bluuebunny/crossref_metadata_2025 huggingface dataset:
Self‐Doping Naphthalene Diimide Conjugated Polymers for Flexible Unipolar n‐Type OTFTs
Authors: Chen Pinyu , Wang Dongyang , Luo Liang , Meng Jinqiu , Zhou Zhaoqiong , Dai Xiaojuan , Zou Ye , Tan Luxi , Shao Xiangfeng , Di Chong‐an , Jia Chunyang , Zhang Hao‐Li , Liu Zitong
Published: February 2023

The development of high‐performance organic thin‐film transistor (OTFT) materials is vital for flexible electronics. Numerous OTFTs are so far reported but obtaining high‐performance and reliable OTFTs simultaneously for flexible electronics is still challenging. Herein, it is reported that self‐doping in conjugated polymer enables high unipolar n‐type charge mobility in flexible OTFTs, as well as good operational/ambient stability and bending resistance. New naphthalene diimide (NDI)‐conjugated polymers PNDI2T‐NM17 and PNDI2T‐NM50 with different contents of self‐doping groups on their side chains are designed and synthesized. The effects of self‐doping on the electronic properties of resulting flexible OTFTs are investigated. The results reveal that the flexible OTFTs based on self‐doped PNDI2T‐NM17 exhibit unipolar n‐type charge‐carrier properties and good operational/ambient stability thanks to the appropriate doping level and intermolecular interactions. The charge mobility and on/off ratio are fourfold and four orders of magnitude higher than those of undoped model polymer, respectively. Overall, the proposed self‐doping strategy is useful for rationally designing OTFT materials with high semiconducting performance and reliability.
DTRMWXHS‐12, a novel Bruton tyrosine kinase inhibitor, in combination with everolimus and pomalidomide in patients with relapsed/refractory lymphomas: An open‐label, multicenter, phase 1a/1b study
Authors: Huntington Scott F. , Schuster Stephen J. , Ding Wei , Koehler Amber B. , Brander Danielle M. , Rosenthal Allison C. , Leis Jose F. , Tun Han W. , Moustafa Muhamad Alhaj , Iqbal Madiha , He Wei , Kearney Albert S. , McKinlay Timothy P. , Gui Min , Mato Anthony R.
Published: February 2023

Preclinical studies have shown augmented activity when combining Bruton tyrosine kinase inhibitors (BTKi) with inhibitors of mammalian target of rapamycin (mTOR) and immunomodulatory agents (IMiD). We conducted a phase 1, open‐label study at five centers in USA to evaluate the safety of triplet BTKi/mTOR/IMiD therapy. Eligible patients were adults aged 18 years or older with relapsed/refractory CLL, B cell NHL, or Hodgkin lymphoma. Our dose escalation study used an accelerated titration design and moved sequentially from single agent BTKi (DTRMWXHS‐12), doublet (DTRMWXHS‐12 + everolimus), and then to triplet therapy (DTRMWXHS‐12 + everolimus + pomalidomide). All drugs were dosed once daily on days 1–21 of each 28‐day cycle. The primary goal was to establish the recommended phase 2 dose of the triplet combination. Between September 27, 2016, and July 24, 2019, a total of 32 patients with a median age of 70 years (range 46 to 94 years) were enrolled. No MTD was identified for monotherapy and the doublet combination. The MTD for the triplet combination was determined to be DTRMWXHS‐12 200 mg + everolimus 5 mg + pomalidomide 2 mg. Responses across all studied cohorts were seen in 13 of 32 (41.9%). Combining DTRMWXHS‐12 with everolimus and pomalidomide is tolerable and shows clinical activity. Additional trials could confirm benefit of this all‐oral combination therapy for relapsed/refractory lymphomas.
Development of adiposity among Ju/’Hoansi Hunter‐Gatherers
Authors: Campbell Benjamin C. , Hackman Joe V. , Kramer Karen L.
Published: February 2023

Objectives

To characterize the development of childhood adiposity among the Ju’/Hoansi, a well‐known hunter‐gather group, to compare our results to U.S. references and to recently published results from Savanna Pume’ foragers of Venezuela, with the goal of expanding our understanding of adipose development among human hunter‐gatherers.

Methods

Triceps, subscapular, and abdominal skinfolds, along with height and weight from ~120 Ju’/Hoansi girls and ~103 boys, ages 0 to 24 years, collected in 1967–1969 were analyzed using best‐fit polynomial models and penalized spines to characterize age‐specific patterns of adiposity and their relationship to changes in height and weight.

Results

Overall, Ju/’Hoansi boys and girls exhibit small skinfolds with a decline in adiposity from 3 to 10 years, with no consistent differences among the three skinfolds. Increases in adiposity during adolescence precede peak height and weight velocities. Adiposity declines during young adulthood for girls and remains largely constant for boys.

Discussion

Compared to U.S. standards, the Ju/’Hoansi show a strikingly different pattern of adipose development, including the lack of an adiposity rebound at the onset of middle childhood, and clear increases in adiposity only at adolescence. These findings are consistent with published results from the Savanna Pumé hunter‐gatherers of Venezuela, a group with a very different selective history, suggesting that the adiposity rebound does not characterize hunter‐gathering populations more generally. Similar analyses in other subsistence populations are called for to confirm our results, and help distinguish the impact of specific environmental and dietary factors on adipose development.
Obesity impacts the expression of Alzheimer's disease–related genes: The Framingham Heart Study
Authors: Charisis Sokratis , Lin Honghuang , Ray Roshni , Joehanes Roby , Beiser Alexa S , Levy Daniel , Seshadri Sudha , Sargurupremraj Muralidharan , Satizabal Claudia L
Published: February 2023

INTRODUCTION

We investigated associations of obesity with the expression of Alzheimer's disease (AD)–related genes in a large community‐based cohort.

METHODS

The sample consisted of 5619 participants from the Framingham Heart Study. Obesity metrics included body mass index (BMI) and waist‐to‐hip ratio (WHR). Gene expression was measured for a set of 74 AD‐related genes, derived by integrating genome‐wide association study results with functional genomics data.

RESULTS

Obesity metrics were associated with the expression of 21 AD‐related genes. The strongest associations were observed with CLU, CD2AP, KLC3, and FCER1G. Unique associations were noted with TSPAN14, SLC24A4 for BMI, and ZSCAN21, BCKDK for WHR. After adjustment for cardiovascular risk factors, 13 associations remained significant for BMI and 8 for WHR. Dichotomous obesity metrics exhibited unique associations with EPHX2 for BMI, and with TSPAN14 for WHR.

DISCUSSION

Obesity was associated with AD‐related gene expression; these findings shed light on the molecular pathways linking obesity to AD.
Probing the Przybylski star for deuterium
Authors: Andrievsky Sergei M. , Kovtyukh Valery V.
Published: February 2023

The Przybylski star spectrum has been studied in order to search for deuterium lines. Since this star is extremely enriched in the s‐process elements, which are the product of interaction between free neutrons and seed nuclei, we might as well expect to detect deuterium in this star. However, no visible spectroscopic manifestation of deuterium has been detected. Perhaps, the reason of this result is the convective “destruction” of this isotope.
A novel “spectral‐ratio model fitting” to resolve complicated X‐ray spectral variations in active galactic nuclei
Authors: Midooka Takuya , Mizumoto Misaki , Ebisawa Ken
Published: February 2023

Radiation‐magnetohydrodynamic simulation of the active galactic nuclei predicts the presence of the strong accretion disk wind, which gets unstable far from the central region and turns into gas clumps. These inner wind and outer clumps may be actually observed as the ultrafast outflows (UFOs) and the clumpy absorbers, respectively. We call this picture as the “hot inner and clumpy outer wind model.” Observationally, it is challenging to place constraints on the origin of the UFOs and clumpy absorbers due to complicated spectral variations. We developed a novel method, “spectral‐ratio model fitting,” to resolve parameter degeneracy of the clumpy absorbers and other spectral components. In this method, the parameters of the absorber in the line of sight are estimated from the ratio of the partially absorbed spectrum to the non‐absorbed one. We applied this method to the narrow‐line Seyfert 1 galaxy IRAS 13224–3809 observed byXMM‐Newtonin 2016 for 1.5 Ms, where the source showed extreme spectral variability and complex absorption features. As a result, we found that the soft spectral variation is mostly explained by a change in the covering fraction of the mildly‐ionized clumpy absorbers, and that these absorbers are outflowing with such a high velocity that is comparable to that of the UFO (∼0.2–0.3 c).
Preparation of nanopillar array electrode of iridium oxide for high performance of pH sensor and its real‐time sweat monitoring
Authors: Yoon Eun Seop , Park Hong Jun , Kil Min Sik , Kim Jueun , Lee Kyoung G. , Choi Bong Gill
Published: February 2023

A highly sensitive potentiometric pH sensor was developed based on nanopillar array electrodes of iridium oxide. The as‐prepared pH sensor exhibited a high pH sensitivity (69.43 mV/pH), fast response time (8.1 s), and good durability (0.76 mV/h). The sensing performance of the pH sensor was maintained under mechanical bending and even after 1000 repetitive bending/releasing cycles. As a proof‐of‐concept, a wearable headband sensor was fabricated by integrating the pH sensor with a wireless electronic module based on a printed circuit board. The on‐body test indicated that the wearable pH sensor provides reliable and stable data in the real‐time monitoring of pH changes in human sweat during stationary indoor cycling. The pH sensors based on nanopillar array electrodes of iridium oxide have great potential in many portable or wearable applications in healthcare systems, non‐invasive diagnostics, environmental analysis, and food sensors.
A retrospective analysis of the prognosis of Japanese patients with sarcoma brain metastasis
Authors: Toda Yu , Kobayashi Eisuke , Kubota Daisuke , Miyakita Yasuji , Narita Yoshitaka , Kawai Akira
Published: February 2023

Background

Bone and soft tissue sarcomas are rare tumors and extremely rarely metastasize to the brain. Previous studies have examined the characteristics and poor prognostic factors in cases of sarcoma brain metastasis (BM). Due to the rarity of cases of BM from sarcoma, limited data exist concerning the prognostic factors and treatment strategies.

Methods

A retrospective single‐center study was performed on sarcoma patients with BM. The clinicopathological characteristics and treatment options for BM of sarcoma were investigated to identify predictive prognostic factors.

Results

Between 2006 and 2021, 32 patients treated for newly diagnosed BM at our hospital were retrieved among 3133 bone and soft tissue sarcoma patients via our database. The most common symptom was headache (34%), and the most common histological subtypes were alveolar soft part sarcoma (ASPS) and undifferentiated pleomorphic sarcoma (25%). Non‐ASPS (p = 0.022), presence of lung metastasis (p = 0.046), a short duration between initial metastasis, and the diagnosis of brain metastasis (p = 0.020), and the absence of stereotactic radiosurgery for BM (p = 0.0094) were significantly correlated with a poor prognosis.

Conclusions

In conclusion, the prognosis of patients with brain metastases of sarcomas is still dismal, but it is necessary to be aware of the factors associated with a relatively favorable prognosis and to select treatment options appropriately.
Essential Oil of Cestrum diurnum L.: GC/MS Analysis, in Vitro and in Silico Anti‐HCoV‐229E Effects and Inhibitory Activity against LPS‐Induced Inflammation
Authors: Bahgat Dina M. , Gad Haidy A. , Al‐Sayed Eman , Mahmoud Sara H. , Mostafa Ahmed , Mahfouz Nadia M. , Eldahshan Omayma A. , Nasser B. Singab Abdel
Published: February 2023

Cestrum diurnum L. (Solanaceae) is a fragrant ornamental tree cultivated in different parts around the world. In this study, the essential oil (EO) of the aerial parts was extracted by hydrodistillation (HD), steam distillation (SD) and microwave‐assisted hydro‐distillation (MAHD). GC/MS analysis of the three EOs revealed that phytol represents the major component in SD‐EO and MAHD‐EO (40.84 and 40.04 %, respectively); while in HD‐EO it only represented 15.36 %. The SD‐EO showed a strong antiviral activity against HCoV‐229E with IC50 of 10.93 μg/mL, whereas, MAHD‐EO and HD‐EO showed a moderate activity with IC50 values of 119.9 and 148.2 μg/mL, respectively. The molecular docking of EO major components: phytol, octadecyl acetate and tricosane showed a strong binding to coronavirus 3‐CL (pro). Moreover, the three EOs (50 μg/mL) decreased the levels of NO, IL‐6 and TNF‐α and suppressed IL‐6 and TNF‐α gene expression in LPS‐induced inflammation model in RAW264.7 macrophage cell lines.
Design and Synthesis of (3‐Phenylisoxazol‐5‐yl)methanimine Derivatives as Hepatitis B Virus Inhibitors
Authors: Liang Zhengcheng , Tan Yongqing , Huang Yunhou , Liang Taoyuan , Wei Wanxing , Wang Mian , Shi Kaichuang
Published: February 2023

Series of (3‐phenylisoxazol‐5‐yl)methanimine derivatives were synthesized, and evaluated for anti‐hepatitis B virus (HBV) activity in vitro. Half of them more effectively inhibited HBsAg than 3TC, and more favor to inhibit secretion of HBeAg than to HBsAg. Part of the compounds with significant inhibition on HBeAg were also effectively inhibit replication of HBV DNA. Compound (E)‐3‐(4‐fluorophenyl)‐5‐((2‐phenylhydrazineylidene)methyl)isoxazole inhibited excellently HBeAg with IC50 in 0.65 μM (3TC(Lamivudine) in 189.90 μM), inhibited HBV DNA in 20.52 μM (3TC in 26.23 μM). Structures of compounds were determined by NMR and HRMS methods, and chlorination on phenyl ring of phenylisoxazol‐5‐yl was confirmed by X‐ray diffraction analysis, and the structure–activity relationships (SARs) of the derivatives was discussed. This work provided a new class of potent non‐nucleoside anti‐HBV agents.
Supramolecular Interactions‐Assisted Polymorphism and Unique Mechanofluorochromism in 9,10‐Bis((E)‐4‐(trifluoromethyl)styryl)anthracene
Authors: Suresh Sumi K. , Raju Princy Deni , Krishnan Aravind , Ramachandran Lekshmi M. , Suneesh Chettiyam Veettil
Published: February 2023

A fluorinated distyrylanthracene (DSA) derivative, 9, 10‐bis((E)‐4‐(trifluoromethyl)styryl)anthracene abbreviated as4FDSAwith two crystalline polymorphs (4FDSA‐G(green emission) and4FDSA‐O(orange emission)), showing remarkable aggregation‐induced enhanced emission and mechanofluorochromic characteristics, was developed. One of the polymorphs in its crystalline arrangement exhibits the hardly seen F…F interactions. It questions the conventional belief of the non‐polarisable nature of fluorine atoms in forming the halogen bond. The twisted molecular conformation facilitated by the various supramolecular interactions resulted in the formation of another intensely emissive bluer nanocrystal (4FDSA‐NC) at aggregating conditions. Even though, the both polymorphs show distinct tricolor luminescence switching on the action of mechanical force, fumigation of ground crystals with solvent vapor resulted in the formation of a more thermodynamically favorable4FDSA‐NCform. The work demonstrates the effect of supramolecular interactions assisted conformational changes in tuning the unique mechanofluorochromic characteristics of the polymorphic crystals.
Progress in Predicting Ionic Cocrystal Formation: The Case of Ammonium Nitrate
Authors: Bennett Andrew J. , Matzger Adam J.
Published: February 2023

In contrast to the mature predictive frameworks applied to neutral cocrystals, ionic cocrystals, those including an ion pair, are difficult to design. Furthermore, they are generally excluded categorically from studies which correlate specific molecular properties to cocrystal formation, leaving the prospective ionic cocrystal engineer with few clear avenues to success. Herein ammonium nitrate, an energetic oxidizing salt, is targeted for cocrystallization in a potential coformer group selected based on likely interactions with the nitrate ion as revealed in the Cambridge Structural Database; six novel ionic cocrystals were discovered. Molecular descriptors previously identified as being related to neutral cocrystal formation were examined across the screening group but showed no relationship with ionic cocrystal formation. High packing coefficient is shown to be a constant among the successful coformers in the set and is utilized to directly target two more successful coformers, bypassing the need for a large screening group.
Mo Cluster Support on C2N as a Highly‐efficient Catalyst for Electrocatalytic Nitrogen Reduction Reaction
Authors: Chen Yuke , Zhao Ming , Wang Zhili , Jiang Qing
Published: February 2023

The conversion of nitrogen to ammonia by electrocatalysis under mild conditions is a valuable research direction, which has been a sustainable alternative to the traditional Haber‐Bosch method. However, the conversion remains a huge challenge in chemistry at this time. In this work, the density functional theory (DFT) is used to study the electrocatalytic nitrogen reduction reaction (NRR) performance of Mo12 clusters on C2N monolayer (Mo12−C2N). It is found that the diversity of active sites of the Mo12 cluster provides favorable reaction paths for intermediates, which reduces reaction barrier of NRR. Mo12−C2N shows excellent NRR performances with limiting potentials of −0.26 V vs. reversible hydrogen electrode (RHE).
How Different are the Diamagnetic and Paramagnetic Contributions to Off‐Nucleus Shielding in Aromatic and Antiaromatic Rings?
Authors: Karadakov Peter B.
Published: February 2023

The spatial variations in the diamagnetic and paramagnetic contributions to the off‐nucleus isotropic shielding,
, and to the zz component of the off‐nucleus shielding tensor,
, around benzene (C6H6) and cyclobutadiene (C4H4) are investigated using complete‐active‐space self‐consistent field wavefunctions. Despite the substantial differences between
and
around the aromatic C6H6 and the antiaromatic C4H4, the diamagnetic and paramagnetic contributions to these quantities,
and
, and
and
, are found to behave similarly in the two molecules, shielding and deshielding, respectively, each ring and its surroundings. The different signs of the most popular aromaticity criterion, the nucleus‐independent chemical shift (NICS), in C6H6 and C4H4 are shown to follow from a change in the balance between the respective diamagnetic and paramagnetic contributions. Thus, the different NICS values for antiaromatic and antiaromatic molecules cannot be attributed to differences in the ease of access to excited states only; differences in the electron density, which determines the overall bonding picture, also play an important role.
Residual Dipolar Coupling Based Conformational Analysis Allows the Configurational Assessment of Steroids with up to Eight Stereocenters
Authors: Venturi Luca , Bua Emanuela , Caputo Giulia , Mileo Valentina
Published: February 2023

Residual dipolar couplings (RDCs) induced by anisotropic media have been proved as a powerful tool for the structure elucidation of organic molecules in solution in nuclear magnetic resonance (NMR) based analysis. The value of dipolar couplings to solve complex conformational and configurational problems represents indeed an appealing analytical tool for the pharmaceutical industry particularly focusing on the stereochemistry characterization of NCEs since the early phase of the drug development process. In our work, RDCs were used for the conformational and configurational study of synthetic steroids with multiple stereocenters – prednisone and beclomethasone dipropionate (BDP) –. For both molecules the correct relative configuration was identified among all the possible diastereoisomers (32 and 128 respectively) arising from the compounds stereogenic carbons. Only for prednisone the use of additional experimental data (i. e. rOes) was necessary to resolve the right stereochemical structure.
Validity and reliability of the Polish Maladaptive Daydreaming Scale (PMDS‐16) and its short form (PMDS‐5)
Authors: Pietkiewicz Igor Jacob , Hełka Anna M. , Barłóg Mateusz , Tomalski Radosław
Published: February 2023

Maladaptive daydreaming (MD) defines excessive use of fantasy, which replaces human interaction and/or interferes with academic, interpersonal, or vocational functioning. This study tests psychometric properties of the Polish version of the Maladaptive Daydreaming Scale (PMDS‐16) and a short 5‐item version derived from it (PMDS‐5), and their capacity to screen for MD. The relationship between MD, resilience and the quality of life was also explored. Validity and reliability were examined in a sample of 491 participants in nonclinical (n = 315) and mixed‐clinical (n = 176) groups who completed the tests online. The exploratory factor analysis with principal component analysis method of parameter estimation without rotation confirmed a one‐factor solution of both instruments. Reliability of both versions was corroborated by Cronbach's alpha coefficient (PMDS‐16: >.941; PMDS‐5: >.931). The cutoff score maximizing sensitivity and specificity for MD was 42 in both instruments, but the short version had better discriminating properties. People who identified themselves as maladaptive daydreamers in comparison to those who did not had significantly higher scores in both instruments. Maladaptive daydreamers also had lower quality of life in the psychological and social relationships domains and poorer resilience. Both PMDS‐16 and PMDS‐5 proved to have satisfactory psychometric properties. They have similar psychometric properties, although PMDS‐5 has better discriminating power and can be used effectively for the screening of MD.
Concentration‐Dependent Inhibition of Mesophilic PETases on Poly(ethylene terephthalate) Can Be Eliminated by Enzyme Engineering
Authors: Avilan Luisana , Lichtenstein Bruce R. , König Gerhard , Zahn Michael , Allen Mark D. , Oliveira Liliana , Clark Matilda , Bemmer Victoria , Graham Rosie , Austin Harry P. , Dominick Graham , Johnson Christopher W. , Beckham Gregg T. , McGeehan John E. , Pickford Andrew R.
Published: February 2023

Enzyme‐based depolymerization is a viable approach for recycling of poly(ethylene terephthalate) (PET). PETase from Ideonella sakaiensis (IsPETase) is capable of PET hydrolysis under mild conditions but suffers from concentration‐dependent inhibition. In this study, this inhibition is found to be dependent on incubation time, the solution conditions, and PET surface area. Furthermore, this inhibition is evident in other mesophilic PET‐degrading enzymes to varying degrees, independent of the level of PET depolymerization activity. The inhibition has no clear structural basis, but moderately thermostable IsPETase variants exhibit reduced inhibition, and the property is completely absent in the highly thermostable HotPETase, previously engineered by directed evolution, which simulations suggest results from reduced flexibility around the active site. This work highlights a limitation in applying natural mesophilic hydrolases for PET hydrolysis and reveals an unexpected positive outcome of engineering these enzymes for enhanced thermostability.
Urine‐based liquid biopsy in bladder cancer: Opportunities and challenges
Authors: Wang Gang , Jin Wan , Xu Zilin , Ju Lingao , Shan Danni , Li Shenjuan , Yu Mengxue , Cao Xinyue , Liu Nan , Qian Kaiyu , Zhang Yi , Xiao Yu , Wang Xinghuan
Published: February 2023

Bladder cancer (BLCA) is a most common urological tumours with high rate of recurrence, which needs long‐term of follow‐up. To date, diagnosis and surveillance of BLCA still rely on cystoscopy, an invasive and expensive method that increases the difficulty for routine follow‐up. Therefore, exploring new biomarkers or tests is an effective way to improve the current clinical management of BLCA. Recent years, liquid biopsy has received increasing attention, especially for its great potential for clinical application in the non‐invasive detection of tumours. In addition, liquid biopsy involves a wide range of biomarkers, including DNA, RNA, proteins, extracellular vesicles and metabolites in blood, urine or other body fluids. For BLCA, urine is a most ideal body fluid to achieve non‐invasive diagnosis and surveillance. Here, we address recent developments of urine‐based biomarkers or tests for clinical diagnostic challenges in BLCA, such as early detection, minimal residual, recurrence monitoring and therapeutic response. Meanwhile, the many challenges of urine biomarkers that need to be overcome are also discussed.
Investigation of the factors responsible for the low oral bioavailability of alizarin using a sensitive LC‐MS/MS method: In vitro, in situ, and in vivo evaluations
Authors: Seo Seong‐Wook , Han Dong‐Gyun , Baek Young Mee , Park Min Chul , Yoo Jin‐Wook , Jung Yunjin , Maeng Han‐Joo , Myung Heejoon , Yoon In‐Soo
Published: February 2023

Alizarin (1,2‐dihydroxyanthraquinone) is an anthraquinone reddish dye widely used for painting and textile dyeing. As the biological activity of alizarin has recently attracted increasing attention from researchers, its therapeutic potential as complementary and alternative medicine is of interest. However, no systematic research has been conducted on the biopharmaceutical and pharmacokinetic aspects of alizarin. Therefore, this study aimed to comprehensively investigate the oral absorption and intestinal/hepatic metabolism of alizarin using a simple and sensitive tandem mass spectrometry method developed and validated in‐house. The present method for the bioanalysis of alizarin has merits, including a simple pretreatment procedure, small sample volume, and adequate sensitivity. Alizarin exhibited pH‐dependent moderate lipophilicity and low solubility with limited intestinal luminal stability. Based on the in vivo pharmacokinetic data, the hepatic extraction ratio of alizarin was estimated to be 0.165–0.264, classified as a low level of hepatic extraction. In an in situ loop study, considerable fractions (28.2%–56.4%) of the alizarin dose were significantly absorbed in gut segments from the duodenum to ileum, suggesting that alizarin may be classified as the Biopharmaceutical Classification System class II. An in vitro metabolism study using rat and human hepatic S9 fractions revealed that glucuronidation and sulfation, but not NADPH‐mediated phase I reactions and methylation, are significantly involved in the hepatic metabolism of alizarin. Taken together, it can be estimated that the fractions of oral alizarin dose unabsorbed from the gut lumen and eliminated by the gut and liver before reaching the systemic circulation are 43.6%–76.7%, 0.474%–36.3%, and 3.77%–5.31% of the dose, respectively, resulting in a low oral bioavailability of 16.8%. Therefore, the oral bioavailability of alizarin depends primarily on its chemical degradation in the gut lumen and secondarily on first‐pass metabolism.
Colonization of a temperate river by mobile fish following habitat reconnection
Authors: Kiffney P. M. , Lisi P. J. , Liermann M. , Naman S. M. , Anderson J. H. , Bond M. H. , Pess G. R. , Koehler M. E. , Buhle E. R. , Buehrens T. W. , Klett R. S. , Cram J. M. , Quinn T. P.
Published: February 2023

Mobile species are particularly affected by artificial barriers requiring large investments to restore connectivity. However, few large‐scale, long‐term studies have investigated the ecological outcomes of restoring connectivity for these species. Our study, spanning 15–20 years, quantified response trajectories, which represent temporal trends following disturbance, of three native salmonids colonizing 20 km of protected habitat following restoration of fish passage at Landsburg Dam, Cedar River, WA, in 2003. Built in 1901, the dam blocked the upriver movement of native anadromous coho and Chinook salmon and nonanadromous mountain whitefish for 102 years. Restoration effectiveness was also assessed by comparing temporal trends in freshwater productivity of juvenile coho and Chinook salmon in the Cedar River after restoration to a nearby undammed subbasin. We also compared summer densities of juvenile coho and Chinook salmon, and mountain whitefish above the dam measured a decade after restoration to undammed reference systems. Anadromous salmon and nonanadromous mountain whitefish populations increased linearly or nonlinearly following restoration. The positive, asymptotic response represented by adult Chinook salmon counts indicates a slowing in population recovery rate, plateauing a decade after restoration. In contrast, annual abundance of adult coho salmon increased at a constant rate, indicating additional capacity 15 years post‐restoration. Salmonid compositional diversity, driven largely by juvenile coho salmon, also increased nonlinearly, plateauing in a decade. We observed substantial spatial variation in the temporal response, as juvenile coho salmon and mountain whitefish population expansion slowed linearly with upstream distance from the restoration site. There was evidence that some of the annual variation in salmonid biomass in summer was a result of discharge variability in winter and spring, with biomass declining as flow variability increased. Species reintroduction and establishment had no discernible effect on stream‐rearing salmonids living above the dam before restoration, while increasing coho freshwater productivity at the subbasin scale. Results from our study showed recolonization by three mobile species, each with a unique life history, takes at least a decade or more and was dependent on species and life stage, size of the spawning population, distance from restoration site, and annual variability in streamflow.
Long‐term exposure to an invasive fungal pathogen decreases Eptesicus fuscus body mass with increasing latitude
Authors: Simonis Molly C. , Hartzler Lynn K. , Turner Gregory G. , Scafini Michael R. , Johnson Joseph S. , Rúa Megan A.
Published: February 2023

Invasive pathogens threaten wildlife health and biodiversity. Physiological responses of species highly susceptible to pathogen infections following invasion are well described. However, the responses of less susceptible species (relative to highly susceptible species) are not well known. Latitudinal gradients, which can influence body condition via Bergmann's rule and/or reflect the time it takes for an introduced pathogen to spread geographically, add an additional layer for how mammalian species respond to pathogen exposure. Our goal was to understand how hosts less susceptible to pathogen infections respond to long‐term pathogen exposure across a broad latitudinal gradient. We examined changes in body mass throughout pathogen exposure time across the eastern United States (latitude ranging 30.5° N–44.8° N) in Eptesicus fuscus, a bat species classified as less susceptible to infection (relative to highly susceptible species) by the invasive fungal pathogen that causes white‐nose syndrome, Pseudogymnoascus destructans (Pd). Using 30 years of spring through fall adult capture records, we created linear mixed‐effects models for female and male bats to determine how mass or mass variation changed across the eastern United States from pre‐Pd invasion years through Pd invasion (0–1 years with Pd), epidemic (2–4 years with Pd), and established years (5+ years with Pd). By Pd establishment, all female and male bats decreased body mass with increasing latitude across a spatial threshold at 39.6° N. Differences in bat mass north and south of the spatial threshold progressively increased over Pd exposure time‐steps such that body mass was lower in northern latitudes compared to southern latitudes by Pd establishment. Results indicated that the progressive differences in E. fuscus body mass with latitude across the eastern United States are due to long‐term pathogen exposure; however, other environmental and ecological pressures may contribute to decreases in E. fuscus body mass with latitude and long‐term pathogen exposure. As pathogen introductions and emerging infectious diseases become more prevalent on the landscape, it is imperative that we understand how less susceptible species directly and indirectly respond to long‐term pathogen exposure in order to maintain population health in surviving species.
The salmonid and the subsurface: Hillslope storage capacity determines the quality and distribution of fish habitat
Authors: Dralle D. N. , Rossi G. , Georgakakos P. , Hahm W. J. , Rempe D. M. , Blanchard M. , Power M. E. , Dietrich W. E. , Carlson S. M.
Published: February 2023

Water in rivers is delivered via the critical zone (CZ)—the living skin of the Earth, extending from the top of the vegetation canopy through the soil and down to fresh bedrock and the bottom of significantly active groundwater. Consequently, the success of stream‐rearing salmonids depends on the structure and resulting water storage and release processes of this zone. Physical processes below the land surface (the subsurface component of the CZ) ultimately determine how landscapes “filter” climate to manifest ecologically significant streamflow and temperature regimes. Subsurface water storage capacity of the CZ has emerged as a key hydrologic variable that integrates many of these subsurface processes, helping to explain flow regimes and terrestrial plant community composition. Here, we investigate how subsurface storage controls flow, temperature, and energetic regimes that matter for salmonids. We illustrate the explanatory power of broadly applicable, storage‐based frameworks across a lithological gradient that spans the Eel River watershed of California. Study sites are climatically similar but differ in their geologies and consequent subsurface CZ structure that dictates water storage dynamics, leading to dramatically different hydrographs, temperature, and riparian regimes—with consequences for every aspect of salmonid life history. Lithological controls on the development of key subsurface CZ properties like storage capacity suggest a heretofore unexplored link between salmonids and geology, adding to a rich literature that highlights various fluvial and geomorphic influences on salmonid diversity and distribution. Rapidly advancing methods for estimating and observing subsurface water storage dynamics at large scales present new opportunities for more clearly identifying landscape features that constrain the distributions and abundances of organisms, including salmonids, at watershed scales.
Estimating recruitment rate and population dynamics at a migratory stopover site using an integrated population model
Authors: Tucker Anna M. , McGowan Conor P. , Nuse Bryan L. , Lyons James E. , Moore Clinton T. , Smith David R. , Sweka John A. , Anstead Kristen A. , DeRose‐Wilson Audrey , Clark Nigel A.
Published: February 2023

Consideration of the full annual cycle population dynamics can provide useful insight for conservation efforts, but collecting data needed to estimate demographic parameters is often logistically difficult. For species that breed in remote areas, monitoring is often conducted during migratory stopover or at nonbreeding sites, and the recruitment rate of new breeding adults can be difficult to estimate directly. Here, we present an integrated population model that uses mark‐resight and count data to estimate survival probability, population growth rate, and recruitment rate for an Arctic‐breeding shorebird of conservation concern, the red knot (Calidris canutus rufa), from data collected during spring stopover in Delaware Bay, USA, from 2005 to 2018. At this site, red knots feed primarily on the eggs of spawning horseshoe crabs (Limulus polyphemus), a legally harvested species. We used this model to estimate the relationship between horseshoe crab abundance and red knot demographics, which informed a recent revision to the framework used to establish horseshoe crab harvest regulations. Our analysis indicates that the red knot population was most likely stable from 2005 to 2018 (average λ = 1.03, 95% credible interval [CRI]: 0.961, 1.15) despite low recruitment rates (average ρ = 0.088, 95% CRI: 0.012, 0.18). Adult survival probability was positively associated with horseshoe crab abundance in the same year (β = 0.35, 95% CRI: 0.09, 0.63), but we found no effect of horseshoe crab abundance two years previously on recruitment of new adults (β = −0.08, 95% CRI: −0.41, 0.38). Our approach demonstrates the utility of integrated population models for understanding population dynamics, even when data are only available from migratory stopover monitoring.
F‐Tag Induced Acyl Shift in the Photochemical Cyclization of o‐Alkynylated N‐Alkyl‐N‐acylamides to Indoles**
Authors: Simek Tosino Helena , Jung André , Fuhr Olaf , Muhle‐Goll Claudia , Jung Nicole , Bräse Stefan
Published: February 2023

A photochemical cyclization of F‐tagged, o‐alkynylated N‐alkylamides to indoles catalyzed by [Ir(dF(CF3)ppy)2(dtbpy)]PF6 is presented. This straightforward and efficient reaction involves an intramolecular rearrangement due to the presence of an electron withdrawing group in the acyl moiety and is the first example of photochemically induced 1,3‐acyl shift in the cyclization towards 3‐acylindoles. A four‐step reaction sequence including the photoreaction as a key step to the desired indoles has been developed and optimized. The compatibility of differently substituted F‐tagged precursors with the photocyclization step was investigated and the robustness of this step towards modifications could be shown. In total, 16 so far unknown derivatives with diverse modifications in positions N1 and C2, bearing a pentadecafluorooctanoyl moiety as F‐tag, were synthesized in very good yields and fully characterized.
Ictal vocalizations in the Scn1a+/− mouse model of Dravet syndrome
Authors: Anderson Lyndsey L. , Everett‐Morgan Declan , Petkova Stela P. , Silverman Jill L. , Arnold Jonathon C.
Published: February 2023

Objective

Ictal vocalizations have shown diagnostic utility in epilepsy patients. Audio recordings of seizures have also been used for seizure detection. The present study aimed to determine whether generalized tonic–clonic seizures in the Scn1a+/− mouse model of Dravet syndrome are associated with either audible mouse squeaks or ultrasonic vocalizations.

Methods

Acoustic recordings were captured from group‐housed Scn1a+/− mice undergoing video‐monitoring to quantify spontaneous seizure frequency. We generated audio clips (n = 129) during a generalized tonic–clonic seizure (GTCS) that included 30 seconds immediately prior to the GTCS (preictal) and 30 seconds following the conclusion of the seizure (postictal). Nonseizure clips (n = 129) were also exported from the acoustic recordings. A blinded reviewer manually reviewed the audio clips, and vocalizations were identified as either an audible (<20 kHz) mouse squeak or ultrasonic (>20 kHz).

Results

Spontaneous GTCS in Scn1a+/− mice were associated with a significantly higher number of total vocalizations. The number of audible mouse squeaks was significantly greater with GTCS activity. Nearly all (98%) the seizure clips contained ultrasonic vocalizations, whereas ultrasonic vocalizations were present in only 57% of nonseizure clips. The ultrasonic vocalizations emitted in the seizure clips were at a significantly higher frequency and were nearly twice as long in duration as those emitted in the nonseizure clips. Audible mouse squeaks were primarily emitted during the preictal phase. The greatest number of ultrasonic vocalizations was detected during the ictal phase.

Significance

Our study shows that ictal vocalizations are exhibited by Scn1a+/− mice. Quantitative audio analysis could be developed as a seizure detection tool for the Scn1a+/− mouse model of Dravet syndrome.
Anxiety attenuates learning advantages conferred by statistical stability and induces loss of volatility‐attuning in brain activity
Authors: Rowe Elise G. , Harris Clare D. , Dzafic Ilvana , Garrido Marta I.
Published: February 2023

Anxiety can alter an individual's perception of their external sensory environment. Previous studies suggest that anxiety can increase the magnitude of neural responses to unexpected (or surprising) stimuli. Additionally, surprise responses are reported to be boosted during stable compared to volatile environments. Few studies, however, have examined how learning is impacted by both threat and volatility. To investigate these effects, we used threat‐of‐shock to transiently increase subjective anxiety in healthy adults while they performed an auditory oddball task under stable and volatile environments and while undergoing functional Magnetic Resonance Imaging (fMRI) scanning. We then used Bayesian Model Selection (BMS) mapping to identify the brain areas where different models of anxiety displayed the highest evidence. Behaviourally, we found that threat‐of‐shock eliminated the accuracy advantage conferred by environmental stability over volatility. Neurally, we found that threat‐of‐shock led to attenuation and loss of volatility‐attuning of brain activity evoked by surprising sounds across most subcortical and limbic regions including the thalamus, basal ganglia, claustrum, insula, anterior cingulate, hippocampal gyrus and the superior temporal gyrus. Taken together, our findings suggest that threat eliminates learning advantages conferred by statistical stability compared to volatility. Thus, we propose that anxiety disrupts behavioural adaptation to environmental statistics, and that multiple subcortical and limbic regions are implicated in this process.
Fine scale 20‐year timeseries of plantation forest evapotranspiration for the lower limestone coast
Authors: Doody Tanya M. , Benyon Richard G. , Gao Sicong
Published: February 2023

Commercial plantation forestry is a vital industry worldwide, providing natural resources for humans and playing an important role in carbon sequestration. Historically, impacts of plantation development to natural resources such as surface and groundwater was not considered, however demand for water and drying climates has focussed attention on sustainable water use and extraction. The Lower Limestone Coast region of south‐east South Australia has an extensive softwood plantation estate. The region is characterised by minimal surface water and substantial, fresh karstic groundwater resources, often <6 m below ground. Rapid expansion over shallow groundwater of the plantation hardwood estate from 2000, prompted concern about impacts of deep‐rooted plantations on water resources and notably contracting wetlands. To quantify plantation estate water use, an extensive evapotranspiration (ET) field study (1999–2008) identified plantation areas with <6 m to groundwater as groundwater users, leading to water policy whereby plantations are considered licenced water users. To enable plantation expansion in the region, fine resolution, broadscale ET data is required to ensure optimum use of water licences in the forest industry and account for plantation groundwater extraction. As continual field studies are not feasible, this 20‐year, monthly 30 m ET dataset for the region was developed to improve estimates of plantation water use, enabling improved, dynamic estimates of groundwater extraction. The dataset was developed using 21 long‐term field sites where ET was derived based on field measured transpiration, soil moisture, canopy interaction and rainfall data. Region specific field ET was combined with machine learning and additional remote sensing layers to estimate monthly ET (R2 = 0.86) across the plantation estate, improving on a national remote sensing ET product. Currently, groundwater extraction is accounted for via modelling which excludes dynamic changes in plantation groundwater extraction, limiting understanding of the hydrological processes influencing available water resources and potentially impeding economic growth.
Exploring heterosexism through participatory theater: An experiment
Authors: Emert Toby
Published: February 2023

Using Augusto Boal's Theater of the Oppressed (1985) playmaking structures, students in an undergraduate education course, Educating for Social Justice, developed forum plays—brief improvisational scenes designed to provoke discussions of power imbalances. The plays focused on “gay rights,” a topic the participants self‐selected through guided discussions about injustice. The plays were performed for an English class of tenth‐grade high school students. As a mode of investigating the efficacy of this instructional strategy to spur self‐reflexivity, data about the college students' experiences were collected during each class session and in subsequent semi‐structured group interviews. This article describes the project and the participants' reactions to the invitation to step into the role of ensemble member and play‐maker, as well as the development of their critical consciousness about the effects of cultural bias.
Evaluating the effect of ginsenoside Rg1 on CPF‐induced brain injury in mice via PI3k/AKT pathway
Authors: Liu Silu , Pei Hongyan , Chen Weijia , Zhu Xiaoying , Wang Yu , Li Jianming , He Zhongmei , Du Rui
Published: February 2023

Organophosphorus pesticides (OPs) have long been used extensively on agricultural land and can lead to significant improvements in crop yields. Due to occupational exposure, humans are exposed to pesticides through dermal contact, inhalation, and ingestion. The effects of OPs on the organism are currently studied for their effects on livers, kidneys, hearts, blood indicators, neurotoxicity, and teratogenic, carcinogenic, and mutagenic effects, while studies in the direction of brain tissue damage have not been reported in detail. Previous reports have confirmed that ginsenoside Rg1 is a prominent and representative tetracyclic triterpenoid derivative rich in ginseng and has good neuroprotective activity. Considering that, the aim of this study was to establish a mouse model of brain tissue injury by using the OP‐type pesticide chlorpyrifos (CPF) and to explore the therapeutic effects and possible molecular mechanisms of Rg1. Mice in the experimental group were pre‐protected with Rg1 by gavage for 1 week, and brain tissue damage was induced using CPF (5 mg/kg for 1 week) to assess the effect of Rg1 (80 and 160 mg/kg for 3 weeks) in alleviating brain damage. Morris water maze and histopathological analysis were performed to assess cognitive function and pathological changes in the mouse brain, respectively. Protein expression levels of Bax, Bcl‐2, Caspase‐3, Cl‐Cas‐3, Caspase‐9, Cl‐Cas‐9, phosphoinositide 3‐kinase (PI3K), phosphorylated‐PI3K, protein kinase B (AKT), and phosphorylated‐AKT were quantified by protein blotting analysis. Rg1 obviously restored CPF‐induced oxidative stress damage in mouse brain tissue, increased the levels of antioxidant parameters (total superoxide dismutase, total antioxidative capacity, and glutathione) in the brain, and significantly reduced the overexpression of apoptosis‐related proteins induced by CPF. At the same time, Rg1 also markedly attenuated the histopathological changes in the brain induced by CPF exposure. Mechanistically, Rg1 could effectively activate the phosphorylation of PI3K/AKT. Furthermore, molecular docking studies revealed a stronger binding capacity between Rg1 and PI3K. Rg1 attenuated neurobehavioural alterations and reduced lipid peroxidation in the mouse brain to a great extent. Apart from that, Rg1 administration improved brain histopathology in CPF‐induced rats. All results suggest that ginsenoside Rg1 has potential antioxidant effects on CPF‐induced oxidative brain injury, and it is evident that Rg1 could be used as a promising therapeutic strategy for the study of brain injury from OP poisoning.