bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Evolution with Autonomous Selection of Mutation Strategies and Control Parameters and Its Application
Authors: Wang Zhenyu , Cao Zijian , Du Zhiqiang , Jia Haowen , Han Binhui , Tian Feng , Liu Fuxi
Published: July 2022

The existing numerous adaptive variants of differential evolution (DE) have been improved the search ability of classic DE to certain extent. Nevertheless, those variants of DE do not obtain the promising performance in solving black box problems with unknown features, which is mainly because the adaptive rules of those variants are designed according to their designers’ cognition on the problem features. To enhance the optimization ability of DE in optimizing black box problems with unknown features, a differential evolution with autonomous selection of mutation strategies and control parameters (ASDE) is proposed in this paper, inspired by autonomous decision‐making mechanism of reinforcement learning. In ASDE, a historical experience archive with population features is utilized to preserve accumulated historical experience of the combination of mutation strategies and control parameters. Furthermore, the accumulated historical experience can be autonomously mapped into rules repository, and the individuals can choose the combination of mutation strategies and control parameters according to those rules. Additionally, an updating and utilization mechanism of the historical experience is designed to assure that the historical experience can be effectively accumulated and utilized efficiently. Compared with some state‐of‐the‐art intelligence algorithms on 15 functions of CEC2015, 28 functions of CEC2017, and parameter extraction problems of the photovoltaic model, ASDE has the advantages of solution accuracy, convergence speed, and robustness in solving black box problems with unknown features.
Analysis on the Correspondence between Sustainable Social Service Design and Humanistic Aesthetic Design and Cognitive Psychological Utility
Authors: Yu Yang , Gao Jiaji , Yukari Nagai
Published: July 2022

In this era of gradual scarcity of resources, sustainable development has become an important issue for society. In this environment, the cultural, economic, and social environment has a decisive influence on sustainable development. This paper mainly starts with service design and humanistic aesthetics and introduces the sustainable design development theory into the design so that the design can better respond to the sustainable development strategy. We established the integration method of marketing and design, through the combination of humanistic art design and the cognitive psychological effect and the cognitive psychological effect of customers, advocating appropriate design and humanism in the information age, which not only improves the sustainable society but also enriches the service design system theory.
Removal of Toxic Metal Presence in the Wastewater and Production of the Biomass from Microalgae Chlorella sp.
Authors: Deepak J. R. , Anbarasu A. , Prabu V.
Published: July 2022

Removal of high toxic metals from the wastewater was one of the mandate options to avoid the environmental pollution caused by the wastewater plant. Microalgae cultivation on the wastewater was one of the hopeful methods to convert the waste into useful by‐product. In this study, the Chlorella sp. was used to remove the presence of the total nitrogen (TN) and total phosphorous (TP) in the wastewater. Added to the above, the biomass and lipids of the Chlorella sp. were examined with respect to the incubation time. Chlorella sp. was cultivated using BG11 medium. Here, two different types of wastewater had been used, one from leather industry and other priggery waste. The respective ratio of leather and piggery wastewater used in the current study was 0 : 100, 25 : 75, 50 : 50, 75 : 25, and 100 : 0. The total percentage of the nitrogen and phosphorous removal by the microalgae within 14 days was determined. Based on the findings, it is clear that Chlorella sp. L33 was highly efficient to absorb the nitrate and phosphorous content in the wastewater. With regard to the biomass production, the priggery wastewater treated reported the maximum biomass for 100 μmol/L with 0.55 g/L. However, the 100 μmol/L has higher pH content than other test samples. By varying the ratio of the wastewater, the removals rates can be improved.
Corner Detection of the Computer VR Microscope Image Based on the 3D Reconstruction Algorithm
Authors: Huang Junjun
Published: July 2022

In order to solve the problem of multisolution and ill-formedness of the 3D reconstruction method of a single image (purpose), the author proposes a microscope image segmentation algorithm based on the Harris multiscale corner detection. Separating complex engineering images into several simple basic geometric shapes, rebuild them separately to avoid the ill-conditioned solution problem of directly recovering depth information. In order to improve the registration accuracy of the corner-based image registration algorithm, the idea of multiresolution analysis was introduced into the classic Harris corner detection, and a gray intensity variation formula based on the wavelet transform was constructed, and a scale transformation characteristic was obtained so that the improved Harris corner detection algorithm is invariant to rotation, translation, and scale. Experimental results show that after reconstruction, the error between the length of the object measured based on the point cloud data and the actual length of the object is small, and both remain within the error range of 3 mm. The experiment verifies the fast, accurate, and stable characteristics of the improved algorithm.
Activating mTOR Mutations Are Detrimental in Nutrient-Poor Conditions
Authors: Bielska Agata A. , Harrigan Caitlin F. , Kyung Yeon Ju , Morris Quaid , Palm Wilhelm , Thompson Craig B.
Published: July 2022

The mTOR is a key regulator of cell growth that integrates growth factor signaling and nutrient availability and is a downstream effector of oncogenic receptor tyrosine kinases (RTK) and PI3K/Akt signaling. Thus, activating mTOR mutations would be expected to enhance growth in many tumor types. However, tumor sequencing data have shown that mTOR mutations are enriched only in renal clear cell carcinoma, a clinically hypervascular tumor unlikely to be constrained by nutrient availability. To further define this cancer-type–specific restriction, we studied activating mutations in mTOR. All mTOR mutants tested enhanced growth in a cell-type agnostic manner under nutrient-replete conditions but were detrimental to cell survival in nutrient-poor conditions. Consistently, analysis of tumor data demonstrated that oncogenic mutations in the nutrient-sensing arm of the mTOR pathway display a similar phenotype and were exceedingly rare in human cancers of all types. Together, these data suggest that maintaining the ability to turn off mTOR signaling in response to changing nutrient availability is retained in most naturally occurring tumors.

Significance:

This study suggests that cells need to inactivate mTOR to survive nutrient stress, which could explain the rarity of mTOR mutations and the limited clinical activity of mTOR inhibitors in cancer.
Dual Inhibition of CDK12/CDK13 Targets Both Tumor and Immune Cells in Ovarian Cancer
Authors: Cheng Lin , Zhou Shichao , Zhou Shaoqing , Shi Kaixuan , Cheng Yan , Cai Mei-Chun , Ye Kaiyan , Lin Lifeng , Zhang Zhenfeng , Jia Chenqiang , Xiang Huaijiang , Zang Jingyu , Zhang Meiying , Yin Xia , Li Ying , Di Wen , Zhuang Guanglei , Tan Li
Published: July 2022

Therapeutic perturbation of cyclin-dependent kinase 12 (CDK12) is proposed to have pleiotropic effects in ovarian cancer, including direct cytotoxicity against tumor cells and indirect induction of immunogenicity that confer synthetic sensitivity to immune-based treatment. However, formal testing of this hypothesis has been hindered by an insufficient mechanistic understanding of CDK12 and its close homolog CDK13, as well as generally unfavorable pharmacokinetics of available CDK12/CDK13 covalent inhibitors. In this study, we used an innovative arsenous warhead modality to develop an orally bioavailable CDK12/CDK13 covalent compound. The dual CDK12/CDK13 inhibitors ZSQ836 exerted potent anticancer activity in cell culture and mouse models and induced transcriptional reprogramming, including downregulation of DNA damage response genes. CDK12 and CDK13 were both ubiquitously expressed in primary and metastatic ovarian cancer, and the two kinases performed independent and synergistic functions to promote tumorigenicity. Unexpectedly, although ZSQ836 triggered genomic instability in malignant cells, it counterintuitively impaired lymphocytic infiltration in neoplastic lesions by interfering with T-cell proliferation and activation. These findings highlight the Janus-faced effects of dual CDK12/CDK13 inhibitors by simultaneously suppressing tumor and immune cells, offering valuable insights into the future direction of drug discovery to pharmacologically target CDK12.

Significance:

This study dissects the specific roles of CDK12 and CDK13 in ovarian cancer and develops a CDK12/CDK13 inhibitor that impairs both tumor and immune cells, which could guide future CDK12 inhibitor development.
Cell–Cell Interactions Drive Metastasis of Circulating Tumor Microemboli
Authors: Tao Jianxin , Zhu Lei , Yakoub Mina , Reißfelder Christoph , Loges Sonja , Schölch Sebastian
Published: July 2022

Circulating tumor cells are the cellular mediators of distant metastasis in solid malignancies. Their metastatic potential can be augmented by clustering with other tumor cells or nonmalignant cells, forming circulating tumor microemboli (CTM). Cell–cell interactions are key regulators within CTM that convey enhanced metastatic properties, including improved cell survival, immune evasion, and effective extravasation into distant organs. However, the cellular and molecular mechanism of CTM formation, as well as the biology of interactions between tumor cells and immune cells, platelets, and stromal cells in the circulation, remains to be determined. Here, we review the current literature on cell–cell interactions in homotypic and heterotypic CTM and provide perspectives on therapeutic strategies to attenuate CTM-mediated metastasis by targeting cell–cell interactions.
Menthol Cigarette Smoking Trends among United States Adults, 2003–2019
Authors: Seaman Elizabeth L. , Corcy Nalini , Chang Joanne T. , Chomenko Dana , Hartman Anne M. , Kittner Deirdre Lawrence , Reyes-Guzman Carolyn M.
Published: July 2022

Background:

Smoking is declining, except among current menthol cigarette smokers. This study examines menthol cigarette smoking in the United States.

Methods:

Cross-sectional data from 35,279 self-respondent current adult smokers who selected menthol cigarettes as their usual type, across the 2003, 2006–2007, 2010–2011, 2014–2015, and 2018–2019 waves of the nationally-representative Tobacco Use Supplement to the Current Population Survey, were analyzed in SAS/SUDAAN. Menthol cigarette smoking among current smokers was assessed by sex, age, race/ethnicity, employment, geography, and educational attainment. Linear contrasts were used to assess trends.

Results:

Overall cigarette smoking (12.6% in 2018–2019 from 17.3% in 2003) and menthol cigarette smoking (4.0% in 2018–2019 from 4.7% in 2003) in the population decreased in 2018–2019 from 2003 (both P < 0.001). Using predicted marginals, adjusted by demographics, menthol smoking among current smokers increased to 33.8% in 2018–2019 from 27.9% in 2003 (P < 0.001). Among current smoking adults, increases in menthol smoking were observed among non-Hispanic Black persons (76.8% in 2018–2019 from 73.0% in 2003), young adults (37.7% in 2018–2019 from 31.7% in 2003), and women (39.6% in 2018–2019 from 32.1% in 2003).

Conclusions:

Smoking and menthol smoking in the population has decreased, yet menthol smoking among current smokers increased from 2003 to 2018–2019. Young adult, female, and non-Hispanic Black current smokers were more likely to use menthol cigarettes than their counterparts; these differences have persisted.

Impact:

Increased menthol smoking among current smokers, notably young adults, women, and non-Hispanic Black individuals, highlights the need for targeted tobacco control interventions for these health disparity populations.
Scoring-Systeme zur Bewertung der Krankheitsaktivität bei Morbus-Behçet-Chorioretinitis und ihre Anwendung
Authors: Ernst Sophie-Christin 
Published: July 2022

Behçet’s disease is a multi-organ inflammatory disorder with systemic vasculitis of unknown etiology. Ocular lesions occur in about 70% of patients with Behçet’s disease, and it is more frequent and severe in men. The frequency of ocular inflammatory attacks has been used as a main outcome measure to assess the efficacy of therapy on uveoretinitis in patients with Behçet’s disease. The ocular Behçet’s disease research group of Japan have recently proposed a new scoring system, Behçet’s disease ocular attack score 24 (BOS24), to assess the disease activity of ocular Behçet’s disease. This review highlights the efficacy and application of the BOS24 scoring system in clinical practice for patients with ocular Behçet’s disease. In addition, a new semi-quantitative scoring system to evaluate the degree of retinal vascular leakage on fluorescein angiography reported by our group is described.
Teaching Radiographic Caries Detection and Treatment Planning: A Seminar Using an Audience Response System
Authors: Young Alix , Skudutyte-Rysstad Rasa , Torgersen Gerald , Giertsen Elin
Published: July 2022

This study presents a seminar model for teaching radiographic caries detection and treatment planning at the Faculty of Dentistry, University of Oslo. The seminar is based partly on an audience response system (ARS) and uses patient cases to focus on caries risk assessment and treatment planning. This paper describes the seminar design, implementation, learning outcomes, and observational study of variability in caries registrations and students’ attitudes to use of ARS. Dental and dental hygiene students participate in two seminar modules. Module 1 aims to develop and increase individual student skills in radiographic caries lesion detection, scoring, and differential diagnosis. Students perform trial registrations on bitewings using an ARS with anonymous live polling, and scorings are discussed in plenum. Students then perform individual registrations on 12 bitewing pairs. Using digital scoring, students detect and grade caries lesions on all approximal and occlusal tooth surfaces. After the session, students use the ARS to repeat scorings on selected tooth surfaces, and results are again discussed in plenum. Module 2 involves group exercises on 4 patient cases that are later presented with plenary discussions. In total, 1,624 caries registrations performed by 150 students attending the seminar between 2016 and 2018 were assessed for variability between students. As expected, variations in caries registrations were observed between students, mostly related to restored surfaces or tooth surfaces that were otherwise difficult to register. In 2022, 63 dental and dental hygiene students attending the seminar answered a questionnaire about use of ARS. The responses were scored using a five-point Likert scale. Overall, no significant difference in satisfaction with the ARS-based module was observed between dental and dental hygiene students (χ2 test, p > 0.05). The majority of the students were positive toward the use of ARS (94%), but some disagreed on the role of ARS in usefulness for understanding the seminar content (3.2%), and in increasing their confidence in radiographic registration of caries (3.2%). The ARS-based module provides a positive learning environment that ensures student anonymity, interactivity, and engagement, and combined with the other seminar module gives students basic skills in caries detection and treatment planning.
Coping with habitat disturbance: camera-traps reveal cathemerality of Prolemur simus in the community-managed area of Tsaratanana, eastern Madagascar
Authors: Nazim Aleksandra , Reuillon Laurine , Randrianarijaona Avotra , Roullet Delphine , Donati Giuseppe
Published: July 2022

This study provides new findings on the flexible activity of Prolemur simus in an anthropogenically modified habitat in the rural commune of Tsaratanana, eastern Madagascar. Based on camera-trap data, we compared the temporal distribution of activity of one group of lemurs between the forest edge and the forest core. We also investigated the possible influence of nocturnal luminosity on the activity cycle. The analysis was conducted using Kernel Density estimates and the R package OVERLAP. The distribution across the 24-h cycle confirmed that Prolemur simus is cathemeral in the wild. The lemurs displayed three peaks of activity: one during the night and two coinciding with morning and evening twilights. The highest proportions of nocturnal activity occurred at the forest edge and at low moon luminosity suggesting a possible anti-predator and/or human-avoidance strategy. The flexible activity of Prolemur simus may contribute to the tolerance of this Critically Endangered species to anthropogenic disturbance.
Mortal Mistakes
Authors: Christie Lars
Published: July 2022

What are the justifications for and constraints on the use of force in self-defense? In his book The Morality of Defensive Force, Jonathan Quong presents the moral status account to address this and other fundamental questions. According to the moral status account, moral liability to defensive harm is triggered by treating others with less respect than they are due. At the same time, Quong rejects the relevance of culpability to the morality of defensive harming. In this article I argue that this rejection of culpability is unfounded and that Quong fails to establish his account as superior to the culpability account of liability to defensive harm.
Against the Worse Than Nothing Account of Harm: A Reply to Immerman
Authors: Johansson Jens , Risberg Olle
Published: July 2022

The counterfactual comparative account of harm (cca) faces well-known problems concerning preemption and omission. In a recent article in this journal, Daniel Immerman proposes a novel variant of cca, which he calls the worse than nothing account (wtna). According to Immerman, wtna nicely handles the preemption and omission problems. We seek to show, however, that wtna is not an acceptable account of harm. In particular, while wtna deals better than cca with some cases that involve preemption and omission, it has implausible implications in other similar cases – cases that, moreover, pose no problems for cca.
Une histoire intellectuelle de la tripartition notion, concept, idée selon les dictionnaires philosophiques
Authors: Roux Sophie
Published: July 2022

Cet article esquisse une généalogie du privilège que le terme concept a acquis en français par rapport à notion et à idée en se fondant non seulement sur les ouvrages des philosophes, mais sur des dictionnaires de langue philosophique. Il comprend quatre parties chronologiques. Après avoir étudié l’introduction des termes concept, notion, idée dans la langue philosophique, la première partie répertorie leurs usages dans les dictionnaires scolastiques du SVIIe siècle. La deuxième montre que Descartes a imposé idée en donnant de ce terme une acception large et que les dictionnaires post-cartésiens la reprenne. La troisième établit que Kant a, contre cette acception large, introduit une distinction entre Begriff et Idee, mais que, initialement, les dictionnaires français refusèrent cette distinction. La quatrième et dernière partie est consacrée à un XXe siècle marqué par l’idéalisme allemand et l’analyse logique : aussi différentes qu’aient été ces deux traditions, elles ont été d’accord pour consacrer la prééminence du terme concept.
Molecular identification of Isospora coerebae Berto, Flausino, Luz, Ferreira & Lopes, 2010 (Chromista: Miozoa: Eimeriidae) from the bananaquit Coereba flaveola (Linnaeus, 1758) (Passeriformes: Thraupidae: Coerebinae) from Brazil
Authors: ORTÚZAR-FERREIRA CARLOS NEI , ANDRADE LUCAS DE ASSIS S. , GENOVEZ-OLIVEIRA JHON LENNON , OLIVEIRA MARIANA S. , MELLO ERICSON R. , CARDOZO SERGIAN V. , OLIVEIRA ÁGUIDA A. , LIMA VIVIANE M. , FERREIRA ILDEMAR , BERTO BRUNO P.
Published: July 2022

Isospora coerebae Berto, Flausino, Luz, Ferreira & Lopes, 2010 is a coccidian protozoan described from bananaquits Coereba flaveola (Linnaeus, 1758), on Marambaia Island, which is located on the southeastern Brazilian coast. In this current work, I. coerebae is identified from C. flaveola in a protected area close to Marambaia Island, but on the mainland, establishing a new location of parasitism, in addition to providing a preliminary genotypic characterization via sequencing of two regions of the mitochondrial cytochrome c oxidase subunit 1 (COI) gene. Its oocysts are sub-spherical, 24.4 × 22.9 μm, with smooth, bilayered wall, ~1.7 μm thick. Micropyle, polar granules and oocyst residuum are absent. Sporocysts are elongate ovoidal, 17.6 × 10.5 μm. Stieda body prominent and rounded and sub-Stieda body short and wide. Sporocyst residuum is composed of scattered granules of different sizes. Sporozoites are vermiform with a prominent posterior refractile body. The oocysts of the current work are morphologically equivalent to the original description of I. coerebae, which have a typical and easily identifiable morphology, mainly in the Stieda and Sub-Stieda bodies. The two sequenced gene regions of the COI gene approximated I. coerebae to Isospora spp. from Southeastern Brazil, but also from Isospora spp. from passerines of North America, Europe and Asia. Although there is a small overlap between the two genic regions sequenced in the current work, it is estimated that the longer COI sequence, which was recently designed and still not widespread, should show better phylogenetic results in the future.
A new genus and four new species of Gyponini (Insecta: Hemiptera: Cicadellidae) with long ovipositors from Amazonas, Brazil
Authors: DA SILVA MARCELO PEIXOTO GOMES , GONÇALVES CLAYTON CORRÊA , TAKIYA DANIELA MAEDA
Published: July 2022

A new leafhopper genus of the tribe Gyponini, Domahovana gen. nov., is proposed and described based on four newly described species from Amazonas State, Northern Brazil: Domahovana icamiabas sp. nov. (type species) and Domahovana mani sp. nov. from Reserva Biológica do Cuieiras, Manaus and Domahovana naia sp. nov. and Domahovana yamurikuma sp. nov. from Comunidade Lago Grande no Seringal do Recreio, Rio Gregório, Ipixuna. The new genus can be distinguished from other Gyponini mainly by the combination of the following morphological features: body medium-sized; head short with distinct foliaceous transition between crown and face; forewing with m-cu1 crossvein absent and m-cu2 crossvein basad of r-m1 crossvein for a long distance; male pygofer long and without process; subgenital plate subtriangular, ventrally covered by long hair-like setae; style long and narrow, with a ventromesal tooth; aedeagus atrium with single or paired short ventral processes, shaft short, with dorsal apodeme well developed and expanded laterally; and ovipositor extremely long, narrow and straight, with other terminalia also elongate, a unique feature among female Gyponini. A key to the four known species of Domahovana is provided.
Targeted Therapy of Lung Adenocarcinoma by the Nanoplatform Based on Milk Exosomes Loaded with Paclitaxel
Authors: Chen Junge , Cao Fengqiang , Cao Yang , Wei Shujin , Zhu Xiurui , Xing Wanli
Published: July 2022

Lung cancer is the most common cancer throughout the world. Currently, most lung cancer therapies are still limited by serious side effects caused. This paper reports a biocompatible drug delivery system that utilizes milk-derived exosomes to deliver paclitaxel to treat lung adenocarcinoma.
First, milk-derived exosomes were modified with integrin αVβ3, αVβ5-binding peptide iRGD so that they could successfully target lung adenocarcinoma cells. Then, iRGD modified exosomes were loaded
with paclitaxel (PAC) via electroporation and used for tumor therapy. These modified exosomes proved effective in killing lung adenocarcinoma cells, and the exosome-based nanoplatform showed no obvious toxicity to normal cells. Further more, the exosome-based nanoplatform could effectively
penetrate the interior of the 3D tumor sphere, reaching more tumor cells and demonstrating that it is a promising tool for lung adenocarcinoma therapy.
Resveratrol Nanoparticles Suppresses Migration and Invasion of Renal Cell Carcinoma Cells by Inhibiting Matrix Metalloproteinase 2 Expression and Extracellular Signal-Regulated Kinase Pathway
Authors: Zhu Xing-Wang , Dong Feng-Ming , Liu Jia , Li Ming-Shan
Published: July 2022

The aim of this study was to examine the impact of Resveratrol nanoparticles on migration/invasion capacity of renal cell carcinoma (RCC) cells and its mechanism. Human RCC cells were exposed to dimethyl sulfoxide or gradient concentrations of Resveratrol nanoparticles respectively,
and U0126 were also added in some experiments. We examined renal cell viability by MTT assay, and wound healing test and Transwell assays were used detect invasion and migration capability of RCC cells. We used Western blotting assay to analyze the protein levels in extracellular signal-regulated
kinase (ERK) signaling. We also detected the enzymatic capacity of matrix metalloproteinase 2 (MMP-2) in cells by gelatin enzymatic profiling. Resveratrol nanoparticles treatment significantly suppressed cell viability to migrate and invade RCC cells in a dose-dependent manner. Also, notably
were reduced MMP-2 activity and expression, and elevated TIMP-2 level were observed in RCC cells exposed with Resveratrol nanoparticles. Further, Resveratrol nanoparticles treatment significantly decreased only the expression of p-ERK1/2, but not p-p38 and p-JNK. Moreover, U0126, which is
the ERK inhibitor, exerted similar role as Resveratrol nanoparticles did. Of note was that, combined use of U0126 and Resveratrol nanoparticles displayed a more intense suppression of MMP-2 activity and expression, and also the viability to migrate and invade the RCC cells, compared with Resveratrol
nanoparticles treatment alone. The Resveratrol nanoparticles inhibited RCC cells migration and invasion by regulating MMP2 expression and ERK pathways.
Research on Mechanism of Nanometric Bone Pulp Activated with Double Gene as Bone Morphogenetic Protein 1 and Vascular Endothelial Growth Factor for Improving the Strength of Centrum in Osteoporosis
Authors: Zhang Cheng-Liang , Song Da-Jiang , Zhang Li-Dong , Liu Lei , Zhu Bao-Lin
Published: July 2022

The aim of this study was assessing the mechanism of nanometric bone pulp activated with double gene as bone morphogenetic protein 1 (BMP-1) and vascular endothelial growth factor (VEGF) in improving the strength of centrum in osteoporosis (OP). The model of nanometric bone pulp activated
with BMP-1 and VEGF double gene was established and validated. Under maximum condition of load and collapsed fragments, the model was analyzed through biomechanical test. The conditions for ALP, BGP, MLL and BMD in the model were also analyzed, and three-dimensional structural transformation
was analyzed. Western blot and qRT-PCR were used to detect the effect of adding or not adding dual gene activated nano-bone stickers on OC-specific protein and mRNA; ELISA kits were used to detect the changes of RANKL pathway RANKL, OPG and TRACP5b. The maximum conformed quality and condensed
intensity were strengthened with the nanometric bone pulp activated with BMP-1 and VEGF double gene. The maximum load in centrum was extremely elevated in the model, and the condition of ALP and its effect on bone was partly improved in the model. The precision and efficiency in the quality
of BMD were continuously decreased. The BMD and MLF were strengthened notably in the model, and their effect on the bone was extremely improved. There was tight displayed model of trabecular in centrum and porosity was also continuously reduced. After adding the double-gene activated nano-bone
stickers, the results from qRTPCR and Western blot showed that the changes of osteoclast-related genes and protein expressions were significantly down-regulated. The nanometric bone pulp activated with BMP-1 and VEGF double gene was one of ideal filled criterion. The BMD and bone strength
were also elevated.
Carrier-Free Nanomedicine for Cancer Immunotherapy
Authors: Fu Yu , Bian Xufei , Li Pingrong , Huang Yulan , Li Chong
Published: July 2022

With the rapid development of nanotechnology, carrier-based nano-drug delivery systems (DDSs) have been widely studied due to their advantages in optimizing pharmacokinetic and distribution profiles. However, despite those merits, some carrier-related limitations, such as low drug-loading
capacity, systematic toxicity and unclear metabolism, usually prevent their further clinical transformation. Carrier-free nanomedicines with non-therapeutic excipients, are considered as an excellent paradigm to overcome these obstacles, owing to their superiority in improving both drug delivery
efficacy and safety concern. In recent years, carrier-free nanomedicines have opened new horizons for cancer immunotherapy, and have already made outstanding progress. Herein, in this review, we are focusing on making an integrated and exhaustive overview of lately reports about them. Firstly,
the major synthetic strategies of carrier-free nanomedicines are introduced, such as nanocrystals, prodrug-, amphiphilic drug-drug conjugates (ADDCs)-, polymer-drug conjugates-, and peptide-drug conjugates (PepDCs)-assembled nanomedicines. Afterwards, the typical applications of carrier-free
nanomedicines in cancer immunotherapy are well-discussed, including cancer vaccines, cytokine therapy, enhancing T-cell checkpoint inhibition, as well as modulating tumor microenvironment (TME). After that, both the advantages and the potential challenges, as well as the future prospects of
carrier-free nanomedicines in cancer immunotherapy, were discussed. And we believe that it would be of great potential practiced and reference value to the relative fields.
Protective Effect of Iron Oxide Nanoparticles on Periodontal Injury in Rats by Inhibiting Collagenase-1 and Alkaline Phosphatase Expression
Authors: Wang Yirui , Liang Zhixiong , Chen Liang , Yang Guosheng , Xu Jing , Deng Chunmei , Wang Chun , Lei Changjiang
Published: July 2022

This study intends to assess whether iron oxide nanoparticles affect periodontal injury and collagenase-1 (COL-1), and alkaline phosphatase (ALP) in rats. In this study, the ALP activity and Col-1 concentration in rats with periodontal injury were determined.We detected the periodontal
histopathological changes and expression of periodontal pocket depth (PD) and attachment loss (AL) by Hematoxylin and eosin (HE) staining.We also detected Col-1 and ALP proteins in periodontal tissues by Western blot. Real-time reverse transcription–polymerase chain reaction (RT-PCR)
detected Col-1 and ALP mRNA level in periodontal tissues of rats in each group, while ALP activity and Col-1 concentration in gingival crevicular fluid in model group increased compared to sham group (P < 0.05). After intervention by iron oxide nanoparticles, ALP activity and Col-1
concentration in the gingival crevicular fluid of model rats decreased greatly (P < 0.05). The gingival atrophy was more serious in model group, and many inflammatory cells infiltrated into the tissue and destroyed the alveolar tissue. Meanwhile, the periodontal tissue from rats
in intervention group was greatly improved, and the degree of alveolar bone destruction was also significantly reduced, while the PD and AL periodontal indexes were significantly inhibited (P < 0.05). The protein and relative expression showed that the protein and mRNA expressions
of ALP and Col-1 in periodontal tissue from model group were lower than those in sham group (P < 0.05). After intervention by iron oxide nanoparticles, the protein and mRNA expressions of ALP and Col-1 in the periodontal tissues in intervention group increased (P < 0.05).
Iron oxide nanoparticles can thus inhibit the expression of ALP and COL-1 in periodontal injury rats, and improve the periodontal injury tissue.
Preliminary Study of an Adjustable, Wearable, Noninvasive Vest Providing Chest Compression to Assist with Breathing
Authors: Li Jianwen , Li Yujiang , Liu Huazhu , Lin Shengxin , Xie Haihui , Pan Ruilan , Chang Xueqin , Lu Jianfeng , Li Songbo , Zhou Jianping
Published: July 2022

Respiratory muscle paralysis caused by acute cervical spinal cord injury usually leads to pulmonary ventilation dysfunction and even death from respiratory failure. In addition to invasive treatments such as mechanical ventilation, the utilization of noninvasive respiratory support
equipment plays an important role in long-term assisted breathing. In this study, we describes a wearable, noninvasive vest with adjustable pressure that enables assisted breathing and with an automatic alarm, and we aims to explore its safety and effectiveness on healthy adult participants.
The vest monitors the human heart rate and the blood oxygen index data in real time, the alarm is automatically activated when the data is abnormal. Eight healthy participants had no obvious discomfort during the test while wearing the vest. Lung volumes, antero-posterior diameters, and left-right
diameters at the second, fourth, and sixth ribs levels were acquired before and after inflation of the vest airbag, the data acquired by the imaging analysis using chest computed tomography showed significant differences before and after the inflation (p < 0.05). Thus, The vest designed
for this study can achieve uniform and effective compression of the thorax, significantly changed the size of the thorax and lungs. It is expected to be applied as noninvasive support for patients with respiratory dysfunction.
Decadal Variability of Rainfall in Senegal: Beyond the Total Seasonal Amount
Authors: Badji Aïssatou , Mohino Elsa , Diakhaté Moussa , Mignot Juliette , Gaye Amadou Thierno
Published: July 2022

Rainfall characteristics are crucial in monsoon regions, in particular for agriculture. Crop yields indeed depend on the rainfall seasonal amounts, but also on other rainfall characteristics such as the onset of the rainy season or the distribution of rainy days. In the Sahel region, while the average amount of seasonal rainfall has been shown to be marked by strong decadal variability, the modulation of rainfall characteristics has received less attention in the literature so far. In this study, we show that the frequency of light, heavy, and extreme rainfall events and the mean intensity of rainfall events in Senegal exhibit a marked decadal variability over the 1918–2000 period, strongly similar to that of the mean seasonal rainfall. The decadal modulations of these events show a strong and positive link with the Atlantic multidecadal variability (AMV). Indeed, positive sea surface temperature anomalies over the North Atlantic and Mediterranean related to a warm AMV phase are associated with negative sea level pressure anomalies over the northern Atlantic and a northward shift of the intertropical convergence zone. We also find that the onset and cessation dates as well as the length of the rainy season show relatively less decadal variability, which is more related to the interdecadal Pacific oscillation (IPO), a positive phase of the latter leading to a late onset, an early cessation, and an overall shorter rainy season in Senegal.
Role of the Climatological North Pacific High in the North Tropical Atlantic–ENSO Connection
Authors: Park Jae-Heung , Kug Jong-Seong , Yang Young-Min , Oh Hyoeun , Zhao Jiuwei , Wu Yikai
Published: July 2022

Observational and climate model analysis showed that the anomalous sea surface temperature in the north tropical Atlantic (NTA) in boreal spring can trigger El Niño–Southern Oscillation (ENSO) in the subsequent winter. Similarly, the climate models participating in phase 5 of the Coupled Model Intercomparison Project (CMIP5) are known to reasonably simulate the NTA effect. Nevertheless, the strengths of the NTA effect on ENSO among the climate models are also diverse. In this light, we revisited the possible causes that contributed to the different NTA effects on ENSO in the CMIP5 climate models. We found that the strength of the NTA triggering ENSO in the climate model tended to be proportional to the intensity of the climatological subtropical North Pacific high system in boreal spring. The stronger climatological subtropical North Pacific high accompanied enhanced trade wind, precipitation reduction, and cold sea surface temperature over the subtropics. Under these conditions, the moist static energy feedback process, also known as the moist enthalpy advection mechanism, effectively operated around the Pacific intertropical convergence zone. That is, the NTA-induced signals in the subtropical North Pacific readily intruded into the deep tropical Pacific with the aid of the feedback processes, leading to an ENSO event. Consistent with the CMIP5 analysis results, the observed NTA effect on ENSO became stronger during the decades when the climatological North Pacific subtropical high intensified, underpinning the importance of climatology in the subtropical North Pacific in the NTA–ENSO connection.
Large-Amplitude Internal Wave Transformation into Shallow Water
Authors: Sinnett Gregory , Ramp Steven R. , Yang Yiing J. , Chang Ming-Huei , Jan Sen , Davis Kristen A.
Published: July 2022

Large-amplitude internal solitary wave (ISW) shoaling, breaking, and run-up was tracked continuously by a dense and rapidly sampling array spanning depths from 500 m to shore near Dongsha Atoll in the South China Sea. Incident ISW amplitudes ranged between 78 and 146 m with propagation speeds between 1.40 and 2.38 m s−1. The ratio between wave amplitude and a critical amplitude A0 controlled breaking type and was related to wave speed cp and depth. Fissioning ISWs generated larger trailing elevation waves when the thermocline was deep and evolved into onshore propagating bores in depths near 100 m. Collapsing ISWs contained significant mixing and little upslope bore propagation. Bores contained significant onshore near-bottom kinetic and potential energy flux and significant offshore rundown and relaxation phases before and after the bore front passage, respectively. Bores on the shallow forereef drove bottom temperature variation in excess of 10°C and near-bottom cross-shore currents in excess of 0.4 m s−1. Bores decelerated upslope, consistent with upslope two-layer gravity current theory, though run-up extent Xr was offshore of the predicted gravity current location. Background stratification affected the bore run-up, with Xr farther offshore when the Korteweg–de Vries nonlinearity coefficient α was negative. Fronts associated with the shoaling local internal tide, but equal in magnitude to the soliton-generated bores, were observed onshore of 20-m depth.
Vortex Sheet Sensitivity to Low-Level Vertical Shear and Airmass Temperature Perturbation
Authors: Houston Adam L. , Limpert George
Published: July 2022

A theoretical, numerical-modeling-based examination of the sensitivity of vortex sheets along airmass boundaries to the following three characteristics is presented: 1) boundary-normal component of the vertical wind shear, 2) boundary-parallel component of the vertical wind shear, and 3) temperature perturbation within the parent air mass of the boundary. The overall aim of this work is to advance understanding of the sensitivity of micro-α- to meso-γ-scale vortex generation along airmass boundaries to the ambient environment. Density currents are simulated in a 2D domain that does not allow baroclinic generation of near-surface vertical vorticity (ζns) with parameterized latent heating for convection initiated at the associated airmass boundary and Coriolis turned on. Despite the absence of baroclinically generated ζns, with Coriolis turned on and without any boundary-parallel shear, ζns more than two orders of magnitude larger than planetary vorticity is generated along the boundary and located within the cold air. The magnitude of ζns is found to increase with increasing boundary-normal shear with statistically significant intra-experiment separations. Near-surface vertical vorticity ζns is found to scale inversely with boundary-parallel shear with a transition to negative leading-edge ζns in several of the larger boundary-normal shear simulations. An inverse and statistically significant relationship is found between ζns and the temperature perturbation within the parent air mass of the boundary (Δθ), and is a direct consequence of the dependence of boundary propagation speed on Δθ.

Significance Statement

Research presented in this article aims to contribute to an improved understanding of the environmental controls on the generation of small-scale vortices along airmass boundaries. Vertical shear, both along and across an airmass boundary, as well as temperature of the air mass on the cool side of an airmass boundary are found to regulate the magnitude of near-surface vertical vorticity available to small-scale vortices.
Unsteady and hysteretic behavior of a magnetorheological fluid damper: Modeling, modification, and experimental verification
Authors: Du Xinxin , Zhang Yonghao , Li Jiahao , Liao Changrong , Zhang Honghui , Xie Lei , Gan Bin , Lu Jun
Published: July 2022

Although the quasi-static model is widely employed in various engineering fields to guide the design of magnetorheological (MR) dampers, it is not accurate enough to describe the dynamic behaviors of MR dampers. In this study, an unsteady Bingham plastic (US-BP) model that considers fluid inertia is established. The proposed model can realize flexible switching between flow mode and mixed mode by introducing a mode parameter. To employ the US-BP model for MR dampers under different excitations, a technique combining the Fourier series method and Laplace transform is developed to deduce the velocity profiles of MR fluids. Based on the US-BP model, the damping characteristics of an MR damper under different excitation frequencies, yield stresses, and mode parameters are theoretically investigated. Furthermore, an unsteady hysteretic Bingham plastic (USHY-BP) model that incorporates particle chain deflection theory is developed to characterize the hysteretic behavior and inertia effect of the damping force. Comparisons between the simulation results and the experimental data reveal that the US-BP model can predict the unsteady behaviors of damping forces caused by fluid inertia but fails to capture the hysteresis characteristic. The USHY-BP model achieves good performance and accuracy in characterizing the dynamic properties of MR dampers.
Venetoclax synergizes with gilteritinib in FLT3 wild-type high-risk acute myeloid leukemia by suppressing MCL-1
Authors: Janssen Maike , Schmidt Christina , Bruch Peter-Martin , Blank Maximilian F. , Rohde Christian , Waclawiczek Alexander , Heid Daniel , Renders Simon , Göllner Stefanie , Vierbaum Lisa , Besenbeck Birgit , Herbst Sophie A. , Knoll Mareike , Kolb Carolin , Przybylla Adriana , Weidenauer Katharina , Ludwig Anne Kathrin , Fabre Margarete , Gu Muxin , Schlenk Richard F. , Stölzel Friedrich , Bornhäuser Martin , Röllig Christoph , Platzbecker Uwe , Baldus Claudia , Serve Hubert , Sauer Tim , Raffel Simon , Pabst Caroline , Vassiliou George , Vick Binje , Jeremias Irmela , Trumpp Andreas , Krijgsveld Jeroen , Müller-Tidow Carsten , Dietrich Sascha
Published: July 2022

BCL-2 inhibition has been shown to be effective in acute myeloid leukemia (AML) in combination with hypomethylating agents or low-dose cytarabine. However, resistance and relapse represent major clinical challenges. Therefore, there is an unmet need to overcome resistance to current venetoclax-based strategies. We performed high-throughput drug screening to identify effective combination partners for venetoclax in AML. Overall, 64 antileukemic drugs were screened in 31 primary high-risk AML samples with or without venetoclax. Gilteritinib exhibited the highest synergy with venetoclax in FLT3 wild-type AML. The combination of gilteritinib and venetoclax increased apoptosis, reduced viability, and was active in venetoclax-azacitidine–resistant cell lines and primary patient samples. Proteomics revealed increased FLT3 wild-type signaling in specimens with low in vitro response to the currently used venetoclax-azacitidine combination. Mechanistically, venetoclax with gilteritinib decreased phosphorylation of ERK and GSK3B via combined AXL and FLT3 inhibition with subsequent suppression of the antiapoptotic protein MCL-1. MCL-1 downregulation was associated with increased MCL-1 phosphorylation of serine 159, decreased phosphorylation of threonine 161, and proteasomal degradation. Gilteritinib and venetoclax were active in an FLT3 wild-type AML patient-derived xenograft model with TP53 mutation and reduced leukemic burden in 4 patients with FLT3 wild-type AML receiving venetoclax-gilteritinib off label after developing refractory disease under venetoclax-azacitidine. In summary, our results suggest that combined inhibition of FLT3/AXL potentiates venetoclax response in FLT3 wild-type AML by inducing MCL-1 degradation. Therefore, the venetoclax-gilteritinib combination merits testing as a potentially active regimen in patients with high-risk FLT3 wild-type AML.
MicroRNA-205-5p plays a suppressive role in the high-fat diet-induced atrial fibrosis through regulation of the EHMT2/IGFBP3 axis
Authors: Xiao Zezhou , Xie Yu , Huang Fangze , Yang Jie , Liu Ximao , Lin Xuefeng , Zhu Peng , Zheng Shaoyi
Published: July 2022

Objective

MicroRNAs (miRNAs) targeting has been revealed to be an appealing strategy for the treatment and management of atrial fibrillation (AF). In this research, we aimed to explore the mechanisms of miR-205-5p in reducing the high-fat diet (HFD)-induced atrial fibrosis through the EHMT2/IGFBP3 axis.

Methods

Expression levels of miR-205-5p, IGFBP3 and EHMT2 were determined in AF patients, cell fibrosis models and mouse atrial fibrosis models. Luciferase activity and RIP assays were performed to detect the binding between miR-205-5p and EHMT2, and ChIP assays were implemented to detect the enrichment of H3K9me2 and H3K4me3 in the promoter region of IGFBP3 in cells. The related experiments focusing on the inflammatory response, atrial fibrosis, mitochondrial damage, and metabolic abnormalities were performed to figure out the roles of miR-205-5p, IGFBP3, and EHMT2 in cell and mouse atrial fibrosis models.

Results

Low expression levels of miR-205-5p and IGFBP3 and a high expression of EHMT2 were found in AF patients, cell fibrosis models and mouse atrial fibrosis models. Upregulation of miR-205-5p reduced the expression of TGF-β1, α-SMA, Col III and other fibrosis-related proteins. miR-205-5p overexpression targeted EHMT2 to regulate the methylation of H3 histones to promote IGFBP3 expression, which in turn affected the fibrosis of atrial muscle cells. In HFD-induced atrial fibrosis mice, upregulated miR-205-5p or elevated IGFBP3 alleviated atrial fibrosis, mitochondrial damage, and metabolic abnormalities.

Conclusion

This study suggests that miR-205-5p attenuates HFD-induced atrial fibrosis via modulating the EHMT2/IGFBP3 axis.

Graphical Abstract

miR-205-5p alleviates high-fat diet-induced atrial fibrosis in mice via EHMT2/IGFBP3.