bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tuning the Elasticity of Polymersomes for Brain Tumor Targeting
Authors: Zheng Meng , Du Qiuli , Wang Xin , Zhou Yuan , Li Jia , Xia Xue , Lu Yiqing , Yin Jinlong , Zou Yan , Park Jong Bae , Shi Bingyang 
Published: August 2021

AbstractNanoformulations show great potential for delivering drugs to treat brain tumors. However, how the mechanical properties of nanoformulations affect their ultimate brain destination is still unknown. Here, a library of membrane‐crosslinked polymersomes with different elasticity are synthesized to investigate their ability to effectively target brain tumors. Crosslinked polymersomes with identical particle size, zeta potential and shape are assessed, but their elasticity is varied depending on the rigidity of incorporated crosslinkers. Benzyl and oxyethylene containing crosslinkers demonstrate higher and lower Young's modulus, respectively. Interestingly, stiff polymersomes exert superior brain tumor cell uptake, excellent in vitro blood brain barrier (BBB) and tumor penetration but relatively shorter blood circulation time than their soft counterparts. These results together affect the in vivo performance for which rigid polymersomes exerting higher brain tumor accumulation in an orthotopic glioblastoma (GBM) tumor model. The results demonstrate the crucial role of nanoformulation elasticity for brain‐tumor targeting and will be useful for the design of future brain targeting drug delivery systems for the treatment of brain disease.
Application of Resistive Random Access Memory in Hardware Security: A Review
Authors: Rajendran Gokulnath , Banerjee Writam , Chattopadhyay Anupam , Aly Mohamed M. Sabry 
Published: August 2021

AbstractNowadays, advancements in the design of trusted system environments are relying on security provided by hardware‐based primitives, while replacing resource‐hungry software security measures. Emerging nonvolatile memory devices are promising candidates to provide the required hardware security functionalities at very low area‐energy‐runtime budget. Resistive random access memory (RRAM) offers high‐density integration with outstanding performance among the state‐of‐the‐art nonvolatile memory devices. The RRAM device technology is currently getting significant attention from both academia and industry for constructing beyond Von Neumann architectures. This technology's strength is its scalable two‐terminal structure, the availability of wide range of functional materials, and multi‐bit storage capability. The fluctuations in switching resistances, random telegraph noise, and sneak path current are detrimental characteristics of RRAM integrations for storage and in‐memory computing applications, and more research focuses on alleviating these effects. Interestingly, these characteristics make them suitable for designing security hardware. In recent times, there has been significant progress in the design and analysis of RRAM‐based security primitives such as, Physical Unclonable Function, true random number generator, and hash function. This review discusses the detailed developments in RRAM security and presents the demanded security requirement and available opportunities to be explored.
Red‐ and Far‐Red‐Emitting Zinc Probes with Minimal Phototoxicity for Multiplexed Recording of Orchestrated Insulin Secretion
Authors: Zhang Junwei , Peng Xiaohong , Wu Yunxiang , Ren Huixia , Sun Jingfu , Tong Shiyan , Liu Tianyan , Zhao Yiwen , Wang Shusen , Tang Chao , Chen Liangyi , Chen Zhixing 
Published: August 2021

AbstractZinc biology, featuring intertwining signaling networks and critical importance to human health, witnesses exciting opportunities in the big data era of physiology. Here, we report a class of red‐ and far‐red‐emitting Zn2+ probes with Kd values ranging from 190 nM to 74 μM, which are particularly suitable for real‐time monitoring the high concentration of Zn2+ co‐released with insulin during vesicular secretory events. Compared to the prototypical rhodamine‐based Zn2+ probes, the new class exploits morpholino auxochromes which eliminates phototoxicity during long‐term live recording of isolated islets. A Si‐rhodamine‐based Zn2+ probe with high turn‐on ratio (>100), whose synthesis was enabled by a new route featuring late‐stage N‐alkylation, allowed simultaneous recording of Ca2+ influx, mitochondrial signal, and insulin secretion in isolated mouse islets. The time‐lapse multicolor fluorescence movies and their analysis, enabled by red‐shifted Zn2+ and other orthogonal physiological probes, highlight the potential impact of biocompatible fluorophores on the fields of islet endocrinology and system biology.
Silica nanoparticle‐modified microcomb electrode for voltammetry detection of osteopontin with high sensitivity
Authors: Shu Hexi , Zhao Liangliang , Li Xiaoxia , Gong Jinpeng , Yin Guorui , Chen Hulin 
Published: August 2021

AbstractOsteosarcoma is a commonly occurring bone malignancy, and it is the second most common cause of cancer deaths in adolescents and children. A sensitive silica nanoparticle (Si‐NP) modified current‐volt sensor was introduced to identify the osteopontin antigen, a well‐known biomarker for osteosarcoma. Si‐NP was extracted from the rice husk ash and utilized for the surface functionalization on the interdigitated microelectrode sensing surface. Extracted Si‐NP has a spherical shape with uniform distribution, and it is confirmed by field emission scanning electron microscopy and field‐emission transmission electron microscopy. Si‐NP was layered on the electrode surface through a (3‐aminopropyl)triethoxysilane amine linker, and the antibody was immobilized on Si‐NP through a glutaraldehyde linker. Osteopontin was effectively detected on the antibody‐attached surface, and the determination limit was 0.6 ng/mL. The regression was determined asy= 0.9366x− 1.1113 and the R2 value was 0.9331 and the detection limit of osteopontin was 0.6 ng/mL in the range between 0.3 and 5 ng/mL. In addition, control performance with nonimmune antibodies and albumin did not change the current volt, showing the specific osteopontin identification. This research work brings out the easy and cost‐effective method to diagnose osteosarcoma and its etiology.
Three‐dimensional‐poly(lactic acid) scaffolds coated with gelatin/magnesium‐doped nano‐hydroxyapatite for bone tissue engineering
Authors: Swetha Sampath , Balagangadharan Kalimuthu , Lavanya Krishnaraj , Selvamurugan Nagarajan 
Published: August 2021

AbstractBackgroundTreatment of critical‐sized bone defects has progressively evolved over the years from metallic implants to more ingenious three‐dimensional‐based scaffolds. The use of three‐dimensional scaffolds for bone regeneration from biodegradable polymers like poly(lactic acid) (PLA) is gaining popularity. Scaffolds with surface functionalization using gelatin (Gel) have the advantages of biocompatibility and cell adhesion. Nano‐hydroxyapatite (nHAp) is one of the most promising implant materials utilized in orthopaedics. The osteogenic potential of the nHAp can be improved by the substitution of magnesium (Mg) ions onto the crystal lattice of nHAp. Thus, the goal of this work was to make three‐dimensional‐PLA scaffolds covered with Gel/Mg‐nHAp for osteogenic effect.Methods and resultsThe designed three‐dimensional‐PLA/Gel/Mg‐nHAp scaffolds were attributed to various characterizations for the examination of their physicochemical, mechanical properties, cyto‐compatibility, and biodegradability as well as their ability to promote osteogenesis in vitro. Mouse mesenchymal stem cells (mMSCs) were cytocompatible with these scaffolds. The osteogenic potential of three‐dimensional‐PLA/Gel/Mg‐nHAp scaffolds employing mMSCs was validated at the cellular and molecular levels. The three‐dimensional‐PLA/Gel/Mg‐nHAp scaffolds stimulated the differentiation of mMSCs towards osteoblastic lineage.ConclusionBased on these findings, we suggest that the three‐dimensional‐PLA/Gel/Mg‐nHAp scaffolds' osteogenic capability may be advantageous in the mending of bone defects in orthopedic applications.
Prediction of dispositional dialectical thinking from resting‐state electroencephalography
Authors: Huang Kun , Chen Dian , Wang Fei , Yang Lijian 
Published: August 2021

AbstractThis study aims to explore the possibility of predicting the dispositional level of dialectical thinking using resting‐state electroencephalography signals. Thirty‐four participants completed a self‐reported measure of dialectical thinking, and their resting‐state electroencephalography was recorded. After wave filtration and eye movement removal, time‐frequency electroencephalography signals were converted into four frequency domains: delta (1–4 Hz), theta (4–7 Hz), alpha (7–13 Hz), and beta (13–30 Hz). Functional principal component analysis with B‐spline approximation was then applied for feature reduction. Five machine learning methods (support vector regression, least absolute shrinkage and selection operator, K‐nearest neighbors, random forest, and gradient boosting decision tree) were applied to the reduced features for prediction. The model ensemble technique was used to create the best performing final model. The results showed that the alpha wave of the electroencephalography signal in the early period (12–15 s) contributed most to the prediction of dialectical thinking. With data‐driven electrode selection (FC1, FCz, Fz, FC3, Cz, AFz), the prediction model achieved an average coefficient of determination of 0.45 on 200 random test sets. Furthermore, a significant positive correlation was found between the alpha value of standardized low‐resolution electromagnetic tomography activity in the right dorsal anterior cingulate cortex and dialectical self‐scale score. The prefrontal and midline alpha oscillations of resting electroencephalography are good predictors of the dispositional level of dialectical thinking, possibly reflecting these brain structures’ involvement in dialectical thinking.
Effect of electroacupuncture on inhibition of inflammatory response and oxidative stress through activating ApoE and Nrf2 in a mouse model of spinal cord injury
Authors: Dai Ni , Tang Chenglin , Liu Hui , Huang Siqin 
Published: August 2021

AbstractIntroductionElectroacupuncture protects neurons and myelinated axons after spinal cord injury by mitigating the inflammatory response and oxidative stress, but how it exerts these effects is unclear.Methods and resultsSpinal cord injury was induced in C57BL/6 wild‐type and apolipoprotein E (ApoE) knockout (ApoE–/–) mice, followed by electroacupuncture or ApoE mimetic peptide COG112 treatment. Mice with spinal cord injury suffered loss of myelinated axons and hindlimb motor function through the detections of Basso mouse scale, histology, and transmission electron microscopy; electroacupuncture partially reversed these effects in wild‐type mice but not in ApoE–/–mice. Combining exogenous ApoE administration with electroacupuncture significantly mitigated the effects of spinal cord injury in both mouse strains, and these effects were associated with up‐regulation of anti‐inflammatory cytokines and down‐regulation of pro‐inflammatory cytokines which were detected by quantitative reverse transcription‐polymerase chain reaction. Combination treatment also reduced oxidative stress by up‐regulating ApoE and Nrf2/HO‐1 signaling pathway through the detections of immunofluorescence and western blot analysis.ConclusionsThese results suggest that electroacupuncture protects neurons and myelinated axons following spinal cord injury through an ApoE‐dependent mechanism.
Simplified Derivatives of Dibenzylbutyrolactone Lignans from Hydrocotyle bonariensis as Antitrypanosomal Candidates
Authors: Souza Dalete Christine S. , Costa‐Silva Thais A. , Morais Thiago R. , Brito Juliana R. , Ferreira Edgard A. , Antar Guilherme M. , Sartorelli Patricia , Tempone Andre G. , Lago João Henrique G. 
Published: August 2021

AbstractThe search for the pharmacophore of a bioactive compound, crucial for drug discovery studies, involves the adequate arrangement of different atoms in the molecule. As part of a continuous work aiming discovery of new drug candidates against the protozoan parasite Trypanosoma cruzi, the hexane extract of Hydrocotyle bonariensis was subjected to a bioactivity‐guided fractionation to afford two chemically related dibenzylbutyrolactone lignans – hinokinin (1) and hibalactone (2). Compounds 1 and 2 showed activity against trypomastigote with EC50 values of 17.0 and 69.4 μM, respectively. Compound 1 was also active against the clinically relevant form of the parasite, amastigotes, displaying an EC50 value of 34.4 μM. The structure‐activity relationship (SAR) indicated that the absence of the double bond at C‐7 is a crucial feature for the increment of the antiparasitic activity. The lethal action of the most potent compound 1 was investigated in the trypomastigotes. The fluorescent‐based assay with SYTOX Green demonstrated a significant alteration of the plasma membrane permeability of the parasite. Additionally, compound 1 demonstrated no significant hemolytic activity in mice erythrocytes at 200 μM. To search the pharmacophore, three different simplified compounds – 3,4‐methylenedioxydihydrocinnamic acid (3), 3,4‐methylenedioxydihydrocinnamic alcohol (4) and 3,4‐methylenedioxycinnamic acid (5) – were prepared and tested against T. cruzi. These derivatives displayed EC50 values of 37.2 (3), 25.8 (4) and 73.5 (5) μM against trypomastigotes, and 41.3 (3) and 48.2 (4) μM against amastigotes, whereas compound 5 was inactive. Except for compound 2, which resulted in a CC50 value of 114.5 μM, all compounds showed no mammalian cytotoxicity at 200 μM. An in silico ADMET study was performed and predicted values demonstrated an acceptable drug‐likeness profile for compounds 1–5. Despite the minor reduction in the potency, the simplified derivatives retained the antitrypanosomal activity against the intracellular amastigotes, even with 95 % reduction of their molecular weight. Additionally, in silico studies suggested them as more soluble compounds, making these simplified structures promising scaffolds for optimization studies in Chagas disease.
Gold‐Catalyzed Direct C(sp3)−H Acetoxylation of Saturated Hydrocarbons
Authors: Jo Tae Geun , Klein Johannes E. M. N. 
Published: August 2021

AbstractIn this communication we report our studies towards the development of a gold‐catalyzed direct acetoxylation of C(sp3)−H bonds. We achieve this through the use of the hypervalent iodine reagent PhI(OAc)2 in combination with a simple gold salt (HAuBr4) as the catalyst. Through a comparison of the reactivities of cyclooctane and adamantane we judge the reaction to proceed via hydride transfer. This is further substantiated through computational studies of the relative energies for the anions, radicals and cations derived from C−H bond cleavage of cyclooctane and adamantane relevant to the C−H cleaving step.
The preparation of optically active epineoclausenamide and enantiomeric separation of its racemate
Authors: Yan Yixiao , Zhu Senmei , Luo Xuna , Rao Yu , Su Jinlong , He Guantao , Lin Hansen 
Published: August 2021

AbstractWe synthesized the optically active epineoclausenamide by utilizing chiral reagents, such as R‐α‐methylbenzylamine and S‐α‐methylbenzylamine, for the resolution of the intermediate (trans‐3‐phenyl‐oxiranecarboxylic acid 12), followed by amide exchange, cyclization, and reduction, unlike previously reported methods. The Meerwein–Ponndorf–Verley reduction was used to asymmetrically reduce neoclausenamidone. A plausible reduction mechanism of this method was elucidated. Thereafter, high‐performance liquid chromatography (HPLC) was investigated for the resolution of the epineoclausenamide enantiomers. HPLC was also used to determine the optical purity of these isomers. Two chiral stationary phases (CSPs) for separating the enantiomers were compared. Different mobile phase compositions were tested at 298.15 K. The results showed that the best separation was obtained when the mobile phase was composed of n‐hexane and isopropanol (IPA) (75/25, v/v), the racemate was separated on a Chiralcel OJ‐H column, and the flow rate was 1.0 mL/min at a wavelength of 210 nm and a temperature of 25°C. The enantiomeric ratio (e.r.) values of both the synthetic (−)‐epineoclausenamide and (+)‐epineoclausenamide were 1.3(+):98.7(−) and 99.3(+):0.7(−), respectively. In this study, a new synthetic route was designed with a yield of 12.3–14.1%, and a quick (8 min) effective separation method was obtained. This provides basis for pharmacological research and quality control of clausenamide analogues.
Drug Repurposing for the SARS‐CoV‐2 Papain‐Like Protease
Authors: Cho Chia‐Chuan , Li Shuhua G. , Lalonde Tyler J. , Yang Kai S. , Yu Ge , Qiao Yuchen , Xu Shiqing , Ray Liu Wenshe 
Published: August 2021

AbstractAs the pathogen of COVID‐19, SARS‐CoV‐2 encodes two essential cysteine proteases that process the pathogen's two large polypeptide products pp1a and pp1ab in the human cell host to form 15 functionally important, mature nonstructural proteins. One of the two enzymes is papain‐like protease or PLPro. It possesses deubiquitination and deISGylation activities that suppress host innate immune responses toward SARS‐CoV‐2 infection. To repurpose drugs for PLPro, we experimentally screened libraries of 33 deubiquitinase and 37 cysteine protease inhibitors on their inhibition of PLPro. Our results showed that 15 deubiquitinase and 1 cysteine protease inhibitors exhibit strong inhibition of PLPro at 200 μM. More comprehensive characterizations revealed seven inhibitors GRL0617, SJB2‐043, TCID, DUB‐IN‐1, DUB‐IN‐3, PR‐619, and S130 with an IC50 value below 40 μM and four inhibitors GRL0617, SJB2‐043, TCID, and PR‐619 with an IC50 value below 10 μM. Among four inhibitors with an IC50 value below 10 μM, SJB2‐043 is the most unique in that it does not fully inhibit PLPro but has a noteworthy IC50 value of 0.56 μM. SJB2‐043 likely binds to an allosteric site of PLPro to convene its inhibition effect, which needs to be further investigated. As a pilot study, the current work indicates that COVID‐19 drug repurposing by targeting PLPro holds promise, but in‐depth analysis of repurposed drugs is necessary to avoid omitting critical allosteric inhibitors.
Increasing referral of at‐risk women for genetic counseling and BRCA testing using a screening tool in a community breast imaging center
Authors: Arun Banu K. , Peterson Susan K. , Sweeney Lilian E. , Bluebond Rachel D. , Tidwell Rebecca S. S. , Makhnoon Sukh , Kushwaha Anne C. 
Published: August 2021

BackgroundGenetic evaluation and testing for hereditary breast and ovarian cancer (HBOC) remain suboptimal. The authors evaluated the feasibility of using a screening tool at a breast imaging center to increase HBOC assessment referrals.MethodsA brief questionnaire based on the National Comprehensive Cancer Network HBOC genetic counseling referral guidelines was developed and added to the standard intake forms of patients undergoing mammography at a community breast imaging center from 2012 through 2015. Patients who met the criteria in the guidelines were referred for genetic counseling.ResultsA total of 34,851 patients were screened during the study period, and 1246 (4%) patients were found to be eligible for referral; 245 of these patients made a genetic counseling appointment, and 142 patients received genetic counseling. Forty patients (28%) had a personal history of breast cancer but were not previously tested. Following counseling, 105 patients were tested for BRCA1/2. Eight patients (8%) tested positive for a pathogenic mutation and nine (9%) had a variant of unknown significance. Although they tested negative, many patients met the criteria to add breast magnetic resonance imaging to their screening due to greater than 20% lifetime breast cancer risk based on their family cancer history. This study led to improved clinical risk management in 67% of the patients who underwent genetic counseling.ConclusionsThis study shows that large‐scale screening of patients for HBOC syndromes at time of breast imaging is practical and highly feasible. The screening tool identified women with actionable BRCA1/2 mutations and mutation‐negative but high‐risk women, leading to significant changes in their risk management; these women would otherwise have been missed.Lay Summary

Hereditary breast and ovarian cancer (HBOC) caused by pathogenic mutations in breast cancer genes (BRCA1/BRCA2) increase an individual's lifetime risk of getting HBOC.

Identifying these high‐risk individuals and using proven preventive clinical risk management strategies can significantly reduce their lifetime risk of HBOC.

Using an innovative family cancer history questionnaire, 34,000 women were screened at a community breast imaging center, and genetic counseling and testing were provided to eligible women from the screening.

Several women at high risk for HBOC were identified and this led to positive clinical risk management changes.

These women would have been missed if not for intervention.
Early life stress alters emotional learning in a sex‐ and age‐dependent manner with no impact on emotional behaviors
Authors: Zanta Natália C. , Suchecki Deborah , Girardi Carlos Eduardo Neves 
Published: August 2021

AbstractNeonatal adversity can impact neurodevelopmental trajectories. This study examined the long‐term effects of maternal deprivation on day 9 (DEP9), associated or not to a stressor (saline injection [SAL]), on contextual fear conditioning (Experiment 1) and emotional behaviors (Experiment 2) in Wistar rats. Whole litters were either assigned to DEP9 or control groups, and on day 10, half of the litters in each group received an SAL or not (NSAL). DEP9‐SAL male adolescents showed the longest freezing time and DEP9 adult males froze more than females. Females exhibited less anxiety‐like behavior than males; DEP9‐SAL females spent more time in the open arms and DEP9 males visited less the extremity of the open arm in the elevated plus maze. Early life stress increased conditioned and innate fear in males, but not in females, indicating a clear sexual dimorphism in the response to potentially threatening stimuli.
Genetic differential susceptibility to the parent–child relationship quality and the life span development of compassion
Authors: Dobewall Henrik , Keltikangas‐Järvinen Liisa , Saarinen Aino , Lyytikäinen Leo‐Pekka , Zwir Igor , Cloninger Robert , Raitakari Olli T. , Lehtimäki Terho , Hintsanen Mirka 
Published: August 2021

AbstractThe development of compassion for others might be influenced by the social experiences made during childhood and has a genetic component. No research has yet investigated whether the parent–child relationship quality interacts with genetic variation in the oxytocin and dopamine systems in predicting compassion over the life span. In the prospective Young Finns Study (N= 2099, 43.9% men), we examined the interaction between mother‐reported emotional warmth and intolerance toward their child assessed in 1980 (age of participants, 3–18 years) and two established genetic risk scores for oxytocin levels and dopamine signaling activity. Dispositional compassion for others was measured with the Temperament and Character Inventory 1997, 2001, and 2012 (age of participants, 20–50 years). We found a gene–environment interaction (p= .031) that remained marginally significant after adjustment for multiple testing. In line with the differential susceptibility hypothesis, only participants who carry alleles associated with low dopamine signaling activity had higher levels of compassion when growing up with emotionally warm parents, whereas they had lower levels of compassion when their parents were emotionally cold. Children's genetic variability in the dopamine system might result in plasticity to early environmental influences that have a long‐lasting effect on the development of compassion. However, our findings need replication.