bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep Downregulation of PD‐L1 by Caged Peptide‐Conjugated AIEgen/miR‐140 Nanoparticles for Enhanced Immunotherapy
Authors: Dai Jun , Hu Jing‐Jing , Dong Xiaoqi , Chen Biao , Dong Xiyuan , Liu Rui , Xia Fan , Lou Xiaoding
Published: February 2022

Downregulating programmed cell death ligand 1(PD‐L1) protein levels in tumor cells is an effective way to achieve immune system activation for oncology treatment, but current strategies are inadequate. Here, we design a caged peptide‐AIEgen probe (GCP) to self‐assemble with miR‐140 forming GCP/miR‐140 nanoparticles. After entering tumor cells, GCP/miR‐140 disassembles in the presence of Cathepsin B (CB) and releases caged GO203 peptide, miR‐140 and PyTPA. Peptide decages in the highly reductive intracellular environment and binds to mucin 1 (MUC1), thereby downregulating the expression of PD‐L1. Meanwhile, miR‐140 reduces PD‐L1 expression by targeting downregulation of PD‐L1 mRNA. Under the action of PyTPA‐mediated photodynamic therapy (PDT), tumor‐associated antigens are released, triggering immune cell attack on tumor cells. This multiple mechanism‐based strategy of deeply downregulating PD‐L1 in tumor cells activates the immune system and thus achieves effective immunotherapy.
Reconfiguration and Reorganization of Bottlebrush Polymer Surfactants
Authors: Seong Hong‐Gyu , Chen Zhan , Emrick Todd , Russell Thomas P.
Published: February 2022

Bottlebrush random copolymers (BRCPs), having randomly distributed hydrophilic and hydrophobic side chains, are shown to reconfigure into hydrophilic‐rich and hydrophobic‐rich conformations at liquid–liquid interfaces to reduce interfacial energy. Both the degree of polymerization (NBB) and extent of grafting in these BRCPs were found to impact surface coverage and assembly kinetics. The time‐dependence of the interfacial tension is described as the sum of two exponential relaxation functions characterizing BRCP diffusion, interfacial adsorption, and reorganization. Interfacial tension (γ) and fluorescence recovery after photobleaching (FRAP) results showed that higher molecular weight BRCPs require longer time to adsorb to the water–oil interface, but less time for interfacial reorganization. Overall, this work describes fundamental principles of BRCP assembly at liquid–liquid interfaces, with implications pertaining to polymer design with enhanced understanding of emulsification, adhesion, and related properties in fluids and at interfaces.
Effects of composite reinforcing filler, vulcanizing temperature, and pressure on mechanical properties of gasket material for proton exchange membrane fuel cells
Authors: Hou Qiong , Yin Li , Xu Lifeng , Tan Jinzhu
Published: February 2022

Gasket is one of the key components in proton exchange membrane fuel cells (PEMFCs), and the performance of the gasket can directly affect the durability and electrochemical performance of the PEMFCs. In this paper, the silicone rubber material, which is being considered as gasket material for PEMFC, was fabricated with different composite reinforcing fillers at different vulcanizing temperatures under different vulcanizing pressures. Effects of the composite reinforcing fillers (i.e., gas‐phase SiO2and nano‐CaCO3), vulcanizing temperatures, and pressures on mechanical properties of the silicone rubber material were investigated. The tensile, hardness measurement, compression set, and compression stress relaxation experimental results show that the mass ratios of the gas‐phase SiO2to nano‐CaCO3, curing temperatures, and pressures had a significant impact on the mechanical properties of PEMFC gasket materials. It is found that the silicone rubber material cured at a vulcanization temperature of 160 °C and a vulcanization pressure of 10 MPa had good compression mechanical properties compared to the materials cured at the other curing temperatures and curing pressures. Orthogonal test results show that, when mass ratio of the gas‐phase SiO2to nano‐CaCO3was 25:20, the silicone rubber material cured at the curing temperature of 160 °C and under the curing pressure of 10 MPa had good compressive stress relaxation performance in this work.
Synthesis of oxazolo‐annulated 3‐benzazepines designed by merging two negative allosteric NMDA receptor modulators
Authors: Markus Alexander , Schepmann Dirk , Wünsch Bernhard
Published: February 2022

To improve the metabolic stability and receptor selectivity of ifenprodil (1), the benzoxazolone moiety of besonprodil (2) and the 3‐benzazepone moiety of WMS‐1410 (3) were merged to obtain oxazolobenzazepines of type 4. The 5‐(hydroxyethyl)benzoxazolone 7 representing the first key intermediate was prepared in four steps starting with the 4‐(2‐hydroxyethyl)phenol (8). Mitsunobu reaction of primary alcohol 7 with N‐sulfonylated glycine esters established the necessary side chain. The intramolecular Friedel–Crafts acylation of acid 12a containing the N‐tosyl protective group led upon decarbonylation exclusively to the tricyclic tetrahydroisoquinoline 14. Protection of the amino moiety by the stronger electron‐withdrawing triflyl group resulted in the desired 3‐benzazepine 15 without the formation of analogous isoquinoline. The triflyl protective group was cleaved off by K2CO3‐induced elimination of trifluoromethanesulfinate. In a one‐pot three‐step procedure, various oxazolobenzazepinediones 15 were obtained, which were reduced to afford the desired secondary alcohols 18.
Überwachung der Brücke am Altstädter Bahnhof
Authors: Kaplan Felix , Steinbock Oliver , Saloga Katrin , Ebell Gino , Schmidt Sebastian
Published: February 2022

Die B 1‐Brücke am Altstädter Bahnhof war der wichtigste Verkehrsknotenpunkt in Brandenburg an der Havel. Im Dezember 2019 wurden die überführte Bundesstraße und die Straßenbahnlinie für den Verkehr gesperrt. Grund für die Sperrung war eine einsetzende Rissbildung in den Längsträgerstegen in Verbindung mit Hohlstellen, die letztlich auf gerissene Spanndrähte zurückgeführt werden. Um eine Sperrung der hoch frequentierten unterführten Verkehrswege zu verhindern, wurde ein umfangreiches Überwachungskonzept erforderlich. Wesentlicher Bestandteil dieses Konzepts war ein auf der Schallemissionsanalyse basierendes Monitoringsystem, mit dessen Hilfe Spanndrahtbrüche aufgezeichnet und lokalisiert werden konnten. Auf Grundlage der so gewonnenen Ergebnisse konnten Schwerpunkte für die Bauwerksprüfung abgeleitet werden. In diesem Bericht werden die gewonnenen Erkenntnisse zum messtechnisch erfassten Schadensfortschritt und den damit verbundenen visuell festgestellten Schäden beschrieben. Dabei werden die Besonderheit des verbauten konzentrierten Spannglieds (Spannblockverfahren nach TGL 173‐33) und des Spannstahls in Bezug auf die Schadensbilder dargestellt. Die gewonnenen Erkenntnisse sollten bei der Beurteilung anderer Bauwerke mit vergleichbarer Bauart berücksichtigt werden.
Hierarchical Fibrous Honeycomb Ceramics with High Load Capability and Low Light‐Off Temperature for the Next‐Generation Auto Emissions Standards
Authors: Du Pengpeng , Min Xin , Li Hongwei , Liu Zhenglian , Wu Xiaowen , Liu Yangai , Huang Zhaohui , Fang Minghao
Published: February 2022

Novel and stringent automotive exhaust gas emissions standards are urgently needed to counter the problems posed by the worsening global climate and environment. However, the traditional cordierite‐based honeycomb ceramics substrates with ultimate pore density have seriously restricted the establishment of new emission standards. Herein, we introduce a novel robust substrate with tailored volume‐specific surface area and low heat capacity. This substrate employs the synergy of high‐strength ceramic fibers and ultrathin TiO2 nanosheets. The micro‐sized fibers provide support to ensure structural strength during the catalytic reaction, while the nanosheets play the dual role of connecting the fibers and providing a high surface area for catalyst immobilization. The new three‐dimensional (3D) microarchitecture exhibits a high volume‐specific surface area of 3.59×104 cm2/cm3, a compressive strength of 2.01 MPa, and remarkable stability after high‐speed air erosion at 800 °C. The honeycomb‐like structure exhibit low resistance to gas flow. Furthermore, after loading with Pt and Pd nanoparticles, the composite 3D microarchitecture delivered an excellent catalytic performance and prominent structural stability, with a super low light‐off temperature of 150 °C. The outstanding mechanical and thermal stability and the high surface area and light‐off temperature of the new substrate indicate its potential for use as a highly efficient catalytic carrier to meet the next‐generation auto emissions standards.
Bis‐Phosphaketenes LM(PCO)2 (M=Ga, In): A New Class of Reactive Group 13 Metal‐Phosphorus Compounds
Authors: Sharma Mahendra K. , Dhawan Pratima , Helling Christoph , Wölper Christoph , Schulz Stephan
Published: February 2022

Phosphaketenes are versatile reagents in organophosphorus chemistry. We herein report on the synthesis of novel bis‐phosphaketenes, LM(PCO)2 (M=Ga 2 a, In 2 b; L=HC[C(Me)N(Ar)]2; Ar=2,6‐i‐Pr2C6H3) by salt metathesis reactions and their reactions with LGa to metallaphosphenes LGa(OCP)PML (M=Ga 3 a, In 3 b). 3 b represents the first compound with significant In−P π‐bonding contribution as was confirmed by DFT calculations. Compounds 3 a and 3 b selectively activate the N−H and O−H bonds of aniline and phenol at the Ga−P bond and both reactions proceed with a rearrangement of the phosphaethynolate group from Ga−OCP to M−PCO bonding. Compounds 2–5 are fully characterized by heteronuclear (1H, 13C{1H}, 31P{1H}) NMR and IR spectroscopy, elemental analysis, and single crystal X‐ray diffraction (sc‐XRD).
Evaluation of Shell Powder Remediation Effect in Cadmium‐Contaminated Soil: A Score Approach Based on Entropy Indexes
Authors: Zhao Haodong , Du Liyu , An Tingting , Wu Yan , Zhao Yuhao
Published: February 2022

A highly effective, economical, and replicable way is imperative to remediate Cadmium (Cd)‐polluted soil. Shell powder is sometimes used to remediate soil contaminated with potentially toxic metals. However, information is limited regarding shell powder assessment. Shell powder is thermally modified at 400, 600, and 800 °C and is added to Cd‐polluted soil for 50 days. The repair effects of shell powder on Cd‐polluted soil are investigated. Compared with the control, the addition of shell powder passivator reduces the content of exchangeable Cd in the soil and converts the exchangeable fraction into other unavailable fractions, especially carbonate‐bound Cd. On average, the value of soil pH increases by one to two units after the application of the powder. Shell powder improves the physical and chemical properties of the soil. Redundancy analysis, entropy method, literature analysis, and theoretical analysis are used for evaluation. Finally, the repair effect score for each treatment group is obtained, and it proves to be a more intuitive method of evaluation. Overall, the results of this study indicate that shell powder is a suitable passivator for the remediation of Cd‐polluted soil. Using a score to express the repair effect is an appropriate evaluation method.
Contribution of Knoevenagel Condensation Products toward the Development of Anticancer Agents: An Updated Review
Authors: Tokala Ramya , Bora Darshana , Shankaraiah Nagula
Published: February 2022

Knoevenagel condensation is an entrenched, prevailing, prominent arsenal following greener principles in the generation of α, β‐unsaturated ketones/carboxylic acids by involving carbonyl functionalities and active methylenes. This reaction has proved to be a major driving force in many multicomponent reactions indicating the prolific utility toward the development of biologically fascinating molecules. This eminent reaction was acclimatised on different pharmacophoric aldehydes (benzimidazole, β‐carboline, phenanthrene, indole, imidazothiadiazole, pyrazole etc.) and active methylenes (oxindole, barbituric acid, Meldrum's acid, thiazolidinedione etc.) to generate the library of chemical compounds. Their potential was also explicit to understand the significance of functionalities involved, which thereby evoke further developments in drug discovery. Furthermore, most of these reaction products exhibited remarkable anticancer activity in nanomolar to micromolar ranges by targeting different cancer targets like DNA, microtubules, Topo‐I/II, and kinases (PIM, PARP, NMP, p300/CBP) etc. This review underscores the efficiency of the Knoevenagel condensation explored in the past six‐year to generate molecules of pharmacological interest, predominantly toward cancer. The present review also provides the aspects of structure‐activity relationships, mode of action and docking study with possible interaction with the target protein.
A prediction model for early systemic recurrence in breast cancer using a molecular diagnostic analysis of sentinel lymph nodes: A large‐scale, multicenter cohort study
Authors: Osako Tomo , Matsuura Masaaki , Yotsumoto Daisuke , Takayama Shin , Kaneko Koji , Takahashi Mina , Shimazu Kenzo , Yoshidome Katsuhide , Kuraoka Kazuya , Itakura Masayuki , Tani Mayumi , Ishikawa Takashi , Ohi Yasuyo , Kinoshita Takayuki , Sato Nobuaki , Tsujimoto Masahiko , Nakamura Seigo , Tsuda Hitoshi , Noguchi Shinzaburo , Akiyama Futoshi
Published: February 2022

Background

The one‐step nucleic acid amplification (OSNA) assay can quantify the cytokeratin 19 messenger RNA copy number as a proxy for sentinel lymph node (SN) metastasis in breast cancer. A large‐scale, multicenter cohort study was performed to determine the prognostic value of the SN tumor burden based on a molecular readout and to establish a model for the prediction of early systemic recurrence in patients using the OSNA assay.

Methods

SN biopsies from 4757 patients with breast cancer were analyzed with the OSNA assay. The patients were randomly assigned to the training or validation cohort at a ratio of 2:1. On the basis of the training cohort, the threshold SN tumor burden value for stratifying distant recurrence was determined with Youden's index; predictors of distant recurrence were investigated via multivariable analyses. Based on the selected predictors, a model for estimating 5‐year distant recurrence–free survival was constructed, and predictive performance was measured with the validation cohort.

Results

The prognostic cutoff value for the SN tumor burden was 1100 copies/μL. The following variables were significantly associated with distant recurrence and were used to construct the prediction model: SN tumor burden, age, pT classification, grade, progesterone receptor, adjuvant cytotoxic chemotherapy, and adjuvant anti–human epidermal growth factor receptor 2 therapy. The values for the area under the curve, sensitivity, specificity, and accuracy of the prediction model were 0.83, 63.4%, 81.7%, and 81.1%, respectively.

Conclusions

Using the OSNA assay, the molecular readout–based SN tumor burden is an independent prognostic factor for early breast cancer. This model accurately predicts early systemic recurrence and may facilitate decision‐making related to treatment.
Reductive Amination of 5‐Hydroxymethylfurfural to 2,5‐Bis(aminomethyl)furan over Alumina‐Supported Ni‐Based Catalytic Systems
Authors: Wei Zuojun , Cheng Yuran , Huang Hao , Ma Zhihe , Zhou Kuo , Liu Yingxin
Published: February 2022

Mono‐ and bimetallic Ni‐based catalysts were prepared by screening 6 supports and 14 secondary metals for reductive amination of 5‐hydroxymethylfurfural (5‐HMF) into 2,5‐bis(aminomethyl)furan (BAMF), among which γ‐Al2O3 and Mn were the best candidates. By further optimization of the reaction conditions at 0.4 g catalyst loading for 0.5 g substrate of 5‐HMF and 160 °C of reaction temperature, 10Ni/γ‐Al2O3 and 10NiMn(4 : 1)/γ‐Al2O3 achieved the highest BAMF yields of 86.3 and 82.1 %, respectively. Although the BAMF yield values were comparable with that over Raney Ni, the turnover frequencies based on the initial BAMF yield and unit weight of Ni for 10NiMn(4 : 1)/γ‐Al2O3, 10Ni/γ‐Al2O3, and Raney Ni were calculated as 0.41, 0.09, and 0.04 h−1, respectively. X‐ray diffraction, transmission electron microscopy, and X‐ray photoelectron spectroscopy showed that the existence of MnOx well dispersed on the γ‐Al2O3 support and its electron transfer effect with Ni particles on the surface of the support contributed to the high efficiency and better recyclability for the five‐time reused 10NiMn(4 : 1)/γ‐Al2O3 catalyst.
Facile Synthesis of Benzimidazole and Benzothiazole Compounds Mediated by a Zinc Precatalyst Supported by an Iminopyrrole‐Morpholine Ligand
Authors: Bano Kulsum , Kisan Devadkar Ajitrao , Panda Tarun K.
Published: February 2022

Three zinc complexes, with the general formula {κ2‐C4H3NH[2‐CH=NCH2CH2N(CH2CH2)2O]ZnX2} [X=Cl (2 a), Br (2 b), I (2 c)], supported by a neutral iminopyrrole‐morpholine ligand, were synthesized by the reaction between {C4H3NH‐2‐[CH=NCH2CH2N (CH2CH2)2O]} (1) and anhydrous zinc dihalides (ZnCl2, ZnBr2, ZnI2) at ambient temperature in dry methanol. The zinc complexes were fully characterized using multinuclear NMR spectroscopic techniques and the molecular structures of complexes 2 a and 2 c in their solid states were determined by single‐crystal X‐ray diffraction analysis. The zinc diiodo complex (2 c) proved to be a competent precatalyst in the formation of a wide range of benzimidazole and benzothiazole compounds, via aerobic oxidative condensation of several benzylamines with o‐phenylenediamine, N‐phenyl‐o‐phenylene‐diamine, and o‐mercaptoaniline. The benzimidazole and benzothiazole derivatives were successfully characterized using 1H and 13C{1H} NMR spectroscopy.
Composition, nutritional value, and uses of Ricinodendron heudelotii, Vitex doniana, and Cleome gynandra seed oil, three indigenous oil species sources of omega 3, 6, and 9 fatty acids: A review
Authors: Adome Nadjidath Founmilayo , Chadare Flora Josiane , Honfo Fernande , Hounhouigan Djidjoho Joseph
Published: February 2022

Ricinodendron heudelotii, Vitex doniana, and Cleome gynandra are three indigenous species of Benin/West Africa. This review focuses on the physicochemical characteristics of their seeds and the nutritional and functional properties of their oils. In this systematic review, scientific articles and reports were used to collect information. The minima, maxima, and mean values were considered and converted into a dry basis and/or the same units by using the international system of units when needed to allow comparison. Seeds of Ricinodendron, Vitex and Cleome fat contents were 51.83 g/100 g dw, 28.55 g/100 g dw and 27.35 g/100 g dw, respectively. The three seed oils contained 58.54% to 87% mono and polyunsaturated fatty acids. Ricinodendron seed oil contained a conjugated polyunsaturated fatty acid α‐eleostearic acid (49.3%–51.1%). Data varied from one author to another due to the methods used. R. heudelotii seeds oil is traditionally used for the treatment of several diseases. Its oil showed phytochemical and antimicrobial properties suggesting its possible use in pharmaceutical industries. Ricinodendron and Vitex seed oil should not be used for cooking at high temperatures or frying because of their high and medium levels of unsaturation.
Biology of IDH mutant cholangiocarcinoma
Authors: Wu Meng‐Ju , Shi Lei , Merritt Joshua , Zhu Andrew X. , Bardeesy Nabeel
Published: February 2022

Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are the most frequently mutated metabolic genes across human cancers. These hotspot gain‐of‐function mutations cause the IDH enzyme to aberrantly generate high levels of the oncometabolite, R‐2‐hydroxyglutarate, which competitively inhibits enzymes that regulate epigenetics, DNA repair, metabolism, and other processes. Among epithelial malignancies, IDH mutations are particularly common in intrahepatic cholangiocarcinoma (iCCA). Importantly, pharmacological inhibition of mutant IDH (mIDH) 1 delays progression of mIDH1 iCCA, indicating a role for this oncogene in tumor maintenance. However, not all patients receive clinical benefit, and those who do typically show stable disease rather than significant tumor regressions. The elucidation of the oncogenic functions of mIDH is needed to inform strategies that can more effectively harness mIDH as a therapeutic target. This review will discuss the biology of mIDH iCCA, including roles of mIDH in blocking cell differentiation programs and suppressing antitumor immunity, and the potential relevance of these effects to mIDH1‐targeted therapy. We also cover opportunities for synthetic lethal therapeutic interactions that harness the altered cell state provoked by mIDH1 rather than inhibiting the mutant enzyme. Finally, we highlight key outstanding questions in the biology of this fascinating and incompletely understood oncogene.
Nonalcoholic steatohepatitis is the most common indication for liver transplantation among the elderly: Data from the United States Scientific Registry of Transplant Recipients
Authors: Stepanova Maria , Kabbara Khaled , Mohess Denise , Verma Manisha , Roche‐Green Alva , AlQahtani Saleh , Ong Janus , Burra Patrizia , Younossi Zobair M.
Published: February 2022

As the US population ages, more elderly patients may need liver transplantation. Our aim was to assess recent trends among elderly individuals requiring liver transplant in the United States. Scientific Registry of Transplant Recipients data (2002–2020) were used to select elderly (≥65 years) liver transplant candidates and assess on‐list and posttransplant outcomes. During the study period, 31,209 liver transplant candidates ≥65 years were wait listed. Common etiologies included nonalcoholic steatohepatitis (NASH; 31%), hepatitis C (23%), and alcoholic liver disease (18%); 30% also had hepatocellular carcinoma (HCC). Over time, the proportion of patients ≥65 years among all adult liver transplant candidates increased from 9% (2002–2005) to 23% (2018–2020) (trend, p < 0.0001). The proportion of NASH among elderly candidates increased from 13% (2002–2005) to 39% (2018–2020). Of the elderly candidates, 54% eventually received transplants. In multivariate analysis, independent predictors of a higher chance of receiving a transplant for the elderly included more recent years of listing, male sex, higher Model for End‐Stage Liver Disease (MELD) score, and HCC (all p < 0.01). Posttransplant mortality in elderly transplant recipients was higher than in younger patients but continued to decrease over time. In multivariate analysis, independent predictors of higher posttransplant mortality for elderly transplant recipients were earlier years of transplantation, older age, male sex, higher MELD score, history of diabetes, retransplantation, and having HCC (all p < 0.01). The proportion of elderly patients in need of liver transplantation in the United States is sharply increasing. NASH is the most common indication for liver transplantation among the elderly. The outcomes of these patients have been improving in the past 2 decades.
Addressing childhood obesity in Queensland: Aboriginal and Torres Strait Islander Health Worker perspectives and practices
Authors: Vincze Lisa , Boswell Megan , Atkins Heidi , Littlewood Robyn , Williams Lauren
Published: February 2022

Issue Addressed

Obesity disproportionately impacts Aboriginal and Torres Strait Islander children compared to non‐Indigenous children. Aboriginal and Torres Strait Islander Health Workers (AHWs) in Queensland support the health of Aboriginal and Torres Strait Islander peoples. However, little is known about their perspectives and practices on addressing childhood obesity. The aim of this study was to investigate AHW perspectives and clinical practice behaviours with Aboriginal and Torres Strait Islander children and their families.

Methods

In a cross‐sectional mixed‐methods approach, a purpose‐developed online survey (25 items) was distributed to the AHW workforce in Queensland (~100 AHWs). The survey explored [1] role characteristics, [2] current attitudes and beliefs about childhood obesity, [3] barriers to discussing weight management, [4] clinical practice behaviours and [5] demographic characteristics. Eight AHWs responding to the survey also participated in semi‐structured telephone interviews to discuss their survey responses.

Results

Fifty‐five AHWs responded and 45 completed the survey. While the majority of respondents (91%) agreed that addressing childhood obesity was an important part of their role, fewer (67%) agreed that obesity was an issue in Aboriginal and Torres Strait Islander peoples. Over half (55%) found it difficult to discuss overweight and obesity with children and families and only 22.5% reported measuring height and weight often. Key themes included a willingness to address childhood obesity, with experience and training being key enablers to discussing the issue. There was a perceived lack of culturally appropriate programs to support AHWs working with families.

Conclusions

AHWs report a willingness to address childhood obesity within their roles, however many find it difficult to raise the issue with families, with even fewer routinely undertaking obesity assessment practices.

So what?

These findings could inform training initiatives for AHWs to optimise screening, identification, referral, and treatment of childhood obesity in Aboriginal and Torres Strait Islander communities.
Are Brazilian catchments gaining or losing water? The effective area of tropical catchments
Authors: Schwamback Dimaghi , Gesualdo Gabriela C. , Sone Jullian S. , Kobayashi Alex Naoki A. , Bertotto Luis Eduardo , Garcia Maria Vitória S. , Almagro André , Oliveira Paulo Tarso S.
Published: February 2022

Similar to most countries, the Brazilian water resources management considers topographically delineated catchment as a territorial unit for policy implementation. Yet, previous studies have shown that catchments are not hydrologically isolated, and topographic limits often neglect the groundwater boundaries. Thus, studies on effective catchment areas are promising for shedding light on inter‐catchment groundwater flow. Here, we investigated the deviation between the topographic and effective areas across Brazil. We applied the effective catchment area index (ECI) to 733 Brazilian catchments and identified the most influencing attributes on the ECI by using principal component and random forest analyses (PCA and RFA, respectively). Further analysis was carried out by contrasting the ECI values against the expected range of the Budyko curve, considering both topographic and effective catchment areas (classic and adjusted framework, respectively). We noted that nearly 32% of the Brazilian catchments presented more than 30% of difference between the effective area and its topographic boundaries. In general, the more arid biomes in Brazil—the Cerrado and Caatinga—are prone to have smaller effective areas while larger effective areas were mostly found in the Atlantic Forest biome, a humid tropical region with a higher mean elevation. Our findings indicate that the aridity index was the main driving factor and negatively correlated with ECI followed by mean slope, precipitation seasonality, and mean elevation. We highlight the potential of adopting a pooling of catchments based on their interconnectivity to minimize management costs while maximizing synergies and lessening trade‐offs between ecosystem functioning and water transfer processes. Our results contribute to a better country‐wide understanding of hydrological connectivity among catchments and highlight the need to consider the effective catchment area to overcome water‐food‐energy security challenges on multiple scales.
Marine macroalgae as a feasible and complete resource to address and promote Sustainable Development Goals (SDGs)
Authors: García-Poza Sara , Pacheco Diana , Cotas João , Marques João C. , Pereira Leonel , Gonçalves Ana M. M.
Published: February 2022

Because the world's population is increasing, science-based policies are needed to promote sustainable global development. It is important to maintain and restore the environment and help human society overcome the risks from industrialization and unsustainable exponential growth. In recent years, many studies have highlighted that macroalgae represent a key marine resource for ecological and sustainable living, thus helping to address today's global problems, such as water pollution, ocean acidification, and global warming. Macroalgae show the potential to provide innovative, ecofriendly, and nutritious food sources and natural compounds for various industries, such as biomedical, food, agricultural, and pharmaceutical industries. This review discusses how macroalgae can help us today and how they can promote a more sustainable way of life in the future. It also discusses the potential danger for ecosystems and the global population if these organisms are not part of the solution but part of the problem. Integr Environ Assess Manag 2022;18:1148–1161. © 2022 SETAC

KEY POINTS

Macroalgae can play a fundamental role in the development of compliance within the SDGs. On an ecological scale and referring to coastal and oceanic habitats, macroalgae have a key role, because not only do they represent unique nursery areas with a high ecological relevance, but they are also agents for the removal of inorganic pollutants, thus contributing to water bioremediation. Macroalgae endorse complex food webs in marine habitats and act as a coastal defense by damping waves’ energy; moreover, they contribute to carbon dioxide sequestration, minimizing our carbon footprint and mitigating climate change impacts, as they are photosynthetic organisms. Macroalgae aquaculture can help to reduce the effects of ocean acidification while responding to the global need of feed, fuel, pharmaceuticals, and food by becoming a source to combat malnutrition.
A Review of Big Data Research in Accounting
Authors: Aboagye‐Otchere Francis , Agyenim‐Boateng Cletus , Enusah Abdulai , Aryee Theodora Ekua
Published: February 2022

The impending fourth industrial revolution has enhanced the role of big data analytics in today’s business practice. Consequently, many now consider big data as the most strategic resource in business to the extent that organizations that fail to utilize it may become competitively disadvantaged. Following these developments, questions have been raised about the future of the accounting discipline, especially in terms of how it can continue to add value to organizations. While some scholars have attempted to address this question, it remains an abstract concept requiring further investigation. Therefore, this study conducts a systematic literature review to determine the status of accounting research on big data analytics and provides avenues for further studies. By conducting co‐occurrence network analysis on 52 peer‐reviewed articles published from 2010 to 2020, three broad themes emerged, entailing big data implications for accounting practice, education, and research design. A further examination of the themes revealed few empirical studies on the phenomenon, as conceptual research dominates the field. Although external audit implications of big data are widely discussed, other accounting domains (e.g., managerial accounting and taxation) are underexplored. Therefore, future studies may focus on the implications of big data on variables such as performance measurement, information governance, tax behavior, curriculum design, and pedagogy.
Effects of bone marrow‐derived mesenchymal stem cells on doxorubicin‐induced liver injury in rats
Authors: Celik Samanci Tugba , Gökcimen Alpaslan , Kilic Eren Mehtap , Gürses Kadri Murat , Pilevneli Hatice , Kuyucu Yurdun
Published: February 2022

Doxorubicin (DOX) is a potent chemotherapeutic agent and has toxic effects on various organs, including the liver. In the current study, we aimed to investigate the effects of bone‐marrow‐derived mesenchymal stem cell (BM‐MSC) administration on DOX‐induced hepatotoxicity in rats. 24 Wistar‐albino rats were divided into three groups: Control, DOX, and DOX+MSC. DOX (20 mg/kg) was administered to the DOX group. In the DOX + MSC group, BM‐MSCs (2 × 106) were given through the tail vein following DOX administration. DOX administration led to significant structural liver injury. Besides this, oxidative balance in the liver was impaired following DOX administration. DOX administration also led to an increase in apoptotic cell death in the liver. Structural and oxidative changes were significantly alleviated with the administration of BM‐MSCs. Furthermore, BM‐MSC administration suppressed excessive apoptotic cell death. Our findings revealed that BM‐MSC administration may alleviate DOX‐induced liver injury via improving the oxidative status and limiting apoptotic cell death in the liver tissue.
Benzimidazolium salts bearing the trifluoromethyl group as organofluorine compounds: Synthesis, characterization, crystal structure, in silico study, and inhibitory profiles against acetylcholinesterase and α‐glycosidase
Authors: Tezcan Burcu , Gök Yetkin , Sevinçek Resul , Taslimi Parham , Taskin‐Tok Tugba , Aktaş Aydın , Güzel Bilgehan , Aygün Muhittin , Gülçin İlhami
Published: February 2022

Here, we report the synthesis, characterization, and biological activities of a series of benzimidazolium salts bearing the trifluoromethylbenzyl group. All benzimidazolium salts were characterized by using nuclear magnetic resonance (NMR) (1H NMR and 13C NMR), Fourier transform‐infrared spectroscopy, and elemental analysis techniques. The crystal structures of some of these compounds were obtained by the single‐crystal X‐ray diffraction method. Furthermore, the acetylcholinesterase (AChE) and α‐glycosidase (α‐Gly) enzyme inhibition activities of these compounds were investigated. The obtained results revealed that2e, withKivalue of 1.36 ± 0.34 µM against AChE and3dwithKivalue of 91.37 ± 10.38 µM against α‐Gly, were the most potent compounds against both assigned enzymes. It should be noted that most of the synthesized compounds were more potent than standard inhibitor tacrine (TAC) against AChE. In silico studies, we focused on compound2e, 3d, 3e, and3fas potent inhibitors of AChE and α‐Gly, the compound2eshowed good binding energy (−10.23 kcal/mol), among the three selected compounds and positive control (−10.18, −10.08, and −7.37 kcal/mol for3d, 3f, and TAC, respectively). Likewise, as a result of the same compounds against the α‐Gly enzyme, the compound3dhad the highest binding affinity (−8.39 kcal/mol) between the four selected compounds and the positive control (−8.27, −8.10, −8.06, and −7.53 kcal/mol for3f, 3e, 2e, and acarbose, respectively). From the absorption, distribution, metabolism, excretion, and toxicity analyses, it can be concluded that the compounds under consideration exhibited more drug‐likeness properties in the prediction studies compared to positive controls.
Human outgrowth knee fibroblasts from patients undergoing total knee arthroplasty exhibit a unique gene expression profile and undergo myofibroblastogenesis upon TGFβ1 stimulation
Authors: Bayram Banu , Thaler Roman , Bettencourt Jacob W. , Limberg Afton K. , Sheehan Kevin P. , Owen Aaron R. , Berry Daniel J. , Morrey Mark E. , Sanchez‐Sotelo Joaquin , van Wijnen Andre J. , Dudakovic Amel , Abdel Matthew P.
Published: February 2022

Arthrofibrosis is characterized by excessive extracellular matrix (ECM) deposition that results in restricted joint motion after total knee arthroplasties (TKAs). Currently, treatment options are limited. Therefore, an in vitro model of knee‐related myofibroblastogenesis is valuable to facilitate investigation of the arthrofibrotic process, diagnostic and therapeutic options. In this study, we obtained intraoperative posterior capsule (PC), quadriceps tendon (QT), and suprapatellar pouch (SP) tissues from the knees of four patients undergoing primary TKAs for osteoarthritis. From these tissues, we isolated primary cells by the outgrowth method and subsequently characterized these cells in the absence and presence of the pro‐myofibroblastic cytokine, transforming growth factor beta 1 (TGFβ1). Light microscopy of knee outgrowth cells revealed spindle‐shaped cells, and immunofluorescence (IF) analysis demonstrated staining for the fibroblast‐specific markers TE‐7 and vimentin (VIM). These knee outgrowth fibroblasts differentiated readily into myofibroblasts as reflected by enhanced α‐smooth muscle actin (ACTA2) mRNA and protein expression and increased mRNA expression of collagen type 1 (COL1A1) and type 3 (COL3A1) with collagenous matrix deposition in the presence of TGFβ1. Outgrowth knee fibroblasts were more sensitive to TGFβ1‐mediated myofibroblastogenesis than adipose‐derived mesenchymal stromal/stem cells (MSCs). While outgrowth knee fibroblasts isolated from three anatomical regions in four patients exhibited similar gene expression, these cells are distinct from other fibroblastic cell types (i.e., Dupuytren's fibroblasts) as revealed by RNA‐sequencing. In conclusion, our study provides an in vitro myofibroblastic model of outgrowth knee fibroblasts derived from patients undergoing primary TKA that can be utilized to study myofibroblastogenesis and assess therapeutic strategies for arthrofibrosis.
Thermal tolerance and acclimation capacity in the European common frog (Rana temporaria) change throughout ontogeny
Authors: Ruthsatz Katharina , Dausmann Kathrin H. , Peck Myron A. , Glos Julian
Published: February 2022

Phenotypic plasticity may allow ectotherms with complex life histories such as amphibians to cope with climate‐driven changes in their environment. Plasticity in thermal tolerance (i.e., shifts of thermal limits via acclimation to higher temperatures) has been proposed as a mechanism to cope with warming and extreme thermal events. However, thermal tolerance and, hence, acclimation capacity, is known to vary with life stage. Using the common frog (Rana temporaria) as a model species, we measured the capacity to adjust lower (CTmin) and upper (CTmax) critical thermal limits at different acclimation temperatures. We calculated the acclimation response ratio as a metric to assess the stage‐specific acclimation capacity at each of seven consecutive ontogenetic stages and tested whether acclimation capacity was influenced by body mass and/or age. We further examined how acclimation temperature, body mass, age, and ontogenetic stage influenced CTminand CTmax. In the temperate population ofR. temporariathat we studied, thermal tolerance and acclimation capacity were affected by the ontogenetic stage. However, acclimation capacity at both thermal limits was well below 100% at all life stages tested. The lowest and highest acclimation capacity in thermal limits was observed in young and late larvae, respectively. The relatively low acclimation capacity of young larvae highlights a clear risk of amphibian populations to ongoing climate change. Ignoring stage‐specific differences in thermal physiology may drastically underestimate the climate vulnerability of species, which will hamper successful conservation actions.
Gene duplication, conservation, and divergence of activating transcription factor 5 gene in zebrafish
Authors: Zhu Huihui , Zhang Xiaoyi , Xu Shifan , Wu Jiawen , Hou Mengying , Zhao Haobin , Zhou Qingchun , Zhong Xueping
Published: February 2022

Activating transcription factor 5 (Atf5) is a member of the ATF/CREB family of transcription factors and involved in diverse cellular functions and diseases in mammals. However, the function of atf5 remains largely unknown in fish. Here, we report the expression pattern and function of duplicated atf5 genes in zebrafish. The results showed that the gene structures of zebrafish atf5a and atf5b were similar to their mammalian orthologs. Zebrafish Atf5a and Atf5b shared an amino acid sequence identity of 40.7%. Zebrafish atf5a and atf5b had maternal origin with dynamic expression during embryonic development. Zebrafish atf5a mRNA is mainly enriched in olfactory epithelium, midbrain, and hindbrain, while zebrafish atf5b mRNA is mainly detected in midbrain, hindbrain, and liver during embryogenesis. The results of acute hypoxia experiment showed that atf5a mRNA was significantly upregulated in the brain, liver, and muscle, while atf5b mRNA was just increased significantly in the brain. Functional analysis showed that knockdown of atf5a affects the development of the ciliated neurons in zebrafish embryos. The effect was enhanced when atf5a MO was co‐injected with atf5b MO. The development of ciliated neurons in zebrafish embryos was not affected by injection of atf5b MO alone. atf5a knockdown also affects the development of early‐born olfactory neurons. The effects caused by atf5a knockdown could be rescued by atf5b mRNA. These results suggest that the duplicated atf5 genes may have evolved divergently and play redundant biological roles in the development of olfactory sensory neurons in zebrafish.
Size and shape of the semicircular canal of the inner ear: A new marker of pig domestication?
Authors: Evin Allowen , David Loïc , Souron Antoine , Mennecart Bastien , Orliac Maeva , Lebrun Renaud
Published: February 2022

Domestication has led to many changes in domestic animal biology, including their anatomy. The shape of the inner ear, part of the mammalian ear, has been found particularly relevant for discriminating domesticated species, their hybrids or differentiating the wild and domestic populations of a single species. Here we assessed the use of the size and shape of the semicircular canals (SCC) of the inner ear as a marker of pig domestication. We studied a total of 63 petrosal bones belonging to wild boar (Sus scrofa, two populations) and domestic pigs (extensively and intensively reared specimens) that were µCT‐scanned and from which the size and the shape of the inner ear were quantified through geometric morphometrics, analyzing the 3D coordinates of 6 landmarks and 60 sliding semilandmarks localized on the SCC and the common crus. The domestic pigs have larger SCC than the wild boar from which they also strongly differ in shape (correct cross validation of 95.5%, confidence interval: 92.3%–98.1%). Strong shape differences were detected between the two populations of wild boar, as well as a sexual size dimorphism. All together the results highlight the taxonomic discriminant power of the SCC of the inner ear shape, and its relevance for domestication studies.
Counting spanning trees in a complete bipartite graph which contain a given spanning forest
Authors: Dong Fengming , Ge Jun
Published: February 2022

In this article, we extend Moon's classic formula for counting spanning trees in complete graphs containing a fixed spanning forest to complete bipartite graphs. Let be the bipartition of the complete bipartite graph with and . We prove that for any given spanning forest of with components , the number of spanning trees in which contain all edges in is equal to
where and for .
Geochemical focusing and burial of sedimentary iron, manganese, and phosphorus during lake eutrophication
Authors: Scholtysik Grzegorz , Goldhammer Tobias , Arz Helge W. , Moros Matthias , Littke Ralf , Hupfer Michael
Published: February 2022

The redistributive transport of sedimentary, redox‐sensitive metals such as iron (Fe) and manganese (Mn) along depth gradients in lakes or marine basins, and in particular the concentration of these elements at local depressions, has been described as “geochemical focusing.” However, the impact of variable redox conditions at the sediment–water interface on this process is not entirely understood. In this study, we report that the enrichment and burial of Fe, Mn, and associated phosphorus (P) in dimictic Lake Arendsee, Germany, has been affected by a transition from oligo‐mesotrophic to eutrophic conditions in the first half of the 20th century. Eleven sediment cores (<50 cm long) were obtained from water depths ranging from 38.5 to 49.5 m, and analyzed for their elemental composition. The older, non‐varved section, which was deposited prior ca. 1940 during oligo‐mesotrophic conditions, contains up to 10 times higher Mn and 2.5 times higher Fe contents at the deep sites compared to corresponding intervals at shallower sites. Due to their high Fe content, sediments in this interval also contain up to eight times more P, at least partly owing to vivianite authigenesis. Burial of Mn occurred via Mn‐carbonate authigenesis, possibly as rhodochrosite. Since ca. 1940, calcite and diatom varves have formed under eutrophic conditions, whereas Fe enrichment decreased and finally stopped due to fixation as pyrite in the shallow sites. Our results suggest that redox‐controlled geochemical focusing determines the distribution of Mn and Fe, as well as the occurrence of authigenic minerals such as vivianite and Mn‐carbonate.
Results of a multidisciplinary strategy to improve the management of cardiovascular risk factors after liver transplantation
Authors: Sastre Lydia , García Raquel , Viñals Clara , Amor Antonio J. , Yago Gema , Hervás Alicia , Sánchez Lorena , Trabal Joan , Molero Judit , Escudé Laia , Pagano Giulia , Blasco Miquel , Gilabert Rosa , Ruiz Pablo , Colmenero Jordi , Navasa Miquel , Ortega Emilio , Crespo Gonzalo
Published: February 2022

Although liver transplantation (LT) recipients are at high cardiovascular risk (CVR), the management of CVR factors (CVRF) after LT is far from optimal and needs to be improved. For this reason, we developed a multidisciplinary protocol to standardize the identification, risk stratification, management, and targets of therapy of CVRF during the first post‐LT year. The grade of identification and control of CVRF 12 months after LT in the postintervention cohort (LT January 2018–January 2020, n = 150) were compared with a control cohort who underwent LT between July 2015 and December 2016 (n = 100). Before LT, the prevalence of metabolic‐associated fatty liver disease as the indication of LT and the presence of obesity were significantly higher in the postintervention cohort, whereas the prevalence of other CVRF and renal dysfunction tended to be higher. Cyclosporine A was used less frequently in the postintervention cohort, whereas everolimus tended to increase. At 12 months after LT, the proportion of patients with measured blood pressure (88% vs. 56%), glycosilated hemoglobin (HbA1c; 96% vs. 72%), and high‐density lipoprotein/low‐density lipoprotein cholesterol (67% vs. 33%) was higher in the postintervention than in the control cohort (all p < 0.001). Blood pressure (64% vs. 36%, p = 0.02) and HbA1c (85% vs. 70%, p = 0.1) were within target in more individuals with hypertension and diabetes mellitus, respectively, in the postintervention cohort. Median total cholesterol levels were lower in the postintervention (184 mg/dl; interquartile range [IQR], 160–210 mg/dl) than in the control cohort (212 mg/dl; IQR, 186–240 mg/dl; p = 0.02). At 2 years after LT, the incidence of cardiovascular events was 14% in the control cohort and 6% in the postintervention cohort (p = 0.063). In conclusion, a multidisciplinary, multiprofessional strategy can achieve a higher grade of assessment and management of post‐LT CVR despite a worsening metabolic profile of LT recipients.