bluuebunny/crossref_metadata_2025 huggingface dataset:
Senolytics: Eliminating Senescent Cells and Alleviating Intervertebral Disc Degeneration
Authors: Wu Yuhao , Shen Shiwei , Shi Yifeng , Tian Naifeng , Zhou Yifei , Zhang Xiaolei
Published: March 2022

Intervertebral disc degeneration (IVDD) is the main cause of cervical and lumbar spondylosis. Over the past few years, the relevance between cellular senescence and IVDD has been widely studied, and the senescence-associated secretory phenotype (SASP) produced by senescent cells is found to remodel extracellular matrix (ECM) metabolism and destruct homeostasis. Elimination of senescent cells by senolytics and suppression of SASP production by senomorphics/senostatics are effective strategies to alleviate degenerative diseases including IVDD. Here, we review the involvement of senescence in the process of IVDD; we also discuss the potential of senolytics on eliminating senescent disc cells and alleviating IVDD; finally, we provide a table listing senolytic drugs and small molecules, aiming to propose potential drugs for IVDD therapy in the future.
Theaflavin Attenuates TBHP-Induced Endothelial Cells Oxidative Stress by Activating PI3K/AKT/Nrf2 and Accelerates Wound Healing in Rats
Authors: Chen Dalei , Wu Zhijian , Wu Lu-Ning , Jiang Jingtao , Hu Gui-Nv
Published: March 2022

The treatment of wounds remains a clinical challenge because of poor angiogenesis under the wound bed, and increasingly, the patients’ need for functional and aesthetically pleasing scars. Previous reports have shown that Theaflavin can induce angiogenesis and terminate the progression of ischemic cardiovascular disease, but limited therapy is available for the management of cutaneous wounds. In this study, our in vitro work discovered that human umbilical vein endothelial cells (HUVECs) exposed to Theaflavin can alleviate apoptosis and cell dysfunction induced by tert-butyl hydroperoxide (TBHP). The cellular activity of HUVECs were assessed by cell tube formation, migration and adhesion. Mechanistically, Theaflavin protected HUVECs from TBHP-stimulated cell apoptosis through the activation of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor (erythroid-derived 2)-like 2 (Nrf2) axis, so Nrf2 silencing can partly eliminate the cytoprotective effect of Theaflavin treatment. In in vivo experiments, administering Theaflavin orally can enhance vascularization in regenerated tissues and accelerate wound healing. In summary, our data served as a novel evidence for the wound healing treatment with Theaflavin, and certified the potential mechanism of Theaflavin, which can be used as a potential agent for cutaneous wound therapy.
Negative Modulation of Macroautophagy by Stabilized HERPUD1 is Counteracted by an Increased ER-Lysosomal Network With Impact in Drug-Induced Stress Cell Survival
Authors: Vargas Gabriela , Cortés Omar , Arias-Muñoz Eloisa , Hernández Sergio , Cerda-Troncoso Cristobal , Hernández Laura , González Alexis E. , Tatham Michael H. , Bustamante Hianara A. , Retamal Claudio , Cancino Jorge , Varas-Godoy Manuel , Hay Ronald T. , Rojas-Fernández Alejandro , Cavieres Viviana A. , Burgos Patricia V.
Published: March 2022

Macroautophagy and the ubiquitin proteasome system work as an interconnected network in the maintenance of cellular homeostasis. Indeed, efficient activation of macroautophagy upon nutritional deprivation is sustained by degradation of preexisting proteins by the proteasome. However, the specific substrates that are degraded by the proteasome in order to activate macroautophagy are currently unknown. By quantitative proteomic analysis we identified several proteins downregulated in response to starvation independently of ATG5 expression. Among them, the most significant was HERPUD1, an ER membrane protein with low expression and known to be degraded by the proteasome under normal conditions. Contrary, under ER stress, levels of HERPUD1 increased rapidly due to a blockage in its proteasomal degradation. Thus, we explored whether HERPUD1 stability could work as a negative regulator of autophagy. In this work, we expressed a version of HERPUD1 with its ubiquitin-like domain (UBL) deleted, which is known to be crucial for its proteasome degradation. In comparison to HERPUD1-WT, we found the UBL-deleted version caused a negative role on basal and induced macroautophagy. Unexpectedly, we found stabilized HERPUD1 promotes ER remodeling independent of unfolded protein response activation observing an increase in stacked-tubular structures resembling previously described tubular ER rearrangements. Importantly, a phosphomimetic S59D mutation within the UBL mimics the phenotype observed with the UBL-deleted version including an increase in HERPUD1 stability and ER remodeling together with a negative role on autophagy. Moreover, we found UBL-deleted version and HERPUD1-S59D trigger an increase in cellular size, whereas HERPUD1-S59D also causes an increased in nuclear size. Interestingly, ER remodeling by the deletion of the UBL and the phosphomimetic S59D version led to an increase in the number and function of lysosomes. In addition, the UBL-deleted version and phosphomimetic S59D version established a tight ER-lysosomal network with the presence of extended patches of ER-lysosomal membrane-contact sites condition that reveals an increase of cell survival under stress conditions. Altogether, we propose stabilized HERPUD1 downregulates macroautophagy favoring instead a closed interplay between the ER and lysosomes with consequences in drug-cell stress survival.
Neutrophil Migratory Patterns: Implications for Cardiovascular Disease
Authors: Dahdah Albert , Johnson Jillian , Gopalkrishna Sreejit , Jaggers Robert M. , Webb Darren , Murphy Andrew J. , Hanssen Nordin M. J. , Hanaoka Beatriz Y. , Nagareddy Prabhakara R.
Published: March 2022

The body’s inflammatory response involves a series of processes that are necessary for the immune system to mitigate threats from invading pathogens. Leukocyte migration is a crucial process in both homeostatic and inflammatory states. The mechanisms involved in immune cell recruitment to the site of inflammation are numerous and require several cascades and cues of activation. Immune cells have multiple origins and can be recruited from primary and secondary lymphoid, as well as reservoir organs within the body to generate an immune response to certain stimuli. However, no matter the origin, an important aspect of any inflammatory response is the web of networks that facilitates immune cell trafficking. The vasculature is an important organ for this trafficking, especially during an inflammatory response, mainly because it allows cells to migrate towards the source of insult/injury and serves as a reservoir for leukocytes and granulocytes under steady state conditions. One of the most active and vital leukocytes in the immune system’s arsenal are neutrophils. Neutrophils exist under two forms in the vasculature: a marginated pool that is attached to the vessel walls, and a demarginated pool that freely circulates within the blood stream. In this review, we seek to present the current consensus on the mechanisms involved in leukocyte margination and demargination, with a focus on the role of neutrophil migration patterns during physio-pathological conditions, in particular diabetes and cardiovascular disease.
The Role of Non-Coding RNAs in Autophagy During Carcinogenesis
Authors: de la Cruz-Ojeda Patricia , Flores-Campos Rocío , Navarro-Villarán Elena , Muntané Jordi
Published: March 2022

Macroautophagy (autophagy herein) is a cellular stress response and a survival pathway involved in self-renewal and quality control processes to maintain cellular homeostasis. The alteration of autophagy has been implicated in numerous diseases such as cancer where it plays a dual role. Autophagy serves as a tumor suppressor in the early phases of cancer formation with the restoration of homeostasis and eliminating cellular altered constituents, yet in later phases, autophagy may support and/or facilitate tumor growth, metastasis and may contribute to treatment resistance. Key components of autophagy interact with either pro- and anti-apoptotic factors regulating the proximity of tumor cells to apoptotic cliff promoting cell survival. Autophagy is regulated by key cell signaling pathways such as Akt (protein kinase B, PKB), mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) involved in cell survival and metabolism. The expression of critical members of upstream cell signaling, as well as those directly involved in the autophagic and apoptotic machineries are regulated by microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Consequently, non-coding RNAs play a relevant role in carcinogenesis and treatment response in cancer. The review is an update of the current knowledge in the regulation by miRNA and lncRNA of the autophagic components and their functional impact to provide an integrated and comprehensive regulatory network of autophagy in cancer.
Phosphorylation of MAD2 at Ser195 Promotes Spindle Checkpoint Defects and Sensitizes Cancer Cells to Radiotherapy in ATM Deficient Cells
Authors: Wang Yang , Yu Tianyu , Han Yi , He Yazhi , Song Yiran , Guo Leiming , An Liwei , Yang Chunying , Wang Feng
Published: March 2022

The spindle assembly checkpoint (SAC) is a critical monitoring device in mitosis for the maintenance of genomic stability. Specifically, the SAC complex comprises several factors, including Mad1, Mad2, and Bub1. Ataxia-telangiectasia mutated (ATM) kinase, the crucial regulator in DNA damage response (DDR), also plays a critical role in mitosis by regulating Mad1 dimerization and SAC. Here, we further demonstrated that ATM negatively regulates the phosphorylation of Mad2, another critical component of the SAC, which is also involved in DDR. Mechanistically, we found that phosphorylation of Mad2 is aberrantly increased in ATM-deficient cells. Point-mutation analysis further revealed that Serine 195 mainly mediated Mad2 phosphorylation upon ATM ablation. Functionally, the phosphorylation of Mad2 causes decreased DNA damage repair capacity and is related to the resistance to cancer cell radiotherapy. Altogether, this study unveils the key regulatory role of Mad2 phosphorylation in checkpoint defects and DNA damage repair in ATM-deficient cells.
Targeting the Ubiquitin-Proteasome System in Limb-Girdle Muscular Dystrophy With CAPN3 Mutations
Authors: Lasa-Elgarresta Jaione , Mosqueira-Martín Laura , González-Imaz Klaudia , Marco-Moreno Pablo , Gerenu Gorka , Mamchaoui Kamel , Mouly Vincent , López de Munain Adolfo , Vallejo-Illarramendi Ainara
Published: March 2022

LGMDR1 is caused by mutations in the CAPN3 gene that encodes calpain 3 (CAPN3), a non-lysosomal cysteine protease necessary for proper muscle function. Our previous findings show that CAPN3 deficiency leads to reduced SERCA levels through increased protein degradation. This work investigates the potential contribution of the ubiquitin-proteasome pathway to increased SERCA degradation in LGMDR1. Consistent with our previous results, we observed that CAPN3-deficient human myotubes exhibit reduced SERCA protein levels and high cytosolic calcium concentration. Treatment with the proteasome inhibitor bortezomib (Velcade) increased SERCA2 protein levels and normalized intracellular calcium levels in CAPN3-deficient myotubes. Moreover, bortezomib was able to recover mutated CAPN3 protein in a patient carrying R289W and R546L missense mutations. We found that CAPN3 knockout mice (C3KO) presented SERCA deficits in skeletal muscle in the early stages of the disease, prior to the manifestation of muscle deficits. However, treatment with bortezomib (0.8 mg/kg every 72 h) for 3 weeks did not rescue SERCA levels. No change in muscle proteasome activity was observed in bortezomib-treated animals, suggesting that higher bortezomib doses are needed to rescue SERCA levels in this model. Overall, our results lay the foundation for exploring inhibition of the ubiquitin-proteasome as a new therapeutic target to treat LGMDR1 patients. Moreover, patients carrying missense mutations in CAPN3 and presumably other genes may benefit from proteasome inhibition by rescuing mutant protein levels. Further studies in suitable models will be necessary to demonstrate the therapeutic efficacy of proteasome inhibition for different missense mutations.
Modeling Human Primary Microcephaly With hiPSC-Derived Brain Organoids Carrying CPAP-E1235V Disease-Associated Mutant Protein
Authors: An Hsiao-Lung , Kuo Hung-Chih , Tang Tang K.
Published: March 2022

The centrosome is composed of a pair of centrioles and serves as the major microtubule-organizing center (MTOC) in cells. Centrosome dysfunction has been linked to autosomal recessive primary microcephaly (MCPH), which is a rare human neurodevelopmental disorder characterized by small brain size with intellectual disability. Recently, several mouse models carrying mutated genes encoding centrosomal proteins have been generated to address the genotype–phenotype relationships in MCPH. However, several human-specific features were not observed in the mouse models during brain development. Herein, we generated isogenic hiPSCs carrying the gene encoding centrosomal CPAP-E1235V mutant protein using the CRISPR-Cas9 genome editing system, and examined the phenotypic features of wild-type and mutant hiPSCs and their derived brain organoids. Our results showed that the CPAP-E1235V mutant perturbed the recruitment of several centriolar proteins involved in centriole elongation, including CEP120, CEP295, CENTROBIN, POC5, and POC1B, onto nascent centrioles, resulting in the production of short centrioles but long cilia. Importantly, our wild-type hiPSC-derived brain organoid recapitulated many cellular events seen in the developing human brain, including neuronal differentiation and cortical spatial lamination. Interestingly, hiPSC-CPAP-E1235V-derived brain organoids induced p53-dependent neuronal cell death, resulting in the production of smaller brain organoids that mimic the microcephaly phenotype. Furthermore, we observed that the CPAP-E1235V mutation altered the spindle orientation of neuronal progenitor cells and induced premature neuronal differentiation. In summary, we have shown that the hiPSC-derived brain organoid coupled with CRISPR/Cas9 gene editing technology can recapitulate the centrosome/centriole-associated MCPH pathological features. Possible mechanisms for MCPH with centriole/centrosome dysfunction are discussed.
The Role of Extracellular Vesicles in Systemic Lupus Erythematosus
Authors: Zheng Chenghui , Xie Lin , Qin Haihong , Liu Xiao , Chen Xi , Lv Fan , Wang Li , Zhu Xiaohua , Xu Jinhua
Published: March 2022

Extracellular Vesicles (EVs) are small vesicles that can be actively secreted by most cell types into the extracellular environment. Evidence indicates that EVs can carry microRNAs (miRNAs), long non-coding RNAs (lncRNAs), tRNA-derived small RNAs (tsRNAs), proteins, and lipids to target cells or tissue organizations. Latest studies show that EVs play a vital role in the immune modulation and may contribute to the pathogenesis of autoimmune diseases. Systemic lupus erythematosus (SLE) is a common autoimmune disease characterized by abnormal T cell activation and sustained production of autoantibodies against self-antigens, resulting in inflammation and damage to multiple systems. Pathogenic mechanisms of SLE, however, are still not well understood. In this review, we summarize the latest research advances on the functions and mechanisms of EVs, and its role in the pathogenesis, diagnosis, and treatment of SLE.
Targeting MALT1 Suppresses the Malignant Progression of Colorectal Cancer via miR-375/miR-365a-3p/NF-κB Axis
Authors: Qian Rui , Niu Xinli , Wang Yinghui , Guo Zhi , Deng Xuyi , Ding Zhenhua , Zhou Meijuan , Deng Haijun
Published: March 2022

Colorectal cancer (CRC) is a malignant tumor with the second highest morbidity and the third highest mortality in the world, while the therapeutic options of targeted agents remain limited. Here, mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), known as the upstream of the NF-κB signaling pathway, was identified to be highly upregulated in CRC tumors and cell lines. Furthermore, the downregulation of MALT1 or inhibition of its proteolytic function by MI-2 suppressed the cell proliferation and migration of CRC cells. In vivo, suppressing the MALT1 expression or its proteasome activity effectively reduced the size of the subcutaneous tumor in nude mice. Mechanistically, miR-375 and miR-365a-3p were identified to inhibit NF-κB activation via targeting MALT1. Overall, our results highlight that a novel regulatory axis, miRNA-MALT1-NF-κB, plays a vital role in the progression of CRC and provides novel and hopeful therapeutic targets for clinical treatment.
Prevalence of Eimeria Spp. Among Goats in China: A Systematic Review and Meta-Analysis
Authors: Diao Nai-Chao , Zhao Bo , Chen Yu , Wang Qi , Chen Zi-Yang , Yang Yang , Sun Yu-Han , Shi Jun-Feng , Li Jian-Ming , Shi Kun , Gong Qing-Long , Du Rui
Published: March 2022

Eimeria spp. infection can cause weight loss in goats, and severe cases can lead to the death of lambs, resulting in economic losses to the goat industry. To explore the pooled prevalence of Eimeria spp. in goats in China, we obtained 70 related publications from five databases and conducted a meta-analysis. In China, the combined prevalence of Eimeria spp. in goats was 78.7% (95% confidence interval (CI): 68.15–87.67). Among them, the most serious infections occurred in Northeast China (88.0%, 95% CI: 83.54–91.86). The main Eimeria species were E. alijevi (43.7%, 95% CI: 29.53–58.45), E. arloingi (49.7%, 95% CI: 34.83–64.49), E. christenseni (41.2%, 95% CI: 27.07–56.16), and E. ninakohlyakimovae (35.9%, 95% CI: 21.02–52.31). In the sampling year subgroup, 2006 or later presented a lower prevalence (75.3%, 95%CI: 58.72–88.72). In terms of age, the point estimate for young goats (≤ 1 year) was higher (89.9%, 95% CI: 80.82–96.48). The Float (NaCl) method showed the lowest prevalence of Eimeria spp. in goats (75.9%, 95%CI: 62.00–87.46). In the season subgroup, the highest prevalence was in summer (81.5%, 95%CI: 49.62–99.18). Female goats presented a higher prevalence of Eimeria spp. infection than male goats (70.7%, 95%CI: 27.90–98.96). The prevalence was lower in the intensive feeding model (77.4%, 95%CI: 66.56–86.67) and higher in free feeding goats (79.4%, 95%CI: 66.46–89.92). In addition, we also analyzed the potential relationship between geographical factors and the prevalence of Eimeria spp. infection in goats in China. Our findings suggested that Eimeria spp. infection in goats is widespread in China. Despite the overall downward trend, this infection cannot be ignored. We recommend that breeders use anticoccidial drugs to prevent and treat this disease, while improving the feeding conditions and managemental practices to reduce the economic losses caused by Eimeria infection to the goat industry.
Long-Term Post-COVID-19 Associated Oral Inflammatory Sequelae
Authors: Alfaifi Areej , Sultan Ahmed S. , Montelongo-Jauregui Daniel , Meiller Timothy F. , Jabra-Rizk Mary Ann
Published: March 2022

The oral cavity remains an underappreciated site for SARS-CoV-2 infection despite the myriad oral conditions observed in COVID-19 patients. Recently, replicating SARS-CoV-2 was found inside salivary epithelial cells resulting in inflammation and atrophy of salivary glands. Saliva possesses healing properties crucial for maintaining the health of the oral mucosa. Specifically, salivary antimicrobial peptides, most notable, histatin-5 exclusively produced in salivary glands, plays a vital role in innate immunity against colonizing microbial species. The demonstration of SARS-CoV-2 destruction of gland tissue where histatin-5 is produced strongly indicate that histatin-5 production is compromised due to COVID-19. Here we present a case of a patient presenting with unexplained chronic oral dysesthesia and dysgeusia post-recovery from COVID-19. To explore potential physiological mechanisms behind the symptoms, we comparatively analyzed saliva samples from the patient and matched healthy subject for histatin-5 and key cytokines. Findings demonstrated significantly reduced histatin-5 levels in patient’s saliva and activation of the Th17 inflammatory pathway. As histatin-5 exhibits potent activity against the opportunistic oral pathogen Candida albicans, we evaluated saliva potency against C. albicans ex vivo. Compared to control, patient saliva exhibited significantly reduced anti-candidal efficacy. Although speculative, based on history and salivary analysis we hypothesize that salivary histatin-5 production may be compromised due to SARS-CoV-2 mediated salivary gland destruction. With the current lack of emphasis on implications of COVID-19 on oral health, this report may provide lacking mechanistic insights that may lead to reassessment of risks for oral opportunistic infections and mucosal inflammatory processes in acutely-ill and recovered COVID-19 patients.
High Genetic Diversity and Rickettsia felis in Pediculus humanus Lice Infesting Mbuti (pygmy people), -Democratic Republic of Congo
Authors: Amanzougaghene Nadia , Drali Rezak , Shako Jean-Christophe , Davoust Bernard , Fenollar Florence , Raoult Didier , Mediannikov Oleg
Published: March 2022

Pediculus humanus is an obligate bloodsucking parasite of humans that has two ecotypes, the head louse and the body louse, which share an intimate history of coevolution with their human host. In the present work, we obtained and analysed head and body lice collected from Mbuti pygmies living in the Orientale province of the Democratic Republic of the Congo. Cytochrome b DNA analysis was performed in order to type the six known lice clades (A, D, B, F, C and E). The results revealed the presence of two mitochondrial clades. Clade D was the most frequent (61.7% of 47), followed by clade A (38.3% of 47). Sixteen haplotypes were found in 47 samples, of which thirteen were novel haplotypes, indicating an unusually high genetic diversity that closely mirrors the diversity of their hosts. Moreover, we report for the first time the presence of the DNA of R. felis in three (6.4% of 47) head and body lice belonging to both clades A and D. Additional studies are needed to clarify whether the Pediculus lice can indeed transmit this emerging zoonotic bacterium to their human hosts.
A CRISPR-Cas12a-Assisted Fluorescence Platform for Rapid and Accurate Detection of Nocardia cyriacigeorgica
Authors: Liu Xueping , Qiu Xiaotong , Xu Shuai , Che Yanlin , Han Lichao , Kang Yutong , Yue Yuan , Chen Shenglin , Li Fang , Li Zhenjun
Published: March 2022

Nocardia cyriacigeorgica has gradually become a common pathogen in clinical microbial infections. Identification of Nocardia at the species level is essential to assess the susceptibility and pathogenicity of antimicrobials. However, there is no suitable method for rapid and accurate laboratory detection of N. cyriacigeorgica. In this study, we combined PCR amplification with the CRISPR-Cas12a system to establish a novel detection platform, named CRISPR-PCR, and applied it to the detection of N. cyriacigeorgica in clinical samples. The Cas12a protein exhibited collateral cleavage activity following CRISPR RNA binding to specific targets, then indiscriminately cleaved nearby single-stranded DNA, and this was evaluated for diagnostic nucleic acid detection by measuring the fluorescence signal using a fluorescence reader. The assay takes only 2 h, including DNA extraction for 20 min, nucleic acid pre-amplification for 70 min, and fluorescence detection for 20 min. The limit of detection for N. cyriacigeorgica was 10-3 ng and the specificity was 100%. Thus, the N. cyriacigeorgica CRISPR-PCR assay is a rapid and specific method for detecting N. cyriacigeorgica, and the CRISPR-PCR fluorescence detection platform has great potential for detection of other pathogens.
Solo Dining at Home in the Company of ICT Devices
Authors: Nicolau i Torra Núria , Lemke Mailin , Huisman Gijs
Published: March 2022

The consumption of a solo meal is often subject to negative associations. Studies indicate that solo diners use information and communication technology (ICT) devices such as smartphones, to mitigate negative experiences such as boredom and loneliness, especially when dining in a public context. However, we know less about the motivation to use such devices and consequent meal experiences in a private context. For this exploratory qualitative study, we asked participants to fill out a cultural probe kit to capture their dining experience and use of ICT devices over a period of seven days. Once completed, the content was discussed with participants during a semi-structured interview. Data was analyzed using thematic analysis in a deductive and inductive form leading to four themes: (1) The experience of eating with others; (2) The use of electronic devices while eating; (3) The meaning of food; and (4) Relaxing features and influences. Participants indicated that eating alone can be a pleasurable experience that people enjoy and perceive as relaxing. ICT devices were named to play an essential part in the dining experience. The entertainment that devices provide can mitigate feelings of loneliness and uncomfortable silence when eating by oneself. We reflect on the findings and point out potential design avenues for future studies.
Proteomic Analysis Suggests Altered Mitochondrial Metabolic Profile Associated With Diabetic Cardiomyopathy
Authors: Gomes Karina P. , Jadli Anshul S. , de Almeida Luiz G. N. , Ballasy Noura N. , Edalat Pariya , Shandilya Ruchita , Young Daniel , Belke Darrell , Shearer Jane , Dufour Antoine , Patel Vaibhav B.
Published: March 2022

Diabetic cardiomyopathy (DbCM) occurs independently of cardiovascular diseases or hypertension, leading to heart failure and increased risk for death in diabetic patients. To investigate the molecular mechanisms involved in DbCM, we performed a quantitative proteomic profiling analysis in the left ventricle (LV) of type 2 diabetic mice. Six-month-old C57BL/6J-lepr/lepr (db/db) mice exhibited DbCM associated with diastolic dysfunction and cardiac hypertrophy. Using quantitative shotgun proteomic analysis, we identified 53 differentially expressed proteins in the LVs of db/db mice, majorly associated with the regulation of energy metabolism. The subunits of ATP synthase that form the F1 domain, and Cytochrome c1, a catalytic core subunit of the complex III primarily responsible for electron transfer to Cytochrome c, were upregulated in diabetic LVs. Upregulation of these key proteins may represent an adaptive mechanism by diabetic heart, resulting in increased electron transfer and thereby enhancement of mitochondrial ATP production. Conversely, diabetic LVs also showed a decrease in peptide levels of NADH dehydrogenase 1β subcomplex subunit 11, a subunit of complex I that catalyzes the transfer of electrons to ubiquinone. Moreover, the atypical kinase COQ8A, an essential lipid-soluble electron transporter involved in the biosynthesis of ubiquinone, was also downregulated in diabetic LVs. Our study indicates that despite attempts by hearts from diabetic mice to augment mitochondrial ATP energetics, decreased levels of key components of the electron transport chain may contribute to impaired mitochondrial ATP production. Preserved basal mitochondrial respiration along with the markedly reduced maximal respiratory capacity in the LVs of db/db mice corroborate the association between altered mitochondrial metabolic profile and cardiac dysfunction in DbCM.
Efficacy and Safety of Veno-Arterial Extracorporeal Membrane Oxygenation in the Treatment of High-Risk Pulmonary Embolism: A Retrospective Cohort Study
Authors: Tsai Hao-Yu , Wang Yu-Tang , Lee Wei-Chieh , Yen Hsu-Ting , Lo Chien-Ming , Wu Chia-Chen , Huang Kwan-Ru , Chen Yin-Chia , Sheu Jiunn-Jye , Chen Yen-Yu
Published: March 2022

Objectives

Veno-arterial extracorporeal membrane oxygenation (ECMO) is increasingly used to treat high-risk pulmonary embolism (PE). However, its efficacy and safety remain uncertain. This retrospective cohort study aimed to determine whether ECMO could improve the clinical outcomes of patients with high-risk PE.

Methods

Forty patients with high-risk PE, who were admitted to Kaohsiung Chang Gung Memorial Hospital between January 2012 and December 2019, were included in this study. Demographic data and clinical outcomes were compared between patients treated without ECMO (non-ECMO group) and those treated with ECMO (ECMO group). Appropriate statistical tools were used to compare variables between groups and the survival was analyzed using the Kaplan–Meier method.

Results

The overall in-hospital mortality rate was 55%, in which 65% (26/40) of patients presented with cardiac arrest with a mortality rate of 77%, which was higher than that of patients without cardiac arrest (14%). There was no significant difference in major complications and in-hospital mortality between the non-ECMO and ECMO groups. However, in subgroup analysis, compared with patients treated without ECMO, earlier ECMO treatment was associated with a reduced risk of cardiac arrest (P = 0.023) and lower in-hospital mortality (P = 0.036). A log-rank test showed a significantly higher cumulative overall survival in the earlier ECMO treatment group (P = 0.033).

Conclusions

In this retrospective cohort study, earlier ECMO treatment was associated with lower in-hospital mortality among unstable patients without cardiac arrest. Our findings suggest that ECMO can be considered as an initial treatment option for patients with high-risk PE in higher-volume hospitals.
High Prevalence of Asymptomatic Intracranial Atherosclerosis in Elder Women With Tubal Ligation: Result From a Community-Based Study in Shandong, China
Authors: Ma Xiaotong , Sang Shaowei , Zhao Yuanyuan , Wang Xiang , Ji Xiaokang , Shao Sai , Wang Guangbin , Xue Fuzhong , Du Yifeng , Lv Ming , Sun Qinjian
Published: March 2022

Background

In addition to traditional cardiovascular risk factors, gender-specific factors may also contribute to intracranial atherosclerosis. This study aimed to comprehensively investigate the association between asymptomatic intracranial atherosclerosis (aICAS) and menstrual or reproductive history (MRH), namely, menstruation, pregnancy, childbirth, menopause, and contraception.

Methods

Participants in this study were selected from the Kongcun town aICAS study. MRH was collected through structured case report forms, in which menarche age, menstrual regularity, dysmenorrhea, number of pregnancies, number of childbirths, age of first pregnancy, breastfeeding, menopause, menopause age, and contraceptive methods were all involved. All characteristics were compared by chi-squared and nonparametric tests as applicable. Logistic regression model and sensitivity analysis were used to analyze the association between aICAS and MRH.

Results

A total of 1,052 female participants were involved in this study, of which 5.7% had moderate to severe aICAS. Tubal ligation was significantly associated with aICAS in univariate analysis [crude odds ratio (OR), 2.85; 95% CI, 1.22–6.62; P = 0.015]. This association was still significant among female participants over 60 years old after multivariate adjustment (adjusted OR, 4.36; 95% CI, 1.55–12.24; P = 0.005). Sensitivity analysis showed a similar result (adjusted OR, 3.76; 95% CI, 1.24–11.41; P = 0.020). Menopause lost significant association with aICAS after multivariate adjustment (adjusted OR, 1.68; 95% CI, 0.66–4.24; P = 0.275). No other MRH factors were found to be associated with aICAS.

Conclusion

Tubal ligation may be associated with a higher prevalence of aICAS in Chinese elderly women. This provides a new perspective to study the epidemiological characteristics of ICAS.
Paroxysmal Atrial Fibrillation in Elderly: Worldwide Preliminary Data of LINAC-Based Stereotactic Arrhythmia Radioablation Prospective Phase II Trial
Authors: Di Monaco Antonio , Gregucci Fabiana , Bonaparte Ilaria , Troisi Federica , Surgo Alessia , Di Molfetta Domenico , Vitulano Nicola , Quadrini Federico , Carbonara Roberta , Martinelli Gaetano , Guida Pietro , Ciliberti Maria Paola , Fiorentino Alba , Grimaldi Massimo
Published: March 2022

Treatment approach for elderly patients with atrial fibrillation (AF) is difficult. The present prospective phase-II trial evaluated LINAC-based stereotactic arrhythmia radioablation safety in this population. The reported data of the first 5 patients worldwide, showed no side effects, absence of AF episodes and without antiarrhythmic drugs.

Trial Registration:

ClinicalTrials.gov, identifier: NCT04575662.
The Role of Glutamine and Glutaminase in Pulmonary Hypertension
Authors: Wang Shang , Yan Yi , Xu Wei-Jie , Gong Su-Gang , Zhong Xiu-Jun , An Qin-Yan , Zhao Ya-Lin , Liu Jin-Ming , Wang Lan , Yuan Ping , Jiang Rong
Published: March 2022

Pulmonary hypertension (PH) refers to a clinical and pathophysiological syndrome in which pulmonary vascular resistance and pulmonary arterial pressure are increased due to structural or functional changes in pulmonary vasculature caused by a variety of etiologies and different pathogenic mechanisms. It is followed by the development of right heart failure and even death. In recent years, most studies have found that PH and cancer shared a complex common pathological metabolic disturbance, such as the shift from oxidative phosphorylation to glycolysis. During the shifting process, there is an upregulation of glutamine decomposition driven by glutaminase. However, the relationship between PH and glutamine hydrolysis, especially by glutaminase is yet unclear. This review aims to explore the special linking among glutamine hydrolysis, glutaminase and PH, so as to provide theoretical basis for clinical precision treatment in PH.
Geoarchaeology and Heritage Management: Identifying and Quantifying Multi-Scalar Erosional Processes at Kisese II Rockshelter, Tanzania
Authors: Patania Ilaria , Porter Samantha T. , Keegan William F. , Dihogo Rukia , Frank Sara , Lewis Jason , Mashaka Husna , Ogutu Julius , Skosey-Lalonde Elena , Tryon Christian A. , Niespolo Elizabeth M. , Colarossi Debra , Ranhorn Kathryn L.
Published: March 2022

Natural and anthropogenically induced soil erosion can cause serious loss of the archaeological record. Our work shows the value of multi-scalar geoarchaeological study when excavating and re-excavating rockshelters in a highly dynamic sedimentary environment where erosion is prominent. Here we present our work on Kisese II rockshelter, Tanzania, originally excavated in the 1950s and largely unpublished, that preserves an important Pleistocene-Holocene archaeological record integral to understanding the deep history of the Kondoa Rock-Art World Heritage Center. Unlike rockshelters in quiescent tectonic settings, like much of central Europe or South Africa, Kisese II exists in highly dynamic sedimentary environments associated with the active tectonics of the Great Rift Valley system exacerbated by human-induced environmental and climate change. We report on our 2017 and 2019 exploratory research that includes integrated regional-, landscape-, and site-scale geoarchaeological analyses of past and present sedimentary regimes and micromorphological analyses of the archaeological sediments. Historical records and aerial photographs document extensive changes in vegetation cover and erosional regimes since the 1920s, with drastic changes quantified between 1960 and 2019. Field survey points to an increased erosion rate between 2017 and 2019. To serve future archaeologists, heritage specialists, and local populations we combine our data in a geoarchaeological catena that includes soil, vegetation, fauna, and anthropogenic features on the landscape. At the site, micromorphological coupled with chronological analyses demonstrate the preservation of in situ Pleistocene deposits. Comparison of photographs from the 1956 and 2019 excavations show a maximum sediment loss of 68 cm in 63 years or >10% of >6-m-thick sedimentary deposit. In the studied area of the rockshelter we estimate ~1 cm/yr of erosion, suggesting the ongoing removal of much of the higher archaeological sediments which, based on the coarse stratigraphic controls and chronology of the original Inskeep excavations, would suggest the loss of much of the archaeological record of the last ~4000 years. These multi-scalar data are essential for the construction of appropriate mitigation strategies and further study of the remaining stratigraphy.
Involving Risk Reduction Practitioners and Other Experts in the Management of Super-Catastrophes via an Online Interactive Platform
Authors: Mignan Arnaud , Mochel Loïc , Ducos Géraldine
Published: March 2022

Super-catastrophes that lead to extensive disruption and loss amplification are frequently due to domino effects crossing natural, technological, and socio-economic systems. Although secondary effects of natural disasters are often considered in official hazard assessment platforms (e.g., landslides following earthquakes, storm surges), the main catalysts of long chains-of-events, which are network failure and business interruption, are generally not. This is partly due to the difficulty in handling complex and systemic situations. Yet in an increasingly interdependent world, crisis management requires foresight with the ability to consider those secondary effects. Such an ability can be brought in using interactive numerical tools. We have developed an online interactive platform for the pre-assessment phase of super-catastrophes based on Markov chain theory. The tool is centered on the elaboration of a transition matrix of event interactions, from which domino effects can be modeled and ranked in the background. Risk practitioners and other experts first list hazardous events, which are then populated in the matrix in both rows (trigger events) and columns (target events). As the square matrix grows, the platform’s users indicate which events can directly trigger another event in a binary approach. With enough participants, those binary decisions turn into weighted rules of interactions. In the process, the participants may discover missing links and update the matrix accordingly. To cover the full space of possibilities, three categories of events are systematically considered: natural, technological, and socio-economic. A group of experts can generate a transition matrix to explore the concept of super-catastrophe in general or to draw up possible crisis scenarios for decision-makers at any level of a territory (from a city to a country). Use of such a tool in practical situations, its integration into the management of prevention, planning for potential crisis situations, and training are discussed. Particular attention is given to the ability of this platform to help decision making within the context of a crisis unit with the need for quick evaluations.
Numerical Simulation Study on Dust Suppression Mechanism of Burning Rock Blasting in Open-Pit Mine
Authors: Jia ZhengZhao , Song ZiLing , Fan JunFu , Jiang JuYu , Guo ShuPeng
Published: March 2022

In an open-pit mine in Xinjiang, part of the stripped area is covered by burnt rock. Due to the low strength and fragility of burnt rock, dust is more easily generated during blasting. Taking the mining area as the research background, the mechanical property parameters of burnt rock were tested, and the blasting parameter design of on-site operation was understood. The blasting numerical simulation of burnt rock step was carried out by using a numerical simulation software (LS-DYNA). From the angle of stress on rock, the stress cloud and stress curve of numerical simulation are analyzed, and it is concluded that the fundamental reason for the large dust production in blasting operation is that the burnt rock is crushed excessively after the action of explosion wave, and the explosive energy is too large, which is converted into kinetic energy to drive the dust to escape. In order to improve the utilization rate of explosives and reduce the output of blasting dust, the original blasting parameters were optimized as 8-m hole spacing, 6.5-m row spacing, 0.21-kg/m³ unit explosive consumption, 1-m interval charge, and 55-ms short-delay blasting through numerical simulation and orthogonal experiment. In the mining area, the measures of dustproof and dust reduction by blasting protection blanket and dust absorption cotton are adopted. Combined with the optimized blasting parameters, the field test proves that the dust removal efficiency is up to 82.4%.
Accelerating the Change to Smart Societies- a Strategic Knowledge-Based Framework for Smart Energy Transition of Urban Communities
Authors: Zaidan Esmat , Ghofrani Ali , Abulibdeh Ammar , Jafari Mohsen
Published: March 2022

Urban communities differ in their social, economic, and environmental characteristics, as well as in the approach to energy use. Dynamic energy use and available on-site resources allow interaction with the surroundings and contribute to the key performance indicators of smart cities. This study aimed at proposing systematically a strategic framework for smart cities development by gradually transforming urban communities into smart-energy systems. This framework is based on multidisciplinary practices regarding the staged planning of smart communities and develops smart transformation concepts to enhance capacities toward the preservation, revitalization, livability, and sustainability of a community. In this study, we focused on the concept of smart and zero-carbon communities by using technology and infrastructure. We also considered the premise of the “community” and the related social, technological, and economic aspects. The decision constructs are explained from the perspective of a bottom-up approach ranging from preliminary inspections to economic investment planning. The study proposed a set of decision constructs aimed at allowing planners, engineers, and investors to have different alternatives at their disposal and select a feasible set of practical solutions for smart transformations accordingly.
Effects of In Situ Remediation on Copper Distribution and Soil Aggregate Adsorption–Desorption Characteristics in Smelter-Impacted Soil
Authors: Xu Lei , Xing Xiangyu , Peng Jianbiao , Ji Mingfei
Published: March 2022

To evaluate the effect of in situ chemical remediation on copper (Cu) immobilisation and migration, in situ chemically remediated soils from a smelter-impacted field were partitioned into four aggregate size fractions and their Cu adsorption characteristics were investigated. The results indicate that the highest Cu concentration occurred in the <0.053 mm size fraction, while the highest Cu mass loading was obtained in the 0.25–2 mm size fraction (39.9–42.5%). However, in situ remediation increased the Cu mass loading levels in the >0.25 mm aggregates. A pseudo-second-order model was used to fit the adsorption process obtained in kinetic experiments, while the data from isothermal experiments were described using the Freundlich model. The fastest adsorption rate was observed in the <0.053 mm fraction, and the adsorption capacity of the soil aggregates improved after combined in situ remediation. The amount of Cu2+ adsorbed increased with increasing pH. The <0.053 mm fraction exhibited lower desorption compared with the other fractions at low pH values. In addition, all particle size aggregates treated with apatite and Elsholtzia splendens had the lowest desorption rates at different pH values.
Structural Features of China's Industrial Pollution Inequality: A Spatial-Temporal Distribution Perspective
Authors: Luo Jin , Wang Yuan , Zhu Lin , Jiang Pei-Pei , He Yan-Min , Hao Ting-Ting
Published: March 2022

With growing concerns about the allocation inequality of environmental benefits and pollution, it is crucial to investigate whether a special characteristic of China’s environmental inequality has emerged. The present study aims to elucidate the regional spatial features of industrial pollution inequality (IPI) (waste gas, wastewater, and solid waste measured by the Theil index separately) and their relevance to national territorial space planning strategies. Furthermore, we make a novel attempt to develop an integrated framework that employs a developed-Kaya identity with the Logarithmic Mean Divisia Index method to uncover the driving force of IPI disparities. We make use of the data published recently by the provincial panel of China, during the period 2000–2015. Based on this information, we found notable spatial-temporal heterogeneity in China’s IPI, highly correlated to China’s core national territorial space planning strategy, the “T-shaped” spatial development strategy. The empirical results support the “structural features” hypothesis in IPI for China. In particular, the Coastal Region has a great edge in industrial pollution equality. In most provinces in the Inland Corridor along the Yangtze River, the trend of IPI has been alleviated to some extent. However, provinces further inland that are off-side the two axes of “T-shaped” spatial development strategy have to respond to the two-fold challenge of the exacerbated trend in IPI both within and between the regions. Our findings also indicate that the effect of technological inequality is the main driving force for IPI in the earlier stage of development. However, effects of economic inequality together with that of economic structure inequality manifest in the middle or transition period and the economic inequality effect is the determinant in the later stage of development. Additionally, contributions of size effect and inequality effect are changeable over development process, economic inequality effect outweighs the economic size effect for IPI in more developed districts or districts in higher developing phases. These findings may help the government incorporate environmental equality goals into regional policies and contribute to the emerging literature on environmental inequality.
The Effect of Extreme Rainfall Events on Riverbank Slope Behaviour
Authors: Nazrien Ng Jeffery , Mohd Taib Aizat , Razali Irfan Haziq , Abd Rahman Norinah , Wan Mohtar Wan Hanna Melini , A. Karim Othman , Mat Desa Safari , Awang Suriyani , Mohd Mohd Syazwan Faisal
Published: March 2022

Many slope failures take place during or after rainfall events. Landslides are one of the tragedies associated with slope failures and often lead to fatal accidents. A study on the effects of extreme rainfall on slope stability considering the historical rainfall data, slope characteristics and properties, and flow boundary conditions was undertaken. This study investigated the behaviour of the Sg Langat slope under the influence of extreme rainfall gathered from historical data. Sg Langat was selected as the research area because of its high riverbank failures. The focus of this study are as follows: 1) to determine the effect of slope angles on slope stability, 2) to assess the development of pore-water pressure based on the changing groundwater levels, and 3) to analyse the influence of extreme rainfall events on the slope behaviour via numerical modelling. This study enhances the understanding of certain slope conditions and contributes to the analysis of slope stability through numerical modelling, making it relatively convenient to observe the soil conditions for determining the slope stability of the research area in regards to the effect of extreme rainfall. The results were obtained with respect to the changes in the pore-water pressure and the factor of safety. It was observed that the pressure changes were different for every channel, demonstrating that the generation of negative pore-water pressure was not directly affected by the type of analysis and the rainfall infiltration alone. Moreover, the slopes on all channels presented were considered unstable because of the considerable changes in the negative pore-water pressure at a relatively shallow depth, causing soil strength reduction. The factor of safety recorded for Channel 1 was the lowest at 0.18, whereas Channel 3 had the highest factor of safety of 1.11 but was still considered unsafe as it fell below the standard safety margin of 1.3. Apart from the different rainfall intensities applied, the geometry of the slopes also affected the slope stability.