bluuebunny/crossref_metadata_2025 huggingface dataset:
Organising Committee Chair's address: Resilient pastures
Authors: Chapman David
Published: January 2022

High value animal products from New Zealand’s pasture-based livestock systems have consistently earned $25-$30B in export earnings per year for the country over the past 5 years (Ministry for Primary Industries 2021). Total earnings from dairy and meat of $30.5B in 2020 equate to 35% of New Zealand’s total goods and services export earnings of $86.4B. The importance of this revenue to the national economy has been shown in stark relief recently with the Covid-19 pandemic substantially reducing the earnings generated by other key export sectors such as tourism and international education.
While our pasture-based livestock industries have ridden the coronavirus wave well compared with other sectors of the economy, they are facing change at a scale and pace not seen since the far-reaching reforms to the economic settings for agriculture introduced by the Lange Government in the early 1980s. Locally, the ramping-up of government environmental policies beginning c. 2011 has resulted in stringent regulations controlling the amounts of nitrogen (N), phosphorus (P) and sediment that can be discharged into freshwater from farm systems. The most recent iteration in this policy sequence includes new National Environmental Standards for Freshwater, and the new National Policy Statement for Freshwater Management (NPS-FW), which came into force in September 2020.   
These policies reverse the trends of the past two decades when agricultural productivity grew substantially in the virtual absence of regulation to control the environmental externalities of systems intensification. While the initial impacts on land use and farming practices have been localised (e.g., in the lake districts of Rotorua and Taupo), disruption to the farm systems that have emerged over the past two decades, especially intensive dairy systems, will be widespread in the future. For example, Doole et al. (2021) estimated that the new standards introduced in 2020 will require about 40% of New Zealand’s 11400 dairy farms to reduce nitrate leaching by an average of around 42% relative to requirements in previous iterations of the NPS-FW.
The most significant global force driving change in New Zealand agriculture is climate change, via New Zealand’s commitment to the Paris Agreement to reduce carbon (C) emissions to net zero by 2050, C-neutral strategies being implemented by some of our largest customers (e.g., Nestle 2020), and the physical impacts of climate change on conditions for plant growth (e.g., Keller et al. 2021). Of direct and significant relevance to the livestock industries are the methane emission reduction targets proposed by government, of between 27% and 47% below 2017 levels by 2050. Meanwhile our international competitors have been steadily closing the gap in costs of production with New Zealand, and now have other fields on which to out-compete us (e.g., in C footprint) unless we can keep pace.
Penerapan Strategi Bauran Pemasaran Pada Acara Launching Wakai Spring Summer 2020 Collection Di Jakarta
Authors: Anisatul Auliya  , Ema Angelia
Published: January 2022

Penelitian ini adalah untuk menganalisis strategi penerapan bauran pemasaran pada acara peluncuran Wakai Spring Summer 2020 Collection Di Jakarta. Kegiatan penelitian ini dilaksanakan pada bulan Januari-April 2020, metode pengumpulan data dilakukan dengan cara observasi langsung di lapangan, wawancara kepada penyelenggara serta pengunjung dan dokumentasi. Setelah data dikumpulkan dilakukan teknis analisis data dengan menggunakan metode deskriptif kualitatif. Hasil dari penelitian yang sudah dilakukan adalah strategi penerapan bauran pemasaran pada saat penyelenggaraan acara peluncuran wakai spring summer 2020 collection sudah dilaksanakan dengan baik untuk seleuruh komponen produk, harga, lokasi, dan promosi. Produk yang diluncurkan sangat inovatif dan rangkaian acara yang disajikan sangat beragam, Harga yang ditetapkan sudah sesuai dengan kualitas yang diberikan, Lokasi event yang strategis serta mudah diakses dan promosi online serta offline yang sudah dilakukan. Berdasarkan pengamatan dilapangan, perlu ditingkatan lagi kegiatan promosi baik online dan offiline untuk penyelenggaraan event ini kedepannya, agar dapat meningkatkan citra merek, meningkatkan jumlah penjualan serta meningkatkan jumlah pengunjung.
The Influence of Age on Cardiovascular, Motor, and Lifestyle Components in Hispanic-Latinos Living with HIV
Authors: G. Rosario Martín , Orozco Elizabeth
Published: January 2022

Background: People living with HIV experience various comorbidities associated with aging. As this population grows older, these comorbidities cause physical impairments that decrease functional autonomy and quality of life. Purpose: This investigation aims to characterize various components affecting Hispanic Latino people living with HIV (PLHIV) concerning age. Methods: Data was extracted from 323 participants’ records enrolled in La Perla de Gran Precio’s HIV Community Center in Puerto Rico. Participants were allocated into the following age groups for comparison: 40 years or less (L-HIV group) and above 40 years of age (U-HIV group). Multiple one-way ANOVAs were applied to compare the data between the two age groups based on five components: cardio, motor, lipid panel, comorbidities, and lifestyle. Results: There were 44 participants allocated to the L-HIV group (age =35.4+/-3.7) and 279 to the U-HIV group (age=56.3+/-7.4). The cardio components (time completed on the submaximal treadmill test and peak heart rate) were significantly less in the upper age group. The U-HIV group also demonstrated substantially slower gait speed and less inclination achieved on the submaximal treadmill test. Lastly, the U-HIV group consisted of more participants with multiple comorbidities. Conclusion: In Hispanic Latino PLHIV, more significant cardiovascular and motor deficits were identified in the U-HIV group in addition to an increased rate of multi-morbidity. Future inquiries are desired to resolve if the time since diagnosis is an acceptable indicator of cardio-motor deterioration and an upsurge in multiple comorbidities experienced in this population.
iSCAN-V2: A One-Pot RT-RPA–CRISPR/Cas12b Assay for Point-of-Care SARS-CoV-2 Detection
Authors: Aman Rashid , Marsic Tin , Sivakrishna Rao Gundra , Mahas Ahmed , Ali Zahir , Alsanea Madain , Al-Qahtani Ahmed , Alhamlan Fatimah , Mahfouz Magdy
Published: January 2022

Rapid, specific, and sensitive detection platforms are prerequisites for early pathogen detection to efficiently contain and control the spread of contagious diseases. Robust and portable point-of-care (POC) methods are indispensable for mass screening of SARS-CoV-2. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas)-based nucleic acid detection technologies coupled with isothermal amplification methods provide a straightforward and easy-to-handle platform for detecting SARS-CoV-2 at POC, low-resource settings. Recently, we developed iSCAN, a two-pot system based on coupled loop-mediated isothermal amplification (LAMP) and CRISPR/Cas12a reactions. However, in two-pot systems, the tubes must be opened to conduct both reactions; two-pot systems thus have higher inherent risks of cross-contamination and a more cumbersome workflow. In this study, we developed and optimized iSCAN-V2, a one-pot reverse transcription-recombinase polymerase amplification (RT-RPA)-coupled CRISPR/Cas12b-based assay for SARS-CoV-2 detection, at a single temperature in less than an hour. Compared to Cas12a, Cas12b worked more efficiently in the iSCAN-V2 detection platform. We assessed and determined the critical factors, and present detailed guidelines and considerations for developing and establishing a one-pot assay. Clinical validation of our iSCAN-V2 detection module with reverse transcription-quantitative PCR (RT-qPCR) on patient samples showed 93.75% sensitivity and 100% specificity. Furthermore, we coupled our assay with a low-cost, commercially available fluorescence visualizer to enable its in-field deployment and use for SARS-CoV-2 detection. Taken together, our optimized iSCAN-V2 detection platform displays critical features of a POC molecular diagnostic device to enable mass-scale screening of SARS-CoV-2 in low-resource settings.
Deep Learning-Based Imbalanced Classification With Fuzzy Support Vector Machine
Authors: Wang Ke-Fan , An Jing , Wei Zhen , Cui Can , Ma Xiang-Hua , Ma Chao , Bao Han-Qiu
Published: January 2022

Imbalanced classification is widespread in the fields of medical diagnosis, biomedicine, smart city and Internet of Things. The imbalance of data distribution makes traditional classification methods more biased towards majority classes and ignores the importance of minority class. It makes the traditional classification methods ineffective in imbalanced classification. In this paper, a novel imbalance classification method based on deep learning and fuzzy support vector machine is proposed and named as DFSVM. DFSVM first uses a deep neural network to obtain an embedding representation of the data. This deep neural network is trained by using triplet loss to enhance similarities within classes and differences between classes. To alleviate the effects of imbalanced data distribution, oversampling is performed in the embedding space of the data. In this paper, we use an oversampling method based on feature and center distance, which can obtain more diverse new samples and prevent overfitting. To enhance the impact of minority class, we use a fuzzy support vector machine (FSVM) based on cost-sensitive learning as the final classifier. FSVM assigns a higher misclassification cost to minority class samples to improve the classification quality. Experiments were performed on multiple biological datasets and real-world datasets. The experimental results show that DFSVM has achieved promising classification performance.
In Silico Evaluation of Enzymatic Tunnels in the Biotransformation of α-Tocopherol Esters
Authors: Azevedo Tamara Stela Mendonça , Silva Lavínia Kelly Barros , Lima Álvaro Silva , Pereira Matheus Mendonça , Franceschi Elton , Faria Soares Cleide Mara
Published: January 2022

Motivation: α-Tocopherol is a molecule obtained primarily from plant sources that are important for the pharmaceutical and cosmetics industry. However, this component has some limitations such as sensitivity to oxygen, presence of light, and high temperatures. For this molecule to become more widely used, it is important to carry out a structural modification so that there is better stability and thus it can carry out its activities. To carry out this structural modification, some modifications are carried out, including the application of biotransformation using enzymes as biocatalysts. Thus, the application of a computational tool that helps in understanding the transport mechanisms of molecules in the tunnels present in the enzymatic structures is of fundamental importance because it promotes a computational screening facilitating bench applications.

Objective: The aim of this work was to perform a computational analysis of the biotransformation of α-tocopherol into tocopherol esters, observing the tunnels present in the enzymatic structures as well as the energies which correspond to the transport of molecules.

Method: To carry out this work, 9 lipases from different organisms were selected; their structures were analyzed by identifying the tunnels (quantity, conformation, and possibility of transport) and later the calculations of substrate transport for the biotransformation reaction in the identified tunnels were carried out. Additionally, the transport of the product obtained in the reaction through the tunnels was also carried out.

Results: In this work, the quantity of existing tunnels in the morphological conformational characteristics in the lipases was verified. Thus, the enzymes with fewer tunnels were RML (3 tunnels), LBC and RNL (4 tunnels), PBLL (5 tunnels), CALB (6 tunnels), HLG (7 tunnels), and LCR and LTL (8 tunnels) and followed by the enzyme LPP with the largest number of tunnels (39 tunnels). However, the enzyme that was most likely to transport substrates in terms of α-tocopherol biotransformation (in relation to the Emax and Ea energies of ligands and products) was CALB, as it obtains conformational and transport characteristics of molecules with a particularity. The most conditions of transport analysis were α-tocopherol tunnel 3 (Emax: −4.6 kcal/mol; Ea: 1.1 kcal/mol), vinyl acetate tunnel 1 (Emax: −2.4 kcal/mol; Ea: 0.1 kcal/mol), and tocopherol acetate tunnel 2 (Emax: −3.7 kcal/mol; Ea: 2 kcal/mol).
Machine Learning-Derived Multimodal Neuroimaging of Presurgical Target Area to Predict Individual's Seizure Outcomes After Epilepsy Surgery
Authors: Tang Yongxiang , Li Weikai , Tao Lue , Li Jian , Long Tingting , Li Yulai , Chen Dengming , Hu Shuo
Published: January 2022

Objectives: Half of the patients who have tailored resection of the suspected epileptogenic zone for drug-resistant epilepsy have recurrent postoperative seizures. Although neuroimaging has become an indispensable part of delineating the epileptogenic zone, no validated method uses neuroimaging of presurgical target area to predict an individual’s post-surgery seizure outcome. We aimed to develop and validate a machine learning-powered approach incorporating multimodal neuroimaging of a presurgical target area to predict an individual’s post-surgery seizure outcome in patients with drug-resistant focal epilepsy.

Materials and Methods: One hundred and forty-one patients with drug-resistant focal epilepsy were classified either as having seizure-free (Engel class I) or seizure-recurrence (Engel class II through IV) at least 1 year after surgery. The presurgical magnetic resonance imaging, positron emission tomography, computed tomography, and postsurgical magnetic resonance imaging were co-registered for surgical target volume of interest (VOI) segmentation; all VOIs were decomposed into nine fixed views, then were inputted into the deep residual network (DRN) that was pretrained on Tiny-ImageNet dataset to extract and transfer deep features. A multi-kernel support vector machine (MKSVM) was used to integrate multiple views of feature sets and to predict seizure outcomes of the targeted VOIs. Leave-one-out validation was applied to develop a model for verifying the prediction. In the end, performance using this approach was assessed by calculating accuracy, sensitivity, and specificity. Receiver operating characteristic curves were generated, and the optimal area under the receiver operating characteristic curve (AUC) was calculated as a metric for classifying outcomes.

Results: Application of DRN–MKSVM model based on presurgical target area neuroimaging demonstrated good performance in predicting seizure outcomes. The AUC ranged from 0.799 to 0.952. Importantly, the classification performance DRN–MKSVM model using data from multiple neuroimaging showed an accuracy of 91.5%, a sensitivity of 96.2%, a specificity of 85.5%, and AUCs of 0.95, which were significantly better than any other single-modal neuroimaging (all p ˂ 0.05).

Conclusion: DRN–MKSVM, using multimodal compared with unimodal neuroimaging from the surgical target area, accurately predicted postsurgical outcomes. The preoperative individualized prediction of seizure outcomes in patients who have been judged eligible for epilepsy surgery could be conveniently facilitated. This may aid epileptologists in presurgical evaluation by providing a tool to explore various surgical options, offering complementary information to existing clinical techniques.
Deep Learning-Based Morphological Classification of Endoplasmic Reticulum Under Stress
Authors: Guo Yuanhao , Shen Di , Zhou Yanfeng , Yang Yutong , Liang Jinzhao , Zhou Yating , Li Ningning , Liu Yu , Yang Ge , Li Wenjing
Published: January 2022

Endoplasmic reticulum stress (ER stress) is a condition that is defined by abnormal accumulation of unfolded proteins. It plays an important role in maintaining cellular protein, lipid, and ion homeostasis. By triggering the unfolded protein response (UPR) under ER stress, cells restore homeostasis or undergo apoptosis. Chronic ER stress is implicated in many human diseases. Despite extensive studies on related signaling mechanisms, reliable image biomarkers for ER stress remain lacking. To address this deficiency, we have validated a morphological image biomarker for ER stress and have developed a deep learning-based assay to enable automated detection and analysis of this marker for screening studies. Specifically, ER under stress exhibits abnormal morphological patterns that feature ring-shaped structures called whorls (WHs). Using a highly specific chemical probe for unfolded and aggregated proteins, we find that formation of ER whorls is specifically associated with the accumulation of the unfolded and aggregated proteins. This confirms that ER whorls can be used as an image biomarker for ER stress. To this end, we have developed ER-WHs-Analyzer, a deep learning-based image analysis assay that automatically recognizes and localizes ER whorls similarly as human experts. It does not require laborious manual annotation of ER whorls for training of deep learning models. Importantly, it reliably classifies different patterns of ER whorls induced by different ER stress drugs. Overall, our study provides mechanistic insights into morphological patterns of ER under stress as well as an image biomarker assay for screening studies to dissect related disease mechanisms and to accelerate related drug discoveries. It demonstrates the effectiveness of deep learning in recognizing and understanding complex morphological phenotypes of ER.
Generation of NKX2.5GFP Reporter Human iPSCs and Differentiation Into Functional Cardiac Fibroblasts
Authors: López-Muneta Leyre , Linares Javier , Casis Oscar , Martínez-Ibáñez Laura , González Miqueo Arantxa , Bezunartea Jaione , Sanchez de la Nava Ana Maria , Gallego Mónica , Fernández-Santos María Eugenia , Rodriguez-Madoz Juan Roberto , Aranguren Xabier L. , Fernández-Avilés Francisco , Segovia José Carlos , Prósper Felipe , Carvajal-Vergara Xonia
Published: January 2022

Direct cardiac reprogramming has emerged as an interesting approach for the treatment and regeneration of damaged hearts through the direct conversion of fibroblasts into cardiomyocytes or cardiovascular progenitors. However, in studies with human cells, the lack of reporter fibroblasts has hindered the screening of factors and consequently, the development of robust direct cardiac reprogramming protocols.In this study, we have generated functional human NKX2.5GFP reporter cardiac fibroblasts. We first established a new NKX2.5GFP reporter human induced pluripotent stem cell (hiPSC) line using a CRISPR-Cas9-based knock-in approach in order to preserve function which could alter the biology of the cells. The reporter was found to faithfully track NKX2.5 expressing cells in differentiated NKX2.5GFP hiPSC and the potential of NKX2.5-GFP + cells to give rise to the expected cardiac lineages, including functional ventricular- and atrial-like cardiomyocytes, was demonstrated. Then NKX2.5GFP cardiac fibroblasts were obtained through directed differentiation, and these showed typical fibroblast-like morphology, a specific marker expression profile and, more importantly, functionality similar to patient-derived cardiac fibroblasts. The advantage of using this approach is that it offers an unlimited supply of cellular models for research in cardiac reprogramming, and since NKX2.5 is expressed not only in cardiomyocytes but also in cardiovascular precursors, the detection of both induced cell types would be possible. These reporter lines will be useful tools for human direct cardiac reprogramming research and progress in this field.
Identification and Validation of a Prognostic Risk-Scoring Model Based on Ferroptosis-Associated Cluster in Acute Myeloid Leukemia
Authors: Wang Jinghua , Zhuo Zewei , Wang Yanjun , Yang Shuo , Chen Jierong , Wang Yulian , Geng Suxia , Li Minming , Du Xin , Lai Peilong , Weng Jianyu
Published: January 2022

Background: Emerging evidence has proven that ferroptosis plays an important role in the development of acute myeloid leukemia (AML), whereas the exact role of ferroptosis-associated genes in AML patients’ prognosis remained unclear.

Materials and Methods: Gene expression profiles and corresponding clinical information of AML cases were obtained from the TCGA (TCGA-LAML), GEO (GSE71014), and TARGET databases (TARGET-AML). Patients in the TCGA cohort were well-grouped into two clusters based on ferroptosis-related genes, and differentially expressed genes were screened between the two clusters. Univariate Cox and LASSO regression analyses were applied to select prognosis-related genes for the construction of a prognostic risk-scoring model. Survival analysis was analyzed by Kaplan–Meier and receiver operator characteristic curves. Furthermore, we explored the correlation of the prognostic risk-scoring model with immune infiltration and chemotherapy response. Risk gene expression level was detected by quantitative reverse transcription polymerase chain reaction.

Results: Eighteen signature genes, including ZSCAN4, ASTN1, CCL23, DLL3, EFNB3, FAM155B, FOXL1, HMX2, HRASLS, LGALS1, LHX6, MXRA5, PCDHB12, PRINS, TMEM56, TWIST1, ZFPM2, and ZNF560, were developed to construct a prognostic risk-scoring model. AML patients could be grouped into high- and low-risk groups, and low-risk patients showed better survival than high-risk patients. Area under the curve values of 1, 3, and 5 years were 0.81, 0.827, and 0.786 in the training set, respectively, indicating a good predictive efficacy. In addition, age and risk score were the independent prognostic factors after univariate and multivariate Cox regression analyses. A nomogram containing clinical factors and prognostic risk-scoring model was constructed to better estimate individual survival. Further analyses demonstrated that risk score was associated with the immune infiltration and response to chemotherapy. Our experiment data revealed that LGALS1 and TMEM56 showed notably decreased expression in AML samples than that of the normal samples.

Conclusion: Our study shows that the prognostic risk-scoring model and key risk gene may provide potential prognostic biomarkers and therapeutic option for AML patients.
C-Peptide Promotes Cell Migration by Controlling Matrix Metallopeptidase-9 Activity Through Direct Regulation of β-Catenin in Human Endometrial Stromal Cells
Authors: Abdul Khaliq Sana , Umair Zobia , Baek Mi-Ock , Chon Seung Joo , Yoon Mee-Sup
Published: January 2022

The motility of endometrial stromal cells (ESCs) contributes to the restoration of the endometrial functional layer and subsequently supports the trophoblast invasion during early pregnancy. Following ESCs differentiation through decidualization in response to progesterone during the menstrual cycle and embryo implantation, decidualized ESCs (D-ESCs) have greater motility and invasive activity. The human proinsulin-connecting peptide (C-peptide) is produced in equimolar amounts during the proteolysis of insulin in pancreatic β-cells. However, the function of C-peptide in the cellular motility of the human endometrium remains unexamined. In the present study, C-peptide was identified as a determinant of undecidualized human endometrial stromal cells (UnD-ESCs) migration. C-peptide promoted the migration and invasion of UnD-ESCs and trophoblast-derived Jeg3 cells, but not that of ESCs post decidualization, a functional and biochemical differentiation of UnD-ESCs. Both Akt and protein phosphatase 1 regulated β-catenin phosphorylation in UnD-ESCs, not D-ESCs, thereby promoting β-catenin nuclear translocation in C-peptide-treated UnD-ESCs. C-peptide was also observed to increase matrix metallopeptidase-9 (MMP9) activity by increasing MMP9 expression and decreasing the expression of metallopeptidase inhibitor 1 (TIMP1) and TIMP3. Their expression was modulated by the direct binding of β-catenin in the regulatory region of the promoter of MMP9, TIMP1, and TIMP3. Inhibition of either β-catenin or MMP9 dampened C-peptide-enhanced migration in UnD-ESCs. Together, these findings suggest that C-peptide levels are critical for the regulation of UnD-ESC migration, providing evidence for the association between C-peptide levels and the failure rate of trophoblast invasion by inducing abnormal migration in UnD-ESCs in hyperinsulinemia or PCOS patients.
Matrix Vesicles as a Therapeutic Target for Vascular Calcification
Authors: Li Tiantian , Yu Hongchi , Zhang Demao , Feng Tang , Miao Michael , Li Jianwei , Liu Xiaoheng
Published: January 2022

Vascular calcification (VC) is linked to an increased risk of heart disease, stroke, and atherosclerotic plaque rupture. It is a cell-active process regulated by vascular cells rather than pure passive calcium (Ca) deposition. In recent years, extracellular vesicles (EVs) have attracted extensive attention because of their essential role in the process of VC. Matrix vesicles (MVs), one type of EVs, are especially critical in extracellular matrix mineralization and the early stages of the development of VC. Vascular smooth muscle cells (VSMCs) have the potential to undergo phenotypic transformation and to serve as a nucleation site for hydroxyapatite crystals upon extracellular stimulation. However, it is not clear what underlying mechanism that MVs drive the VSMCs phenotype switching and to result in calcification. This article aims to review the detailed role of MVs in the progression of VC and compare the difference with other major drivers of calcification, including aging, uremia, mechanical stress, oxidative stress, and inflammation. We will also bring attention to the novel findings in the isolation and characterization of MVs, and the therapeutic application of MVs in VC.
Nitrogen Fixation at the Edges of Boron Nitride Nanomaterials: Synergy of Doping
Authors: Choutipalli Venkata Surya Kumar , Esackraj Karthikraja , Subramanian Venkatesan
Published: January 2022

Synthesis of ammonia at ambient conditions is very demanding yet challenging to achieve due to the production of ammonia fuel, which is considered to be a future fuel for sustainable energy. In this context, computational studies on the catalytic activity of the edge sites of boron nitride nanomaterials for possible nitrogen reduction into ammonia have been investigated. Geometrical and electronic properties of zigzag and armchair B-open edges of BN sheet (BOE) models have been unraveled to substantiate their catalytic nature. Results reveal that BOE sites exhibit very high potential determining steps (PDS) of 2.0 eV. Doping of carbon (C) at the nitrogen center, which is vicinal to the BOE site reduces the PDS of the N2 reduction reaction (NRR) (to 1.18–1.33 eV) due to the regulation of charge distribution around the active BOE site. Further, the NRR at the C doped at various edge sites of a boron nitride sheet (BNS) has also been studied in detail. Among the 12 new C-doped defective BNS models, 9 model catalysts are useful for nitrogen activation through either chemisorption or physisorption. Among these, ZCN, ACN, and ZCBV models are efficient in catalyzing NRR with lower PDS of 0.86, 0.88, and 0.86 eV, respectively. The effect of carbon doping in tuning the potential requirements of NRR has been analyzed by comparing the relative stability of intermediates on the catalyst with and without carbon doping. Results reveal that C-doping destabilizes the intermediates compared to non-doped systems, thereby reducing the possibility of catalyst poisoning. However, their interactions with catalysts are good enough so that the NRR activity of the catalyst does not decrease due to C-doping.
Structural Characterization and Discrimination of Morinda officinalis and Processing Morinda officinalis Based on Metabolite Profiling Analysis
Authors: Kang Liping , Zhang Yan , Zhou Li , Yang Jian , He Yali , Yang Shuai , Li Gai , Hao Qingxiu , Yu Yi , Guo Lanping
Published: January 2022

Morindae officinalis Radix (MOR) is a famous traditional Chinese medicine (TCM) and functional food material for invigorating kidneys and tonifying yang. Processed Morindae officinalis Radix (PMOR) is obtained by steaming MOR. Traditionally, the clinical effects are discrepant between processing and nonprocessing herbal medicines. MOR and PMOR are commonly used in both clinical practice and dietary supplements, and the effect of invigorating kidneys and tonifying yang of PMOR is stronger than MOR. To clarify the overall chemical composition and the difference of MOR and PMOR, a method was developed with an ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Among the 110 identified components shared by MOR and PMOR, 55 compounds showed significant differences in contents. Among them, the contents of 29 components, including fructooligosaccharides, monotropein, deacetylasperulosidic acid, geniposide, and anthraquinone glycosides, were higher in MOR than in PMOR; the contents of 26 components, including difructose anhydride sucrose, and iridoid glycoside derivatives, were higher in PMOR than in MOR. Difructose anhydrides and iridoid glycoside derivatives were first discovered in PMOR. These results provided a scientific basis for research on the therapeutic material basis of MOR. It would provide a method for the comparison of processing and nonprocessing in Chinese medicines.
Controlled Fabrication of Bioactive Microtubes for Screening Anti-Tongue Squamous Cell Migration Drugs
Authors: Tang Rongbing , Yang Lu , Shen Liheng , Ma Xuan , Gao Yinfeng , Liu Yuan , Bai Zhen , Wang Xuemei
Published: January 2022

The treatment of tongue squamous cell carcinoma (TSCC) faces challenges because TSCC has an aggressive biological behavior and manifests usually as widespread metastatic disease. Therefore, it is particularly important to screen out and develop drugs that inhibit tumor invasion and metastasis. Two-dimensional (2D) cell culture has been used as in vitro models to study cellular biological behavior, but growing evidence now shows that the 2D systems can result in cell bioactivities that deviate appreciably the in vivo response. It is urgent to develop a novel 3D cell migration model in vitro to simulate the tumor microenvironment as much as possible and screen out effective anti-migration drugs. Sodium alginate, has a widely used cell encapsulation material, as significant advantages. We have designed a microfluidic device to fabricate a hollow alginate hydrogel microtube model. Based on the difference in liquid flow rate, TSCC cells (Cal27) were able to be evenly distributed in the hollow microtubes, which was confirmed though fluorescence microscope and laser scanning confocal microscope (LSCM). Our microfluidic device was cheap, and commercially available and could be assembled in a modular way, which are composed of a coaxial needle, silicone hose, and syringes. It was proved that the cells grow well in artificial microtubes with extracellular matrix (ECM) proteins by LSCM and flow cytometry. Periodic motility conferred a different motor state to the cells in the microtubes, more closely resembling the environment in vivo. The quantitative analysis of tumor cell migration could be achieved simply by determining the position of the cell in the microtube cross-section. We verified the anti-migration effects of three NSAIDs drugs (aspirin, indomethacin, and nimesulide) with artificial microtubes, obtaining the same results as conventional migration experiments. The results showed that among the three NSAIDs, nimesulide showed great anti-migration potential against TSCC cells. Our method holds great potential for application in the more efficient screening of anti-migration tumor drugs.
Wolbachia Utilizes lncRNAs to Activate the Anti-Dengue Toll Pathway and Balance Reactive Oxygen Species Stress in Aedes aegypti Through a Competitive Endogenous RNA Network
Authors: Mao Wei , Zeng Qin , She Lingzhi , Yuan Hao , Luo Yuying , Wang Renke , She Yueting , Wang Weifeng , Wang Chaojun , Pan Xiaoling
Published: January 2022

Long non-coding RNAs (lncRNA), a class of RNA molecules without protein coding potential, are more than 200 nucleotides in length and widely present in a variety of species. Although increasing progress in regard to the determination of lncRNA function has been made in vertebrates, Aedes aegypti lncRNAs were only identified recently and the functions of few lncRNAs have been annotated so far. Herein, the genome-wide alteration of the lncRNA expression profile trigged by Wolbachia wAlbB infection was investigated by comparing A. aegypti Aag2 cells and W-Aag2 cells infected with Wolbachia wAlbB. Based on lncRNA sequencing, 3035 differentially expressed lncRNAs (DE lncRNAs) in total were identified upon Wolbachia infection, which were further validated by quantitative PCR. The constructed co-expression network of DE lncRNAs and mRNAs revealed that Wolbachia-induced DE lncRNAs were highly enriched in the oxidative phosphorylation pathway via trans-activity, according to the KEGG pathway enrichment analyses. In addition, the established competitive endogenous RNA (ceRNA) network identifies the DE lncRNAs enriched in cellular oxidant detoxification based on GO enrichment analysis. Furthermore, silencing of aae-lnc-7598, the significantly up-regulated lncRNA with the highest fold change induced by Wolbachia, caused a significant reduction of antioxidant catalase 1B (CAT1B) gene expression as well as the enhancement of mitochondrial reactive oxygen species (ROS) production in living cells. These findings indicate that Wolbachia manipulates lncRNA to balance intracellular ROS stress and ensure its endosymbiosis in host A. aegypti. Notably, the function assay demonstrated that aae-lnc-0165 suppressed by Wolbachia could induce expression of the REL1 gene, the key regulator of downstream Toll pathway, through the sequence-specific binding of aae-miR-980-5p, which contributes to the activation of Toll pathway. Moreover, the depletion of aae-lnc-0165 caused the suppression of mitochondrial ROS levels in living cells. Our data reveal that Wolbachia activates the anti-dengue Toll pathway through a lncRNA-ceRNA pattern. Taken together, our finding suggested that Wolbachia utilizes lncRNAs to activate host anti-dengue Toll pathway via a ceRNA network. Moreover, Wolbachia employs lncRNAs to ensure ROS homeostasis for ROS-based anti-dengue defense through either trans-regulation or the ceRNA network. This study identifies novel potential molecular biomarkers for prevention and control of epidemic dengue.
Paradox of Success-Mediated Conflicts: Analysing Attitudes of Local Communities Towards Successfully Reintroduced Tigers in India
Authors: Malviya Manjari , Kalyanasundaram Sankar , Krishnamurthy Ramesh
Published: January 2022

Conservation programs such as reintroductions are pivotal for the survival and proliferation of endangered species like tigers. However, restoring a carnivore population may create unforeseen problems for communities by fuelling human-wildlife conflict. The long-term persistence of tigers can only be ensured when the support of these local communities is garnered for conservation efforts, especially in release sites from where they were initially eliminated due to anthropogenic causes. The first step to gaining support for tigers and their reintroduction programs is to understand how local communities perceive these large carnivores. This study thus assessed the attitudes of local communities towards the reintroduced tigers of India, in the Panna and Sariska Tiger Reserves, and examined the socio-economic factors that potentially shape their attitudes. Questionnaire surveys were conducted in 330 households across 25 villages in Panna, and 361 households across 32 villages in Sariska. Decision tree and multinomial logistic regression analyses were employed to identify the explanatory variables associated with attitudes. In Panna, more respondents (52.12%) expressed negative opinions about tigers, as compared to positive (24.55%). Whereas in Sariska, more respondents had positive opinions (47.92%) than negative (34.90%). In both the sites, the most frequent reason given by the respondents for their negative attitude towards tigers was “fear.” Regression modelling suggests that gender and education are key factors associated with the attitude of local communities towards reintroduced tigers. Other factors, specific to the reserves, were the age of the respondent, age of lost livestock, compensation received, and value of fodder obtained from the reserve. Community engagement must be integrated into conservation projects with a focus on educating women and the elderly about carnivores, protecting the traditional rights of local communities, and compensating for their losses.
Relationship Between the Lipid Accumulation Product Index and Arterial Stiffness in the Chinese Population With Hypertension: A Report From the China H-Type Hypertension Registry Study
Authors: Shi Yumeng , Hu Lihua , Li Minghui , Zhou Wei , Wang Tao , Zhu Lingjuan , Bao Huihui , Li Ping , Cheng Xiaoshu
Published: January 2022

Background

Lipid accumulation product (LAP) index, as a new index to predict cardiovascular disease (CVD), has attracted the attention of many researchers. The relation of the LAP index with brachial-ankle pulse wave velocity (baPWV) has been evaluated in several previous studies and yielded inconsistent results. This study aimed to investigate the association between the LAP index and arterial stiffness in the Chinese population with hypertension.

Methods

We conducted a cross-sectional analysis in 4,926 Chinese population with hypertension (aged 64.42 ± 9.44 years). The LAP index was developed from population-based frequency plots of adult waist circumferences and circulating triglyceride concentrations according to men and women. Arterial stiffness was determined by measuring baPWV.

Results

The multivariate linear regression analyses showed that the LAP index was independently and positively associated with baPWV [beta coefficients (β), 24.10 cm/s; 95% CI: 5.72, 42.49 cm/s]. Consistently, the multivariate logistic regression analyses showed a positive association between the LAP index risk of elevated baPWV (>75th percentile) [odds ratio (OR), 1.19; 95% CI 1.01, 1.41]. A restricted cubic spline showed that a significant linear association existed between the LAP index and baPWV. In different subgroups of diastolic blood pressure (DBP), there is interaction between the LAP index and baPWV (DBP <90, 90–99, ≥100 mm Hg; p-interaction = 0.006).

Conclusion

LAP is significantly positively associated with baPWV and elevated baPWV in Chinese hypertensive adults and especially among participants with DBP ≤ 99 mm Hg.
Right Ventricular Flow Vorticity Relationships With Biventricular Shape in Adult Tetralogy of Fallot
Authors: Elsayed Ayah , Mauger Charlène A. , Ferdian Edward , Gilbert Kathleen , Scadeng Miriam , Occleshaw Christopher J. , Lowe Boris S. , McCulloch Andrew D. , Omens Jeffrey H. , Govil Sachin , Pushparajah Kuberan , Young Alistair A.
Published: January 2022

Remodeling in adults with repaired tetralogy of Fallot (rToF) may occur due to chronic pulmonary regurgitation, but may also be related to altered flow patterns, including vortices. We aimed to correlate and quantify relationships between vorticity and ventricular shape derived from atlas-based analysis of biventricular shape. Adult rToF (n = 12) patients underwent 4D flow and cine MRI imaging. Vorticity in the RV was computed after noise reduction using a neural network. A biventricular shape atlas built from 95 rToF patients was used to derive principal component modes, which were associated with vorticity and pulmonary regurgitant volume (PRV) using univariate and multivariate linear regression. Univariate analysis showed that indexed PRV correlated with 3 modes (r = −0.55,−0.50, and 0.6, all p < 0.05) associated with RV dilatation and an increase in basal bulging, apical bulging and tricuspid annulus tilting with more severe regurgitation, as well as a smaller LV and paradoxical movement of the septum. RV outflow and inflow vorticity were also correlated with these modes. However, total vorticity over the whole RV was correlated with two different modes (r = −0.62,−0.69, both p < 0.05). Higher vorticity was associated with both RV and LV shape changes including longer ventricular length, a larger bulge beside the tricuspid valve, and distinct tricuspid tilting. RV flow vorticity was associated with changes in biventricular geometry, distinct from associations with PRV. Flow vorticity may provide additional mechanistic information in rToF remodeling. Both LV and RV shapes are important in rToF RV flow patterns.
Mesoscopic Characteristics and Performance Evaluation of Loess Treated by Different Anti-Seismic Subsidence Technologies
Authors: Wang Ping , Xu Shuya , Shao Shengjun , Wang Huijuan , Li Xudong , Qian Ziling
Published: January 2022

The meso-structure of the soil has an important restriction on its engineering properties. Based on dynamic triaxial tests and SEM meso-structure test experiments, this study investigated the meso-scale structural deformation characteristics of Q3 loess samples treated by physical, chemical, and compound improvement methods, before and after strong earthquakes of typical seismic subsidence loess. On this basis, the seismic subsidence performance of the improved method is given under the conditions of frequent earthquakes, fortifying earthquakes, and rare earthquakes. The results show that 1) the physical improvement method has the most obvious effect on the elimination of macropores and overhead pore structures; 2) the chemical method can generate unique glass beads or flocculated fine structures, which can greatly enhance the strength of the soil and play the role of filling, cementing, or buffering, respectively, in the event of a strong earthquake; 3) for several improved treatment methods, the amount of seismic subsidence increases non-linearly with the increase in peak acceleration; and 4) in the event of frequent earthquakes, the earthquake subsidence can be eliminated by the method of adding fly ash, and when the fortification earthquake comes, the dynamic composite method can completely eliminate the seismic subsidence of the site. The related results can give reasonable suggestions for the treatment of seismic subsidence of different foundations in the “resilient urban and rural” and key engineering construction and seismic design of China’s loess area.
Topographic and Climatic Control on Chemical Weathering of Mountainous Riverine Sediments of Hainan Island, South China Sea
Authors: Xu Fangjian , Hu Bangqi , Zhao Jingtao , Liu Xiting , Cui Ruyong , Ding Xue , Wang Guifeng , Huang Jianping
Published: January 2022

Hainan Island, the largest island in the northwestern South China Sea (SCS), is characterized by many tropical mountainous rivers that flow into the SCS. The geochemistry of these riverine sediments and the factors controlling the weathering intensity are still not well understood. In this study, sedimentary geochemistry has been investigated by using 45 riverine sediments collected from 18 major rivers on Hainan Island. The Hainan riverine sediments are only first-cycle rather than polycyclic sediments, and they faithfully reflect the present weathering intensity. The high and steady values of the Chemical Index of Alteration (CIA) indicate that the riverine sediments at different parts of the Hainan Island have overall undergone intensive chemical weathering. The low values of Weathering Index of Parker (WIP) and high αCa, αK, αSr, and αBa values of north Hainan indicate the highest weathering degree, which is mainly influenced by the flat topography. The values of αNa, αK, αSr, and αBa of southwest Hainan which are higher than those of east Hainan suggest that the leaching of elements such as Na, K, Sr, and Ba is more extreme (i.e., more intensive weathering). These are mainly caused by the different physical denudation due to different summer precipitation. Overall, the Hainan Island is featured by intensive chemical weathering and is classified as a typical transport-limited weathering regime. Therefore, the geochemistry of the riverine sediments of the Hainan Island is different from that of sediments in tectonically active regions (e.g., Taiwan Island).
Mixed Integration Scheme for Embedded Discontinuous Interfaces by Extended Finite Element Method
Authors: Yu Peng , Hao Qingshuo , Wang Xiangnan , Yu Yuzhen , Zhan Zhenggang
Published: January 2022

The extended Finite Element Method (XFEM) is derived from the traditional finite element method for discontinuous problems. It can simulate the behavior of cracks, which significantly improves the ability of finite element methods to simulate geotechnical and geological disaster problems. The integration of discontinuous enrichment functions in weak form and the ill-conditioning of the system equations are two major challenges in employing the XFEM in engineering applications. A mixed integration scheme is proposed in this paper to solve these problems. This integration scheme has a simple form and exhibits both the accuracy of the subcell integration method and the well-conditioning of a smeared integration method. The correctness and effectiveness of the proposed scheme were verified through a series of element analyses and two typical examples. For XFEM numerical simulations with unstructured meshes and arbitrary cracks/interfaces, this method guarantees the convergence of nonlinear iterations and yields correct results.
Quantification of Bedding Rock Slope Deformation Rate Using Guided Wave Monitoring
Authors: Zheng Changsong , He Wen , Huang Chongjie , Chen Hao , Xiao Changbo
Published: January 2022

The guided wave technique is applied to slope stability monitoring to overcome the high attenuation characteristics of acoustic emission propagation in rock and soil materials. The shear tests of “guided wave meter” (GWM) with different deformation rates were carried out, and the effects of the material and particle size of the coupling medium and the diameter of the waveguide rod on the flexural guided wave ring down count were studied, and the relationship between the deformation rate of the slope and the flexural guided wave parameters was analyzed. The results show that the flexural guided wave ring down count rate increases with the increase of deformation in the loading process. The GWM filled with quartz sand particles produces more flexural guided wave ring down counts than those filled with gravel particles. From the twelve groups of GWM shear tests, it can be seen that the GWM with the combination of 16 mm waveguide rod and 4–8 mm quartz sand produces the highest cumulative flexural guided wave ring down counts. The combination is used as an optimized GWM. By applying different deformation rates to the optimized GWM, it was found that the flexural guided wave ring down count rate at different deformation rates tended to increase and was distributed in a fan shape. The cumulative flexural guided wave ring down count has an excellent linear correlation with the deformation. The slope of the cumulative ring down count curves and the deformation curves are obtained separately, which shows that the deformation rate has an excellent linear relationship with the slope of the cumulative ring down count curve, and the slope of the cumulative ring down count curve increases with the increase of the deformation rate. It provides theoretical guidance for quantifying the slope deformation rate using the flexural guided waves.