bluuebunny/crossref_metadata_2025 huggingface dataset:
The Urgency of Regulating Tax Law for Vehicles After Natural Disasters in Indonesia
Authors: Asriyani Asriyani , Syamsuddin Adiesty Septhiany Prihatiningsih , Rory Soleman S
Published: February 2022

The occurrence of a natural disaster on 28 September 2018 in the province of Central Sulawesi Indonesia caused vehicle tax arrears to be incurred by people who were victims of natural disasters. This research is socio-legal research with a statutory and comparative approach to find out the legal arrangements related to tax collection after natural disasters and to compare it with the practices in New South Wales, Australia. This study concluded that there is no specific regulation that differentiates the mechanism of tax collection during normal times and the period after a natural disaster in Indonesia. Local governments are given the authority to regulate it based on the scale of the disaster and the affected areas/people in which people lose their homes and livelihoods so they cannot fulfill their obligations to pay for vehicle tax. This resulted in the arrears of tax collection carried out by the fiscus and become an obstacle for local governments to collect taxes as a source of financing rebuilding infrastructure after a natural disaster. As a comparison, an integrated tax reduction system was applied for disaster victims in New South Wales, including for the vehicle tax. The whole process was done online. Indonesia needs to build such a system to anticipate the bad impact of tax collection that can make disaster victims suffer psychologically.
Fulfilling the Right of Education during Covid19 Pandemic Period: A Comparative Study
Authors: Christianto Hwian , Kristina Michelle
Published: February 2022

The right of education for citizens has been fulfilled diversely following the government policies. This study aimed to emphasize the importance of the education right and the imposition of criminal sanctions in order to protect the right of education during the Covid-19 Pandemic particularly in Indonesia, Japan and Australia. Normative juridical research methods described that government policies as outlined in the legislation constantly followed by criminal sanctions. The concept of education right was understood in a different way during the Covid-19 pandemic, as one of the derogable-right or adapted human right. For its fulfillment, some education right uses criminal sanctions as a primum remidium, an ultimum remidium, or does not impose criminal sanctions at all. The right of education still reman as a very important human right even during the pandemic period
Clinical Significance of TET2 in Female Cancers
Authors: Wan Fang , Chen Fangfang , Fan Yangfan , Chen Deqin
Published: February 2022

Female cancers refer to malignant tumors of the female reproductive system and breasts, which severely affect the physical and mental health of women. Although emerging experiment-based studies have indicated a potential correlation between ten-eleven translocation methylcytosine dioxygenase (TET2) and female cancers, no comprehensive studies have been conducted. Therefore, this study aimed to summarize the clinical value and underlying oncogenic functions of TET2 in female cancers, such as breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), ovarian serous cystadenocarcinoma (OV), uterine corpus endometrial carcinoma (UCEC), and uterine carcinosarcoma (UCS), based on the data obtained from The Cancer Genome Atlas. The expression of TET2 was decreased in most female cancers, and its high expression was distinctly associated with the favorable prognosis of most female cancers. Furthermore, CD8+ T-cell infiltration was not correlated with TET2 in OV, UCEC, and UCS, whereas tumor-associated fibroblast infiltration was significantly correlated with TET2 in BRCA, CESC, and OV. TET2 was co-expressed with the immune checkpoint molecules ADORA2A, CD160, CD200, CD200R1, CD44, CD80, NRP1 TNFSF4, and TNFSF15 in most female cancers. Enrichment analysis revealed that some signaling pathways involving TET2 and related genes were related to tumorigenesis. Immunohistochemical and immunofluorescence staining confirmed the results of cancer immune infiltration analysis in BRCA tissues. Therefore, this study provides evidence for the oncogenic functions and clinical value of TET2 in female cancers.
MHC-II Signature Correlates With Anti-Tumor Immunity and Predicts anti-PD-L1 Response of Bladder Cancer
Authors: Yi Ruibin , Hong Shuo , Zhang Yueming , Lin Anqi , Ying Haoxuan , Zou Weidong , Wang Qiongyao , Wei Ting , Cheng Quan , Zhu Weiliang , Luo Peng , Zhang Jian
Published: February 2022

A large proportion of anti-tumor immunity research is focused on major histocompatibility complex class I (MHC-I) molecules and CD8+ T cells. Despite mounting evidence has shown that CD4+ T cells play a major role in anti-tumor immunity, the role of the MHC-II molecules in tumor immunotherapy has not been thoroughly researched and reported. In this study, we defined a MHC-II signature for the first time by calculating the enrichment score of MHC-II protein binding pathway with a single sample gene set enrichment analysis (ssGSEA) algorithm. To evaluate and validate the predictive value of the MHC class II (MHC-II) signature, we collected the transcriptome, mutation data and matched clinical data of bladder cancer patients from IMvigor210, The Cancer Genome Atlas (TCGA) databases and Gene Expression Omnibus (GEO) databases. Comprehensive analyses of immunome, transcriptome, metabolome, genome and drugome were performed in order to determine the association of MHC-II signature and tumor immunotherapy. We identified that MHC-II signature is an independent and favorable predictor of immune response and the prognosis of bladder cancer treated with immune checkpoint inhibitors (ICIs), one that may be superior to tumor mutation burden. MHC-II signature was significantly associated with increased immune cell infiltration and levels of immune-related gene expression signatures. Additionally, transcriptomic analysis showed immune activation in the high-MHC-II signature subgroup, whereas it showed fatty acid metabolism and glucuronidation in the low-MHC-II signature subgroup. Moreover, exploration of corresponding genomic profiles highlighted the significance of tumor protein p53 (TP53) and fibroblast growth factor receptor 3 (FGFR3) alterations. Our results also allowed for the identification of candidate compounds for combined immunotherapy treatment that may be beneficial for patients with bladder cancer and a high MHC-II signature. In conclusion, this study provides a new perspective on MHC-II signature, as an independent and favorable predictor of immune response and prognosis of bladder cancer treated with ICIs.
Protein Posttranslational Signatures Identified in COVID-19 Patient Plasma
Authors: Vedula Pavan , Tang Hsin-Yao , Speicher David W. , Kashina Anna ,   The UPenn COVID Processing Unit
Published: February 2022

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious virus of the coronavirus family that causes coronavirus disease-19 (COVID-19) in humans and a number of animal species. COVID-19 has rapidly propagated in the world in the past 2 years, causing a global pandemic. Here, we performed proteomic analysis of plasma samples from COVID-19 patients compared to healthy control donors in an exploratory study to gain insights into protein-level changes in the patients caused by SARS-CoV-2 infection and to identify potential proteomic and posttranslational signatures of this disease. Our results suggest a global change in protein processing and regulation that occurs in response to SARS-CoV-2, and the existence of a posttranslational COVID-19 signature that includes an elevation in threonine phosphorylation, a change in glycosylation, and a decrease in arginylation, an emerging posttranslational modification not previously implicated in infectious disease. This study provides a resource for COVID-19 researchers and, longer term, and will inform our understanding of this disease and its treatment.
Intragenic CpG Islands and Their Impact on Gene Regulation
Authors: Cain James A. , Montibus Bertille , Oakey Rebecca J.
Published: February 2022

The mammalian genome is depleted in CG dinucleotides, except at protected regions where they cluster as CpG islands (CGIs). CGIs are gene regulatory hubs and serve as transcription initiation sites and are as expected, associated with gene promoters. Advances in genomic annotations demonstrate that a quarter of CGIs are found within genes. Such intragenic regions are repressive environments, so it is surprising that CGIs reside here and even more surprising that some resist repression and are transcriptionally active within a gene. Hence, intragenic CGI positioning within genes is not arbitrary and is instead, selected for. As a wealth of recent studies demonstrate, intragenic CGIs are embedded within genes and consequently, influence ‘host’ gene mRNA isoform length and expand transcriptome diversity.
A Pathway Towards Net-Zero Emissions in Oil Refineries
Authors: Sunny Nixon , Bernardi Andrea , Danaci David , Bui Mai , Gonzalez-Garay Andres , Chachuat Benoît
Published: February 2022

Rapid industrialization and urbanization have increased the demand for both energy and mobility services across the globe, with accompanying increases in greenhouse gas emissions. This short paper analyzes strategic measures for the abatement of CO2 emissions from oil refinery operations. A case study involving a large conversion refinery shows that the use of post-combustion carbon capture and storage (CCS) may only be practical for large combined emission point sources, leaving about 30% of site-wide emissions unaddressed. A combination of post-combustion CCS with a CO2 capture rate well above 90% and other mitigation measures such as fuel substitution and emission offsets is needed to transition towards carbon-neutral refinery operations. All of these technologies must be configured to minimize environmental burden shifting and scope 2 emissions, whilst doing so cost-effectively to improve energy access and affordability. In the long run, scope 3 emissions from the combustion of refinery products and flaring must also be addressed. The use of synthetic fuels and alternative feedstocks such as liquefied plastic waste, instead of crude oil, could present a growth opportunity in a circular carbon economy.
Metallocavitins as Promising Industrial Catalysts: Recent Advances
Authors: Shteinman Albert A.
Published: February 2022

The energy, material, and environmental problems of society require clean materials and impose an urgent need to develop effective chemical processes for obtaining and converting energy to ensure further sustainable development. To solve these challenges, it is necessary, first of all, to learn solar energy harvesting through the development of artificial photosynthesis. In our planet, water, carbon dioxide, and methane are such affordable and inexhaustible clean materials. Electro/photocatalytic water splitting, and also CO2 and CH4 transforming into valuable products, requires the search for relevant efficient and selective processes and catalysts. Of great interest is the emerging new generation of bioinspired catalysts—metallocavitins (MCs). MCs are attracting increasing attention of researchers as advanced models of metalloenzymes, whose efficiency and selectivity are well known. The primary field of MC application is fine organic synthesis and enantioselective catalysis. On the other hand, MCs demonstrate high activity for energy challenging reactions involving small gas molecules and high selectivity for converting them into valuable products. This mini-review will highlight some recent advances in the synthesis of organic substances using MCs, but its main focus will be on the rapid development of advanced catalysts for the activation of small molecules, such as H2O, CO2, and CH4, and the prospects for creating related technological processes in the future.
Trypanosoma Species in Small Nonflying Mammals in an Area With a Single Previous Chagas Disease Case
Authors: Dario Maria Augusta , Lisboa Cristiane Varella , Xavier Samanta Cristina das Chagas , D’Andrea Paulo Sérgio , Roque André Luiz Rodrigues , Jansen Ana Maria
Published: February 2022

Trypanosomatids are hemoflagellate parasites that even though they have been increasingly studied, many aspects of their biology and taxonomy remain unknown. The aim of this study was to investigate the Trypanosoma sp. transmission cycle in nonflying small mammals in an area where a case of acute Chagas disease occurred in Mangaratiba municipality, Rio de Janeiro state. Three expeditions were conducted in the area: the first in 2012, soon after the human case, and two others in 2015. Sylvatic mammals were captured and submitted to blood collection for trypanosomatid parasitological and serological exams. Dogs from the surrounding areas where the sylvatic mammals were captured were also tested for T. cruzi infection. DNA samples were extracted from blood clots and positive hemocultures, submitted to polymerase chain reaction targeting SSU rDNA and gGAPDH genes, sequenced and phylogenetic analysed. Twenty-one wild mammals were captured in 2012, mainly rodents, and 17 mammals, mainly marsupials, were captured in the two expeditions conducted in 2015. Only four rodents demonstrated borderline serological T. cruzi test (IFAT), two in 2012 and two in 2015. Trypanosoma janseni was the main Trypanosoma species identified, and isolates were obtained solely from Didelphis aurita. In addition to biological differences, molecular differences are suggestive of genetic diversity in this flagellate species. Trypanosoma sp. DID was identified in blood clots from D. aurita in single and mixed infections with T. janseni. Concerning dogs, 12 presented mostly borderline serological titers for T. cruzi and no positive hemoculture. In blood clots from 11 dogs, T. cruzi DNA was detected and characterized as TcI (n = 9) or TcII (n = 2). Infections by Trypanosoma rangeli lineage E (n = 2) and, for the first time, Trypanosoma caninum, Trypanosoma dionisii, and Crithidia mellificae (n = 1 each) were also detected in dogs. We concluded that despite the low mammalian species richness and degraded environment, a high Trypanosoma species richness species was being transmitted with the predominance of T. janseni and not T. cruzi, as would be expected in a locality of an acute case of Chagas disease.
Metagenomic Analysis of Togaviridae in Mosquito Viromes Isolated From Yunnan Province in China Reveals Genes from Chikungunya and Ross River Viruses
Authors: Feng Guanrong , Zhang Jinyong , Zhang Ying , Li Chenghui , Zhang Duo , Li Yiquan , Zhou Hongning , Li Nan , Xiao Pengpeng
Published: February 2022

We collected 5,500 mosquitoes belonging to six species in three locations in China. Their viromes were tested using metagenomic sequencing and bioinformatic analysis. The affluent viral sequences that were detected and annotated belong to 22 viral taxonomic families. Then, PCR was performed to confirm the results, followed by phylogenetic analysis. Herein, part of mosquito virome was identified, including chikungunya virus (CHIKV), Getah virus (GETV), and Ross river virus (RRV). After metagenomic analysis, seven CHIKV sequences were verified by PCR amplification, among which CHIKV-China/YN2018-1 had the highest homology with the CHIKV isolated in Senegal, 1983, with a nucleotide (nt) identity of at least 81%, belonging to genotype West Africa viral genes. Five GETV sequences were identified, which had a high homology with the GETV sequences isolated from Equus caballus in Japan, 1978, with a (nt) identity of at least 97%. The newly isolated virus CHIKV-China/YN2018-1 became more infectious after passage of the BHK-21 cell line to the Vero cell line. The newly identified RRV gene had the highest homology with the 2006 RRV isolate from Australia, with a (nt) identity of at least 94%. In addition, numerous known and unknown viruses have also been detected in mosquitoes from Yunnan province, China, and propagation tests will be carried out.
Case Series: Extracorporeal Shockwave Myocardial Revascularization Therapy Improves Ischemic Response, Functional Capacity, and Quality of Life in Indicated CABG-Stable Angina Pectoris Patients
Authors: Akbar Mohammad Rizki , Adiputro Dwi Laksono , Tiksnadi Badai Bhatara , Soeriadi Erwin Affandi , Hasan Melawati , Muttaqien Fauzan , Raharjo Pradana Pratomo , Nurazizah Eliza , Tarsidin Najmi Fauzan
Published: February 2022

Introduction

Extracorporeal shockwave myocardial revascularization (ESMR) is included in the guidelines only for patients with refractory angina pectoris having no option for invasive revascularization. We intend to report a case series with ESMR therapy is indicated patients with coronary artery bypass grafting-stable angina pectoris (CABG-SAP) who refuse the surgery, irrespective of angina symptoms.

Methods

We review medical records of patients with SAP admitted to ESMR therapy in Dr. Hasan Sadikin General Hospital, Bandung, Indonesia from January 2018 to December 2019. Recorded variables at baseline and after therapy extracted, namely, (1) ischemic response, double product, and (2) functional capacity measured as metabolic equivalent (MET) using treadmill test; (3) six-minute walking test distance achieved; and (4) quality of life using SF-36 Questionnaire.

Results

A total of four indicated patients with CABG-SAP from 50 to 75 years old were included in this study. At baseline, one patient is CCS class I and two patients are CCS class II with SDS ranging from 3 to 17. Ischemic response improved in all the patients. The double product improved in patient 1 9,600–14,872 mm Hg × bpm, patient 2 9,460–10,640 mm Hg × bpm, and patient 4 17,220–20,480 mm Hg × bpm. The functional capacity improved in Patient 1 8.07–8.91 METs, patient 2 1.91–4.01 METs, patient 3 3.45–6.39 METs, and patient 4 3.9–4.43 METs. The 6-min walking distance improved in patient 1 540–570 m and patient 2 345–405 m. The CCS class, bodily pain, and general health domain scores improved in all patients.

Conclusion

ESMR therapy might be beneficial for indicated patients with CABG-SAP to improve ischemic response, functional capacity, and physical component of quality of life.
Predicting Diagnostic Gene Biomarkers Associated With Immune Checkpoints, N6-Methyladenosine, and Ferroptosis in Patients With Acute Myocardial Infarction
Authors: Tong Xiao , Zhao Xinyi , Dang Xuan , Kou Yan , Kou Junjie
Published: February 2022

This study aimed to determine early diagnosis genes of acute myocardial infarction (AMI) and then validate their association with ferroptosis, immune checkpoints, and N6-methyladenosine (m6A), which may provide a potential method for the early diagnosis of AMI. Firstly, we downloaded microarray data from NCBI (GSE61144, GSE60993, and GSE42148) and identified differentially expressed genes (DEGs) in samples from healthy subjects and patients with AMI. Also, we performed systematic gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and used STRING to predict protein interactions. Moreover, MCC and MCODE algorithms in the cytoHubba plug-in were used to screen nine key genes in the network. We then determined the diagnostic significance of the nine obtained DEGs by plotting receiver operating characteristic curves using a multiscale curvature classification algorithm. Meanwhile, we investigated the relationship between AMI and immune checkpoints, ferroptosis, and m6A. In addition, we further validated the key genes through the GSE66360 dataset and consequently obtained nine specific genes that can be used as early diagnosis biomarkers for AMI. Through screening, we identified 210 DEGs, including 53 downregulated and 157 upregulated genes. According to GO, KEGG, and key gene screening results, FPR1, CXCR1, ELANE, TLR2, S100A12, TLR4, CXCL8, FPR2 and CAMP could be used for early prediction of AMI. Finally, we found that AMI was associated with ferroptosis, immune checkpoints, and m6A and FPR1, CXCR1, ELANE, TLR2, S100A12, TLR4, CXCL8, FPR2 and CAMP are effective markers for the diagnosis of AMI, which can provide new prospects for future studies on the pathogenesis of AMI.
The Joint Effects of Acoustic and Linguistic Markers for Early Identification of Mild Cognitive Impairment
Authors: Tang Fengyi , Chen Jun , Dodge Hiroko H. , Zhou Jiayu
Published: February 2022

In recent years, behavioral markers such as spoken language and lexical preferences have been studied in the early detection of mild cognitive impairment (MCI) using conversations. While the combination of linguistic and acoustic signals have been shown to be effective in detecting MCI, they have generally been restricted to structured conversations in which the interviewee responds to fixed prompts. In this study, we show that linguistic and acoustic features can be combined synergistically to identify MCI in semi-structured conversations. Using conversational data from an on-going clinical trial (Clinicaltrials.gov: NCT02871921), we find that the combination of linguistic and acoustic features on semi-structured conversations achieves a mean AUC of 82.7, significantly (p < 0.01) out-performing linguistic-only (74.9 mean AUC) or acoustic-only (65.0 mean AUC) detections on hold-out data. Additionally, features (linguistic, acoustic and combination) obtained from semi-structured conversations outperform their counterparts obtained from structured weekly conversations in identifying MCI. Some linguistic categories are significantly better at predicting MCI status (e.g., death, home) than others.
Effect of Velocity Anisotropy in Shale on the Acoustic Emission Events Matching and Location
Authors: Wang Peng , Zhang Feng , Li Xiang-Yang
Published: February 2022

Accurate source event location is important in fracturing monitoring and characterization. Velocity anisotropy has a great influence on both events matching and events location. Failure to take into account the velocity anisotropy can lead to huge errors in locating events. In this article, we have presented an experimental study on lower Silurian shale from the Sichuan Basin. The experimental observations include ultrasonic measurements, acoustic emissions (AEs) in a three-point bend experiment, and CT scanning of the original sample and the fractured sample. The ultrasonic measurements show that the shale sample has strong velocity anisotropy. Initially, AEs are analyzed using the conventional event-matching method and event location method (Geiger’s method), and the detected events are compared to the X-ray image of the fracture. Event-matching aims to obtain AE signals from the same source event and thus assists in selecting valid AE signals that come from the same source and are received by at least four sensors, to determine the location of the source. Although many reliable signals are obtained by isotropic event-matching, fewer sources were located than expected, and the event location results did not match the fracture distribution. To address this problem, an improved event-matching method is proposed using a stricter matching threshold based on directional velocity rather than a single threshold same for all directions. In addition, we propose an improved Geiger’s method using the anisotropic velocity model. The new methods located more sources that better match fracture distribution than the results of the isotropic method. We have concluded that both event-matching and the source location of the fracturing are largely influenced by velocity anisotropy, and thus in practice, the velocity anisotropy information obtained from various measurements (e.g., laboratory measurements, well logs, VSP, and velocity analysis of reflected seismic surveys) should be involved in both processing procedures. This study can be useful to provide some background for monitoring and predicting dynamic geo-hazards in relation to the AE method.
Time-Dependent Framework for Analyzing Emergency Intervention Travel Times and Risk Implications due to Earthquakes. Bucharest Case Study
Authors: Toma-Danila D. , Tiganescu A. , D’Ayala D. , Armas I. , Sun L.
Published: February 2022

Earthquakes can generate a significant number of casualties within seconds, as well as high economic losses. The lack of rapid and coordinated emergency intervention can contribute to much greater losses. In this paper we develop a framework taking advantage of the ArcGis Network Analyst extension, able to account for post-earthquake conditions and reflect travel times. By combining 1) network characteristics with 2) direct seismic damage information, 3) models to determine road obstruction potential, 4) traffic information and time-dependent post-earthquake modeling but also 5) emergency intervention facilities (hospitals or fire stations) and considerations regarding their functional limitations, this framework can provide important support for the management of emergency intervention but also for risk reduction planning. Main results consist of maps showing travel times for various scenarios and moments after an earthquake, inaccessible areas, vital roads for access or an identification of important facilities. As case study we chose Bucharest, one of Europe’s most endangered capitals considering the seismic risk level. The city was and could be considerably affected by earthquakes in the Vrancea Seismic Zone, being characterized by a high number of vulnerable buildings and by one of the greatest typical traffic congestion levels in the world. Compared to previous network studies for Bucharest, the new approach is more complex and customable, providing means for real-time integration and time-dependent analysis. Results, for a worst-case scenario, prove that the risks could be even greater than expected, but also what should be done to mitigate them, such as the construction of a new hospital in the western part of the city, ensuring safe delimited routes for emergency vehicles or expanding the treatment capacity of actual hospitals—some of which also need seismic retrofitting. Results of this study will be integrated in the revised version of the National Conception for Post-Earthquake Response—an operational framework which will lead to risk mitigation through the improvement of post-disaster reaction.
Exploring the Relational Embeddedness of Higher Educational Students During Hungarian Emergency Remote Teaching
Authors: Győri Krisztina , Pusztai Gabriella
Published: February 2022

In 2020, the researchers started studying with utmost haste the effect of the COVID-19 pandemic on teaching. The name of the form of teaching that came to be is disputed, neither the phrase of distance teaching nor digital teaching are professional enough. We use the term of emergency remote teaching (henceforth ERT), which appears in the scientific literature. This refers to the periodical diversion from the normal teaching, and to the emergency distancing in the teaching processes as well. In the present study, we focus on the alteration of student relationships and its correlation with higher educational efficiency because we see the reduction of student relationships as a discriminatory factor of this period. According to the previous results, the institutional embeddedness of students to be an indispensable condition of educational efficiency. In our study, we compared the states of the student relationships before and during the ERT. We hypothesise that the reduction of institutional relations caused by the epidemic is the cause for the student inefficiency, dissatisfaction, and distrust. Our questionnaire was filled by 677 students (172 males, 505 females) from 30 Hungarian higher education institutes altogether. Our results raise attention to the indispensable roles of instructors which are not in close relation to teaching. Furthermore, the results point that the weakening in the student relationships is in correlation with student persistence, student engagement, and institutional trust and satisfaction. According to the study, the reduction of student embeddedness had a negative impact on performance. A further conclusion is that all of this should be taken into consideration when working out a concept for a virtual university.
Adipocytes-Derived Extracellular Vesicle-miR-26b Promotes Apoptosis of Cumulus Cells and Induces Polycystic Ovary Syndrome
Authors: Zhou Guannan , Gu Yuanyuan , Zhou Fangyue , Zhang Hongdao , Zhang Menglei , Zhang Ganrong , Wu Ligang , Hua Keqin , Ding Jingxin
Published: February 2022

Background

Polycystic ovary syndrome (PCOS) is a refractory reproductive disease and also a kind of endocrine and metabolic disease. Adipocyte cells can produce a mass of extracellular vesicles and orchestrate the status of other types cells. The objective of this study was to determine the effects of adipocyte-derived extracellular vesicles-miR-26b on cumulus cells (CCs) and development of PCOS.

Methods

The crosstalk mediated by extracellular vesicle-miR-26b between adipocytes and CCs was determined in CC cells co-cultured with mature adipocytes or incubated with extracellular vesicle isolated from mature adipocytes. CCK-8 assay and flow cytometry were conducted in CCs treated with or without extracellular vesicles; microRNA (miRNA) sequencing was conducted for clarifying the key molecular. Hormone levels and ovary ovulation ability were conducted with animal experiment.

Results

The results revealed that miR-26b was upregulated in extracellular vesicles derived from mature adipocytes. Adipocyte-derived extracellular vesicles inhibited viability and promoted apoptosis in CCs via targeting JAG1. Furthermore, extracellular vesicles derived from mature adipocyte disrupted the ovary ovulation and impaired the hormone levels.

Conclusions

These results identify a novel signaling pathway that adipocytes-derived extracellular vesicles-miR-26b promotes cell apoptosis in CCs and disrupted the ovary ovulation in the development of PCOS. The study indicates that adipose tissue-derived extracellular vesicles-miR-26b may play a key role in the PCOS and also provides insight into developing new therapeutic strategies for PCOS.
Systematic Understanding of Anti-Aging Effect of Coenzyme Q10 on Oocyte Through a Network Pharmacology Approach
Authors: Yang Liuqing , Wang Heng , Song SuJie , Xu Hongbin , Chen Yun , Tian Saisai , Zhang Yiqun , Zhang Qin
Published: February 2022

Background

Maternal oocyte aging is strongly contributing to age-related decline in female fertility. Coenzyme Q10 (CoQ10) exerts positive effects in improving aging-related deterioration of oocyte quality, but the exact mechanism is unclear.

Objective

To reveal the system-level mechanism of CoQ10’s anti-aging effect on oocytes based on network pharmacology.

Methods

This study adopted a systems network pharmacology approach, including target identification, data integration, network and module construction, bioinformatics analysis, molecular docking, and molecular dynamics simulation.

Result

A total of 27 potential therapeutic targets were screened out. Seven hub targets (PPARA, CAT, MAPK14, SQSTM1, HMOX1, GRB2, and GSR) were identified. Functional and pathway enrichment analysis indicated that these 27 putative targets exerted therapeutic effects on oocyte aging by regulating signaling pathways (e.g., PPAR, TNF, apoptosis, necroptosisn, prolactin, and MAPK signaling pathway), and are involved oxidation-reduction process, mitochondrion, enzyme binding, reactive oxygen species metabolic process, ATP binding, among others. In addition, five densely linked functional modules revealed the potential mechanisms of CoQ10 in improving aging-related deterioration of oocyte quality are closely related to antioxidant, mitochondrial function enhancement, autophagy, anti-apoptosis, and immune and endocrine system regulation. The molecular docking study reveals that seven hub targets have a good binding affinity towards CoQ10, and molecular dynamics simulation confirms the stability of the interaction between the hub targets and the CoQ10 ligand.

Conclusion

This network pharmacology study revealed the multiple mechanisms involved in the anti-aging effect of CoQ10 on oocytes. The molecular docking and molecular dynamics simulation provide evidence that CoQ10 may act on these hub targets to fight against oocytes aging.
Establishment of Reference Intervals for Thyroid-Associated Hormones Using refineR Algorithm in Chinese Population at High-Altitude Areas
Authors: Ma Chaochao , Zhong Jian , Zou Yutong , Liu Zhijuan , Li Honglei , Pang Jinrong , Liu Xiaoxing , Zejipuchi  , Tian Liping , Hou Li’an , Wang Danchen , Cheng Xinqi , Qiu Ling
Published: February 2022

Objectives

Diagnosis of thyroid disease among individuals dwelling at high altitude remains a challenge. Reference intervals (RIs) for thyroid-associated hormones among Tibetans living at various high altitudes were established to improve diagnosis.

Methods

One thousand two hundred eighty-one subjects were randomly recruited from Nyingchi, Shigatse/Lhasa, and Ali of Tibet. Thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured by the Cobas e601 electrochemiluminescence analyzer. We used multiple linear regression and variance component analysis to assess the effect of sex, age, and altitude on hormones. RIs were established by refineR algorithm and compared with those provided by the manufacturer.

Results

Serum TSH was significantly lower in males than in females, while FT3 and FT4 were higher in males. Both FT3 and FT4 decreased with increasing age. FT3 increased with altitude, while TSH and FT4 were less influenced by altitude. The RI for TSH was 0.764–5.784 μIU/ml, while for FT4, the RIs were 12.36–19.38 pmol/L in females and 14.84–20.18 pmol/L in males. The RIs for FT3 at Nyingchi, Shigatse/Lhasa, and Ali in females were 4.09–4.98, 4.31–5.45, and 4.82–5.58 pmol/L, while in males, the values were 4.82–5.41, 4.88–5.95, and 5.26–6.06 pmol/L, respectively. The obtained RIs for TSH and FT4 were generally higher, while that for FT3 was narrower than the RIs provided by Cobas.

Conclusions

Specific RIs were established for thyroid-associated hormones among Tibetans, which were significantly different from those provided by the manufacturer.
New Insights and Emerging Therapeutic Approaches in Prostate Cancer
Authors: Licitra Fabrizio , Giovannelli Pia , Di Donato Marzia , Monaco Alessandra , Galasso Giovanni , Migliaccio Antimo , Castoria Gabriella
Published: February 2022

Prostate cancer is the second most frequently diagnosed cancer in men and several therapeutic approaches are currently available for patient’s care. Although the androgen receptor status represents a good predictor of response to androgen deprivation therapy, prostate cancer frequently becomes resistant to this approach and spreads. The molecular mechanisms that contribute to progression and drug-resistance of this cancer remain still debated. However, few therapeutic options are available for patient’s management, at this stage. Recent years have seen a great expansion of the studies concerning the role of stromal-epithelial interactions and tumor microenvironment in prostate cancer progression. The findings so far collected have provided new insights into diagnostic and clinical management of prostate cancer patients. Further, new fascinating aspects concerning the intersection of the androgen receptor with survival factors as well as calcium channels have been reported in cultured prostate cancer cells and mouse models. The results of these researches have opened the way for a better understanding of the basic mechanisms involved in prostate cancer invasion and drug-resistance. They have also significantly expanded the list of new biomarkers and druggable targets in prostate cancer. The primary aim of this manuscript is to provide an update of these issues, together with their translational aspects. Exploiting the power of novel promising therapeutics would increase the success rate in the diagnostic path and clinical management of patients with advanced disease.
Evaluation of Six Satellite-Based Soil Moisture Products Based on in situ Measurements in Hunan Province, Central China
Authors: Fan Jiazhi , Han Qinzhe , Tan Shiqi , Li Ji
Published: February 2022

Long-term near-surface soil moisture (SM) data can be obtained on a regional scale through microwave remote sensing. Therefore, to quantitatively analyze the accuracy of multisource remote sensing–based observation products, improve the retrieval algorithm, and effectively use in terminal environments, a standardized comprehensive evaluation is imperative. The SM data obtained by the China Meteorological Administration and Ministry of Water Resources were used as reference data to verify the performance of six passive microwave remote sensing–based SM products from the SMOS, SMAP, GCOM-W, FY-3B, and FY-3C satellites in Hunan province, China. These data were also used to analyze the effects of topographical, land cover, and meteorological factors on SM retrieval accuracy. Results show that SMAP shows the best overall performance in Hunan province; furthermore, it exhibits stable accuracy and is not easily affected by environmental factors. The FY series of satellite products shows the worst performance, and some grid remote sensing data are negatively correlated with the ground measurement data. AMSR2 possesses the largest amount of data and the largest deviation, and only this product exhibits significant differences with the fluctuation trend of the measured SM and precipitation. Passive microwave detection technology presents the best performance in the central part of Hunan province and the largest bias in the Dongting Lake area. SMOS-L3 and SMOS-IC, two products of the same satellite, show the lowest bias but present differences in the SM fluctuation range, orbital accuracy, as well as dry or wet bias. Furthermore, FY-3B and FY-3C, two satellites belonging to the same series, exhibit excellent consistency in performance. The evaluation results and accuracy variation between products as well as other factors identified in the study provide a baseline reference for improving the retrieval algorithm. This study provides a quantitative basis for developing improved applications of passive microwave SM products.
Evaluation of Marginal Land Potential and Analysis of Environmental Variables of Jerusalem Artichoke in Shaanxi Province, China
Authors: Zhao Danyun , Yin Fang , Ashraf Tariq , Yuan Zheng , Ye Linxiao
Published: February 2022

Based on the maximum entropy modeling (Maxent) and ArcGIS tool, this study assessed the potential of marginal land and analyzed the impact of environmental variables for Jerusalem artichoke (Helianthus tuberosus L.) in Shaanxi Province, China. The results showed that the dominant land type used for the growth of Jerusalem artichoke was moderately dense grassland. Additionally, significant environmental variables of Jerusalem artichoke and their suitable range in Shaanxi Province were average slope (SLP, 0–5°C), average soil depth (DPT, 1.50–1.60 m), max temperature of the warmest month (Bio5, 30–31°C), annual mean temperature (Bio1, 16.5–18.0°C), precipitation of the wettest quarter (Bio16, 0.01–0.02 m), July solar radiation (SR7, 1.66–1.67 × 107 W/m2), precipitation seasonality (Bio15, 50–60%), precipitation of the driest quarter (Bio17, 0–0.005 m), and isothermality (Bio3, 265–275). Furthermore, the suitable area was mainly distributed in southern (mainly Hanzhong, Ankang, and Shangluo) and northern (mainly Yan’an and Yulin) parts of Shaanxi Province, covering around 8.81 × 1010 m2 and accounting for 42.8% of the total area of the Shaanxi Province. This study can provide a reference for the rational planting of Jerusalem artichoke in Shaanxi Province.
Why Home Gardens Fail in Enhancing Food Security and Dietary Diversity
Authors: Du Toit Marié J. , Rendón Olivia , Cologna Viktoria , Cilliers Sarel S. , Dallimer Martin
Published: February 2022

Visions of sustainable cities mostly conjure up well tended home and community gardens, where owners and residents plant fruits and vegetables that supply some of their livelihood needs. Indeed, home gardens can contribute to household food security but often fail to do so. Moreover, gardens can provide several additional ecosystem services and impact entire communities. This paper seeks to answer why these gardens often do not provide adequate services to make a substantial contribution to food security and identifies possible solutions. We undertook a case study in South Africa in a low-income former township area. The area is characterized by poverty, high levels of unemployment and food insecurity. We interviewed 140 respondents with home gardens to determine what role their own garden plays in household food security. Only 10% of households were found to be completely food secure. Of the rest, 39% experienced hunger that affected everyone in the household and 51% were at risk of hunger. Despite the fact that 72% of the respondents planted vegetables or fruits, the gardens did not contribute substantially to food security. The respondents mostly bought their food, with subsequent food shortages when they did not have enough money. The dietary diversity and consumption of vitamin A-rich fruits and vegetables were very low. The most important constraints inhibiting urban agriculture in the study area were cultural practices, such as the presence of large, bare, open spaces, or “lebala,” the focus of home gardeners on ornamental species and lawns; and a reliance on purchasing of foods.
Papua at the Crossroads: A Plea for Systematic Conservation Planning in One of the Largest Remaining Areas of Tropical Rainforest
Authors: Parsch Christoph , Wagner Benjamin , Pangau-Adam Margaretha , Nitschke Craig , Kreft Holger , Schrader Julian
Published: February 2022

Land-use change has progressed rapidly throughout the Indonesian archipelago and is now intruding into western New Guinea (Tanah Papua), one of the world’s last wilderness areas with extensive tracts of pristine and highly diverse tropical rainforests. Tanah Papua has reached a crossroads between accelerating environmental degradation and sustainable development policies entailing landscape-scale conservation targets, pledged in the Manokwari Declaration. We assessed the representation of ecoregions and elevational zones within Tanah Papua’s protected area network to identify its shortcomings at broad spatial scales. Lowland ecoregions are less protected than mountainous regions, with half of the western and southern lowlands designated for land-use concessions. Under the direct threat from land-use change, the political motivation in Tanah Papua toward conservation- and culture-centered land management provides a window of opportunity for scientifically guided, proactive conservation planning that integrates sustainable development for the benefit of Indigenous communities.
Comprehensive Genomic and Epigenomic Analyses on Transcriptomic Regulation in Stomach Adenocarcinoma
Authors: Chen Junxing , Liu Weinan , Du Jiabin , Wang Pengcheng , Wang Jintian , Ye Kai
Published: February 2022

Background: DNA methylation (MET)–mediated transcriptomic disturbance and copy number variations (CNVs) exert a significant influence in stimulating the heterogeneous progression of stomach adenocarcinoma (STAD). Nevertheless, the relation of DNA MET with CNVs, together with its impact on tumor occurrence, is still unclear.

Methods: The messenger RNA (mRNA) expression (EXP) profiles, DNA MET, and DNA copy numbers, together with STAD mutation data, were collected from the TCGA official data portal. We employed circular binary segmentation algorithm in “DNAcopy.” library of R package for mapping DNA CNV data at genetic level for all samples based on the segmented CNV data. Stable clusters of samples were recognized using negative matrix factorization cluster analysis based on 50 iterations and the “brunet” method using the MET-correlated (METcor) and CNV-correlated (CNVcor) genes. The R package “iCluster” method was utilized to comprehensively analyze the EXP, MET, and DNA CNV profiles.

Results: A total of 313 STAD samples were isolated for checking DNA copy numbers and MET and for measuring EXP. In accordance with our results, we discovered obvious co-regulation of CNVcor genes and METcor counterparts. Apart from that, these genes were subject to multi-omics integration. Meanwhile, three subtypes of STAD were detected and confirmed based on independent data. Among them, the subtype with increased aggressiveness was related to decreased mutation frequencies of ARID1A, PIK3CA, ZFHX3, SPECC1, OBSCN, KMT2D, FSIP2, ZBTB20, TTN, and RANBP2, together with the abnormal levels of JPH3, KCNB1, and PLCXD3.

Conclusion: According to the results, these aforementioned genes exerted crucial roles in the development of invasive STAD. Our findings on transcriptomic regulation genomically and epigenetically facilitate the understanding of the STAD pathology from different aspects, which help to develop efficient anti-STAD therapy.
A Novel Variant of the CHD2 Gene Associated With Developmental Delay and Myoclonic Epilepsy
Authors: Zhu Lina , Peng Fujun , Deng Zengwen , Feng Zhichun , Ma Xiuwei
Published: February 2022

Pathogenic variants in CHD2 have been reported to have a wide range of phenotypic variability in neurodevelopmental disorders, such as early-onset epileptic encephalopathy, developmental delay, and behavior problems. So far, there is no clear correlation between genotypes and phenotypes. This study reports a Chinese patient with a novel heterozygous CHD2 mutation (c.4318C>T, pArg1440*). Her main clinical manifestations include developmental delay, myoclonic epilepsy, and hypothyroidism. Then, we reviewed a total of 144 individuals carrying CHD2 variants with epileptic encephalopathy. In terms of clinical manifestations, these patients are usually described with variable epilepsy phenotypes, including idiopathic photosensitive occipital epilepsy, Dravet syndrome, Jeavons syndrome, Lennox–Gastaut syndrome, juvenile myoclonic epilepsy, and non-specific epileptic encephalopathy. Among them, myoclonic seizures and generalized tonic-clonic seizures are the main seizure types in all patients hosting CHD2 single-nucleotide or indel variants (non-CNVs). At the molecular level, there are 102 types of CHD2 non-CNVs in 126 patients, almost one mutational type corresponding to one person, and there is no difference in the incidence ratio of each position. Furthermore, we summarized that a small proportion of patients inherited CHD2 variants, and not all patients with CHD2 variants had seizures. Importantly, the phenotypes, especially seizures control and fever sensitivity, and genotypes had a relative association. These results enriched the database of CHD2-relative neurodevelopmental disorders and provided a theoretical foundation for researching the relationship between genotypes and phenotypes.
Congenital Bilateral Absence of the Vas Deferens
Authors: Cai Zhonglin , Li Hongjun
Published: February 2022

Congenital bilateral absence of the vas deferens (CBAVD) is clinically characterized by the absence of the bilateral vas deferens; the main clinical manifestation is infertility, accounting for 1–2% of male infertility cases. CBAVD may be accompanied by congenital abnormalities in the urogenital system and cystic fibrosis (CF)-related clinical manifestations. CBAVD can develop as a mild manifestation of CF or can be isolated. The main pathogenic mechanism of CBAVD is gene mutation, and CBAVD and CF have a common genetic mutation background. CFTR mutation is the main pathogenic cause of CBAVD and CF, and ADGRG2 mutation is the second most common cause. Although lack of the vas deferens in CBAVD patients causes infertility due to the inability to release sperm, the testes of CBAVD patients have spermatogenic function. Therefore, CBAVD patients can achieve fertility through sperm retrieval surgery and assisted reproductive technology (ART). However, gene mutations in CBAVD patients can have an impact on the ART outcome, and there is a risk of passing on gene mutations to offspring. For CBAVD patients and their spouses, performing genetic counseling (which currently refers mainly to CFTR mutation screening) helps to reduce the risks of genetic mutations being passed on to offspring and of offspring having CF with concomitant CBAVD.