bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myristate induces mitochondrial fragmentation and cardiomyocyte hypertrophy through mitochondrial E3 ubiquitin ligase MUL1
Authors: Vásquez-Trincado César , Navarro-Márquez Mario , Morales Pablo E. , Westermeier Francisco , Chiong Mario , Parra Valentina , Espinosa Alejandra , Lavandero Sergio 
Published: March 2023

Introduction: Cardiovascular diseases, especially metabolic-related disorders, are progressively growing worldwide due to high-fat-containing foods, which promote a deleterious response at the cellular level, termed lipotoxicity, or lipotoxic stress. At the cardiac level, saturated fatty acids have been directly associated with cardiomyocyte lipotoxicity through various pathological mechanisms involving mitochondrial dysfunction, oxidative stress, and ceramide production, among others. However, integrative regulators connecting saturated fatty acid-derived lipotoxic stress to mitochondrial and cardiomyocyte dysfunction remain elusive.Methods: Here, we worked with a cardiomyocyte lipotoxicity model, which uses the saturated fatty acid myristate, which promotes cardiomyocyte hypertrophy and insulin desensitization.Results: Using this model, we detected an increase in the mitochondrial E3 ubiquitin ligase, MUL1, a mitochondrial protein involved in the regulation of growth factor signaling, cell death, and, notably, mitochondrial dynamics. In this context, myristate increased MUL1 levels and induced mitochondrial fragmentation, associated with the decrease of the mitochondrial fusion protein MFN2, and with the increase of the mitochondrial fission protein DRP1, two targets of MUL1. Silencing of MUL1 prevented myristate-induced mitochondrial fragmentation and cardiomyocyte hypertrophy.Discussion: These data establish a novel connection between cardiomyocytes and lipotoxic stress, characterized by hypertrophy and fragmentation of the mitochondrial network, and an increase of the mitochondrial E3 ubiquitin ligase MUL1.
Association between serum uric acid and phase angle in patients with type 2 diabetes mellitus: A cross-sectional study
Authors: Hu Yezi , Liu Jie , Jin Hui 
Published: March 2023

BackgroundThe purpose of this analysis was to investigate the associations between serum uric acid and phase angle in patients with type 2 diabetes mellitus.MethodsIn this retrospective cross-sectional study, we included 200 type 2 diabetes mellitus (T2DM) patients treated during 2018–2019 at Zhongda Hospital Southeast University. Phase angle (PhA) and other body composition indicators were measured by bioelectrical impedance analysis (BIA). All patients underwent routine clinical examinations on the day of hospitalization, and the basic information and clinical symptoms of these patients were recorded.ResultsSerum uric acid (UA) was significantly associated with PhA (p &lt;0.001). Overall, in the crude model and minor, all adjusted models (crude model, Models I–II), the phase angle increased as the tertiles of serum uric acid increased. In the minor adjusted model (Model I, adjustment for age and duration) fully adjusted model (Model II, adjustment for age, duration, Lpa, BMI, and WHR), the adjusted β for participants in tertiles of serum uric acid were 0.26 (95% CI: 0.05–0.46) and 0.32 (95% CI: 0.11–0.54), respectively, compared with those in the lowest tertile 1.ConclusionThere was a nonlinear relationship between serum uric acid and PhA in T2DM patients, and the phase angle increased as uric acid increased within a certain range, and this effect disappeared when uric acid exceeded a certain value.
Effects of aging and macrophages on mice stem Leydig cell proliferation and differentiation in vitro
Authors: Shao Jingjing , Wang Jiexia , Wen Xin , Xie Jiajia , Huang Fu , Guan Xiaoju , Hao Xinrui , Duan Ping , Chen Congde , Chen Haolin 
Published: March 2023

BackgroundTestosterone plays a critical role in maintaining reproductive functions and well-beings of the males. Adult testicular Leydig cells (LCs) produce testosterone and are generated from stem Leydig cells (SLCs) during puberty through adulthood. In addition, macrophages are critical in the SLC regulatory niche for normal testicular function. Age-related reduction in serum testosterone contributes to a number of metabolic and quality-of-life changes in males, as well as age-related changes in immunological functions. How aging and testicular macrophages may affect SLC function is still unclear.MethodsSLCs and macrophages were purified from adult and aged mice via FACS using CD51 as a marker protein. The sorted cells were first characterized and then co-cultured in vitro to examine how aging and macrophages may affect SLC proliferation and differentiation. To elucidate specific aging effects on both cell types, co-culture of sorted SLCs and macrophages were also carried out across two ages.ResultsCD51+ (weakly positive) and CD51++ (strongly positive) cells expressed typical SLC and macrophage markers, respectively. However, with aging, both cell types increased expression of multiple cytokine genes, such as IL-1b, IL-6 and IL-8. Moreover, old CD51+ SLCs reduced their proliferation and differentiation, with a more significant reduction in differentiation (2X) than proliferation (30%). Age matched CD51++ macrophages inhibited CD51+ SLC development, with a more significant reduction in old cells (60%) than young (40%). Crossed-age co-culture experiments indicated that the age of CD51+ SLCs plays a more significant role in determining age-related inhibitory effects. In LC lineage formation, CD51+ SLC had both reduced LC lineage markers and increased myoid cell lineage markers, suggesting an age-related lineage shift for SLCs.ConclusionThe results suggest that aging affected both SLC function and their regulatory niche cell, macrophages.
A first step to assess suspended microplastics in a freshwater wetland from the coastal region of Ecuador
Authors: López Carlos , Soto Luz Marina , Acosta Vanessa , Santana-Piñeros Ana María , Cruz-Quintana Yanis , Gomes-Barbosa Luciana , Stamou Georgia , Karpowicz Maciej , Michaloudi Evangelia , Domínguez-Granda Luis , Steinitz-Kannan Miriam 
Published: March 2023

Introduction: La Segua is an important wetland in Ecuador, recognized as a Ramsar site and of great ecological relevance. Currently, La Segua is threatened by human pressures and unsustainable landscape use associated with agriculture and aquaculture. This study is the first approach to the occurrence of suspended microplastics (SMPs) in an Ecuadorian lentic waterbody and the estimated potential threat of these on the filter and suspension feeders in aquatic food webs.Methods: Surface water samples were collected at 16 sampling points in the wetland to analyze the occurrence, concentration, and horizontal distribution of Suspected Suspended Microplastics (SSMPs) and zooplankton.Results and discussion: SSMPs were found in all sampling sites, and concentrations were between 313 and 490 particles/liter. Fragments were the most abundant category, followed by fibers, films, and pellets. The highest concentration of SSMPs was found in sampled sites on the east coast and in the middle of the wetland. The frequency and concentration of categories of SSMps found in surface water largely reflect the reality of local human activity around the La Segua wetland. Only rotifers and copepod nauplii were found in the zooplankton. The SSMMPs to zooplankton ratio varied between 0.3 and 441 particles/individuals.The SSMPs/zooplankton ratio indicates that fish and other filter and suspension feeders of aquatic food webs could be more likely to feed on suspended microplastics than natural food items around the wetland. SSMPs indicate that microplastics may represent.
PredDSMC: A predictor for driver synonymous mutations in human cancers
Authors: Wang Lihua , Sun Jianhui , Ma Shunshuai , Xia Junfeng , Li Xiaoyan 
Published: March 2023

Introduction: Driver mutations play a critical role in the occurrence and development of human cancers. Most studies have focused on missense mutations that function as drivers in cancer. However, accumulating experimental evidence indicates that synonymous mutations can also act as driver mutations.Methods: Here, we proposed a computational method called PredDSMC to accurately predict driver synonymous mutations in human cancers. We first systematically explored four categories of multimodal features, including sequence features, splicing features, conservation scores, and functional scores. Further feature selection was carried out to remove redundant features and improve the model performance. Finally, we utilized the random forest classifier to build PredDSMC.Results: The results of two independent test sets indicated that PredDSMC outperformed the state-of-the-art methods in differentiating driver synonymous mutations from passenger mutations.Discussion: In conclusion, we expect that PredDSMC, as a driver synonymous mutation prediction method, will be a valuable method for gaining a deeper understanding of synonymous mutations in human cancers.
Vaccinating women previously treated for human papillomavirus-related cervical precancerous lesions is highly cost-effective in China
Authors: Zou Maosheng , Liu Hanting , Liu Huan , Wang Mengjie , Zou Zhuoru , Zhang Lei 
Published: March 2023

BackgroundThe 2021 Chinese Expert Consensus on the Clinical Application of the Human Papillomavirus (HPV) Vaccine recommended vaccination for women who previously received ablative or excisional treatment for high-grade squamous intraepithelial lesion (HSIL). This study evaluates the cost-effectiveness of HPV vaccination in women previously treated for cervical precancerous lesions.MethodsWe used a Markov model to simulate the disease progression of both low- and high-risk HPV subtypes. We followed a cohort of 100,000 women aged 18-45 years who received treatment for cervical precancerous lesions for a lifetime (80 years). We used the Incremental Cost-Effectiveness Ratios (ICER) with a 5% discount rate to measure the cost-effectiveness of nine vaccination strategies, including a combination of HPV bivalent (HPV-2), quadrivalent (HPV-4) and nonavalent vaccine (HPV-9), each with three vaccination doses (one-, two- and three-dose). We conducted one-way sensitivity analysis and probabilistic sensitivity analysis. We followed the CHEERS 2022 guidelines.ResultsCompared to the status quo, the nine vaccination strategies would result in $3.057-33.124 million incremental cost and 94-1,211 incremental quality-adjusted life-years (QALYs) in 100,000 women previously treated for cervical precancerous lesions. Three vaccination strategies were identified on the cost-effectiveness frontier. In particular, ICER for one-dose HPV-4 vaccination was US$10,025/QALY compared to the status quo (no vaccination); ICER for two-dose HPV-4 vaccination was US$17,641//QALY gained compared to one-dose HPV-4 vaccination; ICER for three-dose HPV-4 vaccination was US$27,785/QALY gained compared with two-dose HPV-4 vaccination. With a willingness-to-pay of three times gross domestic product per capita (US$37655), three-dose HPV-4 vaccination was the most cost-effective vaccination strategy compared with the lower-cost non-dominated strategy on the cost-effectiveness frontier. A probabilistic sensitivity analysis confirmed a 99.1% probability of being cost-effective. If the cost of the HPV-9 is reduced to 50% of the current price, three-dose HPV-9 vaccination would become the most cost-effective strategy.DiscussionThree-dose HPV-4 vaccination is the most cost-effective vaccination strategy for women treated for precancerous cervical lesions in the Chinese setting.
Ecosystem-based assessment of a widespread Mediterranean marine habitat: The Coastal Detrital Bottoms, with a special focus on epibenthic assemblages
Authors: Astruch Patrick , Orts Ameline , Schohn Thomas , Belloni Bruno , Ballesteros Enric , Bănaru Daniela , Bianchi Carlo Nike , Boudouresque Charles-François , Changeux Thomas , Chevaldonné Pierre , Harmelin Jean-Georges , Michez Noëmie , Monnier Briac , Morri Carla , Thibaut Thierry , Verlaque Marc , Daniel Boris 
Published: March 2023

IntroductionCoastal detrital bottoms (CDB) are one of the most extensive habitats of the continental shelf worldwide, in the upper levels of the circalittoral zone. Hosting a diverse community structured by sediment grain size, trophic interactions and calcified organisms, CDB exhibit important ecological functions. In the Mediterranean Sea, CDB are constituted by recent elements partly provided by adjacent infralittoral and circalittoral ecosystems. Since the 2010s, the offshore extension of many Marine Protected Areas (MPAs) has resulted in the incorporation of vast areas of CDB, raising the issue of their management. The Marine Strategy Framework Directive (MSFD) has embraced the concept of an ecosystem-based approach involving taking into account the functioning of marine habitats and their related ecosystem services. The purpose of this paper is to propose an ecosystem-based quality index (EBQI) tested on CDB from the north-western Mediterranean Sea, focusing mainly on epibenthic assemblages.MethodsThe first step has been to define a conceptual model of the CDB functioning, including the main trophic compartments and their relative weighting, then to identify appropriate assessment methods and potential descriptors. Twenty-nine sites were sampled along the coast of Provence and French Riviera (Southern France). Study sites were chosen with a view to encompassing a wide range of hydrological conditions and human pressures.ResultsVery well-preserved sites were found in Provence in areas without trawling and terrigenous inputs, while impacted and low-ES sites were located in the vicinity of urbanized areas. The cover of rhodoliths characterizes the seascape and might be an indicator of the good ES of CDB and reduced human pressure. However, the absence of rhodoliths may also be induced by natural phenomena.DiscussionThe EBQI designed for CDB proved representative and useful for a functional assessment based on epibenthic assemblages. However, some descriptors have shown their limitations and should be further explored. We highlight here the priority of establishing an index corresponding to a societal demand (e.g., European Directives, Barcelona convention) as a basis for a broad and large-scale assessment, for practical reasons. We stress the need to better apprehend the role of the macro-infauna and to extend this index over a wider geographical scale.
Quantitative thermal testing as a screening and follow-up tool for diabetic sensorimotor polyneuropathy in patients with type 2 diabetes and prediabetes
Authors: Huang Yu-Chuan , Chuang Yao-Chung , Chiu Wen-Chan , Huang Chih-Cheng , Cheng Ben-Chung , Kuo Chun-En Aurea , Lin Ting-Yin , Chiang Hui-Ching , Lai Yun-Ru 
Published: March 2023

IntroductionThe diagnosis and assessment of neuropathy severity of diabetic sensorimotor polyneuropathy (DSPN) are mainly based on clinical neuropathy scores and electrophysiologic studies. This study aimed to determine whether quantitative thermal testing (QTT) can be used as a screening and follow-up tool for DSPN of prediabetes and type 2 diabetes at baseline and at 1-year follow-up.MethodsAll patients were assessed using the Toronto Clinical Neuropathy Score (TCNS) and underwent electrophysiological testing, including a nerve conduction study (NCS) and QTT, at baseline and at a 1-year follow-up. The TCNS and the composite scores of nerve conduction were used to assess the severity of DSPN. The DSPN status at the 1-year follow-up was classified as remaining no DSPN, remaining DSPN, regression to no DSPN, or progression to DSPN.ResultsDiabetic sensorimotor polyneuropathy was initially diagnosed in 89 patients with prediabetes and type 2 diabetes (22%). The regressed to no DSPN in 29 patients and progressed to DSPN in 20 patients at the 1-year follow-up. TCNS was significantly correlated with composite scores of nerve conduction, hand cold detection threshold (CDT), hand warm detection threshold (WDT), foot CDT, and foot WDT. Stepwise logistic regression demonstrated that the foot CDT (p &lt; 0.0001) was independently associated with the presence of DSPN. The TCNS, composite scores of the nerve conduction, hand WDT, hand CDT, foot WDT, and foot CDT were all statistically significant among the four different DSPN status groups at two different time periods (baseline and the 1-year follow-up).ConclusionThe foot CDT can be used as an initial screening tool for DSPN alternatively. The characteristics of nerve damage after 1 year of DSPN can be progressive or reversible, and the neurological functions of large and small fibers have a parallel trend, which can be objectively measured by NCS and QTT.
Real-world clinical practice and outcomes in treating stage III non-small cell lung cancer: KINDLE-Asia subset
Authors: Prabhash Kumar , Tan Daniel Shao Weng , Soo Ross A. , Sitthideatphaiboon Piyada , Chen Yuh Min , Voon Pei Jye , Syahruddin Elisna , Chu Sojung , Huggenberger Reto , Cho Byoung-Chul 
Published: March 2023

IntroductionStage III non-small cell lung cancer (NSCLC) is a heterogeneous disease requiring multimodal treatment approaches. KINDLE-Asia, as part of a real world global study, evaluated treatment patterns and associated survival outcomes in stage III NSCLC in Asia.MethodsRetrospective data from 57 centers in patients with stage III NSCLC diagnosed between January 2013 and December 2017 were analyzed. Median progression free survival (mPFS) and median overall survival (mOS) estimates with two sided 95% confidence interval (CI) were determined by applying the Kaplan-Meier survival analysis.ResultsOf the total 1874 patients (median age: 63.0 years [24 to 92]) enrolled in the Asia subset, 74.8% were men, 54.7% had stage IIIA disease, 55.7% had adenocarcinoma, 34.3% had epidermal growth factor receptor mutations (EGFRm) and 50.3% had programmed death-ligand 1 (PD-L1) expression (i.e. PD-L1 ≥1%). Of the 31 treatment approaches as initial therapy, concurrent chemoradiotherapy (CRT) was the most frequent (29.3%), followed by chemotherapy (14.8%), sequential CRT (9.5%), and radiotherapy (8.5%). Targeted therapy alone was used in 81 patients of the overall population. For the Asia cohort, the mPFS and mOS were 12.8 months (95% CI, 12.2–13.7) and 42.3 months (95% CI, 38.1–46.8), respectively. Stage IIIA disease, Eastern Cooperative Oncology Group ≤1, age ≤65 years, adenocarcinoma histology and surgery/concurrent CRT as initial therapy correlated with better mOS (p &lt; 0.05).ConclusionsThe results demonstrate diverse treatment patterns and survival outcomes in the Asian region. The high prevalence of EGFRm and PD-L1 expression in stage III NSCLC in Asia suggests the need for expanding access to molecular testing for guiding treatment strategies with tyrosine kinase inhibitors and immunotherapies in this region.
A male mouse model of WIN 55,212–2 self-administration to study cannabinoid addiction
Authors: Cajiao-Manrique María del Mar , Maldonado Rafael , Martín-García Elena 
Published: March 2023

We have established for the first time a mouse model of cannabinoid addiction using WIN 55,212–2 intravenous self-administration (0.0125 mg/kg/infusion) in C57Bl/6J mice. This model allows to evaluate the addiction criteria by grouping them into 1) persistence of response during a period of non-availability of the drug, 2) motivation for WIN 55,212–2 with a progressive ratio, and 3) compulsivity when the reward is associated with a punishment such as an electric foot-shock, in agreement with the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5). This model also allows to measure two parameters that have been related with the DSM-5 diagnostic criteria of craving, resistance to extinction and reinstatement, and two phenotypic traits suggested as predisposing factors, impulsivity and sensitivity to reward. We found that 35.6% of mice developed the criteria of cannabinoid addiction, allowing to differentiate between resilient and vulnerable mice. Therefore, we have established a novel and reliable model to study the neurobiological correlates underlying the resilience or vulnerability to develop cannabinoid addiction. This model included the chemogenetic inhibition of neuronal activity in the medial prefrontal cortex to the nucleus accumbens pathway to assess the neurobiological substrate of cannabinoid addiction. This model will shed light on the neurobiological substrate underlying cannabinoid addiction.
Nanofat lysate ameliorates pain and cartilage degradation of osteoarthritis through activation of TGF-β–Smad2/3 signaling of chondrocytes
Authors: Ge Yanzhi , Xu Wenting , Chen Zuxiang , Zhang Haiyan , Zhang Wenbo , Chen Junjie , Huang Jiefeng , Du Wenxi , Tong Peijian , Shan Letian , Zhou Li 
Published: March 2023

Introduction: Nanofat is an effective cell therapy for osteoarthritis (OA). However, it has clinical limitations due to its short half-life. We developed Nanofat lysate (NFL) to overcome the defect of Nanofat and explore its anti-OA efficacy and mechanism.Methods: Monoiodoacetate (MIA) was employed to establish rat OA model. For pain assessment, paw withdrawal latency (PWL) and thermal withdrawal latency (TWL) were evaluated. Degeneration of cartilage was observed by histopathological and immunohistochemical examination. Primary chondrocytes were treated with TNF-α to establish the cellular model of OA. MTT, wound healing, and transwell assays were performed to assess effects of NFL on chondrocytes. RNA-seq, qPCR and Western blot assays were conducted to clarify the mechanism of NFL.Results and Discussion: The animal data showed that PWL and TWL values, Mankin’s and OARSI scorings, and the Col2 expression in cartilage were significantly improved in the NFL-treated OA rats. The cellular data showed that NFL significantly improved the proliferation, wound healing, and migration of chondrocytes. The molecular data showed that NFL significantly restored the TNF-α-altered anabolic markers (Sox9, Col2 and ACAN) and catabolic markers (IL6 and Mmp13). The RNA-seq identified that TGF-β-Smad2/3 signaling pathway mediated the efficacy of NFL, which was verified by qPCR and Western blot that NFL significantly restored the abnormal expressions of TGFβR2, phosphorylated-Smad2, phosphorylated-Smad2/3, Col2, Mmp13 and Mmp3. After long-term storage, NFL exerted similar effects as its fresh type, indicating its advantage of storability. In sum, NFL was developed as a new therapeutic approach and its anti-OA efficacy and mechanism that mediated by TGF-β-Smad2/3 signaling was determined for the first time. Besides, the storability of NFL provided a substantial advantage than other living cell-based therapies.