bluuebunny/crossref_metadata_2025 huggingface dataset:
rDNA and mtDNA analysis for the identification of genetic characters in the hybrid grouper derived from hybridization of Cromileptes altivelis (female) × Epinephelus lanceolatus (male)
Authors: Cao Liu , Chen Pan , Hou Xingrong , Ma Jun , Yang Ning , Lu Yan , Huang Hai
Published: January 2024

Background

Hybridization is a useful strategy to produce offspring with more desirable phenotypic characteristics than those of parents. The hybrid grouper derived from the cross of Cromileptes altivelis (♀, 2n = 48) with Epinephelus lanceolatus (♂, 2n = 48) exhibits improved growth compared with its female parent, which makes it valuable to aquaculture. However, the genetic traits of the hybrid grouper are poorly understood.

Results

The observations showed that the hybrid grouper was diploid (2n = 48) and displayed intermediate morphology with the parent's measurable characteristics. The ribosomal DNA (rDNA) and mitochondria DNA (mtDNA) were characterized at molecular and phylogenetic level. High similarity and low genetic distance of 5S rDNA and mtDNA sequences between the hybrid grouper and C. altivelis showed that the hybrid grouper had a closer genetic relationship with female parents. The reconstructed phylogenetic tree based on COI gene and D-loop region of mtDNA recovered that mtDNA was maternally inherited in the hybrid grouper. Additionally, the DNA methylation level of 5S rDNA intergenic spacers (IGS) sequence was tested in here. The results showed that the DNA methylation status of the hybrid grouper was significantly lower than that of C. altivelis.

Conclusion

Results of this study provide important data on the genetic characteristics of the hybrid derived from the cross of C. altivelis and E. lanceolatus, and contribute the knowledge of both evolution and marine fish breeding.
Spatial and temporal characterization of the rich fraction of plastid DNA present in the nuclear genome of Moringa oleifera reveals unanticipated complexity in NUPTs´ formation
Authors: Marczuk-Rojas Juan Pablo , Álamo-Sierra Angélica María , Salmerón Antonio , Alcayde Alfredo , Isanbaev Viktor , Carretero-Paulet Lorenzo
Published: January 2024

Background

Beyond the massive amounts of DNA and genes transferred from the protoorganelle genome to the nucleus during the endosymbiotic event that gave rise to the plastids, stretches of plastid DNA of varying size are still being copied and relocated to the nuclear genome in a process that is ongoing and does not result in the concomitant shrinking of the plastid genome. As a result, plant nuclear genomes feature small, but variable, fraction of their genomes of plastid origin, the so-called nuclear plastid DNA sequences (NUPTs). However, the mechanisms underlying the origin and fixation of NUPTs are not yet fully elucidated and research on the topic has been mostly focused on a limited number of species and of plastid DNA.

Results

Here, we leveraged a chromosome-scale version of the genome of the orphan crop Moringa oleifera, which features the largest fraction of plastid DNA in any plant nuclear genome known so far, to gain insights into the mechanisms of origin of NUPTs. For this purpose, we examined the chromosomal distribution and arrangement of NUPTs, we explicitly modeled and tested the correlation between their age and size distribution, we characterized their sites of origin at the chloroplast genome and their sites of insertion at the nuclear one, as well as we investigated their arrangement in clusters. We found a bimodal distribution of NUPT relative ages, which implies NUPTs in moringa were formed through two separate events. Furthermore, NUPTs from every event showed markedly distinctive features, suggesting they originated through distinct mechanisms.

Conclusions

Our results reveal an unanticipated complexity of the mechanisms at the origin of NUPTs and of the evolutionary forces behind their fixation and highlight moringa species as an exceptional model to assess the impact of plastid DNA in the evolution of the architecture and function of plant nuclear genomes.
Association of systemic immunity-inflammation index with metabolic syndrome in U.S. adult: a cross-sectional study
Authors: Zeng Peng , Jiang Cheng , Liu Anbang , Yang Xinyuan , Lin Feng , Cheng Lingli
Published: January 2024

Background

Metabolic syndrome (MetS) is a pathological condition characterized by the abnormal clustering of several metabolic components and has become a major public health concern. We aim to investigate the potential link of Systemic immunity-inflammation index (SII) on MetS and its components.

Methods and result

Weighted multivariable logistic regression was conducted to assess the relationship between SII and MetS and its components. Restricted cubic spline (RCS) model and threshold effect analysis were also performed. A total of 6,999 U.S. adults were enrolled. Multivariate model found that SII were positively associated with MetS (OR = 1.18;95CI%:1.07–1.30) and hypertension (OR = 1.22; 95CI%:1.12–1.34) in a dose-dependent manner. When SII was converted into a categorical variable, the risk of MetS increased by 36% and the risk of hypertension increased by 53% in the highest quantile of SIIs. The RCS model confirmed linear associations between SII and MetS, as well as a non-linear association between SII and certain components of MetS, including hypertension, hyperglycemia, low HDL, and hyperlipidemia. Meanwhile, the relationship between SII and hypertension presents a J-shaped curve with a threshold of 8.27, above which the risk of hypertension increases. Furthermore, in MetS and hypertension, age, sex, body mass index (BMI), and race were not significantly associated with this positive association based on subgroup analyses and interaction tests(p for interaction > 0.05).

Conclusions

The present study indicated that there was a higher SII association with an increased risk of MetS and hypertension in adults. However, further prospective cohort studies are required to establish a causal relationship between SII and MetS, as well as its components.
Does cognitive impairment moderate the relationship between social isolation and anxiety? A 5-year longitudinal study of a nationally representative sample of community residing older adults
Authors: Hwang Yeji , Massimo Lauren , Aryal Subhash , Hirschman Karen B. , Cacchione Pamela Z. , Hodgson Nancy A.
Published: January 2024

Background

Anxiety is common in older adults and social isolation is one of the leading factors associated with their anxiety. However, what is unknown is how the relationship between social isolation and anxiety differs by cognitive status. Therefore, this study was conducted to (1) compare the level of social isolation and anxiety in older adults who developed probable dementia and mild cognitive impairment (MCI) to those who maintained normal cognitive function over 5 years; and (2) determine if cognitive impairment moderates the relationship between changes in social isolation and changes in anxiety over 5 years.

Methods

A secondary data analysis was conducted using the National Social Life, Health, and Aging Project (NSHAP): Wave 2 (2010–2011) and Wave 3 (2015–2016). The participants were categorized into three groups: Participants who developed probable dementia over 5 years (4.3%), developed probable MCI (19.1%), or maintained normal cognitive function (76.6%). Weighted linear regression analyses with a group interaction were used to examine the moderating effect of cognitive impairment on the relationship between changes in social isolation and anxiety.

Results

At the 5-year follow up, there were statistically significant differences in social isolation between the three groups (p = 0.043). Regression analyses showed that increased social isolation over time was related to increased anxiety over 5 years regardless of cognitive status after controlling for covariates (p = 0.017).

Conclusions

The relationship between social isolation and anxiety was a universal phenomenon regardless of cognitive status. Tailored interventions targeting both people with or without cognitive impairment are needed to lessen social isolation and anxiety.
Shorter antitubercular therapy for extrapulmonary tuberculosis - a case report
Authors: Ravikumar Diviya Bharathi , Sivasubramanian Barath Prashanth , Singla Ankur , Venu Rakshaya , Shekar Saketh Palasamudram
Published: January 2024

Introduction

Extrapulmonary tuberculosis (EPTB) adds to India’s significant economic burden, with pericardial effusion being a potentially fatal complication. This case report highlights the need for early diagnosis and the feasibility of shorter-duration treatment for EPTB in developing countries.

Presentation

This case report describes a 19-year-old male from Southeast Asia who had a history of bronchiectasis involving the left lower lobe and the right middle lobe, which was cystic in nature, as well as multiple episodes of non-tuberculous pneumonia. Currently, he presented with fever, hypotension, tachycardia, and acute kidney injury. Echocardiogram showed left ventricular dysfunction with a left ventricular ejection fraction (LVEF) of 45% and moderate pericardial effusion. Early signs of cardiac tamponade were noted, specifically the absence of respiratory variation in the right ventricle and left ventricle collapse. Emergent pericardiocentesis was performed, and hemorrhagic pericardial fluid was aspirated. Fluid analysis revealed high levels of LDH (5000 U/L), polymorphonuclear leukocytosis, and acid-fast bacilli that were visualized on microscopy, which led to the diagnosis of pericardial tuberculosis. A CT of the abdomen showed hepatosplenomegaly and polyserositis. Empirically, antitubercular therapy consisting of isoniazid, rifampin, pyrazinamide, and ethambutol was administered for 2 months and isoniazid along with rifampicin was given for the next 4 months. Serial echocardiograms in the following months showed an improvement in LVEF (55%) and decreased effusion. However, during this treatment period, due to frequent episodes of pneumonia, the evaluation of immunodeficiency disorders was performed and revealed low levels of IgG (4.741 g/L), IgA (0.238 g/L), and IgM (0.098 g/L). He was diagnosed with common variable immunodeficiency disease and received intravenous immunoglobulin therapy.

Conclusion

This report emphasizes the timely identification of cardiac tamponade and the effective management of EPTB through a shorter-than-recommended course of antitubercular therapy, resulting in the alleviation of symptoms and better overall health outcomes.
Palmitic acid-activated GPRs/KLF7/CCL2 pathway is involved in the crosstalk between bone marrow adipocytes and prostate cancer
Authors: Wang Jingzhou , Liu Jie , Yuan Chenggang , Yang Bingqi , Pang Huai , Chen Keru , Feng Jiale , Deng Yuchun , Zhang Xueting , Li Wei , Wang Cuizhe , Xie Jianxin , Zhang Jun
Published: January 2024

Background

Obesity-induced abnormal bone marrow microenvironment is one of the important risk element for bone metastasis in prostate cancer (PCa). The present study aimed to determine whether obesity-induced elevation in palmitic acid (PA), which is the most abundant of the free fatty acids (FFAs), increased CCL2 via the GPRs/KLF7 pathway in bone marrow adipocytes (BMA) to facilitate PCa growth and metastasis.

Methods

We constructed a bone-tumor bearing mouse model with obesity through high-fat diet, and observed the tumor formation ability of PCa cells. In vitro, observe the effect of PA on the expression level of CCL2 in BMA through GPRs/KLF7 signaling pathway. After co-culture of BMA and PCa cells, CCK8 assay and transwell experiment were used to detect the changes in biological behavior of PCa cells stimulated by BMA.

Results

The BMA distribution in the bone marrow cavity of BALB/c nude mice fed with the high-fat diet (HFD) was evidently higher than that in the mice fed with the normal diet (ND). Moreover, HFD-induced obesity promoted KLF7/CCL2 expression in BMA and PCa cell growth in the bone marrow cavity of the mice. In the vitro experiment, a conditioned medium with increased CCL2 obtained from the BMA cultured with PA (CM-BMA-PA) was used for culturing the PCa cell lines, which evidently enhanced the proliferation, invasion, and migration ability. KLF7 significantly increased the CCL2 expression and secretion levels in BMA by targeting the promoter region of the CCL2 gene. In addition, GPR40/120 engaged in the PA-induced high KLF7/CCL2 levels in BMA to facilitate the malignant progression of PC-3 cells.

Conclusions

PA-activated GPRs/KLF7/CCL2 pathway in BMA facilitates prostate cancer growth and metastasis.
Outcome of cataract surgery in children with presumed trematode-induced granulomatous anterior uveitis
Authors: Abdallah Mona , Al-Hussaini Ashraf K. , Soliman Wael , Saleh Mohamed G. A.
Published: January 2024

Purpose

To examine the 6-month visual outcomes and complications following cataract surgery in patients with persumed trematode induced granulomatous anterior uveitis.

Setting

Assiut university hospital, Assiut, Egypt.

Design

This is a retrospective non comparative case series study.

Methods

Patients presenting with significant cataract secondary to uveitis caused by trematode induced anterior chamber granuloma were included in this study.

Cases with active anterior uveitis, within the last 3 months preceding surgery, and those with a history of trauma, were excluded from this study.

Data collected included demographic characteristics, history of the condition including when uveitis started, treatment received and history of other health conditions that may be relevant to uveitis.Complete opthalmologic examination including assessment of best corrected visual acuity (BCVA) and OCT macula, if possible, were done. These was repeated 1 week, 1 month, 3 months and 6 months after surgery. Specular microscopy was performed preoperatively and 3 months after surgery. Patients underwent cataract surgery with posterior chamber intra ocular lens and statistical analysis was performed to compare preoperative and postoperative BCVA and corneal endothelial cell counts. Postoperative complications were recorded.

Results

Five eyes of 5 patients were included in the study. All study eyes showed improvement in the post-operative visual acuity.

A statistically significant improvement was observed in VA in the sixth postoperative month compared to the baseline measurements (p = 0.004). No statistically significant difference was observed between the preoperative and postoperative endothelial cell counts (p = 0.696). Cystoid macular edema did not occur as a postoperative complication.

Conclusion

Visual outcomes of cataract surgery in eyes with persumed trematode induced granulametous anterior uveitis are favorable. No sight threatening complication was observed in our series.
PPI in psychiatry and the problem of knowledge
Authors: Rose Diana , Beresford Peter
Published: January 2024

This article begins by locating Patient and Public involvement ((PPI) historically and argues that ‘mental health’ was a special case. This movement held promise for service users in repositioning them as researchers as opposed to ‘subjects’. We argue, however, that ultimately it failed and was reduced to involved publics ‘tinkering at the edges’. In respect to this we reference institutions, hierarchies, organisations and the overall political climate. Ultimately, however, it failed at the level of knowledge itself in that t he underlying assumptions of conventional researchers, their aims and goals, clashed with those of the assumptions and aims of survivors. However, we argue that all is not lost, the mainstream itself is imploding and beneath the surface forms of distinctly survivor-led knowledge are emerging.
Development and validation of a quality of healthy work environment instrument for shift nurses
Authors: Shin Sun-Hwa , Lee Eun-Hye
Published: January 2024

Background

As the importance of a healthy work environment for nurses’ good practice and patient safety has been recognized, there is a need to assess nurses’ perceptions of the quality of a healthy work environment.

Methods

A conceptual framework and construct components were extracted through a literature review and in-depth interviews with shift nurses. The initial items of the instrument were developed according to the conceptual attributes, and the items were selected through content validity by ten experts. Two hundred and forty-seven shift nurses participated in this study through face-to-face surveys to test the reliability and validity of the instrument. The evaluation was used for item and confirmatory factor analyses to assess the criterion-related validity and internal consistency of the instrument. Test-retest reliability was analyzed using data from thirty-two nurses.

Results

The final instrument consisted of 23 items with five components identified through confirmatory factor analysis. Criterion-related validity was established using the K-PES-NWI (r = .54). Cronbach’s alpha for the total items was 0.85, and test-retest reliability was 0.73.

Conclusion

The quality of the healthy work environment instrument developed in this study was considered reliable and valid. The instrument developed in this study can be used to measure the quality of a healthy work environment as perceived by shift nurses and to identify preventive measures needed to improve the quality of the work environment.
Sequences of vocational rehabilitation services in Germany: a cohort study
Authors: Sternberg Annika , Fauser David , Banaschak Hannes , Bethge Matthias
Published: January 2024

Background

This study aimed to describe sequences of vocational rehabilitation services among individuals with approved vocational rehabilitation in Germany and to identify typical service sequences.

Methods

We used administrative data on vocational rehabilitation services and questionnaire data on health and work ability to describe frequencies and sequences of vocational rehabilitation services financed by the Federal German Pension Insurance. Through sequence analysis, we were able to map the service sequences. We did cluster analyses to identify typical different service sequences.

Results

Our sample included 1,652 individuals with 2,584 services. Integration services and two-year vocational retraining were the most common services. We could identify three different service clusters around integration services: shorter ones, followed by employer benefits and without employer benefits. We found two different clusters around two-year vocational retraining: shorter and longer clusters. Two-year vocational retraining was more often initiated by preparatory services and followed by employer benefits than integration services. Longer services in both clusters were associated with better baseline data for physical health, work ability, risk of future work disability, and younger age than shorter services. People in two-year-vocational retraining reported at baseline better general health, better work ability, low risk of future work disability, and less mental illness compared to people in integration services.

Conclusions

Multiple services, that is, sequences of services, were more likely to occur among individuals with more complex services like two-year vocational retraining. Utilization of complex services and longer services was influenced by health, age, risk of future work disability, and education.

Trial registration

German Clinical Trials Register DRKS00009910, registration 25/01/2016.
A qualitative study on patients’ and health care professionals’ perspectives regarding care delivered during CIED operation
Authors: Zhou Min , Zhou Huilin , Zhang Xiong , Jin Xiaorong , Su Xu , Bai Yangjuan , Wei Wei , Zhang Yimei , Ma Fang
Published: January 2024

Background

Cardiac implantable electronic devices (CIEDs) has proven to be an invaluable tool in the practice of cardiology. Patients who have undergone CIED surgery with local anesthesia may result in fear, insecurity and suffering. Some studies have put efforts on ways to improve intraoperative experience of patients with local anesthesia, but researches concerning experiences of CIED patients during surgery is in its infancy.

Methods

Based on semi-structured and in-depth interviews, a qualitative design was conducted in a tertiary general hospital in China from May 2022 to July 2023.Purposeful sampling of 17 patients received CIED surgery and 20 medical staff were interviewed. Thematic analysis with an inductive approach was used to identify dominant themes.

Results

Four themes emerged from the data: (1) Safety and success is priority; (2) Humanistic Caring is a must yet be lacking; (3) Paradox of surgery information given; (4) Ways to improve surgery experiences in the operation.

Conclusions

Intraoperative care is significant for CIED surgery. To improve care experience during surgery, healthcare professionals should pay attention to patients’ safety and the factors that affecting humanistic caring in clinical practice. In addition, information support should consider information-seeking styles and personal needs. Besides, the four approaches presented in this study are effective to improve the intraoperative care experience.
Exposure to residential green and blue space and the natural environment is associated with a lower incidence of psychiatric disorders in middle-aged and older adults: findings from the UK Biobank
Authors: Liu Bao-Peng , Huxley Rachel R. , Schikowski Tamara , Hu Ke-Jia , Zhao Qi , Jia Cun-Xian
Published: January 2024

Background

There is increasing evidence for the role of environmental factors and exposure to the natural environment on a wide range of health outcomes. Whether exposure to green space, blue space, and the natural environment (GBN) is associated with risk of psychiatric disorders in middle-aged and older adults has not been prospectively examined.

Methods

Longitudinal data from the UK biobank was used. At the study baseline (2006–2010), 363,047 participants (women: 53.4%; mean age 56.7 ± 8.1 years) who had not been previously diagnosed with any psychiatric disorder were included. Follow-up was achieved by collecting records from hospitals and death registers. Measurements of green and blue space modeled from land use data and natural environment from Land Cover Map were assigned to the residential address for each participant. Cox proportional hazard models with adjustment for potential confounders were used to explore the longitudinal associations between GBN and any psychiatric disorder and then by specific psychiatric disorders (dementia, substance abuse, psychotic disorder, depression, and anxiety) in middle-aged and older adults.

Results

During an average follow-up of 11.5 ± 2.8 years, 49,865 individuals were diagnosed with psychiatric disorders. Compared with the first tertile (lowest) of exposure, blue space at 300 m buffer [hazard ratio (HR): 0.973, 95% confidence interval (CI): 0.952–0.994] and natural environment at 300 m buffer (HR: 0.970, 95% CI: 0.948–0.992) and at 1000 m buffer (HR: 0.975, 95% CI: 0.952–0.999) in the third tertile (highest) were significantly associated with lower risk of incident psychiatric disorders, respectively. The risk of incident dementia was statistically decreased when exposed to the third tertile (highest) of green space and natural environment at 1000 m buffer. The third tertile (highest) of green space at 300 m and 1000 m buffer and natural environment at 300 m and 1000 m buffer was associated with a reduction of 30.0%, 31.8%, 21.7%, and 30.3% in the risk of developing a psychotic disorder, respectively. Subgroup analysis suggested that the elderly, men, and those living with some comorbid conditions may derive greater benefits associated with exposure to GBN.

Conclusions

This study suggests that GBN has significant benefits for lowering the risk of psychiatric disorders in middle-aged and older adults. Future studies are warranted to validate these findings and to understand the potential mechanistic pathways underpinning these novel findings.
Engaging leadership and nurse well-being: the role of the work environment and work motivation—a cross-sectional study
Authors: Kohnen Dorothea , De Witte Hans , Schaufeli Wilmar B. , Dello Simon , Bruyneel Luk , Sermeus Walter
Published: January 2024

Background

Healthcare literature suggests that leadership behavior has a profound impact on nurse work-related well-being. Yet, more research is needed to better conceptualize, measure, and analyse the concepts of leadership and well-being, and to understand the psychological mechanisms underlying this association. Combining Self-Determination and Job Demands-Resources theory, this study aims to investigate the association between engaging leadership and burnout and work engagement among nurses by focusing on two explanatory mechanisms: perceived job characteristics (job demands and resources) and intrinsic motivation.

Methods

A cross-sectional survey of 1117 direct care nurses (response rate = 25%) from 13 general acute care hospitals in Belgium. Validated instruments were used to measure nurses’ perceptions of engaging leadership, burnout, work engagement, intrinsic motivation and job demands and job resources. Structural equation modeling was performed to test the hypothesised model which assumed a serial mediation of job characteristics and intrinsic motivation in the relationship of engaging leadership with nurse work-related well-being.

Results

Confirmatory factor analysis indicated a good fit of the measurement model. The findings offer support for the hypothesized model, indicating that engaging leadership is linked to enhanced well-being, as reflected in increased work engagement, and reduced burnout. The results further showed that this association is mediated by nurses’ perceptions of job resources and intrinsic motivation. Notably, while job demands mediated the relationship between EL and nurses’ well-being, the relationship became unsignificant when including intrinsic motivation as second mediator.

Conclusions

Engaging leaders foster a favourable work environment for nursing staff which is not only beneficial for their work motivation but also for their work-related well-being. Engaging leadership and job resources are modifiable aspects of healthcare organisations. Interventions aimed at developing engaging leadership behaviours among nursing leaders and building job resources will help healthcare organisations to create favourable working conditions for their nurses.

Trial Registration: The study described herein is funded under the European Union’s Horizon 2020 Research and Innovation programme from 2020 to 2023 (Grant Agreement 848031). The protocol of Magnet4Europe is registered in the ISRCTN registry (ISRCTN10196901).
Pyroptosis: a double-edged sword in lung cancer and other respiratory diseases
Authors: Liang Xiao , Qin Ya , Wu Dan , Wang Qiong , Wu Hongshuai
Published: January 2024

Pyroptosis is an active cell death process mediated by gasdermin family proteins including Gasdermin A (GSDMA), Gasdermin B (GSDMB), Gasdermin C (GSDMC), Gasdermin D (GSDMD), Gasdermin E (GSDME, DFNA5), and DFNB59. Emerging evidences have shown that pyroptosis contributes to many pulmonary diseases, especially lung cancer, and pneumonia. The exact roles of pyroptosis and gasdermin family proteins are tremendously intricate. Besides, there are evidences that pyroptosis contributes to these respiratory diseases. However, it often plays a dual role in these diseases which is a cause for concern and makes it difficult for clinical translation. This review will focus on the multifaceted roles of pyroptosis in respiratory diseases.
ROS/mtROS promotes TNTs formation via the PI3K/AKT/mTOR pathway to protect against mitochondrial damages in glial cells induced by engineered nanomaterials
Authors: Lin Xinpei , Wang Wei , Chang Xiangyu , Chen Cheng , Guo Zhenkun , Yu Guangxia , Shao Wenya , Wu Siying , Zhang Qunwei , Zheng Fuli , Li Huangyuan
Published: January 2024

Background

As the demand and application of engineered nanomaterials have increased, their potential toxicity to the central nervous system has drawn increasing attention. Tunneling nanotubes (TNTs) are novel cell–cell communication that plays a crucial role in pathology and physiology. However, the relationship between TNTs and nanomaterials neurotoxicity remains unclear. Here, three types of commonly used engineered nanomaterials, namely cobalt nanoparticles (CoNPs), titanium dioxide nanoparticles (TiO2NPs), and multi-walled carbon nanotubes (MWCNTs), were selected to address this limitation.

Results

After the complete characterization of the nanomaterials, the induction of TNTs formation with all of the nanomaterials was observed using high-content screening system and confocal microscopy in both primary astrocytes and U251 cells. It was further revealed that TNT formation protected against nanomaterial-induced neurotoxicity due to cell apoptosis and disrupted ATP production. We then determined the mechanism underlying the protective role of TNTs. Since oxidative stress is a common mechanism in nanotoxicity, we first observed a significant increase in total and mitochondrial reactive oxygen species (namely ROS, mtROS), causing mitochondrial damage. Moreover, pretreatment of U251 cells with either the ROS scavenger N-acetylcysteine or the mtROS scavenger mitoquinone attenuated nanomaterial-induced neurotoxicity and TNTs generation, suggesting a central role of ROS in nanomaterials-induced TNTs formation. Furthermore, a vigorous downstream pathway of ROS, the PI3K/AKT/mTOR pathway, was found to be actively involved in nanomaterials-promoted TNTs development, which was abolished by LY294002, Perifosine and Rapamycin, inhibitors of PI3K, AKT, and mTOR, respectively. Finally, western blot analysis demonstrated that ROS and mtROS scavengers suppressed the PI3K/AKT/mTOR pathway, which abrogated TNTs formation.

Conclusion

Despite their biophysical properties, various types of nanomaterials promote TNTs formation and mitochondrial transfer, preventing cell apoptosis and disrupting ATP production induced by nanomaterials. ROS/mtROS and the activation of the downstream PI3K/AKT/mTOR pathway are common mechanisms to regulate TNTs formation and mitochondrial transfer. Our study reveals that engineered nanomaterials share the same molecular mechanism of TNTs formation and intercellular mitochondrial transfer, and the proposed adverse outcome pathway contributes to a better understanding of the intercellular protection mechanism against nanomaterials-induced neurotoxicity.

Graphical abstract
Study on medicinal food plants in the Gaoligongshan Biosphere Reserve, the richest biocultural diversity center in China
Authors: Cheng Zhuo , Lin Shuyan , Wu Ziyi , Lin Chen , Zhang Qing , Xu Congli , Li Jiahua , Long Chunlin
Published: January 2024

Background

Traditional knowledge associated with medicinal food plants (MFPs) plays a vital role in fighting hidden hunger and safeguarding the health of local people. MFPs resources are abundant in the Gaoligongshan area, a biosphere reserve with the richest biocultural diversity in China. Local people of different linguistic groups also have rich traditional botanical knowledge. However, there are still few comprehensive and systematic studies on MFPs there.

Methods

Ethnobotanical investigation including market survey, semi-structured interviews, free listing and key informant interviews was conducted in the Gaoligongshan area, Western Yunnan, Southwest China. A total of 13 local farmers’ markets were selected and information about medicinal food plants, including food categories, medicinal and edible parts, modes of consumption, medicinal effects, and distribution were collected. The relative occurrence frequency (RFO) and cultural food significance index (CFSI) were calculated to identify the culturally significant MFPs.

Results

A total of 184 species of MFPs, belonging to 83 families, were collected in the Gaoligongshan area, including vegetables (77), medicinal diets (26), fruits (25), spices (18), herbal tea (13), tea substitutes (11), substitutes for staple food (8), nuts (5), oils and fats (4), and dye material (1). The most frequently used families were Fabaceae, Asteraceae and Apiaceae, with 11, 10, and 9 species, respectively. The most frequently used plant parts were the stems, followed by fruits and leaves. Based on the evaluation results of the CFSI and RFO indices, 18 species of MFPs with magnificent local cultural importance have been screened out, such as Houttuynia cordata, Eryngium foetidum, Sechium edule, Centella asiatica and Pseudocydonia sinensis.

Conclusion

These findings have guiding significance for conservation of traditional knowledge associated with MFPs and facilitation of scientific utilization of MFPs to meet local people’s needs for a healthy life.
Iron accumulation induced by hepcidin1 knockout accelerates the progression of aging osteoporosis
Authors: Liu Lu-lin , Liu Zhong-rui , Cao Lu-jun , Wang Jun , Huang San-ming , Hu Shui-gen , Yang Yi-zhong , Li Dong-sheng , Cao Wei-wei , Zeng Qing-bao , Huang Sheng , Wu Qiong , Xiao Jian-hua , Liu Wu-yang , Xiao Yao-sheng
Published: January 2024

Objective

Iron accumulation is associated with osteoporosis. This study aims to explore the effect of chronic iron accumulation induced by hepcidin1 deficiency on aging osteoporosis.

Methods

Iron accumulation in hepcidin1 knockout aging mice was assessed by atomic absorption spectroscopy and Perl’s staining. Bone microarchitecture was observed using Micro-CT. Hepcidin, ferritin, oxidative stress, and markers of bone turnover in serum were detected by enzyme-linked immunosorbent assay. Bone formation and resorption markers were measured by real-time quantitative PCR. Cell aging was induced by D-galactose treatment. CCK-8, flow cytometry, EdU assays, and Alizarin red staining were performed to reveal the role of hepcidin1 knockout in cell model. Iron Colorimetric Assay Kit and western blot were applied to detect iron and ferritin levels in cells, respectively.

Results

In hepcidin1-knockout mice, the ferritin and iron contents in liver and tibia were significantly increased. Iron accumulation induced by hepcidin1 knockout caused a phenotype of low bone mass and deteriorated bone microarchitecture. Osteogenic marker was decreased and osteoclast marker was increased in mice, accompanied by increased oxidative stress level. The mRNA expression levels of osteoclast differentiation markers (RANKL, Mmp9, OPG, Trap, and CTSK) were up-regulated, while bone formation markers (OCN, ALP, Runx2, SP7, and Col-1) were down-regulated in model group, compared to wild type mice. In vitro, hepcidin1 knockdown inhibited proliferation and osteogenic differentiation, while promoted apoptosis, with increased levels of iron and ferritin.

Conclusion

Iron accumulation induced by hepcidin1 deficiency aggravates the progression of aging osteoporosis via inhibiting osteogenesis and promoting osteoclast genesis.
A systematic review of endometrial cancer clinical research in Africa
Authors: Anakwenze Chidinma P. , Ewongwo Agnes , Onyewadume Louisa , Oyekan Ademola , Chigbo Chinelo Onwualu , Valle Luca , Geng Yimin , Olapade Paul , Okwunze Kenechukwu , Lasebikan Nwamaka , Jhingran Anuja , Balogun Onyinye D. , Ntekim Atara
Published: January 2024

Background

Women in Africa are experiencing a rising burden of endometrial cancer. Research and investment to improve treatment and outcomes are critically needed. We systematically reviewed and characterized endometrial cancer-related research within a clinically relevant context to help organize and assess existing endometrial cancer research in Africa.

Methods

According to PRISMA guidelines, we searched online databases for published endometrial cancer articles from African countries from January 1, 2011, to July 20, 2021. Based on our inclusion and exclusion criteria, independent reviewers documented the study design, country/region, human development index, focus of research, type of interventions performed, and histologic and molecular type to illustrate the breadth of research coverage in each region.

Results

A total of 18 research articles were included. With an average Human Development Index (HDI) in Africa of 0.536, the average HDI of the represented countries in this study was 0.709. The majority (88.9%) of prospective endometrial cancer research articles in Africa were from North Africa, with Egypt encompassing 83.3% of the papers. Most of these studies focused on endometrial cancer diagnosis. Research on the treatment of endometrial cancer is still emerging (33% of papers). Of all included articles, only 11.1% represented Sub-Saharan Africa, where the majority population of black Africans reside.

Conclusions

Endometrial cancer research in Africa is extremely limited, with the majority being concentrated in African countries with higher HDIs. As the incidence of endometrial cancer rises in Sub-Saharan Africa, there is a pressing need for more prospective clinical research to tackle the growing disease burden and improve outcomes.
ARMC5 controls the degradation of most Pol II subunits, and ARMC5 mutation increases neural tube defect risks in mice and humans
Authors: Luo Hongyu , Lao Linjiang , Au Kit Sing , Northrup Hope , He Xiao , Forget Diane , Gauthier Marie-Soleil , Coulombe Benoit , Bourdeau Isabelle , Shi Wei , Gagliardi Lucia , Fragoso Maria Candida Barisson Villares , Peng Junzheng , Wu Jiangping
Published: January 2024

Background

Neural tube defects (NTDs) are caused by genetic and environmental factors. ARMC5 is part of a novel ubiquitin ligase specific for POLR2A, the largest subunit of RNA polymerase II (Pol II).

Results

We find that ARMC5 knockout mice have increased incidence of NTDs, such as spina bifida and exencephaly. Surprisingly, the absence of ARMC5 causes the accumulation of not only POLR2A but also most of the other 11 Pol II subunits, indicating that the degradation of the whole Pol II complex is compromised. The enlarged Pol II pool does not lead to generalized Pol II stalling or a generalized decrease in mRNA transcription. In neural progenitor cells, ARMC5 knockout only dysregulates 106 genes, some of which are known to be involved in neural tube development. FOLH1, critical in folate uptake and hence neural tube development, is downregulated in the knockout intestine. We also identify nine deleterious mutations in the ARMC5 gene in 511 patients with myelomeningocele, a severe form of spina bifida. These mutations impair the interaction between ARMC5 and Pol II and reduce Pol II ubiquitination.

Conclusions

Mutations in ARMC5 increase the risk of NTDs in mice and humans. ARMC5 is part of an E3 controlling the degradation of all 12 subunits of Pol II under physiological conditions. The Pol II pool size might have effects on NTD pathogenesis, and some of the effects might be via the downregulation of FOLH1. Additional mechanistic work is needed to establish the causal effect of the findings on NTD pathogenesis.
CompARE: study protocol for a phase III randomised controlled platform trial comparing alternative regimens for escalating treatment of intermediate and high-risk oropharyngeal cancer
Authors: Mehanna Hisham , Gaunt Piers , Kong Anthony , Hartley Andrew , Sanghera Paul , Forster Martin , Sen Mehmet , Paleri Vinidh , Fong Charles , Geropantas Dinos , Srinivasan Devraj , Garikipati Satya , Moleron Rafael , Casswell Georgina , Aynsley Eleanor , Ward Amy , O’Toole Lorcan , Mirza Arafat , Firth Charlotte , Humphreys Isla , Fulton-Lieuw Tessa , Roques Tom , Nankivell Paul
Published: January 2024

Background

Patients with intermediate and high-risk oropharyngeal cancer (OPC) have poorer response to standard treatment and poorer overall survival compared to low-risk OPC. CompARE is designed to test alternative approaches to intensified treatment for these patients to improve survival.

Methods

CompARE is a pragmatic phase III, open-label, multicenter randomised controlled trial with an adaptive multi-arm, multi-stage design and an integrated QuinteT Recruitment Intervention. Eligible OPC patients include those with human papillomavirus (HPV) negative, T1–T4, N1–N3 or T3–4, N0, or HPV positive N3, T4, or current smokers (or ≥ 10 pack years previous smoking history) with T1–T4, N2b–N3. CompARE was originally designed with four arms (one control [arm 1] and three experimental: arm 2—induction chemotherapy followed by arm 1; arm 3—dose-escalated radiotherapy plus concomitant cisplatin; and arm 4—resection of primary followed by arm 1). The three original experimental arms have been closed to recruitment and a further experimental arm opened (arm 5—induction durvalumab followed by arm 1 and then adjuvant durvalumab). Currently recruiting are arm 1 (control): standard treatment of 3-weekly cisplatin 100 mg/m2 or weekly 40 mg/m2 with intensity-modulated radiotherapy using 70 Gy in 35 fractions ± neck dissection determined by clinical and radiological assessment 3 months post-treatment, and arm 5 (intervention): one cycle of induction durvalumab 1500 mg followed by standard treatment then durvalumab 1500 mg every 4 weeks for a total of 6 months. The definitive and interim primary outcome measures are overall survival time and event-free survival (EFS) time, respectively. Secondary outcome measures include quality of life, toxicity, swallowing outcomes, feeding tube incidence, surgical complication rates, and cost-effectiveness. The design anticipates that after approximately 7 years, 84 required events will have occurred to enable analysis of the definitive primary outcome measure for this comparison. Planned interim futility analyses using EFS will also be performed.

Discussion

CompARE is designed to be efficient and cost-effective in response to new data, emerging new treatments or difficulties, with the aim of bringing new treatment options for these patients.

Trial registration

ISRCTN ISRCTN41478539. Registered on 29 April 2015
Efficacy of a 2-week therapy with levofloxacin concomitant versus a levofloxacin sequential regimen for Helicobacter pylori infection in the Syrian population: a study protocol for randomized controlled trial
Authors: Alhalabi Marouf , Almokdad Rasha
Published: January 2024

Background

Treating Helicobacter pylori is becoming increasingly difficult with the development of bacterial resistance to many established treatment regimens. As a result, researchers are constantly looking for novel and effective treatments. This trial aims to establish the efficacy of levofloxacin-based sequential treatment regimen and concomitant levofloxacin-based regimen as empirical first-line therapy in the Syrian population.

Method

This is an open-label, prospective, single-center, parallel, active-controlled, superiority, randomized clinical trial. The recruitment will target Helicobacter pylori-positive males and females between the ages of 18 and 65 to evaluate the efficacy of empirical first-line therapy in the Syrian population. We are planning to recruit up to 300 patients which is twice the required sample size. One hundred fifty individuals will be randomly assigned to undergo either a sequential levofloxacin-based treatment regimen or a concomitant levofloxacin-based regimen. High-dose dual therapy (proton-pump inhibitor and amoxicillin) will be the rescue therapy in the event of first-line failure. The first-line eradication rate in both groups is the primary outcome, and one of the secondary outcomes is the overall eradication rate of high-dose dual therapy in the event of first-line treatment protocol failure. Intention-to-treat analysis and per-protocol analysis will be used to evaluate the eradication rates of Helicobacter pylori for first-line treatment protocols.

Discussion

For the first time in the Syrian population, this randomized controlled trial will provide objective and accurate evidence about the efficacy of a sequential levofloxacin-based treatment regimen.

Trial registration

ClinicalTrials.gov NCT06065267. Registered on October 3, 2023. Prospective registered. Enrollment of the first participant has not started yet.
Age, sex, and mating status discrimination in the sand fly Lutzomyia longipalpis using near infra-red spectroscopy (NIRS)
Authors: Ferreira Tainá Neves , Santos Lilha M. B. , Valladares Vanessa , Flanley Catherine M. , McDowell Mary Ann , Garcia Gabriela A. , Mello-Silva Clélia C. , Maciel-de-Freitas Rafael , Genta Fernando Ariel
Published: January 2024

Background

Understanding aspects related to the physiology and capacity of vectors is essential for effectively controlling vector-borne diseases. The sand fly Lutzomyia longipalpis has great importance in medical entomology for disseminating Leishmania parasites, the causative agent of Leishmaniasis, one of the main neglected diseases listed by the World Health Organization (WHO). In this respect, it is necessary to evaluate the transmission potential of this species and the success of vector control interventions. Near-infrared spectroscopy (NIRS) has been used to estimate the age of mosquitoes in different conditions (laboratory, semi-field, and conservation), taxonomic analysis, and infection detection. However, no studies are using NIRS for sand flies.

Methods

In this study, we developed analytic models to estimate the age of L. longipalpis adults under laboratory conditions, identify their copulation state, and evaluate their gonotrophic cycle and diet.

Results

Sand flies were classified with an accuracy of 58–82% in 3 age groups and 82–92% when separating them into young (<8 days) or old (>8 days) insects. The classification between mated and non-mated sandflies was 98–100% accurate, while the percentage of hits of females that had already passed the first gonotrophic cycle was only 59%.

Conclusions

We consider the age and copula estimation results very promising, as they provide essential aspects of vector capacity assessment, which can be obtained quickly and at a lower cost with NIRS.

Graphical Abstract
Cartilage destruction in early rheumatoid arthritis patients correlates with CD21−/low double-negative B cells
Authors: Thorarinsdottir Katrin , McGrath Sarah , Forslind Kristina , Agelii Monica Leu , Ekwall Anna-Karin Hultgård , Jacobsson Lennart T. H. , Rudin Anna , Mårtensson Inga-Lill , Gjertsson Inger
Published: January 2024

Background

Involvement of B cells in the pathogenesis of rheumatoid arthritis (RA) is supported by the presence of disease-specific autoantibodies and the efficacy of treatment directed against B cells. B cells that express low levels of or lack the B cell receptor (BCR) co-receptor CD21, CD21−/low B cells, have been linked to autoimmune diseases, including RA. In this study, we characterized the CD21+ and CD21−/low B cell subsets in newly diagnosed, early RA (eRA) patients and investigated whether any of the B cell subsets were associated with autoantibody status, disease activity and/or joint destruction.

Methods

Seventy-six eRA patients and 28 age- and sex-matched healthy donors were recruited. Multiple clinical parameters were assessed, including disease activity and radiographic joint destruction. B cell subsets were analysed in peripheral blood (PB) and synovial fluid (SF) using flow cytometry.

Results

Compared to healthy donors, the eRA patients displayed an elevated frequency of naïve CD21+ B cells in PB. Amongst memory B cells, eRA patients had lower frequencies of the CD21+CD27+ subsets and CD21−/low CD27+IgD+ subset. The only B cell subset found to associate with clinical factors was the CD21−/low double-negative (DN, CD27−IgD−) cell population, linked with the joint space narrowing score, i.e. cartilage destruction. Moreover, in SF from patients with established RA, the CD21−/low DN B cells were expanded and these cells expressed receptor activator of the nuclear factor κB ligand (RANKL).

Conclusions

Cartilage destruction in eRA patients was associated with an expanded proportion of CD21−/low DN B cells in PB. The subset was also expanded in SF from established RA patients and expressed RANKL. Taken together, our results suggest a role for CD21−/low DN in RA pathogenesis.