bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Strategies to Target Protein Aggregation in Huntington’s Disease
Authors: Jarosińska Olga D. , Rüdiger Stefan G. D.
Published: November 2021

Huntington’s disease (HD) is a neurodegenerative disorder caused by the aggregation of the mutant huntingtin (mHTT) protein in nerve cells. mHTT self-aggregates to form soluble oligomers and insoluble fibrils, which interfere in a number of key cellular functions. This leads to cell quiescence and ultimately cell death. There are currently still no treatments available for HD, but approaches targeting the HTT levels offer systematic, mechanism-driven routes towards curing HD and other neurodegenerative diseases. This review summarizes the current state of knowledge of the mRNA targeting approaches such as antisense oligonucleotides and RNAi system; and the novel methods targeting mHTT and aggregates for degradation via the ubiquitin proteasome or the autophagy-lysosomal systems. These methods include the proteolysis-targeting chimera, Trim-Away, autophagosome-tethering compound, autophagy-targeting chimera, lysosome-targeting chimera and approach targeting mHTT for chaperone-mediated autophagy. These molecular strategies provide a knowledge-based approach to target HD and other neurodegenerative diseases at the origin.
Effect of Emissary Vein on Hemodynamics of the Transverse- Sigmoid Sinus Junction
Authors: Qiu Xiaoyu , Zhao Pengfei , Li Xiaoshuai , Ding Heyu , Lv Han , Mu Zhenxia , Xue Xiaofei , Gong Shusheng , Yang Zhenghan , Gao Bin , Wang Zhenchang
Published: November 2021

Objective: To investigate the effect of the blood flow direction and afflux location of emissary veins (EVs) on the hemodynamics of the transverse-sigmoid sinus (TS-SS) junction.

Methods: A patient-specific geometric model was constructed using computed tomography venography (CTV) and 4D flow MR data from a venous pulsatile tinnitus (PT) patient. New EV models were assembled with the afflux at the superior, middle and inferior portions of the SS from the original model, and inlet and outlet directions were applied. Computational fluid dynamics (CFD) simulation was performed to analyze the wall pressure and flow pattern of the TS-SS junction in each condition.

Results: Compared to the model without EVs, the wall pressure was greatly increased in models with inlet flow and greatly decreased in models with outlet flow. The more closely the EV approached the TS-SS, the larger the pressure in models with inlet flow, and the smaller the pressure in models with outlet flow. The flow streamline in the lateral part of the TS-SS junction was smooth in all models. The streamlines in the medial part were regular spirals in outlet models and chaotic in inlet models. The streamlines showed no obvious changes regardless of afflux location. The velocity at the TS-SS junction of inlet models were uniform, medium-low flow rate, while in control and outlet models were the lateral high flow rate and the central low flow rate.

Conclusion: The flow direction and afflux location of EVs affect the hemodynamics of the TS-SS junction, which may influence the severity of PT.
The Perspectives of Early Diagnosis of Schizophrenia Through the Detection of Epigenomics-Based Biomarkers in iPSC-Derived Neurons
Authors: Lee Davin , Seo Jinsoo , Jeong Hae chan , Lee Hyosang , Lee Sung Bae
Published: November 2021

The lack of early diagnostic biomarkers for schizophrenia greatly limits treatment options that deliver therapeutic agents to affected cells at a timely manner. While previous schizophrenia biomarker research has identified various biological signals that are correlated with certain diseases, their reliability and practicality as an early diagnostic tool remains unclear. In this article, we discuss the use of atypical epigenetic and/or consequent transcriptional alterations (ETAs) as biomarkers of early-stage schizophrenia. Furthermore, we review the viability of discovering and applying these biomarkers through the use of cutting-edge technologies such as human induced pluripotent stem cell (iPSC)-derived neurons, brain models, and single-cell level analyses.
Differential Effects of Oleic and Palmitic Acids on Lipid Droplet-Mitochondria Interaction in the Hepatic Cell Line HepG2
Authors: Eynaudi Andrea , Díaz-Castro Francisco , Bórquez Juan Carlos , Bravo-Sagua Roberto , Parra Valentina , Troncoso Rodrigo
Published: November 2021

Fatty acid overload, either of the saturated palmitic acid (PA) or the unsaturated oleic acid (OA), causes triglyceride accumulation into specialized organelles termed lipid droplets (LD). However, only PA overload leads to liver damage mediated by mitochondrial dysfunction. Whether these divergent outcomes stem from differential effects of PA and OA on LD and mitochondria joint dynamics remains to be uncovered. Here, we contrast how both fatty acids impact the morphology and interaction between both organelles and mitochondrial bioenergetics in HepG2 cells. Using confocal microscopy, we showed that short-term (2–24 h) OA overload promotes more and bigger LD accumulation than PA. Oxygen polarography indicated that both treatments stimulated mitochondrial respiration; however, OA favored an overall build-up of the mitochondrial potential, and PA evoked mitochondrial fragmentation, concomitant with an ATP-oriented metabolism. Even though PA-induced a lesser increase in LD-mitochondria proximity than OA, those LD associated with highly active mitochondria suggest that they interact mainly to fuel fatty acid oxidation and ATP synthesis (that is, metabolically “active” LD). On the contrary, OA overload seemingly stimulated LD-mitochondria interaction mainly for LD growth (thus metabolically “passive” LDs). In sum, these differences point out that OA readily accumulates in LD, likely reducing their toxicity, while PA preferably stimulates mitochondrial oxidative metabolism, which may contribute to liver damage progression.
A Hypoxia-Associated Prognostic Gene Signature Risk Model and Prognosis Predictors in Gliomas
Authors: Gao Feng , Wang Zhengzheng , Gu Jiajie , Zhang Xiaojia , Wang Huixiao
Published: November 2021

Most solid tumours are hypoxic. Tumour cell proliferation and metabolism accelerate oxygen consumption. The low oxygen supply due to vascular abnormalisation and the high oxygen demand of tumour cells give rise to an imbalance, resulting in tumour hypoxia. Hypoxia alters cellular behaviour and is associated with extracellular matrix remodelling, enhanced tumour migration, and metastatic behaviour. In light of the foregoing, more research on the progressive and prognostic impacts of hypoxia on gliomas are crucial. In this study, we analysed the expression levels of 75 hypoxia-related genes in gliomas and found that a total of 26 genes were differentially expressed in The Cancer Genome Atlas (TCGA) database samples. We also constructed protein–protein interaction networks using the STRING database and Cytoscape. We obtained a total of 10 Hub genes using the MCC algorithm screening in the cytoHubba plugin. A prognostic risk model with seven gene signatures (PSMB6, PSMD9, UBB, PSMD12, PSMB10, PSMA5, and PSMD14) was constructed based on the 10 Hub genes using LASSO–Cox regression analysis. The model was verified to be highly accurate using subject work characteristic curves. The seven-gene signatures were then analysed by univariate and multivariate Cox. Notably, PSMB10, PSMD12, UBB, PSMA5, and PSMB6 were found to be independent prognostic predictive markers for glioma. In addition, PSMB6, PSMA5, UBB, and PSMD12 were lowly expressed, while PSMB10 was highly expressed, in the TCGA and GTEx integrated glioma samples and normal samples, which were verified through protein expression levels in the Human Protein Atlas database. This study found the prognostic predictive values of the hypoxia-related genes PSMB10, PSMD12, UBB, PSMA5, and PSMB6 for glioma and provided ideas and entry points for the progress of hypoxia-related glioma.
Elevated Sodium Pump α3 Subunit Expression Promotes Colorectal Liver Metastasis via the p53-PTEN/IGFBP3-AKT-mTOR Axis
Authors: Wu Di , Yu Hong-Qiang , Xiong Hao-Jun , Zhang Yu-Jun , Lin Xiao-Tong , Zhang Jie , Wu Wu , Wang Teng , Liu Xiao-Yu , Xie Chuan-Ming
Published: November 2021

The sodium pump α3 subunit is associated with colorectal liver metastasis. However, the underlying mechanism involved in this effect is not yet known. In this study, we found that the expression levels of the sodium pump α3 subunit were positively associated with metastasis in colorectal cancer (CRC). Knockdown of the α3 subunit or inhibition of the sodium pump could significantly inhibit the migration of colorectal cancer cells, whereas overexpression of the α3 subunit promoted colorectal cancer cell migration. Mechanistically, the α3 subunit decreased p53 expression, which subsequently downregulated PTEN/IGFBP3 and activated mTOR, leading to the promotion of colorectal cancer cell metastasis. Reciprocally, knockdown of the α3 subunit or inhibition of the sodium pump dramatically blocked this effect in vitro and in vivo via the downregulation of mTOR activity. Furthermore, a positive correlation between α3 subunit expression and mTOR activity was observed in an aggressive CRC subtype. Conclusions: Elevated expression of the sodium pump α3 subunit promotes CRC liver metastasis via the PTEN/IGFBP3-mediated mTOR pathway, suggesting that sodium pump α3 could represent a critical prognostic marker and/or therapeutic target for this disease.
Three Novel and One Potential Hotspot CPT1A Variants in Chinese Patients With Carnitine Palmitoyltransferase 1A Deficiency
Authors: Zhang Weifeng , Chen Yanru , Lin Chunmei , Peng Weilin , Fu Qingliu , Lin Yiming
Published: November 2021

Carnitine palmitoyltransferase 1A (CPT1A) deficiency is an inherited disorder of mitochondrial fatty acid β-oxidation that impairs fasting ketogenesis and gluconeogenesis in the liver. Few studies implementing newborn screening (NBS) for CPT1A deficiency in the Chinese population have been reported. This study aimed to determine the biochemical, clinical, and genetic characteristics of patients with CPT1A deficiency in China. A total of 204,777 newborns were screened using tandem mass spectrometry at Quanzhou Maternity and Children's Hospital between January 2017 and December 2018. Newborns with elevated C0 levels were recruited, and suspected patients were subjected to further genetic analysis. Additionally, all Chinese patients genetically diagnosed with CPT1A deficiency were reviewed and included in the study. Among the 204,777 screened newborns, two patients were diagnosed with CPT1A deficiency; thus, the estimated incidence in the selected population was 1:102,388. In addition to the two patients newly diagnosed with CPT1A deficiency, we included in our cohort 10 Chinese patients who were previously diagnosed. Five of these 12 patients were diagnosed via NBS. All patients exhibited elevated C0 and/or C0/(C16+C18) ratios. No clinical symptoms were observed in the five patients diagnosed via NBS, while all seven patients presented with clinical symptoms, including fever, cough, vomiting, diarrhea, and seizures. Eighteen distinct CPT1A variants were identified, 15 of which have been previously reported. The three novel variants were c.272T>C (p.L91P), c.734G>A (p.R245Q), and c.1336G>A (p.G446S). in silico analysis suggested that all three novel variants were potentially pathogenic. The most common variant was c.2201T>C (p.F734S), with an allelic frequency of 16.67% (4/24). Our findings demonstrated that NBS for CPT1A deficiency is beneficial. The three novel variants expand the mutational spectrum of CPT1A in the Chinese population, and c.2201T>C (p.F734S) may be a potential hotspot CPT1A mutation.
Determining the Maximum States of the Ensemble Distribution of Boolean Networks
Authors: Cui Xiaodong , Ren Binghao , Li Zhenghan
Published: November 2021

Inference of the gene regulation mechanism from gene expression patterns has become increasingly popular, in recent years, with the advent of microarray technology. Obtaining the states of genes and their regulatory relationships would greatly enable the scientists to investigate and understand the mechanisms of the diseases. However, it is still a big challenge to determine relationships from several thousands of genes. Here, we simplify the above complex gene state determination problem as an inference of the distribution of the ensemble Boolean networks (BNs). In order to investigate and calculate the distribution of the BNs’ states, we first compute the probabilities of the different BNs’ states and obtain the number of statesΩ. Then, we find the maximum possible distribution of the number of the BNs’ states and calculate the fluctuation of the distribution. Finally, two representative experiments are conducted, and the efficiency of the obtained results is verified. The proposed algorithm is conceptually concise and easily applicable to many other realistic models; furthermore, it is highly extensible for various situations.
Distinct Physiological Roles of Three Phospholipid:Diacylglycerol Acyltransferase Genes in Olive Fruit with Respect to Oil Accumulation and the Response to Abiotic Stress
Authors: Hernández M. Luisa , Moretti Samuele , Sicardo M. Dolores , García Úrsula , Pérez Ana , Sebastiani Luca , Martínez-Rivas José M.
Published: November 2021

Three different cDNA sequences, designated OepPDAT1-1, OepPDAT1-2, and OepPDAT2, encoding three phospholipid:diacylglycerol acyltransferases (PDAT) have been isolated from olive (Olea europaea cv. Picual). Sequence analysis showed the distinctive features typical of the PDAT family and together with phylogenetic analysis indicated that they encode PDAT. Gene expression analysis in different olive tissues showed that transcript levels of these three PDAT genes are spatially and temporally regulated and suggested that, in addition to acyl-CoA:diacylglycerol acyltransferase, OePDAT1-1 may contribute to the biosynthesis of triacylglycerols in the seed, whereas OePDAT1-2 could be involved in the triacylglycerols content in the mesocarp and, therefore, in the olive oil. The relative contribution of PDAT and acyl-CoA:diacylglycerol acyltransferase enzymes to the triacylglycerols content in olive appears to be tissue-dependent. Furthermore, water regime, temperature, light, and wounding regulate PDAT genes at transcriptional level in the olive fruit mesocarp, indicating that PDAT could be involved in the response to abiotic stresses. Altogether, this study represents an advance in our knowledge on the regulation of oil accumulation in oil fruit.
OVATE Family Protein PpOFP1 Physically Interacts With PpZFHD1 and Confers Salt Tolerance to Tomato and Yeast
Authors: Tan Qiuping , Jiang Shan , Wang Ning , Liu Xiao , Zhang Xinhao , Wen Binbin , Fang Yuhui , He Huajie , Chen Xiude , Fu Xiling , Li Dongmei , Xiao Wei , Li Ling
Published: November 2021

The OVATE family protein (OFP) genes (OFPs) have been shown to respond to salt stress in plants. However, the regulatory mechanism for salt tolerance of the peach (Prunus persica) OFP genePpOFP1has not been elucidated. In this study, using yeast two-hybrid screening, we isolated a nucleus-localized ZF-HD_dimer domain protein PpZFHD1, which interacts with the PpOFP1 protein in the peach cultivar “Zhongnongpan No.10”. A segmentation experiment further suggested that the interaction happens more specifically between the N-terminal, contains ZF-HD_dimer domain, of PpZFHD1 and the C-terminal, consists of OVATE domain, of PpOFP1. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) experiments indicate that transcription of these two genes are induced by 200 mmol/L (mM) NaCl treatment. Heterogeneous transformation experiments suggested that the growth status of transformed yeast strain over-expressing each of these two genes was more robust than that of control (CK). Furthermore, transgenic tomato plants over-expressingPpOFP1were also more robust. They had a higher content of chlorophyll, soluble proteins, soluble sugars, and proline. Activities of the superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) in these plants were higher, and tissues from these plants exhibited a lower relative conductivity and malondialdehyde (MDA) content. These results suggest that PpOFP1 physically interacts with PpZFHD1 and confers salt tolerance to tomato and yeast, thus revealing a novel mechanism for regulating salt tolerance in peach and other perennial deciduous trees.
English as a Foreign Language Teachers’ Critical Thinking Ability and L2 Students’ Classroom Engagement
Authors: Yan Ziguang
Published: November 2021

Critical thinking has been the focus of many studies considering the educational and social contexts. However, English as a foreign language (EFL) context is the one in which studies about critical thinking and its link to classroom engagement have not been carried out as much as expected. Hence, this study investigated to understand the association between EFL teachers’ critical thinking ability and students’ classroom engagement to get a broader understanding of the impact critical thinking has on students’ success. To do this, firstly, both variables of this study are defined and explicated. Then, the relationship between critical thinking and students’ classroom engagement is discussed. Finally, the implications of this research and also its limitations along with suggestions for further studies are put forward.
Diversities of Sexual Activities and Correlates of Safe Sex Practices Among Adolescents in Plateau State, Nigeria
Authors: Envuladu Esther Awazzi , Massar Karlijn , de Wit John B. F.
Published: November 2021

Background:Unsafe sex, particularly, condomless sex exposes adolescents to sexual and reproductive health risks. This study aimed to assess the sexual experiences and to determine the most important covariates of sexual activity and consistent condom use among adolescents in Plateau State, Nigeria.

Methods:A cross sectional survey was conducted among 428 adolescents selected from 6 LGAs through a multistage sampling technique. The data was analyzed using the IBM Statistical package for Social Sciences (SPSS) version 23, multiple logistic regression was conducted to determine the covariates of sexual activity and condom use.

Results:About one third (38%) of the adolescents were sexually active, 5.7% had same sex partners, 70% had more than one sexual partner and majority (72.4%) were not consistently using condom during sex. Logistic regression results showed that older adolescents (OR = 5.73; CI = 3.72–8.12;p= 0.001) and out of school adolescents (OR = 2.68; CI = 1.79–4.00;p= 0.001) were more likely to be sexually active, while multivariable logistic regression analysis showed age (AOR = 0.33; CI = 0.12–0.90;p= 0.031) and gender as important covariates of being sexually active, (AOR = 6.29; CI = 3.18–12.44;p= 0.001). Inconsistent condom use was more likely among adolescents; with lower education, (OR = 2.14; CI = 1.19–3.85;p= 0.011), having sex with older partners (OR = 0.61; CI = 0.42–0.90;P= 0.013) and with low awareness of SRH issues (OR = 2.08; CI = 1.02–4.22;p= 0.044). The multivariable logistic regression however, showed gender, being male (AOR = 0.43; CI = 0.006–3.09;p= 0.023) as covariate of consistent condom use.

Conclusion:Most sexually active adolescents had multiple sexual partners, some had same sex partners and majority were not consistently using condom. Older adolescents and those out of school were more likely to be sexually active. Awareness of SRH issues significantly influenced condom use while gender, specifically being male, was the independent covariate for being sexually active and for consistent condom use. We recommend sexual health intervention targeted at adolescents. In addition, gender should be mainstreamed into adolescent sexual and reproductive health programmes.
A Multi-Year Assessment of Phytoplankton Fluorescence in a Large Temperate River Reveals the Importance of Scale-Dependent Temporal Patterns Associated With Temperature and Other Physicochemical Variables
Authors: Mimouni El-Amine , Ridal Jeffrey J. , Twiss Michael R.
Published: November 2021

An integrated temporal study of a long-term ecological research and monitoring database of the St. Lawrence River was carried out. A long and mostly uninterrupted high temporal resolution record of fluorometric data from 2014 to 2018 was used to examine phytoplankton fluorometric variables at several scales and to identify temporal patterns and their main environmental drivers. Sets of temporal eigenvectors were used as modulating variables in a multiscale codependence analysis to relate the fluorometric variables and various environmental variables at different temporal scales. Fluorometric patterns of phytoplankton biomass in the St. Lawrence River are characterized by large, yearly-scale patterns driven by seasonal changes in water temperature, and to a lesser extent water discharge, over which finer-scale temporal patterns related to colored dissolved organic matter and weather variables can be discerned at shorter time scales. The results suggest that such an approach to characterize phytoplankton biomass in large rivers may be useful for processing large data sets from remote sensing efforts for detecting subtle large-scale changes in water quality due to land use practices and climate change.
Effect of Foot-and-Mouth Disease Vaccine on Pregnancy Failure in Beef Cows
Authors: Garcia-Pintos Camila , Riet-Correa Franklin , Menchaca Alejo
Published: November 2021

This study evaluates whether the foot-and-mouth disease (FMD) vaccination increases pregnancy failures in Bos taurus beef cows. A total of 3,379 cows were assigned to two experimental groups to receive (n = 1,722) or not receive (n = 1,657) a FMD vaccine (commercial preparation containing FMD virus, O1 Campos and A24 Cruzeiro) at different gestational age. Pregnancy diagnosis was performed by ultrasonography at vaccination time (Day 0), and the cows were classified by days of pregnancy as follows: (a) <29 days after mating (presumed pregnant cows, n = 778), (b) between 30 and 44 days of pregnancy (n = 1,100), (c) 45 and 59 days of pregnancy (n = 553), and (d) between 60 and 90 days of pregnancy (n = 948). Pregnancy failure was determined 30 days after vaccination by a second ultrasound examination. Cows that were vaccinated within 29 days after mating had a 7.8% greater pregnancy failure rate than non-vaccinated cows (44.1%, 163/370 vs. 36.3%, 148/408, respectively; P <0.05). Cows vaccinated between 30 and 44 days of gestation had a pregnancy failure rate greater than non-vaccinated cows (4.9%, 28/576 vs. 2.5%, 13/524, respectively; P <0.05). When cows received the vaccine between days 45 and 90 of gestation no differences in pregnancy failure were observed (0.8%, 6/776 vs. 1.2%, 9/725, respectively; P = NS). Body temperature and local adverse reactions to vaccine inoculation were recorded in a subset of 152 multiparous cows. Hyperthermia (>39.5°C) was detected on Day 1 or 2 in 28.0% (21/75) of vaccinated vs. 7.8% (6/77) of non-vaccinated cows (P <0.01). Local adverse reaction to the FMD vaccine inoculation increased from 0.0% (0/75) on Day 0, to 15.7% (11/75) on Day 4, and 38.7% (29/75) on Day 10 (P <0.01). On Day 30 local reaction was detected in 10.5% (34/323) and fell to 2.2% on Day 60 (7/323) post vaccination (P <0.01). In conclusion, FMD vaccine increases pregnancy failure when it is administered before 45 days of gestation, an effect that was associated with hyperthermia and local adverse reaction. No effect on pregnancy failure was found when vaccination was performed after 45 days of gestation.
Virome in Fecal Samples From Wild Giant Pandas (Ailuropoda Melanoleuca)
Authors: Ning Songyi , Lu Xiang , Zhao Min , Wang Xiaochun , Yang Shixing , Shen Quan , Wang Hao , Zhang Wen
Published: November 2021

The giant panda (Ailuropoda melanoleuca) is one of the most endangered mammals in the world; anthropogenic habitat loss and poaching still threaten the survival of wild pandas. Viral infection has become one of the potential threats to the health of these animals, but the available information related to these infections is still limited. In order to detect possible vertebrate viruses, the virome in the fecal samples of seven wild giant pandas from Qinling Mountains was investigated by using the method of viral metagenomics. From the fecal virome of wild giant pandas, we determined six nearly complete genomes belonging to the order Picornavirales, two of which may be qualified as a novel virus family or genus. In addition, four complete genomes belonging to the Genomoviridae family were also fully characterized. This virological investigation has increased our understanding of the gut viral community in giant pandas. Whether these viruses detected in fecal samples can really infect giant panda needs further research.
Therapeutic Effects of Levocarnitine or Vitamin B Complex and E With Selenium on Glycerin-Treated Holstein Friesian Cows With Clinical Ketosis
Authors: Ha Seungmin , Kang Seogjin , Han Manhye , Lee Jihwan , Chung Hakjae , Kim Donghyeon , Park Jinho
Published: November 2021

Currently, ketosis has no fully satisfactory resolution in dairy cows. Here, we investigated the effect of levocarnitine or vitamin B complex and E with selenium on clinically ketotic cows (β-hydroxybutyrate ≥ 3.0 mmol/L and decreased milk yield), fed glycerin. In total, 18 cases of Holstein cows with clinical ketosis during the postpartum transition period were randomly assigned to three treatments (6 cases per group): (1) levocarnitine (C+G), (2) vitamin B complex and E with selenium (VBES+G), and (3) levocarnitine and vitamin B complex and E with selenium (C+VBES+G). All groups were administered glycerin. Treatments were administered daily for 4 days. Blood sampling was performed on the onset day of ketosis (day 0), day 4, and day 6. β-Hydroxybutyrate (BHBA), milk yield (MY), and serum biochemical values were measured. Half of the animals in C+G failed to overcome clinical ketosis. VBES+G treatment ameliorated BHBA (p< 0.05), MY, and glucose on day 4. However, ketosis was exacerbated following the discontinuation of the treatment. C+VBES+G treatment improved BHBA, glucose (p< 0.05), and MY and reduced ketotic cases on days 4 and 6 with greater improvements compared to the others. In conclusion, combined treatment with levocarnitine, vitamin B complex and E with selenium, and glycerin may have the therapeutic effect on clinical ketosis.
Beneficial Effects of Neurotrophin-4 Supplementation During in vitro Maturation of Porcine Cumulus-Oocyte Complexes and Subsequent Embryonic Development After Parthenogenetic Activation
Authors: Kim Mirae , Hwang Seon-Ung , Yoon Junchul David , Lee Joohyeong , Kim Eunhye , Cai Lian , Kim Gahye , Choi Hyerin , Oh Dongjin , Hyun Sang-Hwan
Published: November 2021

Neurotrophin-4 (NT-4) is a neurotrophic factor that plays an important role in follicular development and oocyte maturation. However, it is not yet known whether NT-4 is related to oocyte maturation and follicular development in pigs. This study aims to investigate the effects of NT-4 supplementation during in vitro maturation (IVM) of porcine oocytes and subsequent embryonic development after parthenogenetic activation (PA). First, NT-4 and its receptors (TrkB and p75NTR) were identified through fluorescent immunohistochemistry in porcine ovaries. NT-4 was mainly expressed in theca and granulosa cells; phospho-TrkB and total TrkB were expressed in theca cells, granulosa cells, and oocytes; p75NTR was expressed in all follicular cells. During IVM, the defined maturation medium was supplemented with various concentrations of NT-4 (0, 1, 10, and 100 ng/mL). After IVM, the nuclear maturation rate was significantly higher in the 10 and 100 ng/mL NT-4 treated groups than in the control. There was no significant difference in the intracellular reactive oxygen species levels in any group after IVM, but the 1 and 10 ng/mL NT-4 treatment groups showed a significant increase in the intracellular glutathione levels compared to the control. In matured cumulus cells, the 10 ng/mL NT-4 treatment group showed significantly increased cumulus expansion-related genes and epidermal growth factor (EGF) signaling pathway-related genes. In matured oocytes, the 10 ng/mL treatment group showed significantly increased expression of cell proliferation-related genes, antioxidant-related genes, and EGF signaling pathway-related genes. We also investigated the subsequent embryonic developmental competence of PA embryos. After PA, the cleavage rates significantly increased in the 10 and 100 ng/mL NT-4 treatment groups. Although there was no significant difference in the total cell number of blastocysts, only the 10 ng/mL NT-4 treatment group showed a higher blastocyst formation rate than the control group. Our findings suggest that supplementation with the 10 ng/mL NT-4 can enhance porcine oocyte maturation by interacting with the EGF receptor signaling pathway. In addition, we demonstrated for the first time that NT-4 is not only required for porcine follicular development, but also has beneficial effects on oocyte maturation and developmental competence of PA embryos.
Autoencoder-Based Reduced Order Observer Design for a Class of Diffusion-Convection-Reaction Systems
Authors: Schaum Alexander
Published: November 2021

The application of autoencoders in combination with Dynamic Mode Decomposition for control (DMDc) and reduced order observer design as well as Kalman Filter design is discussed for low order state reconstruction of a class of scalar linear diffusion-convection-reaction systems. The general idea and conceptual approaches are developed following recent results on machine-learning based identification of the Koopman operator using autoencoders and DMDc for finite-dimensional discrete-time system identification. The resulting linear reduced order model is combined with a classical Kalman Filter for state reconstruction with minimum error covariance as well as a reduced order observer with very low computational and memory demands. The performance of the two schemes is evaluated and compared in terms of the approximated L2 error norm in a numerical simulation study. It turns out, that for the evaluated case study the reduced-order scheme achieves comparable performance with significantly less computational load.
A MIM Waveguide Structure of a High-Performance Refractive Index and Temperature Sensor Based on Fano Resonance
Authors: Liu Pengwei , Yan Shubin , Ren Yifeng , Zhang Xiaoyu , Li Tingsong , Wu Xiushan , Shen Lifang , Hua Ertian
Published: November 2021

A plasmonic refractive index nanosensor structure consisting of a metal-insulator-metal (MIM) waveguide with two symmetrical rectangle baffles coupled with a connected-concentric-double rings resonator (CCDRR) is presented. In this study, its transmission characteristics were investigated using the finite element method (FEM). The consequences, studied via simulation, revealed that the transmission spectrum of the system presents a sharp asymmetric Fano profile due to the destructive interference between the wide-band mode of two rectangle baffles on the bus waveguide and the narrow-band mode of the CCDRR. The effects of the geometric parameters of the structure on the transmission characteristics were investigated comprehensively. A sensitivity of 2260 nm/RIU and figure of merit (FOM) of 56.5 were the best levels of performance that the designed structure could achieve. In addition, the system could act as a sensor for use for temperature sensing, with a sensitivity that could reach 1.48 nm/°C. The designed structure advances with technology with new detection positions and has good application prospects in other high-sensitivity nanosensor fields, for example, acting as a biosensor to detect the hemoglobin level in the blood.
Active Sonar Target Classification Method Based on Fisher’s Dictionary Learning
Authors: Sun Tongjing , Jin Jiwei , Liu Tong , Zhang Jun
Published: November 2021

The marine environment is complex and changeable, and the interference of noise and reverberation seriously affects the classification performance of active sonar equipment. In particular, when the targets to be measured have similar characteristics, underwater classification becomes more complex. Therefore, a strong, recognizable algorithm needs to be developed that can handle similar feature targets in a reverberation environment. This paper combines Fisher’s discriminant criterion and a dictionary-learning-based sparse representation classification algorithm, and proposes an active sonar target classification method based on Fisher discriminant dictionary learning (FDDL). Based on the learning dictionaries, the proposed method introduces the Fisher restriction criterion to limit the sparse coefficients, thereby obtaining a more discriminating dictionary; finally, it distinguishes the category according to the reconstruction errors of the reconstructed signal and the signal to be measured. The classification performance is compared with the existing methods, such as SVM (Support Vector Machine), SRC (Sparse Representation Based Classification), D-KSVD (Discriminative K-Singular Value Decomposition), and LC-KSVD (label-consistent K-SVD), and the experimental results show that FDDL has a better classification performance than the existing classification methods.
Smart Design of Portable Indoor Shading Device for Visual Comfort—A Case Study of a College Library
Authors: Xue Jiao , Wang Yibo , Wang Mingxiang
Published: November 2021

With the development of architectural technology, the use of floor-to-ceiling windows has emerged widely. The ensuing problem is that more and more students and office workers are suffering from direct sunlight while working in specific areas. Based on the pain points of the working process, this study designed a portable product for improving visual comfort through field research and environment simulation. It provided a new personalized design for blocking direct sunlight from the working area using a portable and liftable sunshade curtain, allowing the users to control the height and angle of the sunshade curtain through a mobile phone application. It can also adjust itself according to environmental parameters collected by sensors, so as to block sunlight in certain areas. A simulation based on the design features and the light environment of a library is run, proving the model effective in improving these aspects. The study aimed to provide solutions for indoor visual comfort and suggestions for future indoor household designs.
Plant-Derived Substances with Antibacterial, Antioxidant, and Flavoring Potential to Formulate Oral Health Care Products
Authors: Lugo-Flores Marco A. , Quintero-Cabello Karen P. , Palafox-Rivera Patricia , Silva-Espinoza Brenda A. , Cruz-Valenzuela Manuel Reynaldo , Ortega-Ramirez Luis Alberto , Gonzalez-Aguilar Gustavo Adolfo , Ayala-Zavala Jesus Fernando
Published: November 2021

Bacterial diseases and reactive oxygen species can cause dental caries and oral cancer. Therefore, the present review analyzes and discusses the antibacterial and antioxidant properties of synthetic and plant-derived substances and their current and future patents to formulate dental products. The reviewed evidence indicates that chlorhexidine, fluorides, and hydrogen peroxide have adverse effects on the sensory acceptability of oral care products. As an alternative, plant-derived substances have antimicrobial and antioxidant properties that can be used in their formulation. Also, adding plant metabolites favors the sensory acceptability of dental products compared with synthetic compounds. Therefore, plant-derived substances have antibacterial, antioxidant, and flavoring activity with the potential to be used in the formulation of toothpaste, mouth rinses, dentures cleansers-fixatives, and saliva substitutes.
Gas6 Ameliorates Inflammatory Response and Apoptosis in Bleomycin-Induced Acute Lung Injury
Authors: Kim Bo-Min , Lee Ye-Ji , Choi Youn-Hee , Park Eun-Mi , Kang Jihee Lee
Published: November 2021

Acute lung injury (ALI) is characterized by alveolar damage, lung edema, and exacerbated inflammatory response. Growth arrest-specific protein 6 (Gas6) mediates many different functions, including cell survival, proliferation, inflammatory signaling, and apoptotic cell clearance (efferocytosis). The role of Gas6 in bleomycin (BLM)-induced ALI is unknown. We investigated whether exogenous administration of mouse recombinant Gas6 (rGas6) has anti-inflammatory and anti-apoptotic effects on BLM-induced ALI. Compared to mice treated with only BLM, the administration of rGas6 reduced the secretion of proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and macrophage inflammatory protein-2, and increased the secretion of hepatocyte growth factor in bronchoalveolar lavage (BAL) fluid. rGas6 administration also reduced BLM-induced inflammation and apoptosis as evidenced by reduced neutrophil recruitment into the lungs, total protein levels in BAL fluid, caspase-3 activity, and TUNEL-positive lung cells in lung tissue. Apoptotic cell clearance by alveolar macrophages was also enhanced in mice treated with both BLM and rGas6 compared with mice treated with only BLM. rGas6 also had pro-resolving and anti-apoptotic effects in mouse bone marrow-derived macrophages and alveolar epithelial cell lines stimulated with BLM in vitro. These findings indicate that rGas6 may play a protective role in BLM-induced ALI.
The Role of NKL Homeobox Genes in T-Cell Malignancies
Authors: Nagel Stefan
Published: November 2021

Homeobox genes encode transcription factors controlling basic developmental processes. The homeodomain is encoded by the homeobox and mediates sequence-specific DNA binding and interaction with cofactors, thus operating as a basic regulatory platform. Similarities in their homeobox sequences serve to arrange these genes in classes and subclasses, including NKL homeobox genes. In accordance with their normal functions, deregulated homeobox genes contribute to carcinogenesis along with hematopoietic malignancies. We have recently described the physiological expression of eleven NKL homeobox genes in the course of hematopoiesis and termed this gene expression pattern NKL-code. Due to the developmental impact of NKL homeobox genes these data suggest a key role for their activity in the normal regulation of hematopoietic cell differentiation including T-cells. On the other hand, aberrant overexpression of NKL-code members or ectopical activation of non-code members has been frequently reported in lymphoid and myeloid leukemia/lymphoma, demonstrating their oncogenic impact in the hematopoietic compartment. Here, we provide an overview of the NKL-code in normal hematopoiesis and discuss the oncogenic role of deregulated NKL homeobox genes in T-cell malignancies.
Enhanced Breaking of Lignin and Mesopore Formation in Zinc Chloride Assisted Hydrothermal Carbonization of Waste Biomasses
Authors: Multhaupt Hendrik , Bottke Patrick , Wark Michael
Published: November 2021

Hydrochars from hydrothermal carbonization of different biowaste materials (dried dandelion, sawdust, coconut shell powder) formed in the presence of aqueous salt solutions were compared to those obtained by the common method in pure water. Hydrochars with increased carbon contents, pore volume and surface areas were specifically obtained from coconut shell powder in the presence of zinc chloride. Compositional and structural changes within the hydrochar products caused by the process conditions and/or the additive were characterized by solid state 13C NMR spectroscopy, proving that cellulose and, in particular, lignin units in the biomass are more easily attacked in the presence of the salt. Under saline conditions, a distinct particle break-up led to the creation of mesoporosity, as observable from hysteresis loops in nitrogen adsorption isotherms, which were indicative of the presence of pores with diameters of about 3 to 10 nm. The obtained hydrochars were still rich in functional groups which, together with the mesoporosity, indicates the compounds have a high potential for pollutant removal. This was documented by adsorption capacities for the methylene blue and methyl orange dyes, which exceeded the values obtained for other hydrochar-based adsorbers. A subsequent physical activation of the mesoporous hydrochars in steam at different temperatures and times resulted in a further drastic increase in the surface areas, of up to about 750 m2/g; however, this increase is mainly due to micropore formation coupled with a loss of surface functionality. Consequently, the adsorption capacity for the quite large dyes does not provide any further benefit, but the uptake of smaller gas molecules is favored.
PGRMC1 Promotes Progestin-Dependent Proliferation of Breast Cancer Cells by Binding Prohibitins Resulting in Activation of ERα Signaling
Authors: Bai Yingxue , Ludescher Marina , Poschmann Gereon , Stühler Kai , Wyrich Martine , Oles Julia , Franken André , Rivandi Mahdi , Abramova Anna , Reinhardt Florian , Ruckhäberle Eugen , Niederacher Dieter , Fehm Tanja , Cahill Michael A. , Stamm Nadia , Neubauer Hans
Published: November 2021

In previous studies, we reported that progesterone receptor membrane component 1 (PGRMC1) is implicated in progestin signaling and possibly associated with increased breast cancer risk upon combined hormone replacement therapy. To gain mechanistic insight, we searched for potential PGRMC1 interaction partners upon progestin treatment by co-immunoprecipitation and mass spectrometry. The interactions with the identified partners were further characterized with respect to PGRMC1 phosphorylation status and with emphasis on the crosstalk between PGRMC1 and estrogen receptor α (ERα). We report that PGRMC1 overexpression resulted in increased proliferation of hormone receptor positive breast cancer cell lines upon treatment with a subgroup of progestins including norethisterone and dydrogesterone that promote PGRMC1-phosphorylation on S181. The ERα modulators prohibitin-1 (PHB1) and prohibitin-2 (PHB2) interact with PGRMC1 in dependency on S181-phosphorylation upon treatment with the same progestins. Moreover, increased interaction between PGRMC1 and PHBs correlated with decreased binding of PHBs to ERα and subsequent ERα activation. Inhibition of either PGRMC1 or ERα abolished this effect. In summary, we provide strong evidence that activated PGRMC1 associates with PHBs, competitively removing them from ERα, which then can develop its transcriptional activities on target genes. This study emphasizes the role of PGRMC1 in a key breast cancer signaling pathway which may provide a new avenue to target hormone-dependent breast cancer.
Endocrine Treatment for Breast Cancer Patients Revisited—History, Standard of Care, and Possibilities of Improvement
Authors: Nabieva Naiba , Fasching Peter
Published: November 2021

Purpose of review: Due to the findings of current studies and the approval of novel substances for the therapy of hormone-receptor-positive breast cancer patients, the established standards of endocrine treatment are changing. The purpose of this review is to give an overview of the history of endocrine treatment, to clarify its role in the present standard of care, and to discuss the possibilities of improvement. Recent findings: Tamoxifen, aromatase inhibitors, and fulvestrant are the main drugs that have been used for decades in the therapy of hormone-receptor-positive breast cancer patients. However, since a relevant number of women suffer at some point from disease recurrence or progression, several novel substances are being investigated to overcome resistance mechanisms by interfering with certain signaling pathways, such as the PI3K/AKT/mTOR or the CDK4/6 pathways. mTOR and CDK4/6 inhibitors were the first drugs approved for this purpose and many more are in development. Summary: Endocrine treatment is one of the best tolerable cancer therapies available. Continuous investigation serves to improve patients’ outcomes and modernize the current standard of care. Considering the resistance mechanisms and substances analyzed against these, endocrine treatment of hormone-receptor-positive breast cancer is on the brink of a new era.
Biology and Treatment Advances in Cutaneous Squamous Cell Carcinoma
Authors: Thai Alesha A. , Lim Annette M. , Solomon Benjamin J. , Rischin Danny
Published: November 2021

Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer diagnosed worldwide. CSCC is generally localized and managed with local therapies such as excision and/or radiotherapy. For patients with unresectable or metastatic disease, recent improvements in our understanding of the underlying biology have led to significant advancements in treatment approaches—including the use of immune checkpoint inhibition (ICI)—which have resulted in substantial gains in response and survival compared to traditional cytotoxic approaches. However, there is a lack of understanding of the biology underpinning CSCC in immunocompromised patients, in whom the risk of developing CSCC is hundreds of times higher compared to immunocompetent patients. Furthermore, current ICI approaches are associated with significant risk of graft rejection in organ transplant recipients who make up a significant proportion of immunocompromised patients. Ongoing scientific and clinical research efforts are needed in order to maintain momentum to increase our understanding and refine our therapeutic approaches for patients with CSCC.
Isocyanide Substitution in Acridine Orange Shifts DNA Damage-Mediated Phototoxicity to Permeabilization of the Lysosomal Membrane in Cancer Cells
Authors: Bankó Csaba , Nagy Zsolt László , Nagy Miklós , Szemán-Nagy Gábor György , Rebenku István , Imre László , Tiba Attila , Hajdu András , Szöllősi János , Kéki Sándor , Bacso Zsolt
Published: November 2021

In cancer therapy, immunogenic cell death eliminates tumor cells more efficiently than conventional apoptosis. During photodynamic therapy (PDT), some photosensitizer (PS) targeting lysosomes divert apoptosis to the immunologically more relevant necrosis-like cell death. Acridine orange (AO) is a PS targeting lysosome. We synthesized a new compound, 3-N,N-dimethylamino-6-isocyanoacridine (DM), a modified AO, aiming to target lysosomes better. To compare DM and AO, we studied optical properties, toxicity, cell internalization, and phototoxicity. In addition, light-mediated effects were monitored by the recently developed QUINESIn method on nuclei, and membrane stability, morphology, and function of lysosomes utilizing fluorescent probes by imaging cytometry in single cells. DM proved to be a better lysosomal marker at 405 nm excitation and lysed lysosomes more efficiently. AO injured DNA and histones more extensively than DM. Remarkably, DM’s optical properties helped visualize shockwaves of nuclear DNA released from cells during the PDT. The asymmetric polar modification of the AO leads to a new compound, DM, which has increased efficacy in targeting and disrupting lysosomes. Suitable AO modification may boost adaptive immune response making PDT more efficient.
Cancer Immunology and Immunotherapies: Mechanisms That Affect Antitumor Immune Response and Treatment Resistance
Authors: Zhao Xianda , Subramanian Subbaya
Published: November 2021

The past decade has seen immunotherapy rise to the forefront of cancer treatment [...]