bluuebunny/crossref_metadata_2025_split huggingface dataset:
An integrated liver, hippocampus and serum metabolomics based on UPLC–Q‐TOF–MS revealed the therapeutical mechanism of Ziziphi Spinosae Semen in p‐chlorophenylalanine‐induced insomnia rats
Authors: Chu Yingxin , Zhang Yinjie , Liu Jiaxing , Du Chenhui , Yan Yan 
Published: November 2023

AbstractZiziphi Spinosae Semen (ZSS), a well‐known herbal medicine for treating insomnia, is popular in not only China but also in Europe, India and Iran. However, its underlying mechanisms remain unclear. In this work, taking the targeted organs of insomnia, the liver and hippocampus, as the objects, a combination metabolomics based on ultra‐high performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry (UPLC–Q‐TOF–MS) was established to illustrate the abnormality of metabolic characteristics of the liver, hippocampus and serum of p‐chlorophenylalanine (PCPA)‐induced insomnia rats and to demonstrate the mechanism of ZSS in treating insomnia. The results showed that ZSS could restore the brain cell morphology, decrease the degree of hepatocyte necrosis and regulate the disturbance of neurotransmitters and hormones in insomnia rats. In terms of metabolomics, a total of 33 liver metabolites, 25 hippocampal metabolites and 18 serum metabolites were finally selected as the potential biomarkers and an important pathway of phenylalanine, tyrosine and tryptophan biosynthesis was common in three tissues in PCPA rats. Meanwhile, ZSS significantly reversed the levels of 23 liver metabolites, 15 hippocampal metabolites and 5 serum metabolites. The present study demonstrates the actions of ZSS in treating insomnia by enhancing both cerebral and hepatic functions.
How emotions and green altruism explain consumer purchase intention toward circular economy products: A multi‐group analysis on willingness to be environmentally friendly
Authors: Chao Cheng‐Min , Yu Tai‐Kuei 
Published: November 2023

AbstractCircular economy products are one of the solutions that can help solve the current environmental crisis and consequently achieve environmental sustainability. The theory of planned behavior (TPB) is the most important social psychological theory to explain individual purchasing behavior. However, the theory lacks a consideration of emotions, green altruism, and other factors. In order to address the research gap, this study proposes and tests a new theoretical model that incorporates variables such as emotions, green altruism, and the willingness to be environmentally friendly (WEF) into its extended model based on the TPB framework, in order to investigate the determinants that have an effect on Taiwanese consumers' purchase intention toward circular economy products. This study also uses multi‐group analysis (MGA) to analyze the moderating effects of WEF on its new theoretical model. It collected data from 387 Taiwanese consumers and analyzed the data using partial least squares (PLS). The research results showed (1) emotions, attitudes, green altruism, and perceived behavior control have a positive effect on consumer purchase intention toward circular economy products; (2) emotions have a positive effect on attitudes, green altruism, subjective norms, and perceived behavior control; and (3) groups with different levels of WEF have significant differences on consumer purchase intention toward circular economy products, in terms of emotions, attitudes, and green altruism. The results of this study can provide a reference for manufacturers and public policy makers to understand how consumers' emotions and green altruism can affect the decision‐making process to making purchase of circular economy products.
An automated high inoculation density fed‐batch bioreactor, enabled through N‐1 perfusion, accommodates clonal diversity and doubles titers
Authors: Olin Mikayla , Wolnick Nicolas , Crittenden Hunter , Quach Anthony , Russell Brian , Hendrick Shannon , Armstrong Julia , Webster Thaddaeus , Hadley Brian , Dickson Marissa , Hodgkins Jessica , Busa Kevin , Connolly Roger , Downey Brandon 
Published: November 2023

AbstractAn important consideration for biopharmaceutical processes is the cost of goods (CoGs) of biotherapeutics manufacturing. CoGs can be reduced by dramatically increasing the productivity of the bioreactor process. In this study, we demonstrate that an intensified process which couples a perfused N‐1 seed reactor and a fully automated high inoculation density (HID) N stage reactor substantially increases the bioreactor productivity as compared to a low inoculation density (LID) control fed‐batch process. A panel of six CHOK1SV GS‐KO® CHO cell lines expressing three different monoclonal antibodies was evaluated in this intensified process, achieving an average 85% titer increase and 132% space–time yield (STY) increase was demonstrated when comparing the 12‐day HID process to a 15‐day LID control process. These productivity increases were enabled by automated nutrient feeding in both the N‐1 and N stage bioreactors using in‐line process analytical technologies (PAT) and feedback control. The N‐1 bioreactor utilized in‐line capacitance to automatically feed the bioreactor based on a capacitance‐specific perfusion rate (CapSPR). The N‐stage bioreactor utilized in‐line Raman spectroscopy to estimate real‐time concentrations of glucose, phenylalanine, and methionine, which are held to target set points using automatic feed additions. These automated feeding methodologies were shown to be generalizable across six cell lines with diverse feed requirements. We show this new process can accommodate clonal diversity and reproducibly achieve substantial titer uplifts compared to traditional cell culture processes, thereby establishing a baseline technology platform upon which further increases bioreactor productivity and CoGs reduction can be achieved.
Prediction of attributable mortality in pediatric patients with cancer admitted to the intensive care unit for suspected infection: A comprehensive evaluation of risk scores
Authors: Rubnitz Zachary , Sun Yilun , Agulnik Asya , Merritt Pamela , Allison Kim , Ferrolino Jose , Dallas Ronald , Tang Li , Wolf Joshua 
Published: November 2023

AbstractObjectiveTo evaluate the performance of existing sepsis scores for prediction of adverse outcomes in children with cancer admitted to the ICU with suspected sepsis.DesignRetrospective chart review using data available at 1, 6, 12, and 24 h after ICU admission to calculate the Pediatric Risk of Mortality 3 (PRISM‐3), Pediatric Sequential Organ Failure Assessment (pSOFA), Paediatric Logistic Organ Dysfunction 2 (PELOD‐2), and Quick Pediatric Sequential Organ Failure Assessment (qSOFA) scores.Area under the receiver operator characteristic curve (AUROC) was used to evaluate performance for prediction of attributable mortality. Sensitivity analyses included recalculation of scores using worst preceding values for each variable, excluding hematologic parameters, and prediction of alternative outcomes.SettingSt. Jude Children's Research Hospital, a pediatric comprehensive cancer center in the USA.PatientsPediatric patients (<25 years of age) receiving conventional therapy for cancer admitted to the ICU with suspected sepsis between 2013 and 2019.ResultsOf 207 included episodes of suspected sepsis, attributable mortality was 16 (7.7%) and all evaluated sepsis scores performed poorly (maximal AUROC of 0.73 for qSOFA at 1 and 24 h). Sensitivity analyses did not identify an alternative approach that significantly improved prediction.ConclusionsCurrently available sepsis scores perform poorly for prediction of attributable mortality in children with cancer who present to ICU with suspected sepsis. More research is needed to identify reliable predictors of adverse outcomes in this population.
Ningalins, Pyrrole‐Bearing Metabolites Isolated from Didemnum spp. Synthesis and MDR‐Reversion Activity in Cancer Therapy
Authors: Segura‐Quezada Luis A. , Hernández‐Velázquez Edson D. , Corrales‐Escobosa Alma R. , de León‐Solis Claudia , Solorio‐Alvarado César R. 
Published: November 2023

AbstractMulti‐Drug Resistance (MDR) is one of the most frequent problems observed in the course of cancer chemotherapy. Cells under treatment, tend to develop survival mechanisms to drug‐action thus generating drug‐resistance. One of the most important mechanism to get it is the over expression of P‐gp glycoprotein, which acts as an efflux‐pump releasing the drug outside of the cancer cell. A strategy for a succesfull treatment consists in the co‐administration of one compound that acts against P‐gp and another which acts against the cell during chemotherapy. Ningalins are pyrrole‐containing naturally occurring compounds isolated mainly from the marine tunicate Didemnum spp and also they are some of the top reversing agents in MDR treatment acting on P‐gp. Considering the relevance displayed for some of these isolated alkaloids or their core as a drug for co‐administration in cancer therapy, all the total synthesis described to date for the members of ningalins family are reviewed herein.
Inhibition of mitochondria induces apoptosis and reduces telomere length and activity in acute myeloid leukemia stem cells
Authors: Valipour Behnaz , Davari Sahar , Farahzadi Raheleh , Pourrasol Shahram , Mehran Niloofar , Dizaji Asl Khadijeh , Altaha Seyed Mansour , Hojjati Zahra , Nozad Charoudeh Hojjatollah 
Published: November 2023

AbstractAcute myeloid leukemia (AML) is a highly lethal hematological malignancy in adults and children. Abnormal proliferation of leukemia stem cells (LSC) with CD34+ and CD38− phenotypes are the main clinical features of AML. Patients with AML face drug resistance and treatment failure due to a default in stem and progenitor cells. Therefore, defining LSC properties is necessary for targeting leukemia‐initiating cells. Mitochondrial mass and activity increase in AML initiating cells compared with normal stem cells. This idea has offered the inhibition of the mitochondrial translation machinery to reduce the number of leukemia‐initiating cells in patients with AML Tigecycline is an FDA‐approved microbial antibiotic that inhibits oxidative phosphorylation in mitochondria, resulting in the suppression of leukemia cell proliferation with little toxicity to normal cells. Thus, the present study was conducted to evaluate whether LSC is influenced by mitochondrial inhibition. We measured the IC50 of tigecycline in KG‐1a AML cell lines. KG‐1a AML cell lines were separated into CD34+ and CD34− cells by MACS. In the following, these cells were treated with 20 µM (IC50) tigecycline. The expression of Annexin/PI, Caspase 3, apoptotic genes (BCL2, BCLX, BAX, BAD, and P53) and proteins (P53, BAX, BCL2 and Caspase 9) was evaluated in CD34+, CD34− and KG‐1a AML cells. In addition, the telomere length and expression of hTERT were evaluated in this study. The results indicated that BCl2 (gene and protein) and BCLX gene dramatically decreased. In addition, BAD, BAX, and P53 gene and protein expression significantly increased in CD34+ AML cells compared to CD34− AML cells. The results also suggested that tigecycline induced intrinsic (Cleaved‐caspase 9/Pro‐Caspase 9 ratio) and p53‐mediated apoptosis. Furthermore, hTERT gene expression and telomere length decreased in the tigecycline‐treated groups. Taken together, our findings indicate that inhibition of mitochondrial activity with tigecycline can induce apoptosis in cancer stem cells and can be used as a novel method for cancer therapy.
Diverting Ni‐Catalyzed Direct Benzylic C−H Hydroxylation towards Trifluoroethoxylation
Authors: Bushmin Dmitry S. , Samsonenko Denis G. , Talsi Evgenii P. , Lyakin Oleg Y. , Bryliakov Konstantin P. 
Published: November 2023

AbstractNickel(II) complexes with the simple N4 donor aminopyridine ligands BPMEN (N,N′‐dimethyl‐N,N′‐bis(2‐pyridylmethyl)‐1,2‐diaminoethane) and TPA (tris(2‐pyridylmethyl)amine) have been demonstrated to perform as efficient catalysts for the regioselective oxygenation of benzylic C−H groups with m‐chloroperoxybenzoic acid under mild conditions (at 20 °C), typically ensuring >90 % substrate conversions within 1 h at 1 mol % catalyst loadings. Unprecedentedly, replacing the commonly used mixed reaction solvent CH3CN/CH2Cl2 with 2,2,2‐trifluoroethanol diverts the selectivity of the above Ni‐based catalyst systems from hydroxylation/ketonization to trifluoroalkoxylation, with the formation of 1‐phenylalkyl 2,2,2‐trifluoroethyl ethers. The use of 2,2,2‐trifluoroethanol ensures high substrate conversion values (up to 97 %), as well as high selectivity for the ether formation (up to 92 %). Preliminary discussion of the reaction mechanism is given based on the catalytic and literature data.
Barbier Polymerization‐Induced Emission towards Fully Substituted Polyethylene Analogues with Non‐Traditional Intrinsic Luminescence
Authors: Xiao Hang , Shi Quan‐Xi , Li Qian , Cai Hua‐Wen , Sun Xiao‐Li , Wan Wen‐Ming , Qian Qing‐Rong 
Published: November 2023

AbstractThe properties of polyethylene are highly dependent on the variety and quantity of substitutions. Generally, polyethylene can only be fully substituted with fluorine atoms, mainly e. g., polytetrafluoroethylene and nafion, because atomic radius of fluorine atom is small enough. The preparation of fully substituted polyethylene analogues (FSPEA) and their non‐traditional intrinsic luminescence (NTIL) are attractive, especially for substitutions with relatively larger atomic radii than a fluorine atom. Here, Barbier polymerization‐induced emission (PIE) is demonstrated as a universal method for the molecular design of NTIL type FSPEAs with intriguing aggregation‐induced emission (AIE) behaviors. Through Barbier polymerization of diphenyldichloromethane and different peroxyesters in the presence of Mg in one pot, a series of FSPEAs, including polytriphenylethanol (PTPE), polydiphenylfurylethanol (PDPFE), polydiphenylthiophenylethanol (PDPTE) and polydiphenylnaphthylethanol (PDPNE) have been successfully prepared. Further potential applications for explosive detection, artificial light‐harvesting system and white phosphor‐converted light‐emitting diode are investigated. Therefore, this work opens up a new approach for the molecular design of FSPEA with non‐conjugated luminescence, which may cause inspirations to different research fields like polyolefin and luminescent materials.
Evaluation of sulfate metabolites as markers of topical testosterone administration in Caucasian and Asian populations
Authors: Bressan Claudia , Alechaga Élida , Monfort Nuria , Ventura Rosa 
Published: November 2023

AbstractSulfate metabolites of endogenous anabolic androgenic steroids (EAAS) have been shown to prolong the detection times compared with the conventional urinary markers of the steroid profile for oral and intramuscular administrations of testosterone (T). In this work, the sensitivity of sulfate EAAS markers for the detection of T gel administration has been evaluated in six Caucasian and six Asian male volunteers. Fourteen sulfate metabolites were measured in basal and post‐administration samples after multiple doses of T gel (100 mg/day, three consecutive days), and the detection times based on individual thresholds for each volunteer were evaluated. Sulfate concentrations did not show adequate sensitivity, but the results of sulfate ratios were much more promising. Androsterone sulfate/testosterone sulfate (A‐S/T‐S), epiandrosterone sulfate/epitestosterone sulfate (epiA‐S/E‐S), epiA‐S/T‐S, and etiocholanolone sulfate/epitestosterone sulfate (Etio‐S/E‐S) provided the most consistent detectability for all volunteers and populations, with detection times ranging from 60 to 96 h since the first dose. Additional ratios improved detectability to up to 7 days, but only in particular volunteers. In general, sensitivity was similar to or better than the conventional testosterone/epitestosterone ratio (T/E) of the steroid profile, which further reinforces the conclusion that sulfate EAAS metabolites can be a good complement for the current steroid profile.
Eat or be eaten: Implications of potential exploitative competition between wolves and humans across predator‐savvy and predator‐naive deer populations
Authors: Candler Ellen M. , Chakrabarti Stotra , Severud William J. , Bump Joseph K. 
Published: November 2023

AbstractRecolonization of predators to their former ranges is becoming increasingly prevalent. Such recolonization places predators among their prey once again; the latter having lived without predation (from such predators) for a considerable time. This renewed coexistence creates opportunities to explore predation ecology at both fundamental and applied levels. We used a paired experimental design to investigate white‐tailed deer risk allocation in the Upper and Lower Peninsulas (UP and LP) in Michigan, USA. Wolves are functionally absent in the LP, while deer in the UP coexist with a re‐established wolf population. We treated 15 sites each in UP and LP with wolf olfactory cues and observed deer vigilance, activity, and visitation rates at the interface of habitat covariates using remote cameras. Such a paired design across wolf versus no‐wolf areas allowed us to examine indirect predation effects while accounting for confounding parameters such as the presence of other predators and human activity. While wolf urine had no effect across most metrics in both UP and LP, we observed differences in deer activity in areas with versus without wolves. Sites treated with wolf urine in the UP showed a reduction in crepuscular deer activity, compared to control/novel‐scent treated sites. Furthermore, we observed a strong positive effect of vegetation cover on deer vigilance in these sites. This indicates that simulated predator cues likely affect deer vigilance more acutely in denser habitats, which presumably facilitates predation success. Such responses were however absent among deer in the LP that are presumably naïve toward wolf predation. Where human and non‐human predators hunt shared prey, such as in Michigan, predators may constrain human hunting success by increasing deer vigilance. Hunters may avoid such exploitative competition by choosing hunting/bait sites located in open areas. Our results pertaining to fundamental predation ecology have strong applied implications that can promote human–predator coexistence.
Assessing the diet and seed dispersal ability of non‐native sambar deer (Rusa unicolor) in native ecosystems of south‐eastern Australia
Authors: Quin Matthew J. , Morgan John W. , Murphy Nicholas P. 
Published: November 2023

AbstractUnderstanding the influence of non‐native herbivores on ecosystems by means of dietary foraging and seed dispersal is important for understanding how non‐native species can alter an invaded landscape, yet requires multiple methodologies. In south‐eastern Australia, introduced sambar deer (Rusa unicolor) are rapidly expanding in range and placing native ecosystems at risk through browsing and as vectors for seed dispersal. We simultaneously investigated sambar deer dietary composition and seed dispersal using DNA sequencing and germination trials, from faecal pellets collected in alpine and wet forest ecosystems. This allowed us to contrast the dietary impacts of introduced sambar deer in different environments, and to explore the potential for habitat‐specific variation in diet. DNA sequencing of the trnL, ITS2 and rbcL gene regions revealed a diverse plant species dietary composition comprising 1003 operational taxonomic units (OTUs). Sambar deer exhibited intermediate feeder behaviours dominated by forbs in alpine and shrubs in wet forest ecosystems. A large proportion of plant OTUs were considered likely to be native, however, the proportion of exotic species in the diet in both ecosystems was greater than would be expected based on the proportion of exotic species in each of the two landscapes. Seed germination trials indicated that sambar deer can disperse a substantial number of native and exotic species in both alpine and wet forest ecosystems. In alpine ecosystems, an individual sambar deer was estimated to disperse on average 816 (±193) seeds per day during the study period, of which 652 (±176) were exotic. Synthesis and applications. Our results suggest that native plant species comprise the majority of sambar deer diets in Australian ecosystems and that the introduced species is dispersing both native and exotic plant species via endozoochory. However, exotic species seedling germination numbers were significantly higher in alpine ecosystems, and given the large daily movements of sambar deer, represents a significant vector for the spread of exotic plant species. Management of native plant species and vegetation communities of conservation significance, or at risk to sambar deer browsing is of high priority, through either the removal of sambar deer or implementation of exclusion‐based methods.
Spatial scaling in bed‐site selection by roe deer fawns: Implications for mitigating neonatal mortality during mowing
Authors: Baur Sophie , Kauffert Johanna , Hewison A. J. Mark , Reinermann Sophie , König Andreas , Menzel Annette , Peters Wibke 
Published: November 2023

AbstractWhen habitat use by field‐dwelling animals coincides in space and time with agricultural practices such as spring mowing of meadows, human‐wildlife conflicts can have deadly consequences for wildlife. Roe deer (Capreolus capreolus L.) fawns are particularly vulnerable because they hide in meadows during the rearing phase. Thus, a better understanding of the habitat drivers of bed‐site selection is critical to mitigating fawn mortality during mowing. Here, we tease apart the among‐field (presumably driven by maternal behaviour) and within‐field (driven by fawn behaviour) components of bed‐site selection of roe deer during the spring mowing season. We collected over 600 fawn bed sites across an environmentally diverse study region. At the among‐field scale, we implemented a used versus available design and employed a two‐part statistical model (GAMLSS) to identify habitat characteristics that were linked to either fawn presence (vs. absence) or abundance on a given field. At the within‐field scale, we compared habitat characteristics at fawn bed‐sites with paired random sites using a conditional logistic regression model. At the among‐field scale, fawns were more likely to be present, and were more abundant, in fields within more diverse, rural landscapes, with nearby woodland. Surprisingly, fawns were more often present in fields that were near roads and had lower vegetation productivity. At the within‐field scale, however, fawns preferred bed‐sites which were further from both roads and woodland, but that provided the best visual cover to minimise predation risk. Our findings revealed substantial and novel scale‐dependent differences in the drivers of habitat selection of mothers and fawns, which, together, determine the precise locations of bed‐sites between and within meadows. These results may aid wildlife managers in identifying areas where there is a high probability of encountering a roe deer fawn so as to initiate targeted searches prior to mowing and, ultimately, mitigate fawn mowing mortality.