bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transgene expression in mice of the Opa1 mitochondrial transmembrane protein through bicontinuous cubic lipoplexes containing gemini imidazolium surfactants
Authors: Muñoz-Úbeda Mónica , Semenzato Martina , Franco-Romero Anais , Junquera Elena , Aicart Emilio , Scorrano Luca , López-Montero Iván 
Published: December 2021

Abstract
Background
Lipoplexes are non-viral vectors based on cationic lipids used to deliver DNA into cells, also known as lipofection. The positively charge of the hydrophilic head-group provides the cationic lipids the ability to condensate the negatively charged DNA into structured complexes. The polar head can carry a large variety of chemical groups including amines as well as guanidino or imidazole groups. In particular, gemini cationic lipids consist of two positive polar heads linked by a spacer with different length. As for the hydrophobic aliphatic chains, they can be unsaturated or saturated and are connected to the polar head-groups. Many other chemical components can be included in the formulation of lipoplexes to improve their transfection efficiency, which often relies on their structural features. Varying these components can drastically change the arrangement of DNA molecules within the lamellar, hexagonal or cubic phases that are provided by the lipid matrix. Lipofection is widely used to deliver genetic material in cell culture experiments but the simpler formulations exhibit major drawbacks related to low transfection, low specificity, low circulation half-life and toxicity when scaled up to in vivo experiments.

Results
So far, we have explored in cell cultures the transfection ability of lipoplexes based on gemini cationic lipids that consist of two C16 alkyl chains and two imidazolium polar head-groups linked with a polyoxyethylene spacer, (C16Im)2(C4O). Here, PEGylated lipids have been introduced to the lipoplex formulation and the transgene expression of the Opa1 mitochondrial transmembrane protein in mice was assessed. The addition of PEG on the surface of the lipid mixed resulted in the formation of Ia3d bicontinuous cubic phases as determined by small angle X-ray scattering. After a single intramuscular administration, the cubic lipoplexes were accumulated in tissues with tight endothelial barriers such as brain, heart, and lungs for at least 48 h. The transgene expression of Opa1 in those organs was identified by western blotting or RNA expression analysis through quantitative polymerase chain reaction.

Conclusions
The expression reported here is sufficient in magnitude, duration and toxicity to consolidate the bicontinuous cubic structures formed by (C16Im)2(C4O)-based lipoplexes as valuable therapeutic agents in the field of gene delivery.

Graphical Abstract
Nanofactory for metabolic and chemodynamic therapy: pro-tumor lactate trapping and anti-tumor ROS transition
Authors: He Ruiqing , Zang Jie , Zhao Yuge , Liu Ying , Ruan Shuangrong , Zheng Xiao , Chong Gaowei , Xu Dailin , Yang Yan , Yang Yushan , Zhang Tingting , Gu Jingjing , Dong Haiqing , Li Yongyong 
Published: December 2021

AbstractLactate plays a critical role in tumorigenesis, invasion and metastasis. Exhausting lactate in tumors holds great promise for the reversal of the immunosuppressive tumor microenvironment (TME). Herein, we report on a “lactate treatment plant” (i.e., nanofactory) that can dynamically trap pro-tumor lactate and in situ transformation into anti-tumor cytotoxic reactive oxygen species (ROS) for a synergistic chemodynamic and metabolic therapy. To this end, lactate oxidase (LOX) was nano-packaged by cationic polyethyleneimine (PEI), assisted by a necessary amount of copper ions (PLNPCu). As a reservoir of LOX, the tailored system can actively trap lactate through the cationic PEI component to promote lactate degradation by two-fold efficiency. More importantly, the byproducts of lactate degradation, hydrogen peroxide (H2O2), can be transformed into anti-tumor ROS catalyzing by copper ions, mediating an immunogenic cell death (ICD). With the remission of immunosuppressive TME, ICD process effectively initiated the positive immune response in 4T1 tumor model (88% tumor inhibition). This work provides a novel strategy that rationally integrates metabolic therapy and chemodynamic therapy (CDT) for combating tumors.
Graphical Abstract
D-dimer for risk stratification and antithrombotic treatment management in acute coronary syndrome patients: a systematic review and metanalysis
Authors: Biccirè Flavio Giuseppe , Farcomeni Alessio , Gaudio Carlo , Pignatelli Pasquale , Tanzilli Gaetano , Pastori Daniele 
Published: December 2021

Abstract
Background
Data on the prognostic role of D-dimer in patients with acute coronary syndrome (ACS) are controversial. Our aim was to summarize current evidence on the association between D-dimer levels and short/long-term poor prognosis of ACS patients. We also investigated the association between D-dimer and no-reflow phenomenon.

Methods
Systematic review and metanalysis of observational studies including ACS patients and reporting data on D-dimer levels. PubMed and SCOPUS databases were searched. Data were combined with hazard ratio (HR) and metanalysed. The principal endpoint was a composite of cardiovascular events (CVEs) including myocardial infarction, all-cause and cardiovascular mortality.

Results
Overall, 32 studies included in the systematic review with 28,869 patients. Of them, 6 studies investigated in-hospital and 26 studies long-term outcomes. Overall, 23 studies showed positive association of high D-dimer levels with CVEs. D-dimer levels predicted poor prognosis in all studies reporting in-hospital outcomes. Five studies satisfied inclusion criteria and were included in the metanalysis, with a total of 8616 patients. Median follow-up was 13.2 months with 626 CVEs. The pooled HR for D-dimer levels and CVEs was 1.264 (95% CI 1.134–1.409). Five out of 7 studies (4195 STEMI patients) investigating the association between D-dimer levels and no-reflow showed a positive correlation of D-dimer levels with no-reflow.

Conclusions
In patients with ACS, D-dimer was associated with higher in-hospital and short/long-term complications. D-dimer was also higher in patients with no-reflow phenomenon. The use of D-dimer may help to identify patients with residual thrombotic risk after ACS.

Trial registration
The review protocol was registered in PROSPERO International Prospective Register of Systematic Reviews: CRD42021267233.
PDIA3 inhibits mitochondrial respiratory function in brain endothelial cells and C. elegans through STAT3 signaling and decreases survival after OGD
Authors: Keasey Matt. P. , Razskazovskiy V. , Jia C. , Peterknecht E. D. , Bradshaw P. C. , Hagg T. 
Published: December 2021

Abstract
Background
Protein disulfide isomerase A3 (PDIA3, also named GRP58, ER-60, ERp57) is conserved across species and mediates protein folding in the endoplasmic reticulum. PDIA3 is, reportedly, a chaperone for STAT3. However, the role of PDIA3 in regulating mitochondrial bioenergetics and STAT3 phosphorylation at serine 727 (S727) has not been described.

Methods
Mitochondrial respiration was compared in immortalized human cerebral microvascular cells (CMEC) wild type or null for PDIA3 and in whole organism C. Elegans WT or null for pdi-3 (worm homologue). Mitochondrial morphology and cell signaling pathways in PDIA3-/- and WT cells were assessed. PDIA3-/- cells were subjected to oxygen–glucose deprivation (OGD) to determine the effects of PDIA3 on cell survival after injury.

Results
We show that PDIA3 gene deletion using CRISPR-Cas9 in cultured CMECs leads to an increase in mitochondrial bioenergetic function. In C. elegans, gene deletion or RNAi knockdown of pdi-3 also increased respiratory rates, confirming a conserved role for this gene in regulating mitochondrial bioenergetics. The PDIA3-/- bioenergetic phenotype was reversed by overexpression of WT PDIA3 in cultured PDIA3-/- CMECs. PDIA3-/- and siRNA knockdown caused an increase in phosphorylation of the S727 residue of STAT3, which is known to promote mitochondrial bioenergetic function. Increased respiration in PDIA3-/- CMECs was reversed by a STAT3 inhibitor. In PDIA3-/- CMECs, mitochondrial membrane potential and reactive oxygen species production, but not mitochondrial mass, was increased, suggesting an increased mitochondrial bioenergetic capacity. Finally, PDIA3-/- CMECs were more resistant to oxygen–glucose deprivation, while STAT3 inhibition reduced the protective effect.

Conclusions
We have discovered a novel role for PDIA3 in suppressing mitochondrial bioenergetic function by inhibiting STAT3 S727 phosphorylation.
Cytoplasmic eIF6 promotes OSCC malignant behavior through AKT pathway
Authors: Zhao Zechen , Chu Weiming , Zheng Yang , Wang Chao , Yang Yuemei , Xu Teng , Yang Xueming , Zhang Wei , Ding Xu , Li Gang , Zhang Hongchuang , Zhou Junbo , Ye Jinhai , Wu Heming , Song Xiaomeng , Wu Yunong 
Published: December 2021

Abstract
Background
Eukaryotic translation initiation factor 6 (eIF6), also known as integrin β4 binding protein, is involved in ribosome formation and mRNA translation, acting as an anti-association factor. It is also essential for the growth and reproduction of cells, including tumor cells. Yet, its role in oral squamous cell carcinoma (OSCC) remains unclear.

Methods
The expression characteristics of eIF6 in 233 samples were comprehensively analyzed by immunohistochemical staining (IHC). Effects of eIF6 over-expression and knockdown on cell proliferation, migration and invasion were determined by CCK-8, wound healing and Transwell assays. Western blot, immunofluorescence (IF) and co-immunoprecipitation (co-IP) were performed for mechanical verification.

Results
We found that cytoplasmic eIF6 was abnormally highly expressed in OSCC tissues, and its expression was associated with tumor size and the clinical grade. Amplification of eIF6 promoted the growth, migration and invasion capabilities of OSCC cell lines in vitro and tumor growth in vivo. Through Western blot analysis, we further discovered that eIF6 significantly promotes epithelial-mesenchymal transformation (EMT) in OSCC cells, while depletion of eIF6 can reverse this process. Mechanistically, eIF6 promoted tumor progression by activating the AKT signaling pathway. By performing co-immunoprecipitation, we discovered a direct interaction between endogenous eIF6 and AKT protein in the cytoplasm.

Conclusion
These results demonstrated that eIF6 could be a new therapeutic target in OSCC, thus providing a new basis for the prognosis of OSCC patients in the future.
The effects of grazing on daily caloric intake and dietary quality
Authors: Zeballos Eliana , Chelius Carolyn 
Published: December 2021

Abstract
Background
The duration and frequency of eating occasions has been identified as a factor contributing to poor dietary quality among U.S. adults. The objective of this study is to examine whether grazing, defined as eating more than three times a day, affects total daily caloric intake and dietary quality measured by the 2015 Healthy Eating Index (HEI-2015).

Methods
We used a multivariate individual fixed-effects model to compare the caloric intake and dietary quality of individuals who grazed on 1 day but not another. This allowed us to control for differences in individual food intake and diet quality preferences among study participants. We use the National Health and Nutrition Examination Survey (NHANES), 2007-2018, and include data for adults aged 18 years or older who reported 2 days of dietary intake and were not pregnant or lactating (n = 27,775).

Results
Grazing increased total daily caloric intake by 205 cal and increased the daily HEI score by 0.59 points. Grazing increased HEI component scores for total fruit, whole fruit, and refined grains, and decreased HEI component scores for saturated fats. Morning grazing increased total daily caloric intake by 159 cal and increased the daily HEI score by 0.87 points — primarily by increasing component scores for total fruit, whole fruit, whole grains, total dairy, seafood and plant proteins, and sodium. Evening grazing increased daily caloric intake by 76 cal and decreased the daily HEI score by 0.41 points — primarily by decreasing the component scores for total fruit, whole grains, fatty acids, and saturated fats. Evening grazing increased HEI component scores for sodium and refined grains.

Conclusions
Grazing increases daily caloric intake and can decrease dietary quality (particularly when grazing in the evening).
Exploring the associations of depressive symptoms with healthy eating self-efficacy over time amongst women in the READI cohort study
Authors: Opie Rachelle , Abbott Gavin , Crawford David , Ball Kylie 
Published: December 2021

Abstract
Background
There is growing evidence that diet is associated with both depressive symptoms and clinical depression, likely through biological mechanisms. However, it is also plausible that depression impacts diet, for example by impairing the personal drivers of healthy eating behaviors such as self-efficacy. This study is one of the first to explore the association of depressive symptoms with healthy eating self-efficacy over time.

Methods
Data was drawn from the Resilience for Eating and Activity Despite Inequality (READI) longitudinal study, a prospective cohort study of socioeconomically disadvantaged Australian women. This analysis includes a sub-sample of 1264 women. Linear mixed models, with random intercepts for suburb of residence, were performed to explore the relationships between total healthy eating self-efficacy at 5-years follow-up and depressive symptoms over time, whilst adjusting for potential confounders. To assess different trajectories of depressive symptoms over time, four categories were created; 1. no depressive symptoms (n = 667), 2. resolved depressive symptoms (n = 165), 3. new depressive symptoms (n = 189), and 4. persistent depressive symptoms (n = 243).

Results
There was very strong evidence of a difference in total healthy eating self-efficacy at follow-up between the four depressive symptoms trajectory categories (F(3,235) = 7.06,p < .0001), after adjusting for potential confounders. Pairwise comparisons indicated strong evidence of higher healthy eating self-efficacy among individuals with no depressive symptoms compared to individuals with persistent depressive symptoms (B = 1.97[95%CI: 0.60,3.33],p = .005). Similarly, there was evidence of higher healthy eating self-efficacy in individuals with resolved depressive symptoms than those with persistent depressive symptoms (B = 1.95[95%CI: 0.18,3.72],p = .031).

Conclusions
This study provides new insights demonstrating differences in total healthy eating self-efficacy at 5-year follow-up according to trajectory of depressive symptoms over time. Future interventions should focus on strategies that enhance self-efficacy among individuals with or at risk of depressive symptoms for supporting healthier dietary practices, which in turn, may contribute to reducing the highly burdensome mental health condition.
Colonization of fecal microbiota from patients with neonatal necrotizing enterocolitis exacerbates intestinal injury in germfree mice subjected to necrotizing enterocolitis-induction protocol via alterations in butyrate and regulatory T cells
Authors: He Yu , Du Weixia , Xiao Sa , Zeng Benhua , She Xiang , Liu Dong , Du Hua , Li Luquan , Li Fang , Ai Qing , He Junli , Song Chao , Wei Hong , Zhao Xiaodong , Yu Jialin 
Published: December 2021

Abstract
Background
Necrotizing enterocolitis (NEC) remains a life-threatening disease in neonates. Numerous studies have shown a correlation between the intestinal microbiota and NEC, but the causal link remains unclear. This study aimed to demonstrate the causal role of gut microbiota in NEC and explore potential mechanisms involved.

Methods
Eighty-one fecal samples from patients with NEC and eighty-one matched controls (matched to the NEC infants by gestational age, birth weight, date of birth, mode of delivery and feeding patterns) were collected. To explore if altered gut microbiota contributes to the pathogenesis of NEC, fecal microbiota transplantation (FMT) was carried out in germ-free (GF) mice prior to a NEC-induction protocol that included exposure to hypoxia and cold stress. Butyric acid was also administered to demonstrate its role in NEC. The fecal microbiota from patients and mice were analyzed by 16S rRNA gene sequencing analysis. Short chain fatty acid (SCFA) levels were measured by gas chromatography-mass spectrometry (GC–MS). The ontogeny of T cells and regulatory T cells (Tregs) in lamina propria mononuclear cells (LPMC) from the ileum of patients and mice were isolated and analyzed by flow cytometry.The transcription of inflammatory cytokines was quantified by qRT-PCR.

Results
NEC patients had increased Proteobacteria and decreased Firmicutes and Bacteroidetes compared to fecal control samples, and the level of butyric acid in the NEC group was lower than the control group. FMT in GF mice with samples from NEC patients achieved a higher histological injury scores when compared to mice that received FMT with control samples. Alterations in microbiota and butyrate levels were maintained in mice following FMT. The ratio of Treg/CD4+T (Thelper) cells was reduced in both NEC patients and mice modeling NEC following FMT.

Conclusions
The microbiota was found to have NEC and the microbial butyrate-Treg axis was identified as a potential mechanism for the observed effects.
Eye-gaze control of a wheelchair mounted 6DOF assistive robot for activities of daily living
Authors: Sunny Md Samiul Haque , Zarif Md Ishrak Islam , Rulik Ivan , Sanjuan Javier , Rahman Mohammad Habibur , Ahamed Sheikh Iqbal , Wang Inga , Schultz Katie , Brahmi Brahim 
Published: December 2021

AbstractBackgroundBuilding control architecture that balances the assistive manipulation systems with the benefits of direct human control is a crucial challenge of human–robot collaboration. It promises to help people with disabilities more efficiently control wheelchair and wheelchair-mounted robot arms to accomplish activities of daily living.MethodsIn this study, our research objective is to design an eye-tracking assistive robot control system capable of providing targeted engagement and motivating individuals with a disability to use the developed method for self-assistance activities of daily living. The graphical user interface is designed and integrated with the developed control architecture to achieve the goal.ResultsWe evaluated the system by conducting a user study. Ten healthy participants performed five trials of three manipulation tasks using the graphical user interface and the developed control framework. The 100% success rate on task performance demonstrates the effectiveness of our system for individuals with motor impairments to control wheelchair and wheelchair-mounted assistive robotic manipulators.ConclusionsWe demonstrated the usability of using this eye-gaze system to control a robotic arm mounted on a wheelchair in activities of daily living for people with disabilities. We found high levels of acceptance with higher ratings in the evaluation of the system with healthy participants.
Alleviating the effect of quinoa and the underlying mechanism on hepatic steatosis in high-fat diet-fed rats
Authors: Song Chenwei , Lv Wei , Li Yahui , Nie Pan , Lu Jun , Geng Yanlou , Heng Zhang , Song Lihua 
Published: December 2021

Abstract
Background
Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic component of metabolic syndrome and has attracted widespread attention due to its increased prevalence. Daily dietary management is an effective strategy for the prevention of NAFLD. Quinoa, a nutritious pseudocereal, is abundant in antioxidative bioactive phytochemicals. In the present study, the effects of different amounts of quinoa on the progression of NAFLD and the related molecular mechanism were investigated.

Methods
Male SD rats were simultaneously administered a high fat diet (HF) and different amounts of quinoa (equivalent to 100 g/day and 300 g/day of human intake, respectively). After 12 weeks of the intervention, hepatic TG (triglyceride) and TC (total cholesterol) as well as serum antioxidative parameters were determined, and hematoxylin–eosin staining (H&E) staining was used to evaluate hepatic steatosis. Differential metabolites in serum and hepatic tissue were identified using UPLC-QTOF-MSE. The mRNA expression profile was investigated using RNA-Seq and further verified using real-time polymerase chain reaction (RT-PCR).

Results
Low amounts of quinoa (equivalent to 100 g/d of human intake) effectively controlled the weight of rats fed a high-fat diet. In addition, quinoa effectively inhibited the increase in hepatic TG and TC levels, mitigated pathological injury, promoted the increase in SOD and GSH-Px activities, and decreased MDA levels. Nontarget metabolic profile analysis showed that quinoa regulated lipid metabolites in the circulation system and liver such as LysoPC and PC. RNA-Seq and RT-PCR verification revealed that a high amount of quinoa more effectively upregulated genes related to lipid metabolism [Apoa (apolipoprotein)5, Apoa4, Apoc2] and downregulated genes related to the immune response [lrf (interferon regulatory factor)5, Tlr6 (Toll-like receptor), Tlr10, Tlr11, Tlr12].

Conclusion
Quinoa effectively prevented NAFLD by controlling body weight, mitigating oxidative stress, and regulating the lipid metabolic profile and the expression of genes related to lipid metabolism and the immune response.
One year of COVID-19 pandemic: a cross sectional study on teaching oral and maxillofacial surgery
Authors: Bock Anna , Peters Florian , Winnand Philipp , Kniha Kristian , Heitzer Marius , Lemos Martin , Hölzle Frank , Modabber Ali 
Published: December 2021

Abstract
Background
The pandemic has challenged educational institutions to catalyze digitalization and rapidly develop online teaching formats. The aim of the study was to evaluate the teaching offered for oral and maxillofacial surgery at our university during the pandemic and to investigate the students’ perceptions of the current situation.

Methods
A 38-item questionnaire with five sections (demographic information, lectures, internships, e-learning, and pandemic-related solutions/effects) was created online. Most questions were answered on a 10-point Likert scale, with 1 indicating “fully agree/positive” and 10 indicating “totally disagree/negative.” The remaining questions were either answered with yes/no, percent value, or open-ended text responses. All 3rd-5th year dental students were invited to voluntarily participate and were sent a link by email in a general mail shot.

Results
A total of 63.7% of the participants had no prior experience with online courses before the pandemic. The students stated that the change from face-to-face to online teaching worked very well in the last two semesters (mean = 2.73, standard deviation = 2.05). Overall, the pandemic had a rather positive influence on the acquisition of theoretical skills and a negative influence on the acquisition of practical skills (p < 0.0001). The evaluation showed that, compared to other dental clinics at our university, the department for oral and maxillofacial surgery was well prepared for the pandemic.

Conclusion
Digitalization of oral and maxillofacial surgery teaching in dental education is possible but depends on the institution’s preparatory work and technological possibilities. The students declared a high acceptance of digital learning formats and indicated an increased motivation to learn due to e-learning. The pandemic’s influence on the students’ education was rated ambivalent.