bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel regulatory loop FBXW7/MAP4 promotes esophageal squamous cell carcinoma progression via ERK phosphorylation
Authors: Pan Yunzhi , Yu Jing , Guo Yuqing , Gao Yingyin , Wang Changxing , Liang Zhipan , Wu Meiying , Li Yinyan , Shen Jingyi , Lu Chenchen , Ma Sai 
Published: July 2022

Abstract
Background:
Increasing evidence suggests that FBXW7 has a high frequency of mutations in esophageal squamous cell carcinoma (ESCC). However, the function of FBXW7, especially the mutations, is not clear. This study was designed to investigate the functional significance of FBXW7 loss of function and underlying mechanism in ESCC.
Methods:
Immunofluorescence was applied to clarify the localization and main isoform of FBXW7 in ESCC cells. Sanger sequencing were performed to explore the mutation of FBXW7 in ESCC tissues. Proliferation, colony and invasion assay were performed to examine the functional roles of FBXW7 in ESCC cells in vitro and in vivo. Real-time RT-PCR, immunoblotting, GST-pulldown, LC-MS/MS and co-immunoprecipitation assay were used to explore the molecular mechanism underlying the actions of FBXW7 functional inactivation in ESCC cells. Immunohistochemical staining were used to explore the expression of FBXW7 and MAP4 in ESCC tissues.
Results:
The main FBXW7 isoform in ESCC cells was the β transcript in the cytoplasm. Functional inactivation of FBXW7 led to activation of the MAPK signaling pathway and upregulation of the downstream MMP3 and VEGFA, which enhanced tumor proliferation and cell invasion. Among the five mutation forms screened, S327X (X means truncated mutation) had an effect similar to the FBXW7 deficiency and led to the inactivation of FBXW7 in ESCC cells. Three other point mutations, S382F, D400N and R425C, attenuated but did not eliminate FBXW7 function. The other truncating mutation, S598X, which is located outside of the WD40 domain, did not reveal the function of FBXW7. Notably, MAP4 was identified as a potential target of FBXW7. The No. 521 tyrosine residue of MPA4, which was phosphorylated by CHEK1, played a key role in the FBXW7-related degradation system. MAP4 also inhibited the protein level of FBXW7 by enhancing the expression of phosphorylated ERK. Immunohistochemical staining indicated that FBXW7 loss of function was associated with tumor stage and shorter survival of patients with ESCC. Univariate and multivariate Cox proportional hazards regression analyses showed that high FBXW7 and low MAP4 was an independent prognostic indicator and prospective longer survival. Moreover, a combination regimen that included MK-8353 to inhibit the phosphorylation of ERK and bevacizumab to inhibit VEGFA produced potent inhibitory effects on the growth of xenograft tumors in vivo.
Conclusions:
This study provided evidence that FBXW7 loss of function promoted ESCC via MAP4 overexpression and ERK phosphorylation, and this novel FBXW7/MAP4/ERK axis may be an efficient target for ESCC treatment.
Roll stamped Ni/MWCNT composites for highly reliable cellulose paper-based strain sensor
Authors: Qi Xue , Matteini Paolo , Hwang Byungil , Lim Sooman 
Published: July 2022

Abstract
Printing technology for electronic devices has received significant attention owing to its fast and massive productivity under ambient conditions. In this study, a facile approach was proposed for manufacturing cellulose paper-based strain sensors with Ni/ multi-walled carbon nanotubes (MWCNT) composites using roll stamping technology. This process enables fabrication of stable sensing structures owing to the formation of stable Ni core enveloping structures in the MWCNT interlacing network. In particular, the rheological properties of the composites revealed shear thinning and thixotropic behaviors, which resulted in fine printing of the sensing electrodes. Furthermore, the shape of the printed patterns, impacted by the pattern morphology, significantly influenced the strain-sensing performance. In particular, the Ni/MWCNT composite-based strain sensor exhibited higher gauge factor of 13.9 with high sensing recovery of 90.4% and stability for 23,500 bending cycles test.
Imbalance in ALR ubiquitination accelerates the progression of nonalcoholic steatohepatitis to hepatocellular carcinoma
Authors: An Wei , Zheng Mingzhe , Ai Ziwei , Chen Yujiao , xie ping 
Published: July 2022

Abstract
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. Accumulating evidence indicates that non-alcoholic steatohepatitis (NASH) is a key predisposing factor for HCC occurrence. However, the precise mechanisms driving NASH transition to HCC remain largely obscure. Augmenter of liver regeneration (ALR) is a sulfhydryl oxidase and cytochrome c reductase that functions as an important regulator of mitochondrial dynamics. In this study, we focused on ALR ubiquitination-mediated degradation and its potential contribution to NASH-driven HCC progression at the mitochondrial level. Hepatic ALR expression in HCC patients was determined using immunohistochemical analysis. Mice with liver-specific deletion of ALR (ALRCKO) and ALRWT mice were fed a western diet (WD) and high-sugar solution for induction of NASH. HCC in animals was induced via peritoneal administration of CCl4. ALR expression was markedly decreased in liver tissues of patients with NASH and HCC compared with non-NASH and non-tumor tissues. Similarly, in ALRWT mice, the ALR level in tumor tissue was reduced relative to that in para-tumor tissue. In the ALRCKO group, mice fed WD plus CCl4 developed HCC starting at week 12 while ALRWT mice fed WD plus CCl4 developed HCC at week 24. Analysis of protein posttranslational modifications revealed ubiquitylation (Ub) and deubiquitination (DUb) of ALR by murine double minute 2 (MDM2) and ubiquitin-specific protease 36 (USP36), respectively. Imbalance between Ub and DUb of ALR resulted in profound ALR degradation, which appeared to be reversibly associated with Edmondson-Steiner tumor grade. Rescue of ALR levels via gene transfection abolished tumor malignant features to a certain extent in vitro. Notably, ALR deletion substantially enhanced mitochondrial fission by activating Drp1 phosphorylation, thus disrupting the balance of mitochondrial dynamics between fission and fusion and severely impairing oxidative phosphorylation (OXPHOS) and ATP synthesis, instead enhancing anaerobic metabolism, which might be attributed to steatotic hepatocyte transition into the malignant HCC phenotype. Hepatic ALR depletion via dysregulation of ubiquitination is a critical aggravator of NASH-HCC progression and represents a promising therapeutic target for related liver diseases.
Treatment of renal interstitial fibrosis with an agonistic Tie2 monoclonal antibody via amelioration of peritubular capillary lesions in a mouse model of nephropathy
Authors: Jiang Lu , Hu Xiaohan , Feng Yajun , Wang Zhen , Tang Hanyun , Lin Qiang , Shen Yunyan , Zhu Yun , Xu Qinying , Li Xiaozhong 
Published: July 2022

Abstract
Background: Chronic kidney disease (CKD) eventually manifests as renal interstitial fibrosis, and loss of peritubular capillaries in the fibrotic area is the main marker of disease progression. Tie2, as the main functional receptor of angiopoietin, is characteristically expressed in vascular endothelial cells. This study aimed to evaluate the effect and mechanism of an agonistic Tie2 monoclonal antibody on folic acid (FA)-induced renal fibrosis (FAN) in mice.Methods: Mice were randomly divided into wild-type mice, FAN model mice, and FAN model mice treated with the agonistic Tie2 antibody. Human umbilical vein endothelial cells with lipopolysaccharide-induced injury were treated with the agonistic Tie2 antibody in vitro.Results: FA-induced renal tubulointerstitial lesions could be prevented with the agonistic Tie2 antibody. The extent of renal fibrosis induced by FA was suppressed by treatment with the agonistic Tie2 antibody. The level of fibroblast-specific protein 1 was reduced in mice that were administered the agonistic Tie2 antibody. Further, the agonistic Tie2 antibody inhibited FA‐induced vascular inflammation by downregulating vascular cell adhesion molecule-1. In addition, peritubular capillary density was upregulated by agonistic Tie2 antibody treatment, as evidenced by an increase in the level of cluster of differentiation 31. These findings were verified by the in vivo results, which showed that the levels of VCAM-1, Bax, and α-smooth muscle actin were downregulated after treatment with the agonistic Tie2 antibody.Conclusions: Based on all these findings, it appears that the agonistic Tie2 antibody attenuated renal interstitial fibrosis in FAN model mice by promoting peritubular capillary regeneration, inhibiting inflammation, and improving peritubular capillary lesions, and therefore, it may have promise for the treatment of CKD.
Cerebrovascular Complications of COVID-19 on Venovenous Extracorporeal Membrane Oxygenation
Authors: Zaaqoq Akram M. , Griffee Matthew J , Kelly Thu-Lan , Fanning Jonathon , Heinsar Silver , Suen Jacky , Mariani Silvia , Bassi Gianluigi Li , Jacobs Jeffrey , White Nicole , Fraser John F , Lorusso Roberto , Peek Giles , Cho Sung-Min ,   COVID-19 Critical Care Consortium (COVID Critical) N/A
Published: July 2022

Abstract

Background: Evidence of cerebrovascular complications in Coronavirus disease 2019 (COVID-19) requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO) is limited. The aim of our study is to characterize the prevalence and risk factors of stroke secondary to COVID-19 in patients on V-V ECMO. Methods: We analyzed prospectively collected observational data of adults from 380 institutions of 53 countries in the COVID-19 Critical Care Consortium (COVID Critical) registry. We used univariable and multivariable survival modeling to identify risk factors for stroke during ECMO. Cox proportional hazards and Fine-Gray models were used, with death and discharge treated as competing risks. Results: 595 patients (median age [IQR]: 51 years [42-59]; male: 70.8%) had V-V ECMO support. Forty-three patients (7.2%) suffered strokes, 83.7% of which were hemorrhagic. In multivariable survival analysis, obesity [adjusted Hazard Ratio (aHR)=2.19, 95% CI=1.05–4.59] and use of vasopressors before ECMO (aHR=2.37, 95% CI =1.08–5.22) were associated with an increased risk of stroke. Relative ΔPaCO2 of negative 26% and relative ΔPaO2 of positive 24% at 48-hours of ECMO initiation were observed in stroke patients in comparison to relative ΔPaCO2 of negative 17% and relative ΔPaO2 of positive 7% in the non-stroke group. Patients with acute stroke had a 79% in-hospital mortality compared with a 45% mortality for stroke-free patients.Conclusion: Our study highlights the association of obesity and pre-ECMO vasopressor use with the development of stroke in COVID-19 patients on V-V ECMO. Also, the importance of relative decrease in PaCO2 and moderate hyperoxia within 48-hours after ECMO initiation were additional risk factors.
Clinical and aesthetic outcomes of different papillae width following modified coronally advanced tunnel technique: A retrospective study
Authors: Chen Huiwen , Dong Jiachen , Wu Sicheng , Song Zhongchen 
Published: July 2022

Abstract
ObjectiveThis study was to investigate whether the width of the interdental papillae could contribute to clinical and aesthetic outcomes of the modified coronally advanced tunnel technique (MCAT).Materials and MethodsA total of 28 patients with 70 class RT1 single and multiple gingival recessions (GRs) were treated by MCAT between March 2017 and March 2021. The apex angle of the mesial and distal papillae adjacent to the involved tooth were recorded at baseline. Clinical outcomes (mean root coverage (mRC) and complete root coverage (CRC)) were recorded at 12 months after surgery. Periodontal clinical parameters (keratinized tissue width (KTW), gingival index (GI), plaque index (PLI), periodontal probing depth (PPD), and clinical attachment loss (CAL)) were recorded at baseline and 12 months after surgery. Aesthetic evaluation was carried out using the root coverage esthetic score (RES) and patients’ visual analogue scale (VAS). The possible relationship between papilla width and clinical and/or aesthetic outcomes was discerned by multiple linear regression and logistic regression.ResultsThe mean width of papilla ranged from 22.6° to 74.65° with a median of 42.32° (IQR: 16.98°). For single GRs, the papilla width was not significantly correlated to mRC, RES, CRC, VAS gain, CAL gain, and KTW gain. The RES and CRC were only associated with papilla width in multiple GRs (P = 0.012). At 12 months, 95.79 ± 10.17% and 92.94 ± 10.64% of mRC were obtained for multiple GRs and single GRs, respectively. Better results in terms of CRC were obtained from multiple GRs compared with single GRs (78.94% vs. 66.67%). For aesthetic outcomes, 8.84 ± 1.54 and 9.16 ± 1.53 of RES were observed at single and multiple GR defects.ConclusionsThe CRC and RES of multiple GRs following MCAT is significantly correlated to papillae width. Relatively wide gingival papillae tend to have a greater chance to achieve complete root surface coverage.Clinical relevance:The width of the gingival papilla helps to speculate on the clinical outcome of root surface coverage. Although the findings are not yet highly predictable, the MCAT can yield better results in the wider gingival papilla area.
Complexation between aluminum ion and glycolic acid under acidic condition
Authors: Etou Mayumi , Taketatsu Toshifumi , Okaue Yoshihiro , Inoue Takanori , Yokoyama Takushi 
Published: July 2022

Abstract
The complexation between Al3+ ([Al(H2O)6]3+) and glycolic acid (GA, C2H4O3) which has a carboxyl group and a hydroxyl group in a molecule was investigated under acidic condition using 27Al NMR, 13C NMR and ESI-MS techniques. The five peaks including a peak due to Al3+ were observed in 27Al NMR spectra for the mixed solution of Al3+ and GA, suggesting the existence of at least four Al-GA complexes. The results of NMR and ESI-MS measurements revealed that GA and Al3+ can form one monodentate complex (AlGA2+) and three bidentate complexes (AlGA+, AlGA2−, and AlGA33−) complexes. From the deconvolution of 27Al NMR spectra and pKa value of GA, the conditional formation constants (log K) of each complex (GA/Al molar ratio of 25 in mixed solution) can be determined to be 0.94 (AlGA2+), -0.96 (AlGA+), -0.77 (AlGA2-) and − 2.21 (AlGA33-), respectively. In addition, the overall formation constant of three bidentate complex at pH 3 was also calculated to be -1.65.
First record of black spot bandfish: Acanthocepola limbata (Valenciennes, 1835) from Northern Bay of Bengal
Authors: Kumar J. S. Yogesh , Panda Pradip , Sen Arya 
Published: July 2022

Abstract
Acanthocepola limbata (Valenciennes, 1835) is reported for the first time from Northern Bay of Bengalon the basis of specimens collected from Petuaghat fish landing, West Bengal coast and this species reported from Karnataka, Maharastra, Kerala, west coast of India and Gulf of Mannar, east coast of India. In this manuscript, details on the morphological characters have been provided and discussed with all the reported species in the genus found in India.
Direct method for the determination of docosahexaenoic acid (DHA ) in human milk: optimization by factorial design
Authors: Kus-Yamashita Mahyara Markievicz Mancio , Cano Cristiane Bonaldi , Monteiro Vânia Claudia Barros , Catarino Regina Maria 
Published: July 2022

Abstract
Human milk provides all the nutrients required by babies during the first six months of their life. Human milk lipids represent the main source of energy, contributing almost 50% of the total energy content. Additionally, fatty acids ensure the correct development of children in the prenatal, postnatal, and infant phases. Docosahexaenoic acid (DHA) is essential for visual and cognitive development, and its presence during childhood can affect long-term health. This study aimed to optimize and validate a methodology for the direct determination of DHA in human milk. We used 20 samples of human milk from lactating women living in the city of Itu, São Paulo, who attended Basic Health Units from September 2019 to September 2020, and a sample of certified reference material from the National Institute of Standards and Technology. The proposed methodology consists of a validated mixed transesterification process without prior lipid extraction, optimized by factorial design. This methodology can be successfully used in human milk samples, as it is both precise and accurate. The values of DHA in the sampled milks were similar to those in other European countries and lower than those in Asian countries due to diet.
Stable response of tree growth to climate variations over the last five centuries
Authors: Trevino Aleyda , Stine Alexander , Huybers Peter 
Published: July 2022

Abstract
Changes in the environmental limitations upon tree-ring growth have been documented during the instrumental periods, but it is more difficult to examine whether environmental change altered dendroclimatological responses over the longer timescales applicable to paleoclimate reconstructions. We present a method to evaluate changes in the relationship between temperature and tree-ring growth over the last five centuries that leverages nonlinear growth relationships between individuals trees within a stand as suggested by Liebig's Law of the Minimum. Furthermore, using this method, we show that regional tree growth was more sensitive to temperature during colder climates over the last five centuries at global and regional scales. These results provide strong confirmation that climate variations alter dendrochronological sensitivity to temperature over the last five centuries. Change in sensitivity is small, however, with an average stand-level increase in sensitivity of 2.7% per °C warming. Our results thus also demonstrate that dendroclimatological reconstructions are generally stable over at least the last five centuries. It may also be possible to use the nonlinear inter-relationships among tree growth within a stand as an independent proxy of low-frequency fluctuations in climate.
Association analysis of social support and poverty in older adults
Authors: Liao Hui , Li Sangsang , Han Dan , Zhang Mei , Zhao Jie , Wu Yunyi , Ma Ying , Yan Chaoyang , Wang Jing 
Published: July 2022

Abstract
Background: With population aging becoming a pressing global concern, social support is more meaningful for older adults. In particular, financial supports, such as health insurance and financial assistance derived from family, all play great role in assistance affairs. Research shows social support possibly has an impact on poverty, but the association between formal and informal supports is unclear. We are aimed at verifying the association between distinct social supports and exploring whether this association would affect poverty alleviation for older adults.Methods: A total of 2,683 individuals aged 60 years or older who have medical expenses were included in a survey conducted by the China Health and Retirement Longitudinal Study in 2018. A chi-square analysis and an independent samples T test all were used to explore the differences of social supports among old people with different economic condition. A binary logistic regression was aimed at analyzing the association between social supports and poverty for older adults. The structural equation model was established to evaluate the association between formal support and informal support and the mechanism(s) of social supports affecting poverty.Results: The overall average rate of reimbursement for outpatient care was 0.20 with standard deviation 0.22, and the average reimbursement rate of inpatient care for the poor older adults is nearly 5% lower than the average of the non-poor older adults. We found that having private health insurance and higher reimbursement rate of inpatient care were associated with lower likelihood of living in poverty for older adults. Formal support would directly affect poverty, but its impact on poverty through informal support is insignificant even if formal support is negatively associated with informal support. Conclusion: A dilemma in reducing the economic burden of disease and receiving family assistance for older adults was revealed, and a more complete health security and higher level of medical expenses compensation would be beneficial to prevent poverty. Optimizing the primary healthcare and increasing the percentage of insurance compensation, policies that focus on the specific cultural values and strengthening the role of supplementary insurance are advantaged for alleviating poverty among older adults.
The G nucleotide guides codon usage bias in genes associated with depression
Authors: Khandia Rekha , Puranik Nidhi , Pandey Megha , Dhama Kuldeep , Khan Azmat Ali , Alexiou Athanasios , Batiha Gaber El-Saber , Elsayad Mohamed 
Published: July 2022

Abstract
Depression or major depressive disorder is a psychiatric disorder affecting mood, behavior, and mental and physical health. Depression runs in families, suggestive of the genetic basis of the disease. Much research is going to understand the molecular basis of depression. In the present work, we tried to envisage the codon usage pattern analysis of genes involved in depression. The investigation revealed that all the genes were highly expressed, and codon usage bias (CUB) is influenced by the length of the gene, nucleotide disproportion, nucleotide compositional constraints, and CAI. The detailed investigation related to the effect of codon composition of CUB revealed that out of 20 compositional constraints, only G nucleotide showed a relationship at overall %G, %G2, %G3 and %GC2 positions. E of composition is further evidenced by the relationship between CUB and nucleotide skew. Neutrality, parity, P2 analysis, suppression of CpG, and TpA dinucleotide and over-representation of TpG dinucleotide followed by under abundance of TpA and CpG encompassing codons and over-representation of CTG and GTG codons all indicated towards the selectional force in shaping codon usage in genes linked to depression. The genes showed a significant positive correlation with each other based on RSCU value indicative of similar codon usage. Based on protein properties, all genes correlated with each other except for the CYP3A4 gene. The association is suggestive of identical protein properties also of genes involved. The analysis helps unveil the compositional features and various forces affecting codon usage of the gene.