bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro selection and optimization of high-affinity aptamer for milk allergen α-lactalbumin and its application in dual-mode detection
Authors: Liu Ruobing , Zhang Fuyuan , Shi Minghui , Sang Yaxin , Wang Xianghong
Published: October 2022

Milk is one of the most common sources of protein in people’s daily lives, and it is also recognized by the World Health Organization (WHO) as one of the eight categories of food allergies to human beings. α-lactalbumin (α-La) is the main cause of milk allergy. In this study, a single-stranded DNA aptamer with high binding affinity to α-La were selected using systematic evolution of ligands by exponential enrichment (SELEX) method. Compared with the full-length sequence, the binding affinity of the truncated aptamer LA-1t for α-La was increased six times using fluorescence analysis. Circular dichroism (CD) indicated that the secondary structure of LA-1t contained a typical hairpin structure. Through the docking simulation of LA-1t and α-La, these experimental results were further explained theoretically, and the recognition mechanism was explained. Finally, the colorimetric and fluorescence signal of boron nitride quantum dots anchored to porous CeO2 nanorods (BNQDs/CeO2) were modulated by FAM-labeled LA-1t to achieve highly selective and sensitive determination of α-La. This dual-mode sensing strategy displayed sensitive recognition for α-La in a linear range of 5–4,000 ng/ml with the LOD was 3.32 ng/ml (colorimetry) and 0.71 ng/ml (fluorescence), respectively. Simultaneously, the colorimetry/fluorescence dual-mode sensing strategy was applied for detecting α-La in spiked real samples and demonstrated good stability and reliability.
Characteristics of the enzyme-induced release of bitter peptides from wheat gluten hydrolysates
Authors: Sun Xiaorui , Zheng Jiayi , Liu Boye , Huang Zehua , Chen Fusheng
Published: October 2022

Bitter peptides in the enzymatic hydrolysates were prepared and purified from wheat gluten using aqueous ethanol solutions and macroporous resin, which has opened a new road for the extraction and separation of bitter peptides. This report contains the release regularity of bitter peptides and the factors affecting the change of bitter intensity during enzymatic hydrolysis, providing a scientific basis for the research on debitterizing method. In this study, the effects of different degrees of hydrolysis (DH) and enzyme active sites on the bitter peptide content and bitter taste thresholds were discussed. The relationship between amino acid composition, molecular weight distribution, surface hydrophobicity and bitter taste thresholds was extensively researched. The results showed the exposure of hydrophobic amino acids and the bitterness intensity of the hydrolysates increased as the DH increased, and the bitterness of wheat gluten hydrolysates (WGHs) hydrolyzed by Alcalase was stronger than that of Trypsin. According to correlation analysis, the proportion of total hydrophobic amino acid is the first factor that affects the sensory properties of bitter peptide, and the release content of bitter peptides and the content of total bitter amino acids are the second, following by the content of peptide in the molecular weight range of 500–1,000 Da and the surface hydrophobicity. The amino acid sequence of bitter peptides from WGHs were identified and predicted using high performance liquid chromatography-mass spectrometry (HPLC-MS/MS) and bioinformatics. It was found that the molecular weight of most of the peptides was below 1,500 Da, and the Q value was higher than 5.86 kJ/mol.
Soilless biofortification, bioaccessibility, and bioavailability: Signposts on the path to personalized nutrition
Authors: Renna Massimiliano , D’Imperio Massimiliano , Maggi Stefania , Serio Francesco
Published: October 2022

Propelled by an ever-growing awareness about the importance of following dietary recommendations meeting specific biological requirements linked to a person health status, interest in personalized nutrition is on the rise. Soilless biofortification of vegetables has opened the door to the potential for adapting vegetable production to specific dietary requirements. The evolution of vegetables biofortification toward tailored food is examined focusing on some specific categories of people in a context of personalized nutrition instead to simple describe developments in vegetables biofortification with reference to the single element or compound not adequately present in the daily diet. The concepts of bioavailability and bioaccessibility as a useful support tool for the precision biofortification were detailed. Key prospects for challenges ahead aiming to combine product quality and sustainable are also highlighted. Hydroponically cultivation of vegetables with low potassium content may be effective to obtain tailored leafy and fruit vegetable products for people with impaired kidney function. Simultaneous biofortification of calcium, silicon, and boron in the same vegetable to obtain vegetable products useful for bone health deserve further attention. The right dosage of the lithium in the nutrient solution appears essential to obtain tailored vegetables able to positively influence mental health in groups of people susceptible to mental illness. Modulate nitrogen fertilization may reduce or enhance nitrate in vegetables to obtain tailored products, respectively, for children and athletes. Future research are needed to produce nickel-free vegetable products for individuals sensitized to nickel. The multidisciplinary approach toward tailored foods is a winning one and must increasingly include a synergy between agronomic, biological, and medical skills.
Relationship between standardized uptake value on 18F-FDG PET and PD-L1 expression in clear cell renal cell carcinoma
Authors: Liu Ying , Huo Yanlei , Ma Chao , Lv Zhongwei
Published: October 2022

Purpose

Partial clear cell renal cell carcinoma (CCRCC) may be sensitive to immune checkpoint inhibitor treatment targeting the programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) pathway. Assessing the levels of PD-L1 using non-invasive imaging is useful to select immunotherapy-sensitive patients. Currently, whether PD-L1 levels in CCRCC correlate with 18F fluorodeoxyglucose (18F-FDG) uptake is unknown. This study aimed to assess whether 18F-FDG-positron emission tomography (PET) imaging could be used to infer PD-L1 levels in CCRCC.

Methods

Immunohistochemistry (IHC) was used to assess PD-L1 levels in samples of tumors obtained retrospectively from a cohort of 58 patients with CCRCC who also received 18F-FDG PET/CT imaging. The IHC scores for PD-L1 were compared with the 18F-FDG maximum standardized uptake value (SUVmax), and the mean standardized uptake value (SUVmean) value, with the clinical characteristics of CCRCC, and with the IHC scores of enzymes related to glucose metabolism (glucose transporter type 1 (GLUT1), hexokinase 2 (HK2), lactate dehydrogenase A (LDHA)), and Von Hippel-Lindau tumor suppressor (VHL).

Results

Increased renal venous invasion, lymph node metastasis, tumor size, SUVmean, and SUVmax correlated significantly with higher PD-L1 levels (P < 0.05). The IHC scores of VHL and LDHA correlated positively with those of PD-L1 (P = 0.035, P = 0.011, respectively). Significant correlations between PD-L1 levels and SUVmean and lymph node metastasis were observed upon multivariate analysis. SUVmean combined with lymph node metastasis predicted that 20.59% of the low probability group would express PD-L1, 29.41% of the medium probability group would express PD-L1, and 71.43% of the high probability group would express PD-L1.

Conclusion

The status of lymph node metastasis, SUVmax, and SUVmean of the primary lesion correlated with PD-L1 levels in CCRCC. A combination of lymph node metastasis status and SUVmean could be utilized to predict PD-L1 levels, thus allowing monitoring of a tumor’s immunotherapy response.
Setup error assessment based on “Sphere-Mask” Optical Positioning System: Results from a multicenter study
Authors: Zhang Yan , Zhou Han , Chu Kaiyue , Wu Chuanfeng , Ge Yun , Shan Guoping , Zhou Jundong , Cai Jing , Jin Jianhua , Sun Weiyu , Chen Ying , Huang Xiaolin
Published: October 2022

Background

The setup accuracy plays an extremely important role in the local control of tumors. The purpose of this study is to verify the feasibility of "Sphere-Mask" Optical Positioning System (S-M_OPS) for fast and accurate setup.

Methods

From 2016 to 2021, we used S-M_OPS to supervise 15441 fractions in 1981patients (with the cancer in intracalvarium, nasopharynx, esophagus, lung, liver, abdomen or cervix) undergoing intensity-modulated radiation therapy (IMRT), and recorded the data such as registration time and mask deformation. Then, we used S-M_OPS, laser line and cone beam computed tomography (CBCT) for co-setup in 277 fractions, and recorded laser line-guided setup errors and S-M_OPS-guided setup errors with CBCT-guided setup result as the standard.

Results

S-M_OPS supervision results: The average time for laser line-guided setup was 31.75s. 12.8% of the reference points had an average deviation of more than 2 mm and 5.2% of the reference points had an average deviation of more than 3 mm. Co-setup results: The average time for S-M_OPS-guided setup was 7.47s, and average time for CBCT-guided setup was 228.84s (including time for CBCT scan and manual verification). In the LAT (left/right), VRT (superior/inferior) and LNG (anterior/posterior) directions, laser line-guided setup errors (mean±SD) were -0.21±3.13mm, 1.02±2.76mm and 2.22±4.26mm respectively; the 95% confidence intervals (95% CIs) of laser line-guided setup errors were -6.35 to 5.93mm, -4.39 to 6.43mm and -6.14 to 10.58mm respectively; S-M_OPS-guided setup errors were 0.12±1.91mm, 1.02±1.81mm and -0.10±2.25mm respectively; the 95% CIs of S-M_OPS-guided setup errors were -3.86 to 3.62mm, -2.53 to 4.57mm and -4.51 to 4.31mm respectively.

Conclusion

S-M_OPS can greatly improve setup accuracy and stability compared with laser line-guided setup. Furthermore, S-M_OPS can provide comparable setup accuracy to CBCT in less setup time.
Development and feasibility evaluation of an AR-assisted radiotherapy positioning system
Authors: Zhang Gongsen , Liu Xinchao , Wang Linlin , Zhu Jian , Yu Jinming
Published: October 2022

Purpose

The aim of this study is to develop an augmented reality (AR)–assisted radiotherapy positioning system based on HoloLens 2 and to evaluate the feasibility and accuracy of this method in the clinical environment.

Methods

The obtained simulated computed tomography (CT) images of an “ISO cube”, a cube phantom, and an anthropomorphic phantom were reconstructed into three-dimensional models and imported into the HoloLens 2. On the basis of the Vuforia marker attached to the “ISO cube” placed at the isocentric position of the linear accelerator, the correlation between the virtual and real space was established. First, the optimal conditions to minimize the deviation between virtual and real objects were explored under different conditions with a cube phantom. Then, the anthropomorphic phantom–based positioning was tested under the optimal conditions, and the positioning errors were evaluated with cone-beam CT.

Results

Under the normal light intensity, the registration and tracking angles are 0°, the distance is 40 cm, and the deviation reached a minimum of 1.4 ± 0.3 mm. The program would not run without light. The hologram drift caused by the light change, camera occlusion, and head movement were 0.9 ± 0.7 mm, 1.0 ± 0.6 mm, and 1.5 ± 0.9 mm, respectively. The anthropomorphic phantom–based positioning errors were 3.1 ± 1.9 mm, 2.4 ± 2.5 mm, and 4.6 ± 2.8 mm in the X (lateral), Y (vertical), and Z (longitudinal) axes, respectively, and the angle deviation of Rtn was 0.26 ± 0.14°.

Conclusion

The AR-assisted radiotherapy positioning based on HoloLens 2 is a feasible method with certain advantages, such as intuitive visual guidance, radiation-free position verification, and intelligent interaction. Hardware and software upgrades are expected to further improve accuracy and meet clinicalbrendaannmae requirements.
Pediatric non–Down’s syndrome acute megakaryoblastic leukemia patients in China: A single center's real-world analysis
Authors: Zhang Aoli , Liu Lipeng , Zong Suyu , Chen Xiaoyan , Liu Chao , Chang Lixian , Chen Xiaojuan , Yang Wenyu , Guo Ye , Zhang Li , Zou Yao , Chen Yumei , Zhang Yingchi , Ruan Min , Zhu Xiaofan
Published: October 2022

Non-Down’s syndrome acute megakaryocytic leukemia (non-DS-AMKL) is a subtype of childhood acute myeloid leukemia (AML), whose prognosis, prognostic factors and treatment recommendations have not yet to be defined in children. We conducted a retrospective study with 65 newly diagnosed non-DS-AMKL children from August 2003 to June 2020 to investigate the clinical impact of factors and clinical outcome. Among all 65 patients, 47 of them were treated at our center who received three different regimens due to time point of admission (CAMS-another, CAMS-2009 and CAMS-2016 protocol), and the efficacy were compared. Patients with newly diagnosed non-DS-AMKL accounted for 7.4% of pediatric AML cases. The median age of the patients was 18 months at diagnosis, and over 90% of them were under three-years-old. The overall survival (OS) rates were 33.3% ± 1.7%, 66.7% ± 24.4% and 74.2% ± 4.0% for three groups (CAMS-another, CAMS-2009 and CAMS-2016 regimen), respectively. In CAMS-2016 group, the complete remission (CR) rate after induction was 67.7% (21/31), while the total CR rate after all phases of chemotherapy was 80.6% (25/31). The 2-year survival probability did not significantly improve in patients underwent HSCT when compared with non-HSCT group (75.0% ± 4.7% vs. 73.9% ± 4.6%, p=0.680). Those who had a “dry tap” during BM aspiration at admission had significantly worse OS than those without “dry tap” (33.3% ± 8.6% vs. 84.0% ± 3.6%, p=0.006). Moreover, the results also revealed that patients with CD34+ had significantly lower OS (50.0% ± 6.7% vs. 89.5% ± 3.5%, p=0.021), whereas patients with CD36+ had significantly higher OS than those who were negative (85.0% ± 4.0% vs. 54.5% ± 6.6%, p=0.048). In conclusion, intensive chemotherapy resulted in improved prognosis of non-DS-AMKL children and subclassification may base on “dry tap” and immunophenotypic. Although some progress has been made, outcomes of non-DS-AMKL children remain unsatisfactory, especially in HSCT group, when compared with other AML types.
Identification of fatty acid signature to predict prognosis and guide clinical therapy in patients with ovarian cancer
Authors: Cao Tiefeng , Dong Jiaqi , Huang Jiaming , Tang Zihao , Shen Huimin
Published: October 2022

High-grade serous ovarian cancer (HGSOC) is a heterogeneous cancer characterized by high relapse rate. Approximately 80% of women are diagnosed with late-stage disease, and 15–25% of patients experience primary treatment resistance. Ovarian cancer brings tremendous suffering and is the most malignant type in all gynecologic malignancies. Metabolic reprogramming in tumor microenvironment (TME), especially fatty acid metabolism, has been identified to play a crucial role in cancer prognosis. Yet, the underlying mechanism of fatty acid metabolism on ovarian cancer progression is severely understudied. Recently, studies have demonstrated the role of fatty acid metabolism reprogramming in immune cells, but their roles on cancer cell metastasis and cancer immunotherapy response are poorly characterized. Here, we reported that the fatty acid–related genes are aberrantly varied between ovarian cancer and normal samples. Using samples in publicly databases and bio-informatic analyses with fatty acid–related genes, we disentangled that cancer cases can be classified into high- and low-risk groups related with prognosis. Furthermore, the nomogram model was constructed to predict the overall survival. Additionally, we reported that different immune cells infiltration was presented between groups, and immunotherapy response differed in two groups. Results showed that our signature may have good prediction value on immunotherapy efficacy, especially for anti–PD-1 and anti–CTLA-4. Our study systematically marked the critical association between cancer immunity in TME and fatty acid metabolism, and bridged immune phenotype and metabolism programming in tumors, thereby constructed the metabolic-related prognostic model and help to understand the underlying mechanism of immunotherapy response.
Uterine leiomyoma in pediatric population: A case report and review of the literature
Authors: Martucci Cristina , Crocoli Alessandro , Persano Giorgio , Bonito Marco , Stracuzzi Alessandra , Alaggio Rita , Bertocchini Arianna , Accinni Antonella , Inserra Alessandro
Published: October 2022

Uterine leiomyomas are rare in the pediatric population with less than 20 cases in adolescences reported in the literature. Furthermore, these masses represent a common presentation of gynecologic tumors with increasing age. We report a case of a 14-year-old female who presented with abdominal pain and increasing abdominal girth. Workup with ultrasound, CT and MRI demonstrated a large pelvic mass. Complete resection by median laparotomy was performed. The mass weighed 5,596 g and was 29.5 cm × 27 cm × 19 cm; the pathological examination confirmed the hypothesis of leiomyoma. The patient remained asymptomatic at 3 months follow up.
Case report: A novel de novo IGF2 missense variant in a Finnish patient with Silver-Russell syndrome
Authors: Loid Petra , Lipsanen-Nyman Marita , Ala-Mello Sirpa , Hannula-Jouppi Katariina , Kere Juha , Mäkitie Outi , Muurinen Mari
Published: October 2022

Silver-Russell syndrome (SRS, OMIM 180860) is a rare imprinting disorder characterized by intrauterine and postnatal growth restriction, feeding difficulties in early childhood, characteristic facial features, and body asymmetry. The molecular cause most commonly relates to hypomethylation of the imprinted 11p15.5IGF2/H19domain but remains unknown in about 40% of the patients. Recently, heterozygous paternally inherited pathogenic variants inIGF2, the gene encoding insulin-like growth factor 2 (IGF2), have been identified in patients with SRS. We report a novelde novomissense variant inIGF2(c.122T > G, p.Leu41Arg) on the paternally derived allele in a 16-year-old boy with a clinical diagnosis of SRS. The missense variant was identified by targeted exome sequencing and predicted pathogenic by multiplein silicotools. It affects a highly conserved residue on a domain that is important for binding of other molecules. Our finding expands the spectrum of disease-causing variants inIGF2. Targeted exome sequencing is a useful diagnostic tool in patients with negative results of common diagnostic tests for SRS.
Pharmacokinetics, bioavailability, and plasma protein binding study of glytrexate, a novel multitarget antifolate
Authors: Xiang Jiahong , Wu Mengqi , Wang Jianchao , Lin Mengmeng , Sun Mengmeng , Li Xin , Xing Ruijuan , Guo Ran , Gu Jianmin , Lyu Tao , Wang Lei , Shi Xiaowei
Published: October 2022

Glytrexate, developed by our team, as a novel multitarget folate antagonist, has inhibitory effects on a variety of cancer cell types, especially KB tumor cells (IC50 0.078 nM), and thus has antitumor drug development prospects. However, its pharmacokinetics and plasma protein binding properties remain unknown. In this study a selective and sensitive liquid chromatography-tandem mass spectrometry (LC‒MS/MS) method was developed and verified to facilitate biological analysis. The bioanalysis method was applied to evaluate the stability, plasma protein binding, and pharmacokinetics of glytrexate. Glytrexate is more stable in human plasma than in rat plasma and in human liver microsomes. The binding of glytrexate to human plasma proteins was higher than that to rat plasma proteins, both of which were less than 30%, suggesting that glytrexate may be at a higher concentration at the pharmacologic target receptor(s) in tissues. Pharmacokinetic characteristics were determined by noncompartmental analysis after administration of single oral (12.5, 25 and 50 mg/kg) and intravenous (2 mg/kg) doses in rats. According to the rat oral pharmacokinetic characteristics, glytrexate had linear dynamics in a dose range of 12.5–50 mg/kg and a poor oral bioavailability of 0.57–1.15%. The investigation revealed that the intravenous half-life, AUC, and Cmax of glytrexate were higher than those of pemetrexed. Pemetrexed is generally produced as an injection preparation. This provides ideas for the development of glytrexate formulations. Therefore, glytrexate injection has clinical application prospects compared to oral administration. This study provides a basis for further investigations into the pharmacological effects and clinical uses of glytrexate.
AMFR and DCTN2 genes cause transplantation resistance of adipose-derived mesenchymal stem cells in type 1 diabetes mellitus
Authors: Horiguchi Michiko , Tsurudome Yuya , Ushijima Kentaro
Published: October 2022

Type 1 diabetes mellitus (T1DM) is characterized by pancreatic beta cell destruction by autoantibodies and other factors, resulting in insulin secretion deficiency. Therefore, beta cell regeneration would be necessary to cure the disease. Nevertheless, the impact of type 1 diabetes on the stemness and transplantation efficiency of stem cells has not been previously described. In this study, we used next-generation sequencing to identify genes differentially expressed in T1DM adipose-derived stem cells (T1DM ADSCs) that originate from patients with type 1 diabetes. Furthermore, we evaluated their effects on transplantation efficiency following xenotransplantation into immunodeficient mice. In the T1DM ADSCs transplant group, the volume and weight of the graft were significantly reduced and the transplant efficiency was reduced. Next-generation sequencing and quantitative PCR results showed that T1DM ADSCs had significantly increased expression of AMFR and DCTN2. AMFR and DCTN2 gene knockdown in T1DM ADSC significantly restored cell proliferation and stem cell marker expression. Therefore, transplantation of T1DM ADSCs, in which AMFR and DCTN2 were knocked down, into immunodeficient mice improved transplant efficiency. This study revealed that AMFR and DCTN2 can reduce transplantation efficiency of T1DM ADSCs. Focusing on AMFR and DCTN2 is expected to increase the efficiency of stem cell transplantation therapy for diabetic patients.
Mechanism of calcitriol regulating parathyroid cells in secondary hyperparathyroidism
Authors: Xiang Zeli , Wang Ming , Miao Changxiu , Jin Die , Wang Hongyue
Published: October 2022

A common consequence of chronic renal disease is secondary hyperparathyroidism (SHPT) and is closely related to the mortality and morbidity of uremia patients. Secondary hyperparathyroidism (SHPT) is caused by excessive PTH production and release, as well as parathyroid enlargement. At present, the mechanism of cell proliferation in secondary hyperparathyroidism (SHPT) is not completely clear. Decreased expression of the vitamin D receptor (VDR) and calcium-sensing receptor (CaSR), and 1,25(OH)2D3 insufficiency all lead to a decrease in cell proliferation suppression, and activation of multiple pathways is also involved in cell proliferation in renal hyperparathyroidism. The interaction between the parathormone (PTH) and parathyroid hyperplasia and 1,25(OH)2D3 has received considerable attention. 1,25(OH)2D3 is commonly applied in the therapy of renal hyperparathyroidism. It regulates the production of parathormone (PTH) and parathyroid cell proliferation through transcription and post-transcription mechanisms. This article reviews the role of 1,25(OH)2D3 in parathyroid cells in secondary hyperparathyroidism and its current understanding and potential molecular mechanism.
Trends in Brazilian market of antidepressants: A five-year dataset analysis
Authors: Hoefler Rogério , Galvão Taís Freire , Ribeiro-Vaz Inês , Silva Marcus Tolentino
Published: October 2022

Introduction: Depression is an emotional disorder associated with morbidities and disabilities worldwide. The growing use of antidepressants is a concern for health managers because there are still unanswered questions on the effectiveness and safety of these medicines. Drug sales have increased in Brazil in recent years, but investigations on antidepressants sales are not available. We aimed to describe the trends in the antidepressant commerce in Brazil in a five-year period.

Materials and Methods: We performed an ecological study on antidepressant sales in Brazil, from November 2014 to October 2019, using data from IQVIA™, a data provider of pharmaceutical sales. Antidepressants were coded by the Anatomical Therapeutic Chemical classification system, and sales were presented in defined daily doses (DDDs) and DDDs per 1,000 inhabitants per day (DIDs). The results were expressed in absolute quantities and growth rates.

Results: The analyzed dataset contained 23 active substances in 780 products. The total sales of antidepressants increased from 23.3 DIDs in November 2014 to 38.3 DIDs in October 2019 (p = 0.002). Selective serotonin reuptake inhibitors were the most sold category of drugs (+5.7 million DDDs) in the period. ‘Other’ antidepressants presented the largest growth rate (104.7%). Individually, the most sold active substance was escitalopram (+1.8 million DDDs), and vortioxetine had the largest growth rate (336.2%). Tricyclic sales remained unchanged, and monoamine oxidase inhibitors had low and even decreasing sales (−9.5%).

Discussion: The total sales of antidepressants increased in Brazil from November 2014 to October 2019. The higher sale volumes of selective serotonin reuptake inhibitors and higher growth rate of ‘other’ antidepressants, with low sale volume of tricyclics and a decrease of monoamine oxidase inhibitors, suggest the replacement of older drugs by newer ones following a global trend. Therapeutic advances and commercial promotion efforts on new products might explain these findings.
Design, synthesis, molecular modeling, and bioactivity evaluation of 1,10-phenanthroline and prodigiosin (Ps) derivatives and their Copper(I) complexes against mTOR and HDAC enzymes as highly potent and effective new anticancer therapeutic drugs
Authors: Cetin M. Mustafa , Peng Wenjing , Unruh Daniel , Mayer Michael F. , Mechref Yehia , Yelekci Kemal
Published: October 2022

Breast cancer is the second type of cancer with a high probability of brain metastasis and has always been one of the main problems of breast cancer research due to the lack of effective treatment methods. Demand for developing an effective drug against breast cancer brain metastasis and finding molecular mechanisms that play a role in effective treatment are gradually increasing. However, there is no effective anticancer therapeutic drug or treatment method specific to breast cancer, in particular, for patients with a high risk of brain metastases. It is known that mTOR and HDAC enzymes play essential roles in the development of breast cancer brain metastasis. Therefore, it is vital to develop some new drugs and conduct studies toward the inhibition of these enzymes that might be a possible solution to treat breast cancer brain metastasis. In this study, a series of 1,10-phenanthroline and Prodigiosin derivatives consisting of their copper(I) complexes have been synthesized and characterized. Their biological activities were tested in vitro on six different cell lines (including the normal cell line). To obtain additional parallel validations of the experimental data, some in silico modeling studies were carried out with mTOR and HDAC1 enzymes, which are very crucial drug targets, to discover novel and potent drugs for breast cancer and related brain metastases disease.
Statistical analysis of resilience in an air transport network
Authors: Xu Guoqiang , Zhang Xuejun
Published: October 2022

The resilience of an air transport network represents its ability to adapt and stay operational at the required level of safety and efficiency during the impact of various disturbances. These disturbances, which can compromise the resilience of a given air transport network, include inclement weather conditions, human-intended interruptions (such as terrorist attacks, air traffic controller strikes, or pilots strikes), or unexpected mechanical failures (such as aircraft component breakdown or runway system failures). The mitigating actions such as delaying, canceling, and rerouting affected flights aim at maintaining both the network’s resilience and safety at the acceptable level under given conditions. It is of great significance to understand and quantify resilience in the complex socio-technical air transport network, which has attracted extensive attentions. In this study, statistical analysis of China air traffic data is applied to investigate the emergence of resilience in the air transport network. The Granger causality test is adopted to evaluate the causality relationship between different elements of a complex system. We construct the hourly delay propagation networks and analyze the resilience of the air transport system through the evolution of delay propagation networks. The useful measurement metric of resilience is proposed, and evolution patterns of generation and recovery of flight delays are also investigated. In addition, the relationship between initial delay, scheduled flights, and resilience loss is studied to reveal further understanding of resilience in the air transport system.
RagC GTPase regulates mTOR to promote chemoresistance in senescence-like HepG2 cells
Authors: Jiang Wei , Ou Zhenglin , Zhu Qin , Zai Hongyan
Published: October 2022

Radiotherapy and chemotherapy can arrest cancer cells in a senescence-like state, which can lead to therapy resistance and cancer relapse. mTOR is hyperactivated in senescent cells but the mechanisms remain unclear. In this study, we examine the roles of several mTOR-regulated GTPases in senescence-like liver cancer cells and the mechanisms in drug resistance. We show that although RagC, Rheb, Rab1A, Rab5 and Arf1 GTPases were required for optimal mTOR activation in proliferating HepG2 cells, only RagC and Rheb are required in the senescence-like counterparts. Consistently, the drug resistance of the senescence-like HepG2 can be reduced by knocking down RagC and Rheb but not the other GTPases. Autophagic and lysosomal activity were increased in senescence-like cells; pharmacological inhibition of autophagy-lysosome decreased mTOR activity and preferentially sensitized senescence-like HepG2 cells to chemotherapy drugs including trametinib, cisplatin, and doxorubicin. In liver cancer patients, expression of RagC and Rheb but not other GTPases examined was associated with unfavorable prognosis. Our study therefore has defined a key role of Rag-Rheb GTPase in mediating mTOR activation and drug resistance in senescence-like HepG2 cells, which could have important implications in developing second-line treatments for liver cancer patients.
Characterization of cerebral blood flow during open cardiac massage in swine: Effect of volume status
Authors: Patel Neerav , Edwards Joseph , Abdou Hossam , Stonko David P. , Treffalls Rebecca N. , Elansary Noha N. , Ptak Thomas , Morrison Jonathan J.
Published: October 2022

Introduction: Patients in cardiac arrest treated with resuscitative thoracotomy and open cardiac massage (OCM) have high rates of mortality with poor neurological outcomes. The aim of this study is to quantitate cerebral perfusion during OCM using computed tomography perfusion (CTP) imaging in a swine model of normo- and hypovolemia.

Methods: Anesthetized swine underwent instrumentation with right atrial and aortic pressure catheters. A catheter placed in the ascending aorta was used to administer iodinated contrast and CTP imaging acquired. Cerebral blood flow (CBF; ml/100 g of brain) and time to peak (TTP; s) were measured. Animals were then euthanized by exsanguination (hypovolemic group) or potassium chloride injection (normovolemic group) and subjected to a clamshell thoracotomy, aortic cross clamping, OCM, and repeated CTP. Data pertaining to peak coronary perfusion pressure (pCoPP; mmHg) were collected and % CoPP > 15 mmHg (% CoPP; s) calculated post hoc.

Results: Normovolemic animals (n = 5) achieved superior pCoPP compared to the hypovolemic animals (n = 5) pCoPP (39.3 vs. 12.3, p < 0.001) and % CoPP (14.5 ± 1.9 vs. 30.9 ± 6.5, p < 0.001). CTP acquisition was successful and TTP elongated from spontaneous circulation, normovolemia to hypovolemia (5.7 vs. 10.8 vs. 14.8, p = 0.01). CBF during OCM was similar between hypovolemic and normovolemic groups (7.5 ± 8.1 vs. 4.9 ± 6.0, p = 0.73) which was significantly lower than baseline values (51.9 ± 12.1, p < 0.001).

Conclusion: OCM in normovolemia generates superior coronary hemodynamics compared to hypovolemia. Despite this, neither generates adequate CBF as measured by CTP, compared to baseline. To improve the rate of neurologically intact survivors, novel resuscitative techniques need to be investigated that specifically target cerebral perfusion as existing techniques are inadequate.
Function of Vitellogenin receptor gene in reproductive regulation of Zeugodacus cucurbitae (Coquillett) after short-term high-temperature treatment
Authors: Lian Yuyang , Peng Sihua , Jia Jingjing , Li Jinlei , Wang Aqiang , Yang Shuyan , Zheng Rongjiao , Yang Xiaofeng , Zhou Shihao
Published: October 2022

Climate change has increased the frequency of extreme heat events. Zeugodacus cucurbitae (Coquillett) is an important tropical pest that typically changes its reproductive strategies in response to extremely high temperatures. Newly emerged adults of three consecutive generations (F1, F2, and F3) of Z. cucurbitae (Coquillett) were exposed to 25°C, 33°C, 37°C, 41°C, and 45°C treatments for 1 h to clarify the effects of short-term high temperatures on its reproduction. The influence of these temperatures on reproduction was evaluated using indicators, such as egg number. Newly emerged adults were exposed to 25°C and 45°C treatments for 1 h, and the expression of Vitellogenin receptor (VgR) gene in females was interfered with siRNA, and silencing efficiency of RNAi was evaluated. Results showed that short-term high temperatures, except for F1 treated at 45°C for 1 h to stimulate oviposition, exert a general adverse effect on the reproduction of Z. cucurbitae (Coquillett). All F3 died after the 45°C treatment for 1 h. Silencing of the VgR gene resulted in the significant downregulation of VgR gene expression at both 24 and 72 h. The egg number, oviposition days, and hatchability of eggs were significantly lower than those of other treatment groups after interference, and the inhibition effect of egg number was the most evident, with a decrease of 88.4% and 95.2% at 25°C and 45°C, respectively, compared with that of the Control Check (CK). Ovarian development speed and diameter were also significantly lower than those of other treatment groups after the interference. The results of this study can provide a theoretical reference for the integrated control of Z. cucurbitae (Coquillett) during high-temperature seasons.
De novo genome assembly of rice bean (Vigna umbellata) – A nominated nutritionally rich future crop reveals novel insights into flowering potential, habit, and palatability centric – traits for efficient domestication
Authors: Kaul Tanushri , Easwaran Murugesh , Thangaraj Arulprakash , Meyyazhagan Arun , Nehra Mamta , Raman Nitya Meenakshi , Verma Rachana , Sony Sonia Khan , Abdel Khaled Fathy , Bharti Jyotsna , Gayacharan  , Badapanda Chandan , Balasubramanian Balamuralikrishnan
Published: October 2022

Rice bean is a less-known underutilized legume crop with a high nutritional value among members of the Vigna family. As an initiative to compose rice bean (Vigna umbellata) genomic resource, the size of 414 mega-base pairs with an estimated identification of 31,276 high confidence index genes via 15,521 scaffolds generated from Illumina and PacBio platform 30X coverage data has achieved 96.08% functional coverage data from Illumina and PacBio platform. Rice bean genome assembly was found to be exquisitely close to Vigna angularis (experimental control/outgroup), Vigna radiata, and Vigna unguiculata, however, Vigna angularis being the closest. The assembled genome was further aligned with 31 leguminous plants (13 complete genomes and 18 partial genomes), by collinearity block mapping. Further, we predicted similar discriminant results by complete coding sequence (CDS) alignment. In contrast, 17 medically influential genomes from the National Institute of General Medical Sciences-National Institutes of Health NIGMS-NIH, when compared to rice bean assembly for LCB clusters, led to the identification of more than 18,000 genes from the entire selected medicinal genomes. Empirical construction of all genome comparisons revealed symplesiomorphic character in turn uncovering the lineage of genetic and functional features of rice beans. Significantly, we found deserving late-flowering genes, palatably indexed uncommon genes that regulate various metabolite pathways, related to abiotic and biotic stress pathways and those that are specific to photoperiod and disease resistance and so on. Therefore, the findings from this report address the genomic value of rice bean to be escalated via breeding by allied and applied approaches.
Identification of long non-coding RNAs involved in floral scent of Rosa hybrida
Authors: Shi Shaochuan , Zhang Shiya , Wu Jie , Liu Xintong , Zhang Zhao
Published: October 2022

Long non-coding RNAs (lncRNAs) were found to play important roles in transcriptional, post-transcriptional, and epigenetic gene regulation in various biological processes. However, lncRNAs and their regulatory roles remain poorly studied in horticultural plants. Rose is economically important not only for their wide use as garden and cut flowers but also as important sources of natural fragrance for perfume and cosmetics industry, but presently little was known about the regulatory mechanism of the floral scent production. In this paper, a RNA-Seq analysis with strand-specific libraries, was performed to rose flowers in different flowering stages. The scented variety ‘Tianmidemeng’ (Rosa hybrida) was used as plant material. A total of 13,957 lncRNAs were identified by mining the RNA-Seq data, including 10,887 annotated lncRNAs and 3070 novel lncRNAs. Among them, 10,075 lncRNAs were predicted to possess a total of 29,622 target genes, including 54 synthase genes and 24 transcription factors related to floral scent synthesis. 425 lncRNAs were differentially expressed during the flowering process, among which 19 were differentially expressed among all the three flowering stages. Using weighted correlation network analysis (WGCNA), we correlate the differentially-expressed lncRNAs to synthesis of individual floral scent compounds. Furthermore, regulatory function of one of candidate lncRNAs for floral scent synthesis was verified using VIGS method in the rose. In this study, we were able to show that lncRNAs may play important roles in floral scent production in the rose. This study also improves our understanding of how plants regulate their secondary metabolism by lncRNAs.
Functional whole-brain mechanisms underlying effects of tDCS on athletic performance of male rowing athletes revealed by resting-state fMRI
Authors: Ma Ming , Xu Yan , Xiang Ziliang , Yang Xi , Guo Jianye , Zhao Yong , Hou Zhenghua , Feng Yuxu , Chen Jianhuai , Yuan Yonggui
Published: October 2022

Introduction

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that applied to modulate brain activity and enhance motor recovery. However, the neurobiological substrates underlying the effects of tDCS on brain function remain poorly understood. This study aimed to investigate the central mechanisms of tDCS on improving the athletic performance of male rowing athletes.

Methods

Twelve right-handed male professional rowing athletes received tDCS over the left primary motor cortex while undergoing regular training. The resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired before and after tDCS. Measures of amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were calculated and compared between baseline and follow-up, as well as topological measures including global and local efficiency of functional brain networks constructed by graph theoretical analysis.

Results

Male rowing athletes showed increased isokinetic muscle strength of the left knee and left shoulder after tDCS. Increased ALFF values were found in the right precentral gyrus of male rowing athletes after tDCS when compared with those before tDCS. In addition, male rowing athletes showed increased ReHo values in the left paracentral lobule following tDCS. Moreover, increased nodal global efficiency was identified in the left inferior frontal gyrus (opercular part) of male rowing athletes after tDCS.

Conclusion

The findings suggested that simultaneous tDCS-induced excitation over the primary motor cortex might potentially improve the overall athletic performance in male rowing athletes through the right precentral gyrus and left paracentral lobule, as well as left inferior frontal gyrus.
Effects of intimate partner violence against women in international micro and small enterprises relationships: The mediator role of capabilities
Authors: Ponce-Gómez Jazmín E. , Vara-Horna Arístides , Valenciano-Mañé Alba , Dornberger Utz
Published: October 2022

While previous studies have explored multiple constraints affecting women exporters, the effects of intimate partner violence against women (IPVAW) are still unexplored in the literature. Thus, this study aims to probe first whether women owners of micro and small enterprises (MSEs) in export markets experience IPVAW. Secondly, it aims to explore the effect of IPVAW on their relationship quality with business partners, mediated by the performance of export capabilities. Using a structured questionnaire applied through personal interviews, we surveyed 57 female owners of exporting MSEs in Peru. Partial least squares structural equation modeling was used to analyze the data and test the model. The preliminary findings indicate that women exporters who experience IPVAW are more likely to face problems performing export capabilities. In turn, these performance problems seem to affect the quality of their relationships with importers and suppliers. Moreover, there is a direct relationship between IPVAW and problems in performing export capabilities and between issues performing capabilities and the relationship quality. Our theoretical contribution is a conceptual model that proposes the variable “Problems Performing Capabilities” as a mediator to measure the effects of IPVAW on exporting MSEs owned by women. Our findings urge policymakers and trade organizations boosting women-owned export enterprises to include initiatives that address and prevent IPVAW in their export promotion programs.
Flashforward imagery in speech anxiety: Characteristics and associations with anxiety and avoidance
Authors: Thunnissen Marjolein R. , Nauta Maaike H. , de Jong Peter J. , Rijkeboer Marleen M. , Voncken Marisol J.
Published: October 2022

Speech anxiety (SA) is a highly prevalent social fear. Prospective ‘flashforward’ (FF) imagery of an upcoming social catastrophe may be a particularly important cognitive factor in SA persistence via eliciting anxiety and avoidance behaviors. Since earlier research on imagery and social anxiety has not strictly differentiated between types of negative imagery, the occurrence, precise features, and impact of FF imagery remain unclear. We therefore examined the phenomenological characteristics of FF imagery in SA and mapped the relationship between FF imagery features and anxiety and avoidance. Female participants who approached clinical levels of SA (N = 60) completed questionnaires on SA and avoidance behaviors, and rated anxiety and avoidance in anticipation of an actual speech. FF imagery and emotionally linked autobiographical memories were assessed with semi-structured interviews. All participants reported recurring FF images, which were experienced as vivid, distressing, field perspective images with accompanying negative feelings. Image distress and feelings of threat showed most consistent associations with SA and avoidance measures. Findings add to the conceptualization of SA, and support the clinical relevance of assessing FF imagery. Future experimental studies on FF imagery characteristics are necessary to test the proposed causal impact in SA persistence and to inform additional treatment targets.
Association between caregiver ability and quality of life for people with inflammatory bowel disease: The mediation effect of positive feelings of caregivers
Authors: Fang Ning , Deng Haijun , Fu Tian , Zhang Zinan , Long Xiuyan , Wang Xiaoyan , Tian Li
Published: October 2022

Inflammatory bowel disease (IBD) is an incurable digestive disease. Since patients have to live with it, improving patients’ quality of life is important. Caregiver’s positive feelings and closeness may have a positive effect on patients’ quality of life. We hypothesized that caregiver’s positive feeling affected patient’s quality of life through caregiver’s caring ability, and closeness might be the upstream of this chain. In this study, we conducted a single-center cross-sectional survey by questionnaire in China to tested the hypothesis. A total of 181 patient-caregiver pairs were included. The short version of the IBD questionnaire (SIBDQ), the twelve-item short-form health survey (SF-12), the positive aspects of caregiving (PAC) and Capacity Scale of caregivers were used to collect data. All the data were collected in one interview. Spearman correlation and Bootstrap method were used to analyze the data. Mediation analysis results indicated that caregiver’s caring ability mediated the association between caregiver’s positive feelings and patients’ quality of life (p < 0.01), which explained 34.1% of the total variation of patients’ quality of life. Mediation analysis results also revealed that patient-evaluated or caregiver-evaluated closeness had a positive effect on patients’ quality of life through caregiver’s positive feeling and caregiver’s caring ability (p < 0.05), which explained 2.1 and 2.3% of the variation of patients’ quality of life. Caregiver’s positive feelings were related to caregivers’ quality of life (p < 0.01), but there was no significant association between caregivers’ ability and caregivers’ quality of life. In summary, our model revealed that caregiver’s positive feeling affected patients’ quality of life through caregiver’s caring ability.