bluuebunny/crossref_metadata_2025_split huggingface dataset:
METTL3 exacerbates insulin resistance in hepatocytes by regulating m6A modification of cytochrome P450 2B6
Authors: Li Yongqing , Zhang Dantong , Gao Yinan , Wang Peijun , Wang Zejun , Zhang Bingyang , Liu Junjun , Ye Diwen , Ma Wanshan , Lu Sumei 
Published: September 2023

Abstract
Background
Insulin resistance (IR) in hepatocytes endangers human health, and frequently results in the development of non-alcoholic fatty liver disease (NAFLD). Research on m6A methylation of RNA molecules has gained popularity in recent years; however, the molecular mechanisms regulating the processes of m6A modification and IR are not known. The cytochrome P450 (CYP450) enzyme system, which is mainly found in the liver, is associated with the pathogenesis of NAFLD. However, few studies have been conducted on CYP450 related m6A methylation. Here, we investigated the role of the methyltransferase METTL3 in exacerbating IR in hepatocytes, mainly focusing on the regulation of m6A modifications in CYP2B6.

Methods and results
Analysis using dot blot and epitranscriptomic chips revealed that the m6A modification pattern of the transcriptome in high-fat diet (HFD)-induced fatty liver and free fatty acid (FFA)-induced fatty hepatocytes showed significant changes. CYP450 family members, especially Cyp2b10, whose homolog in humans is CYP2B6, led to a noticeable increase in m6A levels in HFD-induced mice livers. Application of the METTL3 methyltransferase inhibitor, STM2457, increased the level of insulin sensitivity in hepatocytes. We then analyzed the role of METTL3 in regulating m6A modification of CYP2B6 in hepatocytes. METTL3 regulated the m6A modification of CYP2B6, and a positive correlation was found between the levels of CYP2B6 translation and m6A modifications. Furthermore, interference with METTL3 expression and exposure to STM2457 inhibited METTL3 activity, which in turn interfered with the phosphorylated insulin receptor substrate (pIRS)-glucose transporter 2 (GLUT2) insulin signaling pathway; overexpression of CYP2B6 hindered IRS phosphorylation and translocation of GLUT2 to membranes, which ultimately exacerbated IR.

Conclusion
These findings offer unique insights into the role that METTL3-mediated m6A modifications of CYP2B6 play in regulating insulin sensitivity in hepatocytes and provide key information for the development of strategies to induce m6A modifications for the clinical treatment of NAFLD.
Bioremediation of malachite green dye using sodium alginate, Sargassum latifolium extract, and their silver nanoparticles
Authors: El-Sheekh Mostafa M. , Deyab Mohamed A. , Hassan Nagwa I. , Abu Ahmed Seham E. 
Published: September 2023

Abstract
Introduction
The textile, paper, rubber, plastic, leather, cosmetics, pharmaceutical, and food sectors extensively use malachite green (MG). In spite of this, it has mutagenic, carcinogenic, teratogenic, and, in some circumstances causes chronic respiratory disease.

Objectives
In this work, we used sodium alginate, Sargassum latifolium aqueous extract, and their silver nanoparticles to test their potential as inexpensive adsorbent agents to remove malachite green dye from aqueous solutions.

Methods
The removal rate of MG was determined using a series of bioadsorption experiments. Besides, the effect of different factors on bioadsorption, such as pH, adsorbent dose, contact time (min), and different concentrations of MG dye was investigated.

Results
The removal efficiency of MG dye by alginate nanoparticles, alginate, Sargassum latifolium aqueous extract, and S. latifolium aqueous extract nanoparticles was 91, 82, 84, and 68 respectively. The optimal conditions for bioadsorption of malachite green dye were pH 7, a contact time of 180 min, and an adsorbent dose of 0.02 g. The adsorption isotherm was fitted to Langmuir and Freundlich isotherm. Also, UV and FT–IR before and after the bioadsorption of MG were performed to confirm the bioadsorption process.

Conclusion
Our results indicated that alginate nanoparticles were the most effective bioadsorbent agent.
Association between adiposity and facial aging: results from a Mendelian randomization study
Authors: Liu Meiqi , Feng Jingwei 
Published: September 2023

Abstract
Background
Skin, as a sociologically meaningful interface, has psychological implications different from other organs, particularly in the context of the global population aging. Growing evidence suggests that facial aging is associated with an increased risk of adiposity. Existing research, however, were observational, and while they may find some correlations, it is difficult to simply disentangle non-causal or reverse-causal links because these associations may be confounded or fail to accurately reflect true causative linkages.

Objectives
We conducted a 2-sample Mendelian randomization (MR) study to examine the potential effect of facial aging on the risk of broad obesity and its three major adiposity indicators, including body mass index (BMI), body fat percentage (BF%) and waist circumference (WC).

Methods
Genetic instruments from IEU OpenGWAS project, one of the largest available genome-wide association studies (GWAS) for facial aging (423,999 samples) were used to investigate the relation to broad obesity (32,858 cases, 65,839 controls). Using the inverse-variance weighted (IVW) technique, single nucleotide polymorphisms (SNPs) associated with adiposity indicators (BMI (461,460 samples), BF% (454,633 samples), and WC (462,166 samples)) were investigated in relationship to facial aging. Further sensitivity analyses were performed, including Mendelian randomization-Egger (MR-Egger), weighted median estimates, and leave-one-out analysis, to evaluate the consistency of the results and related potential issues in MR studies.

Results
We identified strong and significant correlations between adiposity and facial aging in the 17 broad obesity-associated SNPs (IVW estimate of odds ratio OR = 1.020, 95% CI 1.010–1.029, P = 7.303e − 05), 458 BMI-associated SNPs (IVW estimate of odds ratio OR = 1.047, 95% CI 1.0357–1.058, P = 1.154e − 16),for the 395 BF%-associated SNPs (OR = 1.056, 95%CI 1.040–1.072,P = 7.617e − 12), or for the 374 WC-associated SNPs (OR = 1.072, 95% CI 1057–1.087,P = 1.229e − 23). A range of complementary methodologies have been employed to evaluate horizontal pleiotropy and related potential caveats occurring in MR research.

Conclusions
Using Mendelian randomization as an alternative approach to investigate causality, we found a causal relationship between adiposity and facial aging, which was statistically strong and significant.
An in vivo study to investigate an original intramedullary bone graft harvesting technology
Authors: Laubach Markus , Bessot Agathe , McGovern Jacqui , Saifzadeh Siamak , Gospos Jonathan , Segina Daniel N. , Kobbe Philipp , Hildebrand Frank , Wille Marie-Luise , Bock Nathalie , Hutmacher Dietmar W. 
Published: September 2023

AbstractBackgroundHarvesting bone graft (BG) from the intramedullary canal to treat bone defects is largely conducted using the Reamer–Irrigator–Aspirator (RIA) system. The RIA system uses irrigation fluid during harvesting, which may result in washout of osteoinductive factors. Here, we propose a new harvesting technology dedicated to improving BG collection without the potential washout effect of osteoinductive factors associated with irrigation fluid. This novel technology involves the conceptual approach of first aspirating the bone marrow (BM) with a novel aspirator prototype, followed by reaming with standard reamers and collecting the bone chips with the aspirator (reaming–aspiration method, R–A method). The aim of this study was to assess the harvesting efficacy and osteoinductive profile of the BG harvested with RIA 2 system (RIA 2 group) compared to the novel harvesting concept (aspirator + R–A method, ARA group).MethodsPre-planning computed tomography (CT) imaging was conducted on 16 sheep to determine the femoral isthmus canal diameter. In this non-recovery study, sheep were divided into two groups: RIA 2 group (n = 8) and ARA group (n = 8). We measured BG weight collected from left femur and determined femoral cortical bone volume reduction in postoperative CT imaging. Growth factor and inflammatory cytokine amounts of the BGs were quantified using enzyme-linked immunosorbent assay (ELISA) methods.ResultsThe use of the stand-alone novel aspirator in BM collection, and in harvesting BG when the aspirator is used in conjunction with sequential reaming (R–A method) was proven feasible. ELISA results showed that the collected BG contained relevant amounts of growth factors and inflammatory cytokines in both the RIA 2 and the ARA group.ConclusionsHere, we present the first results of an innovative concept for harvesting intramedullary BG. It is a prototype of a novel aspirator technology that enables the stepwise harvesting of first BM and subsequent bone chips from the intramedullary canal of long bones. Both the BG collected with the RIA 2 system and the aspirator prototype had the capacity to preserve the BG’s osteoinductive microenvironment. Future in vivo studies are required to confirm the bone regenerative capacity of BG harvested with the innovative harvesting technology.
Preclinical activity of selinexor in combination with eribulin in uterine leiomyosarcoma
Authors: Mittal Sonam , Kadamberi Ishaque Pulikkal , Chang Hua , Wang Feng , Kumar Sudhir , Tsaih Shirng-Wern , Walker Christopher J. , Chaluvally-Raghavan Pradeep , Charlson John , Landesman Yosef , Pradeep Sunila 
Published: September 2023

AbstractLeiomyosarcoma (LMS) is a rare soft tissue sarcoma (STS) that begins in smooth muscle tissue and most often initiates in the abdomen or uterus. Compared with other uterine cancers, uterine LMS (ULMS) is an aggressive tumor with poor prognosis and a high risk of recurrence and death, regardless of the stage at presentation. Selinexor is a first-in-class selective inhibitor of nuclear export (SINE) compound that reversibly binds to exportin 1 (XPO1), thereby reactivating tumor suppressor proteins and downregulating the expression of oncogenes and DNA damage repair (DDR) proteins. In this study, we evaluated the effects of selinexor in combination with doxorubicin and eribulin in the LMS tumor model in vitro and in vivo. Treatment of selinexor combined with eribulin showed synergistic effects on tumor growth inhibition in SK-UT1 LMS-derived xenografts. Immunohistochemical assessment of the tumor tissues showed a significantly reduced expression of proliferation (Ki67) and XPO1 markers following combination therapy compared to the control group. Global transcriptome analyses on tumor tissue revealed that the combination therapy regulates genes from several key cancer-related pathways that are differentially expressed in ULMS tumors. To our knowledge, this is the first preclinical study demonstrating the anti-cancer therapeutic potential of using a combination of selinexor and eribulin in vivo. Results from this study further warrant clinical testing a combination of chemotherapy agents with selinexor to reduce the morbidity and mortality from ULMS.
Retinopathy of prematurity: from oxygen management to molecular manipulation
Authors: Woods Jonathan , Biswas Susmito 
Published: September 2023

Abstract
Introduction
Retinopathy of prematurity (ROP) is a vasoproliferative disorder of the premature retina with the potential to progress to extraretinal neovascularisation. This review serves as an introduction to retinopathy of prematurity (ROP), outlining key parts of ROP pathophysiology, diagnosis and treatment. ROP is traditionally diagnosed by indirect ophthalmoscopy and classified using anatomical zones, stages of disease, and the presence or absence of “plus disease” (dilation and tortuosity of the major retinal arterioles and venules). ROP has a bi-phasic pathophysiology: initial hyperoxia causes reduced retinal vascularisation, followed by pathological vaso-proliferation resulting from subsequent hypoxia and driven by vascular endothelial growth factor (VEGF).

Advancements in management
This review summarises previous trials to establish optimum oxygen exposure levels in newborns and more recently the development of anti-VEGF agents locally delivered to block pathological neovascularisation, which is technically easier to administer and less destructive than laser treatment.

Future directions
There remains an ongoing concern regarding the potential unwanted systemic effects of intravitreally administered anti-VEGF on the overall development of the premature baby. Ongoing dosing studies may lessen these fears by identifying the minimally effective dose required to block extraretinal neovascularisation.
Subliminal perception of others’ physical pain induces personal distress rather than empathic concern
Authors: Song Juan , Zhao Zijing , Jiao Zhibin , Peng Yao , Chu Mingyuan 
Published: September 2023

Abstract
Background
What is our immediate reaction when we witness someone experiencing pain? The empathy-altruism hypothesis predicts that observers would display empathy and a tendency to approach the person in pain. Alternatively, the threat value of pain hypothesis (TVPH) argues that others' pain serves as a signal of threat and should induce observers’ avoidance response.

Methods
To examine these two hypotheses, three experiments were conducted. The experiments aimed to investigate the impact of subliminal exposure to others' physical pain on participants' emotional and behavioural responses.

Results
The results revealed that subliminal pain priming resulted in faster response and attentional bias to fearful faces compared to sad faces (Experiment 1), faster reaction times in recognizing fear-related words compared to anger-related words during a lexical decision task (Experiment 2), and faster avoidance responses towards anger-related words, as opposed to approaching responses towards positive words (Experiment 3).

Conclusions
The consistent findings across all experiments revealed that subliminal perception of pain scenes elicited fear emotion and immediate avoidance responses. Therefore, the outcomes of our study provide supportive evidence for the TVPH.
Online communication and positive psychological capital of college students in China: the mediating role of online social support
Authors: Jiang Ying , Chi Jingming , Wang Li , Geng Xiaomin 
Published: September 2023

AbstractOnline communication is one of the most significant factors that affect the growth and development of contemporary college students. The purpose of this study was to examine the mechanisms of online social support in the relationship between online communication and the positive psychological capital of college students in China. Drawing on social exchange theory, the research employed a sample of 1,212 Chinese college students and incorporated online social support as a mediating variable. The investigation constructed a research model using the College Students’ Online Communication Questionnaire, Online Social Support Questionnaire, and Positive Psychological Capital Questionnaire to examine the intricate relationship among online communication, online social support, and positive psychological capital. The study found that both online self-expression and online extended relationship actions positively influenced students’ positive psychological capital. However, online social participation did not demonstrate an impact on this measure. Furthermore, online social support was found to partially mediate the connection between online self-expression and positive psychological capital as well as between online extended relationships and positive psychological capital. Online social support fully mediated the relationship between online social participation and positive psychological capital.
A systematic review of sodium-glucose cotransporter 2 inhibitors and renal profiles among Japanese patients with type 2 diabetes mellitus
Authors: Mukai Junichi , Okamura Nakaba , Saito Yuki , Kubota Rie 
Published: September 2023

Abstract
Background
We conducted a systematic review and meta-analysis to summarize the available literature and comprehensively appraise the renal profiles of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in Japanese patients with type 2 diabetes mellitus (T2DM).

Methods
The electronic databases MEDLINE, Ichushi-web, and ClinicalTrials.gov were searched for studies without language restrictions from their inception until 20 July 2023 and CENTRAL until 21 September 2021. Studies were included if they were double-masked randomized controlled trials (RCTs) (1) including Japanese patients with T2DM aged > 18 years who received SGLT2i or a placebo, (2) reporting at least one renal outcome of serum creatinine or the estimated glomerular filtration rate (eGFR), and (3) with a follow-up of > 12 weeks. Cross-over and open label trials were excluded. The risk of bias based on the Cochrane risk-of-bias tool for randomized trials (RoB 2) was appraised. We computed the weighed mean difference with 95%CI for each renal outcome and used a random-effects model (inverse variance method).

Results
We ultimately retrieved 13 RCTs including 2687 individuals in our review. The durations of RCTs ranged between 12 and 104 weeks. Only one trial had a longer duration of more than one year. Ten out of 13 RCTs reported serum creatinine, while nine included eGFR. Serum creatinine and eGFR were slightly worse with SGLT2i than with a placebo [mean difference 0.01 (95%CI 0.00 to 0.02) mg/dL, p = 0.002, mean difference − 1.30 (95%CI -2.23 to -0.37) mL/min/1.73 m2, p = 0.006, respectively]. Merged results revealed insignificant heterogeneity (I2 < 30%).

Conclusion
These results suggest that SGLT2i slightly worsens serum creatinine and eGFR in Japanese patients with T2DM. However, since the durations of most RCTs were short, the effects of eGFR in particular may be transient. Further evidence is needed from rigorous studies that focus on renal outcomes with a longer duration to confirm the present results.
Determinant of under nutrition among under five children in Ambo town during covid 19 pandemic in 2020. A community-based cross-sectional study
Authors: Feyisa Beshadu Bedada , Dabu Getu Taresa 
Published: September 2023

Abstract
Background
About 8 to 44% of all child mortality in Africa is associated with undernutrition. To alleviate this problem, it is necessary to determine the magnitude and determinants of undernutrition during Covid 19 pandemic. However, there is scarce evidence in an urban setting like Ambo town. Therefore, this study assessed the magnitude and factors associated with undernutrition among under-five children in Ambo town, west Ethiopia.

Methods and patients
A community-based cross-sectional study was conducted in Ambo town from March 01–30, 2020. The child and mother/caregiver socio-demographic characteristics, child illness and health care utilization, and child feeding practice-related data were collected using the standardized tool adopted from similar studies conducted in Ethiopia. Anthropometric measurements of the child were made using a calibrated scale. A systematic sampling technique was employed to select 363 mothers/caregivers of the child as a source of data. Nutritional status indices were generated using ENASMART software. After testing for collinearity, variables with a p-value < 0.25 in binary logistic regression were interred to backward multiple logistic regressions at a level of significance of p < 0.05.

Results
A total of 363 participants were included in this study providing a 100% response rate and providing the following result. The mean (+ SD) age of children was 28.85 (+ 14.17) months and that of mothers/caregivers was 28.12 + 48 years. This study found 16.00%, 25.30%, and 19.00% of the study participants were underweight, wasted, and stunted respectively. Decisions making on major food purchases, who usually care for the child, the age at which the child starts complimentary food, late introduction of complementary food were positively associated with wasting. Diarrhea, birth weight, child age, age at which the child starts complimentary food, consumption of milk and milk product, and who usually care for the child were significantly associated with being underweight. Consumption of milk and milk products, household food security level, and birth weight were independent determinants of stunting.

Conclusion
This study identified a high prevalence of undernutrition, especially wasting. Childbirth weight, age, diarrhea, feeding practice, household (HH) food security, Decision making on major food purchases, late introduction of complementary food were found to be the potential determinants of undernutrition. Thus there should be an effort to improve the nutritional status of children in the study area by focusing on these factors.
Biological control of arbuscular mycorrhizal fungi and Trichoderma harzianum against Fusarium oxysporum and Verticillium dahliae induced wilt in tomato plants
Authors: Meddad-Hamza A. , Benzina F. , Meddad C. , Hamza N. , Reghmit A. , Ziane H. , Ksentini H. 
Published: September 2023

Abstract
Background
Arbuscular mycorrhizal fungi (AMF) and Trichoderma harzianum are effective bioagents against Fusarium oxysporum and Verticillium dahliae in tomato plants. The objective of the research was to evaluate the in vivo antagonistic activity of AMF and T. harzianum against Verticillium and Fusarium wilt by enhancing the growth and resistance of tomato plants. A completely randomized experimental design was used, consisting of twelve treatments with nine replicates for each treatment. The treatments included combinations of AMF and T. harzianum inoculation, infection or non-infection by F. oxysporum and V. dahliae, while also considering individual and combined treatments. Mycorrhization rates, growth parameters, disease severity, disease progression, and the impact on disease mitigation were evaluated.

Results
The study revealed the superiority of AMF over T. harzianum, resulting in a significant enhancement in the overall extent of mycorrhizal colonization in tomato plants co-inoculated with T. harzianum. Moreover, AMF treatments and the AMF + T. harzianum consortium contributed to the improvement in growth among all plants infected with V. dahliae and F. oxysporum. Both AMF and T. harzianum significantly reduced the progression of Fusarium wilt, resulting in reductions of 45.14 and 44.91%, respectively, than the untreated plants infected with F. oxysporum (initial disease severity of 75.54%). T. harzianum demonstrated greater efficacy in reducing V. dahliae infection, with a reduction of 34.45% compared to 28.26% for AMF, starting from an initial disease severity of 69.85%. Thus, T. harzianum demonstrated greater effectiveness in controlling disease, particularly Verticillium wilt.

Conclusion
The target application of disease control methods in tomato plants revealed the effectiveness of both AMF and T. harzianum in mitigating Fusarium wilt. Furthermore, T. harzianum demonstrated a higher level of effectiveness against Verticillium wilt. These findings emphasize the potential of AMF and T. harzianum as sustainable alternatives in agriculture, providing a viable option to decrease dependence on fungicides.