bluuebunny/crossref_metadata_2025_split huggingface dataset:
NPRL2 down‐regulation facilitates the growth of hepatocellular carcinoma via the mTOR pathway and autophagy suppression
Authors: Wang Ya‐Chin , Tsai Ming‐Chao , Chen Yaw‐Sen , Hsieh Pei‐Min , Hung Chao‐Ming , Lin Hung‐Yu , Hsu Yao‐Chun , Yeh Jen‐Hao , Hsiao Pojen , Su Yu‐Cheih , Ma Ching‐Hou , Lee Chih‐Yuan , Lin Chih‐Che , Shu Chih‐Wen , Li Yu‐Chan , Tsai Mei‐Hsing , Lin James Yu , Peng Wei‐Hao , Yu Ming‐Lung , Lin Chih‐Wen 
Published: November 2022

Abstract
Hepatocellular carcinoma (HCC) is a highly invasive malignancy. Recently, GATOR1 (Gap Activity TOward Rags 1) complexes have been shown to play an important role in regulating tumor growth. NPRL2 is a critical component of the GATOR1 complex. Therefore, this study used NPRL2 knockdown to investigate how GATORC1 regulates the prognosis and development of HCC via the mammalian target of rapamycin (mTOR) and autophagy signaling pathways. We established HepG2 cells with NPRL2 knockdown using small interfering RNA (siRNA) and short hairpin RNA (shRNA) systems. The siRNA‐mediated and shRNA‐mediated NPRL2 down‐regulation significantly reduced the expression of NPRL2 and two other GATPOR1 complex components, NPRL3 and DEPDC5, in HepG2 cells; furthermore, the efficient down‐regulation of NPRL2 protein expression by both the shRNA and siRNA systems enhanced the proliferation, migration, and colony formation in vitro. Additionally, the NPRL2 down‐regulation significantly increased HCC growth in the subcutaneous and orthotopic xenograft mouse models. The NPRL2 down‐regulation increased the Rag GTPases and mTOR activation and inhibited autophagy in vitro and in vivo. Moreover, the NPRL2 level in the tumors was significantly associated with mortality, recurrence, the serum alpha fetoprotein level, the tumor size, the American Joint Committee on Cancer stage, and the Barcelona Clinic Liver Cancer stage. Low NPRL2, NPRL3, DEPDC5, and LC3, and high p62 and mTOR protein expression in the tumors was significantly associated with disease‐free survival and overall survival in 300 patients with HCC after surgical resection. Conclusion: The efficient down‐regulation of NPRL2 significantly increased HCC proliferation, migration, and colony formation in vitro, and increased HCC growth in vivo. Low NPRL2 protein expression in the tumors was closely correlated with poorer clinical outcomes in patients with HCC. These results provide a mechanistic understanding of HCC and aid the development of treatments for HCC.
Light‐Driven Alkyne gem‐Hydrogenation: An Intramolecular Approach to Hoveyda–Grubbs Catalysts
Authors: Saiegh Tomas J. , Biberger Tobias , Zachmann Raphael J. , Fürstner Alois 
Published: November 2022

AbstractThe light‐driven gem‐hydrogenation of internal alkynes in the presence of [(NHC)(η6‐cymene)RuCl2] generates discrete ruthenium carbene complexes. When applied to appropriately designed enyne substrates, the reactive intermediates thus formed will engage the tethered olefin in metathetic ring closure while splitting off a Hoveyda–Grubbs‐type complex as secondary carbene. This unconventional approach to these classical catalysts for olefin metathesis rivals existing methodology in that it is safe, short, phosphine‐free, and uses readily available starting materials.
Exosomal NAMPT from chronic lymphocytic leukemia cells orchestrate monocyte survival and phenotype under endoplasmic reticulum stress
Authors: Ni Jing , Zhang Ju , Liu Jiatao , Fan Lulu , Lin Xiao , Yu Hanqing , Sun Guoping 
Published: November 2022

AbstractEndoplasmic reticulum (ER) stress has been reported to be transmitted from tumor cells to immune cells via exosome and implicated in immune escape. However, the influence of ER stress on monocytes in chronic lymphocytic leukemia (CLL) cells is largely unknown. Here, we observed the expression of ER stress markers (GRP78, ATF6, PERK, IRE1a, and XBP1s) in CLL cells. The increasing mRNA expression of these ER stress response components was positively correlated with more aggressive disease. Exosome from ER stress inducer tunicamycin (TM)‐primed CLL cells (ERS‐exo) up‐regulated the expression of ER stress marker on monocytes, indicating ER stress is transmissible in vitro via exosome. Treatment with ERS‐exo promoted the survival of monocytes and induced phenotypic changes with a significantly larger percentage of CD14+CD16+monocytes. Finally, we identified exosome‐mediated transfer of extracellular nicotinamide phosphoribosyltransferase (eNAMPT) from ER stressed CLL cells into monocytes as a novel mechanism through which ERS‐exo regulated monocytes. Exosomal eNAMPT up‐regulated nicotinamide adenine dinucleotide (NAD+) production which subsequently activated SIRT1‐C/EBPβ signaling pathway in monocytes. Our results suggest the role of ER stress in mediating immunological dysfunction in CLL.
Male involvement in the use of family planning and associated factors in Gondar City, Northwest Ethiopia: A community‐based cross‐sectional study
Authors: Alemu Rediet B. , Delele Tadesse G. , Habitu Yohannes A. 
Published: November 2022

AbstractObjectiveTo assess the level of male involvement in the use of family planning and associated factors among married men.MethodsA community‐based cross‐sectional study was conducted from March to April 2018. Married men were randomly selected from four randomly selected kebeles, the smallest administrative division in Ethiopia. Data were collected using an interviewer‐administered structured questionnaire. A multivariable logistic regression model was fitted to identify the associated factors with male involvement in the use of family planning.ResultsA total of 741 of 744 (99.6%) married men responded to the interview. The overall involvement of men in family planning was 70%. Men aged 25–30 years (adjusted odds ratio [AOR] 3.78, 95% confidence interval [CI] 1.67–8.54), attending secondary school education (AOR 2.25, 95% CI 1.173–4.31), attending college and higher education (AOR 7.49, 95% CI 3.87–14.51), had more than five children (AOR 14.6, 95% CI 4.37–48.97), and had 3–4 children (AOR 16.13, 95% CI 6.31–41.16) were the factors significantly associated with male involvement in family planning.ConclusionThe involvement of married men in family planning was low. Encouraging the education of younger men by considering those who do not have any children is an essential measure to enhance men's involvement in family planning.
Dysfunction of Caveolae-Mediated Endocytic TβRI Degradation Results in Hypersensitivity of TGF-β/Smad Signaling in Osteogenesis Imperfecta
Authors: Shi Changgui , Sun Bin , Wu Huiqiao , Zhang Rongcheng , Wu Lecheng , Guo Lei , Li Changwei , Xi Yanhai , Yuan Wen , Zhang Ying , Xu Guohua 
Published: November 2022

ABSTRACT
Osteogenesis imperfecta (OI) is a genetic disorder caused by mutations of type I collagen-related genes, and excessive transforming growth factor-beta (TGF-β) signaling is a common mechanism. TGF-β/Smad signaling has inhibitory effects on osteoblast differentiation and maturation and is mainly transduced and regulated by the internalization of a tetrameric receptor complex comprising types I and II TGF-β receptors (TβRI and TβRII). During internalization, clathrin-mediated endocytosis enhances TGF-β/Smad signaling via Smad2/3 phosphorylation and receptors recycling, while caveolae-mediated endocytosis turns off TGF-β/Smad signaling by promoting receptor ubiquitination and degradation. In this study, using an animal model of OI (Colla2oim, osteogenesis imperfecta murine [oim]/oim mouse), we found that osteoblastic cells of oim/oim mice were more sensitive to the inhibitory effects of TGF-β on osteoblast differentiation and maturation and had much higher cell membrane protein levels of TGF-β receptors than those of wild-type (wt)/wt mice. Further results showed that clathrin-mediated endocytosis of TβRI was enhanced, whereas caveolae-mediated TβRI endocytic degradation was reduced in oim/oim mice, combined with reduced caveolin-1 (Cav-1) phosphorylation. In addition, type I collagen downregulated TβRI via focal adhesion kinase (FAK) and Src activation-dependent Cav-1 phosphorylation. To further examine this mechanism, 4-week-old oim/oim and wt/wt mice were treated with either TβRI kinase inhibitor (SD-208) or vehicle for 8 weeks. SD-208 treatment significantly reduced the fracture incidence in oim/oim mice. Micro–computed tomography and biomechanical testing showed that femoral bone mass and strength were significantly improved with SD-208 treatment in both genotypes. Additionally, SD-208 significantly promoted osteoblast differentiation and bone formation and inhibited bone resorption. In conclusion, dysfunction of caveolae-mediated endocytic TβRI degradation is a possible mechanism for the enhanced TGF-β/Smad signaling in OI. Targeting this mechanism using a TβRI kinase inhibitor effectively reduced fractures and improved bone mass and strength in OI model and, thus, may offer a new strategy for the treatment of OI. © 2022 American Society for Bone and Mineral Research (ASBMR).
Abstract
In this study, we found that caveolae-mediated endocytic TβRI degradation was reduced in OI due to the impaired regulation of type I collagen on FAK/Src activation-dependent Caveolin-1 phosphorylation, which further enhanced the TGF-β/Smad signaling on the inhibition of osteoblast differentiation. Inhibition of TβRI kinase by SD-208 effectively reduced fractures and improved bone mass and strength in an OI mouse model.
Interpersonal perceptions in treatment sessions: Pathological narcissism predicts self‐rater discrepancies
Authors: Di Sarno Marco , Frisina Simone , Madeddu Fabio , Di Pierro Rossella 
Published: November 2022

AbstractObjectiveEvidence suggests that pathological narcissism impacts psychotherapy process and outcome. This study investigates whether traits of pathological narcissism account for distinctiveness (construal) of patients' interpersonal perceptions in treatment settings.MethodsPatients enrolled in psychological/psychotherapeutic treatment (N = 150) described a segment of a session in a written format and subsequently assessed both self‐ and clinician's behavior on the dimensions of dominance and hostility (patient‐reported ratings), along with their pathological narcissistic traits. Three independent raters also assessed interpersonal behaviors (observer‐reported ratings) based on the written session descriptions. Indices of construal were defined by the residuals of self‐reported (net of observer‐reported) ratings and were regressed onto pathological narcissistic traits.ResultsNo association emerged between pathological narcissism and construal in patients' perceptions of their clinicians. However, grandiose traits of pathological narcissism were related to distinctively perceiving oneself as more dominant, while vulnerable traits were related to distinctively perceiving oneself as more hostile. The former association (but not the latter) also held after incorporating additional observer ratings to investigate the robustness of the results.ConclusionFindings are discussed in light of treatment‐related self‐enhancement and self‐concealment processes.
Grit, general self‐efficacy, and life satisfaction: The mediating role of hope
Authors: Ekinci Nezir , Koç Hayri 
Published: November 2022

AbstractThis study examines the mediating role of hope in the relationship between grit, general self‐efficacy, and life satisfaction. The sample of the study consisted of 485 university students (68.7% female). The age of the participants ranged from 18 to 39 (Mean: 20.85, SD: 2.30). According to the findings of the study, positive significant relationships were found between grit, general self‐efficacy, hope and life satisfaction. hope fully mediated the impact of grit on life satisfaction. Additionally, hope fully mediates the effect of general self‐efficacy on life satisfaction. These findings suggest that grit and general self‐efficacy associated with life satisfaction can be better understood with hope. Hope can be a factor that increases individuals' resilience and general self‐efficacy and is an important aspect of positive‐based interventions.
Systematic review and meta‐analysis of intravenous iron therapy for adults with non‐anaemic iron deficiency: An abridged Cochrane review
Authors: Dugan Cory , Cabolis Katerina , Miles Lachlan F. , Richards Toby 
Published: November 2022

AbstractIron is an essential nutrient for oxygen supply and aerobic metabolism. Iron deficiency impacts cellular respiration and mitochondrial energy metabolism, which can lead to reduced skeletal muscle function and muscle mass, causing sarcopenia. Intravenous iron offers the ability to rapidly correct iron deficiency, but the functional impact on patient mental and physical health is unclear. We assessed the effects of intravenous iron therapy on physical function and quality of life in the treatment of adults with non‐anaemic iron deficiency. An update and reanalysis of a previously published Cochrane systematic review was performed to assess randomized controlled trials that compared any intravenous iron preparation with placebo in adults. The primary functional outcome measure was physical performance as defined by the trial authors. Secondary outcome measures included fatigue and quality‐of‐life scores, and adverse effects at the end of follow‐up. Biochemical efficacy was assessed by change in serum ferritin and haemoglobin concentration levels. Twenty‐one randomized controlled trials, comprising 3514 participants, were included. Intravenous iron compared with placebo resulted in significantly increased physical function measured by mean peak oxygen consumption (mean difference [MD] 1.77 mL/kg/min, 95% confidence interval [CI] 0.57 to 2.97). An overall improvement in fatigue was seen (standardized MD 0.30, 95% CI −0.52 to −0.09) but no overall difference in quality of life (MD 0.15, 95% CI −0.01 to 0.31). Biochemically, intravenous iron resulted in improved serum ferritin (MD 245.52 μg/L, 95% CI 152.1 to 338.9) and haemoglobin levels (MD 4.65 g/L, 95% CI 2.53 to 6.78). There was a higher risk of developing mild adverse events in the intravenous iron group compared with the placebo group (risk ratio 1.77, 95% CI 1.10 to 2.83); however, no differences were seen in serious adverse events (risk difference 0, 95% CI −0.01 to 0.01). The quality of evidence was rated ‘low’ and ‘very low’ for all outcome variables, except for fatigue, mainly due to most studies being judged as having a high risk of bias. In non‐anaemic iron‐deficient adults, the use of intravenous iron compared with placebo improved physical function and reduced fatigue scores. However, we remain uncertain about the efficacy in this population due to low‐quality evidence, and there is a need for further studies to address potential impact on overall quality of life.
Irradiation accelerates SARS‐CoV‐2 infection by enhancing sphingolipid metabolism
Authors: Wei Zhuanzhuan , Jiang Yiyi , Zhao Gaomei , Li Chenwenya , Han Songling , Chen Yin , Wang Tao , Cheng Tianmin , Wang Junping , Wang Cheng 
Published: November 2022

AbstractCancer patients who receive radiotherapy have a high risk of severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2) infection, but the concrete reason remains unclear. Herein, we investigated the influence of irradiation on the vulnerability of cancer cells to SARS‐CoV‐2 using S pseudovirions and probed the underlying mechanism via RNA‐seq and other molecular biology techniques. Owing to the enhancement of sphingolipid metabolism, irradiation accelerated pseudovirion infection. Mechanistically, irradiation induced the expression of acid sphingomyelinase (ASM), which catalyses the hydrolysis of sphingomyelin to ceramide, contributing to lipid raft formation and promoting SARS‐CoV‐2 invasion. Inhibition of lipid raft formation with methyl‐β‐cyclodextrin (MβCD) or the tyrosine kinase inhibitor genistein and ASM suppression through small interfering RNA or amitriptyline (AMT) treatment abolished the enhancing effect of irradiation on viral infection. Animal experiments supported the finding that irradiation promoted SARS‐CoV‐2 S pseudovirion infection in A549 cell tumour‐bearing BALB/c nude mice, whereas AMT treatment dramatically decreased viral infection. This study discloses the role of sphingolipid metabolism in irradiation‐induced SARS‐CoV‐2 infection, thus providing a potential target for clinical intervention to protect patients receiving radiotherapy from COVID‐19.
Gut microbiota dysbiosis is associated with sepsis‐induced cardiomyopathy in patients: A case‒control study
Authors: Deng Fan , Chen Yu , Sun Qi‐Shun , Lin Ze‐Bin , Min Yue , Zhao Bing‐Cheng , Huang Zhi‐Bin , Liu Wei‐Feng , Li Cai , Hu Jing‐Juan , Liu Ke‐Xuan 
Published: November 2022

AbstractBackgroundMyocardial injury is a major complication of sepsis and a key factor affecting prognosis. Therefore, early and accurate diagnosis and timely management of sepsis‐induced cardiomyopathy (SICM) are of great significance for the prevention and treatment of sepsis. The gut microbiota has been shown to be closely associated with sepsis or myocardial injury, but the association between the gut microbiota and SICM is not fully understood. This study aimed to explore the link between gut microbiota composition and SICM.MethodsA case‒control and single‐center study of clinical features and gut microbiota profiles by Metagenome and Virome was conducted in SICM patients (n = 15) and sepsis‐uninduced cardiomyopathy patients (SNICM, n = 16).ResultsCompared with SNICM patients, SICM patients showed significant myocardial injury and higher 28‐day mortality, SOFA scores, lactate levels, and infection levels on admission. Meanwhile, differences in the composition of gut bacteria, archaea, fungi, and viruses were analyzed between the two groups. Differential gut bacteria or viruses were found to have a good predictive effect on SICM. Furthermore, gut bacteria and viruses that differed between the two groups were strongly related. The abundance of Cronobacter and Cronobacter phage was higher in the SICM group than in the SNICM group, and the receiver operating characteristic curve showed that Cronobacter and Cronobacter phage both had a good predictive effect on SICM.ConclusionsSICM patients may have specific gut microbiota signatures, and Cronobacter and Cronobacter phages have a good ability to identify and diagnose SICM.
Spatial‐temporal dynamics and time series prediction of HFRS in mainland China: A long‐term retrospective study
Authors: He Junyu , Wang Yanding , Wei Xianyu , Sun Hailong , Xu Yuanyong , Yin Wenwu , Wang Yong , Zhang Wenyi 
Published: November 2022

AbstractHemorrhagic fever with renal syndrome (HFRS) is highly endemic in mainland China. The current study aims to characterize the spatial‐temporal dynamics of HFRS in mainland China during a long‐term period (1950−2018). A total of 1 665 431 cases of HFRS were reported with an average annual incidence of 54.22 cases/100 000 individuals during 1950−2018. The joint regression model was used to define the global trend of the HFRS cases with an increasing‐decreasing‐slightly increasing‐decreasing‐slightly increasing trend during the 68 years. Then spatial correlation analysis and wavelet cluster analysis were used to identify four types of clusters of HFRS cases located in central and northeastern China. Lastly, the prophet model outperforms auto‐regressive integrated moving average model in the HFRS modeling. Our findings will help reduce the knowledge gap on the transmission dynamics and distribution patterns of the HFRS in mainland China and facilitate to take effective preventive and control measures for the high‐risk epidemic area.
Monkeypox: Early estimation of basic reproduction number R0 in Europe
Authors: Branda Francesco , Pierini Massimo , Mazzoli Sandra 
Published: November 2022

AbstractThis world outbreak of Monkeypox (MPX) infections outside Africa emerged on May 2022 in Europe and spread worldwide with unique characteristics: inter‐human contagion and infection in men without specific previous immunization, prevalently men‐who‐have‐sex‐with‐men (MSM). Phylogenetic analysis confirmed a unique clade, the West African clade, subclade IIb. On August 30, WHO stated 48 895 laboratory confirmed cases from 101 different countries, of which 28 050 were in Europe. It has therefore become important to define new epidemiological indices. Starting from our new surveillance system EpiMPX open data, we defined an early R0 measure, using European ECDC confirmed cases from the epidemic start to the end of August 2022; our early R0 pooled median is 2.44, with high variability between countries. We observed the higher R0 in Portugal and Germany, followed by Italy, Spain, and France. Anyway, these high estimates refer to the MSM group rather than to the general population. Early estimation of R0 can be used to support the epidemiological understanding of transmission dynamics and contain MPX from spreading in naive populations and core groups with risk factors. MPX is in an evolving situation with much to learn and to do to combat the current epidemic outbreak.
Cellular toxicity and pharmacokinetic study of butachlor by ultra‐performance liquid chromatography‐tandem mass spectrometry based on tandem mass spectrometry cubed technique
Authors: Zheng Xinyue , Duan Xujian , Lu Di , Jiang Qiuhong , Liu Yajun , Xue Hongyu , You Jiansong , Yin Lei , Shi Meiyun 
Published: November 2022

Butachlor is an aromatic amide compound that plays a role as a herbicide, a xenobiotic, and an environmental contaminant. The aim of this work was to develop a highly selective and sensitive ultra‐performance liquid chromatography‐tandem mass spectrometry method based on the tandem mass spectrometry cubed technique to determine butachlor in a biological matrix. Butachlor and internal standard acetochlor were separated on a Waters Acquity ultra‐performance liquid chromatography BEH C18 column (2.1 × 50 mm, 1.7 μm) with gradient elution using 0.1% formic acid aqueous solution (A) and acetonitrile (B) as mobile phases. The transitions selected for tandem mass spectrometry cubed quantitative analysis in positive ion mode were: for butachlor, mass‐to‐charge ratio 312.2→238.1→162.1; for acetochlor, mass‐to‐charge ratio 270.1→224.0→148.1. The total running time for each sample was 5.5 min. The ultra‐performance liquid chromatography‐tandem mass spectrometry cubed method showed a linear relationship (R2 ≥ 0.995) in the concentration range of 0.5–100 ng/ml. The intra and interday accuracies are within the range of ‐10.6%–4.3% and precisions are between 4.48% and 13.14%. The novelty of the method is the use of tandem mass spectrometry cubed scanning mode, which improves selectivity and sensitivity. The results indicated that butachlor was cellular toxic. The safety of butachlor should be considered when it is used as a herbicide.