bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiopulmonary exercise test: A 20-year (2002-2021) bibliometric analysis
Authors: Song Lei , Qu Hua , Luo Jinwen , Wang Wenting , Zheng Liying , Xue Mei , Shi Dazhuo
Published: August 2022

Background

The clinical application value of cardiopulmonary exercise test (CPET) has increasingly attracted attention, and related research has been increasing yearly. However, there is no summary analysis of the existing CPET literature. This is the first bibliometric analysis of publications in the CPET.

Methods

CPET-related articles published between 2002 and 2021 were retrieved from the Web of Science Core Collection database. The search was limited to Articles and Reviews in English. CiteSpace software was used to conduct collaborative network analysis of countries/regions, institutions, authors, the co-occurrence of subject categories and keywords, and co-citation analysis of authors, journals, and references.

Results

A total of 4,426 publications were identified. During the study period, the number of published articles increased yearly. Developed countries from the Americas and Europe led the field. The University of Milan was the most prolific institution, with Ross Arena and Wasserman K being the most prolific and co-cited authors in the field, respectively. Cardiovascular System & Cardiology and Respiratory System were the main areas involved. Moreover, heart failure, oxygen uptake, and prognostic value were the central themes.

Conclusions

CPET had attracted widespread attention, and the number of publications will increase substantially according to the current growth trends. In the future, CPET is expected to be further adopted in large-scale clinical studies as a means of assessing the functional ability of patients to verify the efficacy of related interventions. High-quality evidence-based medical CPET-related indicators is expected to be used in clinical diseases risk prediction.
Probabilistic 2-meter surface temperature forecasting over Xinjiang based on Bayesian model averaging
Authors: Aihaiti Ailiyaer , Wang Yu , Ali Mamtimin , Huo Wen , Zhu Lianhua , Liu Junjian , Gao Jiacheng , Wen Cong , Song Meiqi
Published: August 2022

Based on Bayesian model averaging (BMA), the suitability and characteristics of the BMA model for forecasting 2-m temperature in Xinjiang of China were analyzed by using the forecast results of the Desert Oasis Gobi Regional Analysis Forecast System (DOGRAFS) and Rapid-refresh Multiscale Analysis and Prediction System (RMAPS) developed by the Urumqi Institute of Desert Meteorology of the China Meteorological Administration, China Meteorological Administration–Global Forecast System (CMA-GFS) developed by the China Meteorological Administration, and the European Center for Medium-Range Weather Forecasts (ECMWF) developed by the European Center. The results showed that (1) the weight of ECMWF to the 2-m temperature forecast is maintained at about 0.6–0.7 under different lengths of training periods, and the weight of other model products is below 0.15. (2) The forecasts of each model at the four representative stations are quite different, and the maximum forecast error reaches 6.9°C. However, the maximum error of the BMA forecast is only about 2°C. In addition, the forecast uncertainty in southern Xinjiang is greater than that in northern Xinjiang. (3) Compared with multi-model ensembles, the overall prediction performance of the BMA method is more consistent in spatial distribution. Additionally, the standard deviation and correlation coefficient between the BMA forecast and observation were greater than 0.98, and the RMSE decreased significantly. It is feasible to use the BMA method to correct the accuracy of the 2-m temperature forecast in Xinjiang.
Influence of family and academic satisfaction on life satisfaction among Peruvian university students in the times of COVID-19: The mediating role of self-esteem
Authors: Carranza Esteban Renzo Felipe , Mamani-Benito Oscar , Castillo-Blanco Ronald , Lingan Susana K. , Cabrera-Orosco Isabel
Published: August 2022

Objective

To examine the effect of family and academic satisfaction on the self-esteem and life satisfaction among Peruvian university students.

Method

Of the 1,182 Peruvian university students who participated, 364 were male; and 818 were female; and ranged from 17 to 39 years of age (mean = 20.67, SD = 4.4). The family satisfaction scale (FSS), the Escala breve de satisfacción con los estudios (EBSE; Brief Academic Satisfaction Scale in Spanish), Rosenberg’s self-esteem scale (RSES), and the satisfaction with life scale (SWLS) were used to perform the assessments.

Results

The study model showed an adequate fit (χ2 19.5, p < 0.001, CFI = 0.977, RMSEA = 0.057), confirming the association between family satisfaction and life satisfaction (β = 0.26, p < 0.001) and self-esteem (β = 0.35, p < 0.001), and the correlation between academic satisfaction and self-esteem (β = 0.35, p < 0.001) and life satisfaction (β = 0.23, p < 0.001). The model accounted for 42% of life satisfaction.

Conclusion

Family satisfaction and academic satisfaction affect self-esteem and life satisfaction.
Related factor analysis for predicting large-volume central cervical lymph node metastasis in papillary thyroid carcinoma
Authors: Tan Li , Ji Jiaqi , Sharen Gaowa , Liu Yuewu , Lv Ke
Published: August 2022

The aim of this study was to investigate the factors related to large-volume central cervical lymph node metastasis (LNM) in papillary thyroid carcinoma. A retrospective study of 340 patients with 642 papillary thyroid carcinoma nodules who underwent thyroidectomy in Peking Union Medical College Hospital between 2011 and 2015 was conducted. These nodules were divided into two groups by the number of central cervical lymph node metastases: large‐volume central cervical LNM (>5 metastatic lymph nodes, n = 129) and no central cervical LNM (n = 211). We evaluated the correlations between gender, age, chronic lymphocytic thyroiditis, thyroid ultrasonographic features, and large‐volume central cervical LNM. We found that younger age (≤40 years) (OR = 3.796, 95% CI = 2.842, 5.070), male gender (OR = 4.005, 95% CI = 2.858, 5.61), and ultrasonographic features such as tumor macroaxis size (OR = 2.985, 95% CI = 1.581, 5.633), tumor located in the isthmus (OR = 7.578, 95% CI = 4.863, 11.810), ill-defined margin (OR = 3.008, 95% CI = 1.986, 4.556), microcalcification (OR = 2.155, 95% CI = 1.585, 2.929), and abnormal cervical lymph nodes (OR = 13.753, 95% CI = 9.278, 20.385) were independent risk factors for large-volume central cervical LNM in papillary thyroid carcinoma, while chronic lymphocytic thyroiditis (OR = 0.248, 95% CI = 0.172, 0.358) was a protective factor. Younger age (≤40 years), male sex, and ultrasonographic features such as tumor macroaxis size, tumor located in the isthmus, ill-defined margin, microcalcification, and abnormal cervical lymph nodes were independent risk factors for large-volume central cervical LNM in papillary thyroid carcinoma, while chronic lymphocytic thyroiditis can be considered a protective factor. Our results provide a reference for adjusting clinical treatment approaches.
Ovulation induction regimens are associated with a higher rate of livebirth after frozen single-blastocyst transfer among women with polycystic ovary syndrome
Authors: Niu Yue , Zhao Dingying , Wang Yuhuan , Suo Lu , Zou Jialin , Wei Daimin
Published: August 2022

Background

Hormone replacement therapy (HRT) regimen was suggested to be associated with a decreased rate of livebirth and a higher risk of hypertensive disorders of pregnancy (HDP) after frozen cleavage stage embryo transfer in women with polycystic ovary syndrome (PCOS). With the dramatically increased use of elective single embryo transfer, there is great need to explore the impacts of different endometrial preparation regimens on frozen single-blastocyst transfer in women with PCOS.

Methods

In this study, a total of 3941 women who diagnosed with PCOS and underwent single-blastocyst transfer during their first cycles of frozen embryo transfer (FET) between March 2012 and December 2020 were included. We retrospectively compared the pregnancy and neonatal outcomes after frozen single-blastocyst transfer with endometrial preparation by HRT regimen (n = 3540), ovulation induction by human menopausal gonadotropin (hMG) regimen (n = 226), and ovulation induction by letrozole regimen (n = 175).

Results

After adjustment for confounders with multivariable logistic regression, the hMG regimen group [(58.4% vs. 49.6%; adjusted odds ratio (aOR): 1.43; 95% confidence interval (CI): 1.09-1.89)] and letrozole regimen group (58.9% vs. 49.6%; aOR: 1.42; 95% CI: 1.04-1.93) were associated with a higher rate of livebirth (primary outcome), compared with the group with HRT regimen. As to the secondary outcomes, the rate of pregnancy loss in the hMG regimen group (22.8% vs. 30.3%; aOR: 0.69; 95% CI: 0.48-1.00) and letrozole regimen group (16.9% vs. 30.3%; aOR: 0.48; 95% CI: 0.30-0.78) was also lower than that in the HRT regimen group. The pregnancy outcomes between the hMG regimen group and the letrozole regimen group were similar. We did not observe significant difference in the incidences of maternal and neonatal complications among these three groups.

Conclusion

Ovulation induction regimen with letrozole or hMG for endometrial preparation was associated with a higher livebirth rate and a lower pregnancy loss rate in frozen single-blastocyst transfer cycles among women with PCOS.
An Evaluation of the Data-Driven Model for Bubble Maximum Diameter in Subcooled Boiling Flow Using Artificial Neural Networks
Authors: Dong Xiaomeng , Chen Haoxian , Li Changwei , Yang Ming , Yu Yang , Huang Xi
Published: August 2022

In the subcooled boiling flow under low-pressure conditions, bubble characteristic diameter is of great influence on the surface heat transfer coefficient. However, large errors are still found in calculations using traditional mechanistic models or empirical correlations, especially for wide experimental condition. In this paper, we propose a widely applicable data-driven model using artificial neural networks (ANN) to predict the bubble maximum diameter and investigate the effect of experimental conditions. After a series of analyses on structural parameters and input parameters, the ANN model is established and validated based on six available experimental databases. The result shows that the relative error is around 14%. Uncertainty analysis is carried out for the four experimental conditions and two structural conditions. The results show the measuring accuracy of pressure is one of the most sensitive parameters on the prediction of bubble maximum diameter in the subcooled boiling flow under 1.0 MPa, especially for the bubble sizes larger than 0.5 mm. According to the results of uncertainty analysis, a new correlation is proposed for coefficients C and φ, which are used to express the effect of pressure and fluid dynamic. The new correlation works well for all the experimental databases, and the error for bubble datasets of large size is also modified. Furthermore, another independent validation with a low relative error to 14% is provided to prove the accuracy of the new correlation.
Network pharmacological analysis of active components of Xiaoliu decoction in the treatment of glioblastoma multiforme
Authors: Wu Ji , Li Xue-Yu , Liang Jing , Fang Da-Lang , Yang Zhao-Jian , Wei Jie , Chen Zhi-Jun
Published: August 2022

Background: Glioblastoma multiforme (GBM) is the most aggressive primary nervous system brain tumor. There is still a lack of effective methods to control its progression and recurrence in clinical treatment. It is clinically found that Xiaoliu Decoction (XLD) has the effect of treating brain tumors and preventing tumor recurrence. However, its mechanism is still unclear.

Methods: Search the Traditional Chinese Medicine System Pharmacology Database (TCSMP) for efficient substances for the treatment of XLD in the treatment of GBM, and target the targeted genes of the effective ingredients to construct a network. At the same time, download GBM-related gene expression data from the TCGA and GTEX databases, screen differential expression bases, and establish a drug target disease network. Through bioinformatics analysis, the target genes and shared genes of the selected Chinese medicines are analyzed. Finally, molecular docking was performed to further clarify the possibility of XLD in multiple GBMs.

Results: We screened 894 differentially expressed genes in GBM, 230 XLD active ingredients and 169 predicted targets of its active compounds, of which 19 target genes are related to the differential expression of GBM. Bioinformatics analysis shows that these targets are closely related to cell proliferation, cell cycle regulation, and DNA synthesis. Finally, through molecular docking, it was further confirmed that Tanshinone IIA, the active ingredient of XLD, was tightly bound to key proteins.

Conclusion: To sum up, the results of this study suggest that the mechanism of XLD in the treatment of GBM involves multiple targets and signal pathways related to tumorigenesis and development. This study not only provides a new theoretical basis for the treatment of glioblastoma multiforme with traditional Chinese medicine, but also provides a new idea for the research and development of targeted drugs for the treatment of glioblastoma multiforme.
Whole-exome sequencing expands the roles of novel mutations of organic anion transporting polypeptide, ATP-binding cassette transporter, and receptor genes in intrahepatic cholestasis of pregnancy
Authors: Liu Xianxian , Zheng Jiusheng , Xin Siming , Zeng Yang , Wu Xiaoying , Zeng Xiaoming , Lai Hua , Zou Yang
Published: August 2022

Background: Intrahepatic cholestasis of pregnancy (ICP) is associated with a high incidence of fetal morbidity and mortality. Therefore, revealing the mechanisms involved in ICP and its association with fetal complications is very important.

Methods: Here, we used a whole-exome sequencing (WES) approach to detect novel mutations of organic anion transporting polypeptide (OTAP) genes, ATP-binding cassette transporter (ABC) genes, and receptor genes associated with ICP in 249 individuals and 1,029 local control individuals. Two available tools, SIFT and PolyPhen-2, were used to predict protein damage. Protein structuremodeling and comparison between the reference and modified protein structures were conducted by SWISS-MODEL and Chimera 1.14rc software, respectively.

Results: A total of 5,583 mutations were identified in 82 genes related to bile acid transporters and receptors, of which 62 were novel mutations. These novel mutations were absent in the 1,029 control individuals and three databases, including the 1,000 Genome Project (1000G_ALL), Exome Aggregation Consortium (ExAC), and Single-Nucleotide Polymorphism Database (dbSNP). We classified the 62 novel loci into two groups (damaging and probably damaging) according to the results of SIFT and PolyPhen-2. Out of the 62 novel mutations, 24 were detected in the damaging group. Of these, five novel possibly pathogenic variants were identified that were located in known functional genes, including ABCB4 (Ile377Asn), ABCB11 (Ala588Pro), ABCC2 (Ile681Lys and Met688Thr), and NR1H4 (Tyr149Ter). Moreover, compared to the wild-type protein structure, ABCC2 Ile681Lys and Met688Thr protein structures showed a slight change in the chemical bond lengths of ATP-ligand binding amino acid side chains. The combined 32 clinical data points indicate that the mutation group had a significantly (p = 0.04) lower level of Cl ions than the wild-type group. Particularly, patients with the 24 novel mutations had higher average values of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bile acids (TBA), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) than patients with the 38 novel mutations in the probably damaging group and the local control individuals.

Conclusion: The present study provides new insights into the genetic architecture of ICP involving these novel mutations.
EZH2 restricts Tcf7 DNA methylation and promotes TFH differentiation during acute viral infection
Authors: Luo Yuan , Li Dan , Xie Luoyingzi , Lei Shun , Chen Xiangyu , Wang Cong , Yao Dong , Li Lin , Fang Jingyi , Chen Cheng , Yuan Shijie , Li Fei , Xie Xiaorong , Zhang Yan , Li Zhirong , Hu Li , Tang Jianfang , Ye Lilin , Wei Zhengping , He Ran
Published: August 2022

Follicular helper T (TFH) cells provide specialized help for B cells to ensure optimal humoral immunity. The histone methyltransferase EZH2, as a chromatin repressor, secures the TFH differentiation by promoting TFH lineage associated gene expression during acute viral infection, including Tcf7 and Bcl6. By using conditional deletion murine system, we observed that EZH2 ablation in CD4+ T cells was accompanied by aberrant accumulation of DNA methyltransferases (DNMTs) DNMT1 and DNMT3B in TFH cells. And the loss of EZH2 promoted aggravation of DNA methylation status at Tcf7 locus. Therefore, our findings suggested that EZH2 plays an important role in maintenance of hypomethylation at Tcf7 locus thus affecting TFH differentiation during acute viral infection.
Vasculitis associated with VEXAS syndrome: A literature review
Authors: Watanabe Ryu , Kiji Manami , Hashimoto Motomu
Published: August 2022

Vasculitis is an inflammatory disorder of the blood vessels that causes damage to a wide variety of organs through tissue ischemia. Vasculitis is classified according to the size (large, medium, or small) of the blood vessels. In 2020, VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, a novel autoinflammatory syndrome, was described. Somatic mutations in methionine-41 of UBA1, the major E1 enzyme that initiates ubiquitylation, are attributed to this disorder. This new disease entity connects seemingly unrelated conditions: inflammatory syndromes (relapsing chondritis, Sweet's syndrome, or neutrophilic dermatosis) and hematologic disorders (myelodysplastic syndrome or multiple myeloma). Notably, such patients sometimes develop vasculitis, such as giant cell arteritis and polyarteritis nodosa, and fulfill the corresponding classification criteria for vasculitis. Thus, vasculitis can be an initial manifestation of VEXAS syndrome. In this research topic exploring the link between autoinflammatory diseases and vasculitis, we first provide an overview of the disease mechanisms and clinical phenotypes of VEXAS syndrome. Then, a literature review using the PubMed database was performed to delineate the clinical characteristics of vasculitis associated with VEXAS syndrome. Finally, the therapeutic options and unmet needs of VEXAS syndrome are discussed.
Repurposing Dimetridazole and Ribavirin to disarm Pseudomonas aeruginosa virulence by targeting the quorum sensing system
Authors: Yuan Yang , Yang Xiting , Zeng Qianglin , Li Heyue , Fu Ruyi , Du Lianming , Liu Wei , Zhang Yamei , Zhou Xikun , Chu Yiwen , Zhang Xiuyue , Zhao Kelei
Published: August 2022

Pseudomonas aeruginosa relies on its complex cellular regulatory network to produce a series of virulence factors and to cause various acute and chronic infections in a wide range of hosts. Compared with traditional antibiotics which frequently accompany with widespread antibiotic resistance, crippling the virulence system of bacteria is expected to be a promising anti-infective strategy. In this study, Dimetridazole and Ribavirin, which had poor antibacterial activities on P. aeruginosa reference isolate PAO1 in nutrient medium but significantly inhibited the growth of P. aeruginosa PAO1 in M9-adenosine, were selected from 40 marketed compounds with similar core structure (furan, benzofuran, or flavonoids) to the acyl-homoserine lactone signals of P. aeruginosa quorum sensing (QS) system. The production of QS-controlled proteases, pyocyanin, and biofilm formation of P. aeruginosa PAO1 and the clinical isolates were significantly decreased by the presence of Dimetridazole or Ribavirin. Correspondingly, the majority of QS-activated genes in P. aeruginosa, including the key regulatory genes lasR, rhlR, and pqsR and their downstream genes, were significantly inhibited by Ribavirin or Dimetridazole, as determined by RNA-sequencing and quantitative PCR. Furthermore, the susceptibilities of drug-resistant P. aeruginosa isolates to polymyxin B, meropenem, and kanamycin were remarkably promoted by the synergistic application of Dimetridazole or Ribavirin. Finally, the treatment of Ribavirin or Dimetridazole effectively protected Caenorhabditis elegans and mice from P. aeruginosa infection. In conclusion, this study reports the antivirulence potentials of Dimetridazole and Ribavirin on P. aeruginosa and provides structural basis and methodological reference for the development of anti-pseudomonal drugs.
Research on the effect of uncertain rewards on impulsive purchase intention of blind box products
Authors: Zhang Yi , Zhou Hang , Qin Jian
Published: August 2022

Since 2019, China has gradually seen a “blind box” boom, and young people have quickly become the main buying force of blind boxes, promoting the continuous development of the blind box industry. Previous studies have shown that uncertainty in events with positive prospects can play a more positive role than certainty. However, how does uncertainty in the blind box affect consumers’ emotions and cognition and trigger subsequent consumption decisions? To clarify the internal mechanism of this process, this paper takes the blind box as the research object and constructs the mechanism model of perceived uncertainty on consumers’ impulsive purchase intention, based on Stimulus-Organism-Response (SOR) theory. In addition, the curiosity variable and perceived luck variable are introduced according to the information gap theory and optimism theory. On this basis, we conduct an empirical analysis by means of a questionnaire survey. The results show that perceived uncertainty has a positive impact on consumers’ impulsive purchase intentions, in which curiosity plays a mediating role. Besides, perceived luck positively moderates the impact of perceived uncertainty on impulsive purchase intention. This study clarifies the internal impact of perceived uncertainty on impulsive purchase intention of the blind box and enriches the basic theory of uncertainty reward and purchase intention. At the same time, we also offer related recommendations for future enterprises to learn from the marketing model of uncertain rewards.
Detection of deviance in Japanese kanji compound words
Authors: Egashira Yuka , Kaga Yoshimi , Gunji Atsuko , Kita Yosuke , Kimura Motohiro , Hironaga Naruhito , Takeichi Hiroshige , Hayashi Sayuri , Kaneko Yuu , Takahashi Hidetoshi , Hanakawa Takashi , Okada Takashi , Inagaki Masumi
Published: August 2022

Reading fluency is based on the automatic visual recognition of words. As a manifestation of the automatic processing of words, an automatic deviance detection of visual word stimuli can be observed in the early stages of visual recognition. To clarify whether this phenomenon occurs with Japanese kanji compounds—since their lexicality is related to semantic association—we investigated the brain response by utilizing three types of deviants: differences in font type, lexically correct or incorrect Japanese kanji compound words and pseudo-kanji characters modified from correct and incorrect compounds. We employed magnetoencephalography (MEG) to evaluate the spatiotemporal profiles of the related brain regions. The study included 22 adult native Japanese speakers (16 females). The abovementioned three kinds of stimuli containing 20% deviants were presented during the MEG measurement. Activity in the occipital pole region of the brain was observed upon the detection of font-type deviance within 250 ms of stimulus onset. Although no significant activity upon detecting lexically correct/incorrect kanji compounds or pseudo-kanji character deviations was observed, the activity in the posterior transverse region of the collateral sulcus (pCoS)—which is a fusiform neighboring area—was larger when detecting lexically correct kanji compounds than when detecting pseudo-kanji characters. Taken together, these results support the notion that the automatic detection of deviance in kanji compounds may be limited to a low-level feature, such as the stimulus stroke thickness.
The multiscale 3D convolutional network for emotion recognition based on electroencephalogram
Authors: Su Yun , Zhang Zhixuan , Li Xuan , Zhang Bingtao , Ma Huifang
Published: August 2022

Emotion recognition based on EEG (electroencephalogram) has become a research hotspot in the field of brain-computer interfaces (BCI). Compared with traditional machine learning, the convolutional neural network model has substantial advantages in automatic feature extraction in EEG-based emotion recognition. Motivated by the studies that multiple smaller scale kernels could increase non-linear expression than a larger scale, we propose a 3D convolutional neural network model with multiscale convolutional kernels to recognize emotional states based on EEG signals. We select more suitable time window data to carry out the emotion recognition of four classes (low valence vs. low arousal, low valence vs. high arousal, high valence vs. low arousal, and high valence vs. high arousal). The results using EEG signals in the DEAP and SEED-IV datasets show accuracies for our proposed emotion recognition network model (ERN) of 95.67 and 89.55%, respectively. The experimental results demonstrate that the proposed approach is potentially useful for enhancing emotional experience in BCI.
Milk fat globule membrane supplementation to obese rats during pregnancy and lactation promotes neurodevelopment in offspring via modulating gut microbiota
Authors: Yuan Qichen , Gong Han , Du Min , Li Tiange , Mao Xueying
Published: August 2022

Pre-pregnancy obesity and high-fat diet (HFD) during pregnancy and lactation are associated with neurodevelopmental delay in offspring. This study aimed to investigate whether milk fat globule membrane (MFGM) supplementation in obese dams could promote neurodevelopment in offspring. Obese female rats induced by HFD were supplemented with MFGM during pregnancy and lactation. Maternal HFD exposure significantly delayed the maturation of neurological reflexes and inhibited neurogenesis in offspring, which were significantly recovered by maternal MFGM supplementation. Gut microbiota analysis revealed that MFGM supplementation modulated the diversity and composition of gut microbiota in offspring. The abundance of pro-inflammatory bacteria such as Escherichia shigella and Enterococcus were down-regulated, and the abundance of bacteria with anti-inflammatory and anti-obesity functions, such as Akkermansia and Lactobacillus were up-regulated. Furthermore, MFGM alleviated neuroinflammation by decreasing the levels of lipopolysaccharides (LPS) and pro-inflammatory cytokines in the circulation and brain, as well as inhibiting the activation of microglia. Spearman’s correlation analysis suggested that there existed a correlation between gut microbiota and inflammation-related indexes. In conclusion, maternal MFGM supplementation promotes neurodevelopment partly via modulating gut microbiota in offspring.
Effect of new type extrusion modification technology on supramolecular structure and in vitro glycemic release characteristics of starches with various estimated glycemic indices
Authors: Li Bo , Zhang Yanjun , Luo Wanru , Liu Jin , Huang Chongxing
Published: August 2022

Nowadays, the highly effective modified technology to starch with various digestibility is gaining interest in food science. Here, the interactions between glycemic release characteristics and fine supramolecular structure of cassava (ECS), potato (EPS), jackfruit seed (EJFSS), maize (EMS), wheat (EWS), and rice starches (ERS) prepared with improved extrusion modification technology (IEMS) were investigated. The crystalline structures of all extruded cooking starches changed from the A-type to V-type. IEMS-treated cassava, potato, and rice starches had broken α-1.6-glycosidic amylopectin (long chains). The others sheared α-1.4-glycosidic amylopectin. The molecular weight, medium and long chain counts, and relative crystallinity decreased, whereas the number of amylopectin short chains increased. The glycemic index (GI) and digestive speed rate constant (k) of ECS, EPS, EJFSS, and EWS were improved compared to those of raw starch. Although EMS and ERS had degraded molecular structures, their particle morphology changed from looser polyhedral to more compact with less enzymolysis channels due to the rearrangement of side chain clusters of amylopectin, leading to enzyme resistance. The starch characteristics of IEMS-treated samples significantly differed. EPS had the highest amylose content, medium chains, long chains, and molecular weight but lowest GI, relative crystallinity, and k. ERS showed the opposite results. Thus, IEMS may affect starches with different GIs to varying degrees. In this investigation, we provide a basis for wider applications of conventional crop starch in the food industry corresponding to different nutrition audience.
Fatty acid desaturase 1 (FADS1) is a cancer marker for patient survival and a potential novel target for precision cancer treatment
Authors: Heravi Gioia , Jang Hyejeong , Wang Xiaokun , Long Ze , Peng Zheyun , Kim Seongho , Liu Wanqing
Published: August 2022

Fatty Acid Desaturase-1 (FADS1) or delta 5 desaturase (D5D) is a rate-limiting enzyme involved in the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs), i.e., arachidonic acid (ARA) and eicosapentaenoic (EPA). These LC-PUFAs and their metabolites play essential and broad roles in cancer cell proliferation, metastasis, and tumor microenvironment. However, the role of FADS1 in cancers remains incompletely understood. Utilizing The Cancer Genome Atlas (TCGA) database, we explored the role of FADS1 across different cancer types using multiple bioinformatics and statistical tools. Moreover, we studied the impact of a FADS1 inhibitor (D5D-IN-326) on proliferation of multiple cancer cell lines. We identified that FADS1 gene is a predictor for cancer survival in multiple cancer types. Compared to normal tissue, the mRNA expression of FADS1 is significantly increased in primary tumors while even higher in metastatic and recurrent tumors. Mechanistically, pathway analysis demonstrated that FADS1 is associated with cholesterol biosynthesis and cell cycle control genes. Interestingly, FADS1 expression is higher when TP53 is mutated. Tumors with increased FADS1 expression also demonstrated an increased signatures of fibroblasts and macrophages infiltration among most cancer types. Our in vitro assays showed that D5D-IN-326 significantly inhibited cell proliferation of kidney, colon, breast, and lung cancer cell lines in a dose-dependent manner. Lastly, single nucleotide polymorphisms (SNPs) which are well-established expression quantitative trait loci (eQTLs) for FADS1 in normal human tissues are also significantly correlated with FADS1 expression in tumors of multiple tissue types, potentially serving as a marker to stratify cancer patients with high/low FADS1 expression in their tumor tissue. Our study suggests that FADS1 plays multiple roles in cancer biology and is potentially a novel target for precision cancer treatment.
Development of an ultrasound-based radiomics nomogram to preoperatively predict Ki-67 expression level in patients with breast cancer
Authors: Liu Jinjin , Wang Xuchao , Hu Mengshang , Zheng Yan , Zhu Lin , Wang Wei , Hu Jisu , Zhou Zhiyong , Dai Yakang , Dong Fenglin
Published: August 2022

Objective

To develop and validate a radiomics nomogram that could incorporate clinicopathological characteristics and ultrasound (US)-based radiomics signature to non-invasively predict Ki-67 expression level in patients with breast cancer (BC) preoperatively.

Methods

A total of 328 breast lesions from 324 patients with BC who were pathologically confirmed in our hospital from June 2019 to October 2020 were included, and they were divided into high Ki-67 expression level group and low Ki-67 expression level group. Routine US and shear wave elastography (SWE) were performed for each lesion, and the ipsilateral axillary lymph nodes (ALNs) were scanned for abnormal changes. The datasets were randomly divided into training and validation cohorts with a ratio of 7:3. Correlation analysis and the least absolute shrinkage and selection operator (LASSO) were used to select the radiomics features obtained from gray-scale US images of BC patients, and each radiomics score (Rad-score) was calculated. Afterwards, multivariate logistic regression analysis was used to establish a radiomics nomogram based on the radiomics signature and clinicopathological characteristics. The prediction performance of the nomogram was assessed by the area under the receiver operating characteristic curve (AUC), the calibration curve, and decision curve analysis (DCA) using the results of immunohistochemistry as the gold standard.

Results

The radiomics signature, consisted of eight selected radiomics features, achieved a nearly moderate prediction efficacy with AUC of 0.821 (95% CI:0.764-0.880) and 0.713 (95% CI:0.612-0.814) in the training and validation cohorts, respectively. The radiomics nomogram, incorporating maximum diameter of lesions, stiff rim sign, US-reported ALN status, and radiomics signature showed a promising performance for prediction of Ki-67 expression level, with AUC of 0.904 (95% CI:0.860-0.948) and 0.890 (95% CI:0.817-0.964) in the training and validation cohorts, respectively. The calibration curve and DCA indicated promising consistency and clinical applicability.

Conclusion

The proposed US-based radiomics nomogram could be used to non-invasively predict Ki-67 expression level in BC patients preoperatively, and to assist clinicians in making reliable clinical decisions.
Dose rate and dose robustness for proton transmission FLASH-RT treatment in lung cancer
Authors: Wei Shouyi , Lin Haibo , Huang Sheng , Shi Chengyu , Xiong Weijun , Zhai Huifang , Hu Lei , Yu Gang , Press Robert H. , Hasan Shaakir , Chhabra Arpit M. , Choi J. Isabelle , Simone Charles B. , Kang Minglei
Published: August 2022

Purposes

To evaluate the plan quality and robustness of both dose and dose rate of proton pencil beam scanning (PBS) transmission FLASH delivery in lung cancer treatment.

Methods and materials

An in-house FLASH planning platform was used to optimize 10 lung cancer patients previously consecutively treated with proton stereotactic body radiation therapy (SBRT) to receive 3 and 5 transmission beams (Trx-3fds and Trx-5fds, respectively) to 34 Gy in a single fraction. Perturbation scenarios (n=12) for setup and range uncertainties (5 mm and 3.5%) were introduced, and dose-volume histogram and dose-rate-volume histogram bands were generated. Conventional proton SBRT clinical plans were used as a reference. RTOG 0915 dose metrics and 40 Gy/s dose rate coverage (V40Gy/s) were used to assess the dose and dose rate robustness.

Results

Trx-5fds yields a comparable iCTV D2% of 105.3%, whereas Trx-3fds resulted in inferior D2% of 111.9% to the clinical SBRT plans with D2% of 105.6% (p<0.05). Both Trx-5fds and Trx-3fds plans had slightly worse dose metrics to organs at risk than SBRT plans. Trx-5fds achieved superior dosimetry robustness for iCTV, esophagus, and spinal cord doses than both Trx-3fds and conventional SBRT plans. There was no significant difference in dose rate robustness for V40Gy/s coverage between Trx-3fds and Trx-5fds. Dose rate distribution has similar distributions to the dose when perturbation exists.

Conclusion

Transmission plans yield overall modestly inferior plan quality compared to the conventional proton SBRT plans but provide improved robustness and the potential for a toxicity-sparing FLASH effect. By using more beams (5- versus 3-field), both dose and dose rate robustness for transmission plans can be achieved.
Cryo-EM Structure and Activator Screening of Human Tryptophan Hydroxylase 2
Authors: Zhu Kongfu , Liu Chao , Gao Yuanzhu , Lu Jianping , Wang Daping , Zhang Huawei
Published: August 2022

Human tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in the synthesis of serotonin. Its dysfunction has been implicated in various psychiatric disorders such as depression, autism, and bipolar disorder. TPH2 is typically decreased in stability and catalytic activity in patients; thus, screening of molecules capable of binding and stabilizing the structure of TPH2 in activated conformation is desired for drug development in mental disorder treatment. Here, we solved the 3.0 Å cryo-EM structure of the TPH2 tetramer. Then, based on the structure, we conducted allosteric site prediction and small-molecule activator screening to the obtained cavity. ZINC000068568685 was successfully selected as the best candidate with highest binding affinity. To better understand the driving forces and binding stability of the complex, we performed molecular dynamics simulation, which indicates that ZINC000068568685 has great potential to stabilize the folding of the TPH2 tetramer to facilitate its activity. The research might shed light on the development of novel drugs targeting TPH2 for the treatment of psychological disorders.
Pan-cancer analysis suggests histocompatibility minor 13 is an unfavorable prognostic biomarker promoting cell proliferation, migration, and invasion in hepatocellular carcinoma
Authors: Liu Jun , Li Wenli , Wu Liangyin
Published: August 2022

Histocompatibility Minor 13 (HM13) encoding the signal peptide peptidase plays an important role in maintaining protein homeostasis but its role in tumors remains unclear. In this study, 33 tumor RNA-seq datasets were extracted from The Cancer Genome Atlas (TCGA) database, and the pan-cancer expression profile of HM13 was evaluated in combination with The Genotype-Tissue Expression (GTEx) datasets. The prognostic significance of abnormal HM13 pan-cancer expression was evaluated by univariate Cox regression and Kaplan-Meier analyses. Co-expression analysis was performed to examine the correlation between abnormal pan-cancer expression of HM13 and immune cell infiltration, immune checkpoint, molecules related to RNA modification, tumor mutational burden (TMB), microsatellite instability (MSI), and other related molecules. CellMiner database was used to evaluate the relationship between the expression of HM13 and drug sensitivity. The results showed overexpression of HM13 in almost all tumors except kidney chromophobe (KICH). Abnormally high expression of HM13 in adrenocortical carcinoma (ACC), kidney renal papillary cell carcinoma (KIRP), uveal melanoma (UVM), liver hepatocellular carcinoma (LIHC), brain lower grade glioma (LGG), head and neck squamous cell carcinoma (HNSC), and kidney renal clear cell carcinoma (KIRC) was associated with poor prognosis. Expression of HM13 correlated strongly with pan-cancer immune checkpoint gene expression and immune cell infiltration. Drug sensitivity analysis indicated that the expression of HM13 was an excellent predictor of drug sensitivity. We verified that both mRNA and protein levels of HM13 were abnormally upregulated in HCC tissues, and were independent risk factors for poor prognosis. Furthermore, interference with HM13 expression in Huh-7 and HCCLM3 cells significantly inhibited proliferation, migration, and invasion. Therefore, our findings demonstrate that HM13 is a potential pan-cancer prognostic marker, thus providing a new dimension for understanding tumor development.
Effect of troxerutin in counteracting hyperglycemia-induced VEGF upregulation in endothelial cells: a new option to target early stages of diabetic retinopathy?
Authors: Fahmideh F. , Marchesi N. , Campagnoli L. I. M. , Landini L. , Caramella C. , Barbieri A. , Govoni S. , Pascale A.
Published: August 2022

Diabetic retinopathy (DR), one of the most common complications of diabetes mellitus, is characterized by degeneration of retinal neurons and neoangiogenesis. Until today, the pharmacological approaches for DR are limited and focused on counteracting the end-stage of this neurodegenerative disease, therefore efforts should be carried out to discover novel pharmacological targets useful to prevent DR development. Hyperglycemia is a major risk factor for endothelial dysfunction and vascular complication, which subsequently may trigger neurodegeneration. We previously demonstrated that, in the rat retina, hyperglycemia activates a new molecular cascade implicating, up-stream, protein kinase C βII (PKC βII), which in turn leads to a higher expression of vascular endothelial growth factor (VEGF), via the mRNA-binding Hu-antigen R (HuR) protein. VEGF is a pivotal mediator of neovascularization and a well-known vasopermeability factor. Blocking the increase of VEGF via modulation of this cascade can thus represent a new pharmacological option to prevent DR progression. To this aim, proper in vitro models are crucial for drug discovery, as they allow to better identify promising effective molecules. Considering that endothelial cells are key elements in DR and that hyperglycemia triggers the PKCβII/HuR/VEGF pathway, we set up two distinct in vitro models applying two different stimuli. Namely, human umbilical vein endothelial cells were exposed to phorbol 12-myristate 13-acetate, which mimics diacylglycerol whose synthesis is triggered by diabetic hyperglycemia, while human retinal endothelial cells were treated with high glucose for different times. After selecting the optimal experimental conditions able to determine an increased VEGF production, in search of molecules useful to prevent DR development, we investigated the capability of troxerutin, an antioxidant flavonoid, to counteract not only the rise of VEGF but also the activation of the PKCβII/HuR cascade in both in vitro models. The results show the capability of troxerutin to hinder the hyperglycemia-induced increase in VEGF in both models through PKCβII/HuR pathway modulation. Further, these data confirm the key engagement of this cascade as an early event triggered by hyperglycemia to promote VEGF expression. Finally, the present findings also suggest the potential use of troxerutin as a preventive treatment during the early phases of DR.
The crosstalk between sonodynamic therapy and autophagy in cancer
Authors: Zhang Yujie , Zhao Yuanru , Zhang Yuanyuan , Liu Qingguang , Zhang Mingzhen , Tu Kangsheng
Published: August 2022

As a noninvasive treatment approach for cancer and other diseases, sonodynamic therapy (SDT) has attracted extensive attention due to the deep penetration of ultrasound, good focusing, and selective irradiation sites. However, intrinsic limitations of traditional sonosensitizers hinder the widespread application of SDT. With the development of nanotechnology, nanoparticles as sonosensitizers or as a vehicle to deliver sonosensitizers have been designed and used to target tissues or tumor cells with high specificity and accuracy. Autophagy is a common metabolic alteration in both normal cells and tumor cells. When autophagy happens, a double-membrane autophagosome with sequestrated intracellular components is delivered and fused with lysosomes for degradation. Recycling these cell materials can promote survival under a variety of stress conditions. Numerous studies have revealed that both apoptosis and autophagy occur after SDT. This review summarizes recent progress in autophagy activation by SDT through multiple mechanisms in tumor therapies, drug resistance, and lipid catabolism. A promising tumor therapy, which combines SDT with autophagy inhibition using a nanoparticle delivering system, is presented and investigated.
Astragalus mongholicus powder, a traditional Chinese medicine formula ameliorate type 2 diabetes by regulating adipoinsular axis in diabetic mice
Authors: Xu Siyuan , Ye Bixian , Li Jinlei , Dou Yonghui , Yu Yuying , Feng Yifan , Wang Lexun , Wan David Chi-Cheong , Rong Xianglu
Published: August 2022

The global morbidity of obesity and type 2 diabetes mellitus (T2DM) has dramatically increased. Insulin resistance is the most important pathogenesis and therapeutic target of T2DM. The traditional Chinese medicine formula Astragalus mongholicus powder (APF), consists of Astragalus mongholicus Bunge [Fabaceae], Pueraria montana (Lour.) Merr. [Fabaceae], and Morus alba L. [Moraceae] has a long history to be used to treat diabetes in ancient China. This work aims to investigate the effects of APF on diabetic mice and its underlying mechanism. Diabetic mice were induced by High-fat-diet (HFD) and streptozotocin (STZ). The body weight of mice and their plasma levels of glucose, insulin, leptin and lipids were examined. Reverse transcription-polymerase chain reaction, histology, and Western blot analysis were performed to validate the effects of APF on diabetic mice and investigate the underlying mechanism. APF reduced hyperglycemia, hyperinsulinemia, and hyerleptinemia and attenuate the progression of obesity and non-alcoholic fatty liver disease (NAFLD). However, these effects disappeared in leptin deficient ob/ob diabetic mice and STZ-induced insulin deficient type 1 diabetic mice. Destruction of either these hormones would abolish the therapeutic effects of APF. In addition, APF inhibited the protein expression of PTP1B suppressing insulin–leptin sensitivity, the gluconeogenic gene PEPCK, and the adipogenic gene FAS. Therefore, insulin–leptin sensitivity was normalized, and the gluconeogenic and adipogenic genes were suppressed. In conclusion, APF attenuated obesity, NAFLD, and T2DM by regulating the balance of adipoinsular axis in STZ + HFD induced T2DM mice.
Antagonizing Sec62 function in intracellular Ca2+ homeostasis represents a novel therapeutic strategy for head and neck cancer
Authors: Körner Sandrina , Pick Tillman , Bochen Florian , Wemmert Silke , Körbel Christina , Menger Michael D. , Cavalié Adolfo , Kühn Jan-Philipp , Schick Bernhard , Linxweiler Maximilian
Published: August 2022

Various cancer types including head and neck squamous cell carcinomas (HNSCC) show a frequent amplification of chromosomal region 3q26 that encodes, among others, for the SEC62 gene. Located in the ER membrane, this translocation protein is known to play a critical role as a potential driver oncogene in cancer development. High SEC62 expression levels were observed in various cancer entities and were associated with a poor outcome and increased metastatic burden. Because of its intracellular localization the SEC62 protein is poorly accessible for therapeutic antibodies, therefore a functional SEC62 knockdown represents the most promising mechanism of a potential antineoplastic targeted therapy. By stimulating the Ca2+ efflux from the ER lumen and thereby increasing cellular stress levels, a functional inhibition of SEC62 bears the potential to limit tumor growth and metastasis formation. In this study, two potential anti-metastatic and -proliferative agents that counteract SEC62 function were investigated in functional in vitro assays by utilizing an immortalized human hypopharyngeal cancer cell line as well as a newly established orthotopic murine in vivo model. Additionally, a CRISPR/Cas9 based SEC62 knockout HNSCC cell line was generated and functionally characterized for its relevance in HNSCC cell proliferation and migration as well as sensitivity to SEC62 targeted therapy in vitro.