bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous native nephrectomy with renal transplantation: Our experience and a brief literature review
Authors: Karadağ Serdar , Güler Ahmet Faysal , Kargı Taner , Hacıislamoğlu Ahmet , Polat Hakan , Evren İsmail , Ekşi Mithat , Özdemir Osman
Published: February 2022

Objective: There is a need for native kidney nephrectomy to increase renal transplant surgery’s safety or improve postoperative function in some cases. The timing of the procedure is still controversial. This study aimed to present our native nephrectomy procedures performed simultaneously with the transplantation in light of the literature. Material and Methods: A retrospective analysis was performed on the data of 245 patients who underwent renal transplantation due to end-stage renal failure (ESRD) between September 2011 and February 2020. Patients who underwent unilateral or bilateral nephrectomy simultaneously with transplantation were included. Demographic characteristics of the patients, preoperative and postoperative laboratory data, primary disease, presence of comorbid diseases, duration of dialysis, duration of vascular anastomosis, surgical and clinical complications, duration of hospital stay, and graft functions were recorded.  Results: 12 patients underwent ipsilateral or bilateral native nephrectomy simultaneously with renal transplantation. The primary diseases of the patients leading to ESRD were as follows; 6 (50%) patients with Polycystic Kidney Disease (PKD), 5 (41.6%) patients with vesicoureteral reflux (VUR), one (8.3%) patient with kidney stones. Postoperative fever in three patients, erythrocyte replacement therapy in three patients, urosepsis and urinary drainage catheter requirement in one patient due to lymphocele was recorded. Two patients developed humoral rejection, and two patients developed BK virus nephropathy. Conclusion: In the presence of appropriate indications, simultaneous native nephrectomy is a safe and effective method in patients preparing for renal transplantation. In centers with sufficient experience and equipment, it may be preferable to perform native nephrectomy simultaneously with renal transplantation. Keywords: Kidney transplantation, nephrectomy, bilateral nephrectomy, polycystic kidney disease, complications.
Preventive effect of pomegranate juice on ESWL-related renal damage in patients with kidney stones
Authors: Taş Selim , Tuğcu Volkan , Karadağ Serdar , Şahin Selçuk
Published: February 2022

Objective: We aimed to show whether the antioxidant properties of pomegranate juice (PJ) show a protective effect against renal damage associated with oxidative stress caused by Extracorporeal Shock Wave Lithotripsy (ESWL) in patients who have undergone ESWL for kidney stones.  Material and Methods: Ninety patients who were to undergo ESWL for kidney stones were included in the study and were divided into 3 groups with 30 patients each ESWL. Group 1 (control group) patients received only ESWL treatment. Group 2 (study group) patients were recommended to take 30 ml/kg/day pomegranate juice mixture orally for 2 days before ESWL. Group 3 (placebo group) patients were recommended to take 30 mg/kg/day water orally for 2 days before ESWL. All ESWL-treated patients received 2000 to 2500 shock waves at 18 to 24 in order to measure lipid peroxidation markers showing the DNA lesion associated with oxidative stress and to show tubular damage after ESWL,  Results: There was a statistically significant mean increase of 52.39± 10.49 in 8-Hydroxy deoxyguanosine (8-OHdG) levels after treatment compared to pre-treatment levels in Group 1 (p<0.01). There was a statistically significant mean increase of 13.16±7.71 and 33.24±12.82 in Groups 2 and 3, respectively (p<0.01; p<0.01, respectively) There was a statistically significant mean increase of 19.20±5.21 in N-acetyl-beta-D-glucosaminidase (NAG) levels after treatment compared to pre-treatment levels in Group 1 (p<0.01). There was a statistically significant mean increase of 3.44±5.21 and 13.07±5.50 in Groups 2 and 3, respectively (p<0.01; p<0.01, respectively). Conclusion: Our study concluded that pomegranate juice (PJ) has protective effects against ESWL-related renal damage. Keywords: Antioxidant, kidney stones, lithotripsy, pomegranate juice.
An analysis of YouTube videos on female genital mutilation as a global issue
Authors: Demir Murat , Avcı Veli
Published: February 2022

Objective: Female genital mutilation is the removal of female genital organs for non-medical reasons, which is widely practiced worldwide. Female genital mutilation is a dark subject for the scientific world since it is often practiced in closed societies. In this study, we aimed to evaluate the role of YouTube videos in the prevention of female genital mutilation. Material and Methods: In this cross-sectional study, an internet search was conducted on YouTube.com on May 1, 2021, using the keywords «female genital mutilation» and «female circumcision» on a web browser with a clear cache and latest updates. Search results were evaluated in terms of the demographic characteristics of uploaders and the quality and reliability of the videos. Results: Most of the videos were shared by women. The videos shared by women and healthcare professionals were higher quality and more reliable compared to videos uploaded by men and religious personnel. Conclusion: YouTube.com videos may be beneficial for the prevention of female genital mutilation, but more attention should be paid to this issue, particularly by healthcare professionals, and more reliable videos with the higher quality should be shared. Keywords: Circumcision, female, genitalia.
Deforestation: An Implication of High Rate of Unemployed and Low-Income Household Members in Rural Communities in Kebbi, Nigeria.
Authors: Uba Matthew Ndubuisi
Published: February 2022

Deforestation is a major environmental issue in Northern Nigeria. Factors like unemployment and low-income among households in Northern Nigeria results to falling of trees for source of energy for domestic and commercial activities. Secondary dataset was analyzed using R-Programming. Variables describing the employed members of the household, energy sources for lighting fuel and energy sources for cooking fuel for the households were analyzed. Results from the histogram revealed that there are over 3000 households dependent on fuel wood as an energy source. Also, results from the Analysis of Variance revealed that annual income of the households has significant impact on cooking fuel sources (0.0104<0.05) and has a very strong significance on lighting fuel sources (0.000<0.05). The low-income rate of households was evident showing the relationship between employed members of the households with a very strong significance on annual income of the households (0.000375<0.05).
Buprenorphine as a Treatment for Major Depression and Opioid Use Disorder
Authors: Namchuk Amanda B. , Lucki Irwin , Browne Caroline A.
Published: February 2022

Rates of major depressive disorder (MDD) are disproportionally high in subjects with opioid use disorder (OUD) relative to the general population. MDD is often more severe in OUD patients, leading to compliance issues with maintenance therapies and poor outcomes. A growing body of literature suggests that endogenous opioid system dysregulation may play a role in the emergence of MDD. Buprenorphine, a mixed opioid receptor agonist/antagonist approved for the treatment of OUD and chronic pain, may have potential as a novel therapeutic for MDD, especially for patients with a dual diagnosis of MDD and OUD. This paper presents a comprehensive review of papers relevant to the assessment of buprenorphine as a treatment for MDD, OUD, and/or suicide compiled using electronic databases per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The principal goal of this literature review was to compile the clinical studies that have interrogated the antidepressant activity of buprenorphine in opioid-naïve MDD patients and OUD patients with comorbid MDD. Evidence supporting buprenorphine’s superiority over methadone for treating comorbid OUD and MDD was also considered. Finally, recent evidence for the ability of buprenorphine to alleviate suicidal ideation in both opioid-naïve patients and opioid-experienced patients was evaluated. Synthesizing all of this information, buprenorphine emerges as a potentially effective therapeutic for the dual purposes of treating MDD and OUD.
Biomimetic Metal-Organic Framework Nanoparticles for Synergistic Combining of SDT-Chemotherapy Induce Pyroptosis in Gastric Cancer
Authors: Yu Zhu , Cao Wenlong , Han Chuangye , Wang Zhen , Qiu Yue , Wang Jiancheng , Wei Mengda , Wang Junfu , Zhang Siwen , Liu Senfeng , Mo Shutian , Chen Junqiang
Published: February 2022

In recent years, sonodynamic therapy (SDT) has been widely developed for cancer research as a promising non-invasive therapeutic strategy. Here, we synthesized zeolitic imidazole frameworks-8 (ZIF-8) and utilized its properties to encapsulate hydrophobic Chlorin e6 (Ce6) and hydrophilic tirapazamine (TPZ) for a synergistic sonodynamic chemotherapy, which was also accompanied by the modification of cytomembrane of gastric cancer (GC) cells. Thus, we enabled the biomimetic property to achieve targeted delivery. Ce6-mediated SDT, in combination with ultrasound irradiation, could target the release of reactive oxygen species (ROS) to aggravate further hypoxia and activate TPZ. Combining these effects could induce the pyroptosis of GC cells and play the anti-tumor function, which could provide a potential therapeutic method for cancer therapy.
Thermodynamic Constraints on Electromicrobial Protein Production
Authors: Wise Lucas , Marecos Sabrina , Randolph Katie , Hassan Mohamed , Nshimyumukiza Eric , Strouse Jacob , Salimijazi Farshid , Barstow Buz
Published: February 2022

Global consumption of protein is projected to double by the middle of the 21st century. However, protein production is one of the most energy intensive and environmentally damaging parts of the food supply system today. Electromicrobial production technologies that combine renewable electricity and CO2-fixing microbial metabolism could dramatically increase the energy efficiency of commodity chemical production. Here we present a molecular-scale model that sets an upper limit on the performance of any organism performing electromicrobial protein production. We show that engineered microbes that fix CO2 and N2 using reducing equivalents produced by H2-oxidation or extracellular electron uptake could produce amino acids with energy inputs as low as 64 MJ kg−1, approximately one order of magnitude higher than any previous estimate of the efficiency of electromicrobial protein production. This work provides a roadmap for development of engineered microbes that could significantly expand access to proteins produced with a low environmental footprint.
Toward Development of a Diabetic Synovium Culture Model
Authors: Sakhrani Neeraj , Lee Andy J. , Murphy Lance A. , Kenawy Hagar M. , Visco Christopher J. , Ateshian Gerard A. , Shah Roshan P. , Hung Clark T.
Published: February 2022

Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation and inflammation of synovium, the specialized connective tissue that envelops the diarthrodial joint. Type 2 diabetes mellitus (DM) is often found in OA patients, with nearly double the incidence of arthritis reported in patients with diabetes (52%) than those without it (27%). The correlation between OA and DM has been attributed to similar risk factors, namely increasing age and joint loading due to obesity. However, a potential causative link is not well understood due to comorbidities involved with treating diabetic patients, such as high infection rates and poor healing response caused by hyperglycemia and insulin resistance. The purpose of this study was to investigate the effect of hyperglycemic and insulin culture conditions on synovium properties. It was hypothesized that modeling hyperglycemia-induced insulin resistance in synovium would provide novel insights of OA pathogenesis in DM patients. To simulate DM in the synovial joint, healthy synovium was preconditioned in either euglycemic (EG) or hyperglycemic (HG) glucose concentrations with insulin in order to induce the biological response of the diseased phenotype. Synovium biochemical composition was evaluated to determine ECM remodeling under hyperglycemic culture conditions. Concurrent changes in AKT phosphorylation, a signaling pathway implicated in insulin resistance, were measured along with gene expression data for insulin receptors, glucose transporters, and specific glycolysis markers involved in glucose regulation. Since fluid shear stress arising during joint articulation is a relevant upstream stimulus for fibroblast-like synoviocytes (FLS), the predominant cell type in synovium, FLS mechanotransduction was evaluated via intracellular calcium ([Ca2+]i). Incidence and length of primary cilia, a critical effector of cell mechanosensing, were measured as potential mechanisms to support differences in [Ca2+]i responses. Hyperglycemic culture conditions decreased collagen and GAG content compared to EG groups, while insulin recovered ECM constituents. FLS mechanosensitivity was significantly greater in EG and insulin conditions compared to HG and non-insulin treated groups. Hyperglycemic treatment led to decreased incidence and length of primary cilia and decreased AKT phosphorylation, providing possible links to the mechanosensing response and suggesting a potential correlation between glycemic culture conditions, diabetic insulin resistance, and OA development.
Light-Addressable Potentiometric Sensors in Microfluidics
Authors: Li Xueliang , Liu Shibin , Tan Jie , Wu Chunsheng
Published: February 2022

The light-addressable potentiometric sensor (LAPS) is an electrochemical sensor based on the field-effect principle of semiconductors. It is able to sense the change of Nernst potential on the sensor surface, and the measuring area can be controlled by the illumination of a movable light. Due to the unique light-addressable ability of the LAPS, the chemical imaging system constructed with the LAPS can realize the two-dimensional image distribution detection of chemical/biomass. In this review, the advantages of the LAPS as a sensing unit of the microelectrochemical analysis system are summarized. Then, the most recent advances in the development of the LAPS analysis system are explained and discussed. In particular, this review focused on the research of ion diffusion, enzymatic reaction, microbial metabolism, and droplet microfluidics using the LAPS analysis system. Finally, the development trends and prospects of the LAPS analysis system are illustrated.
Yucatan Minipig Knee Meniscus Regional Biomechanics and Biochemical Structure Support its Suitability as a Large Animal Model for Translational Research
Authors: Gonzalez-Leon Erik A. , Hu Jerry C. , Athanasiou Kyriacos A.
Published: February 2022

Knee meniscus injuries are the most frequent causes of orthopedic surgical procedures in the U.S., motivating tissue engineering attempts and the need for suitable animal models. Despite extensive use in cardiovascular research and the existence of characterization data for the menisci of farm pigs, the farm pig may not be a desirable preclinical model for the meniscus due to rapid weight gain. Minipigs are conducive to in vivo experiments due to their slower growth rate than farm pigs and similarity in weight to humans. However, characterization of minipig knee menisci is lacking. The objective of this study was to extensively characterize structural and functional properties within different regions of both medial and lateral Yucatan minipig knee menisci to inform this model’s suitability as a preclinical model for meniscal therapies. Menisci measured 23.2–24.8 mm in anteroposterior length (33–40 mm for human), 7.7–11.4 mm in width (8.3–14.8 mm for human), and 6.4–8.4 mm in peripheral height (5–7 mm for human). Per wet weight, biochemical evaluation revealed 23.9–31.3% collagen (COL; 22% for human) and 1.20–2.57% glycosaminoglycans (GAG; 0.8% for human). Also, per dry weight, pyridinoline crosslinks (PYR) were 0.12–0.16% (0.12% for human) and, when normalized to collagen content, reached as high as 1.45–1.96 ng/µg. Biomechanical testing revealed circumferential Young’s modulus of 78.4–116.2 MPa (100–300 MPa for human), circumferential ultimate tensile strength (UTS) of 18.2–25.9 MPa (12–18 MPa for human), radial Young’s modulus of 2.5–10.9 MPa (10–30 MPa for human), radial UTS of 2.5–4.2 MPa (1–4 MPa for human), aggregate modulus of 157–287 kPa (100–150 kPa for human), and shear modulus of 91–147 kPa (120 kPa for human). Anisotropy indices ranged from 11.2–49.4 and 6.3–11.2 for tensile stiffness and strength (approximately 10 for human), respectively. Regional differences in mechanical and biochemical properties within the minipig medial meniscus were observed; specifically, GAG, PYR, PYR/COL, radial stiffness, and Young’s modulus anisotropy varied by region. The posterior region of the medial meniscus exhibited the lowest radial stiffness, which is also seen in humans and corresponds to the most prevalent location for meniscal lesions. Overall, similarities between minipig and human menisci support the use of minipigs for meniscus translational research.
Toward Quantifying Decentralization of Blockchain Networks With Relay Nodes
Authors: Shahsavari Yahya , Zhang Kaiwen , Talhi Chamseddine
Published: February 2022

In this paper, we present a methodology for quantifying the decentralization degree of a blockchain network. To accomplish this, we use two well-known graph models of Erdös-Rény and Barabási–Albert in order to study the blockchain network topology. We then quantify the decentralization degree using the clustering coefficient of our network models. We validate our approach through extensive simulations and analyze the decentralization degree with respect to network parameters such as the number of connections per node and the peer selection algorithm. Our results expose the trade-off between the average shortest path and the decentralization degree. Furthermore, we observe the impact of the average shortest path on the network speed and traffic overhead. Finally, we demonstrate that the presence of hub-like nodes such as relay gateways negatively impacts the decentralization degree of blockchain networks.
Predicting the Response of Laminated Composite Beams: A Comparison of Machine Learning Algorithms
Authors: Tsiatas George C. , Kotsiantis Sotiris , Charalampakis Aristotelis E.
Published: February 2022

A comparative study of machine learning regression algorithms for predicting the deflection of laminated composite beams is presented herein. The problem of the scarcity of experimental data is solved by ample numerically prepared data, which are necessary for the training, validation, and testing of the algorithms. To this end, the pertinent geometric and material properties of the beam are discretized appropriately, and a refined higher-order beam theory is employed for the accurate evaluation of the deflection in each case. The results indicate that the Extra-Trees algorithm performs best, demonstrating excellent predictive capabilities.
Toward Best Practices for Controlling Mammalian Cell Culture Environments
Authors: Klein Shannon G. , Steckbauer Alexandra , Alsolami Samhan M. , Arossa Silvia , Parry Anieka J. , Li Mo , Duarte Carlos M.
Published: February 2022

The characterization, control, and reporting of environmental conditions in mammalian cell cultures is fundamental to ensure physiological relevance and reproducibility in basic and preclinical biomedical research. The potential issue of environment instability in routine cell cultures in affecting biomedical experiments was identified many decades ago. Despite existing evidence showing variable environmental conditions can affect a suite of cellular responses and key experimental readouts, the underreporting of critical parameters affecting cell culture environments in published experiments remains a serious problem. Here, we outline the main sources of potential problems, improved guidelines for reporting, and deliver recommendations to facilitate improved culture-system based research. Addressing the lack of attention paid to culture environments is critical to improve the reproducibility and translation of preclinical research, but constitutes only an initial step towards enhancing the relevance of in vitro cell cultures towards in vivo physiology.
Evaluation of Parkin in the Regulation of Myocardial Mitochondria-Associated Membranes and Cardiomyopathy During Endotoxemia
Authors: Kim Matthew , Nikouee Azadeh , Sun Yuxiao , Zhang Qing-Jun , Liu Zhi-Ping , Zang Qun Sophia
Published: February 2022

Background: Mitochondrial deficiency is a known pathology in sepsis-induced organ failure. We previously found that mitochondria-associated membranes (MAMs), a subcellular domain supporting mitochondrial status, are impaired in the heart during endotoxemia, suggesting a mechanism of mitochondrial damage occurred in sepsis. Mitophagy pathway via E3 ubiquitin ligase Parkin and PTEN-induced kinase 1 (PINK1) controls mitochondrial quality. Studies described here examined the impact of Parkin on cardiac MAMs and endotoxemia-induced cardiomyopathy. Additionally, point mutation W403A in Parkin was previously identified as a constitutively active mutation in vitro. In vivo effects of forced expression of this mutation were evaluated in the endotoxemia model.

Methods: Mice of wild type (WT), Parkin-deficiency (Park2−/−), and knock-in expression of Parkin W402A (human Parkin W403A) were given lipopolysaccharide (LPS) challenge. Cardiac function was evaluated by echocardiography. In the harvested heart tissue, MAM fractions were isolated by ultracentrifugation, and their amount and function were quantified. Ultrastructure of MAMs and mitochondria was examined by electron microscopy. Mitochondrial respiratory activities were measured by enzyme assays. Myocardial inflammation was estimated by levels of pro-inflammatory cytokine IL-6. Myocardial mitophagy was assessed by levels of mitophagy factors associated with mitochondria and degrees of mitochondria-lysosome co-localization. Parkin activation, signified by phosphorylation on serine 65 of Parkin, was also evaluated.

Results: Compared with WT, Park2−/− mice showed more severely impaired cardiac MAMs during endotoxemia, characterized by disrupted structure, reduced quantity, and weakened transporting function. Endotoxemia-induced cardiomyopathy was intensified in Park2−/− mice, shown by worsened cardiac contractility and higher production of IL-6. Mitochondria from the Park2−/− hearts were more deteriorated, indicated by losses in both structural integrity and respiration function. Unexpectedly, mice carrying Parkin W402A showed similar levels of cardiomyopathy and mitochondrial damage when compared with their WT counterparts. Further, Parkin W402A mutation neither enhanced mitophagy nor increased Parkin activation in myocardium under the challenge of endotoxemia.

Conclusion: our results suggest that Parkin/PINK1 mitophagy participates in the regulation of cardiac MAMs during endotoxemia. Point mutation W402A (human W403A) in Parkin is not sufficient to alleviate cardiomyopathy induced by endotoxemia in vivo.
Multi-Platform-Based Analysis Characterizes Molecular Alterations of the Nucleus in Human Colorectal Cancer
Authors: Zhang Wei , Wu Minmin , Gao Xucan , Ma Chiyu , Xu Huixuan , Lin Liewen , He Jingquan , Cai Wanxia , Zhong Yafang , Tang Donge , Tang Min , Dai Yong
Published: February 2022

Background: The disturbed molecular alterations of nucleus may promote the development of colorectal cancer (CRC). A multi-platform-based analysis of nucleus of CRC patients helps us to better understand the underlying mechanism of CRC and screen out the potential drug targets for clinical treatment. However, such studies on nucleus in human CRC are still lacking.

Methods: We collected the cancerous and para-cancerous tissues from eight CRC patients and performed a multiplex analysis of the molecular changes of the nucleus, including structural variations (SVs), DNA methylation, chromatin accessibility, proteome and phosphorproteome.

Results: In our study, we revealed a significant molecular change of nucleus of CRC patients using our original proteomic and phosphorylomic datasets. Subsequently, we characterized the molecular alterations of nucleus of CRC patients at multiple dimensionalities, including DNA, mRNA, protein and epigenetic modification. Next, we found that the great molecular changes of nucleus might affect the biological processes named endocytosis and ubiquitin-mediated proteolysis. Besides, we identified DYNC1LI2 and TPR as the potentially hub proteins within the network of nuclear genes in CRC cells. Furthermore, we identified 1905 CRC-specific SVs, and proclaimed 17 CRC-specific SVs were probably associated with the disturbance of immune microenvironment of CRC patients. We also revealed that the SVs of CXCL5, CXCL10 and CXCL11 might be the core SVs among all the immune-relevant SVs. Finally, we identified seven genes as the upstream transcriptional factors potentially regulating the expression of nuclear genes, such as YY1 and JUN, using a multi-omics approach.

Conclusion: Here, we characterized the molecular changes of nucleus of CRC patients, disclosed the potentially core nuclear genes within the network, and identified the probable upstream regulator of nucleus. The findings of this study are helpful to understand the pathogenic molecular changes of nucleus in CRC patients and provide a functional context for drug development in future.
Elucidating the Potential Mechanisms Underlying Distraction Spinal Cord Injury-Associated Neuroinflammation and Apoptosis
Authors: Han Bo , Liang Weishi , Hai Yong , Liu Yuzeng , Chen Yuxiang , Ding Hongtao , Yang Jincai , Yin Peng
Published: February 2022

The incidence of distraction spinal cord injury (DSCI), which results from spinal cord ischemia due to vascular compromise and spinal cord tract disturbances, remains high. Furthermore, because no ideal animal model that mimics DSCI in clinical settings is available thus far, the related molecular mechanisms underlying DSCI remain unclear. Thus, this study aimed to establish a porcine model of DSCI and investigate the neuroinflammation and apoptosis mechanisms in these pigs. Before surgery, all pigs were randomly divided into three groups: sham group, osteotomy surgery only; the incomplete distraction spinal cord injury (IDSCI) and complete distraction spinal cord injury (CDSCI) group, osteotomy plus DSCI surgery with a motor-evoked potential (MEP) amplitude decreased by approximately 75% and 100%, respectively. After surgery, modified Tarlov scoring and MRC muscle strength scoring were used to evaluate neurologic function in each group. We observed the distracted spinal cord using MRI, and then all pigs were sacrificed. Inflammatory cytokine levels in the spinal cord and cerebrospinal fluid (CSF) were also analyzed. We used immunofluorescence staining to assess the neuronal and microglial structure and function and astrocyte hyperplasia in the central DSCI lesions (T15). Western blotting was used to determine the expression of apoptosis-related proteins. Results showed that the modified Tarlov scoring and muscle strength decreased significantly in the two DSCI groups. T2-MRI showed a relative enhancement at the center of the DSCI lesions. H&E and Lxol fast blue staining revealed that spinal cord distraction destroyed the normal structure of spinal cord tissues and nerve fiber tracts, exacerbating inflammatory cell infiltration, hyperemia, and edema. The IL-1β, IL-6, and TNF-α levels increased in the spinal cord and CSF following DSCI. Immunofluorescence staining results indicated the GFAP, Iba-1 expression increased following DSCI, whereas the NeuN expression reduced. Moreover, DSCI promoted the protein expression of P53, Bcl-2-associated X protein (Bax), and Caspase-3 in the spinal cord tissues, whereas it reduced the Bcl-2 expression. This study successfully established a porcine DSCI model that closely mimics DSCI in clinical settings, and clarified the mechanisms underlying DSCI-associated neuroinflammation and apoptosis; thus, our findings highlight potential DSCI-treatment strategies for further establishing suitable drug therapies.
The Role of m6A Regulator-Mediated Methylation Modification and Tumor Microenvironment Infiltration in Glioblastoma Multiforme
Authors: Wang Liang , Cao Haiyan , Zhong Ying , Ji Peigang , Chen Fan
Published: February 2022

N6-methyladenosine (m6A) RNA methylation is an emerging epigenetic modification in recent years and epigenetic regulation of the immune response has been demonstrated, but the potential role of m6A modification in GBM tumor microenvironment (TME) cell infiltration and stemness remain unknown. The m6A modification patterns of 310 GBM samples were comprehensively evaluated based on 21 m6A regulators, and we systematically correlated these modification patterns with TME cell infiltration characteristics and stemness characteristics. Construction of m6Ascore to quantify the m6A modification patterns of individual GBM samples using a principal component analysis algorithm. We identified two distinct patterns of m6A modification. The infiltration characteristics of TME cells in these two patterns were highly consistent with the immunophenotype of the GBM, including the immune activation differentiation pattern and the immune desert dedifferentiation pattern. We also identified two modes of regulation of immunity and stemness by m6A methylation. Stromal activation and lack of effective immune infiltration were observed in the high m6Ascore subtype. Pan-cancer analysis results illustrate a significant correlation between m6AScore and tumor clinical outcome, immune infiltration, and stemness. Our work reveals that m6A modifications play an important role in the development of TME and stemness diversity and complexity. Patients with a low m6AScore showed significant therapeutic advantages and clinical benefits. Assessing the m6A modification pattern of individual tumors will help enhance our knowledge of TME infiltration and stemness characteristics, contribute to the development of immunotherapeutic strategies.
Development of Fluorescence Polarization Immunoassay With scFv to Detect Fumonisin Bs in Maize and Simultaneous Study of Their Molecular Recognition Mechanism
Authors: Li Yuan , Yu Qing , Yu Wenbo , Zhang Suxia , Wen Kai , Shen Jianzhong , Wang Zhanhui , Yu Xuezhi
Published: February 2022

In this study, a fluorescence polarization immunoassay (FPIA) was developed based on the single-chain variable fragments (scFvs) for fumonisin Bs (FBs). The scFvs were prepared from FBs-specific monoclonal antibody secreting hybridomas (4F5 and 4B9). The established FPIA could determine the sum of fumonisin B1 (FB1) and fumonisin B2 (FB2) within a short time. The IC50 of FPIA for the detection of FB1 and FB2 were 29.36 ng/ml and 1,477.82 ng/ml with 4F5 scFv, and 125.16 ng/ml and 30.44 ng/ml with 4B9 scFv, so the 4B9 scFv was selected for detection of FB1 and FB2 in maize samples with a limit of detection of 441.54 μg/kg and 344.933 μg/kg. The recoveries ranged from 84.7 to 104.1% with a coefficient of variation less than 14.1% in spiked samples, and the result of the FPIA method was in good consistency with that of HPLC-MS/MS. To supply a better understanding of the immunoassay results, the interactions mechanism of scFvs-FBs was further revealed by the homology modelling, molecular docking, and molecular dynamic simulation. It was indicated that six complementarity-determining regions (CDRs) were involved in 4B9 scFv recognition, forming a narrow binding cavity, and FB1/FB2 could be inserted into this binding cavity stably through strong hydrogen bonds and other interactions. While in 4F5 scFv, only the FB1 stably inserted in the binding pocket formed by four CDRs through strong hydrogen bonds, and FB2 did not fit the binding cavity due to the lack of hydroxyl at C10, which is the key recognition site of 4F5 scFv. Also, the binding energy of FB2-4B9 scFv complex is higher than the FB2-4F5 scFv complex. This study established a FPIA method with scFv for the detection of FB1 and FB1 in maize, and systematically predicted recognition mechanism of FBs and scFvs, which provided a reference for the better understanding of the immunoassay mechanism.
Story, Metaphor, and Altruism in Cross-Cultural Teaching and Learning
Authors: Black Michael P. , Kazama Andy M. , Gyatso Kalden , Dema Thukten
Published: February 2022

The Emory-Tibet Science Initiative (ETSI) is a cross-cultural exchange of Western and Tibetan Buddhist education and scholarship. In this partnership between the Dalai Lama Foundation and Emory University, two visiting Western scientists to Sera, Gaden, and Drepung Monasteries and two monastics who studied at Emory University reflect on their experiences teaching and learning from Western and Buddhist perspectives as part of the ETSI program. Specifically, authors explore the power of story, metaphor, and altruism in Buddhist and Western ways of teaching and learning. Authors consider the pedagogical similarities between (1) the variations of the Greek Method of Loci (Memory Palace) and the paintings and temple decorations found throughout Tibetan architecture and (2) the role of altruism and intrinsic motivation in learning outcomes. Current psychological and neurobiological evidence for the increased recall of episodic memories present in both Buddhist and Western use of story, metaphor, and intrinsic motivation associated with altruism will highlight the underlying principles that support these ancient methods. Finally, considerations on how each perspective informs the other is discussed, as well as practical suggestions for integrating methods across cultures.
Social Media, Social Support, and Mental Health of Young Adults During COVID-19
Authors: Longest Kaitlyn , Kang Jin-Ae
Published: February 2022

The current study examines the impact of COVID-19 on the mental health among young adults in the US, how they use social media and the social support they obtain from the online environment, and the effect on their mental health during stay-at-home orders. Our survey among 18-to-25-year-olds found that women and those uncertain of employment status due to the pandemic experienced elevated depression symptoms. The informational acquisition motive for using social media was positively associated with depression symptoms, and a higher level of online informational support contributed to increasing the symptoms. Young adults showed the lowest level of depression symptoms when they had a higher level of offline emotional support and a lower level of online informational support. Our survey stressed the importance of offline emotional support and reconfirmed that nothing can replace its value.
Profiling Wildlife Crimes Prosecuted Federally by the United States
Authors: Sosnowski Monique C. , Kim Yuna , Petrossian Gohar A. , Asner Marcus
Published: February 2022

Wildlife crime threatens national and global security. Much of the impact of wildlife crime is felt overseas, often in developing countries, where it threatens to catalyze conflicts, hinders economic development, undermines the rule of law, and threatens peace, amongst having other negative socio-economic and security impacts. But the impact of wildlife crime also is felt in United States, both directly by undercutting state and local conservation efforts, and indirectly, by injecting illegal wildlife and wildlife products into United States markets. While some work has delved into the sentencing dynamics of broader environmental crime in the United States, little research has explored the sentencing of wildlife crime, which is recognized as being distinct in nature by both governmental bodies and academics alike. The current study explores the federal prosecutions of wildlife crimes, focusing on profiling the wildlife crime cases charged by the US Department of Justice (DOJ). By profiling cases, we aim to explore (1) the application of charges associated with wildlife crime cases via their judgment documents; (2) the wildlife species involved in prosecuted cases; (3) the distribution of cases across US federal districts; and (4) and the sentencing patterns of wildlife crimes. Further statistical analyses explore the relationships between a variety of the variables extracted. Policy recommendations are set forth accordingly.
Relationship Between Fragmented QRS Complex and Left Ventricular Fibrosis and Function in Patients With Danon Disease
Authors: Xie Jiajun , Liu Yang , Wei Xiaoyu , Ye Weitao , Ma Zelan , Lu Guanyu , Tan Zekun , Li Tingyu , Wang Yining , Zhao Lei , Lu Minjie , Li Xiaohu , Chen Yucheng , Liu Hui
Published: February 2022

Background

Fragmented QRS (f-QRS) complex on the surface ECG is a cardiac conduction abnormality that indicates myocardial scarring. The relationship between the f-QRS complex and cardiac status in patients with Danon disease (DD) remains unclear and will be explored in this study.

Methods

Patients with genetically confirmed DD and cardiac magnetic resonance imaging (CMR) examinations were recruited from multiple centers. The number of leads, pattern, score, and segmental distribution of the f-QRS complex were assessed by surface 12-lead ECG. Cardiac status, such as left ventricular (LV) volume, function, and extent of late gadolinium enhancement (LGE), was demonstrated by CMR. The segmental distribution of LGE was also assessed. Correlations between the f-QRS and cardiac status were assessed.

Results

Fifteen patients (14 men) with DD who underwent 12-lead ECG and CMR imaging were included. The f-QRS complex was documented in all patients (n = 15, 100%). Three patterns of f-QRS were found, with the notched R/S pattern (74%) being the most common, followed by fragmented QRS (16%) and various RSR' (11%). The fragmented QRS pattern showed an association with a higher level of myocardial fibrosis (LGE > 35%). The burden of f-QRS in each patient was assessed by the number of leads with f-QRS (median 7, range 2–12) and the f-QRS score (median 9, range 2–33). In the correlation analysis, the f-QRS score was positively correlated with LGE% (r = 0.726, p = 0.002), negatively correlated with LV ejection function (LVEF; r = −0.617, p = 0.014) as evaluated by CMR. In the local distribution, f-QRS score and LGE% were both predominant in the LV free wall but did not correlate well among the anterior, lateral, and inferior segments.

Conclusion

In this DD cohort, the quantitative f-QRS was correlated well with myocardial fibrosis burden and LV dysfunction in general. This finding suggests that f-QRS can be used as a simple screening tool to assess cardiac status in patients with DD.
Programmed Exercise Attenuates Familial Hypertrophic Cardiomyopathy in Transgenic E22K Mice via Inhibition of PKC-α/NFAT Pathway
Authors: Wang Haiying , Lin Yuedong , Zhang Ran , Chen Yafen , Ji Wei , Li Shenwei , Wang Li , Tan Rubin , Yuan Jinxiang
Published: February 2022

Familial hypertrophic cardiomyopathy (FHCM), an autosomal dominant disease, is caused by mutations in genes encoding cardiac sarcomeric proteins. E22K, a mutation in the myosin regulatory light chain sarcomere gene, is associated with the development of FHCM. However, the molecular mechanisms by which E22K mutation promotes septal hypertrophy are still elusive. The hypertrophic markers, including beta-myosin heavy chain, atrial natriuretic peptide and B-type natriuretic peptide, were upregulated, as detected by fluorescence quantitative PCR. The gene expression profiles were greatly altered in the left ventricle of E22K mutant mice. Among these genes, nuclear factor of activated T cells (NFAT) and protein kinase C-alpha (PKC-α) were upregulated, and their protein expression levels were also verified to be elevated. The fibrosis markers, such as phosphorylated Smad and transforming growth factor beta receptor, were also elevated in transgenic E22K mice. After receiving 6 weeks of procedural exercise training, the expression levels of PKC-α and NFAT were reversed in E22K mouse hearts. In addition, the expression levels of several fibrosis-related genes such as transforming growth factor beta receptor 1, Smad4, and alpha smooth muscle actin in E22K mouse hearts were also reversed. Genes that associated with cardiac remodeling such as myocyte enhancer factor 2C, extracellular matrix protein 2 and fibroblast growth factor 12 were reduced after exercising. Taken together, our results indicate that exercise can improve hypertrophy and fibrosis-related indices in transgenic E22K mice via PKC-α/NFAT pathway, which provide new insight into the prevention and treatment of familial hypertrophic cardiomyopathy.
Astragaloside IV Alleviates Infarction Induced Cardiomyocyte Injury by Improving Mitochondrial Morphology and Function
Authors: Zhang Wen , Zhang Ling , Zhou Huifen , Li Chang , Shao Chongyu , He Yu , Yang Jiehong , Wan Haitong
Published: February 2022

The protective effect of astragaloside IV (AS-IV) on myocardial injury after myocardial infarction has been reported. However, the underlying mechanism is still largely unknown. We established a myocardial infarction model in C57BL/6 mice and injected intraperitoneally with 10 mg/kg/d AS-IV for 4 weeks. The cardiac function, myocardial fibrosis, and angiogenesis were investigated by echocardiography, Masson's trichrome staining, and CD31 and smooth muscle actin staining, respectively. Cardiac mitochondrial morphology was visualized by transmission electron microscopy. Cardiac function, infarct size, vascular distribution, and mitochondrial morphology were significantly better in AS-IV-treated mice than in the myocardial infarction model mice. In vitro, a hypoxia-induced H9c2 cell model was established to observe cellular apoptosis and mitochondrial function. H9c2 cells transfected with silent information regulator 3 (Sirt3) targeting siRNA were assayed for Sirt3 expression and activity. Sirt3 silencing eliminated the beneficial effects of AS-IV and abrogated the inhibitory effect of AS-IV on mitochondrial division. These results suggest that AS-IV protects cardiomyocytes from hypoxic injury by maintaining mitochondrial homeostasis in a Sirt3-dependent manner.
Modular Screening Reveals Driver Induced Additive Mechanisms of Baicalin and Jasminoidin on Cerebral Ischemia Therapy
Authors: Li Bing , Wang Ying , Gu Hao , Yu Yanan , Wang Pengqian , Liu Jun , Zhang Yingying , Chen Yinying , Niu Qikai , Wang Bo , Liu Qiong , Guan Shuang , Li Yanda , Zhang Huamin , Wang Zhong
Published: February 2022

Combination therapy with increased efficacy and reduced toxicity plays a crucial role in treating complex diseases, such as stroke, but it remains an insurmountable barrier to elucidate the mechanisms of synergistic effects. Here, we present a Driver-induced Modular Screening (DiMS) strategy integrated synergistic module and driver gene identification to elucidate the additive mechanisms of Baicalin (BA) and Jasminoidin (JA) on cerebral ischemia (CI) therapy. Based on anti-ischemia genomic networks BA, JA, and their combination (BJ), we obtained 4, 3, and 9 On-modules of BA, JA, and BJ by modular similarity analysis. Compared with the monotherapy groups, four additive modules (Add-module, BJ_Mod-4, 7, 9, and 13), 15 driver genes of BJ were identified by modular similarity and network control methods, and seven driver proteins (PAQR8, RhoA, EMC10, GGA2, VIPR1, FAM120A, and SEMA3F) were validated by animal experiments. The functional analysis found neuroprotective roles of the Add-modules and driver genes, such as the Neurotrophin signaling pathway and FoxO signaling pathway, which may reflect the additive mechanisms of BJ. Moreover, such a DiMS paradigm provides a new angle to explore the synergistic mechanisms of combination therapy and screen multi-targeted drugs for complex diseases.
Distribution Prediction of Shale Deformation Structures in Tectonically Complex Area Based on Relationship Between Geological Structures and Shale Deformation
Authors: Cheng Guoxi , Jiang Bo , Li Fengli , Li Ming , Song Yu
Published: February 2022

The alteration of shale structures and properties induced by tectonic activities is an important factor restricting the efficient utilization of shale gas resources. Predicting the distributions of shale deformation structures is of significance for the potential evaluation and favorable area optimization of shale resources in tectonically complex areas. Taking the Wufeng–Longmaxi shale of the southern Sichuan Basin as the research object, deformation observations of shale outcrops and shale core samples were conducted to reveal the distribution patterns of shale deformation structures in fault and fold structures. On this basis, the distribution rules of shale deformation structures in the unexposed areas were predicted by considering the structural framework of the study area. Our research indicated that faults can cause structural deformation in a limited area and that the influences of reverse faults were relatively more significant. Shale near the fault planes of reverse faults usually showed intense folding deformations, with well-developed bedding-parallel and crumpled cleavages. Strong deformation structures (crumpled, mylonitized, scaly, fractured-crumpled, and flaky structure) were distributed. Structural deformations in shale near normal faults were mainly characterized by the increase of tectonic fractures, and shale usually showed cataclastic structure. In the areas affected by strike-slip faults, bedding-perpendicular fractures and the fractures high-angle oblique to bedding planes were well developed. Folds can cause shale to deform in a larger area than faults. Shale in core zones usually displayed strong deformation structures. In the core–limb transitional areas of folds, shale mainly developed bedding-parallel and bedding-perpendicular fractures, and shale usually displayed platy and cataclastic structure. The observed structural deformations in fold limbs were generally weak, and shale usually showed primary structure and weak brittle deformation structures. According to the structural framework of the study area, it is predicted that strong deformation structures are mainly distributed in the core zones of anticlines (especially the tight and closed ones) and near the fault planes of large-scale reverse faults, while medium-intensity brittle deformation structures (platy and cataclastic structure) are distributed in core–limb transitional areas of anticlines and near the normal and strike-slip faults. In the limbs of anticlines and the areas controlled by synclines (mostly wide and gentle), shale mainly shows primary structure and weak brittle deformation structures.