bluuebunny/crossref_metadata_2025 huggingface dataset:
Causal association between hyperthyroidism and risk of gastroesophageal reflux or esophageal cancer: a bidirectional Mendelian randomization investigation
Authors: Zhu Xingyu , Li Ming , Gan Hanghang , Guo Yingqiang
Published: September 2024

Background

Emerging observational studies indicated an association between hyperthyroidism and gastrointestinal disorders. However, it remains unclear whether this association is causal, particularly in the case of gastroesophageal reflux (GERD) and esophageal cancer.

Methods

To assess the potential causal relationship between hyperthyroidism and GERD or esophageal cancer, we conducted a bidirectional 2-sample Mendelian randomization study. Independent genetic instruments for hyperthyroidism from the UK Biobank (N case=3,545 and N control=459,388) and public genome-wide association study (GWAS) dataset (N case=3,731 and N control=480,867) were used to investigate the association with esophageal cancer in the UK Biobank study (N case=740 and N control=372,016) and GERD in the public GWAS database (N case=20,381 and N control=464,217). Four different approaches (inverse variance weighted (IVW), weighted mode, MR-Egger, and weighted median regression) were used to ensure that our results more reliable. Additional sensitivity analyses were also performed to validate our results.

Results

When hyperthyroidism was considered as the exposure factor, it appeared to act as a protective factor for GERD (ORIVW = 0.88, 95% CI, 0.79-0.99, P = 0.039), while as a risk factor for esophageal cancer (ORIVW = 1.03, 95% CI, 1.01-1.06, P = 0.003). However, there is no evidence supporting a reverse causal relationship between genetic susceptibility to hyperthyroidism and GERD or esophageal cancer.

Conclusion

Our findings provided genetic evidence supporting bidirectional causal relationships between hyperthyroidism and GERD or esophageal cancer. These results substantiate certain discoveries from previous observational studies on a causal level and provide insight into relevant genetic susceptibility factors.
Food antigens suppress small intestinal tumorigenesis
Authors: Sasaki Takaharu , Ota Yuna , Takikawa Yui , Terrooatea Tommy , Kanaya Takashi , Takahashi Masumi , Taguchi-Atarashi Naoko , Tachibana Naoko , Yabukami Haruka , Surh Charles D. , Minoda Aki , Kim Kwang Soon , Ohno Hiroshi
Published: September 2024

Food components suppressing small intestinal tumorigenesis are not well-defined partly because of the rarity of this tumor type compared to colorectal tumors. Using Apcmin/+ mice, a mouse model for intestinal tumorigenesis, and antigen-free diet, we report here that food antigens serve this function in the small intestine. By depleting Peyer’s patches (PPs), immune inductive sites in the small intestine, we found that PPs have a role in the suppression of small intestinal tumors and are important for the induction of small intestinal T cells by food antigens. On the follicle-associated epithelium (FAE) of PPs, microfold (M) cells pass food antigens from lumen to the dendritic cells to induce T cells. Single-cell RNA-seq (scRNA-seq) analysis of immune cells in PPs revealed a significant impact of food antigens on the induction of the PP T cells and the antigen presentation capacity of dendritic cells. These data demonstrate the role of food antigens in the suppression of small intestinal tumorigenesis by PP-mediated immune cell induction.
Machine learning-based identification of an immunotherapy-related signature to enhance outcomes and immunotherapy responses in melanoma
Authors: Deng Zaidong , Liu Jie , Yu Yanxun V. , Jin Youngnam N.
Published: September 2024

Background

Immunotherapy has revolutionized skin cutaneous melanoma treatment, but response variability due to tumor heterogeneity necessitates robust biomarkers for predicting immunotherapy response.

Methods

We used weighted gene co-expression network analysis (WGCNA), consensus clustering, and 10 machine learning algorithms to develop the immunotherapy-related gene model (ITRGM) signature. Multi-omics analyses included bulk and single-cell RNA sequencing of melanoma patients, mouse bulk RNA sequencing, and pathology sections of melanoma patients.

Results

We identified 66 consensus immunotherapy prognostic genes (CITPGs) using WGCNA and differentially expressed genes (DEGs) from two melanoma cohorts. The CITPG-high group showed better prognosis and enriched immune activities. DEGs between CITPG-high and CITPG-low groups in the TCGA-SKCM cohort were analyzed in three additional melanoma cohorts using univariate Cox regression, resulting in 44 consensus genes. Using 101 machine learning algorithm combinations, we constructed the ITRGM signature based on seven model genes. The ITRGM outperformed 37 published signatures in predicting immunotherapy prognosis across the training cohort, three testing cohorts, and a meta-cohort. It effectively stratified patients into high-risk or low-risk groups for immunotherapy response. The low-risk group, with high levels of model genes, correlated with increased immune characteristics such as tumor mutation burden and immune cell infiltration, indicating immune-hot tumors with a better prognosis. The ITRGM’s relationship with the tumor immune microenvironment was further validated in our experiments using pathology sections with GBP5, an important model gene, and CD8 IHC analysis. The ITRGM also predicted better immunotherapy response in eight cohorts, including urothelial carcinoma and stomach adenocarcinoma, indicating broad applicability.

Conclusions

The ITRGM signature is a stable and robust predictor for stratifying melanoma patients into ‘immune-hot’ and ‘immune-cold’ tumors, enhancing prognosis and response to immunotherapy.
Curriculum guide for teaching house officers and faculty: applying procedure codes effectively using chemical denervation as a model
Authors: Berri Maryam , Beydoun Noha , Johnson Martha
Published: September 2024

Introduction

The healthcare system in the United States relies heavily on physician-and house officer-driven initiation of billing and coding for collection of hospital payments and professional fees. Under the umbrella of practice management is the ever-changing and suboptimally taught concept of procedural billing and coding to house officers and faculty. Clinical providers and practitioners initiate billing and coding for performed services based on the procedural visit encounter, supported by the appropriate documentation. Correct charge capture is dependent on accurately linking CPT codes and J codes, including waste documentation, modifiers, and charge collection. We discuss a perspective regarding a new curricular methodology that teaches learners to apply an algorithmic approach for coding CPT codes, J codes, and modifiers for chemical denervation procedures involving high-cost botulinum toxin. We further recommend the use of visuals with algorithm development for other pertinent procedures that are specific to a department.

Methods

We developed a curriculum that includes algorithmic visuals, pre-and post-test questions, and reflections. It was implemented across various learner types.

Results

This chemical denervation curriculum was well-received and impactful in meeting the objectives of the course. It further expanded a learner’s vision of practice management that can be applied to other procedural examples.

Discussion

The results demonstrate a clear gap in practice management education, with pre-education knowledge on applying appropriate codes being particularly low among resident physicians. Learners found the algorithm we developed especially valuable, as it serves as a practical tool for accurately accounting for all aspects of CPT codes, modifiers, and J-codes. The methodology of the algorithmic approach proved to be innovative for avoiding billing write-offs and loopbacks that were beneficial for the training process. Learners indicated that this approach can be applied to other procedural billing.
Clinical profiles of older adults in French Caribbean nursing homes: a descriptive cross-sectional study
Authors: Boucaud-Maitre Denis , Simo Nadine , Villeneuve Roxane , Rambhojan Christine , Thibault Nathalie , Joseph Sarah-Priscilla , Bonnet Michel , Dramé Moustapha , Vainqueur Larissa , Rinaldo Leila , Letchimy Laurys , Dartigues Jean-François , Cesari Matteo , Rolland Yves , Vellas Bruno , Amieva Hélène , Tabué-Teguo Maturin
Published: September 2024

Background

Nursing homes in the Caribbean are scarce and the characteristics of their residents have not been previously documented. This study aimed to describe the clinical profiles of residents living in nursing homes in Guadeloupe and Martinique (French West Indies).

Methods

This is a cross-sectional study of the baseline screening data from the KASEHPAD (Karukera Study of Ageing in nursing homes) study. Clinical characteristics and geriatric scale scores, including the Activities of Daily Living (ADL), Mini-Mental State Examination (MMSE), Mini Nutritional Assessment Short-Form (MNA-SF) and Short Physical Performance Battery (SPPB) were collected and analysed.

Results

A total of 332 older adults were recruited between September 2020 and November 2022. The mean age of the residents was 81.3 ± 10.1, with a male–female ratio of 1:1. Diabetes was reported in 28.3% of the residents, hypertension in 66.6% and heart disease in 18.4%. Dementia was diagnosed in 52.3% of the residents and 74.9% had a MMSE score ≤18. The prevalence of Parkinson’s disease was 9.0%. Additionally, 18.4% were unable to perform any basic activities of daily living (ADL score of 0). The prevalence of physical impairment (SPPB < 8) was 90.0%. One-quarter of the residents were classified as undernourished (MNA-SF score ≤ 7).

Conclusion

Residents in Caribbean nursing homes are younger than in metropolitan France, whereas they present quite similar clinical profiles. Notably, a high prevalence of diabetes, cardiovascular diseases and neurodegenerative diseases was observed. This study represents a preliminary effort to address the knowledge gap regarding the aging trajectories of older adults in the Caribbean and could guide the development of future nursing homes in these countries.
Cytomegalovirus results in poor graft function via bone marrow-derived endothelial progenitor cells
Authors: Lv Weiran , Zhou Ya , Zhao Ke , Xuan Li , Huang Fen , Fan Zhiping , Chang Yuan , Yi Zhengshan , Jin Hua , Liang Yang , Liu Qifa
Published: September 2024

Introduction

Poor graft function (PGF), characterized by myelosuppression, represents a significant challenge following allogeneic hematopoietic stem cell transplantation (allo-HSCT) with human cytomegalovirus (HCMV) being established as a risk factor for PGF. However, the underlying mechanism remains unclear. Bone marrow endothelial progenitor cells (BM-EPCs) play an important role in supporting hematopoiesis and their dysfunction contributes to PGF development. We aim to explore the effects of CMV on BM-EPCs and its underlying mechanism.

Methods

We investigated the compromised functionality of EPCs derived from individuals diagnosed with HCMV viremia accompanied by PGF, as well as after infected by HCMV AD 169 strain in vitro, characterized by decreased cell proliferation, tube formation, migration and hematopoietic support, and increased apoptosis and secretion of TGF-β1.

Results

We demonstrated that HCMV-induced TGF-β1 secretion by BM-EPCs played a dominant role in hematopoiesis suppression in vitro experiment. Moreover, HCMV down-regulates Vitamin D receptor (VDR) and subsequently activates p38 MAPK pathway to promote TGF-β1 secretion by BM-EPCs.

Discussion

HCMV could infect BM-EPCs and lead to their dysfunction. The secretion of TGF-β1 by BM-EPCs is enhanced by CMV through the activation of p38 MAPK via a VDR-dependent mechanism, ultimately leading to compromised support for hematopoietic progenitors by BM EPCs, which May significantly contribute to the pathogenesis of PGF following allo-HSCT and provide innovative therapeutic strategies targeting PGF.
Discovery of GJC1 as a prognostic biomarker in glioma cells: insights into its cell-cycle relationship and differential expression in non-neuronal cells
Authors: Ji Xiangtian , Chen Xin , Lin Guozhong , Ma Kaiming , Yang Junhua , Zhao Xiaofang , Chen Suhua , Yang Jun
Published: September 2024

Background

Gliomas, originating from the most common non-neuronal cells in the brain (glial cells), are the most common brain tumors and are associated with high mortality and poor prognosis. Glioma cells exhibit a tendency to disrupt normal cell-cycle regulation, leading to abnormal proliferation and malignant growth. This study investigated the predictive potential of GJC1 in gliomas and explored its relationship with the cell cycle.

Methods

Retrospective analysis of RNA-seq and single-cell sequencing data was conducted using the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. The differential expression of GJC1 in gliomas with various pathological features and in different non-neuronal cell groups was analyzed. Functional data were examined using gene set variation analysis (GSVA). Furthermore, CellMiner was used to evaluate the relationship between GJC1 expression and predicted treatment response across these databases.

Results

GJC1 expression was enriched in high-grade gliomas and 1p/19q non-codeletion gliomas. GJC1 enrichment was observed in classical and mesenchymal subtypes within the TCGA glioma subtype group. In single-cell subgroup analysis, GJC1 expression was higher in glioma tissues compared to other non-neuronal cells. Additionally, the TCGA classical subtype of glioma cells exhibited more GJC1 expression than the other subgroups. GJC1 emerged as an independent prognostic factor for overall survival in glioma. GSVA unveiled potential mechanisms by which GJC1 may impact cell-cycle regulation in glioma. Finally, a significant correlation was observed between GJC1 expression and the sensitivity of multiple anti-cancer drugs.

Conclusion

These findings confirmed GJC1 as a novel biomarker and provided insights into the differential gene expression in non-neuronal cells and the impact of the cell cycle on gliomas. Consequently, GJC1 may be used to predict glioma prognosis and has potential therapeutic value.
The evolution of public attention in acute kidney injury and continuous renal replacement therapy: trends analysis from 2004 to 2024
Authors: Thongprayoon Charat , Wathanavasin Wannasit , Suppadungsuk Supawadee , Sheikh Mohammad S. , Abdelgadir Yasir H. , Miao Jing , Mao Michael A. , Craici Iasmina M. , Qureshi Fawad , Kashani Kianoush B. , Cheungpasitporn Wisit
Published: September 2024

Background

Acute kidney injury (AKI) and the need for Continuous Renal Replacement Therapy (CRRT) are critically important health concerns. This study analyzes global and regional Internet search queries to understand public attention in AKI and CRRT over time.

Methods

We used Google Trends™ to analyze search queries for AKI and CRRT from January 2004 to March 2024. The study examined global trends and detailed insights from the United States, including state-by-state breakdowns. We identified patterns, peaks of attention, and temporal trends in public attention, comparing regional variations across the US and top-ranking countries worldwide.

Results

Global attention in AKI peaked in October 2022, with Portugal, Zambia, and Spain showing the highest regional attention. Within the United States, peak attention was in February 2008. Tennessee, Pennsylvania, and West Virginia were the top states that paid attention to AKI. Attention in CRRT peaked globally in March 2024. South Korea, Saudi Arabia, and Bahrain have led the global attention to CRRT. In the United States, peak attention was in April 2020. West Virginia, Tennessee, and Kentucky showed the highest state-specific attention in CRRT.

Conclusions

This study reveals significant temporal and geographical variations in online search patterns for AKI and CRRT, suggesting evolving public attention to these critical health issues. This knowledge can guide the development of targeted public health initiatives, enhance medical education efforts, and help healthcare systems tailor their approach to improving awareness and outcomes in kidney health across diverse populations.
Dual-factor model of sleep and diet: a new approach to understanding central fatigue
Authors: Zhang Yifei , Zhang Zehan , Yu Qingqian , Lan Bijuan , Shi Qinghuan , Liu Yan , Zhang Weiyue , Li Feng
Published: September 2024

Background

Numerous studies have recently examined the impact of dietary factors such as high-fat diets on fatigue. Our study aims to investigate whether high-fat diet (HFD) alone or combined with alternate-day fasting (ADF) can lead to the central fatigue symptoms and to investigate the potential integration of dietary and sleep variables in the development of central fatigue models.

Methods

Seventy-five male Wistar rats were divided into five groups: control, HFD, HFD + ADF, modified multiple platform method (MMPM), and MMPM+HFD + ADF. Each group underwent a 21-day modeling period according to their respective protocol. Their behavioral characteristics, fatigue biochemical markers, hippocampal pathological changes, mitochondrial ultrastructure, and oxidative stress damage were analyzed.

Results

Our findings demonstrate that using only HFD did not cause central fatigue, but combining it with ADF did. This combination led to reduced exercise endurance, decreased locomotor activity, impaired learning and memory abilities, along with alterations in serum levels of alanine aminotransferase (ALT), creatine kinase (CK), and lactate (LAC), as well as hippocampal pathological damage and other central fatigue symptoms. Moreover, the MMPM+HFD + ADF method led to the most obvious central fatigue symptoms in rats, including a variety of behavioral changes, alterations in fatigue-related biochemical metabolic markers, prominent pathological changes in hippocampal tissue, severe damage to the ultrastructure of mitochondria in hippocampal regions, changes in neurotransmitters, and evident oxidative stress damage. Additionally, it was observed that rats subjected to HFD + ADF, MMPM, and MMPM+HFD + ADF modeling method exhibited significant brain oxidative stress damage.

Conclusion

We have demonstrated the promotive role of dietary factors in the development of central fatigue and have successfully established a more stable and clinically relevant animal model of central fatigue by integrating dietary and sleep factors.
The key to intestinal health: a review and perspective on food additives
Authors: Wang Haitao , Bai Junyi , Miao Pengyu , Wei Yu , Chen Xiaochao , Lan Haibo , Qing Yong , Zhao Meizhu , Li Yanyu , Tang Rui , Yang Xiangdong
Published: September 2024

In this review, we explore the effects of food additives on intestinal health. Food additives, such as preservatives, antioxidants and colorants, are widely used to improve food quality and extend shelf life. However, their effects on intestinal microecology May pose health risks. Starting from the basic functions of food additives and the importance of intestinal microecology, we analyze in detail how additives affect the diversity of intestinal flora, oxidative stress and immune responses. Additionally, we examine the association between food additives and intestinal disorders, including inflammatory bowel disease and irritable bowel syndrome, and how the timing, dosage, and individual differences affect the body’s response to additives. We also assess the safety and regulatory policies of food additives and explore the potential of natural additives. Finally, we propose future research directions, emphasizing the refinement of risk assessment methods and the creation of safer, innovative additives.
Preoperative MRI-based radiomic nomogram for distinguishing solitary fibrous tumor from angiomatous meningioma: a multicenter study
Authors: Li Mengjie , Fu Shengli , Du Jingjing , Han Xiaoyu , Duan Chongfeng , Ren Yande , Qiao Yaqian , Tang Yueshan
Published: September 2024

Purpose

This study evaluates the efficacy of radiomics-based machine learning methodologies in differentiating solitary fibrous tumor (SFT) from angiomatous meningioma (AM).

Materials and methods

A retrospective analysis was conducted on 171 pathologically confirmed cases (94 SFT and 77 AM) spanning from January 2009 to September 2020 across four institutions. The study comprised a training set (n=137) and a validation set (n=34). All patients underwent contrast-enhanced T1-weighted (CE-T1WI) and T2-weighted(T2WI) MRI scans, from which 1166 radiomics features were extracted. Subsequently, seventeen features were selected through minimum redundancy maximum relevance (mRMR) and the least absolute shrinkage and selection operator (LASSO). Multivariate logistic regression analysis was employed to assess the independence of these features as predictors. A clinical model, established via both univariate and multivariate logistic regression based on MRI morphological features, was integrated with the optimal radiomics model to formulate a radiomics nomogram. The performance of the models was assessed utilizing the area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV).

Results

The radiomics nomogram demonstrated exceptional discriminative performance in the validation set, achieving an AUC of 0.989. This outperformance was evident when compared to both the radiomics algorithm (AUC= 0.968) and the clinical model (AUC = 0.911) in the same validation sets. Notably, the radiomics nomogram exhibited impressive values for ACC, SEN, and SPE at 97.1%, 93.3%, and 100%, respectively, in the validation set.

Conclusions

The machine learning-based radiomic nomogram proves to be highly effective in distinguishing between SFT and AM.
Validation of a novel medical device (Chloe SED®) for the administration of analgesia during manual vacuum aspiration: a randomized controlled non-inferiority pilot study
Authors: Ramanathan Aparna , Samenjo Karlheinz Tondo , Bailey Robert C. , Imbamba Javan , Odenyo Stella , Koksal Erin , Diehl Jan Carel , Omoto Jackton , Gwer Stephen
Published: September 2024

Introduction

Millions of women worldwide annually undergo manual vacuum aspiration (MVA) with no pain medication, which is a violation of their basic human dignity. We designed a novel device (Chloe SED®) to administer paracervical block (PCB) during MVA in countries where pain medication is not typically given due to the high cost of the necessary tools.

Methods

We conducted a single-blinded, randomized controlled non-inferiority trial including 61 patients at two hospitals in Kisumu, Kenya, to validate Chloe SED® for administration of PCB during MVA. PCB administered with Chloe SED® was compared to PCB administered with a standard spinal needle. Patients requiring MVA were block randomized in blocks of six, each provider completing six PCBs—three with the Chloe SED® and three with the standard spinal needle. The trial was registered with the Kenya Pharmacy and Poisons Board, ECCT/19/03/01 (https://ctr.pharmacyboardkenya.org/applications/index/protocol_no:RUNDVC8xOS8wMy8wMQ__/filter:/investigator:/sites:/pages:5/start_date:/end_date:/disease_condition:/users:/ercs:/stages). An intention-to-treat analysis was completed. The primary outcome was the non-inferiority of the pain score during uterine evacuation with a non-inferiority margin of 2 points on an 11-point numerical rating scale. Secondary outcomes included the non-inferiority of the pain score at four other time points and patient satisfaction.

Results

Chloe SED® showed non-inferiority of the primary outcome with a mean pain score during evacuation of 3.8 [90% confidence interval (CI): 3.1–4.6] compared with the spinal needle at 4.1 (90% CI: 3.5–4.7). Non-inferiority of the pain score was shown at all time points. Most patients expressed a desire for the continued use of the device to administer PCB for MVA. No adverse events were noted.

Conclusion

In summary, the Chloe SED® appears non-inferior to the spinal needle and desirable for the administration of PCB during MVA.
Quantitative and functional changes in platelets and fibrinogen following cardiopulmonary by-pass in children
Authors: Plebani Margherita , Longchamp David , Lauwers Pauline , Di Bernardo Stefano , Perez Maria-Helena
Published: September 2024

Introduction

Cardiopulmonary bypass (CPB) causes coagulopathy, increasing the risk of postoperative bleeding and mortality. The underlying causes of post-CPB coagulopathy and the factors associated with its occurrence are not yet fully understood. This study assesses platelet and fibrinogen concentration and function following CPB in children with congenital heart diseases (CHD).

Methods

We analyzed prospective data from 104 patients aged 0–16 years who underwent CPB surgery for CHD. Blood samples were collected before surgery and within 30 min of CPB completion. In addition to usual coagulation tests, functional analyses were performed using point of care systems with thromboelastometry and impedance aggregometry.

Results

Platelet count, fibrinogen concentration, and platelet and fibrinogen activities significantly decreased after CPB. The duration of CPB was directly associated with a reduction in platelet count and fibrinogen level (r = −0.38, p < 0.001; r = −0.21, p = 0.03, respectively), but not with their measured activity. Postoperative percentages of baseline values for platelet count (58.36% [43.34–74.44] vs. 37.44% [29.81–54.17], p < 0.001) and fibrinogen concentration (73.68% [66.67–82.35] vs. 65.22% [57.89–70.83], p < 0.001) were significantly higher in patients who did not experience hypothermia during surgery. Age was inversely associated with the decrease in platelet count (r = 0.63, p < 0.001), TRAPTEM AUC (r = 0.43, p < 0.001), fibrinogen concentration (r = 0.44, p < 0.001) and FIBTEM MCF (r = 0.57, p < 0.001).

Conclusion

Post-CPB coagulopathy is multifactorial and not solely attributed to hemodilution. It also involves functional changes in coagulation cascade components, which can be demonstrated by thromboelastometry and impedance aggregometry. Young children, patients requiring prolonged CPB surgery, or those experiencing hypothermia are particularly affected.
Antibiotics-free compounds for managing carbapenem-resistant bacteria; a narrative review
Authors: Shariati Aref , Kashi Milad , Chegini Zahra , Hosseini Seyed Mostafa
Published: September 2024

Carbapenem-resistant (CR) Gram-negative bacteria have become a significant public health problem in the last decade. In recent years, the prevalence of CR bacteria has increased. The resistance to carbapenems could result from different mechanisms such as loss of porin, penicillin-binding protein alteration, carbapenemase, efflux pump, and biofilm community. Additionally, genetic variations like insertion, deletion, mutation, and post-transcriptional modification of corresponding coding genes could decrease the susceptibility of bacteria to carbapenems. In this regard, scientists are looking for new approaches to inhibit CR bacteria. Using bacteriophages, natural products, nanoparticles, disulfiram, N-acetylcysteine, and antimicrobial peptides showed promising inhibitory effects against CR bacteria. Additionally, the mentioned compounds could destroy the biofilm community of CR bacteria. Using them in combination with conventional antibiotics increases the efficacy of antibiotics, decreases their dosage and toxicity, and resensitizes CR bacteria to antibiotics. Therefore, in the present review article, we have discussed different aspects of non-antibiotic approaches for managing and inhibiting the CR bacteria and various methods and procedures used as an alternative for carbapenems against these bacteria.
Lentivirus-mediated RNA interference targeting HMGB1 modulates AQP1 to reduce pain induced by chronic compression of the dorsal root ganglia
Authors: Li Jinlu , Yang Kaihong , Yao Fuchao , Wei Hui
Published: September 2024

Backgrounds

Neuropathic pain (NP) is a kind of chronic pain that has attracted much attention in clinical practice, characterized by high morbidity, complex mechanisms, and difficulties in clinical treatment, with which the activation of High mobility group box 1 (HMGB1) is closely related. The aim of this study was to investigate the effects of lentivirus-mediated RNA interference gene therapy targeting HMGB1 on neuropathic pain in rats with chronic dorsal root ganglion compression (CCD) and its specific mechanisms, so as to explore new pharmacological targets.

Methods

Adult male Wistar rats were surgically subjected to chronic compression of the dorsal root ganglia (CCD). Behavioral tests were performed by calculating the paw withdrawal mechanical threshold (PWMT) and the thermal paw withdrawal latency (TPWL). Co-immunoprecipitation (CO-IP) was used to clarify protein interactions. Gene silencing was induced by injecting lentivirus expressing HMGB1 short hairpin RNA (shRNA) into rats. An LPS-inflammation-stimulated rat astrocyte model was established to validate the animal experiment results further. Western blot analysis and real-time quantitative PCR were used to detect pathway protein expression.

Results

After first establishing the rat CCD model, both PWMT and PTWL were significantly reduced in rats, indicating that the model construction was successful. After lentiviral silencing of HMGB1 expression, NP was significantly alleviated in CCD rats. CO-IP experiments showed a link between HMGB1 and AQP1; After silencing HMGB1 expression, the expression of AQP1 was significantly reduced, and HMGB1 was able to modulate the effect of AQP1 on NP. Further use of an inhibitor of the HMGB1 receptor showed that after inhibition of RAGE, AQP1 was significantly reduced; HMGB1 may regulate AQP1 through its receptor RAGE to affect NP. Silencing of HMGB1 resulted in a significant decrease in NF-κB, and HMGB1 affects the inflammatory pathways it mediates. After silencing AQP1, NF-κB also decreased significantly, indicating that AQP1 is an upstream regulator of NF-κB.

Conclusion

Lentivirus-mediated RNA interference (RNAi) silencing targeting HMGB1 may play a key role in the development of neuropathic pain in rats by regulating AQP1 expression via RAGE and ultimately activating NF-κB.
Analysis of riociguat and desmethyl riociguat by UPLC-MS/MS and its interaction with quercetin
Authors: Li Qingqing , Chen Xiaohai , Zhang Siping , Li Wanshu , Lin Hangjuan
Published: September 2024

Riociguat, an orally soluble guanylate cyclase (sGC)-promoting drug, is mainly used in the clinical treatment of pulmonary hypertension (PH). In this study, a novel ultra-performance liquid chromatography-tandem mass spectrometry method was developed to quantify the concentrations of riociguat and its metabolite (M1) in plasma. The precision, stability, accuracy, matrix effect, and recovery of the methodology were satisfactory. Quercetin, a well-recognized compound, functions as a novel anticancer agent with the potential to alleviate symptoms of PH. Therefore, the potential interaction between quercetin and riociguat was investigated in this study. The levels of riociguat and M1 in rat plasma were measured using the method developed in this study to evaluate the interactions between riociguat and quercetin in rats. The results revealed that quercetin significantly inhibited riociguat and M1 metabolism with increased systemic exposure.
Genetic dissection of stem and leaf rachis prickles in diploid rose using a pedigree-based QTL analysis
Authors: Rawandoozi Zena J. , Barocco Andrew , Rawandoozi Maad Y. , Klein Patricia E. , Byrne David H. , Riera-Lizarazu Oscar
Published: September 2024

Introduction

Prickles are often deemed undesirable traits in many crops, including roses (Rosa sp.), and there is demand for rose cultivars with no or very few prickles. This study aims to identify new and/or validate reported quantitative trait loci (QTLs) associated with stem and leaf rachis prickle density, characterize the effects of functional haplotypes for major QTLs, and identify the sources of QTL-alleles associated with increased/decreased prickle density in roses.

Methods

QTL mapping using pedigree-based analysis (PBA), and haplotype analysis were conducted on two multi-parental diploid rose populations (TX2WOB and TX2WSE).

Results and discussion

Twelve QTLs were identified on linkage groups (LGs) 2, 3, 4, and 6. The major QTLs for the stem prickle density were located between 42.25 and 45.66 Mbp on chromosome 3 of the Rosa chinensis genome assembly, with individual QTLs explaining 18 to 49% of phenotypic variance (PVE). The remaining mapped QTLs were minor. As for the rachis prickle density, several QTLs were detected on LG3, 4, and 6 with PVE 8 to 17%. Also, this study identified that ancestors R. wichurana ‘Basye’s Thornless’, ‘Old Blush’, and the pollen parent of M4-4 were common sources of favorable alleles (q) associated with decreased prickle density, whereas ’Little Chief’ and ‘Srche Europy’ were the source of unfavorable alleles (Q) in the TX2WOB and TX2WSE populations, respectively. The outcomes of this work complement other studies to locate factors that affect prickle density. These results can also be utilized to develop high-throughput DNA tests and apply parental selection to develop prickle-free rose cultivars.
Experimental evidence of inbreeding depression for competitive ability and its population-level consequences in a mixed-mating plant
Authors: Walker Mark J. , Spigler Rachel B.
Published: September 2024

Inbreeding depression is a key factor regulating the evolution of self-fertilization in plants. Despite predictions that inbreeding depression should evolve with selfing rates as deleterious alleles are increasingly exposed and removed by selection, evidence of purging the genetic load in wild populations is equivocal at best. This discordance could be explained, in part, if the load underlying inbreeding depression is subject to soft selection, i.e., the fitness of selfed individuals depends on the frequency and density of selfed vs. outcrossed individuals in the population. Somewhat counterintuitively, this means that populations with contrasting mutation load can have similar fitness. Soft selection against selfed individuals may be expected when there is inbreeding depression for competitive ability in density-regulated populations. We tested population-level predictions of inbreeding depression in competitive ability by creating a density series of potted plants consisting of either purely outcrossed, purely selfed, or mixed (50% outcrossed, 50% selfed) seed of the mixed-mating biennial Sabatia angularis (Gentianaceae) representing ecological neighborhoods. Focusing on the growth and survival of juveniles, we show that mean plant size is independent of neighborhood composition when resources are limiting, but greatest in outcrossed neighborhoods at low densities. Across a range of densities, this manifests as stronger density-dependence in outcrossed populations compared to selfed or mixed ones. We also found significantly greater size inequalities among individuals in mixed neighborhoods, even at high densities where mean juvenile size converged, a key signature of asymmetric competition between outcrossed and selfed individuals. Our work illustrates how soft selection could shelter the genetic load underlying inbreeding depression and its demographic consequences.
Rice plants treated with biochar derived from Spirulina (Arthrospira platensis) optimize resource allocation towards seed production
Authors: Minello Luana Vanessa Peretti , Kuntzler Suelen Goettems , Lamb Thainá Inês , Neves Cleo de Oliveira , Berghahn Emílio , da Paschoa Roberta Pena , Silveira Vanildo , de Lima Jeferson Camargo , Aguzzoli Cesar , Sperotto Raul Antonio
Published: September 2024

The use of biofertilizers is becoming an economical and environmentally friendly alternative to promote sustainable agriculture. Biochar from microalgae/cyanobacteria can be applied to enhance the productivity of food crops through soil improvement, slow nutrient absorption and release, increased water uptake, and long-term mitigation of greenhouse gas sequestration. Therefore, the aim of this study was to evaluate the stimulatory effects of biochar produced from Spirulina (Arthrospira platensis) biomass on the development and seed production of rice plants. Biochar was produced by slow pyrolysis at 300°C, and characterization was performed through microscopy, chemical, and structural composition analyses. Molecular and physiological analyses were performed in rice plants submitted to different biochar concentrations (0.02, 0.1, and 0.5 mg mL-1) to assess growth and productivity parameters. Morphological and physicochemical characterization revealed a heterogeneous morphology and the presence of several minerals (Na, K, P, Mg, Ca, S, Fe, and Si) in the biochar composition. Chemical modification of compounds post-pyrolysis and a highly porous structure with micropores were observed. Rice plants submitted to 0.5 mg mL-1 of biochar presented a decrease in root length, followed by an increase in root dry weight. The same concentration influenced seed production, with an increase of 44% in the number of seeds per plant, 17% in the percentage of full seeds per plant, 12% in the weight of 1,000 full seeds, 53% in the seed weight per plant, and 12% in grain area. Differential proteomic analyses in shoots and roots of rice plants submitted to 0.5 mg mL-1 of biochar for 20 days revealed a fine-tuning of resource allocation towards seed production. These results suggest that biochar derived from Arthrospira platensis biomass can stimulate rice seed production.
Endophytic bacteria with allelopathic potential regulate gene expression and metabolite production in host Casuarina equisetifolia
Authors: Wang Ying , Chen Pan , Lin Qi , Zuo Linzhi , Li Lei
Published: September 2024

Introduction

Casuarina equisetifolia is a common protective forest in coastal areas. However, artificial C. equisetifolia forests cannot self-renew, mainly due to the accumulation of allelochemicals. Endophytic bacteria may alleviate the root growth inhibition caused by allelochemicals in C. equisetifolia seedlings. B. amyloliquefaciens and B. aryabhattai were endophytic bacteria with strong allelopathy in C. equisetifolia root. The allelopathy mechanism of these two endophytes and their interaction with C. equisetifolia remains to be studied.

Methods

Whole-genome sequencing of B. amyloliquefaciens and B. aryabhattai isolated from the roots of allelochemical-accumulating C. equisetifolia was performed using Illumina Hiseq and PacBio single-molecule sequencing platforms. Sterile seedlings of C. equisetifolia were treated with either individual or mixed bacterial cultures through root drenching. Transcriptional and metabolomics analyses were conducted after 3 days of infection.

Results and discussion

Whole-genome sequencing of Bacillus aryabhattai and Bacillus amyloliquefaciens showed that the two strains contained various horizontal gene transfer elements such as insertion sequence, prophage and transposon. In addition, these two strains also contain numerous genes related to the synthesis and catabolism of allelochemicals. After these two strains of bacteria were individually or mixed infected with C. equisetifolia, metabolomics and transcriptomic analysis of C. equisetifolia showed the 11 important secondary metabolite biosynthesis among them alkaloids biosynthesis, phenylpropanoid and terpenes biosynthesis and related genes were putatively regulated. Correlation analysis revealed that 48 differentially expressed genes had strong positive correlations with 42 differential metabolites, and 48 differentially expressed genes had strong negative correlations with 36 differential metabolites. For example, CMBL gene showed positive correlations with the allelochemical (-)-Catechin gallate, while Bp10 gene showed negative correlations with (-)-Catechin gallate.

Conclusion

The intergenerational accumulation of allelochemicals may induce horizontal gene transfer in endogenic bacteria of Casuarina equisetifolia root. Endophytic Bacillus plays an allelopathic role by assisting the host in regulating gene expression and the production and/or variety of allelochemicals. This comprehensive study sheds light on the intricate genetic and metabolic interactions between Bacillus endophytes and C. equisetifolia. These findings provide insights into endophyte-mediated allelopathy and its potential uses in plant biology and forest sustainability.
Organic waste recycling application increases N availability and mitigates N2O emission without crop yield penalty in the North China Plain
Authors: Chen Lin , Du Hailun , Liu Qing , Gao Wangsheng , Cui Jixiao , Chen Yuanquan
Published: September 2024

Introduction

Agricultural organic waste recycling can supply nutrients for crop production and partially replace chemical nitrogen fertilizers, which is beneficial for waste management and environmental protection. Nevertheless, comprehensive evaluation of the effects of different organic materials applications on crop yield and the environment is limited.

Methods

Therefore, in this study, a comprehensive investigation of the synergistic effects of straw, pig manure, and biogas residue recycling on the wheat (Triticum aestivum L.) and maize (Zea mays L.) systems was carried out in the North China Plain. Field experiments were conducted from 2019 to 2021, comprising five treatments: straw (ST), pig manure (PM), and biogas residue (BR) partially replacing chemical nitrogen fertilizer, sole application of chemical nitrogen fertilizer (CF), and a control with no nitrogen application (WN).

Results and discussion

The results showed that organic materials significantly increased soil total nitrogen (3.04%–9.10%) and N recovery efficiency (REN; 42.21%–44.99%), but pig manure was more beneficial in increasing crop yields (3.50%), especially wheat yields (8.72%), and REN was significantly higher than that of the other treatments. Organic materials performed differently in wheat and maize seasons, and wheat yield could be improved by organic materials return. Organic materials stimulated N2O emission in wheat season (4.28%–32.20%), while biogas residue inhibited the N2O emission in maize season (47.47%). The negative effect of straw and biogas residue on yield decreased with increasing years of return, and pig manure continued to contribute to yield. In conclusion, pig manure is the optimal alternative that can increase crop yield, soil N content, and REN without stimulating N2O emissions.
Integrated volatile metabolome and transcriptome analyses provide insights into the warm aroma formation elicited by methyl jasmonate in carrot root
Authors: Wang Guang-Long , Wu Jia-Qi , Chen Yang-Yang , Xu Yu-Jie , An Ya-Hong , Ren Xu-Qin , Xiong Ai-Sheng
Published: September 2024

Carrot is a highly significant vegetable cultivated worldwide and possesses a unique aroma with abundant edible and medicinal values. However, it remains largely unknown whether jasmonic acid could regulate aroma formation in carrot. Here, an integrated analysis of the volatile metabolome and transcriptome of carrot roots exposed to different concentrations of methyl jasmonate (MeJA) was performed. The results revealed 1,227 volatile organic compounds and 972 differential accumulated metabolites, with terpenes representing the largest portion. MeJA treatment evidently increased the relative odor activity values as well as the accumulation of most volatile compounds. In addition, 4,787 differentially expressed genes were identified and subjected to function enrichment analysis, indicating a role of terpene biosynthesis and metabolism in response to MeJA application. A network consisting of 4,680 transcription factor-structural pairs that showed highly significant positive correlations was constructed, which may be utilized as genetic targets for examining terpene accumulation and aroma formation elicited by methyl jasmonate. The results from the present work substantially improved our understanding of MeJA-mediated aroma formation in carrot.
The effect of chess on cognition: a graph theory study on cognitive data
Authors: Gonzalez-Burgos Lissett , Lozano-Rodriguez Candida , Molina Yaiza , Garcia-Cabello Eloy , Aciego Ramón , Barroso José , Ferreira Daniel
Published: September 2024

Objectives

We aimed to advance our understanding of the effect of chess on cognition by expanding previous univariate studies with the use of graph theory on cognitive data. Specifically, we investigated the cognitive connectome of adult chess players.

Method

We included 19 chess players and 19 controls with ages between 39 and 69 years. Univariate analysis and graph theory included 27 cognitive measures representing multiple cognitive domains and subdomains. Graph analysis included global and nodal measures of integration, segregation, and centrality. We also performed an analysis of community structures to gain an additional understanding of the cognitive architecture of chess players.

Results

The analysis of global graph measures showed that chess players had a higher local efficiency than controls at the cost of a lower global efficiency, which did not permeate segregation aspects of their connectome. The nodal graph measures showed that executive/attention/processing speed and visuoconstructive nodes had a central role in the connectome of chess players. The analysis of communities showed that chess players had a slightly reorganized cognitive architecture into three modules. These graph theory findings were in the context of better cognitive performance in chess players than controls in visuospatial abilities.

Conclusion

We conclude that the cognitive architecture of chess players is slightly reorganized into functionally and anatomically coherent modules reflecting a distinction between visual, verbal, and executive/attention/processing speed-related functions, perhaps reminiscent of right hemisphere and left hemisphere subnetworks orchestrated by the frontal lobe and its white matter connections.
Analyses of single-cell and bulk RNA sequencing combined with machine learning reveal the expression patterns of disrupted mitophagy in schizophrenia
Authors: Yang Wei , Lian Kun , Ye Jing , Cheng Yuqi , Xu Xiufeng
Published: September 2024

Background

Mitochondrial dysfunction is an important factor in the pathogenesis of schizophrenia. However, the relationship between mitophagy and schizophrenia remains to be elucidated.

Methods

Single-cell RNA sequencing datasets of peripheral blood and brain organoids from SCZ patients and healthy controls were retrieved. Mitophagy-related genes that were differentially expressed between the two groups were screened. The diagnostic model based on key mitophagy genes was constructed using two machine learning methods, and the relationship between mitophagy and immune cells was analyzed. Single-cell RNA sequencing data of brain organoids was used to calculate the mitophagy score (Mitoscore).

Results

We found 7 key mitophagy genes to construct a diagnostic model. The mitophagy genes were related to the infiltration of neutrophils, activated dendritic cells, resting NK cells, regulatory T cells, resting memory T cells, and CD8 T cells. In addition, we identified 12 cell clusters based on the Mitoscore, and the most abundant neurons were further divided into three subgroups. Results at the single-cell level showed that Mitohigh_Neuron established a novel interaction with endothelial cells via SPP1 signaling pathway, suggesting their distinct roles in SCZ pathogenesis.

Conclusion

We identified a mitophagy signature for schizophrenia that provides new insights into disease pathogenesis and new possibilities for its diagnosis and treatment.