands and increased for an alpha band in responders, but it was not modified in non-responders. Aperiodic parameters after VNS showed an opposite trend in responders vs. non-responders: both were reduced in responders after VNS, but they were increased in non-responders. Changes in aperiodic parameters correlated with the clinical response.

Conclusion

This study explored the action of VNS therapy from a new perspective and identified EEG aperiodic parameters as a new and promising method to analyze the efficacy of neuromodulation.
Sustainability of large-scale implementation of shared decision making with the SHARE TO CARE program
Authors: Stolz-Klingenberg Constanze , Bünzen Claudia , Coors Marie , Flüh Charlotte , Margraf Nils G. , Wehkamp Kai , Clayman Marla L. , Scheibler Fueloep , Wehking Felix , Rüffer Jens Ulrich , Schüttig Wiebke , Sundmacher Leonie , Synowitz Michael , Berg Daniela , Geiger Friedemann
Published: November 2022

Introduction

SHARE TO CARE (S2C) is a comprehensive implementation program for shared decision making (SDM). It is run at the University Hospital Schleswig-Holstein (UKSH) in Kiel, Germany, and consists of four combined intervention modules addressing healthcare professionals and patients: (1) multimodal training of physicians (2) patient activation campaign including the ASK3 method, (3) online evidence-based patient decision aids (4) SDM support by nurses. This study examines the sustainability of the hospital wide SDM implementation by means of the Neuromedical Center comprising the Departments of Neurology and Neurosurgery.

Methods

Between 2018 and 2020, the S2C program was applied initially within the Neuromedical Center: We implemented the patient activation campaign, trained 89% of physicians (N = 56), developed 12 patient decision aids and educated two decision coaches. Physicians adjusted the patients' pathways to facilitate the use of decision aids. To maintain the initial implementation, the departments took care that new staff members received training and decision aids were updated. The patient activation campaign was continued. To determine the sustainability of the initial intervention, the SDM level after a maintenance phase of 6–18 months was compared to the baseline level before implementation. Therefore, in- and outpatients received a questionnaire via mail after discharge. The primary endpoint was the “Patient Decision Making” subscale of the Perceived Involvement in Care Scale (PICSPDM). Secondary endpoints were an additional scale measuring SDM (CollaboRATE), and the PrepDM scale, which determines patients' perceived health literacy while preparing for decision making. Mean scale scores were compared using t-tests.

Results

Patients reported a significantly increased SDM level (PICSPDMp = 0.02; Hedges' g = 0.33; CollaboRATE p = 0.05; Hedges' g = 0.26) and improved preparation for decision making (PrepDM p = 0.001; Hedges' g = 0.34) 6–18 months after initial implementation of S2C.

Discussion

The S2C program demonstrated its sustainability within the Neuromedical Center at UKSH Kiel in terms of increased SDM and health literacy. Maintaining the SDM implementation required a fraction of the initial intensity. The departments took on the responsibility for maintenance. Meanwhile, an additional health insurance-based reimbursement for S2C secures the continued application of the program.

Conclusion

SHARE TO CARE promises to be suitable for long-lasting implementation of SDM in hospitals.
Effect of doctor–patient news-induced moral judgments on pain empathy for doctors and patients in China
Authors: Li HuiLing , Zhao Dong , Yang BinJie , Zhao YuHui , Huang HanZhi , Jiang Huan , Chen MeiFen , Zhou Qiang , Ying Liang
Published: November 2022

Objective

Pain empathy’s preferential nature tends to trigger prejudice and intergroup conflicts. Given the current degree of proliferation of doctor–patient conflict news in China, this study aims to determine whether readers of doctor–patient news-initiated moral judgments prefer pain empathy for doctors or patients.

Materials and methods

This study utilized localized doctor–patient news with high or low moral performance (based on morality ratings of patients’ behaviors) as moral-judgment-eliciting materials, and painful pictures as pain empathy-eliciting materials. The event-related potential (ERP) technique was utilized to assess moral judgment’s effect on the cognitive empathy component and to investigate electroencephalogram signals’ accuracy in classifying four brain response patterns when facing doctor or patient is experiencing or not experiencing pain.

Results

Under low moral text material, participants exhibited smaller mean wave amplitude of positive 300 (P3) and late positive potential (LPP) to painful pictures than non-painful pictures when facing patients; under high moral text material, participants exhibited larger mean wave amplitude of P3 and LPP to painful pictures than non-painful pictures when facing doctors. Electroencephalogram (EEG) signals’ classification accuracy was significant in 0–1,000 ms in both high and low moral judgments, but the classification accuracy was higher in low moral judgments in some cognitive empathy stages (0.51, 0.53–0.55, 0.66–0.79, and 0.88–1 s).

Conclusion

Under low moral judgment, individuals pay less attention to the patient’s (perpetrator’s) pain; under high moral judgment, individuals empathize with the doctor (the person praised), showing that news-induced moral judgment can sway readers’ empathy for different social groups. In cognitive empathy, individuals’ brain representations are more discriminatory under low than high moral judgments when confronted with pain by doctors and patients, which provides insight into objectively recognizing group bias.
Mapping white matter structural covariance connectivity for single subject using wavelet transform with T1-weighted anatomical brain MRI
Authors: Wang Xun-Heng , Zhao Bohan , Li Lihua
Published: November 2022

Introduction

Current studies of structural covariance networks were focused on the gray matter in the human brain. The structural covariance connectivity in the white matter remains largely unexplored. This paper aimed to build novel metrics that can infer white matter structural covariance connectivity, and to explore the predictive power of the proposed features.

Methods

To this end, a cohort of 315 adult subjects with the anatomical brain MRI datasets were obtained from the publicly available Dallas Lifespan Brain Study (DLBS) project. The 3D wavelet transform was applied on the individual voxel-based morphology (VBM) volume to obtain the white matter structural covariance connectivity. The predictive models for cognitive functions were built using support vector regression (SVR).

Results

The predictive models exhibited comparable performance with previous studies. The novel features successfully predicted the individual ability of digit comparison (DC) (r = 0.41 ± 0.01, p < 0.01) and digit symbol (DSYM) (r = 0.5 ± 0.01, p < 0.01). The sensorimotor-related white matter system exhibited as the most predictive network node. Furthermore, the node strengths of sensorimotor mode were significantly correlated to cognitive scores.

Discussion

The results suggested that the white matter structural covariance connectivity was informative and had potential for predictive tasks of brain-behavior research.
The associations of cerebrospinal fluid biomarkers with cognition, and rapid eye movement sleep behavior disorder in early Parkinson’s disease
Authors: Tao Mingzhu , Dou Kaixin , Xie Yijie , Hou Binghui , Xie Anmu
Published: November 2022

Background

In Parkinson’s disease (PD), levels of cerebrospinal fluid (CSF) biomarkers and progression of non-motor symptoms are associated, but the specifics are not yet clear.

Objective

The aim of this study was to investigate the associations of non-motor symptoms with CSF biomarkers in PD.

Materials and methods

We assessed 487 individuals from the Parkinson’s Progression Markers Initiative (PPMI), consisting of 155 healthy controls (HCs) and 332 individuals with PD. Patients with PD were grouped according to non-motor symptoms and compared CSF α-synuclein (α-syn), amyloid-beta 1-42 (Aβ1–42), and total tau (t-tau) levels. Multiple linear regressions were used in baseline analysis and linear mixed-effects models in longitudinal analysis. Analyses of mediating effects between cognition and CSF biomarkers were also performed.

Results

At baseline, PD patients with cognitive impairment (PDCI) exhibited significantly lower CSF α-syn (β = −0.1244; P = 0.0469), Aβ (β = −0.1302; P = 0.0447), and t-tau (β = −0.1260; P = 0.0131) levels than PD patients without cognitive impairment (PDCU). Moreover, a faster decline of α-syn (β = −0.2152; P = 0.0374) and Aβ (β = −0.3114; P = 0.0023) and a faster rise of t-tau (β = −0.1534; P = 0.0274) have been found in longitudinal analysis. The Aβ positive group showed an earlier decline in cognitive performance (β = −0.5341; P = 0.0180) compared with the negative Aβ group in both analyses. In addition, we found that PD patients with probable rapid eye movement sleep behavior disorder (pRBD) showed decreased CSF α-syn (β = −0.1343; P = 0.0033) levels. Finally, mediation analysis demonstrated that olfactory function partially mediated the relationship between cognition and CSF biomarkers levels.

Conclusion

Our study shows that CSF biomarkers are associated with cognition at baseline and longitudinally. Cognitive impairment is more severe in patients with a heavier Aβ burden. CSF α-syn decreased in PD patients with pRBD. This study suggests that early recognition of the increased risk of non-motor symptoms is important for disease surveillance and may be associated with the pathological progression of CSF markers.
Prognostic value of the geriatric nutritional index in colorectal cancer patients undergoing surgical intervention: A systematic review and meta-analysis
Authors: Mao Yiqing , Lan Jiarong
Published: November 2022

Background

We reviewed the literature to assess the prognostic ability of the geriatric nutritional risk index (GNRI) for patients with colorectal cancer (CRC) undergoing curative surgery.

Methods

The online databases of PubMed, CENTRAL, ScienceDirect, Embase, and Google Scholar were searched for articles reporting the relationship between GNRI and outcomes in CRC patients. English language studies were searched up to 28th April 2022.

Results

Ten studies with 3802 patients were included. Meta-analysis indicated that patients with low GNRI had significantly poor overall survival (HR: 2.41 95% CI: 1.72, 3.41 I2 = 68%) and disease-free survival (HR: 1.92 95% CI: 1.47, 2.49 I2 = 49%) as compared to those with high GNRI. The meta-analysis also indicated a significantly higher risk of complications with low GNRI as compared to high GNRI (HR: 1.98 95% CI: 1.40, 2.82 I2 = 0%). The results did not change on subgroup analysis based on study location, age group, GNRI cut-off, and sample size.

Conclusion

Current evidence indicates that GNRI can be a valuable prognostic indicator for CRC patients undergoing surgical intervention. Patients with low GNRI have poor overall and disease-free survival and a higher incidence of complications. Clinicians could use this simple indicator to stratify patients and formulate personalized treatment plans.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier (CRD42022328374).
The addition of radiotherapy to breast-conserving surgery improves survival for elderly patients with early breast cancer
Authors: Yang Shi-Ping , Tan Lu-Lu , Zhou Ping , Lian Chen-Lu , Wu San-Gang , He Zhen-Yu
Published: November 2022

Purpose

To evaluate whether adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) was associated with better survival among elderly (≥70 years) breast cancer patients with T1-2N0 and estrogen receptor (ER) positive disease.

Methods

We included patients who met the inclusion criteria between 2010 and 2014 from the Surveillance, Epidemiology, and End Results program. Patients were subdivided into three groups based on surgery and RT: BCS alone, BCS plus RT, and refusal of RT. The primary outcomes were breast cancer-specific survival (BCSS) and overall survival (OS). Chi-squared tests, Kaplan–Meier method, and Multivariate Cox regression analysis were used for statistical analysis. Propensity score matching (PSM) was performed to minimize the potential selection bias.

Results

A total of 26586 patients were included in this analysis. The median follow-up was 66 months. Of these patients, 15591 (58.6%) patients received RT, RT was recommended but not performed due to patient refusal for 1270 (4.8%) patients, and RT was not recommended for 9725 (36.6%) patients. The 5-year BCSS was 98.3% for patients receiving RT, 97.1% for patients refusal of RT, and 96.4% for patients not recommended RT (P<0.001). The 5-year OS was 88.6% for patients receiving RT, 77.6% for patients who refused RT, and 72.1% for patients not recommended RT (P<0.001). Multivariate Cox regression analyses showed that patients who received adjuvant RT after BCS had significantly better BCSS (hazard ratio [HR] 0.523, 95%confidence interval [CI] 0.447-0.612, P<0.001) and OS (HR 0.589, 95%CI 0.558-0.622, P<0.001) compared to those without RT. A total of 7721 pairs of patients were matched successfully between those with and without RT using PSM. The results also showed that patients who received RT after BCS had significantly better BCSS (HR 562, 95%CI 0.467-0.676, P<0.001) and OS (HR 0.612, 95%CI 0.0.575-0.652, P<0.001) compared to those without RT.

Conclusions

These data suggest that individual counseling is important for treatment decision-making in elderly breast cancer patients with T1-2N0 and ER-positive disease. Given the relatively lower toxicity of modern RT techniques, adjuvant RT should be recommended in patients with high life expectancy.
Overview of meningococcal epidemiology and national immunization programs in children and adolescents in 8 Western European countries
Authors: Pinto Cardoso Gaëlle , Lagrée-Chastan Marion , Caseris Marion , Gaudelus Joël , Haas Hervé , Leroy Jean-Philippe , Bakhache Pierre , Pujol Jean-François , Werner Andreas , Dommergues Marie-Aliette , Pauquet Emilie , Pinquier Didier
Published: November 2022

Background

In Europe, meningococcal (Men) vaccines are available against 5 of the 6 serogroups responsible of nearly all cases of invasive meningococcal disease (IMD). Meningococcal vaccination has been introduced in the national immunization programs (NIPs) for children and adolescents of numerous European countries, but with no consistent strategy across countries.

Objectives

To describe IMD epidemiology, NIPs, and vaccination coverage rates (VCRs) in children and adolescents in 8 Western European countries.

Methods

Epidemiological data (from 1999 to 2019), NIPs regarding meningococcal vaccination status, and VCRs were collected from the European Centre for Disease Prevention and Control (ECDC) and/or national websites.

Results

MenB was the most common serogroup. In Belgium, Spain, France, the Netherlands, the United Kingdom (UK), and Portugal, incidence was greater for MenW than MenC. In 2019, MenB risk was covered in 2 countries (Italy, UK). MenC risk was covered in all countries, via MenC only (countries: N = 3), MenACWY only (N = 2), or MenC (infants/children) and MenACWY (adolescents) (N = 3) vaccination. VCRs were higher in children than adolescents.

Conclusion

Our study confirmed the diversity of NIPs, including in neighboring European countries with similar factors like economic resources and epidemiological risk, thus indicating that other factors underlie NIPs. Convergence toward a more common immunization program including MenACWY and MenB vaccination would promote equity and safe travel regarding infectious diseases for young people, and possibly improve the understanding of vaccination by patients and healthcare professionals.
Case report: Prenatal diagnosis of fetal non-compaction cardiomyopathy with bradycardia accompanied by de novo CALM2 mutation
Authors: Zhang Wen , Dai Xiaohui , Liu Hanmin , Li Lei , Zhou Shu , Zhu Qi , Chen Jiao
Published: November 2022

We herein report what appears to be the first case of fetal non-compaction cardiomyopathy in both ventricles accompanied by a mutation in the calmodulin gene (CALM2). A 25-year-old woman was referred to our hospital at 25+1 weeks of gestation for evaluation of fetal defects. Prenatal echocardiography showed biventricular non-compaction cardiomyopathy with sinus bradycardia. After termination of the pregnancy, fetal biventricular non-compaction cardiomyopathy was confirmed by autopsy and histopathologic examination. Additionally, whole-exome sequencing of genomic DNA demonstrated a de novo heterozygous mutation (c.389A > G; p.D130G) in CALM2, whereas the parents were normal. In this case report, we highlight the importance of prenatal ultrasound and genetic testing in fetal non-compaction cardiomyopathy with arrhythmia.
The role and mechanism of NLRP3 inflammasome-mediated astrocyte activation in dehydrocorydaline against CUMS-induced depression
Authors: Fang Yu , Guo Hong , Wang Qiannan , Liu Congcong , Ge Shuyi , Yan Bohua
Published: November 2022

Background: Depression is a common and potentially life-threatening mental illness, and currently, there is a lack of effective treatment. It has been reported that dehydrocorydaline (DHC) can inhibit monoamine transporter uptake in depressed CUMS mice, but more possible mechanisms of action remain to be further studied.

Methods: C57BL/6 mice were exposed to chronic unpredictable mild stress (CUMS) for five consecutive weeks. The mice were administrated with dehydrocorydaline or fluoxetine (FLU) for four consecutive weeks. Behavioral tests including sucrose preference test (SPT), tail suspension test (TST), and forced swimming test (FST) were applied. In parallel, hematoxylin and eosin (H&E) staining and Nissl staining were used to explore the effect of DHC on pathological changes in the hippocampus. The concentrations of depression-related factors (5-HT and DA) and inflammatory factors (TNF-α, IL-6, and IL-1β) in the hippocampus and serum were assessed by ELISA assay. NLRP3 inflammasome pathway-related proteins (NLRP3, IL-18, IL-1 IL-1α, and caspase-1) were detected by western blot. The activation of microglia and astrocytes was subjected to immunofluorescent staining. Additionally, microglia were treated with DHC (100 mg/L) for 24 h following incubation with 100 ng/ml LPS for 12 h. ov-NC or ov-NLRP3 plasmid was transfected into microglia 6 h before LPS induction for exploring the effect of NLRP3 overexpression on DHC-inhibited microglia activation. Then, conditioned media of microglia were collected from each group, followed by intervention of astrocytes for 24 h to explore the effect of NLRP3 overexpression of microglia on astrocyte activation.

Results:In vivo administration of DHC was found to ameliorate depressive-like behaviors and attenuate neuron damage of CUMS mice. DHC increased neurotransmitter concentration, reduced the proinflammatory factor levels, attenuated NLRP3 inflammasome activation, and decreased A1 astrocyte and microglia activation in the hippocampus of CUMS mice. Furthermore, in vivo results showed that activated microglia induced activation of A1 astrocytes but not A2 astrocytes.

Conclusion: Taken together, we provided evidence that DHC exhibited antidepressive effects on CUMS mice possibly via NLRP3 inflammasome-mediated astrocyte activation.
The role of IL-6 in coronavirus, especially in COVID-19
Authors: Wang Xinyi , Tang Guozheng , Liu Yuchen , Zhang Lizhi , Chen Bangjie , Han Yanxun , Fu Ziyue , Wang Liuning , Hu Guangzhi , Ma Qing , Sheng Shuyan , Wang Jianpeng , Hu Xinyang , Shao Song
Published: November 2022

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infects both people and animals and may cause significant respiratory problems, including lung illness: Corona Virus Disease 2019 (COVID-19). Swabs taken from the throat and nose of people who have the illness or are suspected of having it have shown this pathogenic virus. When SARS-CoV-2 infects the upper and lower respiratory tracts, it may induce moderate to severe respiratory symptoms, as well as the release of pro-inflammatory cytokines including interleukin 6 (IL-6). COVID-19-induced reduction of IL-6 in an inflammatory state may have a hitherto undiscovered therapeutic impact. Many inflammatory disorders, including viral infections, has been found to be regulated by IL-6. In individuals with COVID-19, one of the primary inflammatory agents that causes inflammatory storm is IL-6. It promotes the inflammatory response of virus infection, including the virus infection caused by SARS-CoV-2, and provides a new diagnostic and therapeutic strategy. In this review article, we highlighted the functions of IL-6 in the coronavirus, especially in COVID-19, showing that IL-6 activation plays an important function in the progression of coronavirus and is a rational therapeutic goal for inflammation aimed at coronavirus.
Primary resistance to first- and second-generation ALK inhibitors in a non-small cell lung cancer patient with coexisting ALK rearrangement and an ALK F1174L-cis-S1189C de novo mutation: A case report
Authors: Zhao Jiuzhou , Li Xiang , Fan Ruizhe , Qin Yaping , Wang Zhizhong , Wang Bo , Li Shaomei , Fan Jianfeng , Wu Xinxin , Liu Hongxia , Guan Yuping , Liang Yinfeng , Zhang Xiao , Guo Yongjun
Published: November 2022

The effectiveness of the tyrosine kinase inhibitor ALK (TKI) for non-small cell lung cancer has been confirmed. However, resistance to ALK-TKIs seems inevitable. Mutations in the ALK kinase domain have been reported as an important mechanism of acquired resistance to ALK therapy. However, patients with de novo ALK kinase domain mutations and ALK rearrangements who were not treated with ALK inhibitors have rarely been reported. Here, we report a case of primary drug resistance to first- and second-generation ALK inhibitors in a NSCLC patient with ALK-rearrangement. The next-generation sequencing test of the pathological biopsy showed that the de novo ALK kinase domain mutation F1174L-cis-S1189C may be the cause of primary drug resistance.
Exploration of the effect of Celastrol on protein targets in nasopharyngeal carcinoma: Network pharmacology, molecular docking and experimental evaluations
Authors: Ling Junjun , Huang Yu , Sun Zhen , Guo Xiaopeng , Chang Aoshuang , Pan Jigang , Zhuo Xianlu
Published: November 2022

Background: Celastrol, an important extract of Tripterygium wilfordii, shows strong antitumor activity in a variety of tumors including nasopharyngeal carcinoma (NPC). However, little is known about its targets in NPC. We aimed to screen the key gene targets of Celastrol in the treatment of NPC by means of in silico analyses (including network pharmacology and molecular docking) and experimental evaluations.

Methods: The main target genes of Celastrol and the genes related to NPC were obtained by retrieving the relevant biological databases, and the common targets were screened. Protein-protein interaction analysis was used to screen the hub genes. Then, a “compound-target-disease” network model was created and molecular docking was used to predict the binding of Celastrol to the candidate hub proteins. Afterward, the expression changes of the candidate genes under the administration of Celastrol were verified in vitro and in vivo.

Results: Sixty genes common to Celastrol and NPC were screened out, which may be related to numerous biological processes such as cell proliferation, apoptosis, and tube development, and enriched in various pathways such as PI3K- Akt, EGFR tyrosine kinase inhibitor resistance, and Apoptosis. The tight binding ability of the candidate hub proteins (TNF, VEGFA, and IL6) to Celastrol was predicted by molecular docking [Docking energy: TNF, −6.08; VEGFA,−6.76; IL6,−6.91(kcal/mol)]. In vitro experiments showed that the expression of TNF and VEGFA decreased while the expression of IL6 increased in NPC cells (CNE2 and HONE1) treated with Celastrol. In vivo experiments suggested that Celastrol significantly reduced the weight and volume of the transplanted tumors in tumor-bearing mice in vivo. The expression of TNF, VEGFA, and IL6 in the transplanted tumor cells could be regulated by using Celastrol, and the expression trends were consistent with the in vitro model.

Conclusion: Several gene targets have been filtered out as the core targets of Celastrol in the treatment of NPC, which might be involved in a variety of signaling pathways. Hence, Celastrol may exert its anti-NPC activity through multiple targets and multiple pathways, which will provide new clues for further research. Future experiments are warranted to validate the findings.
Effects of abiotic stresses on the expression of chitinase-like genes in Acyrthosiphon pisum
Authors: Li Chunchun , Ul Haq Inzamam , Khurshid Aroosa , Tao Yan , Quandahor Peter , Zhou Jing-Jiang , Liu Chang-Zhong
Published: November 2022

Insect chitinases play a crucial part to digest chitin in the exoskeleton during the molting process. However, research on insect chitinase related to the environmental stress response is very limited. This study was the first conducted to expression analysis of chitinase- related genes in A. pisum under abiotic stresses. Here, we identified five chitinase-like proteins (ApIDGF, ApCht3, ApCht7, ApCht10 and ApENGase), and clustered them into five groups (group II, III, V, Ⅹ, and ENGase). Developmental expression analysis revealed that the five A. pisum chitinase-related genes were expressed at whole developmental stages with different relative expression patterns. When aphids were exposed to various abiotic stresses including temperature, insecticide and the stress 20-hydroxyecdysone (20E), all five chitinase genes were differentially expressed in A. pisum. The results showed that insecticide such as imidacloprid down-regulated the expression of these five Cht-related genes. Analysis of temperature stress of A. pisum chitinase suggested that ApCht7 expression was high at 10°C, which demonstrates its important role in pea aphids under low temperature. Conversely, ApCht10 was more active under high temperature stress, as it was significantly up-regulated at 30°C. Besides, 20E enhanced ApCht3 and ApCht10 expression in A. pisum, but reduced ApCht7 expression. These findings provide basic information and insights for the study of the role of these genes under abiotic stress, which advances our knowledge in the management of pea aphids under multiple stresses.
Nutrient additions to seagrass seed planting improve seedling emergence and growth
Authors: Unsworth R.K.F. , Rees S.C. , Bertelli C.M. , Esteban N.E. , Furness E.J. , Walter B.
Published: November 2022

To maximize the opportunities of seagrass as a nature-based solution requires restoration to occur on a large scale. New methods and knowledge are required that can solve ecological bottlenecks, improving its reliability and effectiveness. Although there is increasing interest in the use of seeds for seagrass restoration there exists a limited understanding of how best to plant them with the most knowledge on germination and seedling emergence coming from laboratory studies. Here we present the results of a novel field study on the emergence success of seeds of the seagrass Zostera marina when subjected to varied planting treatments. Seeds were planted into hessian bags according to a factorial design of three treatments (sediment type, detritus addition, and nutrient addition). By adding nutrients to natural sediment, the present study provides some evidence of seagrass shoot emergence and maximum shoot length doubling. The present study provides evidence that even in heavily nutrient-rich environments, seagrass sediments may require additional nutrients to improve seedling emergence and growth. It also highlights the highly variable nature of planting seagrass seeds in shallow coastal environments. Critically this study provides increasing levels of evidence that small subtleties in the method can have large consequences for seagrass restoration and that for restoration to scale to levels that are relevant for nature-based solutions there remain many unknowns that require consideration.
Validation of KASP markers associated with cassava mosaic disease resistance, storage root dry matter and provitamin A carotenoid contents in Ugandan cassava germplasm
Authors: Esuma Williams , Eyoo Oscar , Gwandu Francisca , Mukasa Settumba , Alicai Titus , Ozimati Alfred , Nuwamanya Ephraim , Rabbi Ismail , Kawuki Robert
Published: November 2022

Introduction

The intrinsic high heterozygosity of cassava makes conventional breeding ineffective for rapid genetic improvement. However, recent advances in next generation sequencing technologies have enabled the use of high-density markers for genome-wide association studies, aimed at identifying single nucleotide polymorphisms (SNPs) linked to major traits such as cassava mosaic disease (CMD) resistance, dry matter content (DMC) and total carotenoids content (TCC). A number of these trait-linked SNPs have been converted to Kompetitive allele-specific polymerase chain reaction (KASP) markers for downstream application of marker assisted selection.

Methods

We assayed 13 KASP markers to evaluate their effectiveness in selecting for CMD, DMC and TCC in 1,677 diverse cassava genotypes representing two independent breeding populations in Uganda.

Results

Five KASP markers had significant co-segregation with phenotypes; CMD resistance (2), DMC (1) and TCC (2), with each marker accounting for at least 30% of the phenotypic variation. Markers located within the chromosomal regions for which strong marker-trait association loci have been characterised (chromosome 12 markers for CMD, chromosome 1 markers for DMC and TCC) had consistently superior ability to discriminate the respective phenotypes.

Discussion

The results indicate varying discriminatory abilities of the KASP markers assayed and the need for their context-based use for MAS, with PSY2_572 particularly effective in selecting for high TCC. Availing the effective KASP markers on cost-effective genotyping platforms could facilitate practical implementation of marker-assisted cassava breeding for accelerated genetic gains for CMD, DMC and provitamin A carotenoids.
Response of physiological characteristics of ecological restoration plants to substrate cement content under exogenous arbuscular mycorrhizal fungal inoculation
Authors: Shu Qian , Xia Dong , Ma Yueyang , Zhang Yang , Luo Ting , Ma Jiaxin , Liu Fang , Yan Shuxing , Liu Daxiang
Published: November 2022

Introduction

In order to solve the inhibition of alkaline environment on plants growth at the initial stage of Eco-restoration of vegetation concrete technology, introducing AMF into vegetation concrete substrate is an effective solution.

Methods

In this study, Glomus mosseae (GM), Glomus intraradices (GI) and a mixture of two AMF (MI) were used as exogenous inoculation agents. Festuca elata and Cassia glauca were selected as host plants to explore the relationship between the physiological characteristics of plants and the content of substrate cement under exogenous inoculation of AMF.

Results

The experiment showed that, for festuca elata, the maximum mycorrhizal infection rates of inoculation with GM, MI were when the cement contents ranged 5–8% and that of GI inoculation was with the cement contents ranging 5–10%. Adversely, for Cassia glauca, substrate cement content had little effect on the root system with the exogenous inoculation of AMF. Compared with CK, the effects of AMF inoculation on the physiological characteristics of the two plants were different. When the cement content was the highest (10% and 8% respectively), AMF could significantly increase(p<0.05) the intercellular CO2 concentration (Ci) of Festuca elata. Moreover, for both plants, single inoculation was more effective than mixed inoculation. When the cement content was relatively low, the physiological characteristics of Cassia glauca were promoted more obviously by the inoculation of GI. At higher cement content level, inoculation of GM had a better effect on the physiological characteristics of the two plants.

Conclusion

The results suggest that single inoculation of GM should be selected to promote the growth of Festuca elata and Cassia glauca in higher alkaline environment.
Potential distribution of three types of ephemeral plants under climate changes
Authors: Lan Zhang , Huiliang Liu , Hongxiang Zhang , Yanfeng Chen , Lingwei Zhang , Kudusi Kawushaer , Taxmamat Dilxadam , Yuanming Zhang
Published: November 2022

Background

Arid and semi-arid regions account for about 40% of the world’s land surface area, and are the most sensitive areas to climate change, leading to a dramatic expansion of arid regions in recent decades. Ephemeral plants are crucial herbs in this area and are very sensitive to climate change, but it is still unclear which factors can determine the distribution of ephemeral plants and how the distribution of ephemeral plants responds to future climate change across the globe.

Aims

Understanding the impact of climate change on ephemeral plant distribution is crucial for sustainable biodiversity conservation.

Methods

This study explored the potential distribution of three types of ephemeral plants in arid and semi-arid regions (cold desert, hot desert, and deciduous forest) on a global scale using the MaxEnt software. We used species global occurrence data and 30 environmental factors in scientific collections.

Results

Our results showed that (1) the average value of the area under the receiver operating curve (AUC) of each species was higher than 0.95, indicating that the MaxEnt model’s simulation accuracy for each species was good; (2) distributions of cold desert and deciduous forest species were mainly determined by soil pH and annual mean temperature; the key factor that determines the distribution of hot desert species was precipitation of the driest month; and (3) the potential distribution of ephemeral plants in the cold desert was increased under one-third of climate scenarios; in the hot desert, the potential suitable distribution forAnastatica hierochunticawas decreased in more than half of the climate scenarios, butTrigonella arabicawas increased in more than half of the climate scenarios. In deciduous forests, the ephemeral plantCrocus alatavicusdecreased in nearly nine-tenths of climate scenarios, andGagea filiformiswas increased in 75% of climate scenarios.

Conclusions

The potential suitable distributions of ephemeral plants in the different ecosystems were closely related to their specific adaptation strategies. These results contribute to a comprehensive understanding of the potential distribution pattern of some ephemeral plants in arid and semi-arid ecosystems.
Potassium deficiency causes more nitrate nitrogen to be stored in leaves for low-K sensitive sweet potato genotypes
Authors: Liu Jingran , Xia Houqiang , Gao Yang , Pan Dongyu , Sun Jian , Liu Ming , Tang Zhonghou , Li Zongyun
Published: November 2022

In order to explore the effect of potassium (K) deficiency on nitrogen (N) metabolism in sweet potato (Ipomoea batatas L.), a hydroponic experiment was conducted with two genotypes (Xushu 32, low-K-tolerant; Ningzishu 1, low-K-sensitive) under two K treatments (−K, <0.03 mM of K+; +K, 5 mM of K+) in the greenhouse of Jiangsu Normal University. The results showed that K deficiency decreased root, stem, and leaf biomass by 13%–58% and reduced whole plant biomass by 24%–35%. Compared to +K, the amount of K and K accumulation in sweet potato leaves and roots was significantly decreased by increasing root K+ efflux in K-deficiency-treated plants. In addition, leaf K, N, ammonium nitrogen (NH4+–N), or nitrate nitrogen (NO3−–N) in leaves and roots significantly reduced under K deficiency, and leaf K content had a significant quadratic relationship with soluble protein, NO3−–N, or NH4+–N in leaves and roots. Under K deficiency, higher glutamate synthase (GOGAT) activity did not increase amino acid synthesis in roots; however, the range of variation in leaves was larger than that in roots with increased amino acid in roots, indicating that the transformation of amino acids into proteins in roots and the amino acid export from roots to leaves were not inhibited. K deficiency decreased the activity of nitrate reductase (NR) and nitrite reductase (NiR), even if the transcription level of NR and NiR increased, decreased, or remained unchanged. The NO3−/NH4+ ratio in leaves and roots under K deficiency decreased, except in Ningzishu 1 leaves. These results indicated that for Ningzishu 1, more NO3− was stored under K deficiency in leaves, and the NR and NiR determined the response to K deficiency in leaves. Therefore, the resistance of NR and NiR activities to K deficiency may be a dominant factor that ameliorates the growth between Xushu 32 and Ningzishu 1 with different low-K sensitivities.