bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconfigurable Physically Unclonable Functions Based on Nanoscale Voltage‐Controlled Magnetic Tunnel Junctions
Authors: Shao Yixin , Davila Noraica , Ebrahimi Farbod , Katine Jordan A. , Finocchio Giovanni , Khalili Amiri Pedram
Published: June 2023

With the fast growth of the number of electronic devices on the internet of things (IoT), hardware‐based security primitives such as physically unclonable functions (PUFs) have emerged to overcome the shortcomings of conventional software‐based cryptographic technology. Existing PUFs exploit manufacturing process variations in a semiconductor foundry technology. This results in a static challenge–response behavior, which can present a long‐term security risk. This study shows a reconfigurable PUF based on nanoscale magnetic tunnel junction (MTJ) arrays that uses stochastic dynamics induced by voltage‐controlled magnetic anisotropy (VCMA) for true random bit generation. A total of 100 PUF instances are implemented using 10 ns voltage pulses on a single chip with a 10 × 10 MTJ array. The unipolar nature of the VCMA mechanism is exploited to stabilize the MTJ state and eliminate bit errors during readout. All PUF instances show entropy close to one, inter‐Hamming distance close to 50%, and no bit errors in 104repeated readout measurements.
Comparative productivity of six bioenergy cropping systems on marginal lands in the Great Lakes Region, United States
Authors: Jayawardena Dileepa M. , Robertson G. Philip , Sanford Gregg R. , Thelen Kurt D.
Published: June 2023

Growing lignocellulosic crops on marginal lands is a promising solution for sustainable biofuel production. We evaluated the productivity of bioenergy cropping systems (switchgrass [Panicum virgatum L., var. Cave‐In‐Rock], miscanthus [Miscanthus × giganteus, ‘Illinois clone’], hybrid poplar [Populus nigra × P. maximowiczii A. Henry ‘NM6’], native grasses [five species], early successional vegetation, and restored prairie vs. historical vegetation [as reference control]) with and without nitrogen fertilization on low‐fertility former cropland at five sites in the Great Lakes Region, United States. We reported biomass yields for the first 7 years after establishment. Switchgrass was most consistently productive across all sites but miscanthus was more productive at three of the five sites. When averaged across sites, years, and nitrogen (N) treatments, biomass yields followed the order miscanthus > switchgrass > hybrid poplar ≈ native grasses > restored prairie > early successional vegetation ≈ historical vegetation, but varied substantially by crop and site, with a significant crop by site interaction. Yields of miscanthus and switchgrass peaked after four–five growing seasons and declined thereafter, while yields of both native grasses and restored prairie increased throughout 6 years with no sign of follow‐on decline, suggesting that polycultures may outperform monocultures over the long term. Yields of early successional vegetation—similar in composition to historical vegetation at each site—did not improve with time. Nitrogen fertilization increased the yields of all cropping systems at all sites. Our results demonstrate the viability of low‐productivity former cropland for long‐term bioenergy production and suggest there is no single crop best suited for all low fertility soils.
Precise control on two‐dimensional nanochannels at sub‐nanometer level for customizable gas separation
Authors: Xu Xiaozhi , Han Jinhui , Li Biao , Yang Zeya , Dou Yibo , Han Jingbin
Published: June 2023

Membranes with precise molecular sieving channels that break the permeability‐selectivity trade‐off are desirable for energy‐efficient gas separation. Two‐dimensional (2D) membranes sieve gas through their special interlayer channels between neighboring nanosheets. However, the regulation and precise control of the nanochannels that match well with the size of the gas molecules remains a big challenge. Herein, accurate tuning of the interlayer spacing of layered double hydroxide (LDH) membranes at sub‐nanometer level was achieved by intercalation of Cl−, Br−, I−, and NO3− ions. Such high‐precision control allows customizable gas separation by selecting specific LDH membranes with appropriate channels according to the size of the gas molecules. Two membranes were used for demonstration: Cl‐LDH membrane shows high H2 permeance of ∼1870 GPU and desirable selectivities for H2/CO2(81), H2/N2(197), H2/CH4(320), and H2/C3H8(603); while I‐LDH membrane displays CO2 permeance of ∼1780 GPU and CO2/N2, CO2/CH4 selectivities of 182 and 297, respectively. The simultaneously high permeabilities and selectivities surpass the 2008 Robeson upper bounds. Molecular dynamics simulations quantitatively support the experiment results, further confirming the significant role of interlayer anions in the regulation of gas‐sieving channels. Given the rich variability of layered spacing and interlayer microenvironment for LDH materials, this work provides a platform membrane for various molecular sieving, including gas separation, solvent purification, seawater desalination, and so on.
Human milk immune factors, maternal nutritional status, and infant sex: The INSPIRE study
Authors: Caffé Beatrice , Blackwell Aaron , Fehrenkamp Bethaney D. , Williams Janet E. , Pace Ryan M. , Lackey Kimberly A. , Ruiz Lorena , Rodríguez Juan M. , McGuire Mark A. , Foster James A. , Sellen Daniel W. , Kamau‐Mbuthia Elizabeth W. , Kamundia Egidioh W. , Mbugua Samwel , Moore Sophie E. , Prentice Andrew M. , Kvist Linda J. , Otoo Gloria E. , Pareja Rossina G. , Bode Lars , Gebeyehu Dubale , Gindola Debela K. , Boothman Sarah , Flores Katherine , McGuire Michelle K. , Meehan Courtney L.
Published: June 2023

Objectives

Breastfeeding is an energetically costly and intense form of human parental investment, providing sole‐source nutrition in early infancy and bioactive components, including immune factors. Given the energetic cost of lactation, milk factors may be subject to tradeoffs, and variation in concentrations have been explored utilizing the Trivers‐Willard hypothesis. As human milk immune factors are critical to developing immune system and protect infants against pathogens, we tested whether concentrations of milk immune factors (IgA, IgM, IgG, EGF, TGFβ2, and IL‐10) vary in response to infant sex and maternal condition (proxied by maternal diet diversity [DD] and body mass index [BMI]) as posited in the Trivers‐Willard hypothesis and consider the application of the hypothesis to milk composition.

Methods

We analyzed concentrations of immune factors in 358 milk samples collected from women residing in 10 international sites using linear mixed‐effects models to test for an interaction between maternal condition, including population as a random effect and infant age and maternal age as fixed effects.

Results

IgG concentrations were significantly lower in milk produced by women consuming diets with low diversity with male infants than those with female infants. No other significant associations were identified.

Conclusions

IgG concentrations were related to infant sex and maternal diet diversity, providing minimal support for the hypothesis. Given the lack of associations across other select immune factors, results suggest that the Trivers‐Willard hypothesis may not be broadly applied to human milk immune factors as a measure of maternal investment, which are likely buffered against perturbations in maternal condition.
Fast Modulation of d‐Band Holes Quantity in the Early Reaction Stages for Boosting Acidic Oxygen Evolution
Authors: Zhang Xiuxiu , Yang Chenyu , Gong Chen , Liu Meihuan , Zhou Wanlin , Su Hui , Yu Feifan , Hu Fengchun , Liu Qinghua , Wei Shiqiang
Published: June 2023

Synthesis of highly active and durable oxygen evolution reaction (OER) catalysts applied in acidic water electrolysis remains a grand challenge. Here, we construct a type of high‐loading iridium single atom catalysts with tunable d‐band holes character (h‐HL−Ir SACs, ∼17.2 wt % Ir) realized in the early OER operation stages. The in situ X‐ray absorption spectroscopy reveals that the quantity of the d‐band holes of Ir active sites can be fast increased by 0.56 unit from the open circuit to a low working potential of 1.35 V. More remarkably, in situ synchrotron infrared and Raman spectroscopies demonstrate the quick accumulation of *OOH and *OH intermediates over holes‐modulated Ir sites in the early reaction voltages, achieving a rapid OER kinetics. As a result, this well‐designed h‐HL−Ir SACs exhibits superior performance for acidic OER with overpotentials of 216 mV @10 mA cm−2 and 259 mV @100 mA cm−2, corresponding to a small Tafel slope of 43 mV dec−1. The activity of catalyst shows no evident attenuation after 60 h operation in acidic environment. This work provides some useful hints for the design of superior acidic OER catalysts.
Rhodium‐Catalyzed Enantioselective 1,4‐Oxyamination of Conjugated gem‐Difluorodienes via Coupling with Carboxylic Acids and Dioxazolones
Authors: Li Xingwei , Song Heng , Yu Songjie , Mi Ruijie , Li Xiao‐Xi
Published: June 2023

The incorporation of fluorine atoms in organics improves their bioactivity and lipophilicity. Catalytic functionalization of gem‐difluorodienes represents one of the most straightforward approaches to access fluorinated alkenes. In contrast to the regular 1,3‐dienes that undergo diverse asymmetric di/hydrofunctionalizations, the regio‐ and enantioselective oxyamination of gem‐difluorodienes remains untouched. Herein, we report asymmetric 1,4‐oxyamination of gem‐difluorodiene by chiral rhodium‐catalyzed three‐component coupling with readily available carboxylic acid and dioxazolone, affording gem‐difluorinated 1,4‐amino alcohol derivatives. Our asymmetric protocol exhibits high 1,4‐regio‐ and enantioselectivity with utility in the late‐stage modification of pharmaceuticals and natural products. Stoichiometric experiments provide evidences for the π‐allylrhodium pathway. Related oxyamination was also realized when trifluoroethanol was used as an oxygen nucleophile.
Insights into the Electronic Structure Effect of SnMnOx Nanorod Catalysts for Low‐Temperature Catalytic Combustion of o‐Dichlorobenzene
Authors: Wang Jie , Dong Fang , Tang Zhicheng , Niu Lei , Zhao Xia
Published: June 2023

For the catalytic combustion reaction of chlorinated volatile organic compounds (CVOCs), the redox properties and acid sites of the catalyst surface are key factors in determining the activity, selectivity, and chlorine‐resistance stability. Herein, a series of SnMnOx catalysts for the catalytic combustion of CVOCs were prepared by the changing of Sn‐doping way to regulate the electron valance state of Mn element, including reflux (R‐SnMnOx), co‐precipitation (C‐SnMnOx) and impregnation (I‐SnMnOx). It was discovered that the R‐SnMnOx catalyst had better activity and chlorine resistance than the R‐MnOx, C‐SnMnOx and I‐SnMnOx catalyst, and we discovered that the doping ways of Sn in MnOx catalyst could regulate greatly the surface acidity, active oxygen species, the chemical state of Mnn+ species, and redox ability. Especially, the R‐SnMnOx catalysts exhibit excellent water resistance, and the reasons were related to the strong interaction of Snn+ and Mnn+, which could promote obviously the dispersion of active Mn species, form a large number of acid sites, provide the abundant lattice oxygen species, and own the excellent redox ability, which accelerate the rate of charge transfer between Snn+ and Mnn+ (Sn4++Mn2+→Sn2++Mn4+) to produce the abundant active species and accelerate the rapid conversion of benzene and intermediates conversion.
Revealing the Influence of Electrolyte Additives in Reducing the Heat Generation of High Voltage Lithium‐Ion Batteries using Operando Accelerating Rate Calorimetry (ARC)
Authors: Baazizi Mariam , Sayah Simon , Karbak Mehdi , Hajjaj Oumaima , Aqil Mohamed , Dahbi Mouad , Ghamouss Fouad
Published: June 2023

Lithium‐ion batteries operating at high voltage generally endure drastic capacity fading and serious safety issues. Working on the electrolytes’ stability can be a solution to mitigate these problems related to high voltage. Herein, the beneficial impact of functional electrolyte additives in a state‐of‐the‐art carbonate‐based electrolyte is demonstrated. The combination of fluoroethylene carbonate (FEC) with succinonitrile (SN) as additives was used to enhance the thermal stability of the electrolyte reference 1 M LiPF6 in EC:DMC (1 : 1, by weight) and cycling stability of a high voltage lithium‐ion device, consisting of a LiMn1.5Ni0.5O4 cathode and a metallic lithium anode. The electrolyte using the FEC/SN mixture displayed a wider electrochemical stability window (ESW) exhibited by linear sweep voltammetry (LSV). Furthermore, this electrolyte allowed the device to exhibit better rate capability and a capacity retention of 75 % after 100 cycles. Interestingly, the FEC+SN‐based electrolyte exhibited better thermal stability using operando accelerating rate calorimetry (ARC) by virtue of the lower heat quantity generated by the battery device. The remarkable improvements can be ascribed to the formation of a protective cathode‐electrolyte interface (CEI) produced by interfacial reactions between the cathode surface and electrolyte compounds.
Efficient secretion of mussel adhesion proteins using a chaperone protein Spy as fusion tag inBacillus subtilis
Authors: Wu Panpan , Tao Qing , Liu Yuxuan , Zeng Caiting , Li Yu , Yan Xin
Published: June 2023

Background

Mussel foot proteins (Mfps) are considered as remarkable materials due to their extraordinary adhesive capability. Recombinant expression is an ideal way to synthesis these proteins at large scale. However, secretory expression of Mfps into culture medium has not been achieved in a heterologous host.

Methods and Results

Here, to realize the secretion of Mfp3 and Mfp5 inBacillus subtilis, signal peptide screening was first performed. Minimal Mfp3‐6×His was targeted into the growth medium with AmyE signal peptide. We found that a small chaperone protein Spy was secreted efficiently inB. subtilis, and the fusion proteins Spy‐Mfp3‐6×His and Spy‐Mfp5‐6×His could also be delivered into growth medium well. The yield of Spy‐Mfp3‐6×His and Spy‐Mfp5‐6×His reached 255 and 119 mg L−1at shake flask conditions, respectively. Mfp3‐6×His and Mfp5‐6×His were finally purified via TEV protease cleavage and NTA affinity chromatography.

Conclusion

Mfp3‐6×His and Mfp5‐6×His could be efficiently secreted using a chaperone protein Spy as fusion tag inB. subtilis.
A current view on the neglected topic of male child sexual abuse in the context of literature
Authors: Sari Seda Aybuke , Bilac Oznur , Erten Almak Tilbe , Butun Celal
Published: June 2023

Despite the growing numbers, awareness and reporting rates of male child sexual abuse (MCSA) are still well below the real values, especially in developing countries like Turkey. We examined MCSA to determine the predisposing factors, the characteristics of perpetrators and victims, and the consequences of sexual abuse in a Turkish sample. We retrospectively analysed the files and forensic reports of 51 MCSA victims aged between 6 and 18. The mean age of children was 13.6 ± 3.8 years, and the mean age at the time of abuse was 11.1 ± 3.52. The average exposure time for sexual abuse was 91 ± 226.8 days, and the frequency was 2.4 ± 2.47 times. 17.6 per cent of them had previously been sexually abused. Disclosure times until legal notification was 240.1 ± 552.25 days. Most (56.9 per cent) had suffered anal penetration, developed post traumatic stress disorder, and needed medical treatment. Most perpetrators (58.8 per cent) were strangers outside the family, reaching the children from the neighbourhood. In conclusion, although the number of our sample is limited, the results of our study will contribute valuably to the literature, given that there are few studies on MCSA. Further studies with large samples evaluating MCSA in multidimensional ways are needed to raise awareness and protect vulnerable children.
Combined Metabolite Analysis and Network Pharmacology to Elucidate the Mechanisms of Therapeutic Effect of Melastoma dodecandrum Ellagitannins on Abnormal Uterine Bleeding
Authors: Lu Qiu‐Ping , Wu Miao‐Li , Li Hui‐Lin , Zhou Yu , Xian Ming‐Hua , Huang Wei‐Zhong , Piao Xiu‐Hong , Ge Yue‐Wei
Published: June 2023

The abnormal uterine bleeding (AUB) is complex and usually leads to severe anemia. Melastomadodecandrum (MD) is clinically used for the treatment of metrorrhagia bleeding. The MD ellagitannins (MD‐ETs) had been evidenced being effective at hemorrhage, and exerts biological activities upon their metabolites including ellagic acid and urolithins. In this study, the blood‐permeated metabolites from theMD‐ETs were analyzed using LC‐MS approach, and 19 metabolites including ellagic acid and urolithin A derivatives were identified. Furthermore, a network pharmacology analysis including the target prediction analysis, AUB target analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted to reveal the relationships between “metabolites‐targets‐pathways”, which was further verified by molecular docking analysis. The results showed that methyl ellagic acid, urolithin A and isourolithin A produced from MD‐ETs can be absorbed into the blood, and might act on the core targets of VEGFA, SRC, MTOR, EGFR and CCND1. And the hemostatic effects were exerted through PI3K‐Akt, endocrine resistance and Rap 1 signaling pathways. These results implied the potential effective constituents and action mechanism of MD‐ETs in the therapy of AUB, which will promote the application of MD‐ETs as natural agent for the treatment of gynecological bleeding diseases.
Genome Mining and Molecular Networking Guided Isolation of Antimycin Analogs with Antifeedant Activities from the Deep‐Sea‐Derived Streptomyces sp. NA13
Authors: Bai Yan , Ren Duo , Li Fenglin , Hu Jiangchun , Pan Huaqi
Published: June 2023

Polyphagous insects could affect agricultural production, which leads to serious economic losses. Due to the negative effects of synthesized insecticides, finding eco‐friendly and new biopesticides is emergent. To develop natural origin insecticides, an integrative approach combining antifeedant activity screening, genome mining, and molecular networking has been applied to discover antifeedant secondary metabolites from Streptomyces sp. NA13, which leads to the isolation of a novel antimycin Q (1) and six known antimycin analogs (antimycins A1a, A2a, A3a, A4a, A7a, and N‐formylantimycic acid methyl ester, 2–7). Their structures were identified by high‐resolution mass spectrometry (HR‐MS) and nuclear magnetic resonance (NMR) spectroscopic. The absolute configuration of 1 was elucidated by the comparison of coupling constant, electronic circular dichroism (ECD) analysis, and NMR calculations. 1–6 exhibited different levels of antifeedant activities against Helicoverpa armigera, especially 1–4. At the same time, the antifeedant activity of antimycin was reported firstly.
The s‐p Nonhybrid Nature Causes Adaptive Superatomic States of Bismuth Clusters
Authors: Geng Lijun , Du Qiuying , Li Mengxu , Yin Baoqi , Luo Zhixun , Zhao Jijun
Published: June 2023

We report a joint experimental and theoretical study on the stability and reactivity of Bin+ (n=5–33) clusters. The alternating odd‐even effect on the reaction rates of Bin+ clusters with NO is observed, and Bi7+ finds the most inertness. First‐principles calculation results reveal that the lowest energy structures of Bi6‐9+ exhibit quasi‐spherical geometry pertaining to the jellium shell model; however, the Bin+ (n≥10) clusters adopt assembly structures. The prominent stability of Bi7+ is associated with its highly symmetric structure and superatomic states with a magic number of 34e closed shell. For the first time, we demonstrate that the unique s‐p nonhybrid feature in bismuth rationalizes the stability of Bi6‐9+ clusters within the jellium model, by filling the 6s electrons into the superatomic orbitals (forming “s‐band”). Interestingly, the stability of 18e “s‐band” coincides with the compact structure for Bin+ at n≤9 but assembly structures for n≥10, showing an accommodation of the s electrons to the geometric structure. The atomic p‐orbitals also allow to form superatomic orbitals at higher energy levels, contributing to the preferable structures of tridentate binding units. We illustrate the s‐p nonhybrid nature accommodates the structure and superatomic states of bismuth clusters.
Evolving spectrum of arrhythmogenic cardiomyopathy: Implications for Sports Cardiology
Authors: Graziano Francesca , Cipriani Alberto , Balla Dorottya , Bondarev Sergei , Marra Martina Perazzolo , Bauce Barbara , Vágó Hajnalka , Corrado Domenico , Zorzi Alessandro
Published: June 2023

Arrhythmogenic cardiomyopathy (ACM) is a genetic heart muscle disease, structurally characterized by progressive fibro‐fatty replacement of the normal myocardium and clinically by ventricular arrhythmias (VAs). Predominantly thanks to the use of cardiac magnetic resonance, we have learnt that the spectrum of the disease encompasses not only the classical right ventricular phenotype, but also biventricular and left dominant variants. Sport activity contributes to the phenotypic expression and progression of ACM and may trigger life‐threatening VAs and sudden cardiac death (SCD). We conducted a review of the literature about ACM and its implications in Sport Cardiology and summarized the main findings in this topic. Early identification of affected athletes through preparticipation screening (PPS) is fundamental but, while classical right‐ventricular or biventricular phenotypes are usually suspected because of electrocardiogram (ECG) and echocardiographic abnormalities, variants with predominant left ventricular involvement are often characterized by normal ECG and unremarkable echocardiography. Usually the only manifestations of such variants are exercise‐induced VAs and for this reason exercise testing may empower the diagnostic yield of the PPS. Patients with ACM are not eligible to competitive sports activity, but low‐to‐moderate intensity physical activity under medical supervision is possible in most cases.
Comparative features of calretinin, calbindin, and parvalbumin expressing interneurons in mouse and monkey primary visual and frontal cortices
Authors: Medalla Maria , Mo Bingxin , Nasar Rakin , Zhou Yuxin , Park Junwoo , Luebke Jennifer I.
Published: June 2023

Fundamental differences in excitatory pyramidal cells across cortical areas and species highlight the implausibility of extrapolation from mouse to primate neurons and cortical networks. Far less is known about comparative regional and species‐specific features of neurochemically distinct cortical inhibitory interneurons. Here, we quantified the density, laminar distribution, and somatodendritic morphology of inhibitory interneurons expressing one or more of the calcium‐binding proteins (CaBPs) (calretinin [CR], calbindin [CB], and/or parvalbumin [PV]) in mouse (Mus musculus) versus rhesus monkey (Macaca mulatta) in two functionally and cytoarchitectonically distinct regions—the primary visual and frontal cortical areas—using immunofluorescent multilabeling, stereological counting, and 3D reconstructions. There were significantly higher densities of CB+ and PV+ neurons in visual compared to frontal areas in both species. The main species difference was the significantly greater density and proportion of CR+ interneurons and lower extent of CaBP coexpression in monkey compared to mouse cortices. Cluster analyses revealed that the somatodendritic morphology of layer 2–3 inhibitory interneurons is more dependent on CaBP expression than on species and area. Only modest effects of species were observed for CB+ and PV+ interneuron morphologies, while CR+ neurons showed no difference. By contrast to pyramidal cells that show highly distinctive area‐ and species‐specific features, here we found more subtle differences in the distribution and features of interneurons across areas and species. These data yield insight into how nuanced differences in the population organization and properties of neurons may underlie specializations in cortical regions to confer species‐ and area‐specific functional capacities.
Biomimetic Synthesis and Mechanism of Hydroxyapatite Crystals by Biotemplate of Small Intestinal Submucosa and Bacterial Cellulose
Authors: Zhu Qiuhong , Jiao Hua , Zhao Kang , Gou Xingchun , Tang Yufei , Ji Jingwen
Published: June 2023

Hydroxyapatite (HAp) is coassembled with many organic molecular templates led by collagens in natural bone. In this study, it is presumed that small intestinal submucosa (SIS) with acetamide group chelates calcium ion and bacterial cellulose (BC) has strong intermolecular hydroxyl group and powerful attraction for calcium ion to initiate initial nucleation. Phosphate ions bind calcium ions to form seed crystal of calcium phosphate, which is further directionally grown under the mediation of the template structure and finally forms weakly crystalline HAp, providing an environment for the HAp formation. Besides, the samples are characterized by X‐ray diffraction, Fourier transform infrared, X‐ray photoelectron spectroscopy, scanning electron microscope, and transmission electron microscope to unveil the phase structure, composition, and morphology, and a growth mechanism is proposed. HAp is successfully synthesized on SIS–BC biomineralization template. The results show morphology of samples from sheet‐lamellar‐like to flower‐like or porous‐spheroid‐like from 1 day to 7 days. The plate‐like HAp rods are polycrystal with c‐axis orientation. Interestingly, the HAp/SIS‐BC composites have the least relative mass of HAp on mineralization and the content of HAp (57%) is very close to the human bone tissue in structure (about 60%). Finally, the HAp mineralized films show good biocompatibility through MC3T3‐E1cells test for the potential biomaterials.
Influence of skin type and laser wavelength on laser‐evoked potentials
Authors: Frahm Ken Steffen , Gervasio Sabata , Arguissain Federico , Mouraux André
Published: June 2023

Background

Infrared laser stimulation is a valuable tool in pain research, its primary application being the recording of laser‐evoked brain potentials (LEPs). Different types of laser stimulators, varying in their skin penetrance, are likely to have a large influence on the LEPs, when stimulating different skin types. The aim of this study was to investigate how LEPs depend on laser type and skin location.

Methods

Two different laser stimulators (CO2 and Nd:YAP) were used to compare LEPs in healthy subjects. Stimuli were delivered to the hand dorsum and palm to investigate the effects of skin type on the evoked responses. Stimulus‐evoked brain responses were recorded using EEG and perceived intensity ratings were recorded. Computational modelling was used to investigate the observed differences.

Results

LEPs evoked by stimulation of the hairy skin were similar between CO2 and Nd:YAP stimulation. In contrast, LEPs elicited from the palm were markedly different and barely present for CO2 stimulation. There was a significant interaction between laser type and skin type (RM‐ANOVA, p < 0.05) likely due to smaller CO2 LEPs in the palm. CO2 stimuli to the palm also elicited significantly lower perceived intensities. The computational model showed that the observed differences were explainable by the laser absorption characteristics and skin thickness affecting the temperature profile at the dermo‐epidermal junction (DEJ).

Conclusions

This study shows that LEP elicitation depends on the combination of laser penetrance and skin type. Low penetrance stimuli, from a CO2 laser, elicited significantly lower LEPs and perceived intensities in the palm.

Significance

This study showed that the elicitation of laser‐evoked potentials in healthy humans greatly depends on the combination of laser stimulator type and skin type. It was shown that high penetrance laser stimuli are capable of eliciting responses in both hairy and glabrous skin, whereas low penetrance stimuli barely elicited responses from the glabrous skin. Computational modelling was used to demonstrate that the results could be fully explained by the combination of laser type and skin thickness.
Research and scholarly methods: Studies of workplace well‐being and other organizational phenomena
Authors: Reed Brent N. , McGonagle Alyssa K.
Published: June 2023

As research in pharmacy increasingly focuses on work‐related topics such as burnout, workforce management, and diversity, equity, and inclusion, there is a growing need for scholars to understand and use organizational research methods. However, these skills are not typically taught in pharmacy schools or postgraduate training programs, posing a challenge to researchers and peer reviewers alike. To address this gap, we aim to provide a practical introduction to organizational research methods with a focus on deductive, quantitative approaches. Given the growing interest in studying pharmacists' workplace well‐being, we use this as a theme for our review. We begin by discussing the importance of a thorough literature review and using theory to frame the research, develop study hypotheses, and select an appropriate research design. We also provide a list of example theories that researchers could use to study the topic of workplace well‐being. Next, we discuss key considerations for defining and measuring organizational constructs, including validity and reliability, and highlight potential pitfalls to avoid in survey research. Using several phenomena of interest in studies of workplace well‐being, we provide examples of construct definitions and illustrate how they could be operationalized as variables in a research study. Finally, we discuss important considerations for analyzing organizational data and describe skills that researchers should acquire or seek in potential collaborators. To aid researchers and peer reviewers, we provide a checklist summarizing our recommendations and references to additional resources. By equipping scholars with a better understanding of organizational research methods, we aim to enhance our understanding of pharmacists' work experiences and generate evidence to support workplace improvements that will benefit pharmacists and their efforts to provide patient care.
Nanoscale implant anchorage aided by cement line deposition into titanium dioxide nanotubes
Authors: Grandfield Kathryn , Binkley Dakota Marie , Ay Birol , Liu Zhen Mei , Wang Xiaoyue , Davies John E.
Published: June 2023

The success of titanium dental implants relies on osseointegration, the load‐bearing connection between bone tissue and the device that, in contact osteogenesis, comprises the deposition of bony cement line matrix onto the implant surface. Titanium dioxide nanotubes (NTs) are considered a promising surface for improved osseointegration, yet the mechanisms of cement line integration with such features remains elusive. Herein, we illustrate cement line deposition into NTs on the surface of titanium implants with two underlaying microstructures: a machined surface or a blasted/acid etched surface placed in the tibiae of Wistar rats. After retrieval, scanning electron microscopy of tissue reflected from the implant surface indicated minimal incursion of the cement line matrix into the NTs. To investigate this further, focused ion beam was utilized to prepare cross‐sectional samples that could be characterized using scanning transmission electron microscopy. The cement line matrix covered NTs regardless of underlying microstructure, which was further confirmed by elemental analysis. In some instances, cement line infiltration into the NTs was noted, which reveals a mechanism of nanoscale anchorage. This study is the first to demonstrate cement line deposition into titanium NTs, suggesting nano‐anchorage as a mechanism for the success of the NT modified surfaces in vivo.
Exploring the inhibition mechanism of SARS‐CoV‐2 main protease by ebselen: A molecular docking, molecular dynamics simulation and DFT approach
Authors: You Wanli , Chen Yuandao
Published: June 2023

The main protease (Mpro) of SARS‐CoV‐2 plays an essential role in the virus life cycle and is considered a key target for therapeutic development. This study explores the inhibition mechanism of SARS‐CoV‐2 Mpro by ebselen, an organoselenium drug that shows potent inhibitory activity. By using a combination of multiple computational methods including molecular docking, molecular dynamics simulations, and density functional theory calculations, the complete covalent inhibition process of ebselen is simulated for the first time. Two possible pathways with different bound conformations of ebselen are identified. The hydrolysis of the enzyme‐ebselen adduct is found to be the rate‐determining step. The simulation results show that the behavior of water molecules at the hydrolysis site is crucial to distinguish the two paths energetically. Our simulations, which are in agreement with existing experimental results, provide a theoretical basis for the rational design and mechanism exploration of ebselen‐based inhibitors.
Periodontal ligament‐associated protein‐1 knockout mice regulate the differentiation of osteoclasts and osteoblasts through TGF‐β1/Smad signaling pathway
Authors: Liu Shuang , Yan Xiao , Guo Jing , An Hong , Li Xingrui , Yang Liying , Yu Xijiao , Li Shu
Published: June 2023

It has been known that periodontal ligament‐associated protein‐1 (PLAP‐1/Asporin) not only inhibits cartilage formation in osteoarthritis, but it also influences the healing of skull defect. However, the effect and mechanism of PLAP‐1/Asporin on the mutual regulation of osteoclasts and osteoblasts in periodontitis are not clear. In this study, we utilized a PLAP‐1/Asporin gene knockout (KO) mouse model to research this unknown issue. We cultured mouse bone marrow mesenchymal stem cells with Porphyromonas gingivalis lipopolysaccharide (P.g. LPS) for osteogenic induction in vitro. The molecular mechanism of PLAP‐1/Asporin in the regulation of osteoblasts was detected by immunoprecipitation, immunofluorescence, and inhibitors of signaling pathways. The results showed that the KO of PLAP‐1/Asporin promoted osteogenic differentiation through transforming growth factor beta 1 (TGF‐β1)/Smad3 in inflammatory environments. We further found the KO of PLAP‐1/Asporin inhibited osteoclast differentiation and promoted osteogenic differentiation through the TGF‐β1/Smad signaling pathway in an inflammatory coculture system. The experimental periodontitis model was established by silk ligation and the alveolar bone formation in PLAP‐1/Asporin KO mice was promoted through TGF‐β1/Smad3 signaling pathway. The subcutaneous osteogenesis model in nude mice also confirmed that the KO of PLAP‐1/Asporin promoted bone formation by the histochemical staining. In conclusion, PLAP‐1/Asporin regulated the differentiation of osteoclasts and osteoblasts through TGF‐β1/Smad signaling pathway. The results of this study lay a theoretical foundation for the further study of the pathological mechanism underlying alveolar bone resorption, and the prevention and treatment of periodontitis.
PRPF8 controls alternative splicing of PIRH2 to modulate the p53 pathway and survival of human ESCs
Authors: Sun Yiyang , Zhang Lingling , Fang Zhuoqing , Liu Dingyu , Shao Min , Liu Yujie , Liao Bing , Jin Ying
Published: June 2023

Human embryonic stem cells (hESCs) have great potential for developmental biology and regenerative medicine. However, extensive apoptosis often occurs when hESCs respond to various stresses or injuries. Understanding the molecular control and identifying new factors associated with hESC survival are fundamental to ensure the high quality of hESCs. In this study, we report that PRPF8, an RNA spliceosome component, is essential for hESC survival. PRPF8 knockdown (KD) induces p53 protein accumulation and activates the p53 pathway, leading to apoptosis in hESCs. Strikingly, silencing of p53 rescues PRPF8 KD‐induced apoptosis, indicating that PRPF8 KD triggers hESC apoptosis through activating the p53 pathway. In search for the mechanism by which p53 pathway is activated by PRPF8 KD, we find that PRPF8 KD alters alternative splicing of many genes, including PIRH2 which encodes an E3 ubiquitin ligase of p53. PIRH2 has several isoforms such as PIRH2A, PIRH2B, and PIRH2C. Intriguingly, PRPF8 KD specifically increases the transcript level of the PIRH2B isoform, which lacks a RING domain and E3 ligase activity. Functionally, PIRH2B KD partially rescues the reduction in cell numbers and upregulation of P21 caused by PRPF8 KD in hESCs. The finding suggests that PRPF8 controls alternative splicing of PIRH2 to maintain the balance of p53 pathway activity and survival of hESCs. The PRPF8/PIRH2/p53 axis identified here provides new insights into how p53 pathway and hESC survival are precisely regulated at multiple layers, highlighting an important role of posttranscriptional machinery in supporting hESC survival.
Counterfactual estimation of efficacy against placebo for novel PrEP agents using external trial data: example of injectable cabotegravir and oral PrEP in women
Authors: Donnell Deborah , Gao Fei , Hughes James P. , Hanscom Brett , Corey Lawrence , Cohen Myron S. , Edupuganti Srilatha , Mgodi Nyaradzo , Rees Helen , Baeten Jared M. , Gray Glenda , Bekker Linda‐Gail , Hosseinipour Mina , Delany‐Moretlwe Sinead
Published: June 2023

Introduction

Multiple antiretroviral agents have demonstrated efficacy for human immunodeficiency virus (HIV) pre‐exposure prophylaxis (PrEP). As a result, clinical trials of novel agents have transitioned from placebo‐ to active‐controlled designs; however, active‐controlled trials do not provide an estimate of efficacy versus no use of PrEP. Counterfactual placebo comparisons using other data sources could be employed to provide this information.

Methods

We compared the active‐controlled study (HPTN 084) of injectable cabotegravir (CAB‐LA) versus daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) among women from seven countries in Africa to three external, contemporaneous randomized HIV prevention trials from which we constructed counterfactual placebo estimates. We used direct standardization via analysis weights to achieve the same distribution of person‐years between the external study and HPTN 084, across strata predictive of HIV risk (country and selected risk covariates). We estimated prevention efficacy against a counterfactual placebo to provide information on the use of CAB‐LA and FTC/TDF compared to no intervention. We compared the counterfactual placebo findings for FTC/TDF to previous placebo‐controlled trials, adjusted for observed adherence to daily pills.

Results

Distribution of age and baseline prevalence of gonorrhoea and chlamydia were similar among matched counterfactual placebo and observed HPTN 084 arms after standardization. Counterfactual estimates of CAB‐LA versus placebo in all three settings showed a consistent risk reduction of 93%–94%, with lower bounds of the confidence intervals above 72%. Observed adherence (quantifiable tenofovir in plasma) in HPTN 084 was 54%–56%, and estimated efficacy of daily oral FTC/TDF against a counterfactual placebo was consistent with a predicted risk reduction of 39%–40% for this level of daily pill use.

Conclusions

Counterfactual placebo rates of HIV acquisition derived from external trial data in similar locations and time can be used to support estimates of placebo‐based efficacy of a novel HIV prevention agent. External trial data must be standardized to be representative of the clinical trial cohort testing the novel HIV prevention agent, accounting for confounders.
One‐pot fabrication of magnetic adsorbent based on polymeric ionic liquid/aminated carbon nanotubes composite for efficient capture of synthetic auxins in complex samples prior to chromatographic analysis
Authors: Zhang YueYue , Huang Youfang , Huang Xiaojia
Published: June 2023

Efficient enrichment is a challenging and indispensable step in the quantification of polar synthetic auxins in complex samples. In the current study, a new magnetic adsorbent based on polymeric ionic liquid/aminated carbon nanotube composite was fabricated with a one‐pot precipitation copolymerization strategy and employed as the extraction phase of magnetic solid phase extraction of synthetic auxins. Various characterization techniques were utilized to inspect the morphology, structure, magnetic property, and functional groups of the prepared adsorbent. Under the optimal conditions, the obtained adsorbent displayed satisfactory capture performance towards studied auxins through multiple interactions. Adsorption studies evidenced that the adsorption procedure of the developed method towards analytes was fit for the Freundlich adsorption model and pseudo‐second‐order kinetics. Combining with high‐performance liquid chromatography, sensitive and reliable method for the identification and quantification of trace synthetic auxins in environmental water and fruit juice samples was developed. The obtained limits of detection for water and fruit juice samples located in the ranges of 0.0059–0.013 and 0.018–0.031 μg/L, respectively. Recoveries in actual samples with different fortified contents varied from 82.2% to 117%, with satisfactory reproducibility. The results will evidence that the introduced extraction technique is a useful alternative for the entrapment of trace synthetic auxins from complex samples.
Behavior‐specific habitat selection by raccoons in the Prairie Pothole Region of Manitoba
Authors: Milling Charlotte R. , Gehrt Stanley D.
Published: June 2023

Patterns of resource selection depend upon an animal's behavioral state. Because management strategies are often crafted from an understanding of animal space use, incorporating behavior explicitly into analyses of resource selection has the potential to improve outcomes. In the Prairie Pothole Region of Manitoba, Canada, raccoons (Procyon lotor) are a nest predator of waterfowl, but it is unclear how raccoons use this landscape during the waterfowl nesting season. Our objective was to use high‐resolution global positioning system (GPS) telemetry to differentiate among behaviors by raccoons and evaluate behavior‐specific habitat selection during the waterfowl nesting season. We collected approximately 32,000 locations from 33 animals during the 2018, 2019, and 2021 nesting seasons, amounting to 632 animal‐night's worth of movement data. We used hidden Markov models (HMM) to fit 4‐state models to the movement trajectories, classified observations into discrete behaviors, and fit behavior‐specific random forest resource selection models to evaluate the relative importance of habitat features on selection. Proximity to a wetland was the most important variable contributing to selection for the resting, foraging, and slow travel states. Probability of use was as high as 95% within or immediately adjacent to a wetland for animals engaged in those behaviors, and our best HMM predicted increasing probability of switching from resting or foraging to directed travel with increasing distance from a wetland edge. Human‐use sites were also important to foraging animals, suggesting raccoons subsidize their diet with anthropogenic food resources during spring and summer. These results illuminate the complexity of habitat selection by a waterfowl predator in this patchy landscape, allowing managers to develop effective conservation strategies (e.g., wetland prioritization and conservation, elimination of anthropogenic subsidies) where raccoons are having a disproportionate effect during the waterfowl nesting season.
Effect of continuous local dexamethasone on tissue biomechanics and histology after inhalational burn in a preclinical model
Authors: Malka Ronit , Gonzales Gabriela , Detar Will , Marinelli Lisa , Lee Christine M. , Isaac Alisa , Miar Solaleh , Cook Stacy , Guda Teja , Dion Gregory R.
Published: June 2023

Objective

Inhalational burns frequently lead to dysphonia and airway stenosis. We hypothesize local dexamethasone delivery via a novel drug‐eluting electrospun polymer‐mesh endotracheal tube (ETT) reduces biomechanical and histologic changes in the vocal folds in inhalational burn.

Methods

Dexamethasone‐loaded polymer mesh was electrospun onto ETTs trimmed to transglottic endolaryngeal segments and secured in nine Yorkshire Crossbreed swine with directed 150°C inhalation burns. Uncoated ETTs were implanted in nine additional swine with identical burns. ETT segments were maintained for 3 and 7 days. Vocal fold (VF) structural stiffness was measured using automated‐indentation mapping and compared across groups and to four uninjured controls, and matched histologic assessment performed. Statistical analysis was conducted using two‐way ANOVA with Tukey's post hoc test and Wilcoxon rank‐sum test.

Results

VF stiffness after burn decreased with longer intubation, from 19.4 (7.6) mN/mm at 3 days to 11.3 (5.2) mN/mm at 7 days (p < .0001). Stiffness similarly decreased with local dexamethasone, from 25.9 (17.2) mN/mm at 3 days to 18.1 (13.0) mN/mm at 7 days (p < .0001). VF stiffness in the dexamethasone group was increased compared to tissues without local dexamethasone (p = .0002), and all groups with ETT placement had higher tissue stiffness at 3 days (p < .001). No significant change in histologic evidence of epithelial ulceration or fibrosis was noted, while an increased degree of inflammation was noted in the dexamethasone group (p = .04).

Conclusion

Local dexamethasone delivery increases VF stiffness and degree of inflammation compared to uncoated ETTs in an acute laryngeal burn model, reflected in early biomechanical and histologic changes in an inhalational burn model.
Biocompatible Polymer‐Modified Nanoplatform for Ferroptosis‐Enhanced Combination Cancer Therapy
Authors: He Meng , Dan Yuxin , Chen Mingsheng , Dong Chang‐Ming
Published: June 2023

Ferroptosis is a novel type of iron‐dependent non‐apoptotic pathway that regulates cell death and shows unique mechanisms including causing lipid peroxide accumulation, sensitizing drug‐resistant cancers, priming immunity by immunogenic cell death, and cooperatively acting with other anticancer modalities for eradicating aggressive malignancies and tumor relapse. Recently, there has been a great deal of effort to design and develop anticancer biocompatible polymeric nanoplatforms including polypeptide and PEGylated ones to achieve effective ferroptosis therapy (FT) and synergistic combination therapies including chemotherapy (CT), photodynamic therapy (PDT), sonodynamic therapy (SDT), photothermal therapy (PTT), gas therapy (GT) including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), and immunotherapy (IT). To be noted, the combo therapies such as FT‐CT, FT‐PTT, FT‐GT, and FT‐IT are attracting much efforts to fight against intractable and metastatic tumors as they can generate synergistic antitumor effects and immunogenic cell death (ICD) effects or modulate immunosuppressive tumor microenvironments to initiate strong antitumor immunity and memory effects. The polymeric Fenton nano‐agents with good biosafety and high anticancer efficacy will provide a guarantee for their applications. In this review, various biocompatible polymer‐modified nanoplatforms designed for FT and combo treatments are summarized for anticancer therapies and discussed for potential clinical transitions.
Referral strategy of e‐commerce platform under different selling modes
Authors: Wang Xin , Yu Lin , Zhang Shuhua , Wu Shuping , Yu Baoqin , Ye Xiaofen
Published: June 2023

This study considers a market comprising two suppliers and one e‐commerce platform. The two competitive suppliers sell products to consumers through the platform. The platform can choose three selling modes: reseller, market, and mixed. Additionally, we consider two referral strategies—namely, exclusive and nonexclusive recommendations—and build a three‐party Stackelberg game model. Per the findings, the difference in the players' decision‐making results exhibits an essential relationship with the recommendation market's initial size. A counterintuitive result is that the product price is not affected by the commission rate in the market mode. This provides referential insights for platforms and suppliers.