bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying the causal relationship between sedentary behavior and heart failure: Insights from a Mendelian randomization study and mediation analysis
Authors: Zheng Xifeng , Liu Manqi , Wu Zijun , Jia Zhen
Published: August 2023

Background

Observational studies have revealed that a lack of physical exercise may be linked to a higher risk of heart failure (HF). Here, the causal relationship between sedentary behavior (SB) and HF was investigated using Mendelian randomization (MR).

Hypothesis

SB was considered as an important risk factor of HF.

Methods

Single nucleotide polymorphisms with a genome‐wide statistical significance threshold of <5 × 10−8 among the SB‐proxied phenotypes (TV screen time, computer use, and driving) from genome‐wide association study (GWAS) datasets were identified as instrumental variables (IVs). The MR study was performed using the inverse‐variance weighting (IVW) model as a primary standard to evaluate causal relationships. Simultaneously, MR‐Egger regression, weighted median, and maximum likelihood models were used as supplements. Sensitivity analysis, consisting of a heterogeneity and horizontal pleiotropy test, was performed using Cochran's Q, MR‐Egger intercept, and MR‐PRESSO tests to ensure the reliability of conclusions.

Results

The IVW model results showed that increased TV screen time correlated with a higher genetic susceptibility for HF in both HF‐associated GWAS datasets, which was also supported by weighted median and maximum likelihood model results. The odds ratios with 95% confidence intervals were 1.418 (1.182–1.700) and 1.486 (1.136–1.943), respectively. Although the results of Cochran's Q test indicated certain heterogeneity among the IVs. The MR‐Egger intercept and MR‐PRESSO tests suggested no horizontal pleiotropy and verified the reliability of the conclusion.

Conclusions

This MR study identified that increased TV screen time may predispose individuals to the development of HF.
Autonomous eDNA collection using an uncrewed surface vessel over a 4200‐km transect of the eastern Pacific Ocean
Authors: Preston Christina , Yamahara Kevan , Pargett Douglas , Weinstock Chloe , Birch James , Roman Brent , Jensen Scott , Connon Brian , Jenkins Richard , Ryan John , Scholin Christopher
Published: August 2023

The collection of environmental DNA (eDNA) samples is often laborious, costly, and logistically difficult to accomplish at high frequency in remote locations and over large geographic areas. Here, we addressed those challenges by combining two robotic technologies: an uncrewed surface vessel (USV) fitted with an automated eDNA sample collection device to survey surface waters in the eastern North Pacific Ocean from Alameda, CA to Honolulu, HI. USV Surveyor SD 1200 (Saildrone) carrying the Environmental Sample Processor (ESP) collected 2‐L water samples by filtration followed by RNAlater preservation at regular intervals over a 4200‐km, 29‐day transit. Sixty samples (52 field and 8 controls) were acquired and used to estimate the concentration of specific genes and assess eukaryotic diversity via targeted qPCR and metabarcoding of the cytochrome oxidase subunit I (COI) gene, respectively. Comparisons of control samples revealed important considerations for interpreting results. Samples stored at ambient temperatures onboard Surveyor over the length of the voyage had less total recoverable DNA and specific target gene concentrations compared to the same material immediately flash‐frozen after collection and stored in a laboratory. In contrast, the biodiversity of the COI genes in those samples was similar regardless of sample age and storage condition. COI genes affiliated with 40 eukaryotic phyla were found in native samples collected during the voyage. The distribution and dominance of those phyla varied across different regions, with some taxa spanning large continuous stretches >2000 km, while others were only detected in a single sample. This work highlights the utility and potential of using USVs fitted with autonomous eDNA sample collection devices to improve ocean exploration and support large, basin‐scale, systematic biodiversity surveys. Results of this study also inform future technical considerations for using automated eDNA samplers to acquire material and store it over prolonged periods under prevailing environmental conditions.
Association between epicardial adipose tissue and cardiac dysfunction in subjects with severe obesity
Authors: Chin Jie Fen , Aga Yaar S. , Abou Kamar S. , Kroon D. , Snelder Sanne M. , van de Poll Sweder W.E. , Kardys Isabella , Brugts Jasper J. , de Boer Rudolf A. , van Dalen Bas M.
Published: August 2023

Aim

Epicardial adipose tissue (EAT) plays a role in obesity‐related heart failure with preserved ejection fraction. However, the association of EAT thickness with the development of cardiac dysfunction in subjects with severe obesity without known cardiovascular disease is unclear. The aim of this study was to determine the association between EAT thickness and cardiac dysfunction and describe the potential value of EAT as an early marker of cardiac dysfunction.

Methods and results

Subjects with body mass index ≥35 kg/m2 aged 35 to 65 years, who were referred for bariatric surgery, without suspicion of or known cardiac disease, were enrolled. Conventional transthoracic echocardiography and strain analyses were performed. A total of 186 subjects were divided into tertiles based on EAT thickness, of whom 62 were in EAT‐1 (EAT <3.8 mm), 63 in EAT‐2 (EAT 3.8–5.4 mm), and 61 in EAT‐3 (EAT >5.4 mm). Parameters of systolic and diastolic function were comparable between tertiles. Patients in EAT‐3 had the lowest global longitudinal strain (GLS) and left atrial contractile strain (LASct). Linear regression showed that a one‐unit increase in EAT thickness (mm) was independently associated with a decrease in GLS (%) (β coefficient −0.404, p = 0.002), and a decrease in LASct (%) (β coefficient −0.544, p = 0.027). Furthermore, EAT‐3 independently predicted cardiac dysfunction as defined by a GLS <18% (odds ratio 2.8, p = 0.013) and LASct <14% (odds ratio 2.5, p = 0.045).

Conclusions

Increased EAT thickness in subjects with obesity without known cardiac disease was independently associated with subclinical cardiac dysfunction. Our findings suggest that EAT might play a role in the early stages of cardiac dysfunction in obesity before this may progress to overt clinical disease.
Early left atrial venting versus conventional treatment for left ventricular decompression during venoarterial extracorporeal membrane oxygenation support: The EVOLVE‐ECMO randomized clinical trial
Authors: Park Hanbit , Yang Jeong Hoon , Ahn Jung‐Min , Kang Do‐Yoon , Lee Pil Hyung , Kim Tae Oh , Choi Ki Hong , Kang Pil Je , Jung Sung‐Ho , Yun Sung‐Cheol , Park Duk‐Woo , Lee Seung‐Whan , Park Seung‐Jung , Kim Min‐Seok
Published: August 2023

Aims

Few studies have reported data on the optimal timing of left ventricular (LV) unloading during venoarterial extracorporeal membrane oxygenation (VA‐ECMO) for cardiac arrest or shock. This study evaluated the feasibility of an early LV unloading strategy compared with a conventional strategy in VA‐ECMO.

Methods and results

Between December 2018 and August 2022, 60 patients at two institutions were randomized in a 1:1 ratio to receive early (n = 30) or conventional (n = 30) LV unloading strategies. The early LV unloading strategy was defined as LV unloading performed at the time of VA‐ECMO insertion. LV unloading was performed using a percutaneous transseptal left atrial cannulation via the femoral vein incorporated into the ECMO venous circuit. The early and conventional LV unloading groups included 29 (96.7%) and 23 (76.7%) patients, respectively (median time from VA‐ECMO insertion to LV unloading: 48.4 h, interquartile range 47.8–96.5 h). The groups showed no significant differences in the rate of VA‐ECMO weaning as the primary endpoint (70.0% vs. 76.7%; relative risk 0.91; 95% confidence interval 0.67–1.24; p = 0.386) and survival to discharge (53.3% vs. 50.0%, p = 0.796). However, the pulmonary congestion score index at 48 h after LV unloading was significantly improved only in the early LV unloading group (2.0 ± 0.7 vs. 1.7 ± 0.6 at baseline vs. at 48 h; p = 0.008).

Conclusions

Compared with the conventional approach, early LV unloading did not improve the VA‐ECMO weaning rate, despite the rapid improvement in pulmonary congestion. Therefore, the results of this study do not support the application of this strategy after VA‐ECMO insertion.
Activation and Deactivation of Benzylic C−H Bonds Guided by Stereoelectronic Effects in Hydrogen Atom Transfer from Amides and Amines to Alkoxyl Radicals
Authors: Sisti Sergio , Ioele Fabio , Scarchilli Filippo , Galeotti Marco , DiLabio Gino A. , Salamone Michela , Bietti Massimo
Published: August 2023

Kinetic and product studies on the reactions of tert‐alkoxyl radicals with secondary and tertiary alkanamides bearing benzylic α‐C−H bonds, isoindoline, tetrahydroisoquinoline and the corresponding N‐acetyl derivatives were carried out. Product studies on the reactions with the tert‐butoxyl radical (tBuO⋅) point toward exclusive HAT from the benzylic α‐C−H bonds. Comparison of the kH values measured for reaction with the cumyloxyl radical (CumO⋅) with those obtained previously for the corresponding reactions of N‐alkyl‐ and N,N‐dialkylalkanamides, are indicative of a lack of benzylic activation and the operation of steric and stereoelectronic effects. Compared to N‐methyl and N‐ethyl groups, the presence of N‐benzyl groups increases the barrier required to reach the optimal conformation for HAT, where the α‐C−H bond to be cleaved is perpendicular to the plane of the amide, precluding concurrent overlap with the phenyl π‐system. When the benzylic α‐C−H bonds are in a conformation that allows for optimal overlap with both the phenyl π‐system and the amide π‐system or amine nitrogen lone pair, as in the isoindoline and tetrahydroisoquinoline derivatives, increases in kH that exceed 2‐orders of magnitude were observed, highlighting the strong contribution provided by stereoelectronic activation to these HAT processes.
Synthetic Routes to Imidates and Their Applications in Organic Transformation: Recent Progress
Authors: Chaidali Andriani G. , Lykakis Ioannis N.
Published: August 2023

Recent synthetic approaches and diverse applications of imidates are presented in this review. These motifs are successfully used as intermediates in organic transformations, such as the synthesis of N‐heterocycles, natural products and metal complexes with a potential catalytic effect. Consequently, many attempts have been made for the development of efficient and facile synthetic methods of imidates in the past few years, as a continuum of previous paths. A wide range of organic compounds can be used as starting materials for these syntheses, including nitriles, isocyanides, amides etc. which through simple and flexible processes are converted to the desired imidates. Herein, an exploration of the recent synthetic routes of imidates and their diverse applications in organic transformations has been categorized and summarized.
Optimal tree architecture for high‐yield yellowhorn (Xanthoceras sorbifolium) management
Authors: Wang Xinrui , Wang Qing , Jia Qiang , El‐Kassaby Yousry A. , Ranjitkar Sailesh , Wang Junjie , Xiang Qiuhong , von Kleist Kurt , Guan Wenbin
Published: August 2023

Tree architectural attributes demonstrate a significant association with fruit yield. Yellowhorn is the future bioenergy tree in China; however, the species suffers from high reproductive energy and exceedingly low reproductive output. To optimize yellowhorn management and pinpoint priority trees featuring optimal architecture, we employed machine learning modeling to develop high fruit yielding predictive models using five yield indicators (dependent variables: FrW, SeW, ShW, FrW, and SeN) and five tree characteristics (independent variables: CA, TH, DGL, HLC, and MBN) of yellowhorn. Results showed that trees characterized by a substantial canopy area (>1.70 m2) and a large diameter at ground level (>3.71 cm) have been found to yield a higher fruit production. However, increased tree height does not invariably correlate with an elevated yield. Effective selection of high‐yielding individuals can be accomplished by restricting tree height within the range of 192–232.4 cm. This approach emphasizes the importance of integrating considerations of tree architecture into forestry management practices. Such integration can bolster productivity, thereby contributing to both the sustainability and economic viability of yellowhorn forests.
Study on the antioxidant activity of peptides from soybean meal by fermentation based on the chemical method and AAPH‐induced oxidative stress
Authors: Ma JuanJuan , Su Keying , Chen Meimei , Wang Shuo
Published: August 2023

Preparation and antioxidant activities of soybean peptides using solid fermentation to decrease the content of trypsin inhibitor (TI) and antigen protein were investigated in this study. The results showed the optimal fermentation conditions were as follows: fermentation time 48 h, the ratio of material to solvent 1:2, inoculum size 12%, and the ratio of Lactic acid bacteria and Aspergillus oryzae 2:1. The hydrolysate was were divided into four components of <1, 1–3, 3–5, and >5 kDa by ultrafiltration based on molecular weight, and the <1 kDa peptides expressed the highest antioxidant activities. Meanwhile, the cell antioxidant activity of the <1 kDa soybean peptides was investigated using AAPH‐induced erythrocyte hemolysis, which effectively inhibited erythrocyte hemolysis with the inhibit rate of 85.8% through inhibition of the ROS intracellular generation. In addition, soybean peptides could significantly restore the intracellular antioxidant enzymes (SOD, GSH‐Px, and CAT) activities, as well as inhibited intracellular MDA generation and depletion of GSH. The intracellular antioxidant detoxifying mechanism of soybean peptides was associated with both non‐enzymatic and enzymatic defense systems. According to this study, fermentation could effectively improve the antioxidant activities of soybean peptides.
Identification of pore facies for evaluating the reservoir quality: A case study of the Hartha Formation in X Oilfield, Mesopotamian Basin, Iraq
Authors: Zhang Ke , Saeed Ahsan Mohammed , Wang Hehua , Mi Zhongrong , Qu Jianhua , Jaed Mustafa A. , Wang Zhikun , Liu Hui , Zhang Zhenghong
Published: August 2023

Characterization of pore systems is a key to better understand the heterogeneity of reservoir quality. However, the complicated pore types and pore facies of carbonates in the Hartha Formation of X Oilfield remain poorly understood. In this study, we recognized pore types and explored the impact of depositional environment and diagenetic alterations on pore facies and reservoir heterogeneity. Six types and nine subtypes of pore facies displaying various physical properties and fossils are classified based on the proportion of depositional pores, fabric‐ and non‐fabric‐selective pores. The distribution of pore facies are controlled by the interaction between depositional environment and diagenesis: (i) the depositional environment has an impact on the primary pore types mainly through different lithology and fossils. Micro‐interparticle pores and intraparticle pores of foraminifera are dominated in lagoon, middle ramp and outer ramp, while interparticle pores between grains are dominated in rudist shoal. Rocks deposited in medium‐ to low‐energy shoal contain interparticle pores between grains, micro‐interparticle pores and intraparticle pores of foraminifera. (ii) Major diagenetic events that modify pore types include micritization, fabric‐selective dissolution, cementation, compaction and non‐fabric‐selective dissolution. Micritization facilitates the development of micro‐interparticle pores, while compaction can cause the loss of interparticle pores between grains and micro‐interparticle pores. Cementation destroys not only interparticle pores between grains but also intraparticle pores of foraminifera. Fabric‐ and non‐fabric‐selective dissolution are the main causes for increasing the volume of pores. (iii) The intensity of the diagenetic event is linked to rock composition, rock fabric and palaeotopography that are controlled by depositional environment. Thus, the distribution of pore facies related to the environment is established, which can provide insights for areas lacking cores and adjacent fields with similar settings.
A case of mid‐ureteral stricture with ipsilateral atrophic kidney in a young adult
Authors: Machida Arisa , Abe Masakazu , Ishii Shuhei , Sekiguchi Kie , Takahashi Kenta , Shiomi Ei , Maekawa Shigekatsu , Kato Yoichiro , Uesugi Noriyuki , Obara Wataru
Published: August 2023

Introduction

Most congenital ureteral strictures occur at the ureteropelvic or ureterovesical junction in children. Mid‐ureteral stricture is very rare and can cause congenital hydronephrosis. Only a few studies have reported on coexisting mid‐ureteral stricture with ipsilateral atrophic kidney in young adults.

Case presentation

A 16‐year‐old girl presented with repeated urinary tract infection. Computed tomography revealed a right atrophic kidney and hydroureter. Retrograde pyelography showed a mid‐ureteral stricture. Laparoscopic nephroureterectomy was performed, and histological examination revealed mid‐ureteral stricture with hyperplasia of the fibrous connective tissue and an atrophic kidney.

Conclusion

Mid‐ureteral stricture in a young adult is extremely rare. Appropriate imaging studies including retrograde pyelography are necessary for accurate diagnosis of mid‐ureteral stricture.
Up‐regulation of inflammatory reactions by MPT32, a secreted protein of Mycobacterium tuberculosis in RAW264.7 macrophages
Authors: Kim Hee‐Do , Choi Hyunju , Abekura Fukushi , Park Junyoung , Cho Seung‐Hak , Lee Young‐Choon , Kim Cheorl‐Ho
Published: August 2023

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) and is still one of the global health burdens. The occurrence of various cases and multidrug resistance confirm that TB has not been completely conquered. For these reasons, the present research has been conducted to explore TB vaccine and drug candidate possibility using Mtb‐secreted proteins. Among these proteins, MPT32 is known to have antigenicity and immunogenicity. There has not been a report on the host immune responses and regulation in macrophage cells. The present study was conducted with MPT32 in RAW 264.7 murine macrophage cells that control immune responses by sensing pathogen invasion and environmental change. We have found that MPT32 could activate lipopolysaccharide (LPS)‐induced gene expression of metalloproteinase‐9 (MMP‐9) and inflammation in RAW 264.7 cells. After treating cells with MPT32, the increase in pro‐inflammatory cytokines, such as tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐1β (IL‐1β) and IL‐6, was observed. In addition, activated macrophages expressed inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) to generate various inflammatory mediator molecules, such as nitric oxide (NO). The increase in iNOS and COX‐2 levels, which are up‐regulators of MMP‐9 expression, was also confirmed. The biochemical events are involved in the downstream of activated MAPK signaling and translocation of NF‐κB transcription factor. The present results prove the immunomodulatory effect of MPT32 in the RAW 264.7 murine macrophage cells. it claims the possibility of a TB vaccination and drug candidate using MPT32, contributing to the prevention of TB.
Unveiling the potential of marine compounds as quorum sensing inhibitors targeting Pseudomonas aeruginosa's LasI: A computational study using molecular docking and molecular dynamics
Authors: Singothu Siva , Begum Pathan J. , Maddi Dhanashri , Devsani Namrata , Bhandari Vasundhra
Published: August 2023

Antimicrobial resistance (AMR) poses a significant threat to global public health, with multidrug‐resistant Pseudomonas aeruginosa being a leading cause of mortality, accounting for 18%–61% of deaths annually. The quorum sensing (QS) systems of P. aeruginosa, particularly the LasI‐LasR system, play a crucial role in promoting biofilm formation and expression of virulent genes, which contribute to the development of AMR. This study focuses on LasI, the mediator of biofilm formation for identifying its inhibitors from a marine compound database comprising of 32 000 compounds using molecular docking and molecular simulation techniques. The virtual screening and docking experiments demonstrated that the top 10 compounds exhibited favorable docking scores of <−7.19 kcal/mol compared to the reported inhibitor 3,5,7‐Trihydroxyflavone with a docking score of −3.098 kcal/mol. Additionally, molecular mechanics/Poisson‐Boltzmann generalized born surface area (MM‐GBSA) analyses were conducted to assess these compounds' suitability for further investigation. Out of 10 compounds, five compounds demonstrated high MM‐GBSA binding energy (<−35.33 kcal/mol) and were taken up for molecular dynamics simulations to evaluate the stability of the protein‐ligand complex over a 100 ns period. Based on root mean square deviation, root mean square fluctuation, radius of gyration, and hydrogen bond interactions analysis, three marine compounds, namely MC‐2 (CMNPD13419) and MC‐3 (CMNPD1068), exhibited consistent stability throughout the simulation. Therefore, these compounds show potential as promising LasI inhibitors and warrant further validation through in vitro and in vivo experiments. By exploring the inhibitory effects of these marine compounds on P. aeruginosa's QS system, this research aims to contribute to the development of novel strategies to combat AMR.
Maternal SMC2 is essential for embryonic development via participating chromosome condensation in mice
Authors: Xu Ke , Qiao Jing‐Yi , Zhao Bin‐Wang , Dong Ming‐Zhe , Lei Wen‐Long , Li Yuan‐Yuan , Ju Zhenyu , Schatten Heide , Wang Zhen‐Bo , Liu Kui , Sun Qing‐Yuan
Published: August 2023

During the oocyte growth, maturation and zygote development, chromatin structure keeps changing to regulate different nuclear activities. Here, we reported the role of SMC2, a core component of condensin complex, in oocyte and embryo development. Oocyte‐specific conditional knockout of SMC2 caused female infertility. In the absence of SMC2, oocyte meiotic maturation and ovulation occurred normally, but chromosome condensation showed defects and DNA damages were accumulated in oocytes. The pronuclei were abnormally organized and micronuclei were frequently observed in fertilized eggs, their activity was impaired, and embryo development was arrested at the one‐cell stage, suggesting that maternal SMC2 is essential for embryonic development.
Estrogen increases the expression of BKCa and impairs the contraction of colon smooth muscle via upregulation of sphingosine kinase 1
Authors: Wang Yan , Jiang Ya , Jiang Ling , Xiong Wenjie , Wang Yanjuan , Gao Xiangyue , Chen Qi , Lin Lin , Yu Ting , Tang Yurong
Published: August 2023

Estrogen (E2) may impair the contraction of colonic smooth muscle (SM) leading to constipation. Large conductance Ca2+‐activated K+ channels (BKCa) are widely expressed in the smooth muscle cells (SMCs) contributing to hyperpolarization and relaxation of SMCs. Sphingosine kinase 1 (SphK1) is known to influence the expression of BKCa. We aimed to elucidate the potential underlying molecular mechanism of BKCa and SphK1 that may influence E2‐induced colonic dysmotility.

In ovariectomized rats, SM contraction and expression of BKCa, SphK1, sphingosine‐1‐phosphate receptor (S1PR) were analyzed after the treatment with vehicle, BSA‐E2, E2, and E2 receptor antagonist. The role of BKCa, SphK1, and S1PR in E2‐induced SM dysmotility was investigated in rat colonic SMCs. The effect of SphK1 on SM contraction as well as on the expression of BKCa and S1PR was analyzed in SphK1 knock‐out mutant mice and wild‐type (WT) mice treated with or without E2.

The E2‐treated group exhibited a weak contraction of colonic SM and a delayed colonic transit. The treatment with E2 significantly upregulated the expression of BKCa, SphK1, S1PR1, and S1PR2, but not S1PR3, in colon SM and SMCs. Inhibition of BKCa, SphK1, S1PR1, and S1PR2 expression attenuated the effect of E2 on Ca2+ mobilization in rat colon SMCs. WT mice treated with E2 showed impaired gastrointestinal motility and enhanced expression of BKCa, S1PR1, and S1PR2 compared with those without E2 treatment. Conversely, in SphK1 knock‐out mice treated with E2, these effects were partially reversed. E2 increased the release of S1P which in turn could have activated S1PR1 and S1PR2. Loss of SphK1 attenuated the effect of E2 on the upregulation of S1PR1 and S1PR2 expression. These findings indicated that E2 impaired the contraction of colon SM through activation of BKCa via the upregulation of SphK1 and the release of S1P. In the E2‐induced BKCa upregulation, S1PR1 and S1PR2 might also be involved. These results may provide further insights into a therapeutic target and optional treatment approaches for patients with constipation.
Understanding the molecular pathogenesis of primary central nervous system lymphoma by experimental animal models
Authors: Wu Di , Liu Dahai , Tateishi Kensuke , Qi Fei , Yang Fang , Ke Chao , You Hua
Published: August 2023

Primary central nervous system lymphoma (PCNSL) is a rare and invasive diffuse large B cell lymphoma confined in central nervous system (CNS). The effort to press forward the translational progress has been frustrated by the insufficient understanding of immunophenotype of CNS and tumor genetic alterations of PCNSL, and the lack of validated diagnostic biomarkers. Researchers now have a variety of PCNSL animal models at their disposal that resemble the morphology and immunophenotype of PCNSL, however, a careful and detailed re‐examination of these animal models is needed to clarify the differences in genetic alterations, migration capability, and immune status. In this review, we present the knowledge about the phenotypic and genotypic features of PCNSL tumor cells, and compile the preclinical animal models of PCNSL with regard to various injection sites, cell origins, recipient animals, and immune status, and elaborate on the tropism and migration of tumor cells and novel therapeutic strategies for PCNSL. We envisage that the selection of suitable animal models will serve as a well‐defined preclinical system to understand the molecular pathogenesis of PCNSL, thereby galvanizing the development of novel and potent therapeutic approaches.
Discovery of the ((diaryl)methyl)phosphonic acid derivatives as novel CD73 inhibitors
Authors: Yang Wenyu , Chen Xi , Ning Xiangli , Deng Jianlin , Li Rong , Lei Pengcheng , Wang Yanjun , Liu Jiayu , Zhang Weifeng , Jiang Yingying , Wang Zhouyu , Yang Lingling
Published: August 2023

Ecto‐nucleotidase CD73 inhibits immune function by overproducing adenosine. A series of important studies have shown that CD73 is over‐expressed in many cancers, and CD73 inhibitors are promising drugs for cancer (immunotherapy). Here, we describe the structure optimization of a hit compound obtained through screening an in‐house chemical library, (3‐(4‐(3‐aminophenyl)‐1H‐1,2,3‐triazol‐1‐yl)phenyl‐(naphthalen‐1‐yl)methyl)phosphonic acid (1). A series of ((diphenylmethyl) phosphonic acid) derivatives were synthesized, and all target compounds were characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS). Then structure–activity relationship analysis using the in vitro enzymatic inhibition assay was performed, which led to the discovery of a number of compounds (11, 13, 14, 17, 19, 23, and 27) that exhibited greater inhibitory activity than the lead compound 1. Among them, the compounds 14 and 23, with p‐Cl and p‐ethyl substitution on the terminal phenyl ring respectively, showed the strongest inhibitory activity against CD73, with IC50 values of 2.35 and 2.55 μM respectively. And we believe that compounds 14 and 23 can serve as lead compounds for further research on specific CD73 inhibitors.
Optimal timing of re‐excision in synovial sarcoma patients: Immediate intervention versus waiting for local recurrence
Authors: Zhang Hongqiang , Sun Wei , Huang Wending , Yan Wangjun , Wang Hongbo , Qu Guolun , Wang Kangwei , Qu Xinglong , Wang Chunmeng , Chen Yong
Published: August 2023

Background

To investigate the difference in efficacy of re‐excision in synovial sarcoma patients with and without residual tumor following unplanned excision, and to compare the prognostic outcomes of immediate re‐excision versus waiting for local recurrence.

Method

This study included synovial sarcoma patients who underwent re‐excision at our center between 2009 and 2019, categorized into groups based on unplanned excision and local recurrence. Analyzed endpoints included overall survival (OS), local recurrence‐free survival (LRFS), and distant relapse‐free survival (DRFS). Prognostic factors associated with these three different survival outcomes were analyzed through the use of Kaplan–Meier curves and Cox regression approaches.

Result

In total, this study incorporated 109 synovial sarcoma patients, including 32 (29.4%) with no residual tumor tissue identified after re‐excision, 31 (28.4%) with residual tumor tissue after re‐excision, and 46 (42.2%) with local recurrence after initial excision. Patients were assessed over a median 52‐month follow‐up period. The respective 5‐year OS, 5‐year LRFS, and 5‐year DRFS rates were 82.4%, 76.7%, and 74.2% for the nonresidual group, 80.6%, 80.4%, and 77.3% for the residual tumor tissue group, and 63.5%, 50.7%, and 46.3% for the local recurrence group. There was no significant difference in OS of nonresidual group and residual group patients after re‐excision (p = 0.471). Concurrent or sequential treatment with chemotherapy and radiotherapy significantly reduced the risk of metastasis and mortality when compared with noncombined chemoradiotherapy, and was more effective in the local recurrence group (p < 0.05).

Conclusion

Prompt and adequate re‐excision is crucial for patients with synovial sarcoma who undergo initial inadequate tumor excision, and their prognosis is significantly better compared with patients who delay re‐excision until local recurrence.
Evolution of land cover in the special area of conservation of Monchique (Southern Portugal): Have the objectives of the Natura 2000 network been achieved (1995–2018)?
Authors: Raposo Mauro A. M. , Nunes Leonel J. R. , Pinto‐Gomes Carlos J.
Published: August 2023

The Natura 2000 Network, as the European Union's ecological network, aims to ensure the long‐term conservation of Europe's most threatened species and habitats, helping to stop the loss of biodiversity. Based on this assumption, the changes in land cover in the Special Area of Conservation (SAC) of Monchique between 1995 and 2018 are analysed and related to identify favourable and unfavourable policies concerning the habitats and respective species conservation. The most important land covers are compared with the habitats and species legally protected at the National and European level, as well as the Red List of Vascular Flora of Mainland Portugal. As main results can be highlighted the increase in the forest area occupied by species such as Eucalyptus globulus and Pinus pinaster, and a reduction in the areas of grazing and shrub species. Can also be noted an increase in the areas covered by invasive species, which may be associated with the abandonment of rural areas. We identified 21 taxa with high heritage interest in the Monchique SAC, occurring mainly in forest habitats, namely 91E0, 92A0, 9240, 9330 and 9340, which should be considered in the elaboration of future Territorial Management Plans. Thus, it can be concluded that the objectives initially stipulated by the Natura 2000 Network were not fully achieved within the Monchique SAC. Alternative management methods must be studied to allow conservation in a territory with a high land consolidation and low population density.
Barriers and facilitators for leading nursing homes through the COVID‐19 pandemic: A focus group study in Norway
Authors: Samdal Gro Beate , Alpers Lise‐Merete , Sekse Ragnhild Johanne Tveit , Drageset Sigrunn , Smith‐Strøm Hilde , Oksholm Trine , Ellingsen Sidsel
Published: August 2023

Background

During the COVID‐19 pandemic, nursing home leaders implemented infection control to protect residents and staff.

Aim

To understand the barriers and facilitators for leading nursing homes through the COVID‐19 pandemic.

Methods

We invited 34 nursing homes to participate, and 20 leaders (59%) attended focus group interviews. The COM‐B model and the theoretical domains framework were used in design and analysis of the study.

Results

The barriers for infection control were organisational unpreparedness, high volumes of information, lack of clinical skills, protective equipment, and testing capacity, the nursing home's architectural design, health authorities' low priority of nursing homes, staff's fear, and mental pressure on the leaders over time. The facilitators were having a customised corona plan, change of routines, certification of new skills, access to the municipal quality system, the ability for crisis leadership, loyalty to the nursing home, and support from the environment. The number of part‐time positions and the opportunity to outsource parts of the services were also important determinants for infection control.

Conclusions

The results identify several barriers and facilitators for nursing home leaders' behaviour for infection control. The results confirm the importance of supporting the leaders' resilience and crisis leadership while working in the pressurised environment of a pandemic.

Relevance to Clinical Practice

The study provides important insights into barriers and facilitators for leading nursing homes through the COVID‐19 pandemic, which could help to inform future strategies for infection control.

Patient or Public Contribution

No patient or public contribution.
Novel high‐strength polyester composite scaffolds for bone regeneration
Authors: Katebifar Sara , Arul Michael , Abdulmalik Sama , Yu Xiaojun , Alderete Joseph F. , Kumbar Sangamesh G.
Published: August 2023

Repair of critical‐sized bone defects, particularly in load‐bearing areas, is a major clinical problem that requires surgical intervention and implantation of biological or engineered grafts. For load‐bearing sites, it is essential to use engineered grafts that have both sufficient mechanical strength and appropriate pore properties to support bone repair and tissue regeneration. Unfortunately, the mechanical properties of such grafts are often compromised due to the creation of pores required to facilitate tissue ingrowth following implantation. To overcome the limitations associated with porous scaffolds and their reduced mechanical strength, we have developed a methodology for creating a solid structure that retains its bulk mechanical properties while also evolving into a porous structure in a biological environment through degradation and erosion. In this study, we utilized polyesters that have been approved by the FDA, including poly (lactic acid) (PLA), poly (glycolic acid) (PGA), their copolymer PLGA (PLGA, with a ratio of 85:15 and 50:50 of PLA:PGA), and poly (caprolactone) (PCL). These polymers and their ceramic composites with tricalcium phosphate (TCP) were compression molded into solid forms, which exhibited mechanical properties with compressive modulus as high as 2745 ± 364 MPa within the range of human trabecular bone and in the lower range of human cortical bone. The use of fast‐degrading PLGA (50:50) and PGA as porogens allowed the formation of pores within the solid structures due to their degradation, and the TCP acts as a buffering agent to neutralize their acidic degradation byproducts. These scaffolds facilitated the growth of new blood vessels and tissue ingrowth in a subcutaneous implantation model. In addition, in a rat critical‐sized mandibular bone defects these scaffolds supported bone growth with 70% of new bone volume fraction. Furthermore, the extent of bone regeneration was found to be higher for the scaffolds with bone morphogenic proteins (BMP2), indicating their suitability for bone repair and regeneration.
Effect of initial particle size and surface charge on the formation of the plasma protein corona on chitosan‐based nanoparticles
Authors: Taala Najmeh , Bagheri‐Khoulenjani Shadab
Published: August 2023

When a nanoparticle interacts with the biological environment, its surface is covered by a layer of biomolecules such as proteins and lipids called a protein corona. Given the importance and impact of the protein corona on the fate of nanoparticles in the body, it is important to study the interaction of nanoparticles with proteins. This study investigated the impact of the initial size and surface charge of nanoparticles on the changes in protein corona thickness on chitosan‐based nanoparticles after exposure to blood plasma. To be able to separate the chitosan‐based nanoparticles from the blood plasma, magnetic nanoparticles were coated with chitosan (with a positive charge) and carboxymethyl chitosan (CMC; with a negative charge) in two different size ranges of 200–250 and 300–350 nm. The coated nanoparticles' chemical composition, properties, and morphology were investigated using Fourier‐transform infrared spectroscopy, X‐ray diffraction, dynamic light scattering (DLS), zeta potential measurements, transmission electron microscopy, and field emission scanning electron microscope. The results confirmed the formation of nanoparticles based on chitosan and CMC. Subsequently, these nanoparticles were exposed to blood plasma to examine the protein corona that formed. The DLS and zeta potential measurements showed that the surface charge and particle size of the nanoparticles significantly influenced the formation of the protein corona. The results revealed that the smaller particle size and the positive surface charge of the nanoparticles resulted in the formation of a thicker corona. In addition, it showed that after exposure to the blood plasma proteins, the positive charge of the particles changed to a negative charge.
Physico‐chemical characterization and degradation analysis of mineral paper: Impact of accelerated weathering and aerobic biodegradation
Authors: Fathi Yosra , Abdulkhani Ali , Hamzeh Yahya , Ashori Alireza , Mortha Gerard , Chiani Elahe
Published: August 2023

Mineral paper, a synthetic paper‐like material primarily composed of ground calcium carbonate (CaCO3) and a small amount of high‐density polyethylene (HDPE), has emerged as an important alternative to traditional paper and board due to the increasing demand for pulp and paper and the shortage of trees and fibrous material in many regions worldwide. This study aimed to investigate the impact of accelerated weathering and aerobic biodegradation on three different types of mineral papers. The specimens underwent 1000 h of accelerated weathering using a Gardner weathering device and were also buried in soil at a depth of 5 cm for 3 months with regular watering conditions for biodegradability testing. Physico‐chemical characterizations such as optical (whiteness), surface (roughness, contact angle, and paper topography), and chemical properties of the samples were studied before and after the artificial weathering and biodegradation tests. The results revealed a visible color change (darkening) in mineral papers, with an increase in HDPE content leading to a darker color after weathering and biological degradation. However, there were no significant differences in the color change between weathering and soil‐burial tests. The biodegradability test resulted in a decrease in ash content due to the demineralization process. All samples' surface roughness was reduced after weathering and biodegradation tests. The FT‐IR and EDS analyses confirmed the presence of calcium, carbon, and oxygen elements in all three samples, indicating a large amount of calcium carbonate in the mineral papers. The scanning electron microscopy (SEM) images showed the creation of micro holes and cracks on the surface of the samples after weathering and biodegradation. Overall, the soil‐burial test showed more degradation than the weathering test.

Highlights

The influence of weathering and biodegradation of mineral papers were studied

After soil‐burial test, the ash content decreased due to the demineralization

After weathering, micro cracks were created on the surface of the samples

The degradation of the soil‐burial test was more than the weathering test

Mineral papers most likely contain carbonate calcium and HDPE
Registration of Arkot 1112, Arkot 1114, and Arkot 1115 cotton germplasm lines
Authors: Bourland Fred M. , Jones Don C.
Published: August 2023

Arkot 1112 (Reg. no. GP‐1139, PI 702559), Arkot 1114 (Reg. no. GP‐1140, PI 702560), and Arkot 1115 (Reg. no. GP‐1141, PI 702561) are conventional cotton (Gossypium hirsutum L.) germplasm lines released by the Arkansas Agricultural Experiment Station in November, 2022. The three lines share Arkot 0306 (PI 671966) as a common parent. The second parents for Arkot 1112, Arkot 1114, and Arkot 1115 were ‘UA222’ (US patent no. 8,859,862), Arkot 0309 (PI 669969), and Arkot 0316 (PI 669970), respectively. The three lines were compared with ‘UA48’ and UA222 in replicated field tests at four Arkansas sites over 5 years. Over these tests, each of the three lines produced about 11 and 25% higher lint yields than UA48 and UA222, respectively. Lint yields of Arkot 1115 exceeded those of Arkot 1112 and Arkot 1114. Over 10 locations of the 2019 Regional Breeders Testing Network test, lint yields of Arkot 1112, Arkot 1114, and Arkot 1115 were equal to each other and ranked third, fourth, and fifth, respectively, out of 22 genotypes, indicating that the lines have wide adaptation. Leaf pubescence, stem pubescence, and bract trichome density of the lines were higher than UA48 and similar to UA222. All three lines displayed high resistance to bacterial blight. The lines were more resistant to tarnished plant bug than UA48 but were more susceptible to tarnished plant bug than UA222. Fiber quality of Arkot 1115 approached that of UA48 (excellent fiber quality), whereas Arkot 1112 and Arkot 1114 was similar to UA222 (good fiber quality).
Popular strategies for constructing polymer gel thermoelectric materials
Authors: Sun Xiaohan , Lu Ang
Published: August 2023

Polymeric thermoelectric materials utilizing the Soret effect have the advantages of high Seebeck coefficient, non‐toxicity, light weight, and excellent mechanical properties that make them shine in the field of thermoelectrics. However, ionic thermoelectric systems based on polymer gels are still in their infancy and research is relatively limited, and there is an increasing interest in how to prepare high performance polymer thermoelectric materials. In this paper, we review some of the existing polymer TE materials based on the Soret effect and discuss the different approaches to achieve high Seebeck coefficient and enhanced thermoelectric properties from the perspective of material design strategies. Moreover, we highlight the popular strategies of the construction of thermoelectric materials and provide a brief outlook on the development of the polymer thermoelectric field for its future research.
Locally Reconfigurable Exchange Bias for Tunable Spintronics by Pulsed Current Injection
Authors: Wang Wenli , Chen Yicheng , Wang Bo , Wang Lisong , Han Yongliang , Su Wei , Hu Zhongqiang , Wang Zhiguang , Liu Ming
Published: August 2023

Unidirectional magnetic anisotropy induced by exchange bias (EB) between ferromagnetic and antiferromagnetic layers is of paramount importance in various spintronic devices. Traditional setting and optimization of EB involve cooling through the Néel temperature of the antiferromagnets under biasing field in vacuum furnace which takes hours of time and cannot realize localized control of EB. Herein, an alternative process to configure EB by injection of microsecond current impulse for locally heating of the heterostructure is reported. 180‐degree exchange bias switching has been realized in both anisotropic magnetoresistance and giant magnetoresistance units, resulting in tunable magnetic field sensing functionalities. This mechanism for pinpoint control of EB provides more freedom for the design and optimization of various sensing and logic spintronics.
Diamond MEMS: From Classical to Quantum
Authors: Sun Huanying , Zhang Zilong , Liu Yulong , Chen Guo , Li Tiefu , Liao Meiyong
Published: August 2023

Diamond has numerous outstanding properties in mechanics, physics, chemistry, electronics, thermodynamics, and spintronics for either classic micro/nanoelectromechanical systems (MEMS/NEMS) devices or hybrid quantum MEMS/NEMS systems. The extremely high mechanical strength and the ultra‐wide bandgap energy enable the development of mechanically and thermally robust MEMS/NEMS sensors and switches, while the long coherence time of spin defects center enables the reading out through optical methods, precise quantum sensing, and quantum information processing. In this paper, the development of diamond‐based MEMS/NEMS from the viewpoints of classic devices to quantum systems are reviewed. The fabrication process and the classic applications of diamond MEMS/NEMS devices are first described, including those from micro‐crystalline, nano‐crystalline/ultranano‐crystalline, and single‐crystalline diamonds. Then, the physical properties of nitrogen‐vacancy defect center, as well as the application referred to the hybrid system composed of MEMS structures and nitrogen‐vacancy centers embedded, strain–spin interaction, and diamond‐based optomechanics are introduced. Finally, a conclusion and outlook are presented. It is expected that diamond MEMS/NEMS is not only an ideal platform for high‐performance and high‐reliability advanced classic MEMS devices but also for quantum sensing, information, and exploring the fundamentals of quantum mechanics.
Stabilizing model predictive control synthesis using integral quadratic constraints and full‐block multipliers
Authors: Morato Marcelo M. , Holicki Tobias , Scherer Carsten W.
Published: August 2023

In this paper, we discuss how to synthesize stabilizing model predictive control (MPC) algorithms based on convexly parameterized integral quadratic constraints (IQCs), with the aid of general multipliers. Specifically, we consider Lur'e systems subject to sector‐bounded and slope‐restricted nonlinearities. As the main novelty, we introduce point‐wise IQCs with storage in order to accordingly generate the MPC terminal ingredients, thus enabling closed‐loop stability, strict dissipativity with regard to the nonlinear feedback, and recursive feasibility of the optimization. Specifically, we consider formulations involving both static and dynamic multipliers, and provide corresponding algorithms for the synthesis procedures. The major benefit of the proposed approach resides in the flexibility of the IQC framework, which is capable to deal with many classes of uncertainties and nonlinearities. Moreover, for the considered class of nonlinearities, our method yields larger regions of attraction of the synthesized predictive controllers (with reduced conservatism) if compared to the standard approach to deal with sector constraints from the literature.