bluuebunny/crossref_metadata_2025 huggingface dataset:
Osteocytes Enhance Osteogenesis by Autophagy-Mediated FGF23 Secretion Under Mechanical Tension
Authors: Xu Huiyue , Xia Meng , Sun Lian , Wang Hua , Zhang Wei-Bing
Published: January 2022

Mechanical stimuli control cell behaviors that are crucial for bone tissue repair. Osteocytes sense extracellular mechanical stimuli then convert them into biochemical signals to harmonize bone remodeling. However, the mechanisms underlying this process remain unclear. Autophagy, which is an evolutionarily preserved process, that occurs at a basal level when stimulated by multiple environmental stresses. We postulated that mechanical stimulation upregulates osteocyte autophagy via AMPK-associated signaling, driving osteocyte-mediated osteogenesis. Using a murine model of orthodontic tooth movement, we show that osteocyte autophagy is triggered by mechanical tension, increasing the quantity of LC3B-positive osteocytes by 4-fold in the tension side. Both in vitro mechanical tension as well as the chemical autophagy agonist enhanced osteocyte Fibroblast growth factor 23 (FGF23) secretion, which is an osteogenenic related cytokine, by 2-and 3-fold, respectively. Conditioned media collected from tensioned osteocytes enhanced osteoblast viability. These results indicate that mechanical tension drives autophagy-mediated FGF23 secretion from osteocytes and promotes osteogenesis. Our findings highlight a potential strategy for accelerating osteogenesis in orthodontic clinical settings.
Pan-Cancer Study on Protein Kinase C Family as a Potential Biomarker for the Tumors Immune Landscape and the Response to Immunotherapy
Authors: Abdelatty Alaa , Sun Qi , Hu Junhong , Wu Fubing , Wei Guanqun , Xu Haojun , Zhou Guoren , Wang Xiaoming , Xia Hongping , Lan Linhua
Published: January 2022

The protein kinase C (PKC) family has been described with its role in some cancers, either as a promoter or suppressor. PKC signaling also regulates a molecular switch between transactivation and transrepression activity of the peroxisome proliferator-activated receptor alpha (PPARalpha). However, the role of different PKC enzymes in tumor immunity remains poorly defined. This study aims to investigate the correlation between PKC genes and tumor immunity, in addition to studying the probability of their use as predictive biomarkers for tumor immunity and immunotherapeutic response. The ssGSEA and the ESTIMATE methods were used to assess 28 tumor-infiltrating lymphocytes (TILs) and the immune component of each cancer, then correlated with PKC levels. Prediction of PKC levels-dependent immunotherapeutic response was based on human leukocytic antigen (HLA) gene enrichment scores and programmed cell death 1 ligand (PD-L1) expression. Univariate and multivariate Cox analysis was performed to evaluate the prognostic role of PKC genes in cancers. Methylation level and CNAs could drive the expression levels of some PKC members, especially PRKCI, whose CNGs are predicted to elevate their level in many cancer types. The most crucial finding in this study was that PKC isoenzymes are robust biomarkers for the tumor immune status, PRKCB, PRKCH, and PRKCQ as stimulators, while PRKCI and PRKCZ as inhibitors in most cancers. Also, PKC family gene levels can be used as predictors for the response to immunotherapies, especially HLAs dependent and PD-L1 blockade-dependent ones. In addition to its prognostic function, all PKC family enzymes are promising tumor immunity biomarkers and can help select suitable immune therapy in different cancers.
TNF Family–Based Signature Predicts Prognosis, Tumor Microenvironment, and Molecular Subtypes in Bladder Carcinoma
Authors: Li Huihuang , Liu Siyuan , Li Chenxuan , Xiao Zicheng , Hu Jiao , Zhao Cheng
Published: January 2022

Background: Tumor necrosis factor (TNF) family members play vital roles in cancer development and antitumor immune responses. However, the expression patterns, prognostic values, and immunological characteristics of TNF members in bladder carcinoma (BLCA) remain unclear.

Methods: The training cohort, TCGA-BLCA, was downloaded from The Cancer Genome Atlas; another two Gene Expression Omnibus datasets (GSE13507 and GSE32894) and the Xiangya cohort (RNA-sequencing cohort collected from our hospital) were used as the external validation cohort. The least absolute shrinkage and selection operator (LASSO) algorithm and cross-validation were used to screen variables. Cox regression model and random survival forest (RSF) were used to develop the risk score, respectively. Then, we systematically correlated the TNF risk score with the tumor microenvironment (TME) cell infiltration, molecular subtypes of BLCA, and the potential value for predicting the efficacy of immunotherapy.

Results: We developed two TNF-based patterns, named TNF cluster 1 and TNF cluster 2. TNF cluster 1 exhibited poorer survival outcome and an inflamed TME characteristic compared with TNF cluster 2. We then filtered out 196 differentially expressed genes between the two TNF clusters and applied the LASSO algorithm and cross-validation to screen out 22 genes to build the risk score. For risk score, we found that RSF exhibited higher efficacy than the Cox regression model, and we chose the risk score developed by RSF for the following analysis. BLCA patients in the higher risk score group showed significantly poorer survival outcomes. Moreover, these results could be validated in the external validation cohorts, including the GSE13507, GSE32894, and Xiangya cohorts. Then, we systematically correlated the risk score with TME cell infiltration and found that it was positively correlated with the infiltration of a majority of immune cells. Also, a higher risk score indicated a basal subtype of BLCA. Notably, the relationship between risk score, TME cell infiltration, and molecular subtypes could be validated in the Xiangya cohort.

Conclusion: We developed and validated a robust TNF-based risk score, which could predict prognostic outcomes, TME, and molecular subtypes of BLCA. However, the value of risk score predicting the efficacy of immunotherapy needs further research.
Elevated Hoxb5b Expands Vagal Neural Crest Pool and Blocks Enteric Neuronal Development in Zebrafish
Authors: Howard Aubrey G. A. , Nguyen Aaron C. , Tworig Joshua , Ravisankar Priya , Singleton Eileen W. , Li Can , Kotzur Grayson , Waxman Joshua S. , Uribe Rosa A.
Published: January 2022

Neural crest cells (NCCs) are a migratory, transient, and multipotent stem cell population essential to vertebrate embryonic development, contributing to numerous cell lineages in the adult organism. While great strides have been made in elucidating molecular and cellular events that drive NCC specification, comprehensive knowledge of the genetic factors that orchestrate NCC developmental programs is still far from complete. We discovered that elevated Hoxb5b levels promoted an expansion of zebrafish NCCs, which persisted throughout multiple stages of development. Correspondingly, elevated Hoxb5b also specifically expanded expression domains of the vagal NCC markers foxd3 and phox2bb. Increases in NCCs were most apparent after pulsed ectopic Hoxb5b expression at early developmental stages, rather than later during differentiation stages, as determined using a novel transgenic zebrafish line. The increase in vagal NCCs early in development led to supernumerary Phox2b+ enteric neural progenitors, while leaving many other NCC-derived tissues without an overt phenotype. Surprisingly, these NCC-derived enteric progenitors failed to expand properly into sufficient quantities of enterically fated neurons and stalled in the gut tissue. These results suggest that while Hoxb5b participates in vagal NCC development as a driver of progenitor expansion, the supernumerary, ectopically localized NCC fail to initiate expansion programs in timely fashion in the gut. All together, these data point to a model in which Hoxb5b regulates NCCs both in a tissue specific and temporally restricted manner.
TMAO-Activated Hepatocyte-Derived Exosomes Impair Angiogenesis via Repressing CXCR4
Authors: Liu Xiang , Shao Yijia , Tu Jiazichao , Sun Jiapan , Dong Bing , Wang Zhichao , Zhou Jianrong , Chen Long , Tao Jun , Chen Jimei
Published: January 2022

Objective: Trimethylamine-N-oxide (TMAO) was found to play crucial roles in vascular endothelial function. However, the exact molecular mechanisms are not yet entirely clear. Recently, we found that exosomes (Exos) isolated from TMAO-treated hepatocytes (TMAO-Exos) contained a distinctive profile of miRNAs compared to those from the TMAO-free group (Control-Exos). Furthermore, TMAO-Exos could notably promote inflammation, damage vascular endothelial cells (VECs), and impair endothelium-dependent vasodilation. This study aimed to further evaluate the effects of TMAO-Exos on VECs and explore the underlying mechanisms.

Methods: Exos were isolated from the hepatocyte culture supernatant with or without TMAO, using differential centrifugation. Then, VECs were treated with these Exos for 48 h and subjected to RNA-sequencing for detecting the changes of alternative polyadenylation (APA) and mRNA. After validation by qPCR and western blotting, the recombinant viruses were used to mediate the overexpression of C-X-C motif chemokine receptor 4 (CXCR4). The in vitro VEC function was evaluated by cell migration and tube formation, and in vivo angiogenesis was investigated in hindlimb ischemia models.

Results: Exos released from hepatocytes were differentially regulated by TMAO; both could be taken up by VECs; and furthermore, TMAO-Exos significantly reduced cell migration and tube formation in vitro and impaired perfusion recovery and angiogenesis after hindlimb ischemia, by down-regulating the CXCR4 expression. However, TMAO-Exos failed to regulate the splicing events, at least in this experimental setting, which suggested that TMAO-Exos may affect CXCR4 expression via an APA-independent manner.

Conclusions: Our findings revealed a novel indirect mechanism by which TMAO impaired endothelial function through stimulating hepatocytes to produce Exos that possessed distinctive activity. The crosstalk between the liver and vascular endothelial mediated by these Exos may offer a new target for restraining the harmful effects induced by TMAO.
Role of ARHGEF3 as a GEF and mTORC2 Regulator
Authors: Khaliq Sana Abdul , Umair Zobia , Yoon Mee-Sup
Published: January 2022

Guanine nucleotide exchange factors (GEFs) activate GTPases by stimulating the release of guanosine diphosphate to permit the binding of guanosine triphosphate. ARHGEF3 or XPLN (exchange factor found in platelets, leukemic, and neuronal tissues) is a selective guanine nucleotide exchange factor for Rho GTPases (RhoGEFs) that activates RhoA and RhoB but not RhoC, RhoG, Rac1, or Cdc42. ARHGEF3 contains the diffuse B-cell lymphoma homology and pleckstrin homology domains but lacks similarity with other known functional domains. ARHGEF3 also binds the mammalian target of rapamycin complex 2 (mTORC2) and subsequently inhibits mTORC2 and Akt. In vivo investigation has also indicated the communication between ARHGEF3 and autophagy-related muscle pathologies. Moreover, studies on genetic variation in ARHGEF3 and genome-wide association studies have predicted exciting novel roles of ARHGEF3 in controlling bone mineral density, platelet formation and differentiation, and Hirschsprung disease. In conclusion, we hypothesized that additional biochemical and functional studies are required to elucidate the detailed mechanism of ARHGEF3-related pathologies and therapeutics.
Novel Non-Invasive Diagnosis of Bladder Cancer in Urine Based on Multifunctional Nanoparticles
Authors: Xu Jinshan , Zeng Shuxiong , Li Jun , Gao Li , Le Wenjun , Huang Xin , Wang Guandan , Chen Bingdi , Zhang Zhensheng , Xu Chuanliang
Published: January 2022

Objectives: Tumor cells were reported to have perpetual negative surface charges due to elevated glycolysis, and multifunctional nanoprobes (Fe3O4@SiO2, mNPs) could attach onto tumor cells via opposite surface charges. We thus evaluated whether mixing mNPs with urine could improve the sensitivity of urine cytology test (UCT).

Methods: We developed a novel UCT method by mixing urine with mNPs (Nano-cytology) to harvest more tumor cells during UCT procedures. The same voided urine sample was divided equally for the Nano-cytology and UCT assay, and evaluated by cytopathologists in a blinded way. The accuracy of UCT, Nano-cytology, and the combination of the two approaches (Nano-UCT) for detecting bladder cancer were determined.

Results: Urine samples were prospectively collected from 102 bladder cancer patients and 49 non-cancer participants from June 2020 to February 2021 in Changhai Hospital. Overall sensitivity of the Nano-cytology assay was significantly higher than that of the UCT assay (82.4 vs. 59.8%, p < .01). Sensitivity for low- and high-grade tumors was 79.1% and 39.5% (p < .01) and 84.7% and 74.6% (p = .25) for Nano-cytology and UCT, respectively. Specificity of Nano-cytology was slightly lower than that of UCT (89.8% vs. 100%, p = .022), which is mainly caused by severe urinary tract infection. In addition, Nano-UCT showed increased sensitivity with 90.2% for overall patients, and 83.7% and 94.9% for low- and high-grade tumor, respectively.

Conclusion: The Nano-cytology assay had a significantly improved sensitivity compared with UCT for detecting bladder cancer patients. It represents a promising tool for diagnosis of bladder cancer in clinical practice.
Electron Dynamics and Correlations During High-Order Harmonic Generation in Be
Authors: Kutscher Eric , Artemyev Anton N. , Demekhin Philipp V.
Published: January 2022

We investigate theoretically the high-order harmonic generation in beryllium atom irradiated by a short 1850 nm linearly polarized laser pulse in the intermediate strong-field ionization regime with the Keldysh parameter of 0.85. To this end, the respective time-dependent Schrödinger equation is solved by the time-dependent restricted-active-space configuration-interaction (TD-RASCI) method. By systematically increasing the active space of included configurations, we demonstrate an individual effect of different physical processes evoked by the pulse, which, all together, significantly enrich and extend the computed high-order harmonic generation spectrum.
Commensal Bacteria in the Cystic Fibrosis Airway Microbiome Reduce P. aeruginosa Induced Inflammation
Authors: Tony-Odigie Andrew , Wilke Leonie , Boutin Sébastien , Dalpke Alexander H. , Yi Buqing
Published: January 2022

Chronic Pseudomonas aeruginosa infections play an important role in the progress of lung disease in patients suffering from cystic fibrosis (CF). Recent studies indicate that polymicrobial microbiome profiles in the airway are associated with less inflammation. Thus, the hypothesis was raised that certain commensal bacteria might protect the host from inflammation. We therefore performed a screening study with commensals isolated from CF airway microbiome samples to identify potential beneficial commensals. We isolated more than 80 aerobic or facultative anaerobic commensal strains, including strains from genera Streptococcus, Neisseria, Actinomyces, Corynebacterium, Dermabacter, Micrococcus and Rothia. Through a screening experiment of co-infection in human epithelial cell lines, we identified multiple commensal strains, especially strains belonging to Streptococcus mitis, that reduced P. aeruginosa triggered inflammatory responses. The results were confirmed by co-infection experiments in ex-vivo precision cut lung slices (PCLS) from mice. The underlying mechanisms of the complex host-pathogen-commensal crosstalk were investigated from both the host and the bacterial sides with a focus on S. mitis. Transcriptome changes in the host in response to co-infection and mono-infection were evaluated, and the results indicated that several signalling pathways mediating inflammatory responses were downregulated by co-infection with S. mitis and P. aeruginosa compared to P. aeruginosa mono-infection, such as neutrophil extracellular trap formation. The genomic differences among S. mitis strains with and without protective effects were investigated by whole genome sequencing, revealing genes only present in the S. mitis strains showing protective effects. In summary, through both in vitro and ex vivo studies, we could identify a variety of commensal strains that may reduce host inflammatory responses induced by P. aeruginosa infection. These findings support the hypothesis that CF airway commensals may protect the host from inflammation.
When Ecological Analysis Reveals Hidden Human Dimensions: Building on Long-Term Community Participation to Enable a Conservation Translocation of Mountain Bongo in Kenya
Authors: Sheppard Donna J. , Brichieri-Colombi Typhenn A. , Stark Danica J. , Lambrechts Christian , Moehrenschlager Axel , McPherson Jana M.
Published: January 2022

Conservation translocations have traditionally focused on ecological aspects while overlooking or underestimating the importance of human dimensions. Here, we present a feasibility analysis for a conservation translocation that up front took a holistic approach by investigating both ecological and socio-economic suitability of reinforcing mountain bongo in Eburu National Forest, Kenya. From 2018 to 2019, we set up 50 cameras to detect mountain bongo and searched for secondary signs in a grid overlaying Eburu. We also conducted surveys with 200 households surrounding the forest and interviewed 300 students to understand local perceptions of and interactions with Eburu Forest and their desire for a mountain bongo translocation. We used data from camera trapping and secondary signs in a MaxEnt model to determine the amount and location of available habitat for a bongo conservation translocation. Camera traps recorded only five bongo events in the 2-year study, and MaxEnt models revealed that these antelopes were relegated to less than 2.5 km of available habitat. Socio-economic surveys indicated local support for the conservation of bongo and their habitat, and yet our camera traps uncovered threatening illicit activities that could jeopardize both bongo survival and any attempt at boosting the remnant population with captive-bred individuals. We report how we built on long-term community and stakeholder engagement to mitigate these threats and provide concrete recommendations for how to proceed with a conservation translocation in terms of both the biological aspects and continued efforts to integrate socio-economic needs and community engagement.
Human Dimensions of the Reintroduction of Brazilian Birds
Authors: Martins Flávia de Campos , Engel Mônica T. , Schulz Francine , Martins Cláudia S. G.
Published: January 2022

People's acceptability for wildlife, stakeholders' engagement and involvement are acknowledged as key factors for the success of wildlife reintroduction projects. We analyzed the main National Action Plans (NAPs) (the Brazilian management participatory instrument for the conservation of endangered species) for eight bird species and conducted an online questionnaire with researchers and practitioners involved in those species reintroduction programs. The assessment of the main Brazilian bird's reintroduction programs showed that, in general, efforts have been made to integrate local people into it. Nevertheless, the actions were disconnected, isolated and fragmented. A formal protocol, designed, discussed and approved by experts aiming to address the human dimensions (HD) of human-bird interactions (HBI), preferably to be used in each stage of the reintroduction programs, was not found. Actions considered related to human dimensions are mainly under the umbrella of environmental education interventions or campaigns, more directed to children and youth; correspond to activities performed by locals with the birds and/or captive birds facilities; or, fostering artcraft production or bird watching activities. The weak or sometimes absent human dimensions approach to this important conservation tool may indicate either the novelty for Brazilian researchers and managers of the science of human dimensions within the field of wildlife management or the lack of dialogue between natural and social sciences when wildlife conservation is at stake. Reintroductions are expensive, sensitive, and labor-intensive processes. It becomes necessary due the conservation status of the species and its implementation follows a careful research of biological, ecological and socio-institutional regional background that identifies the drivers of species extinction and plans according to it. Understanding and predicting people's behaviors and its triggers are paramount to successful reintroduction projects. Thus, making use of well-planned HD studies in HBI may be the watershed between success or failure of reintroduction programs. This study was a pioneer initiative of its kind and it aimed to provide sound recommendations for managers, researchers and practitioners to acknowledge the relevance of HD and its core role in the reintroduction of endangered bird species.
Newly Developed Graft Failure Detected Using Computed Tomography Within 1 Year After Coronary Artery Bypass Grafting Surgery: One Single-Center Experience
Authors: Li Zhaoshui , Qiao Youjin , Sheng Wei , Chi Yifan
Published: January 2022

Background

Newly developed graft failure negatively affects the short- and long-term outcomes of patients who experience coronary artery bypass grafting (CABG) surgery. This study explored the value of transit time flow measurement (TTFM) parameters for predicting the risk of newly developed graft failure that occurs within 1 year after CABG, as well as investigated the relationship between newly developed graft failure and adverse cardiovascular events.

Methods

A total of 134 patients who underwent CABG and had CT angiography (CTA) data (1 year post-operatively) were divided into two groups: the patient group, in which patients did not have newly developed graft failure, and the occluded group, in which patients developed newly developed graft failure between 1 and 12 months after CABG. The patency rate of grafts in different targets was analyzed. The correlations between graft failure and TTFM parameters and between graft failure and the occurrence of adverse cardiovascular events were investigated.

Results

The overall rate of newly developed graft failure was 7.2%, the venous graft failure was 10.8%, and the arterial graft failure was 0.7%. The occluded group had a higher pulse index (PI) (2.9 vs. 2.4, P = 0.007), a lower mean graft flow (MGF) (20 vs. 25 ml/min, P = 0.028), and a lower diastolic flow fraction (DF) (63.5 vs. 70%, P = 0.019) than the patent group. The cut-off value for predicting newly developed graft failure was PI > 2.75 (P = 0.007), MGF < 23.5 ml/min (P = 0.03), and DF < 65.5% (P = 0.019). Compared with the patent group, the newly developed graft failure group had higher rates of recurrent angina (13.6 vs. 0.9%, P = 0.0014) and revascularization intervention (9.1 vs. 0% P = 0.026). However, there were no differences in death, cardiac death, myocardial infarction, and cerebral infarction after CABG operation between these two groups (P > 0.05).

Conclusions

A high PI and low MGF and DF are risk factors for newly developed graft failure. The patients with newly developed graft failure had higher rates of recurrent angina and revascularization intervention. TTFM parameters may be used to predict the occurrence of newly developed graft failure in patients after CABG surgery.
Hybrid CMR- and FDG-PET-Imaging Gives New Insights Into the Relationship of Myocardial Metabolic Activity and Fibrosis in Patients With Becker Muscular Dystrophy
Authors: Vehof Volker , Büther Florian , Florian Anca , Drakos Stefanos , Chamling Bishwas , Kies Peter , Stegger Lars , Yilmaz Ali
Published: January 2022

Background

Cardiac involvement in patients with Becker muscular dystrophy (BMD) is an important predictor of mortality. The cardiac phenotype of BMD patients is characterized by slowly progressive myocardial fibrosis that starts in the left ventricular (LV) free wall segments and extends into the septal wall during the disease course.

Purpose

Since the reason for this characteristic cardiac phenotype is unknown and comprehensive approaches using e.g. hybrid imaging combining cardiovascular magnetic resonance (CMR) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) are limited, the present study addressed this issue by a comprehensive non-invasive imaging approach.

Methods

Hybrid CMR- and FDG-PET-imaging was performed in N = 14 patients with BMD on a whole-body Biograph mMR system (Siemens, Erlangen, Germany). The CMR protocol comprised cine- and late-gadolinium-enhancement (LGE)-imaging. Metabolism was assessed with FDG-PET after oral glucose loading to effect myocardial carbohydrate uptake. PET was acquired for 65 min starting with tracer injection. Uptake values from 60 to 65 min p.i. were divided by the area under the blood activity curve and reported as percentages relative to the segment with maximal myocardial FDG uptake.

Results

A characteristic pattern of LGE in the LV lateral wall was observed in 13/14 patients whereas an additional septal LGE pattern was documented in 6/14 patients only. There was one patient without any LGE. Segmental FDG uptake was 88 ± 6% in the LV lateral wall vs. 77 ± 10% in the septal wall (p < 0.001). There was an inverse relationship between segmental FDG activity compared to segmental LGE extent (r = −0.33, p = 0.089). There were N = 6 LGE-positive patients with a segmental difference in FDG uptake of >15% in the LV lateral wall compared to the septal wall = ΔFDG-high group (lateral FDG = 91±3% vs. septal FDG = 69±8%; p < 0.001) while the remaining N = 7 LGE-positive patients showed a segmental difference in FDG uptake of ≤ 15% = ΔFDG-low group (lateral FDG = 85±7% vs. septal FDG = 83 ± 5%; p = 0.37). Patients in the ΔFDG-high group showed only a minor difference in the LGE extent between the LV lateral wall vs. septal wall (p = 0.09) whereas large differences were observed in the ΔFDG-low group (p < 0.004).

Conclusions

Segmental FDG uptake—reflecting myocardial metabolic activity—is higher in the LV free wall of BMD patients—possibly due to a higher segmental work load. However, segmental metabolic activity seems to be dependent on and limited by the respective segmental extent of myocardial fibrosis as depicted by LGE-imaging.
Damage Types and Deterioration Characteristics of Check Dams Built on Mountain Streams in Southeast Korea
Authors: Lee Ki-Hwan , Ewane Ewane Basil , Uchida Taro , Woo Choong-Shik
Published: January 2022

Check dams are one of representative structural measures to reduce sediment disaster at a forest watershed. Therefore, it is essential to assess the structural vulnerability and functionality of check dams in the management of sediment disaster risk at watersheds. This study examined the main types of damages and deterioration characteristics in concrete and stone check dams, which comprise more than 80.0% of Korea’s check dam stock. This was based on the 4-step condition assessment, which is the modified version of condition assessment methodology for embankment dams to meet the characteristics of check dams. As a result, the damages and deterioration of concrete check dams were classified into ten representative types. And representative damage types of stone check dams were classified into nine types. The condition assessment results demonstrated that the spillway part frequently contacted with water and debris flows was deteriorated approximately 1.2 times faster than the wing parts for both concrete and stone check dams, and the maintenance demands of both types of check dams increased 15–20 years after construction. Thus, these deterioration characteristics of concrete and stone check dams should be considered in decision-making to determine maintenance priorities among the check dams stock. Furturemore, we analyzed the relationship between condition index and service time in the examined concrete and stone check dams. The degree of deterioration in concrete and stone check dams increased significantly as the service time increased. Based on the relationship between condition index and service time, we classified deterioration characteristics of check dams into two groups: 1) those that follow the average deterioration trends of their facility group (Group II) and 2) those that undergo an unexpected end-of-service life because of exceptional incidents or severe defects (Group I). We hope that our work will form a useful resource for engineers and decision-makers involved in planning, designing, constructing, and maintaining check dams.
Subseasonal Variation of 2020 Meiyu Rainfall With Extremely Long Duration Over the Yangtze–Huaihe River Basin in China
Authors: Chen Shengjie , Kang Zhiming , Liu Mei , Lv Runqing , Ma Jing , He Jinhai
Published: January 2022

An observed fact is proposed that the 2020 record-breaking Meiyu over the Yangtze–Huaihe River Basin (YHRB) is characteristic of significant subseasonal variation. The anomalously enhanced rainfall experiences a southward retreat from the northern YHRB in June to the southern YHRB in July. The meridional shift of abnormal rainbelt is closely related to the different anomalous Meiyu front circulations. The first stage features a warm Meiyu front with an extremely strong northward transport of warm-and-wet air, whereas a cold front forms with a convergence between the strong northeasterlies and southwesterlies in July. Another significant subseasonal variation of the 2020 Meiyu is that the Meiyu rainfall evolves in a periodic quasi-biweekly oscillation (QBWO). On the scale of the QBWO, the cold air activities over East Asia contribute significantly to Meiyu; each intense southward invasion of cold air corresponds well to the enhancement of Meiyu rainfall. However, the location of the western Pacific subtropical high, the subtropical East Asia summer monsoon (SEASM), and the intensity of the East Asia subtropical westerly jet exhibit opposite QBWO characteristics in June and July. For an increasing (decreasing) of Meiyu rainfall, the western Pacific subtropical high marches northward (retreats southward), the subtropical East Asia summer monsoon weakens (strengthens), and the East Asia subtropical westerly jet accelerates (decelerates) in June. The opposite holds true in July. Further analyses reveal that the filtered cyclone over Northeast China benefiting the southward intrusion of cold air is associated with the eastward propagation of a wave train over the mid-high latitudes in June, whereas it arises from both the westward propagation of a wave train over the mid-high latitudes and the northward propagation of cyclonic circulation from the tropics in July.
Analysis of Flexural Toppling Failure of Anti-Dip Rock Slopes Due to Earthquakes
Authors: Zhang Hong , Wu Yihan , Huang Shiting , Zheng Lu , Miao Yuanbing
Published: January 2022

Flexural toppling is one of the failure modes of anti-dip rocks, is often triggered by seismic load, occurs haphazardly under an earthquake scenario, and is characterized by high speed and extreme energy, leading to catastrophic disaster consequences and huge losses. However, there is limited literature that reveals its failure mechanisms and describes the failure surface due to earthquakes. Therefore, based on the limit equilibrium analysis method, the horizontal pseudo-static load was applied to improve the geological mechanical model under gravity only, and the stability analysis process was derived. The failure surface and failure mode of the slope under different seismic loads were analyzed. The results indicated that, with the increasing seismic load, an increase in the number of rock layers with sliding failure increased the number of rock layers with cantilever toppling failure; in contrast, the number of rock layers with overlapping toppling failure decreased. The slope toe was more prone to sliding and the slope top was more prone to cantilever toppling under an earthquake, which decreased the stability of the anti-dip rock slope.
Flow Characteristics and Structure Optimization of a Baffle Plate Heat Exchanger
Authors: Lu Mengshi , Feng Zhuoheng , Wang Yungang , Yang Hongwei , Xia Wenqing , Zhu Haimiao , Hua Dan
Published: January 2022

In this study, a theoretical model of the hot and cold fluid flow, heat transfer, and thermal stress coupling in a baffle plate heat exchanger is established, and numerical simulation is carried out. The flow field in the heat exchanger and the deformation of the heat exchange tube bundles in the baffle plate heat exchanger are studied. The optimization effect of the diversion grid on the flow field at the inlet of the variable section is emphasized. The influence of grid arrangement on the flow field and the performance of the tube bundles are analyzed and discussed. The results show that the backflow situation can be effectively improved and the vortex intensity in the straight section of the cold fluid inlet can be greatly reduced by adding the grid. The deformation of the heat exchange tube bundles illustrates the maximum deformation with 1.39 mm at the position of the strongest backflow. The deformation can be reduced by 26% due to the arrangement of the diversion grid, which is helpful to improve the safety of the device.
Natural Antioxidants can Improve Microplastics-Induced Male Reproductive Impairment in the African Catfish (Clarias Gariepinus)
Authors: El-Din H. Sayed Alaa , Hamed Mohamed , Ismail Rania F.
Published: January 2022

This study was conducted to explore the protective potential of three different antioxidant supplements, lycopene, citric acid, andChlorella, against reproductive injuries induced by microplastics (MPs) in freshwater mature male catfish. A total of 150 mature male African catfish (Clarias gariepinus) were assigned to five treatment groups as follows: control group fish were fed with control diet, the second group fish were fed with 500 mg/kg MP diet, and the remaining three groups of fish were fed with 500 mg/kg MP diet plus lycopene (500 mg/kg diet), citric acid (30 g/kg diet), andChlorella(50 g/kg diet), respectively, for 15 days. Ingestion of MPs significantly decreased serum luteinizing hormone, follicle-stimulating hormone, sex steroid (testosterone and estradiol) levels and sperm count, spermatocrit, motility, and viability. It also induced histological alterations and degenerative changes in testicular tissues. Administration of lycopene andChlorellawith MP diets maintained hormone levels comparable to those in the control group, enhanced sperm quality, and decreased testicular histological damage.Chlorellawas more effective in enhancing sperm quality, and lycopene was more efficient in alleviating testicular tissue damage. Citric acid supplementation was irrelevant in mitigating MP-induced injury. This study indicated that both lycopene andChlorellaameliorated the MP-induced reproductive dysfunction by improving reproductive hormonal levels, sperm parameters, and histological configuration, whereas the citric acid dose used in this study was not effective in ameliorating the MP-induced reproductive stress. Additional research and monitoring of MP-induced pollution in freshwater ecosystems are required to avoid the severity of reproductive toxicity in freshwater fish.
Urinary Sediment mRNA Level of CREBBP and CYBA in Children With Steroid-Resistant Nephrotic Syndrome
Authors: Li Wei , Shou Xinyi , Xiang Wenqing , He Lin , Li Lin , Fu Haidong , Mao Jianhua
Published: January 2022

Background

This study aimed to evaluate gene expression patterns in urinary sediment samples of children with steroid-resistant nephrotic syndrome (SRNS).

Methods

The messenger RNA (mRNA) levels of 770 immune-related genes were detected using a NanoString nCounter platform. To verify the NanoString results, quantitative analysis of nine gene mRNAs was performed using real-time RT-PCR in more samples.

Results

Firstly, compared with the steroid-sensitive nephrotic syndrome (SSNS) group (n=3), significant changes were observed in the mRNA level of 70 genes, including MAP3K14, CYBA, SLC3A2, CREB-binding protein (CREBBP), CD68, forkhead box P1 (FOXP1), CD74, ITGB2, IFI30, and so forth, in the SRNS group (n=3). A total of 129 children with idiopathic nephrotic syndrome (INS), 15 with acute glomerulonephritis, and 6 with immunoglobulin A nephropathy (IgAN) were enrolled to verify the NanoString results. Compared with patients with IgAN, those with INS had significantly lower levels of FOXP1 (P=0.047) and higher levels of CREBBP (P=0.023). Among SSNS, the mRNA level of ITGB2 was significantly lower in the non-relapse group than in the non-frequent relapse and frequent-relapse groups (P=0.006). Compared with the SSNS group, CREBBP was significantly elevated in the SRNS group (P=0.02). Further, CYBA significantly decreased in the SRNS group (P=0.01). The area under the curve (AUC) for CREBBP and CYBA was 0.655 and 0.669, respectively. CREBBP had a sensitivity of 83.3% and a specificity of 49.4% and CYBA had a sensitivity of 58.3% and a specificity of 83.1% to rule out SSNS and SRNS. The diagnosis value was better for CREBBP+CYBA than for CREBBP or CYBA alone, indicating that the combination of CREBBP and CYBA was a more effective biomarker in predicting steroid resistance (AUC=0.666; sensitivity=63.9%; specificity=76.4%).

Conclusions

This study was novel in investigating the urinary sediment mRNA level in children with INS using high-throughput NanoString nCounter technology, and 70 genes that may relate to SRNS were found. The results revealed that the urinary sediment mRNA level of ITGB2 was significantly lower in the non-relapse group than in the non-frequent relapse and frequent-relapse groups. Meanwhile, CREBBP was significantly elevated and CYBA was significantly lowered in the SRNS group compared with the SSNS group.
Multifocal Cerebral Microinfarcts Modulate Early Alzheimer’s Disease Pathology in a Sex-Dependent Manner
Authors: Lecordier Sarah , Pons Vincent , Rivest Serge , ElAli Ayman
Published: January 2022

Alzheimer’s disease (AD) constitutes a major cause of dementia, affecting more women than men. It is characterized by amyloid-β (Aβ) deposition and neurofibrillary tangles (NFTs) formation, associated with a progressive cognitive decline. Evidence indicates that AD onset increases the prevalence of cerebral microinfarcts caused by vascular pathologies, which occur in approximately in half of AD patients. In this project, we postulated that multifocal cerebral microinfarcts decisively influence early AD-like pathology progression in a sex dependent manner in young APP/PS1 mice. For this purpose, we used a novel approach to model multifocal microinfarcts in APP/PS1 mice via the sporadic occlusions of the microvasculature. Our findings indicate that microinfarcts reduced Aβ deposits without affecting soluble Aβ levels in the brain of male and female APP/PS1 mice, while causing rapid and prolonged cognitive deficits in males, and a mild and transient cognitive decline in females. In male APP/PS1 mice, microinfarcts triggered an acute hypoperfusion followed by a chronic hyperperfusion. Whereas in female APP/PS1 mice, microinfarcts caused an acute hypoperfusion, which was recovered in the chronic phase. Microinfarcts triggered a robust microglial activation and recruitment of peripheral monocytes to the lesion sites and Aβ plaques more potently in female APP/PS1 mice, possibly accounting for the reduced Aβ deposition. Finally, expression of Dickkopf-1 (DKK1), which plays a key role in mediating synaptic and neuronal dysfunction in AD, was strongly induced at the lesion sites of male APP/PS1 mice, while its expression was reduced in females. Our findings suggest that multifocal microinfarcts accelerate AD pathology more potently in young males compared to young females independently upon Aβ pathology via modulation of neurovascular coupling, inflammatory response, and DKK1 expression. Our results suggest that the effects of microinfarcts should be taken into consideration in AD diagnosis, prognosis, and therapies.
Decidualization of Stromal Cells Promotes Involvement of Mast Cells in Successful Human Pregnancy by Increasing Stem Cell Factor Expression
Authors: Ueshima Chiyuki , Kataoka Tatsuki R. , Osakabe Mitsumasa , Sugimoto Akihiko , Ushirokawa Akihiko , Shibata Yuji , Nakamura Hiroya , Shibuya Rintaro , Minamiguchi Sachiko , Sugai Tamotsu , Haga Hironori
Published: January 2022

Decidualization of endometrial stromal cells and the presence of immunocompetent cells, including human mast cells, play important roles in the establishment of pregnancy. In the present study, the effects of decidualization of endometrial stromal cells on the function of decidual mast cells were elucidated. The in vitro assay revealed that decidualization of an endometrial stromal cell line, T HESCs, increased stem cell factor (SCF) mRNA expression. Decidualization of T HESCs enhanced the production of leukemia inhibitory factor (LIF), and the migration of LAD2 cells when co-cultured with T HESCs and LAD2 cells. In addition, decidualization of T HESCs enhanced cell migration in a human trophoblast cell line, HTR-8/SVneo, increased CD9 expression, a marker for extravillous trophoblast (EVT) differentiation, and decreased the secretion of β human chorionic gonadotropin (hCG), a marker for syncytiotrophoblast (ST) differentiation, when co-cultured with T HESCs, LAD2 cells, and HTR-8/SVneo cells, in a LIF-dependent manner. Histological samples from uterine pregnancies, including decidual stromal cells, showed increased SCF mRNA expression, mast cell numbers and LIF mRNA expression thereof compared with tubal pregnancy. SCF produced by decidual stromal cells enhanced the migration and LIF production of mast cells, and promoted the migration and differentiation of trophoblasts to increase the likelihood of successful human pregnancy.
The ECSIT Mediated Toll3-Dorsal-ALFs Pathway Inhibits Bacterial Amplification in Kuruma Shrimp
Authors: Ding Ding , Sun Xue-jun , Yan Meng , Chen Qi , Gao Lin , Kang Cui-jie
Published: January 2022

The Toll signaling pathway plays an important role in animal innate immunity. However, its activation and signal transmission greatly differ across species and need to be investigated. Shrimp farming is a worldwide economic activity affected by bacterial disease from the 1990s, which promoted research on shrimp immunity. In this study, we first proved that, among the three identified Toll receptors in Marsupenaeus japonicus kuruma shrimp, Toll 3 plays a pivotal role in initiating the antibacterial response in vivo, especially upon anti-Staphylococcus aureus infection. Further research showed that this result was due to the activation of the Dorsal transcription factor, which induced the expression of two anti-lipopolysaccharide factors (Alfs). Moreover, the evolutionarily conserved signaling intermediate in Toll pathways, ECSIT, was proved to be needed for signal transmission from Toll 3 to Dorsal and the expression of anti-lipopolysaccharide factors. Finally, the mortality assay showed that a Toll3-ECSIT-Dorsal-Alf axis was functional in the anti-S.aureus immunity of M. japonicus shrimp. The results provide new insights into the function and signal transduction of the Toll pathway in aquatic species and offer basic knowledge for shrimp disease control and genetic breeding.
Shallow Sea Gas Manifestations in the Aegean Sea (Greece) as Natural Analogs to Study Ocean Acidification: First Catalog and Geochemical Characterization
Authors: Daskalopoulou Kyriaki , D’Alessandro Walter , Longo Manfredi , Pecoraino Giovannella , Calabrese Sergio
Published: January 2022

The concepts of CO2 emission, global warming, climate change, and their environmental impacts are of utmost importance for the understanding and protection of the ecosystems. Among the natural sources of gases into the atmosphere, the contribution of geogenic sources plays a crucial role. However, while subaerial emissions are widely studied, submarine outgassing is not yet well understood. In this study, we review and catalog 122 literature and unpublished data of submarine emissions distributed in ten coastal areas of the Aegean Sea. This catalog includes descriptions of the degassing vents through in situ observations, their chemical and isotopic compositions, and flux estimations. Temperatures and pH data of surface seawaters in four areas affected by submarine degassing are also presented. This overview provides useful information to researchers studying the impact of enhanced seawater CO2 concentrations related either to increasing CO2 levels in the atmosphere or leaking carbon capture and storage systems.
Offshore Spreading of a Supercritical Plume Under Upwelling Wind Forcing: A Case Study of the Winyah Bay Outflow
Authors: Yankovsky Alexander E. , Fribance Diane B. , Cahl Douglas , Voulgaris George
Published: January 2022

In this study, we present observations of the Winyah Bay (WB) plume (SC, United States) formed by high freshwater discharge and a moderate upwelling-favorable wind acting continuously for ∼1.5 days prior to the shipboard survey. If a similar wind forcing persists over a longer period, the plume turns upstream (against its natural propagation) and curves offshore forming a “filament” with minimal transverse spreading, as seen in numerous satellite images. The observed plume comprises a train of tidal sub-plumes undergoing rotational adjustment and being transported offshore by Ekman dynamics. The WB outflow is supercritical in terms of the interior Froude number. Moderate wind extends this supercritical regime farther offshore. The plume is characterized by interior fronts associated with consecutive tidal pulses. Age of the buoyant water can be distinguished by the buoyant layer mixing (evident in the layer’s thickness and salinity anomaly) along with the transformation of its TS properties. However, relatively little transverse (lateral) spreading of buoyant water occurs: the equivalent freshwater layer thickness remains surprisingly consistent, approximately 0.8 m, over more than 20 km in the direction of the bulge extension. It is hypothesized that the supercritical regime constrains the transverse spreading of a plume. Microstructure measurements reveal higher dissipation rates below the base of the older (offshore) part of the plume. This is attributed to internal wave radiation from a newly discharged tidal pulse into an older plume, with the buoyant layer acting as a waveguide. Theoretical estimations of the internal wave properties show that the interior front is highly supercritical, while the observed dissipation maximum agrees with the theoretical wave structure.