bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcome of IWGT workshop on transcriptomic biomarkers for genotoxicity: Key considerations for bioinformatics
Authors: Meier Matthew J. , Caiment Florian , Corton J. Christopher , Frötschl Roland , Fujita Yurika , Jennen Danyel , Mezencev Roman , Yauk Carole
Published: December 2024

As a part of the International Workshop on Genotoxicity Testing (IWGT) in 2022, a workgroup was formed to evaluate the level of validation and regulatory acceptance of transcriptomic biomarkers that identify genotoxic substances. Several such biomarkers have been developed using various molecular techniques and computational approaches. Within the IWGT workgroup on transcriptomic biomarkers, bioinformatics was a central topic of discussion, focusing on the current approaches used to process the underlying molecular data to distill a reliable predictive signal; that is, a gene set that is indicative of genotoxicity and can then be used in later studies to predict potential DNA damaging properties for uncharacterized chemicals. While early studies used microarray data, a technological shift occurred in the past decade to incorporate modern transcriptome measuring techniques such as high‐throughput transcriptomics, which in turn is based on high‐throughput sequencing. Herein, we present the workgroup's review of the current bioinformatic approaches to identify genes comprising transcriptomic biomarkers. Within the context of regulatory toxicology, the reproducibility of a given analysis is critical. Therefore, the workgroup provides consensus recommendations on how to facilitate sufficient reporting of experimental parameters for the analytical procedures used in a transcriptomic biomarker study, including the recommendation to develop a biomarker‐specific reporting module within the OECD Omics Reporting Framework.
Creating a new way to judge community college students’ successes
Authors: D’Orio Wayne
Published: December 2024

Are community colleges producing better outcomes than they are typically given credit for? The Federal Reserve Bank of Richmond thinks they are, and the independent research agency has created a new set of benchmarks to try to show these achievements.
Wandering campus footloose: Honoring and developing connections to campus buildings
Authors: Fatzinger Jim , Darville Dub
Published: December 2024

Campus buildings have been part of our community conversations of late, usually as leaders determine whether or not those particular founders or donors should be honored. But, as writer Goldie Blumenstyk recently shared, sometimes a building's name offers a sense of inclusion. Other authors have also discussed of late how physical infrastructure can help maximize campus pride, publicity, and even investment.
Faux Feminisms: Why feminism is a fight against oppression, not an individual cause
Authors: Arnett Autumn A.
Published: December 2024

In her forthcoming book, Faux Feminisms: Why We Fall for White Feminism and How We Can Stop, Jay Newman Chair in Philosophy of Culture at Brooklyn College, NY, and Professor of Philosophy and Women's and Gender Studies at the CUNY Graduate Center Serene Khader sets out to reframe the feminist movement as one for the collective advancement of all women.
A Modified Strain‐Wedge Model for Small Strain Rigid Piles in Sand
Authors: Yin Yisheng , Wang Dongyuan , Cui Kai
Published: December 2024

This paper develops a modified strain‐wedge (MSW) model that accounts for the resistance to bending moments caused by the lateral frictional resistance and axial forces of piles in the small‐strain regime in sands and algorithmizes a finite differential analysis program. Two cases of rigid pile tests, one in Blessington and another in Shenton Park were used to calibrate the finite element analysis model and verify the proposed modified model. The results show that the analysis of pile‐side resistance is pivotal for rigid horizontally loaded monopiles, and the MSW model is the most accurate at predicting lateral displacement and the moments. Its accuracy in a small‐strain regime to predict the pile rotation points and the maximum bending moment is almost three times that of other models. With the increase of the soil strain, the accuracy of the MSW decreases. On the contrary, the prediction accuracy of numerical analysis using the UBC3D‐PLM constitutive model increases.
Analytical Derivations and Numerical Verifications on the Asymmetric Dynamic Responses of the Buried Steel Pipelines Under Seismic Active Faults
Authors: Yang Denglian , Luo Zhongya , Li Zhaochao
Published: December 2024

The seismic ground movements may lead to significant bending, tensile, and compressive strains to the buried steel pipelines. This study concerns the dynamic behavior of the buried pipeline at its yielding state to offer preliminary design criteria in the geohazard region. An analytical scheme is proposed to assess the responses of the pipelines under a normal fault or a strike‐slip fault. A piecewise function is assumed to describe the deformed S‐shaped pipeline under the seismic fault. Then, the explicit strain and displacement are obtained by considering the asymmetry of curvature and pipeline‐soil interaction. Moreover, the deformed length and yield displacement are predicted explicitly based on the first yielding theory of the classical beam for both asymmetric and symmetric cases. In addition, the proposed analytical results, characterized by the deformed shape and the yield displacement, are verified efficiently by developing a three‐dimensional (3D) finite element model (FEM) in the present study, as well as other predictions elsewhere. It is found that the present study offers a good reference for strength evaluation and failure analysis of pipelines subjected to a normal fault or a strike‐slip fault.
Invasion risk posed by the pet trade
Authors: Evans Luke J , Baecher J Alex , Scheffers Brett R
Published: December 2024

The legal trade in exotic pets is linked to the establishment of nonnative species and climate change compounds the risk of invasion, overwhelming management efforts. We characterized the world's largest market for exotic pets—the US—by providing a real‐time snapshot of species with invasion potential, and assessed the current and future risk posed to native systems. We found a diverse marketplace of 1178 terrestrial vertebrates, predominantly tropical species. Using 2818 brick‐and‐mortar pet stores, we developed spatial models of propagule risk, from which it was determined that future climate change may increase climate suitability by 194%, which in turn equates to 83% of total land area in the contiguous US becoming suitable for invasion by 2080. Rapid growth in the exotic pet trade industry is expected to exacerbate current findings, especially at southernmost latitudes. The real‐time nature of this study provides more actionable management information than outdated import data.
The Spatial Organization of Ascending Auditory Pathway Microstructural Maturation From Infancy Through Adolescence Using a Novel Fiber Tracking Approach
Authors: Lynch Kirsten M. , Bodison Stefanie C. , Cabeen Ryan P. , Toga Arthur W. , Voelker Courtney C. J.
Published: December 2024

Auditory perception is established through experience‐dependent stimuli exposure during sensitive developmental periods; however, little is known regarding the structural development of the central auditory pathway in humans. The present study characterized the regional developmental trajectories of the ascending auditory pathway from the brainstem to the auditory cortex from infancy through adolescence using a novel diffusion MRI‐based tractography approach and along‐tract analyses. We used diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to quantify the magnitude and timing of auditory pathway microstructural maturation. We found spatially varying patterns of white matter maturation along the length of the tract, with inferior brainstem regions developing earlier than thalamocortical projections and left hemisphere tracts developing earlier than the right. These results help to characterize the processes that give rise to functional auditory processing and may provide a baseline for detecting abnormal development.
Fibroblast growth factor receptor four inhibitor FGF401 improves the efficacy of trastuzumab in FGFR4‐overexpressing breast cancer cells
Authors: Cheng Tzu‐Chun , Huang Bu‐Miin , Liao You‐Cheng , Chang Han‐Sheng , Tu Shih‐Hsin , Ho Yuan‐Soon , Chen Li‐Ching
Published: December 2024

Breast cancer is the most common cancer among women. Among them, human epidermal growth factor receptor‐positive (HER2+) breast cancer is more malignant. Fortunately, many anti‐HER2 drugs are currently used in clinical treatments to increase patient survival. However, some HER2+ patients (~15%) still develop drug resistance after receiving trastuzumab treatment, leading to treatment failure. Using CCLE and METABRIC database analyses, we found that fibroblast growth factor receptor 4 (FGFR4) mRNA was highly detected in tumors from HER2+ breast cancer patients (p < .001) and was associated with poorer survival in breast cancer patients. Through retrospective immunohistochemical staining analysis, we detected higher expression of FGFR4 protein in breast cancer tissues collected from patients who were resistant to trastuzumab therapy compared with breast cancer patients who responded to treatment. An FGFR4 inhibitor (FGF401) effectively inhibits tumor growth in trastuzumab‐insensitive patient‐derived xenograft (PDX) tumor‐bearing mice. For molecular mechanism studies, we demonstrated that HER2/FGFR4 protein complexes were detected on the cell membrane of the tumor tissues in these trastuzumab‐insensitive PDX tumor tissues. After trastuzumab treatment in these drug‐resistant breast cancer cells, FGFR4 translocates and enters the nucleus. However, trastuzumab‐induced nuclear translocation of FGFR4/HER2‐intracellular domain protein complex in trastuzumab‐resistant cancer cells is blocked by FGF401 treatment. We believe that FGFR4 overexpression and complex formation with HER2 can serve as molecular markers to assist clinicians in identifying trastuzumab‐resistant tumors. Our results suggest that FGF401 combined with trastuzumab as adjuvant therapy for patients with trastuzumab‐resistant breast cancer may be a potential new treatment strategy.
Pulsed Red Photobiomodulation Boosts the Inhibition of Oxytocin‐Induced Primary Dysmenorrhea in Mice by Suppressing Oxidative Stress and Inflammation
Authors: Fu Qiqi , Yang Jiali , Jiang Hui , Ren Yi , Huo Longfei , Liu Muqing
Published: December 2024

Increasing evidence has underscored the pivotal role of red photobiomodulation (R‐PBM) in analgesic and anti‐inflammatory processes; nonetheless, research concerning the effects of pulsed wave on primary dysmenorrhea (PD) remains sparse. This study found that pulsed R‐PBM significantly diminished pain responses and levels of PGF2α/PGE2, mitigated uterine swelling, augmented antioxidant capacity, and lowered MDA concentrations, which outperformed continuous wave at the same average irradiance. Furthermore, PW treatment substantially reduced ROS levels and enhanced cell viability in PGF2α induced HUSM cells. NOS levels, especially iNOS, were markedly diminished in the uteri of PD mice, accompanied by significant alterations in inflammation‐related genes (Jun, Fos, IL1rn, IL17b) and protein levels, along with pronounced downregulation of calcium ion concentrations after pulsed R‐PBM intervention. These findings indicated that pulsed R‐PBM may mitigate pain by modulating ROS and NO/NOS, mediated oxidative stress and inflammatory responses. Consequently, pulsed R‐PBM emerges as a promising therapeutic strategy for PD.
Assessment of Microcirculation and Microrheological Parameters of Blood in Patients With Type 2 Diabetes Mellitus Using Biophotonics Techniques
Authors: Umerenkov D. A. , Ermolinskiy P. B. , Lugovtsov A. E. , Fabrichnova A. A. , Gurfinkel Yu. I. , Dyachuk L. I. , Priezzhev A. V.
Published: December 2024

In this study, the parameters of blood microcirculation and microrheology were measured using the methods of laser aggregometry and optical tweezers in vitro, as well as the method of digital capillaroscopy in vivo. It was shown that in patients suffering from type 2 diabetes mellitus, an increase in the number of RBC aggregates passing through the narrow capillaries leads to a significant decrease in the velocity of the capillary blood flow, which can be explained by the increased viscosity of the whole blood and decreased deformability of RBCs. Also, for the group of patients, a statistically significant increase in the rate of RBC aggregation and the hydrodynamic strength of aggregates, RBC aggregation and disaggregation forces were observed compared to the control group. We have demonstrated the possibility of using these methods to assess changes in microrheological and microcirculatory parameters of the blood.
Peaking Today, Taking It Easy Tomorrow: Daily Performance Dynamics of Working Long Hours
Authors: ten Brummelhuis Lieke L. , Calderwood Charles , Rosen Christopher C. , Gabriel Allison S.
Published: December 2024

Underlying the “ideal worker” image that pervades many organizational cultures is the assumption that working longer hours equates to higher performance, despite recovery research that suggests that long work hours might actually impair future work performance. In an effort to reconcile these differences in how long work hours are thought to relate to job performance, we develop and test a conceptual model in which daily boosts in same‐day performance associated with working longer hours could be offset by lower next‐day performance. More specifically, we examine if working a longer day than usual reduces sleep, which has the potential to diminish physical (i.e., physical energy) and psychological (i.e., resilience) resources the next morning, consequently impairing next‐day work performance. In a 5‐day experience sampling study of 67 employee–coworker dyads (276 days), using sleep data from a wearable device (i.e., Fitbit) in combination with daily self‐report surveys and coworker performance ratings, results indicated that daily work hours were positively related to same‐day work performance. Our results further indicated that work hours were negatively related to next‐day work performance through reduced sleep duration and morning resilience, but not through diminished physical energy. Together, our findings indicate that although employees may experience same‐day performance gains related to working long hours, they also may pay a price the following day, as longer workdays prevent employees from recovering overnight.
Flexible bezel‐less thin‐film transistor backplane with through‐plastic‐vias for seamless tiling
Authors: Tsuji Hiroshi , Miyakawa Masashi , Takei Tatsuya , Fujisaki Yoshihide , Nakata Mitsuru
Published: December 2024

Tiling with a variety of panel units is a promising approach to customizing displays in terms of size, shape, and aspect ratio. However, tiled displays with conventional panel units have a major drawback in that they suffer from noticeable seams due to the bezels of the panel units. Here, we demonstrate a flexible bezel‐less thin‐film transistor (TFT) backplane for seamless tiling. By using through‐plastic‐vias (TPVs) that penetrate an ultrathin polyimide (PI) film substrate, a bezel‐less backplane with an ultra‐narrow bezel width of 8 μm was realized, in which oxide TFTs in pixel circuits on the backplane are driven from the back side of the PI film substrate using three‐dimensional signal wires, which go through the TPVs. The resistance of a TPV was evaluated with a TPV chain with 1000 TPVs connected in series and was found to be as small as 1.3 Ω. Furthermore, the transfer characteristics of an oxide TFT in a test element group for a pixel circuit were evaluated from the back side of the PI film substrate. The TFT exhibited clear switching behavior with an on/off current ratio of more than 108 and a high mobility of 25 cm2/Vs, which are sufficient to drive light‐emitting devices.
Explicit Symmetry Breaking of Generalized Angular Momentum by Second‐Harmonic Generation in Underdense Plasmas
Authors: Voisine Alexis , Béjot Pierre , Billard Franck , Marroux Hugo , Faucher Olivier , Hertz Edouard
Published: December 2024

Light beams possess two intrinsic quantized degrees of freedom, related to spin angular momentum (SAM) and orbital angular momentum (OAM), whose manipulation enables extensive control over the topological properties of electromagnetic fields. In this context, structured fields constructed from a non‐separable combination of SAM and OAM have recently gained sustained interest. Such states are eigenstates of the so‐called generalized angular momentum (GAM), a mixed angular momentum operator encompassing both SAM and OAM components, which can result in astonishing fractional eigenvalues. The demonstration of GAM conservation under harmonic generation has suggested a potential relevance of this new form of angular momentum as a meaningful quantum number. In the present work, the scope of evaluation is expanded by investigating its conservation law with second‐harmonic generation in an underdense isotropic inhomogeneous plasma that relies on dipole‐forbidden interaction implying spin‐orbit coupling. This study reveals that the symmetry and topological properties of the field are disrupted during the nonlinear process, the GAM charge being only conserved on average. This symmetry breaking can be exploited to provide an easily detectable signature of the driving field topology or to create a robust topological attractor.
Tensile Properties of Epoxy Composites Filled With Graphene Nanoplatelets and PUF Microcapsules
Authors: Nascimento Ana Paula , Ribeiro Cesar G. , Zoschke Gustavo H. , Njuguna James , Pezzin Sergio H.
Published: December 2024

This work evaluates the effect of poly(urea‐formaldehyde) (PUF) microcapsules filled with aminated polydimethylsiloxane (PDMS‐a), a self‐healing agent, on the tensile properties of epoxy composites reinforced with graphene nanoplatelets (GNP). The microcapsules are produced by interfacial polymerization and later are infiltrated with the healing agent (PDMS‐a). GNP are dispersed in epoxy resin using sonication, followed by the addition of hollow or filled PUF microcapsules to the system, using mechanical stirring, just before the addition of the curing agent (hardener). The mixture is then cast in soft molds to produce specimens for tensile tests. The results show that the presence of 1 wt% GNP changes the properties of the composites with an improvement in tensile strength and modulus, which achieves 37.4 MPa and 2.8 GPa, respectively, in comparison with neat epoxy and specimens containing just microcapsules. The addition of 2 wt% GNP, however, impairs these properties, with tensile strength and Young's modulus decreasing to 24.9 MPa and 2.3 GPa, due to the presence of GNP agglomerates. The presence of the microcapsules, however, decreases the immediate (no self‐healing) tensile performance of the composites.
Using mark–recapture techniques to evaluate catch and release, recycling, and associated survival probabilities of stocked Muskellunge at two Ohio reservoirs
Authors: Page Kevin S. , Wagner Curtis P. , Lewis Edward
Published: December 2024

Objective

Muskellunge Esox masquinongy fisheries in Ohio are almost exclusively catch and release. Catch and release is expected to benefit anglers via recaptures of previously caught fish (i.e., recycling). We used mark–recapture techniques to evaluate catch-and-release dynamics over multiple years in two stocked Muskellunge fisheries in Ohio.

Methods

Muskellunge were collected and tagged each spring by the Ohio Department of Natural Resources, Division of Wildlife (ODNR-DOW) at Clearfork Reservoir (1991–2006) and Leesville Lake (2016–2022). A total of 4139 Muskellunge were tagged, of which 38% (n = 1575) were recaptured at least once by either the ODNR-DOW or anglers. A total of 252 anglers reported 1339 catches of tagged fish. Multistate modeling was used to estimate survival and transition probabilities across years for the following marked fish states: at large (L, ODNR-DOW marked fish not reported caught by anglers); catch and release (C, those fish reported caught and released by anglers); and recycled (R, catch-and-release fish caught and reported by anglers again). Transition probabilities between states L to C and C to R estimated Muskellunge catch and release and recycling, respectively.

Result

Raw angler catch reports indicated that intra-annual recycling was rare, with the median time between recapture events exceeding a year. Modeled annual survival probability of L fish at Clearfork Reservoir and Leesville Lake was 0.67 and 0.87, respectively. About a quarter of these fish were caught and released by anglers at both reservoirs. Survival of C fish was lower than L fish at both reservoirs (Clearfork Reservoir = 0.58; Leesville Lake = 0.67), suggesting a “catch-and-release effect” on survival. Joint probability of catch-and-release fish surviving and being recycled annually was 0.24 and 0.23 for Clearfork Reservoir and Leesville Lake, respectively.

Conclusion

Integration of survival and catch probabilities over the long-term provides a comprehensive evaluation of catch-and-release dynamics. Estimates suggest that post-catch-and-release survival and probability of recycling may be lower than anticipated, which may have implications for managing Muskellunge fisheries and angler expectations.
Abiotic and biotic factors related to growth of nonnative Walleyes in Lake Pend Oreille, Idaho
Authors: Frawley Susan E. , Corsi Matthew P. , Dux Andrew M. , Hardy Ryan S. , Quist Michael C.
Published: December 2024

Objective

Understanding factors influencing growth is vital to effective management of fish populations. This study investigated potential factors influencing growth of an established nonnative population of Walleyes Sander vitreus in the Lake Pend Oreille system in northern Idaho.

Methods

We used relative growth index to describe growth of Walleyes relative to populations across North America. Mixed-effects modeling was used to relate growth to abiotic (i.e., mean summer water temperature, river inflow) and biotic (i.e., kokanee Oncorhynchus nerka abundance and biomass; opossum shrimp Mysis diluviana density) variables. Models were ranked using Akaike's information criterion corrected for small sample size. Individual variability in growth was related to diet represented by stable isotopes (i.e., δ15N, δ13C) using linear regression for age-1, age-2, age-3, and age-5 individuals. Subsequently, for each age-class, we evaluated differences in δ15N and δ13C between fast-growing (i.e., 75th and higher percentiles of growth) and slow-growing (i.e., 25th and lower percentiles of growth) individuals.

Result

Walleyes grew fast relative to other populations. Growth of Walleyes was positively associated with temperature as well as abundance and biomass of kokanee; growth was unrelated to river inflow and opposum shrimp density. The top model indicated that growth of Walleyes was related to temperature and kokanee abundance. An equally plausible model explaining growth consisted of only temperature. Generally, fast-growing Walleyes exhibited higher δ15N than slow-growing individuals. Similarly, δ13C was more depleted in the fast-growing individuals for all ages except age 1. This suggests that fast-growing individuals likely consumed prey items at higher trophic positions and fast-growing Walleyes (except age 1) used higher proportions of pelagic prey items.

Conclusion

This study showed that kokanee abundance and temperature likely influenced growth of Walleyes in the Lake Pend Oreille system. Additionally, variability in growth was apparently related to variability in diet, particularly for age-1 Walleyes.
Performance analysis of 3D orthogonal polymeric composites reinforced with metallic and glass fibrous z‐binders of varying sizes
Authors: Ghandour A. Ashraf , Selmy A. I. , Megahed M. , Kabeel A. M. , Ibrahim Ahmed
Published: December 2024

Despite the wide use of three‐dimensional (3D) woven composites in different applications, their production is often costly. This study explores cost‐effective 3D orthogonal woven polymer composites to enhance mechanical performance. Four 3D composite variants, each incorporating different volumes of z‐binders (copper wires or glass fibers), were compared to a 2D woven composite. All composites were produced using a simple, economical hand lay‐up method. Wear resistance, in‐plane shear strength, and impact strength were assessed. Results indicated that all 3D composites surpassed the 2D composite in impact strength, especially those reinforced with glass fiber z‐binders. The single glass fiber z‐binder composite exhibited the highest impact strength increase (20.6%). Most 3D composites showed slightly reduced in‐plane shear strength compared to the 2D composite, with the smallest decrease (1.68%) observed in specimens with a small copper z‐binder. Notably, all 3D composites demonstrated superior wear resistance to 2D counterparts under various loads. Glass fiber z‐binder reinforcements outperformed copper z‐binders, with double fiber z‐binders yielding the maximum wear resistance enhancement. These findings underscore the potential of 3D woven composites for applications demanding high impact and wear resistance, such as automotive, structural components, and sports equipment.

Highlights

3D woven composites are widely used in various engineering applications.

Limited studies explore the in‐plane shear and wear behavior of 3D composites.

Copper and glass fiber z‐binders were used in manufacturing 3D woven composites.

The used hand lay‐up method reduces manufacturing costs.

3D woven composites improve impact and wear resistance compared to 2D ones.
Flow modeling in a metering section of a single screw extruder with a small helix angle based on the energy dissipation rate
Authors: Gao Xuesi , Kim Hyoung Bum , Hwang Wook Ryol
Published: December 2024

In the present work, an approach based on energy dissipation rate was presented for quantifying the screw characteristics, effective Reynolds number, viscosity, and shear rate of non‐Newtonian fluids in the metering zone of a single screw extruder, characterized by a small helix angle. The flow is separated into two individual flows: one induced by the screw rotation, known as rotational flow, and another driven by back‐pressure from the die, known as pressure‐driven flow. We start by investigating the individual flow problems separately, specifically focusing on the torque and rotation speed correlations in the rotational flow and exploring pressure buildup and flow rate correlations in the pressure‐driven flow. Following this, a method to quantify the combined flow, which includes both rotational and pressure‐driven flows, is formulated by blending the relationships from each of the individual flow, employing mixture rules to determine shear rate. The mixture rules involve a key parameter, the velocity ratio, to define the flow rate contribution of the two individual flows to the combined flow. The proposed method for quantifying flow is confirmed, by comparing the results with numerical simulations employing three different inelastic non‐Newtonian fluids. The proposed method can be employed to predict the pressure buildup and the torque and to monitor the viscosity behavior of the material as a function of the shear rate. A comparison of the theoretical predictions and the numerical simulation results for the estimation of pressure buildup, torque, and shear‐rate dependent viscosity revealed discrepancies of 11.7%, 3.6%, and 6.2%, respectively. Furthermore, we report that the commonly used relationship between dimensionless pressure number and dimensionless throughput number for a Newtonian fluid is applicable to that of non‐Newtonian fluids, with the effective viscosity employed in the present study.

Highlights

Accurate estimation of representative viscosity of non‐Newtonian fluids for the flow in a single screw.

The flow in the screw is split into a rotating flow and a pressure‐driven flow.

Representative shear rates can be determined by rotational speed and flow rate.
Current and emerging PCSK9‐directed therapies to reduce LDL‐C and ASCVD risk: A state‐of‐the‐art review
Authors: Garwood Candice L. , Cabral Katherine P. , Brown Roy , Dixon Dave L.
Published: December 2024

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide. Lowering low‐density lipoprotein cholesterol (LDL‐C) levels is a primary strategy to reduce ASCVD risk. Although statin therapy remains the initial therapy of choice to reduce LDL‐C and ASCVD risk, statin intolerance and suboptimal LDL‐C lowering response prompts the need for additional non‐statin therapies. Ezetimibe and bempedoic acid are reasonable options but they modestly reduce LDL‐C levels (15% to 25%). Therapies directed at the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme, however, reduce LDL‐C levels by 50%–60% when added to background statin therapy. PCSK9 is an enzyme synthesized by the liver that facilitates the degradation of LDL receptors and prevents their recycling to the hepatocyte surface to remove LDL‐C from circulation. Approaches to inhibit this effect have centered on monoclonal antibodies (mAbs) (alirocumab, evolocumab) targeting PCSK9 functionality and small interfering RNA (siRNA) therapies (inclisiran) targeting the hepatic synthesis of PCSK9. Randomized controlled trials have demonstrated beneficial cardiovascular outcomes of PCSK9 mAbs, but such evidence is not yet available for inclisiran. Current clinical practice guidelines generally recommend PCSK9‐directed therapies for higher‐risk patients with established ASCVD and those with familial hypercholesterolemia. This approach is, in part, due to their cost and uncertain economic value, but also because these therapies require subcutaneous administration, which is not preferred by some patients. Oral therapies targeting PCSK9 are, however, in development. This scoping review covers the development of current and emerging PCSK9‐directed therapies, their efficacy, safety, and role in clinical practice.
Thiol‐dithioester reaction: An approach to the end‐group removal and end‐functionalization of RAFT‐synthesized polymers
Authors: Huang Shan , Zhao Hanying
Published: December 2024

Reversible addition−fragmentation chain transfer (RAFT) polymerization has been one of the most versatile methods in the synthesis of well‐defined polymers. The stability of the thiocarbonylthio chain transfer agents (CTAs) in the polymerization and the removal of CTAs after the polymerization are the two great concerns for the applications of RAFT polymerization. In this research, thiol‐dithioester reaction under the catalysis of triethylamine (TEA) is studied. In a model reaction, thiolate anion has nucleophilic addition reaction with dithioester compound, resulting in the synthesis of a new dithioester and a new thiol compound. The effects of TEA to dithioester molar ratio and reaction time on the yield of the product are investigated. The application of thiol‐dithioester reaction in the removal of end CTAs from polymer chains is studied. 1H NMR, UV–vis, and size‐exclusion chromatography (SEC) results all demonstrate the effective removal of CTAs and the generation of thiol groups at polymer chain ends. The thiol groups can be further used for the terminal functionalization of polymers. In this research, alkyne‐terminated poly(methyl methacrylate) and FMOC‐l‐Cys‐labeled poly(di‐[ethylene glycol] methyl ether methacrylate) are synthesized by TEA‐catalyzed thiol‐ene reaction and thiol‐disulfide reaction, respectively. Thiol‐dithioester reaction provides an effective approach to the removal of CTAs and end functionalization of RAFT synthesized polymers.
Proliferation dynamic of Paranosema locustae after infection and histopathogenic features on Locusta migratoria
Authors: Huo Fan , Liu Huixia , Guo Weiqi , Kang Hanye , Zhang Huihui , Jashenko Roman , Ji Rong , Hu Hongxia
Published: December 2024

Paranosema locustae are specialized parasites of Orthoptera that have been applied widely in the control of grasshoppers in many parts of the world. However, it is slow to kill insects, and how it works in the host is unclear. This work aimed to examine the proliferation of P. locustae within locust tissues and characterize the histological alterations occurring in the midgut, hindgut, and gonads of infected Locusta migratoria. The results showed that during the later stage of infection, the reproduction of P. locustae was most prominent in the fat body and salivary glands (109.26 and 108.91 copies /ug DNA, respectively). In contrast, the load of P. locustae was least in the craw and midgut (107.37 and 107.58 copies /ug DNA, respectively), illustrating that the proliferation of P. locustae in the body of locusts had a tissue tendency. The histopathological study revealed that lesions in the hindgut occurred prior to those in the midgut, indicating that P. locustae may have a mechanism for survival that enables it to avoid immune responses in specific organs. The testis exhibited earlier lesions compared to the ovaries, and in the advanced stages of infection, the testis harbored a higher load of P. locustae than the ovaries, suggesting a more pronounced impact on the male reproductive organs in comparison to the female ones. The results of our study enhance our comprehension of the rapid growth and disease‐causing mechanism of P. locustae, which can serve as a basis for enhancing its ability to kill insects. © 2024 Society of Chemical Industry.
Abaloparatide
Authors: Chaplin Steve
Published: December 2024

Abaloparatide stimulates osteoblast activity and is licensed for treating postmenopausal women with fracture risk. Here, we discuss the clinical evidence for benefit and also the drug adverse effect profile.
Superior Temperature Sensing and Capacitive Energy‐Storage Performance in Pb‐Free Ceramics
Authors: Zeng Xiangfu , Zhang Yangdong , Shen Jie , Jiang Xingan , Wang Simin , Dai Haoyu , Wu Xiao , Gao Min , Zhao Chunlin , Lin Tengfei , Luo Laihui , Lin Jinfeng , Sa Baisheng , Lin Cong
Published: December 2024

The ultrafast charge/discharge rate and high power density (PD) endow lead‐free dielectric energy storage ceramics (LDESCs) with enormous application potential in electric vehicles. However, their low energy storage density and single energy storage performance (ESP) limit their further development and applicability in rugged environments. Here, through the design of vacancy defects and phase structure regulation, Pb‐free (Bi0.5Na0.5)TiO3‐based ceramics with an optimal composition can achieve a large maximum polarization (>44 µC cm−2) under a moderate electric field (410 kV cm−1), resulting in an extremely high recoverable energy storage density (≈6.14 J cm−3), nearly ideal energy storage efficiency (91.32%), a very short time (≈67 ns) to release 90% of the energy, and a high PD (243.57 MW cm−3). More importantly, the energy storage capacities of these ceramics remain stable over a wide temperature range (25–220 °C) and for a wide range of fatigue cycles (1‐106). Additionally, the real‐time temperature sensing performance with high sensitivity (with a relative sensitivity of up to ≈0.04 K−1) in the ceramics is developed based on Yb3+ and Tm3+ codoping, which further supports the potential application of LDESCs to automotive batteries with a temperature monitoring function.
A Self‐Cascading Catalytic Therapy and Antigen Capture Scaffold‐Mediated T Cells Augments for Postoperative Brain Immunotherapy
Authors: Yalamandala Bhanu Nirosha , Moorthy Thrinayan , Liu Zhuo‐Hao , Huynh Thi My Hue , Iao Hoi Man , Pan Wan‐Chi , Wang Kang‐Li , Chiang Chi‐Shiun , Chiang Wen‐Hsuan , Liao Lun‐De , Liu Yu‐Chen , Hu Shang‐Hsiu
Published: December 2024

The recruitment of T lymphocytes holds great potential for suppressing the most aggressive glioblastoma (GBM) recurrence with immunotherapy. However, the phenomenon of immune privilege and the generally low immunogenicity of vaccines often reduce the presence of lymphocytes within brain tumors, especially in brain tumor recurrence clusters. In this study, an implantable self‐cascading catalytic therapy and antigen capture scaffold (CAS) that can boost catalytic therapy efficiency at post‐surgery brain tumor and capture the antigens via urethane‐polyethylene glycol‐polypropylene glycol (PU‐EO‐PO) segments are developed for postoperative brain immunotherapy. The CAS consists of 3D‐printed elastomers modified with iron (Fe2+) metal‐organic frameworks (MOFs, MIL88) and acts as a programmed peroxide mimic in cancer cells to initiate the Fenton reaction and sustain ROS production. With the assistance of chloroquine (CQ), autophagy is inhibited through lysosome deacidification, which interrupts the self‐defense mechanism, further enhances cytotoxicity, and releases antigens. Then, CAS containing PU‐EO‐PO groups acts as an antigen depot to detain autologous tumor‐associated antigens to dendritic cells maturation and T cell augments for sustained immune stimulation. CAS enhanced the immune response to postoperative brain tumors and improved survival through brain immunotherapy.
Non‐Conjugated Gridized Nanopolymers as an Efficient Hole‐Transport Material for Blue Perovskite Light‐Emitting Diodes
Authors: Tao Fangju , Wei Ying , Chen Jian , Li Yang , Wang Yongxia , Zhang Zheng , Pu Yueting , Wang Kuande , Li Hao , Li Xiaoyan , Feng Quanyou , Chen Shufen , Yang Tonglin , Liu Lihui , Xie Linghai , Huang Wei
Published: December 2024

Despite the remarkable advancements in perovskite light‐emitting diode (PeLED) technology, the development of blue PeLEDs has lagged. The primary bottleneck lies in the difficulty of finding hole transport materials (HTMs) that can both match the energy levels of blue perovskite materials and exhibit efficient hole transport performance. Herein, a novel non‐conjugated polyethylene carbazole‐based polymer (P‐AGCz) is developed that has excellent solution processability and serves as an efficient dopant‐free HTM for PeLEDs. The flexible non‐conjugated polyethylene backbone of P‐AGCz provides exceptional film‐forming capabilities. Moreover, the A‐shaped carbazole‐based side chains deepen the HOMO energy level and minimize the recombination energy, enhancing its ability to inject and transport holes within PeLEDs. The PeLEDs employing P‐AGCz as a low‐cost, dopant‐free polymer HTM have attained an external quantum efficiency (EQE) of 3.26%, which is 1.54 times greater than poly(N‐vinylcarbazole) (PVK)‐based devices, with a brightness enhancement of 584 cd m−2 over the PVK‐based devices. Furthermore, the P‐AGCz‐based devices exhibit higher current efficiency at lower driving voltages, indicating reduced energy consumption and expanded potential for future applications.
Nanostructured Boron‐Doped Ultra‐Nanocrystalline Diamond Micro‐Pyramids: Efficient Electrochemical Supercapacitors
Authors: Suman Shradha , Sharma Dhananjay Kumar , Szabo Ondrej , Rakesh Benadict , Marton Marian , Vojs Marian , Sankaran Kamatchi Jothiramalingam , Kromka Alexander
Published: December 2024

The miniaturization of electrochemical supercapacitors (EC‐SCs) requires electrode materials that are both durable and efficient. Boron‐doped diamond (BDD) films are an ideal choice for EC‐SC due to their durability and exceptional electrochemical performance. In this study, nanostructured boron‐doped ultra‐nanocrystalline diamonds (NBUNCD) are fabricated on Si micro‐pyramids (SiP) using a simple reactive ion etching (RIE) process. During the etching process, the high aspect ratio and the induction of sp2 graphite in these nanorod electrodes achieved a maximum specific capacitance of 53.7 mF cm−2 at a current density of 2.54 mA cm−2, with a 95.5% retention after 5000 cycles. Additionally, the energy density reached 54.06 µW h cm−2 at a power density of 0.25 µW cm−2. A symmetric pouch cell using NBUNCD/SiP exhibited a specific capacitance of 0.23 mF cm−2 at 20 µA cm−2, an energy density of 31.98 µW h cm−2, and a power density of 0.91 µW cm−2. These superior EC properties highlight NBUNCD/SiP’s potential for advancing miniaturized supercapacitors with high capacitance retention, cycle stability, and energy density.
Engineered Aptamer‐Derived Fluorescent Aptasensor: the Label‐Free, Single‐Step, Rapid Detection of Vancomycin in Clinical Samples
Authors: Liu Zhou‐Jie , Liang Yu‐Qi , Li Jia‐Yi , Wu Bing , Huang Chen , Liu Yi‐Wei , Zhang Chen‐Zhi , Yang Ye , Cai Nai‐Qing , Chen Jin‐Yuan , Lin Xin‐Hua
Published: December 2024

Currently, the reported vancomycin (VCM) aptamers, including the 3‐ (Kd  =  9.13 × 10−6 m) and 4‐truncated variants (Kd = 45.5 × 10−6 m), are engineered via stem truncation of the VCM parent aptamer, which inevitably compromises their affinities, thus affecting their clinical application within the VCM therapeutic window of 6.9–13.8 × 10−6 m. Herein, the binding pocket of the VCM parent aptamer is elucidated for the first time and we implemented the Post‐SELEX modification strategy involving truncation and mutagenesis to refined the VCM parent aptamer. This yielded a VCM aptamer (ABC20‐11) with an intramolecular G‐triplex, an enhanced thioflavin T (ThT) fluorescence intensity, and an improved affinity (Kd = 0.591 × 10−6 m) and specificity (one‐methyl level) for VCM. Utilizing a portable fluorescence detector specifically designed for rapidly detecting VCM concentration and leveraging the competitive binding between VCM and ThT to ABC20‐11, a label‐free fluorescent aptasensor is developed. This aptasensor exhibits exceptional analytical performances across various clinical samples (serum, cerebrospinal fluid, and joint fluid), with corresponding linear ranges of 0.5–50, 0.5–40, and 0.5–50 × 10−6 m and detection limits at 0.11, 0.12, and 0.16 × 10−6 m, respectively. Consequently, the proposed VCM aptasensor displays considerable clinical value and potential for use in rapid VCM detection.
Ferroelastic Domain Switching and Time‐Resolved Negative Capacitance in Polar‐Axis‐Oriented Hf0.5Zr0.5O2 Grown by Atomic Layer Epitaxy
Authors: Jiang Yu‐Sen , Lin Wei‐En , Shiojiri Makoto , Yin Yu‐Tung , Su Yu‐Cheng , Nien Chih‐Hung , Hsu Chen‐Feng , Hou Vincent Duen‐Huei , Chang Chih‐Sheng , Radu Iuliana , Chen Miin‐Jang
Published: December 2024

Ferroelectric properties of Hf0.5Zr0.5O2 are strongly correlated with its crystallographic orientation, with the [001] direction serving as the polar axis. However, the epitaxial growth of highly polar‐axis‐oriented Hf0.5Zr0.5O2 layers with pronounced ferroelectricity is rarely reported. Here epitaxial (001)‐oriented Hf0.5Zr0.5O2 thin films grown by atomic layer epitaxy (ALE) is demonstrated, which achieve a state‐of‐the‐art ferroelectric polarization up to 78.9 µC cm−2. The epitaxial Hf0.5Zr0.5O2 layer experiences a lattice reorientation from (010) to (001) during the wake‐up process, as evidenced by plane‐view precession electron diffraction. Accordingly, a two‐step, 90° ferroelastic domain switching model is proposed to elucidate multiple polarization switching. Furthermore, the observed polarization switching dynamics closely match with the time‐resolved negative capacitance, which is quantified as an equivalent high dielectric constant of −170. This study highlights the capability of ALE to precisely control the crystallographic orientation of Hf0.5Zr0.5O2 thin films, providing deep insights into fundamental ferroelectric mechanisms.
Constructing a Conductive Micro/Nano Network Within Interpenetrating Phase Composites for Triboelectric Nanogenerators
Authors: Su Yujie , Wang Yunxia , Li Xiaojuan , Liu Hao , Wang Jianzhang , Wang Daoai , Yu Qiangliang , Zhou Feng
Published: December 2024

Interpenetrating phase composites (IPCs) are gaining popularity because of their unique topological characteristics, which include their light weight and ability to conduct electricity. Herein, a novel metal‒polymer IPC composed mainly of a 3D nickel foam(NF) at the microscale and a polytetrafluoroethylene (PTFE) matrix are developed. Moreover, a nanonetwork composed of carbon nanotubes (CNTs) bridging the nickel skeleton and PTFE matrix is created within the IPC via a simple impregnation method. The construction of a micro/nano hybrid network not only enhances the tribological performance and friction heat dissipation but also increases the triboelectric output response, which is 30 and 7.5 times greater than that of pristine PTFE and binary NF‐PTFE IPC, respectively. The fabricated IPC endures long‐term tests after 36 000 cycles without notable wear scarring, exhibiting great potential for future optimization of triboelectric nanogenerator(TENG) durability and potential application in a variety of fields, such as wear‐resisting materials, high‐performance energy absorption and heat management.
ROS Regulation in CNS Disorder Therapy: Unveiling the Dual Roles of Nanomedicine
Authors: Quan Zhengyang , Wang Sa , Xie Huanhuan , Zhang Jiayi , Duan Ranran , Li Menglin , Zhang Jinfeng
Published: December 2024

The treatment of brain diseases has always been the focus of attention. Due to the presence of the blood‐brain barrier (BBB), most small molecule drugs are difficult to reach the brain, leading to undesirable therapeutic outcomes. Recently, nanomedicines that can cross the BBB and precisely target lesion sites have emerged as thrilling tools to enhance the early diagnosis and treat various intractable brain disorders. Extensive research has shown that reactive oxygen species (ROS) play a crucial role in the occurrence and progression of brain diseases, including brain tumors and neurodegenerative diseases (NDDs) such as Alzheimer's disease, Parkinson's disease, stroke, or traumatic brain injury, making ROS a potential therapeutic target. In this review, on the structure and function of BBB as well as the mechanisms are first elaborated through which nanomedicine traverses it. Then, recent studies on ROS production are summarized through photodynamic therapy (PDT), chemodynamic therapy (CDT), and sonodynamic therapy (SDT) for treating brain tumors, and ROS depletion for treating NDDs. This provides valuable guidance for the future design of ROS‐targeted nanomedicines for brain disease treatment. The ongoing challenges and future perspectives in developing nanomedicine‐based ROS management for brain diseases are also discussed and outlined.
Ameliorating Defects in Wide Bandgap Tin Perovskite Solar Cells Using Fluorinated Solvent and Hydrazide
Authors: Khadka Dhruba B. , Shirai Yasuhiro , Sahara Ryoji , Yanagida Masatoshi , Miyano Kenjiro
Published: December 2024

Surface passivation with multifunctional molecules is an effective strategy to mitigate the defect and improve the performance and stability of perovskite solar cells (PSCs). Here, the fabrication of a wide bandgap‐PSC is reported with tin perovskite (WB‐Sn‐HP; bandgap: 1.68 eV), followed by molecular surface passivation using 4‐Fluoro‐benzohydrazide (F‐BHZ). WB‐Sn‐PSC has demonstrated a promising device efficiency of 11.14% with improved device stability. The key to enhancing device performance lies in the meticulous engineering of both surface and bulk properties of WB‐Sn‐HP film with F‐BHZ treatment as a consequence of stronger electrostatic potential and molecular interaction with hydrazine and carbonyl functionalities. A compact perovskite film and highly crystalline film growth results in a longer carrier lifetime and surface defect mitigation with the control of Sn2+ oxidation as supported by theoretical calculations. This work underlines the promising potential of chemical engineering to improve the device performance of WB‐Sn‐PSC and stability using multifunctional passivating molecules.