bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the impact of rational emotive behavior therapy on post-traumatic stress in farmers with experiences of natural disaster
Authors: Nwankwo Clara U. , Egbule Elizabeth Osita , Ede Kelechi Ruth , Ede Moses Onyemaechi , Victor-Aigbodion Vera , Ifere Paul Ikechukwu , Nweze Celestina Adaeze , Obeagu Emmanuel Ifeanyi
Published: October 2024

Background/objective:

This study was necessary due to the increasing number of cases of natural disasters such as flood, air pollution, erosion, etc in Nigeria, particularly in the Abia state, as well as the accompanying psychological and health issues affecting individuals within families and society as a whole. The study aimed to examine the impact of rational emotive behavior therapy on farmers’ post-traumatic stress (PTS) in Abia State, Nigeria.

Method:

A randomized control trial was conducted in Abia state, with a sample size of 118 farmers with experiences of natural disasters. Two assessments were conducted before the treatment, immediately after the treatment, and 2 months later to evaluate PTS and irrational beliefs among the farmers. The treatment involved a self-developed PTS-focused rational emotive behavior therapy manual, consisting of 12 sessions lasting 60 minutes each, delivered by counseling psychologists trained in rational emotive behavior and family therapies. Data from the pretest, posttest, and follow-up test were analyzed using chi-square, percentage, partial eta squared, and analysis of covariance statistical tools.

Results:

The results showed no significant gender differences in the socioeconomic status, employment, and debt status of the participants. The rational emotive behavior therapy was effective in reducing PTS caused by the flood among farmers. Gender did not have a significant moderating effect on farmers’ experiences with PTS.

Conclusion:

The study suggested that family health specialists and rational-emotive therapists collaborate with local authorities to provide career counseling services to farmers and establish community-based rational emotive institutes in each state of Nigeria.
Nursing bibliometric analysis of wound infections
Authors: Liu Mengdi , Ma Cuifang , Dong Xiaowei , Gu Mengyi , Wang Zheng , Gao Qian , Guo Xiaoyu
Published: October 2024

Background:

This paper aims to perform a bibliometric analysis of research pertaining to the nursing care of infected wounds. It also aims to examine the current focal points and trends in research development. The paper offers research references that may be useful for practitioners interested in related areas.

Methods:

The Web of Science Core Collection database was queried for publications pertaining to infected wound care. Publication trends and proportions were analyzed using Graphpad Prism v8.0.2. CiteSpace (6.2.4R [64-bit]) and VOSviewer (version 1.6.18) were employed to assess the literature and conduct mapping.

Results:

The Web of Science Core Collection database contains 3868 literature related to wound infection care, including 3327 articles and 541 reviews. The literature concerned 117 countries and territories, 4673 institutions, and 20,161 authors. The growth rate of literature was relatively slow before 2015 and markedly accelerated after 2016. Among them, the United States occupies the absolute dominance in research in this field, publishing 37.25% of the papers, and the United States occupies 8 of the top 10 scientific institutions that publish papers. The University of Harvard has published the largest number of papers. Keyword analysis shows a total of 1125 keywords, and through reference literature and time clustering analysis shows that wound healing, sepsis, spine surgery, postoperative infection, nanocrystalline silver, beta lactamase are the current research hotspots.

Conclusion:

The escalating rate of literary expansion since 2016 suggests that this domain is garnering an increasingly significant amount of interest. Minimizing the risk of patient wound infection is crucial in reducing patients’ discomfort and facilitating their prompt recovery. The literature analysis presented in this study serves as a valuable resource for comprehending the current state of the subject and identifying the current areas of focus.
Global research landscape on the genetics of congenital heart disease: A bibliometric and visualized analysis via VOSviewer and CiteSpace
Authors: Zhang Fan , Qi Lei , Zhao Mingxue , Han Shuming , Zhang Haoran , Wang Guangxin
Published: October 2024

Genetic factors play a significant role in the development of congenital heart disease (CHD). Many studies on the genetics of CHD have been published worldwide; however, no research has assessed and mapped the global research landscape of these studies. This bibliometric and visualized study aimed to delineate research hotspots and trends in the field of CHD genetics. Scientific papers on the genetics of CHD from January 1, 1950, to December 31, 2023, were obtained by searching the Web of Science Core Collection. The bibliometric metadata of each chosen research paper were extracted, analyzed, and visualized using tools such as Microsoft Excel 2021, VOSviewer, and CiteSpace. The final analysis included 5317 papers discussing the genetics of CHD. The countries and journals that published the highest number of papers were the United States (n = 2118), and American Journal of Medical Genetics Part A (n = 332), respectively. In addition to CHD and genetics, keywords such as tetralogy of Fallot, ventricular septal defect, and atrial septal defect appeared most frequently among 8365 keywords. Eight clusters were formed to categorize the keywords. Keywords such as case–control study, whole genome sequencing, and whole exome sequencing in clusters 6, 7, and 8, respectively, had the latest average publication year among all clusters. To the best of our knowledge, this is the first bibliometric analysis of CHD genetics studies. Tetralogy of Fallot, ventricular septal defect, and atrial septal defect are global research topics. The interactions between environmental and genetic factors in the pathogenesis of CHD, genetic etiology of CHD-associated pulmonary arterial hypertension, and molecular genetics of CHD via high-throughput genomic technology are possible areas of future research on the genetics of CHD.
Genetic evidence supporting the causal role of 25-hydroxyvitamin D levels in the prognosis of ER− breast cancer: A Mendelian randomization study
Authors: Wu Shang , Ma Xin-Di , Zhang Xiang-Mei , Shi Chao , Du Kai-Ye , Liu Yun-Jiang
Published: October 2024

This study aims to investigate the connection between 25-hydroxyvitamin D (25(OH)D) levels and the prognosis of breast cancer with various estrogen receptor (ER) statuses. The summary statistics of 25(OH)D levels was obtained from a GWAS of 441,291 individuals and the information of breast cancer was collected from the Breast Cancer Association Consortium. We analyzed the causal association between 25(OH)D levels and breast cancer prognosis using a number of approaches, including inverse variance weighting (IVW). The heterogeneity test was performed using Cochran Q test. IVW, Mendelian randomization (MR)-Egger, and MR Pleiotropy RESidual Sum and Outlier methods were used for sensitivity analysis. In addition, a multivariate MR adjusted for total triglycerides, total cholesterol, and body mass index was used for further analysis. Two-sample MR results showed that 25(OH)D levels were not associated with prognosis in overall breast cancer (odds ratio [OR] = 0.93, 95% confidence interval [CI] = 0.73–1.19, IVW exam) and estrogen receptor positive (ER+) breast cancers (OR = 1.12, 95% CI = 0.77–1.63, IVW exam) and were protective associated with prognosis in estrogen receptor negative (ER−) breast cancers (OR = 0.55, 95% CI = 0.34–0.87, IVW exam). Sensitivity analysis did not observe the presence of heterogeneity and horizontal pleiotropy. In multivariate MR analysis, after adjusting for total triglycerides, total cholesterol, and body mass index, the correlation between the protective relationship between 25(OH)D levels and the prognosis for ER− breast cancer remained and became increasingly significant (OR = 0.51, 95% CI = 0.31–0.83, P = .007). This study demonstrated a protective relationship between 25(OH)D levels and the prognosis of ER− breast cancer, but there was no connection between 25(OH)D levels and the prognosis of ER+ breast cancer.
A bibliometric and visualization analysis of global trends and frontiers on macrophages in abdominal aortic aneurysms research
Authors: Zhang Liang , Li Dongyu , Bao Shiyang
Published: October 2024

Background:

Macrophages are key regulators of the inflammatory and innate immune responses. Researchers have shown that aberrant expression of macrophages contributes to the development of abdominal aortic aneurysms (AAA). However, a comprehensive bibliometric analysis exploring the research status and knowledge mapping of this area is lacking. This study aimed to explore the research status, knowledge mapping and hotspots of macrophages in AAA research from a bibliometric perspective.

Methods:

In this study, we retrieved articles published between 2000 and 2022 on macrophages associated with AAA research from the Web of Science Core Collection (WoSCC) database. The retrieved literature data were further analyzed using Citespace and VOSviewer software.

Results:

A total of 918 qualified publications related to AAA-associated macrophages were retrieved. The number of publications in this field has been increasing annually. China and the United States were the 2 main drivers in this field, contributing to more than 64% of the publications. In addition, the US had the most publications, top institutions, and expert researchers, dominating in research on macrophages in AAA. The Harvard University was the most productive institution, with 60 publications. The journal with the most publications was Arteriosclerosis, Thrombosis, and Vascular Biology (86). Daugherty Alan was the most prolific author (28 publications) and he was also the most cited co- author. Furthermore, the exploration of established animal models, macrophage-related inflammatory-microenvironment, macrophage-related immune mechanism, clinical translation and molecular imaging research remained future research directions in this field.

Conclusions:

Our findings offered new insights for scholars in this field. They will help researchers explore new directions for their work.
Clinical efficacy of single-channel percutaneous endoscopic nucleotomy with annulus fibrosus suturing for lumbar disc herniation: A retrospective study
Authors: Fu Song , Lv Renhua , Wang Zhenyu , Wang Fengming , Huang Xiaoling , Wang Longqiang , Gao Hao , Zhao Wei , Wang Yanan
Published: October 2024

This retrospective study aimed to investigate the clinical efficacy of single-channel percutaneous endoscopic nucleotomy combined with annulus fibrosus suturing for treating lumbar disc herniation (LDH). The study included 86 patients with LDH treated in our spinal department from August 2020 to January 2022. The suture group consisted of 26 males and 18 females, while the control group (nucleotomy alone) included 25 males and 17 females. All patients were followed for at least 1 year, with follow-up points at 3 days, 3 months, and 12 months postoperatively. Various clinical and radiological indicators were used to evaluate and compare the efficacy and safety of the 2 procedures. No statistically significant differences were observed in age, sex, BMI, surgical segments, degree of disc degeneration, or postoperative length of hospital stay. However, the suture group had a longer operative time (63.28 ± 4.17 minutes vs 54.71 ± 4.89 minutes, t = 8.759, P < .05). At 12 months postoperatively, neither group showed aggravated disc degeneration. There was also no significant difference in excellent rates between the 2 groups (95.45% vs 92.86%, X
2=0.265, P = .607). However, the suture group had a lower intervertebral disc height loss rate compared to the control group (22.3% ± 4.6% vs 29.8% ± 6.2%, X
2=6.390, P < .001). In conclusion, single-channel percutaneous endoscopic nucleotomy combined with annulus fibrosus suturing is a safe and reliable treatment for LDH. It effectively reduces the recurrence rate, slows disc degeneration and loss of disc height, and achieves excellent early outcomes.
Mediators of the association between educational attainment and carpal tunnel syndrome: A 2-sample, 2-step Mendelian randomization study
Authors: Lai Yunrong , Hu Weiquan , Hu Suping , Liu Qinglin , Huang Xianping , Zhao Qinfei
Published: October 2024

To clarify the causal relationship and potential mediators between educational attainment and carpal tunnel syndrome (CTS), as well as to evaluate whether educational attainment, cognition, and intelligence independently exert causal effects on CTS, we employed univariable Mendelian randomization (MR), multivariable MR, reverse MR, and 2-step MR approaches. Our research demonstrates that educational attainment exerts an independent causal effect on CTS, with this causal relationship being unidirectional. Five mediators were identified as significant influencers within the causal pathways connecting educational attainment and CTS. Targeting these mediators may be beneficial in the prevention of CTS.
Automation and innovation in home hemodialysis machines
Authors: Shamy Osama El , Sloand James A.
Published: October 2024

Purpose of review

In this review, we discuss the timeline of innovation and technologic development in home hemodialysis (HHD) in the United States and the legislative approvals that accompanied them.

Recent findings

The most recently FDA-approved home hemodialysis devices provide features that include on-demand and batch dialysate generation, access disconnect for venous needle dislodgement, touchscreen interface with visual and auditory prompts and animations, drop-in sterilized cartridges with prestrung tubing, hot water disinfection of tubing allowing extended-use, dialysate flow rates as high as 500 ml/min, as well as remote treatment monitoring capabilities. Furthermore, wearable/portable dialysis devices are currently under development to simplify dialysis delivery to patients with end-stage kidney disease.

Home hemodialysis devices providing longitudinal hemodialysis across different clinical settings, virtual reality headsets for more personalized training, automated patient support, as well as wearable device development and innovations give hope for a future where home hemodialysis is more accessible and seamless.
Emerging CART Therapies for Pediatric Acute Myeloid Leukemia
Authors: Ceolin Valeria , Spadea Manuela , Apolito Vincenzo , Saglio Francesco , Fagioli Franca
Published: October 2024

The prognosis of children with acute myeloid leukemia (AML) has improved incrementally over the last decades. However, at relapse, overall survival (OS) ∼40% to 50% and is even lower for patients with chemorefractory disease. Effective and less-toxic therapies are urgently needed for these children. In the last years, immune-directed therapies such as chimeric antigen receptor (CAR)-T cells were introduced, which showed outstanding clinical activity against B-cell malignancies. CART therapies are being developed for AML on the basis of the results obtained for other hematologic malignancies. The biggest challenge of CART therapy for AML is to identify a specific target antigen, since antigens expressed in AML cells are usually shared with healthy hematopoietic stem cells. An overview of prospects of CART in pediatric AML, focused on the common antigens targeted by CART in AML that have been tested or are currently under investigation, is provided in this manuscript.
Sustainable Development Goals for Cleft Care
Authors: Mustakim Kezia Rachellea , Eo Mi Young , Mustakim Inggrid Grace , Kim Soung Min
Published: October 2024

The sustainable development goals (SDGs) are a blueprint for a better and more sustainable future for all. Understanding these initiatives helps everyone develop insights into critical global issues, including health care management, education, gender equality, and other challenges related to the 17 SDGs. Implementing these goals will contribute to sustainable development for cleft care in the least developed countries. The authors critically reviewed relevant articles on cleft lip and palate from 2014 to 2022. The authors' review utilized the online search tools Springer Nature, PubMed, and Google Scholar, using keywords of “cleft lip and palate,” “cleft outreach program,” “sustainable cleft care,” “sustainable development goals for cleft,” and “sustainable outreach program.” In addition, the authors investigated the potentially necessary SDGs for sustainable cleft care management.
The Key to Successful Social Interactions
Authors: Brien Ashley R. , Hutchins Tiffany L.
Published: October 2024

Autobiographical memory (ABM) is memory for past personal experiences and is foundational to the development of many cognitive processes. As such, ABM and social learning are developmentally intertwined and functionally dependent, and impairments in each are well-documented in autism. Evidence suggests that elaborative reminiscing (ER) causally and positively impacts neurotypical children’s ABM and social learning. The purpose of this study was to evaluate the effectiveness of a new caregiver-mediated ABM intervention that adapts the principles of ER in ways that align with best practices for supporting social learning in autistic children. Participants were 26 caregiver-child dyads; all children (ages 6–15 years) had a diagnosis of autism. We hypothesized that: (1) caregivers would demonstrate improvements in ER across three phases of study (pre-treatment, post-treatment, and follow-up) and (2) children would demonstrate improvements in supported and unsupported ABM and social learning. Results indicated that caregivers demonstrated increased elaborativeness at post-intervention, and that this was maintained at follow-up. Additionally, children demonstrated improvements in supported memory and some measures of social learning at post-intervention, and this was maintained at follow-up. Children also showed improvements in unsupported memory at post-intervention; however, this was not maintained. Results suggest that caregivers of autistic children can be trained to use ER, and that ER is associated with the development of supported memory in autistic children across a wide range of ages. Clinical applications include supporting social learning and connection in autism using ER.
SPP1+ tumor-associated macrophages induce radioresistance of nasopharyngeal carcinoma through crosstalk with the tumor microenvironment
Authors: Zhang Wenda , Lin Lili , Haoxuan Ying , Li Nan , Zhou Xinyi , Yang Qi , Hu Shulu , Cai Jiayi , Lin Anqi , Quan Cheng , Liu Zaoqu , Zhang Jian , Luo Peng , Wei Ting
Published: October 2024

The function and phenotype of tumor-associated macrophages (TAMs) influence the efficacy of radiotherapy. However, the effect of different subsets of TAMs on the radioresistance in nasopharyngeal carcinoma (NPC) still needs to be further explored. This study utilized single-cell RNA sequencing (scRNA-seq) to analyze 120,579 cells obtained from 15 NPC samples. Cell annotation, cell‒cell communication analysis, and functional annotation were used to investigate the impact of TAMs on the effectiveness of radiotherapy in NPC patients. Additionally, we employed RNA-seq data and clinical information from many patients, including 24 NPC samples from Zhujiang Hospital, 3,934 samples from patients with a history of radiotherapy, for further validation. We identified a hub TAM subpopulation, SPP1+ TAMs, that induced radioresistance in NPC based on single-cell RNA sequencing (scRNA-seq) data. We combined many public datasets to confirm their prognostic value in radiotherapy patients. We found that SPP1+ TAMs had stronger protumorigenic and immunosuppressive effects in the postradiotherapy recurrent tumor (PRRT) group. SPI1 transcription factor efficiently regulates the expression level of SPP1 in macrophages. In addition, we validated the underlying mechanisms by molecular docking, multiplex immunofluorescence and cellular experiments. In conclusions, by forming an immunosuppressive microenvironment and promoting tumor cell proliferation, SPP1+ TAMs leading to radioresistance and poor clinical prognosis in NPC patients. Targeting SPP1+ TAMs could provide new insights into improving the efficacy of radiotherapy in NPC patients.
Oatk: a de novo assembly tool for complex plant organelle genomes
Authors: Zhou Chenxi , Brown Max , Blaxter Mark ,   The Darwin Tree of Life Project Consortium, McCarthy Shane A. , Durbin Richard
Published: October 2024

Plant organelle genomes, particularly the large mitochondrial genomes with intricate repetitive structures, present significant challenges for assembly. The advent of long-read sequencing technologies provides a transformative opportunity to generate complete genomes, but problems of resolving alternative structures remain. Here we introduce a novel tool for plant organelle genome assembly from high-accuracy long reads. Our method employs ak-mer based assembler for rapid assembly graph construction, integrates a profile HMM gene database for robust organelle sequence annotation, and leverages a new search method to find the best supported path through the assembly graph. We describe high-quality organelle assemblies for 195 plant species and demonstrate improvements over other methods. The assembled genomes provide multiple insights into structural complexity, heteroplasmy, and DNA exchange between organelles.
Dietary Fiber Modulates Macrophage Activity in a Microfluidic Model of Colonocyte-Microbiota Interactions in Colorectal Cancer
Authors: Penarete-Acosta Daniel , Mittal Mohet , Chakraborty Sanjukta , Han Arum , Jayaraman Arul
Published: October 2024

Dietary fiber has been consistently associated with a decreased risk of colorectal cancer (CRC) development. While the apoptotic effect of dietary fiber microbial fermentation products on tumor colonocytes is well established, the role of these products on other components of the tumor microenvironment remains unexplored. Tumor associated macrophages play a critical role in tumor development in the colon; however, the effect of dietary fiber fermentation by microbiota on macrophage-colonocyte interaction in colorectal cancer has been difficult to dissect due to a lack of complexin vitromodels of CRC containing both immune cells and microbiota. Recently, we developed a microfluidic model that facilitates the coculture of CRC spheroids with complex microbial communities. Here, we expand our model to include macrophages and employ it to study the impact of dietary fiber on macrophage-colonocyte interaction. We optimized monocyte differentiation parametersin vitroand demonstrated the capacity of our model to recapitulate changes in microbiota composition and metabolic output associated with dietary fiber administrationin vivo. Combinatorial coculture of colonocytes with microbiota and macrophages revealed that alterations in microbial production of SCFA derived from dietary fiber fermentation correlated with enhanced colonocyte death, possibly mediated by an increase in transcription of tumor pro-apoptotic signals by macrophages. Our work highlights the capacity of complexin vitrosystems to study the role of microbial metabolism of dietary molecules on CRC colonocyte viability and macrophage activity.
Dopamine controls the Sensitivity to Manganese induced Dopaminergic neurotoxicity inCaenorhabditis elegans
Authors: Raj Vishnu , Thekkuveettil Anoopkumar
Published: October 2024

Manganism, a disease with characteristic degeneration of dopamine neurons, has distinct aetiology and clinical manifestations, striking similarities with Parkinson’s Disease (PD). Environmental exposure to manganese (Mn) is one of the risk factors for the occurrence of PD. The definitive role of dopamine (DA) in Mn mediated neurodegeneration, and its developmental impact has not been well studied. To understand the pathways involved in Mn-induced neurotoxicity, we usedC. elegansas the model system. Our results showed that adult worms treated with 50 and 100 mM MnCl2significantly increased DA neurodegeneration. L1 larvae spared without neurodegeneration when treated with MnCl2alone showed a significant increase in neurodegeneration (>50%) when MnCl2exposure was given after DA pretreatment. However, both adult and larval exposure to MnCl2demonstrated significant toxicity by reducing the survival rate. In adult worms, 100 mM MnCl2treatment after DA pretreatment further elevated the percentage of neurodegeneration. The Mn or DA alone exposed adult worms showed recovery of neuronal dopamine function within 24 hours, although exogenous DA and Mn treated worms showed prolonged behavioural defects.Cat-2mutants, without DA, were resistant to Mn mediated neurodegeneration. In contrast,Cat-2overexpressing strain displayed severe neurodegeneration at lower concentrations of MnCl2(50 mM). Our results on biochemical, behavioural and genetic assays proved endogenous/exogenous DA level controls the sensitivity to Mn induced dopaminergic neurotoxicity.
FoldMark: Protecting Protein Generative Models with Watermarking
Authors: Zhang Zaixi , Jin Ruofan , Fu Kaidi , Cong Le , Zitnik Marinka , Wang Mengdi
Published: October 2024

Protein structure is key to understanding protein function and is essential for progress in bioengineering, drug discovery, and molecular biology. Recently, with the incorporation of generative AI, the power and accuracy of computational protein structure prediction/design have been improved significantly. However, ethical concerns such as copyright protection and harmful content generation (biosecurity) pose challenges to the wide implementation of protein generative models. Here, we investigate whether it is possible to embed watermarks into protein generative models and their outputs for copyright authentication and the tracking of generated structures. As a proof of concept, we propose a two-stage method FoldMark as a generalized watermarking strategy for protein generative models. FoldMark first pretrain watermark encoder and decoder, which can minorly adjust protein structures to embed user-specific information and faithfully recover the information from the encoded structure. In the second step, protein generative models are fine-tuned with Low-Rank Adaptation modules with watermark as condition to preserve generation quality while learning to generate watermarked structures with high recovery rates. Extensive experiments are conducted on open-source protein structure prediction models (e.g., ESMFold and MultiFlow) and de novo structure design models (e.g., FrameDiff and FoldFlow) and we demonstrate that our method is effective across all these generative models. Meanwhile, our watermarking framework only exerts a negligible impact on the original protein structure quality and is robust under potential post-processing and adaptive attacks.
Activating p53Y220Cwith a Mutant-Specific Small Molecule
Authors: Zhu Xijun , Byun Woong Sub , Pieńkowska Dominika Ewa , Nguyen Kha The , Gerhartz Jan , Geng Qixiang , Qiu Tian , Zhong Jianing , Jiang Zixuan , Wang Mengxiong , Sarott Roman C. , Hinshaw Stephen M. , Zhang Tinghu , Attardi Laura D. , Nowak Radosław P. , Gray Nathanael S.
Published: October 2024

TP53is the most commonly mutated gene in cancer, but it remains recalcitrant to clinically meaningful therapeutic reactivation. We present here the discovery and characterization of a small molecule chemical inducer of proximity that activates mutant p53. We named this compoundTRanscriptionalActivator ofp53 (TRAP-1) due to its ability to engage mutant p53 and BRD4 in a ternary complex, which potently activates mutant p53 and triggers robust p53 target gene transcription. Treatment of p53Y220Cexpressing pancreatic cell lines withTRAP-1results in rapid upregulation of p21 and other p53 target genes and inhibits the growth of p53Y220C-expressing cell lines. Negative control compounds that are unable to form a ternary complex do not have these effects, demonstrating the necessity of chemically induced proximity for the observed pharmacology. This approach to activating mutant p53 highlights how chemically induced proximity can be used to restore the functions of tumor suppressor proteins that have been inactivated by mutation in cancer.
The diversification of mealybugs was triggered by new symbiont acquisitions and followed by adaptive radiations on host plants
Authors: Choi Jinyeong , Palanichamy Pradeep , Lee Seunghwan , Husnik Filip
Published: October 2024

Symbiotic microorganisms play a critical role in supplementing beneficial nutrients to herbivorous insects feeding on unbalanced diets. These microbial symbionts can both facilitate or constrain plant-feeding insects’ adaptations to certain host plants, depending on their gene content and metabolic potential. The diet breadth of herbivorous insects is considered an important evolutionary factor affecting genotypic and phenotypic changes associated with host shifts. Acquiring new symbionts can, therefore, drive changes in niche breadth and subsequent adaptive radiation(s). Mealybugs comprise one of the major groups of scale insects, most of which feed on diverse angiosperms. Different sub-lineages of mealybugs also house different lineages of bacteria and fungi as their obligate symbionts. Here, we use mealybugs as a model system to test the hypothesis that the evolution of herbivorous insects is driven by both obligate symbionts and host plants. Based on metagenome analyses of 28 host species as well as a literature survey, we identified Betaproteobacteria, Gammaproteobacteria, Flavobacteriia, andOphiocordycepsfungi as obligate symbionts of the major clades of mealybugs. A time-calibrated phylogenetic tree of mealybugs allowed us to infer the ancestral obligate symbionts of the major mealybug clades. Our results indicate that the emergence of major mealybug lineages coincided with the acquisitions of new obligate endosymbionts. Subsequent radiations of mealybugs were inferred to have mostly resulted from the adaptive radiation through continuous host shifts on angiosperms. The contribution of microbial symbiosis to the diversification of herbivorous insects is thus likely limited by new symbiont origins or replacements, and insect adaptations play a larger role in further plant switches.
A tumor-secreted protein utilizes glucagon release to cause host wasting
Authors: Ding Guangming , Li Yingge , Cheng Chen , Tan Kai , Deng Yifei , Pang Huiwen , Wang Zhongyuan , Dang Peixuan , Wu Xing , Rushworth Elisabeth , Yuan Yufeng , Yang Zhiyong , Song Wei
Published: October 2024

Tumor-host interaction plays a critical role in malignant tumor-induced organ wasting across multiple species. Despite known regulation of regional wasting of individual peripheral organs by tumors, whether and how tumors utilize critical host catabolic hormone(s) to simultaneously induce systemic host wasting, however, is largely unknown. Using the conserved yki3SA-tumor model inDrosophila, we discovered that tumors increase the production of adipokinetic hormone (Akh), a glucagon-like catabolic hormone, to cause systemic host wasting, including muscle dysfunction, lipid loss, hyperglycemia, and ovary atrophy. We next integrated RNAi screening and Gal4-LexA dual expression system to identify that yki3SA-gut tumors secrete Pvf1 to remotely activate its receptor Pvr in Akh-producing cells (APCs), ultimately promoting Akh production. The underlying molecular mechanisms involved the Pvf1-Pvr axis that triggers Mmp2-dependent ECM remodeling of APCs and enhances innervation from the excitatory cholinergic neurons. Interestingly, we also confirmed the similar mechanisms governing tumor-induced glucagon release and organ wasting in mammals. Blockade of either glucagon or PDGFR (homolog of Pvr) action efficiently ameliorated organ wasting in the presence of malignant tumors. Therefore, our results demonstrate that tumors remotely promote neural-associated Akh/glucagon production via Pvf1-Pvr axis to cause systemic host wasting.
Point mutations of the mitochondrial chaperone TRAP1 affect its functions and pro-neoplastic activity
Authors: Laquatra Claudio , Magro Alessia , Guarra Federica , Lambrughi Matteo , Fracasso Giulio , Bacchin Melissa , Ferrone Lavinia , La Spina Martina , Moroni Elisabetta , Papaleo Elena , Colombo Giorgio , Rasola Andrea
Published: October 2024

The mitochondrial chaperone TRAP1 is a key regulator of cellular homeostasis and its activity has important implications in neurodegeneration, ischemia and cancer. Recent evidence has indicated that TRAP1 mutations are involved in several disorders, even though the structural basis for the impact of point mutations on TRAP1 functions has never been studied. By exploiting a modular structure-based framework and molecular dynamics simulations, we investigated the effect of five TRAP1 mutations on its structure and stability. Each mutation differentially impacts long-range interactions, intra and inter-protomer dynamics and ATPase activity. Changes in these parameters influence TRAP1 functions, as revealed by their effects on the activity of the TRAP1 interactor succinate dehydrogenase (SDH). In keeping with this, TRAP1 point mutations affect the growth and migration of aggressive sarcoma cells, and alter sensitivity to a selective TRAP1 inhibitor. Our work provides new insights on the structure-activity relationship of TRAP1, identifying crucial amino acid residues that regulate TRAP1 proteostatic functions and pro-neoplastic activity.
Cytokine-induced reprogramming of human macrophages toward Alzheimer’s disease-relevant molecular and cellular phenotypesin vitro
Authors: Podlesny-Drabiniok Anna , Romero-Molina Carmen , Patel Tulsi , See Wen Yi , Liu Yiyuan , Marcora Edoardo , Goate Alison M.
Published: October 2024

Myeloid cells including brain-resident (microglia) and peripheral macrophages play a crucial role in various pathological conditions, including neurodegenerative disorders like Alzheimer’s disease (AD). They respond to disruption of tissue homeostasis associated with disease conditions by acquiring various transcriptional and functional states. Experimental investigation of these states is hampered by the lack of tools that enable accessible and robust reprogramming of human macrophages toward Alzheimer’s disease-relevant molecular and cellular phenotypesin vitro. In this study, we investigated the ability of a cytokine mix, including interleukin-4 (IL4), colony stimulating factor 1 (CSF1/MCSF), interleukin 34 (IL34) and transforming growth factor beta (TGFβ), to induce reprogramming of cultured human THP-1 macrophages. Our results indicate this treatment led to significant transcriptomic changes, driving THP-1 macrophages towards a transcriptional state reminiscent of disease-associated microglia (DAM) and lipid-associated macrophages (LAM) collectively referred to as DLAM. Transcriptome profiling revealed gene expression changes related to oxidative phosphorylation, lysosome function, and lipid metabolism. Single-cell RNA sequencing revealed an increased proportion of DLAM clusters in cytokine mix-treated THP-1 macrophages. Functional assays demonstrated alterations in cell motility, phagocytosis, lysosomal activity, and metabolic and energetic profiles. Our findings provide insights into the cytokine-mediated reprogramming of macrophages towards disease-relevant states, highlighting their role in neurodegenerative diseases and potential for therapeutic development.
Effect of thermoneutral housing on MASLD severity, hepatic gene expression, and BAT activation during β3-adrenergic stimulation in mice
Authors: Pauline Martin Céline Marie , Polizzi Arnaud , Alquier-Bacquié Valérie , Huillet Marine , Rives Clémence , Dauriat Charlène , Bruse Justine , Melin Valentine , Naylies Claire , Lippi Yannick , Lasserre Frédéric , Wan JingHong , Flores-Flores Rémy , Bertrand-Michel Justine , Blas-Y-Estrada Florence , Rousseau-Bacquié Elodie , Levade Thierry , Rémignon Hervé , Langin Dominique , Mouisel Etienne , Lotersztajn Sophie , Chassaing Benoit , Gamet-Payrastre Laurence , Guillou Hervé , Ellero-Simatos Sandrine , Fougerat Anne , Loiseau Nicolas
Published: October 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD), and its more advanced stage metabolic dysfunction-associated steatohepatitis, is the most common chronic liver disease, constituting a major public health issue. No medication is approved for MASLD treatment, and relevant preclinical models are needed to define molecular mechanisms underlying MASLD pathogenesis, and evaluate therapeutic approaches. Here we demonstrated that compared to standard temperature housing, thermoneutral housing aggravated western diet (WD)-induced obesity, diabetes, and steatosis in male mice, which was associated with increased hepatic expression of inflammation- and fibrosis-related genes. Accordingly, compared to standard-housed mice, thermoneutral-housed WD-fed mice developed more severe hepatic inflammation and fibrosis. The liver is the central metabolic organ in whole-body metabolic homeostasis. We used thermoneutrally housed mice with WD-induced MASLD to examine the effect of MASLD during β3- adrenergic stimulation, and found that diet-induced MASLD was associated with defective inter- organ metabolic cross-talk, leading to impaired brown adipose tissue activation.

Highlights

Thermoneutral housing promotes WD-induced obesity and MASLD in mice

Thermoneutral housing fosters WD-induced change in gene expression

Thermoneutral housing fosters hepatic inflammation and fibrosis

MASLD is associated with defective BAT response to β3-adrenergic stimulation
SPONGE: Simple Prior Omics Network GEnerator
Authors: Hovan Ladislav , Kuijjer Marieke L.
Published: October 2024

Gene regulatory networks modelled from experimental data can be improved through the use of prior biological knowledge on e.g. transcription factor binding. There are several tools that utilise this information. However, the prior networks used with them are often not updated and may fail to reflect the most up-to-date information. Here we present SPONGE, a Python module designed to access information across biological databases, chiefly JASPAR and STRING, to model two types of networks—a prior gene regulatory network mapping transcription factors to genes based on their predicted binding sites, and a prior protein-protein interaction network mapping potential interactions between transcription factors. SPONGE is mainly designed to work with the PANDA algorithm and the corresponding NetZoo family of tools. However, the networks are provided in an easily adaptable format for other tools. SPONGE was designed with ease of use in mind, and it provides sensible default values for all of its parameters while giving the users freedom to fine-tune them. The code for the Python module and the documentation can be found inour GitHub repository.
Serum and Tear Autoantibodies from NOD and NOR Mice as Potential Diagnostic Indicators of Local and Systemic Inflammation in Sjögren’s Disease
Authors: Kakan Shruti Singh , Abdelhamid Sara , Ju Yaping , MacKay J Andrew , Edman Maria C. , Raman Indu , Zhu Chengsong , Raj Prithvi , Hamm-Alvarez Sarah F
Published: October 2024

Background

Sjögren’s Disease (SjD) is an autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands (LG). The LG produces the protein-rich aqueous component of tears, and SjD-associated autoimmune dacryoadenitis (AD) may thus alter tear autoantibody composition.

Methods

The presence of tertiary lymphoid structures (TLS) in LG from two murine models of SjD-associated AD, male NOD and male NOR mice, were evaluated using immunofluorescence. IgG and IgA reactivity in serum and tears from these models were probed in three studies against a panel of 80-120 autoantigens using autoantibody microarrays relative to serum and tears from healthy male BALB/c mice. Data were analyzed by R package Limma.

Results

Analysis of immunofluorescence in LG sections from both SjD models showed TLS. Only one autoantibody was significantly elevated in tears and serum in both SjD models across all studies. Three autoantibodies were significantly elevated in serum but not in tears in both SjD models across all studies. Conversely, six IgG and thirteen IgA autoantibodies (6 sharing the same autoantigen) were significantly elevated in tears but not serum in both SjD models.

Conclusion

NOD and NOR mice with SjD-associated AD have distinct autoantibody profiles in tears and serum. Tear IgA isotype autoantibodies showed a greater diversity than tear IgG autoantibodies. TLS observed in LG are a likely source of the tear autoantibodies.
Pseudomonas aeruginosametabolite 3-oxo-C12HSL induces apoptosis through T2R14 and the mitochondrial calcium uniporter
Authors: Miller Zoey A. , Mueller Arielle , Thompson Joel C. , Sywanycz Sarah M. , Hill Brianna L. , Carey Ryan M. , Lee Robert J.
Published: October 2024

Head and neck squamous cell carcinomas (HNSCCs) arise in the mucosal lining of the upper aerodigestive tract. HNSCCs have high mortality rates and current treatments can be associated with severe morbidities. It is vital to discover effective, minimally invasive therapies that improve survival and quality of life. We previously discovered that bitter taste receptor 14 (T2R14), a GPCR, kills HNSCC cells when activated by bitter agonists. We are now investigating endogenous bitter ligands that exist in HNSCC tumor microenvironment (TME). The TME includes cells, signaling molecules, and microbes that can greatly influence treatment responses and overall prognosis in HNSCC.Pseudomonas aeruginosais a gram-negative bacterium that colonizes/infects HNSCC patients. 3-oxo-C12SHL is a quorum-sensing N-acyl homoserine lactone (AHL) secreted byP. aeruginosawhich is also a bitter compound. 3-oxo-C12HSL induces apoptosis but this has never been linked to T2R activation. We hypothesized that 3-oxo-C12HSL induces apoptosis in HNSCC via T2R14. We show that 3-oxo-C12HSL activates intracellular Ca2+responses in HNSCC cells. This is inhibited with T2R14 antagonization. 3-oxo-C12HSL may activate additional Ca2+channels as the Ca2+dynamics are independent from store-operated calcium entry (SOCE). 3-oxo-C12HSL inhibits cell viability, depolarizes mitochondria, and produces ROS. This induces apoptosis in HNSCC cells. In a comparative screen of quorum-sensing AHLs, 3-oxo-C12HSL was the only AHL that elicited both a Ca2+response and reduced cell viability. These results suggest thatP. aeruginosamay play a significant role in modulating an anti-tumor TME through 3-oxo-C12HSL. Moreover, 3-oxo-C12HSL could be a novel, higher-affinity bitter therapeutic for HNSCC. Further research is warranted to elucidate the mechanisms of other endogenous T2R agonists present in the TME.
A comparative network analysis of high-risk MYCN amplified and high-risk MYCN non-amplified neuroblastoma patients
Authors: Chang Erin , Chou Charissa , Chang Wen-I , Honeyman Joshua N , Uzun Alper
Published: October 2024

Neuroblastoma is the most common extracranial solid tumor in children. Under contemporary staging guidelines, amplification of MYCN, defined as possessing 10 or more copies of the MYCN gene, is sufficient to classify a patient as high-risk. We aim to investigate the complex genetic landscape of neuroblastoma through a network biology perspective, focusing on complex protein-protein interaction (PPI) networks. Reanalyzing three historical neuroblastoma RNA-Seq datasets, we conducted a comparative network analysis of high-risk MYCN amplified patients and high-risk MYCN non-amplified patients to identify PPI networks that serve as predictive biomarkers for developing high-risk disease. We used R scripts to extract the top 100 most highly expressed genes from each dataset and then analyzed the expression profiles using Proteinarium, a network analysis tool that identifies clusters of patients with shared PPI networks. Statistically significant clusters were annotated and analyzed for network similarity between datasets. Our study isolated four significant clusters with majority high-risk MYCN amplified patients. We annotated the genes unique to high-risk MYCN amplified patients and identified several potential network biomarkers for this particular genotype of neuroblastoma, including ribosome biogenesis (RPL7A, RPL30, RPL35, RPS8), heat shock protein (HSPA8, HSP90AA1, HSP90AB1), matrix metallopeptidase (MMP2, MMP9, MMP13), and collagen (COL2A1, COL5A3, COL6A2, COL11A1, COL16A1) gene networks. The results of this study provide potential therapeutic targets for high-risk MYCN amplified neuroblastoma.
Lactoferrin-Derived Peptide Chimera Induces Caspase-independent Cell Death in Multiple Myeloma
Authors: Jang Young-Saeng , Dehkohneh Shima Barati , Lim Jaewon , Kim Jaehui , Ahn Donghwan , Choi Sun Shim , Kang Seung Goo
Published: October 2024

Lactoferrin-derived peptide chimera is a synthetic peptide that mimics the functional unit of lactoferrin with antibacterial activity. Antimicrobial peptides are promising candidates for cancer treatment. Although LF is known to have anticancer effects, to the best of our knowledge, its effects on multiple myeloma have not yet been studied. In this study, we explored the potential of lactoferrin-derived chimera for the treatment of multiple myeloma, a malignant clonal plasma cell disease of the bone marrow. Lactoferrin-derived chimera effectively inhibited MM1S, MM1R, and RPMI8226 multiple myeloma cell growth and induced the early and late phases of apoptosis, but not in normal peripheral blood mononuclear cells. Furthermore, lactoferrin-derived chimera modulates the relative expression of genes involved in survival, apoptosis, and mitochondrial dysfunction at the transcriptional level. Mitochondrial analysis revealed that lactoferrin-derived chimera triggered oxidative stress in multiple myeloma cells, leading to the generation of reactive oxygen species and a decline in mitochondrial membrane potential, resulting in mitochondrial dysfunction. Although lactoferrin-derived chimera did not cause caspase-dependent cell death, it induced nuclear translocation of apoptosis-inducing factor and endonuclease G, indicating the initiation of caspase-independent apoptosis. Overall, our data suggest that lactoferrin-derived chimera induces caspase-independent programmed cell death in multiple myeloma cell lines by increasing the nuclear translocation of apoptosis-inducing factor/endonuclease G. Therefore, lactoferrin-derived chimera has potential in multiple myeloma cancer therapies.