bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and structure–activity relationships of tanshinones as selective 11β-hydroxysteroid dehydrogenase 1 inhibitors
Authors: Deng Xu , Huang Su-Ling , Ren Jian , Pan Zheng-Hong , Shen Yu , Zhou Hao-Feng , Zuo Zhi-Li , Leng Ying , Zhao Qin-Shi 
Published: September 2022

Abstract11β-Hydroxysteroid dehydrogenase 1 (11β-HSD1) represents a promising drug target for metabolic syndrome, including obesity and type 2 diabetes. Our initial screen of a collection of natural products from Danshen led to the identification of tanshinones as the potent and selective 11β-HSD1 inhibitors. To improve the druggability and explore the structure–activity relationships (SARs), more than 40 derivatives have been designed and synthesized using tanshinone IIA and cryptotanshinone as the starting materials. More than 10 derivatives exhibited potent in vitro 11β-HSD1 inhibitory activity and good selectivity over 11β-HSD2 across human and mouse species. Based on the biological results, SARs were further discussed, which was also partially rationalized by a molecular docking model of 1 bound to the 11β-HSD1. Remarkably, compounds 1, 17 and 30 significantly inhibited 11β-HSD1 in 3T3-L1 adipocyte and in livers of ob/ob mice, which merits further investigations as anti-diabetic agents. This study not only provides a series of novel selective 11β-HSD1 inhibitors with promising therapeutic potentials in metabolic syndromes, but also expands the boundaries of the chemical and biological spaces of tanshinones.
Graphic Abstract
Examining ecosystem services and disservices through deliberative socio-cultural valuation
Authors: Baltazar D. S. , Labadz J. , Smith R. , Telford A. , Di Bonito M. 
Published: September 2022

AbstractThe deliberative socio-cultural valuation of ecosystem services (ES) and disservices (EDS) is an understudied area of ES and EDS research. Participatory methods have been applied to ES and EDS valuation, but little is known on how these approaches could reveal and form shared values and impact decision-making. This paper presents the deliberative socio-cultural valuation of the Jose Rizal Plaza in Calamba City, The Philippines. The study aimed to assess how stakeholders value the ES and EDS of the park and examine how these values change in different situations. Online focus groups were carried out, and in each, the participants were asked to distribute importance and concern points to the various park ES and EDS, respectively. The valuation exercise was performed six times, changing the source and constituency of the valuation, and introducing discussions. Results confirm significant differences in the values assigned to several ES and EDS across the valuation exercises. Varying the sources and constituencies proved useful in revealing the participants’ shared assigned values. The participants share a high appreciation for enjoyment and spending free time, sports and physical fitness, relaxation and mental recreation, social relationships, and local identity and cultural heritage. For EDS, they share a significant concern only for the risk of anti-social behaviour. This type of valuation could be further explored using other parks and cities to test if it will have consistent results. For the Jose Rizal Plaza, spaces for sports should be maintained and security should be improved.
Building energy flexibility with battery energy storage system: a comprehensive review
Authors: Xu Xinhua , Fu Yuting , Luo Yongqiang 
Published: September 2022

AbstractBuilding energy flexibility (BEF) is getting increasing attention as a key factor for building energy saving target besides building energy intensity and energy efficiency. BEF is very rich in content but rare in solid progress. The battery energy storage system (BESS) is making substantial contributions in BEF. This review study presents a comprehensive analysis on the BEF with BESS, in terms of the current study statues, connection to building energy management, integration with renewable energy sources and electric vehicles. In addition, electric vehicle (EV) is found to be flexible by itself for BEF. This study delivers some new insights and findings that the synchronized aging of building and battery and complex optimization with multiple indexes, is still challenging. Additionally, the opportunities behind the challenges are also highlighted that the higher level of BEF can be achieved by tackling the higher level of system complexity. Further, the suggestions about distributed energy control for distributed energy system, as well as coupling building energy pattern with users’ behavior pattern, are also proposed. The review study may further facilitate the BEF with BESS and push forward the synergistic improvement of building energy efficiency, intensity, and flexibility.
Management of recurrent colostomy prolapse by Laparoscopic Enteropexy for Prolapsing Stoma (LEPS) technique; case report
Authors: Saleem Athary , Alawadhi Abrar , Almarri Mohammad , Al Safi Sarah , Alkhamis Ahmed 
Published: September 2022

Abstract

Background
Stoma prolapse is a well-known complaint following colostomy or ileostomy that can be reduced by either conservative and/or surgical approaches.

Presentation
A 46-year-old male patient who developed colostomy prolapse as an early postoperative complication. The first episode occurred 4 days following the creation of a temporary loop colostomy to allow the initiation of neoadjuvant chemoradiotherapy for an obstructive locally advanced rectal cancer. The prolapse was associated with incarceration which was not amenable for bedside reduction. This was managed by loop colostomy revision into an end-loop colostomy. Two weeks later, a repeated episode of incarcerated colostomy prolapse occurred. This episode was managed, using Laparoscopic Enteropexy for Prolapsing Stoma (LEPS) technique. The postoperative period, two days, was uneventful and no evidence of recurrence occurred to date.

Discussion
temporary colostomy prolapse with acute incarceration is a highly challenging event that requires innovative intervention. Usually, it is considered a late complication in contrast to our case where the patient presented with prolapsed colostomy as an early complication. The surgical options to manage the colostomy prolapse can be either local and/or intra-abdominal techniques.

Conclusion
LEPS is a valid approach to managing prolapsed stoma that has been formed as a temporary bridge to definitive surgery. It is a simple low-risk procedure that allows fast recovery so patients can proceed with further treatment plans.

Highlights
Reflections on implementation of a failure-point–focused outpatient parenteral antimicrobial therapy management program
Authors: Hemenway Alice N. , Stewart Rebecca L. 
Published: September 2022

Abstract
Management of outpatient parenteral antimicrobial therapy (OPAT) is complex, and incorporation of a pharmacist can improve outcomes. The creation of new clinical programs is often limited by staffing resources. We describe our collaborative program that utilized a failure-point–focused design process to optimize OPAT activities and management.
When Dragon Meets Elephant in Africa: The Rivalry on Distinctive Competitiveness
Authors: Xie Zhenzhen , Chen Xuanjin , Wang Hao 
Published: September 2022

ABSTRACTThe increasing FDI in Africa from China and India in recent years has drawn the attention of scholars, policy makers, and the media. Africa is an arena where the two emerging giants compete on different bases. Indian firms have the advantage of institutional proximity and large diaspora communities in Africa, while Chinese firms rely on government-to-government relationship-building. The rivalry between India's soft power and Chinese hard power in Africa will continue for the foreseeable future.
An additional medium renewal of D4 embryo culture improves the concordance of noninvasive chromosome screening with trophectoderm biopsy
Authors: Li Hong-Xing , Pang Yan , Zhang Xue-Hong , Cao Di , Ma Xiao-Ling 
Published: September 2022

SummaryOur research question was to evaluate the chromosome concordance of trophectoderm (TE) biopsy with noninvasive chromosome screening (NICS) using embryo culture medium renewed twice on Day 3 (D3) and Day 4 (D4). In this study, we evaluated 64 cycles with 223 biopsied blastocysts. These were categorized into two groups based on replacing embryo culture medium on D3 (control group) or on D3 and D4 (experimental group). The fundamental characteristics and main outcomes were compared. The concordance rates of NICS results with TE biopsy were determined according to next generation sequencing results. In total, 103 experimental and 120 control embryo cultures were collected, and the euploid status was analyzed using NICS technology. The overall concordance rates with TE biopsy of the experimental and control groups were 0.86 and 0.75, respectively. Statistically significant difference was found between the two groups. An additional medium renewal of the D4 embryo culture can improve the concordance of NICS with TE biopsy.
Morphological characterization of the digestive tube of hawksbill sea turtle (Eretmochelys imbricata) hatchlings
Authors: Oliveira Radan Elvis Matias de , Attademo Fernanda Loffler Niemeyer , Sousa Ana Caroline Freitas Caetano de , Gurgel João Vitor de Oliveira , Magalhães Marcela dos Santos , Moura Carlos Eduardo Bezerra de , Fragoso Ana Bernadete Lima , Silva Flávio José de Lima , Oliveira Moacir Franco de 
Published: September 2022

Abstract
Morphological studies concerning the digestive system can further information on animal diets, thus aiding in the understanding of feeding behavior. Given the scarcity of information on sea turtle digestive system morphology, the aim of the present study was to describe the digestive tube (DT) morphology of Eretmochelys imbricata hatchlings to further understand the diet of these individuals in the wild. DT samples from 10 stillborn turtles (undefined sex) were analyzed at the macro and microscopic levels. The esophagus, stomach, small intestine (SI), and large intestine (LI) are described. Histologically, the DT is formed by four tunics, the mucosa, submucosa, muscular, and adventitia or serosa. The esophagus is lined by keratinized stratified squamous epithelium, while the remainder of the DT is lined by a simple columnar epithelium. The esophagus mucosa is marked by conical, pointed papillae. The stomach comprises three regions, the cardiac, fundic, and pyloric and is covered by neutral mucous granular cells. The intestinal mucosa presents absorptive cells with microvilli, neutral and acidic goblet cells, and mucosa-associated lymphoid tissue. The SI is significantly longer than the LI (p value = 0.006841). These morphological findings are strong indications of adaptations to a carnivorous diet in this hawksbill turtle age group.
Monitoring Seismic Velocity Changes Across the San Jacinto Fault Using Train‐Generated Seismic Tremors
Authors: Sheng Y. , Mordret A. , Sager K. , Brenguier F. , Boué P. , Rousset B. , Vernon F. , Higueret Q. , Ben‐Zion Y. 
Published: September 2022

AbstractMicroseismic noise has been used for seismic velocity monitoring. However, such signals are dominated by low‐frequency surface waves that are not ideal for detecting changes associated with small tectonic processes. Here we show that it is possible to extract stable, high‐frequency body waves using seismic tremors generated by freight trains. Such body waves allow us to focus on small velocity perturbations in the crust with high spatial resolution. We report on 10 years of seismic velocity temporal changes at the San Jacinto Fault. We observe and map a two‐month‐long episode of velocity changes with complex spatial distribution and interpret the velocity perturbation as produced by a previously undocumented slow‐slip event. We verify the hypothesis through numerical simulations and locate this event along a fault segment believed to be locked. Such a slow‐slip event stresses its surroundings and may trigger a major earthquake on a fault section approaching failure.
The Color of Earth’s Lakes
Authors: Yang Xiao , O’Reilly Catherine M. , Gardner John R. , Ross Matthew R. V. , Topp Simon N. , Wang Jida , Pavelsky Tamlin M. 
Published: September 2022

AbstractAlthough water color is a fundamental property of freshwater ecosystems, the global distribution of lake color remains unknown. Here, we used 5.14 million color records derived from satellite images during 2013–2020 to determine the modal water color of 85,360 representative lakes worldwide. We find that globally, lake modal colors span the visible spectrum with a bimodal distribution of blue versus non‐blue (green‐brown), with 31% of lakes being blue and 69% being non‐blue. Both climate and lake morphology influence lake modal color. Blue lakes are associated with cooler summer air temperature, winter ice cover, and higher precipitation. Under a 3°C increase in summer air temperature, 14% of blue lakes could shift to a non‐blue regime, representing a substantial change to their underlying ecology. As lake ecosystems continue to face a range of stressors, this study provides a critical baseline for understanding lake responses to global environmental change.
FAK promotes stromal PD-L2 expression associated with poor survival in pancreatic cancer
Authors: Davidson Catherine , Taggart David , Sims Andrew H. , Lonergan David W. , Canel Marta , Serrels Alan 
Published: September 2022

Abstract
Background
Pancreatic Cancer is one of the most lethal cancers, with less than 8% of patients surviving 5 years following diagnosis. The last 40 years have seen only small incremental improvements in treatment options, highlighting the continued need to better define the cellular and molecular pathways contributing to therapy response and patient prognosis.

Methods
We combined CRISPR, shRNA and flow cytometry with mechanistic experiments using a KrasG12Dp53R172H mouse model of pancreatic cancer and analysis of publicly available human PDAC transcriptomic datasets.

Results
Here, we identify that expression of the immune checkpoint, Programmed Death Ligand 2 (PD-L2), is associated with poor prognosis, tumour grade, clinical stage and molecular subtype in patients with Pancreatic Ductal Adenocarcinoma (PDAC). We further show that PD-L2 is predominantly expressed in the stroma and, using an orthotopic murine model of PDAC, identify cancer cell-intrinsic Focal Adhesion Kinase (FAK) signalling as a regulator of PD-L2 stromal expression. Mechanistically, we find that FAK regulates interleukin-6, which can act in concert with interleukin-4 secreted by CD4 T-cells to drive elevated expression of PD-L2 on tumour-associated macrophages, dendritic cells and endothelial cells.

Conclusions
These findings identify further complex heterocellular signalling networks contributing to FAK-mediated immune suppression in pancreatic cancer.
Inhibition of cannabinoid receptor type 1 sensitizes triple-negative breast cancer cells to ferroptosis via regulating fatty acid metabolism
Authors: Li Pengyun , Lin Qiaohong , Sun Shiyang , Yang Ning , Xia Yu , Cao Shengjie , Zhang Wenjuan , Li Qian , Guo Haoxin , Zhu Maoxiang , Wang Yilong , Zheng Zhibing , Li Song 
Published: September 2022

AbstractTriple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer that displays highly aggressive with poor prognosis. Owing to the limited targets and drugs for TNBC clinical therapy, it is necessary to investigate the factors regulating cancer progression and develop novel therapies for cancer treatment. Ferroptosis, a nonapoptotic form of programmed cell death characterized by accumulation of iron-dependent peroxidation of phospholipids, is regulated by cellular metabolism, redox homeostasis, and various cancer-related signaling pathways. Recently, considerable progress has been made in demonstrating the critical role of lipid metabolism in regulating ferroptosis, indicating potential combinational therapeutic strategies for cancer treatment. In this study, by drug combination screen of lipid metabolism compounds with ferroptosis inducers in decreasing TNBC cell viability, we found potent synergy of the CB1 antagonist rimonabant with erastin/(1 S, 3 R)-RSL3 (RSL3) in inhibiting TNBC cell growth both in vitro and in vivo via promoting the levels of lipid peroxides, malondialdehyde (MDA), 4-hydroxynonenal (4-HNE) and cytosolic reactive oxygen species (ROS) production, enhancing intracellular glutathione (GSH) depletion and inducing G1 cell cycle arrest. We identified that inhibition of CB1 promoted the effect of erastin/RSL3 on inducing ferroptosis and enhanced their inhibitory effect on tumor growth. Using RNA-Seq, fatty acid analyses and functional assays, we found that CB1 regulated stearoyl-CoA desaturase 1 (SCD1)- and fatty acyl desaturase 2 (FADS2)-dependent fatty acid metabolism via phosphatidylinositol 3 kinase (PI3K)-AKT and mitogen-activated protein kinase (MAPK) signaling pathways to modulate ferroptosis sensitivity in TNBC cells. These data demonstrate that dual targeting of CB1 and ferroptosis could be a promising therapeutic strategy for TNBC.
Repeating fast radio burst 20201124A originates from a magnetar/Be star binary
Authors: Wang F. Y. , Zhang G. Q. , Dai Z. G. , Cheng K. S. 
Published: September 2022

AbstractFast radio bursts (FRBs) are cosmic sources emitting millisecond-duration radio bursts. Although several hundreds FRBs have been discovered, their physical nature and central engine remain unclear. The variations of Faraday rotation measure and dispersion measure, due to local environment, are crucial clues to understanding their physical nature. The recent observations on the rotation measure of FRB 20201124A show a significant variation on a day time scale. Intriguingly, the oscillation of rotation measure supports that the local contribution can change sign, which indicates the magnetic field reversal along the line of sight. Here we present a physical model that explains observed characteristics of FRB 20201124A and proposes that repeating signal comes from a binary system containing a magnetar and a Be star with a decretion disk. When the magnetar approaches the periastron, the propagation of radio waves through the disk of the Be star naturally leads to the observed varying rotation measure, depolarization, large scattering timescale, and Faraday conversion. This study will prompt to search for FRB signals from Be/X-ray binaries.
The SARS-CoV-2 Omicron BA.1 spike G446S mutation potentiates antiviral T-cell recognition
Authors: Motozono Chihiro , Toyoda Mako , Tan Toong Seng , Hamana Hiroshi , Goto Yoshihiko , Aritsu Yoshiki , Miyashita Yusuke , Oshiumi Hiroyuki , Nakamura Kimitoshi , Okada Seiji , Udaka Keiko , Kitamatsu Mizuki , Kishi Hiroyuki , Ueno Takamasa 
Published: September 2022

AbstractAlthough the Omicron variant of the SARS-CoV-2 virus shows resistance to neutralizing antibody, it retains susceptibility to the cellular immune response. Here we characterize vaccine-induced T cells specific for various SARS-CoV-2 variants and identified HLA-A*24:02-restricted CD8+ T cells that strongly suppress Omicron BA.1 replication in vitro. Mutagenesis analyses revealed that a G446S mutation, located just outside the N-terminus of the cognate epitope, augmented TCR recognition of this variant. In contrast, no enhanced suppression of replication is observed against cells infected with the prototype, Omicron BA.2, and Delta variants that express G446. The enhancing effect of the G446S mutation is lost when target cells are treated with inhibitors of tripeptidyl peptidase II, a protein that mediates antigen processing. These ex vivo analysis and in vitro results demonstrate that the G446S mutation in the Omicron BA.1 variant affects antigen processing/presentation and potentiates antiviral activity by vaccine-induced T cells, leading to enhanced T cell recognition towards emerging variants.
A de novo matrix for macroscopic living materials from bacteria
Authors: Molinari Sara , Tesoriero Robert F. , Li Dong , Sridhar Swetha , Cai Rong , Soman Jayashree , Ryan Kathleen R. , Ashby Paul D. , Ajo-Franklin Caroline M. 
Published: September 2022

AbstractEngineered living materials (ELMs) embed living cells in a biopolymer matrix to create materials with tailored functions. While bottom-up assembly of macroscopic ELMs with a de novo matrix would offer the greatest control over material properties, we lack the ability to genetically encode a protein matrix that leads to collective self-organization. Here we report growth of ELMs from Caulobacter crescentus cells that display and secrete a self-interacting protein. This protein formed a de novo matrix and assembled cells into centimeter-scale ELMs. Discovery of design and assembly principles allowed us to tune the composition, mechanical properties, and catalytic function of these ELMs. This work provides genetic tools, design and assembly rules, and a platform for growing ELMs with control over both matrix and cellular structure and function.
Improved pea reference genome and pan-genome highlight genomic features and evolutionary characteristics
Authors: Yang Tao , Liu Rong , Luo Yingfeng , Hu Songnian , Wang Dong , Wang Chenyu , Pandey Manish K. , Ge Song , Xu Quanle , Li Nana , Li Guan , Huang Yuning , Saxena Rachit K. , Ji Yishan , Li Mengwei , Yan Xin , He Yuhua , Liu Yujiao , Wang Xuejun , Xiang Chao , Varshney Rajeev K. , Ding Hanfeng , Gao Shenghan , Zong Xuxiao 
Published: September 2022

AbstractComplete and accurate reference genomes and annotations provide fundamental resources for functional genomics and crop breeding. Here we report a de novo assembly and annotation of a pea cultivar ZW6 with contig N50 of 8.98 Mb, which features a 243-fold increase in contig length and evident improvements in the continuity and quality of sequence in complex repeat regions compared with the existing one. Genome diversity of 118 cultivated and wild pea demonstrated thatPisum abyssinicumis a separate species different fromP. fulvumandP. sativumwithinPisum. Quantitative trait locus analyses uncovered two known Mendel’s genes related to stem length (Le/le) and seed shape (R/r) as well as some candidate genes for pod form studied by Mendel. A pan-genome of 116 pea accessions was constructed, and pan-genes preferred inP. abyssinicumandP. fulvumshowed distinct functional enrichment, indicating the potential value of them as pea breeding resources in the future.
Crystal field splitting and spontaneous polarization in InP crystal phase quantum dots
Authors: Patera Martyna , Zieliński Michał 
Published: September 2022

AbstractCrystal phase quantum dots are formed by vertically stacking zinc-blende and wurtzite phases during nanowire growth. In this work, we show, using an atomistic many-body approach, that crystal field splitting in the wurtzite phase, as well as spontaneous polarization originating from the phase interfaces, will strongly affect the properties of lowest hole states in InP crystal phase quantum dots, and in turn the excitonic optical spectra. We also show that the artifact-free modeling of crystal phase quantum dots should incorporate any additional potentials on equal footing with the electron-hole interaction. In this paper, we discuss a reliable theoretical framework that can be applied to investigate the electronic and optical properties of InP-based crystal phase quantum dots. The importance of accurate excitonic calculations for such systems is highlighted in view of their potential applications in nanowire photonics, yet further research is necessary for bringing theory and experiment in agreement.