bluuebunny/crossref_metadata_2025 huggingface dataset:
In Silico Design and Investigation of Novel Thiazetidine Derivatives as Potent Inhibitors of PrpR in Mycobacterium tuberculosis
Authors: Dasmahapatra Upala , Rajasekhar Sreerama , Neelima Grandhe , Maiti Barnali , Karuppasamy Ramanathan , Murali Poornima , MM Balamurali , Chanda Kaushik
Published: December 2022

Tuberculosis is one of the most life‐threatening acute infectious diseases diagnosed in humans. In the present investigation, a series of 16 new disubstituted 1,3‐thiazetidines derivatives is designed, and investigated via various in silico methods for their potential as anti‐tubercular agent by evaluating their ability to block the active site of PrpR transcription factor protein of Mycobacterium tuberculosis. The efficacy of the molecules was initially assessed with the help of AutoDock Vina algorithm. Further Glide module is used to redock the previously docked complexes. The binding energies and other physiochemical properties of the designed molecules were evaluated using the Prime‐MM/GBSA and the QikProp module, respectively. The results of docking revealed the nature, site of interaction and the binding affinity between the proposed candidates and the active site of PrpR. Further the inhibitory effect of the scaffolds was predicted and evaluated employing a machine learning‐based algorithm and was used accordingly. Further, the molecular dynamics simulation studies ascertained the binding characteristics of the unique 13, when analysed across a time frame of 100 ns with GROMACS software. The results show that the proposed 1,3‐thiazetidine derivatives such as 10, 11, 13 and 14 could be potent and selective anti‐tubercular agents as compared to the standard drug Pyrazinamide. Finally, this study concludes that designed thiazetidines can be employed as anti‐tubercular agents. Undeniably, the results may guide the experimental biologists to develop safe and non‐toxic drugs against tuberculosis by demanding further in vivo and in vitro analyses.
Investigation of the equilibrium constant of NO absorption into diethylenetriaminecobalt(II) solution
Authors: Chen Pei‐Yun , Li Zi‐Qiu , Long Xiang‐Li
Published: December 2022

Diethylenetriaminecobalt(II), [Co(DETA)2]2+, formed by diethylenetriamine (DETA) coordinating with Co(II) ion, can be used to remove NO from flue gas. Diethylenetriaminecobalt(II) is capable of binding NO to form metal nitroso complexes. The determination of the equilibrium constant of the reaction between [Co(DETA)2]2+ and NO is important to the development of the technology for the elimination of NO from exhausted gas streams with diethylenetriaminecobalt solution. In this paper, the equilibrium constants of this reaction have been determined by a series of experiments in a bubble reactor at the range of 30–70°C under atmospheric pressure in the [Co(DETA)2]2+ solution of pH 7.5. All experimental data are in good agreement with the following equation: , where the changes in enthalpy and entropy are ΔH0 = −38.89 kJ ⋅ mol−1 and ΔS0 = −109.7 J ⋅ K−1 ⋅ mol−1, respectively.
Carbon dioxide reduction mechanism via single‐atom nickel supported on graphitic carbon nitride
Authors: Wu Jiang , Wang Guanqi , Liu Qizhen , Ling Yang , Zhang Ruitao , Sun Ningchao , Gao Yingchao , Chen Zhihao , Sun Yijing , Gao Yunfei
Published: December 2022

In many photocatalytic reaction paths, the breaking of the first CO bond in a CO2 molecule is often the key step that becomes the rate‐controlled reaction step. In this paper, a graphitic carbon nitride (g‐C3N4) supported nickel single‐atom catalyst (Ni@g‐C3N4) was successfully constructed, and the mechanism of CO2 catalytic reduction was systematically studied based on density functional theory (DFT). The introduction of nickel promotes the adsorption of small molecules, especially for the CO2 activation. According to density of states (DOS) and frontier orbital analysis, the photogenerated carriers tend to jump from nitrogen atoms to carbon atoms, forming an electron transfer in real space, after g‐C3N4 is excited by light. With the appearance of nickel‐doped levels, the DOS of Ni@g‐C3N4 is no longer symmetric with respect to the spin up and down, especially around the original band gap of g‐C3N4. Single‐atom nickel has abundant frontier orbitals and high activity and is a favourable place for chemical reactions. The presence of surface hydrogen can promote the recovery of CO2, and the energy barrier of Ni@g‐C3N4 with hydrogen is only 15% of the clean g‐C3N4 surface. This paper provides a new idea for the development of efficient single‐atom catalysts for CO2 reduction.
Beyond the Michaelis–Menten: Accurate Prediction of Drug Interactions Through Cytochrome P450 3A4 Induction
Authors: Vu Ngoc‐Anh Thi , Song Yun Min , Tran Quyen Thi , Yun Hwi‐yeol , Kim Sang Kyum , Chae Jung‐woo , Kim Jae Kyoung
Published: December 2022

The US Food and Drug Administration (FDA) guidance has recommended several model‐based predictions to determine potential drug–drug interactions (DDIs) mediated by cytochrome P450 (CYP) induction. In particular, the ratio of substrate area under the plasma concentration‐time curve (AUCR) under and not under the effect of inducers is predicted by the Michaelis–Menten (MM) model, where the MM constant () of a drug is implicitly assumed to be sufficiently higher than the concentration of CYP enzymes that metabolize the drug () in both the liver and small intestine. Furthermore, the fraction absorbed from gut lumen () is also assumed to be one because is usually unknown. Here, we found that such assumptions lead to serious errors in predictions of AUCR. To resolve this, we propose a new framework to predict AUCR. Specifically, was re‐estimated from experimental permeability values rather than assuming it to be one. Importantly, we used the total quasi‐steady‐state approximation to derive a new equation, which is valid regardless of the relationship between and , unlike the MM model. Thus, our framework becomes much more accurate than the original FDA equation, especially for drugs with high affinities, such as midazolam or strong inducers, such as rifampicin, so that the ratio between and becomes low (i.e., the MM model is invalid). Our work greatly improves the prediction of clinical DDIs, which is critical to preventing drug toxicity and failure.
Examining the quality of the consolidated mandatory non‐financial statements of a cooperative banking group: A longitudinal analysis
Authors: Veltri Stefania , Cristiano Elena , Ferraro Olga
Published: December 2022

With the 2014/95/EU Directive, implemented in Italy with the Legislative Decree no. 254/2016, public interest entities with specific requirements, among which credit institutions, have been obliged to report several aspects of non‐financial information (NFI) in a non‐financial statement (NFS). It remains an open question whether NFI disclosure regulations leads to an improvement in reporting quality. In this article, we investigate the quality of the consolidated mandatory NFSs (CNFSs) for the Iccrea Cooperative Banking Group (ICBG) for the 2017–2020 period. This article is the first study exploring the quality of mandatory NFDs using a longitudinal approach for a cooperative banking group, and it is also the first to use three different meanings of quality in the same study (quality as compliance to the Decree requirements, as multidimensional construct, and as completeness) under the theoretical lens of material legitimacy.
Corporate social responsibility reporting and capital structure: Does board gender diversity mind in such association?
Authors: Pucheta‐Martínez María Consuelo , Bel‐Oms Inmaculada , Gallego‐Álvarez Isabel
Published: December 2022

This research aims to shed light on the effect of corporate social responsibility (CSR) disclosure on capital structure, a significant strategic policy for all listed companies. Furthermore, it aims to explore the moderating effect of the presence of female directors on corporate boards on the relationship between CSR disclosure and capital structure. We use an international sample of 48 countries for the years 2007–2019 collected from the Thomson Reuters database. This study uses the GMM procedure to estimate the model of the association between the disclosure of CSR information and capital structure and the moderating effect of board gender diversity in such relationship. Drawing on agency theory, the results support the negative relationship between CSR disclosure and capital structure. Moreover, our findings also reveal that board gender diversity does not moderate the association between CSR disclosure and capital structure.
Recovery Of Zinc from Scrap Steel Using Zinc‐Bromine Battery Technology
Authors: Standing Rhys , Laycock Christian J. , Lloyd Gareth , Dinsdale Richard M. , Guwy Alan J.
Published: December 2022

Secondary production of steel is known to significantly decrease the CO2 emissions of steelmaking, but only 40 % of steel is produced through recycling, which is made difficult by contamination of scrap resources with nonferrous metals and nonmetal debris. These contaminants include zinc, towards which blast furnace and electric arc systems have a low tolerance (<0.02 wt %). In this work, clean and efficient recovery of zinc from the surface of steel substrates was investigated using a custom‐made low‐cost membrane‐free non‐flow zinc‐bromine battery (ZBB) that enabled rapid and straightforward integration and removal of steel substrates. The electrical performance of the cell was characterized by charge‐discharge profiles, and zinc removal and recovery onto electrodes was characterized by using scanning electron microscopy (SEM) and energy‐dispersive spectroscopy (EDS). Upon discharging, the cell efficiently removed >99.9 wt % zinc from steel surfaces. On recharging the cell, zinc was re‐electroplated onto a carbon foam electrode in an easily recoverable form and with high purity. The process was repeated over 30 cycles to demonstrate robustness. The work shows the importance of the cutoff voltage upon discharging: if less than 0.5 V, the cell co‐extracted iron into the electrolyte solution, affecting cell durability and zinc purity. A two‐stage process for recovering zinc from scrap steel is proposed, illustrating how ZBB technology could enable efficient and clean recovery of zinc from complex scrap steel resources in the steel industry.
Chromium (VI) promotes lung cancer initiation by activating EGF/ALDH1A1 signalling
Authors: Metropulos Anastasia E. , Becker Jeffrey H. , Principe Daniel R.
Published: December 2022

Lung cancer is the leading cause of cancer‐related death worldwide and is strongly associated with tobacco smoke exposure. Although smoking remains the most important and best studied risk factor, recent data suggest that several other carcinogens have a driving role in lung cancer development, particularly in select populations at risk of high or prolonged exposure. Hexavalent chromium [Cr(VI)] is a known carcinogen that is widely used in the manufacturing industry. While the link between Cr(VI) and lung cancer incidence is well‐accepted, the mechanisms through which Cr(VI) promotes lung cancer development are poorly understood. In the present study by Ge and colleagues published in Clinical and Translational Medicine, the authors explored the effects of prolonged Cr(VI) on non‐malignant lung epithelial cells. They determined that Cr(VI) initiates lung tumourigenesis by transforming a subpopulation of stem‐like, tumour initiating cells with increased expression of Aldehyde dehydrogenase 1 family member A1 (ALDH1A1). The observed increase in ALDH1A1 was dependent on transcriptional upregulation via Krüppel‐like factor 4 and associated with enhanced epidermal growth factor biosynthesis. Cr(VI)‐transformed tumour initiating cells accelerated tumour formation in vivo, which was ameliorated by therapeutic inhibition of ALDH1A1. Importantly, ALDH1A1 inhibition also sensitized Cr(VI)‐driven tumours to Gemcitabine chemotherapy and extended overall survival in mice. This study not only offers novel insight into the mechanisms through which Cr(VI) exposure initiates lung tumourigenesis but identifies a potential therapeutic target for patients with lung cancer secondary to Cr(VI) exposure. Additionally, this study underscores the importance of limiting exposure to Cr(VI) in the workplace and finding safer alternatives for use in the manufacturing industry.
Scrape cytology and radiological solid size correlation can be used in the intraoperative management of subsolid lung nodules
Authors: Bulutay Pınar , Atasoy Çetin , Erus Suat , Tanju Serhan , Dilege Şükrü , Fırat Pınar
Published: December 2022

Background

The term radiologic subsolid lung nodule (SLN) represents a heterogeneous group of non‐neoplastic and neoplastic lesions. Intraoperative evaluation (IO) is often required to differentiate and diagnose. The current study aims to investigate the feasibility and reliability of scrape cytology (SC) and radiologic solid size correlation for the IO diagnosis of SLNs.

Methods

Sixty‐eight patients with SLN signs were eligible to take part in the study due to intraoperatively prepared SC slides. We managed to complete the blind radiologic solid size measurement and cytologic evaluation retrospectively. Cases were grouped into three categories based on their cytological features: Group‐0 (Benign), Group‐1 (mild atypical features), and Group‐2 (severe atypical features/unequivocally carcinoma). IO diagnoses were given by combining the radiologic solid size and cytological findings.

Results

Cytological features of Group‐1 were observed in 100%, 93%, 32.5%, and 17% of the AIS, MIA, IA, and benign lesions, respectively. Cytological features of Group‐2 were observed in 67.5%, and 7% of the IA and MIA, respectively. By combining cytology with radiologic solid size, 100%, 85%, 71%, and 83% of the AIS, IA, MIA, and benign lesions respectively were diagnosed correctly. Fifteen (15%) percent of the IA cases were underdiagnosed as MIA since their radiological solid sizes were less than 0.5 cm with cytological features of Group‐1. Conversely, 29% of the MIA cases were overdiagnosed as IA since their radiological solid sizes were greater than 0.5 cm.

Conclusion

SLNs should be handled with caution in terms of IO management. SC and radiologic solid size correlation both provide a practical and tissue‐protecting approach for the IO evaluation of SLNs, ensuring a high consistency between IO and definitive diagnosis.
A mechanistic staging model of reward processing alterations in individuals with binge‐type eating disorders
Authors: Bodell Lindsay P. , Racine Sarah E.
Published: December 2022

Altered reward processing is thought to characterize binge‐type eating disorders, but the exact nature of these alterations is unclear. A more fine‐grained understanding of whether specific aspects of reward processing contribute to the development or maintenance of binge eating may point to new therapeutic targets and personalized treatments. The incentive sensitization theory of addiction proposes that repeated use of a substance increases the desire to approach a reward (‘wanting’) but not pleasure when consuming the reward (‘liking’), suggesting that reward processes driving addiction change over time. We hypothesize that the same may be true for binge eating. Further, consistent with the maladaptive scaling hypothesis, reward processing may be heightened for multiple reinforcers in at‐risk individuals but become tuned toward food once binge eating is initiated. In this article, we propose a mechanistic staging model of reward processing in binge‐type eating disorders that synthesizes existing data and posits that alterations of reward processing depend on illness stage and reward type. We outline translational methods for testing key hypotheses and discuss clinical implications. Considering reward processing alterations in relation to illness stage has the potential to improve treatment outcomes by ensuring that the mechanisms targeted are personalized to the individual patient.

Public Significance

Individuals with binge‐type eating disorders experience alterations in their desire for, and pleasure from, food. We believe that the exact nature of these alterations in reward processing change over the course of illness—from the at‐risk state to an established illness. If true, treatments for binge‐type eating disorders that target reward processing should be personalized to the illness stage of the patient.
Communities of endophytic fungi in a Puerto Rican rainforest vary along a gradient of disturbance due to Hurricane Maria
Authors: Colón Carrión Nicole , Troche Chad Lozada , Arnold A. Elizabeth
Published: December 2022

Increases in the frequency and intensity of hurricanes influence the structure, function, and resilience of Caribbean forests. Trees in such forests harbor diverse fungal endophytes within leaves and roots. Fungal endophytes often are important for plant health and stress responses, but how their communities are impacted by hurricanes is not well known. We measured forest disturbance in Carite State Forest in Puerto Rico ca. 16 months after the passage of Hurricane Maria, a Category 4 storm. In three sites, each comprising three plots representing a local gradient of hurricane disturbance, we evaluated soil chemistry and used culture‐free analyses to measure richness, phylogenetic diversity, and composition of endophyte communities in leaves and roots. We found that endophyte richness did not vary significantly among plant families or as a function of soil chemistry. Instead, leaf endophytes peaked in richness and decreased in phylogenetic diversity at intermediate levels of disturbance. Root endophytes did not show such variation, but both leaf‐ and root endophyte communities differed in species composition as a function of disturbance across the forest. Locations with less disturbance typically hosted distinctive assemblages of foliar endophytes, whereas more disturbed locations had more regionally homogeneous endophyte communities. Together, our results show that changes in endophyte richness and phylogenetic diversity can be detected in aboveground tissues more than a year after major storms. In turn, pervasive shifts in endophyte community composition both aboveground and belowground suggest a subtle and lasting effect of hurricanes that merits further study, potentially contributing to the promotion of spatially heterogeneous endophyte assemblages at a landscape scale in these diverse island forests.
The impact of SNP density on quantitative genetic analyses of body size traits in a wild population of Soay sheep
Authors: James Caelinn , Pemberton Josephine M. , Navarro Pau , Knott Sara
Published: December 2022

Understanding the genetic architecture underpinning quantitative traits in wild populations is pivotal to understanding the processes behind trait evolution. The ‘animal model’ is a popular method for estimating quantitative genetic parameters such as heritability and genetic correlation and involves fitting an estimate of relatedness between individuals in the study population. Genotypes at genome‐wide markers can be used to estimate relatedness; however, relatedness estimates vary with marker density, potentially affecting results. Increasing density of markers is also expected to increase the power to detect quantitative trait loci (QTL). In order to understand how the density of genetic markers affects the results of quantitative genetic analyses, we estimated heritability and performed genome‐wide association studies (GWAS) on five body size traits in an unmanaged population of Soay sheep using two different SNP densities: a dataset of 37,037 genotyped SNPs and an imputed dataset of 417,373 SNPs. Heritability estimates did not differ between the two SNP densities, but the high‐density imputed SNP dataset revealed four new SNP‐trait associations that were not found with the lower density dataset, as well as confirming all previously‐found QTL. We also demonstrated that fitting fixed and random effects in the same step as performing GWAS is a more powerful approach than pre‐correcting for covariates in a separate model.
Bottom‐up and top‐down pressures mediate competition between two generalist insects
Authors: Barnes Elizabeth E. , Murphy Shannon M.
Published: December 2022

The effects of competition can have far‐reaching consequences for individuals, populations, and communities and therefore we should strive toward a deeper understanding of competitive interactions. In some cases, dietary generalists may be predicted to experience weak competition effects because of their ability to use a wide range of host plants. However, competition between insects frequently occurs indirectly, which can hinder insects' abilities to avoid competitive interactions. Therefore, competition may be as strong among dietary generalists as among dietary specialists. Yet competition between insects that are dietary generalists is infrequently studied. We tested for evidence of competitive interactions between two common, temporally separated, generalist insects: the western tent caterpillar (Malacosoma californicum), which feeds early in the season, and the fall webworm (Hyphantria cunea), which feeds later in the season. Both species frequently use a common host plant species (chokecherry) as a preferred host at our field sites. We tested the relative strength of bottom‐up effects resulting from competitive interactions between these two generalists with laboratory‐rearing trials at the relevant time of year for each insect. We recorded three common fitness measures (development time, pupal mass, and survival) for caterpillars reared on chokecherry with no damage from either of our focal species, with tent caterpillar damage, and with fall webworm damage. To test the strength of top‐down pressures on fall webworm larval fitness and any potential interactions with bottom‐up effects, we reared larvae in the field either exposed to or protected from predators on host plants that either did or did not have tent caterpillars feeding on them earlier in the season. We found evidence of bottom‐up fitness effects on tent caterpillars and top‐down and bottom‐up fitness effects on fall webworms confirming that tent caterpillars and fall webworms compete indirectly. Tent caterpillars had lower pupal mass when reared on leaves from shrubs damaged by fall webworms. Fall webworms had lower pupal mass and longer development time when reared on leaves from shrubs damaged by tent caterpillars. In field trials, fall webworms reared on shrubs damaged by tent caterpillars had a lower survival and pupal mass. We show evidence of indirect competition in temporally separated generalists through leaf quality (bottom‐up effects) and natural enemies (top‐down effects).
Evaluation of visual functions in Iranian hypothyroid adults
Authors: Boomi Quchan Atigh Somayyeh , Sadat Shakeri Habibe , Esmaily Habibollah , Darvishi Azam , Hamidi Aghdas , Heravian Shandiz Javad
Published: December 2022

Introduction

The aim of this study was to investigate the effects of hypothyroidism on visual functions such as visual acuity, refractive errors, colour vision, and contrast sensitivity, among hypothyroid adults.

Methods

Forty‐three patients with clinical hypothyroidism along with 43 age‐ and sex‐matched healthy individuals underwent visual examinations, including visual acuity, refractive errors, eye deviations with the cover test, colour vision with the D15 test, and contrast sensitivity with Pelli‐Robson test.

Results

It was indicated that visual acuity, refractive errors, phoria, and colour vision had no significant difference between the hypothyroid and control groups. Contrast sensitivity decreased in hypothyroid subjects as compared with controls. The mean values of binocular contrast sensitivity were 1.85 ± 0.09 log in the hypothyroid group and 1.93 ± 0.09 log in controls, which showed a statistically significant difference (p = .03).

Conclusions

Our findings illustrated a reduced contrast sensitivity in adult hypothyroidism. Since CS is related to functioning and quality of life, a comprehensive and detailed eye examination may be beneficial for hypothyroidism patients.
The Second National Workshop on Marine eDNA: A workshop to accelerate the incorporation of eDNA science into environmental management applications
Authors: Stepien Carol A. , Theroux Susanna , Weisberg Stephen B.
Published: December 2022

The Second National Workshop on Environmental DNA was held on September 12–15, 2022, at the Southern California Coastal Water Research Project (SCCWRP) in Southern California and was focused on transitioning eDNA from research to management applications. The Workshop was attended by 150 people in‐person and an additional 200 more online. Workshop attendees represented a broad cross‐section of disciplines and backgrounds, including research scientists, state, and federal agencies, and those in the environmental management sector. This diverse collection of attendees assembled with the goal of achieving cross‐sector collaboration and working together to identify the necessary next steps to move eDNA methods into the management application mainstream. The Workshop structure included a Training Day oriented towards environmental managers and those new to eDNA science, to facilitate a common ground for discussions on subsequent days. The Plenary Day focused on case studies about eDNA applications and culminated with a roundtable panel discussion with local, state, and federal agency representatives on eDNA method readiness and the road to method adoption. Among the key takeaways from the Workshop was bridging the communication gap between researchers and managers because scientists often focus on technical details and the unknowns, giving the impression that eDNA science is not yet mature, whereas managers want to hear consensus statements about readiness and a roadmap for method adoption, including standard operating procedures, lab accreditation, and unified sequence libraries. This outcome was a clear directive for many scientists in attendance that it is time to stop letting perfect be the enemy of good and to focus future efforts on method harmonization and a national strategy towards method adoption. The Workshop concluded with a working session of invited participants to identify key priorities and needs to achieve the goals highlighted in the Workshop discussions.
Dynamic Operation of a Heat Exchanger in a Thermally Integrated Photovoltaic Electrolyzer
Authors: Kemppainen Erno , Bagacki Rory , Schary Christian , Bao Fuxi , Dorbandt Iris , Janke Stefan , Emery Quiterie , Stannowski Bernd , Schlatmann Rutger , Calnan Sonya
Published: December 2022

The outdoor operation of an up‐scaled thermally photovoltaic electrolyzer (PV EC), constructed using a heat exchanger (HE) made of low‐cost materials, compared to its nonintegrated counterpart to quantify heat transfer and its effects, is studied. Thermal coupling of the PV and EC can reduce the difference between their temperatures, benefitting device performance. Such devices can produce hydrogen at rooftop installations of small‐to‐medium‐sized nonindustrial buildings. The devices are tested outdoors using automated real‐time monitoring. Under ≈880 W m−2 peak irradiance, they produced hydrogen at ≈120 and ≈110 mL min−1 rate with and without HE, respectively, corresponding to about 8.5% and 7.8% solar‐to‐hydrogen efficiencies. During about 700 h of testing, the HE is beneficial at over ≈500 W m−2 due to cyclic device operation. Under lower irradiance levels, pumping previously heated electrolyte through the HE increases the PV and reduces the electrolyte temperature, reducing the device performance. The HE increases the cumulative hydrogen production (≈800 L from both devices), so even relatively modest heat transfer rates can improve the PV EC operation. Improving the HE should further increase the benefits, but additional measures may be needed to maximize the hydrogen production.
Tuned Band Structure of I‐BiOBr/g‐C3N4 Heterostructure for Enhanced Photocatalytic Performance
Authors: Li Wenxin , Ruan Xiaowen , Wei Zhong , Lian Shuang , Cui Xiaoqiang , Wang Jiku
Published: December 2022

Semiconductor photocatalysis with the Z‐scheme mechanism is regarded as a promising approach in enhancing photocatalytic performance. A novel Z‐scheme I‐BiOBr/C3N4 heterostructure is successfully synthesized via a hydrothermal method. The as‐prepared catalyst exhibits superior photocatalytic degradation performance of various organic pollutants (tetracycline, rhodamine, and norfloxacin). Meanwhile, the optimized catalyst shows an enhanced photocatalytic hydrogen evolution rate in contrast to pristine BiOBr, I‐BiOBr, and g‐C3N4. The enhanced photocatalytic performance is ascribed to the widened visible light absorption range and efficient carriers’ transportation. The Z‐scheme mechanism is based on X‐ray photoelectron spectroscopy, active radical capture experiments, and electron spin resonance spectroscopy. This research work provides an angle of view on designing other Z‐scheme photocatalytic materials.
Effect of MP‐AzeFlu compared to monotherapy on COX‐2, PGE2, and EP2 gene expression in upper airway mucosa
Authors: Vicens‐Artes Sonia , Roca‐Ferrer Jordi , Tubita Valeria , Fuentes Mireya , Alobid Isam , Valero Antonio , Kopietz Ferdinand , Nguyen DucTung , Mullol Joaquim
Published: December 2022

MP‐AzeFlu (intranasal fluticasone and azelastine) has been widely studied and has demonstrated efficacy in Allergic rhinitis with a superior effect compared to these drugs administered individually; however, the mechanism by which MP‐AzeFlu produces this improved clinical effect has not yet been fully explained. In this study, we investigated the effect of MP‐AzeFlu and fluticasone propionate (FP) on arachidonic acid metabolism as measured by changes in regulation of cyclooxygenase (COX) isoforms, prostaglandin (PG) D2, PGE2, PGE2 receptor (EP) 2, and EP3. Expression of these key inflammation markers was assessed through an in vitro model of upper airway inflammation using fibroblasts derived from both healthy and inflamed upper airway mucosa. Both MP‐AzeFlu and FP inhibited interleukin‐1β‐induced COX‐2 messenger RNA (mRNA) and protein expression and PGE2 secretion in vitro. MP‐AzeFlu and FP both upregulated EP2 mRNA expression, though neither upregulated EP2 protein expression. This downregulation of COX‐2 and PGE2 coupled with upregulation of EP2 receptor expression reinforces the anti‐inflammatory effect of MP‐AzeFlu in upper airway inflammation.
4‐1BB and cytokines trigger human NK, γδ T, and CD8+ T cell proliferation and activation, but are not required for their effector functions
Authors: Vidard Laurent
Published: December 2022

Introduction

This study was designed to compare the costimulatory molecules and cytokines required to trigger the proliferation and activation of natural killer (NK), γδ T, and CD8+ T cells, and gain in‐depth insight into the mechanisms shifting tolerance to immunity.

Methods

K562‐derived artificial antigen‐presenting cells (aAPCs); that is, K562 forced to express CD86 and 4‐1BBL costimulatory receptors, in the presence of cytokines, were used to mimic dendritic cells (DCs) and provide signals to support the proliferation and activation of NK, γδ T, and CD8+ T cells.

Results

Three signals are required to trigger optimal proliferation in MART‐1‐specific CD8+ T cells: activation of T‐cell receptors (TCRs) by the major histocompatibility complex (MHC) I/peptide complexes (signal 1); 4‐1BB engagement (signal 2); and IL‐15 and IL‐21 receptor co‐signaling (signal 3). NK and γδ T cell proliferation also require three signals, but the precise nature of signal 1 involving cell‐to‐cell contact was not determined. Once they become effectors, only signal 1 determines the sensitivity or resistance of the target cells to cytolysis by killer lymphocytes. When freshly purified, none had effector functions, except the NK cells, which could be activated by CD16 engagement.

Conclusions

Therefore, lymphocytes committed to kill are produced as inactive precursors, and the license to kill is delivered by three signals, allowing for extensive proliferation and effector function acquisition. This data challenges the paradigm of anergy and supports the danger signal theory originally proposed by Polly Matzinger, which states that killer cells are tolerant by default, thereby protecting the mammalian body from autoimmunity.
Kinetochore‐catalyzed MCC formation: A structural perspective
Authors: Fischer Elyse S.
Published: December 2022

The spindle assembly checkpoint (SAC) is a cellular surveillance mechanism that functions to ensure accurate chromosome segregation during mitosis. Macromolecular complexes known as kinetochores, act as the interface of sister chromatid attachment to spindle microtubules. In response to unattached kinetochores, the SAC activates its effector, the mitotic checkpoint complex (MCC), which delays mitotic exit until all sister chromatid pairs have achieved successful attachment to the bipolar mitotic spindle. Formation of the MCC (composed of Mad2, BubR1, Bub3 and Cdc20) is regulated by an Mps1 kinase‐dependent phosphorylation signaling cascade which assembles and repositions components of the MCC onto a catalytic scaffold. This scaffold functions to catalyze the conversion of the HORMA‐domain protein Mad2 from an “inactive” open‐state (O‐Mad2) into an “active” closed‐Mad2 (C‐Mad2), and simultaneous Cdc20 binding. Here, our current understanding of the molecular mechanisms underlying the kinetic barrier to C‐Mad2:Cdc20 formation will be reviewed. Recent progress in elucidating the precise molecular choreography orchestrated by the catalytic scaffold to rapidly assemble the MCC will be examined, and unresolved questions will be highlighted. Ultimately, understanding how the SAC rapidly activates the checkpoint not only provides insights into how cells maintain genomic integrity during mitosis, but also provides a paradigm for how cells can utilize molecular switches, including other HORMA domain‐containing proteins, to make rapid changes to a cell's physiological state.
Three‐dimensional nanofibrous and porous scaffolds of poly(ε‐caprolactone)‐chitosan blends for musculoskeletal tissue engineering
Authors: Pereira Andreia Leal , Semitela Ângela , Girão André F. , Completo António , Marques Paula A. A. P. , Guieu Samuel , Fernandes Maria Helena V.
Published: December 2022

One of the established tissue engineering strategies relies on the fabrication of appropriate materials architectures (scaffolds) that mimic the extracellular matrix (ECM) and assist the regeneration of living tissues. Fibrous structures produced by electrospinning have been widely used as reliable ECM templates but their two‐dimensional structure restricts, in part, cell infiltration and proliferation. A recent technique called thermally‐induced self‐agglomeration (TISA) allowed to alleviate this drawback by rearranging the 2D electrospun membranes into highly functional 3D porous‐fibrous systems. Following this trend, the present research focused on preparing polycaprolactone/chitosan blends by electrospinning, to then convert them into 3D structures by TISA. By adding different amounts of chitosan, it was possible to accurately modulate the physicochemical properties of the obtained 3D nanofibrous scaffolds, leading to highly porous constructs with distinct morphologic and mechanical features. Viability and proliferation studies using adult human chondrocytes also revealed that the biocompatibility of the scaffolds was not impaired after 28 days of cell culture, highlighting their potential to be included into musculoskeletal tissue engineering applications, particularly cartilage repair.
Plasma proteome profiling of healthy subjects undergoing bed rest reveals unloading‐dependent changes linked to muscle atrophy
Authors: Murgia Marta , Brocca Lorenza , Monti Elena , Franchi Martino V. , Zwiebel Maximilian , Steigerwald Sophia , Giacomello Emiliana , Sartori Roberta , Zampieri Sandra , Capovilla Giovanni , Gasparini Mladen , Biolo Gianni , Sandri Marco , Mann Matthias , Narici Marco V.
Published: December 2022

Background

Inactivity and unloading induce skeletal muscle atrophy, loss of strength and detrimental metabolic effects. Bed rest is a model to study the impact of inactivity on the musculoskeletal system. It not only provides information for bed‐ridden patients care, but it is also a ground‐based spaceflight analogue used to mimic the challenges of long space missions for the human body. In both cases, it would be desirable to develop a panel of biomarkers to monitor muscle atrophy in a minimally invasive way at point of care to limit the onset of muscle loss in a personalized fashion.

Methods

We applied mass spectrometry‐based proteomics to measure plasma protein abundance changes in response to 10 days of bed rest in 10 young males. To validate the correlation between muscle atrophy and the significant hits emerging from our study, we analysed in parallel, with the same pipeline, a cohort of cancer patients with or without cachexia and age‐matched controls. Our analysis resulted in the quantification of over 500 proteins.

Results

Unloading affected plasma concentration of proteins of the complement cascade, lipid carriers and proteins derived from tissue leakage. Among the latter, teneurin‐4 increased 1.6‐fold in plasma at bed rest day 10 (BR10) compared with BR0 (6.E9 vs. 4.3E9, P = 0.02) and decreased to 0.6‐fold the initial abundance after 2 days of recovery at normal daily activity (R + 2, 2.7E9, P = 3.3E‐4); the extracellular matrix protein lumican was decreased to 0.7‐fold (1.2E9 vs. 8.5E8, P = 1.5E‐4) at BR10 and remained as low at R + 2. We identified six proteins distinguishing subjects developing unloading‐mediated muscle atrophy (decrease of >4% of quadriceps cross‐sectional area) from those largely maintaining their initial muscle mass. Among them, transthyretin, a thyroid hormone‐binding protein, was significantly less abundant at BR10 in the plasma of subjects with muscle atrophy compared with those with no atrophy (1.6E10 vs. 2.6E10, P = 0.001). Haptoglobin‐related protein was also significantly reduced in the serum of cancer patients with cachexia compared with that of controls.

Conclusions

Our findings highlight a combination or proteomic changes that can be explored as potential biomarkers of muscle atrophy occurring under different conditions. The panel of significant proteomic differences distinguishing atrophy‐prone and atrophy‐resistant subjects after 10 days of bed rest need to be tested in a larger cohort to validate their potential to predict inactivity‐triggered muscle loss in humans.
Pattern‐setting for improving risky decision‐making
Authors: Arfer Kodi B.
Published: December 2022

Self‐control can be defined as making choices in accordance with long‐term, rather than short‐term, patterns of behavior. Rachlin (2016) suggested a novel technique to enhance self‐control, by which individual choices carry the weight of a larger pattern of choices. This report describes a study of 169 college students who made repeated choices between two gambles. The better of the two gambles had a greater win probability but required waiting an uncertain amount of time. Some “patterned” subjects were forced to repeat their previous choices according to a schedule, while control subjects could choose freely on every trial. It was found that on free‐choice trials, the patterned subjects chose the better gamble more often than controls. There was stronger evidence for such an effect appearing immediately than for it developing gradually from a process of learning over the course of the task. An additional condition in which subjects were forced to choose the better gamble yielded inconsistent results. Overall, the results support the use of pattern‐setting as a strategy to improve decision‐making.
Governance diversity: Its impact on strategic variation and results
Authors: Samara Ihssan , Nandakumar M. K. , O'Regan Nicholas , Almoumani Hanada M.
Published: December 2022

This paper investigates the impact of four drivers of Governance diversity, namely gender, tenure, age, and educational attainment, on strategic direction and variation. It then incorporates corporate financial results as a moderating variable, testing how it impacts the links between board diversity and strategic variation. Strategic variation or change is assessed based on measuring deviation from past strategies. Our sample consists of 5011 firm‐year observations from 930 firms in the United States between 2010 and 2018. The findings indicate that the four drivers of Governance diversity show a positive relationship between the corporate board of directors and strategic variation/change. However, the strength of the effect depends on overall firm results/performance.
Integrative analysis of transcriptome and metabolome reveals probiotic effects on cecal metabolism in broilers
Authors: Wang Yanfei , Liu Xuan , Jia Hao , Zhang Ruonan , Guan Jiawei , Zhang Lihuan
Published: December 2022

BACKGROUND

Probiotics play an important role in the host and have attracted widespread attention as an alternative to antibiotics. Arbor Acres broilers were used in the present experiment and fed different doses of compound probiotics at 1, 5, and 10 g kg−1. The effects of compound probiotics on broiler growth performance and cecal transcriptome and metabolome were investigated.

RESULTS

We discovered 425 differentially expressed genes (DEGs; upregulated: 256; downregulated: 169) in the cecal transcriptome study. These DEGs were assigned to fat metabolic pathways, such as the peroxisome proliferator‐activated receptor (PPAR) signaling pathway, according to KEGG analysis. Probiotics downregulated LPL and upregulated PPARα expression in the cecum. In metabolome analysis of the cecum of cecum, we screened 86 differential metabolites and performed KEGG enrichment analysis of these metabolites. The KEGG analysis showed that these differentially expressed metabolites were annotated to nucleotide metabolism‐related pathways, such as purine metabolism. In the cecum, probiotics upregulated the content of guanine, AMP, 3′‐AMP, adenylosuccinate, deoxyguanosine, and ADP‐ribose, whereas they downregulated the content of 5‐hydroxyisourate. Comprehensive transcriptome and metabolome analysis revealed that glycolysis, gluconeogenesis, and glycerophospholipid metabolism pathways were jointly enriched in cecum of broilers fed a probiotic‐containing diet.

CONCLUSION

This study provides valuable information for studying the regulation and gene metabolism network of probiotics on cecal metabolism in broilers. © 2022 Society of Chemical Industry.
Photocurable Nitric Oxide‐Releasing Copolyester for the 3D Printing of Bioresorbable Vascular Stents
Authors: de Oliveira Matheus F. , da Silva Laura C. E. , Catori Daniele M. , Lorevice Marcos V. , Galvão Karen E. A. , Millás Ana L. G. , de Oliveira Marcelo G.
Published: December 2022

The design of bioresorbable vascular stents (BVS) capable of releasing nitric oxide (NO) at the implant site may enable BVS to mimic the antiplatelet, antiproliferative, and pro‐endothelial actions of NO, overcoming complications of BVS such as late thrombosis and restenosis. In this study, the fabrication of BVS composed of methacrylated poly(dodecanediol citrate‐co‐dodecanediol S‐nitroso‐mercaptosuccinate) (mP(DC‐co‐DMSNO)), a novel elastomeric, bioabsorbable, and photocurable copolyester, containing covalently bound S‐nitrosothiol groups in the carbon backbone of the polymer, is reported. The mP(DC‐co‐DMSNO) stents are manufactured via photoinduced 3D printing and allow deployment via a self‐expansion process from a balloon catheter. After deployment, hydration of the stents triggers the release of NO, which is maintained during the slow hydrolysis of the polymer. Real‐time NO release measurements show that by varying the copolyester composition and the strut geometry of the mP(DC‐co‐DMSNO) stents, it is possible to modulate their NO release rate in the range of 30–52 pmol min−1 cm−2. Preliminary biological assays in cell culture show that endothelial cells adhere to the surface of the stents and that NO release favors their endothelization. Thus, mP(DC‐co‐DMSNO) may emerge as a new platform for the fabrication of advanced BVS.
Existence study of semilinear fractional differential equations and inclusions for multi–term problem under Riemann–Liouville operators
Authors: Hadjadj Elhabib , Meftah Safia , Bensayah Abdallah , Tellab Brahim
Published: December 2022

In the present paper, we study the existence and uniqueness of the solution for multi–term fractional boundary value problem under Riemann–Liouville fractional operators by using Banach's fixed point theorem. Afterward, we investigate some existence results for a semilinear fractional differential inclusions multi–term problem by using some notions and properties on set‐valued maps together with classical fixed point theorems due to Leray–Schauder. The cases when the set‐valued function has convex as well as nonconvex values are considered. Finally, some examples are given to illustrate our main results.
Porphyra haitanensis Polysaccharides Attenuates Blood Lipid via Gut‐Liver Axis in Diet‐Induced High‐Fat Mesocricetus auratus through Multiple Integrated Omics
Authors: Zeng Hongliang , Chen Peilin , Wang Zhiyun , Hu Xiaoke , Zhang Yi , Zheng Baodong
Published: December 2022

Scope

Hyperlipidemia is currently a global public health problem severely affecting people's physical and mental health, as well as their quality of life.

Methods and results

The present study is aimed at revealing the mechanism of Porphyra haitanensis polysaccharide (PHP) in decreasing blood lipids by acting through gut‐liver axis in Mesocricetus auratus fed a high‐fat diet. PHP significantly prevented increases in serum total cholesterol, triglycerides and low‐density lipoprotein cholesterol, and alleviated damage to liver cells induced by a high‐fat diet M. auratus, in a dose‐dependent manner. PHP promotes proliferation of Muribaculaceae and Faecalibaculum, thereby enhancing the production of butyric acid both in the colon and liver, particularly high‐dose PHP (HPHP). Low‐dose PHP (LPHP) promotes the expression of phosphatidylcholine metabolites and fatty acid transport genes, and inhibits the expression of genes involved in fat degradation (Abhd5), adipogenesis (Me1), fatty acid synthesis (Fasn and Pnpla3), and fatty acid chain elongation (Elovl6) in the liver. However, HPHP inhibits the expression of triglyceride metabolites and promotes the expression of fatty acid transporter (CD36), fatty acid oxidation (Acacb), and peroxisome proliferator‐activated receptor gamma (PPARg) genes in the liver.

Conclusion

PHP regulates lipid metabolism through the gut microbiota, and the gut‐liver axis plays an important role in its hypolipidemic effects.