bluuebunny/crossref_metadata_2025 huggingface dataset:
Model‐Informed Approach Supporting Drug Development and Regulatory Evaluation for Rare Diseases
Authors: Li Ruo‐Jing , Ma Lian , Li Fang , Li Liang , Bi Youwei , Yuan Ye , Li Yangbing , Xu Yuan , Zhang Xinyuan , Liu Jiang , Bhattaram Venkatesh Atul , Wang Jie , Schuck Robert , Pacanowski Michael , Zhu Hao
Published: December 2022

A rare disease is defined as a condition affecting fewer than 200 000 people in the United States by the Orphan Drug Act. For rare diseases, it is challenging to enroll a large number of patients and obtain all critical information to support drug approval through traditional clinical trial approaches. In addition, over half of the population affected by rare diseases are children, which presents additional drug development challenges. Thus, maximizing the use of all available data is in the interest of drug developers and regulators in rare diseases. This brings opportunities for model‐informed drug development to use and integrate all available sources and knowledge to quantitatively assess the benefit/risk of a new product under development and to inform dosing. This review article provides an overview of 4 broad categories of use of model‐informed drug development in drug development and regulatory decision making in rare diseases: optimizing dose regimen, supporting pediatric extrapolation, informing clinical trial design, and providing confirmatory evidence for effectiveness. The totality of evidence based on population pharmacokinetic simulation as well as exposure‐response relationships for efficacy and safety, provides the regulatory ground for the approval of an unstudied dosing regimen in rare diseases without the need for additional clinical data. Given the practical and ethical challenges in drug development in rare diseases, model‐informed approaches using all collective information (eg, disease, drug, placebo effect, exposure‐response in nonclinical and clinical settings) are powerful and can be applied throughout the drug development stages to facilitate decision making.
Until My Son Calls Me Dad: Quest to Find a Treatment for Ultra‐Rare Disease
Authors: Ramesh Sanath Kumar
Published: December 2022

Rare diseases are affecting 400 million patients worldwide, with 95% of them suffering without treatments. In this article, I make a plea, as a parent of a rare disease kid, and as a drug developer, to turn the attention of pharmacologists to such rare and devastating diseases.
The contribution of non‐tropical cyclone vortices to the rainfall of the Philippines
Authors: Olaguera Lyndon Mark P. , Matsumoto Jun , Manalo John A.
Published: December 2022

Weaker disturbances than tropical cyclones (TCs) such as tropical depressions and cold surges can significantly induce heavy rainfall and flooding events over the Philippines. However, the analysis of these disturbances including their rainfall contributions are often neglected in previous studies. As the first attempt to address this research gap, this study investigates the rainfall contribution of non‐TC vortices over the Philippines from 1979 to 2020. Only those rainfall‐producing non‐TC vortices that formed and appeared within a 500‐km radius from the Philippine coastline were examined in this study. A total of 7,686 non‐TC vortex days (50% of the total days during the analysis period) were identified. The mean rainfall contribution of these non‐TC vortices was found to be highest over the northeastern Mindanao Island (80–90% of the mean daily rainfall) and lowest over the central and western regions of Luzon Island (50–60%). Seasonal analysis of the occurrence frequency of these vortices shows that they are most frequent during the December–February (DJF) season. In this season, the rainfall contribution may increase to 50–80% of the mean daily rainfall over the whole country, while in the other seasons, the rainfall contribution may only increase to as much as 60%. Higher frequency of extreme rainfall days associated with these non‐TC vortices were also found during the DJF season. The frequency of occurrence and percentage rainfall contribution of these non‐TC vortices in relation to the different phases of the Boreal Summer Intraseasonal Oscillation (BSISO) during boreal summer (June–October) and the Madden–Julian Oscillation (MJO) during boreal winter (December–April) were also examined. Higher frequency and percentage rainfall contribution over the country were found during Phases 4–6 of both the BSISO and MJO, during which their respective active convections transition from the Maritime Continent to the western North Pacific.
Interannual variability of the double easterly jets over the tropical western Pacific and their effects on tropical cyclone genesis
Authors: Zhan Xinyue , Wen Zhiping , Guo Yuanyuan , Huang Sihua
Published: December 2022

Different from other upper‐tropospheric jet stream that owns the single jet axis, the tropical easterly jet (TEJ) generally splits into two branches over the tropical western Pacific where the TEJ inflows from June to September, with the north branch locating near 20°N and the south branch appearing near the equator. However, how these double easterly jets change from year to year and whether they have effects on the tropical cyclones (TCs) over the tropical western Pacific are still unknown. Observational evidence has demonstrated that the double easterly jets in the TEJ's inflow region exhibit an out‐of‐phase relationship in the interannual time scale and is significantly related to the TCs genesis. Corresponding to a stronger south branch and a weaker north branch, the accelerated (decelerated) easterly wind for the south (north) branch would induce a northerly (southerly) ageostrophic wind, thus triggering an upper‐tropospheric divergence between the double easterly jets. This divergence can further lead to anomalous ascending flows over the western North Pacific, which turns out to be the primary cause that increases the TCs number over there. The results highlight that the out‐of‐phase variation of the double easterly jets could dynamically modulate the occurrence of the TCs over the western North Pacific by inducing the secondary vertical circulation.
Effects of sous vide cooking combined with ultrasound pretreatment on physicochemical properties and microbial communities of Russian sturgeon meat (Acipenser gueldenstaedti)
Authors: Yuan Yan‐wei , Cai Wen‐qiang , Wang Meng‐zhen , Liu Yu‐ting , Fu Jing‐jing , Chen Yue‐wen
Published: December 2022

BACKGROUND

The production of Russian sturgeon is expanding rapidly in China but it is necessary to adopt measures to extend the shelf life of sturgeon meat. Previous studies found that sous vide cooking (SVC) at 60 °C increased the protein and lipid oxidation. The addition of antioxidant substances reduced the acceptance of the product. The effect of combination SVC and ultrasound pretreatment was therefore investigated.

RESULTS

Results showed that SVC at 50 °C combined with ultrasound effectively restrained the growth of total viable counts (TVC) in samples. Meanwhile, the main dominant genera changed from Pseudomonas to Carnobacterium and the number of microbial species decreased. The odor profile of Russian sturgeon meat was more stable and the lipoxygenase (LOX) activity decreased more rapidly after treating with SVC and ultrasound. Importantly, more stable protein aggregates were formed in samples treated by SVC 50 °C together with ultrasound pretreatment, so the protein and lipid oxidation were slowed during storage. Higher springiness values were obtained and the color of sturgeon meat was lighter under these conditions.

CONCLUSION

The combination of SVC 50 °C and ultrasound pretreatment effectively inhibited the microbial growth of Russian sturgeon meat at lower oxidation levels. These findings theoretically support the preservation and development of sturgeon meat, and the application of SVC technology. © 2022 Society of Chemical Industry.
Imaging Cloaked Objects: Diffraction Tomography of Realistic Invisibility Devices
Authors: Díaz‐Fernández Francisco J. , Martí Javier , García‐Meca Carlos
Published: December 2022

Invisibility cloaks have become one of the most outstanding developments among the wide range of applications in the field of metamaterials. So far, most efforts in invisibility science have been devoted to achieving practically realizable cloak designs and to improving the effectiveness of these devices in reducing their scattering cross‐section (SCS), a scalar quantity accounting for the total electromagnetic energy scattered by an object. However, little attention has been paid to the opposite side of the technology: the development of more efficient techniques for the detection of invisibility devices. For instance, the SCS ignores the phase change introduced by the cloak, as well as the angular dependence of the incident and scattered waves. Here, a different path is proposed, which takes advantage of the smarter way in which diffraction tomography processes all this overlooked information to improve the efficiency in unveiling the presence of invisibility devices. This approach not only results in a considerable sensitivity enhancement in the detection of different kinds of cloaks based on both scattering cancellation and transformation optics, but also enables us to obtain images depicting the approximate shape and size of the cloak. The proposed method can be extended to the detection of sound cloaks.
Exotic Photonic Spin Hall Effect from a Chiral Interface
Authors: Sheng Lijuan , Zhou Xinxing , Zhong Yuhan , Zhang Xinyan , Chen Yu , Zhang Zhiyou , Chen Hongsheng , Lin Xiao
Published: December 2022

The photonic spin Hall effect provides a quantitative way to characterize the spin–orbit interaction of light and enables many applications, such as the precise metrology, since this effect is featured with a spin‐dependent transverse shift of the light beam. This transverse shift is generally nonzero during the reflection/transmission process, and it is sensitive to the polarization and the incident angle of the light beam. By contrast, here it is revealed that for the transmitted light, the transverse shift can be always zero and polarization‐independent, irrespective of the incident angle. The underlying mechanism is that the conversion between the spin and orbit angular momenta of light is fully suppressed during the transmission process. Such an exotic photonic spin Hall effect occurs, if , , and , where t stands for the transmission coefficient and its first (second) superscript represents the polarization of the transmitted (incident) light, and () is the transmitted (incident) angle. These transmission conditions are achievable, e.g., by exploiting an interface only with a chiral surface conductivity. Similarly, a polarization‐independent photonic spin Hall effect is revealed for the reflected light.
Maximally Chiral Emission via Chiral Quasibound States in the Continuum
Authors: Lim Yeonsoo , Seo In Cheol , An Soo‐Chan , Kim Younggon , Park Chaejin , Woo Byung Hoon , Kim Seongheon , Park Hyeong‐Ryeol , Jun Young Chul
Published: December 2022

Although numerous natural materials exhibit chiral optical phenomena, they are typically very weak. Chiral nanophotonic structures can significantly enhance the chiroptical responses and provide unprecedented design flexibility. However, achieving extreme chirality that approaches the ultimate theoretical limit remains challenging. Here, chiral quasibound states in the continuum are realized in the visible range, and maximally chiral emission from a perovskite metasurface is demonstrated. A perovskite film is spin‐coated on a patterned glass substrate. Grayscale lithography is employed to control the etching depths in the substrate and induce out‐of‐plane symmetry breaking. An extremely high level of chiral emission is experimentally achieved in the normal direction at room temperature. Chiral emission is maximally enhanced for one helicity via critical coupling, while strongly suppressed for the other helicity. The physical mechanism is explained using the reciprocity principle. Approaching the ultimate limit of chiral responses may lead to far‐reaching consequences in various important applications as well as fundamental studies.
Evaluation of Biocompatible Films Using Copolymers of N‐Vinylbenzamide with Cationic Moieties by Hydrolysis of N‐Vinylformamide
Authors: Kawatani Ryo , Hamawaki Taiga , Waku Tomonori , Tanaka Naoki , Ajiro Hiroharu
Published: December 2022

Biocompatible materials using poly(N‐vinylamide) derivatives are developed via a recently designed synthetic route. N‐Vinylbenzamide (NVB) is synthesized as typical hydrophilic N‐vinylamide monomer, then copolymerized with N‐vinylformamide (NVF) by free radical polymerization, which can convert to cationic polyvinylamine unit by hydrolysis. Cell toxicity on the surface of copolymer films is investigated, revealing that poly(N‐vinylamide) derivatives show biocompatibility regardless of the cationic ratio.
Programmable Thermo‐Responsive Actuation of Hydrogels via Light‐Guided Surface Growth of Active Layers on Shape Memory Substrates
Authors: Fan Guang‐Lin , Wang Shu‐Wei , Zhang Ying‐Ying , Liu Zhao‐Tie , Liu Zhong‐Wen , Wang Lei , Jiang Jin‐Qiang , Li Guo
Published: December 2022

Hydrogel shape memory and actuating functionalities are heavily pursued and have found great potential in various application fields. However, their combination for more flexible and complicated morphing behaviors is still challenging. Herein, it is reported that by controlling the light‐initiated polymerization of active hydrogel layers on shape memory hydrogel substrates, advanced morphing behaviors based on programmable hydrogel shapes and actuating trajectories are realized. The formation and photo‐reduction‐induced dissociation of Fe3+‐carboxylate coordination endow the hydrogel substrates with the shape memory functionality. The photo‐reduced Fe2+ ions can diffuse from the substrates into the monomer solutions to initiate the polymerization of the thermally responsive active layers, whose actuating temperatures and amplitudes can be facially tuned by controlling their thicknesses and compositions. One potential application, a shape‐programmable 3D hook that can lift an object with a specific shape, is also unveiled. The demonstrated strategy is extendable to other hydrogel systems to realize more versatile and complicated actuating behaviors.
Further characterization of the 9q31 microdeletion phenotype; delineation of a common region of overlap containing ZNF462
Authors: Brady Lauren , Ballantyne Mark , Duck John , Fisker Thomas , Kleefman Ryan , Li Chumei , Nfonsam Landry , Schultz Lee‐Anne , Tarnopolsky Mark , McCready Elizabeth
Published: December 2022

Background

Loss of function variants and whole gene deletions of ZNF462 has been associated with a novel phenotype of developmental delay/intellectual disability and distinctive facial features. Over two dozen cases have been reported to date and the condition is now known as Weiss‐Kruszka syndrome (OMIM# 618619). There are several older reports in the literature and DECIPER detailing individuals with interstitial deletions of 9q31 involving the ZNF462 gene. Many of the characteristic facial features described in these microdeletion cases are similar to those who have been diagnosed with Weiss‐Kruszka syndrome.

Methods

We describe three additional patients with overlapping 9q31 deletions and compare the phenotypes of the microdeletion cases reported in the literature to Weiss‐Kruszka syndrome.

Results

Phenotypic overlap was observed between patients with 9q31 deletions and Weiss‐Kruszka syndrome. Several additional features were noted in 9q31 deletion patients, including hearing loss, small head circumference, palate abnormalities and short stature.

Conclusions

The common region of overlap of microdeletion cases implicates ZNF462 as the main driver of the recognizable 9q31 microdeletion phenotype. The observation of additional features in patients with 9q31 microdeletions that are not reported in Weiss‐Kruszka syndrome further suggests that other genes from the 9q31 region likely act synergistically with ZNF462 to affect phenotypic expression.
Artificial neural network models driven novel virtual screening workflow for the identification and biological evaluation of BACE1 inhibitors
Authors: Kashyap Kushagra , Panigrahi Lalita , Ahmed Shakil , Siddiqi Mohammad Imran
Published: December 2022

Beta‐site amyloid‐β precursor protein‐cleaving enzyme 1 (BACE1) is a transmembrane aspartic protease and has shown potential as a possible therapeutic target for Alzheimer's disease. This aggravating disease involves the aberrant production of β amyloid plaques by BACE1 which catalyzes the rate‐limiting step by cleaving the amyloid precursor protein (APP), generating the neurotoxic amyloid β protein that aggregates to form plaques leading to neurodegeneration. Therefore, it is indispensable to inhibit BACE1, thus modulating the APP processing. In this study, we present a workflow that utilizes a multi‐stage virtual screening protocol for identifying potential BACE1 inhibitors by employing multiple artificial neural network‐based models. Collectively, all the hyperparameter tuned models were assigned a task to virtually screen Maybridge library, thus yielding a consensus of 41 hits. The majority of these hits exhibited optimal pharmacokinetic properties confirmed by high central nervous system multiparameter optimization (CNS‐MPO) scores. Further shortlisting of 8 compounds by molecular docking into the active site of BACE1 and their subsequent in‐vitro evaluation identified 4 compounds as potent BACE1 inhibitors with IC50 values falling in the range 0.028–0.052 μM and can be further optimized with medicinal chemistry efforts to improve their activity.
Asymptotic analysis of SIR epidemic model with nonlocal diffusion and generalized nonlinear incidence functional
Authors: Djilali Salih , Chen Yuming , Bentout Soufiane
Published: December 2022

We aim in this research to determine the global stability of equilibrium states for an SIR epidemic model with nonlocal diffusion and nonlinear incidence function in a heterogeneous environment. For achieving this result, we consider that the model parameters are Lipschitz continuous functions. At the infection free‐equilibrium, the eigenvalue problem has a principal simple eigenvalue
corresponding to strictly positive eigenfunction which is expressed as
. By a Lyapunov function approach, we show the global stability of drug‐free equilibrium for
. For
, and using persistence theory for dynamical systems, we show that the epidemic will persist and the unique endemic equilibrium state is globally stable by constructing a proper Lyapunov function.
A miniaturized ultra‐wideband filter with ultra‐wide stopband and high selectivity using a capacitive loading stub in a multimode structure
Authors: Liu Zhi‐Hao , Liu Bao‐Guang , Wang Yu‐Chen , Cheng Chong‐Hu
Published: December 2022

In this paper, a miniaturized ultra‐wideband filter with ultra‐wide stopband and high selectivity using a capacitive loading stub in a multimode structure is proposed. The second, third, and fourth harmonics of the proposed filter are all suppressed on account of using a capacitive loading stub, which makes it have the characteristic of an ultra‐wide stopband. In addition, there are two transmission zeros located at the upper stopband close to the passband, which improves the selectivity of the proposed filter. The proposed filter is fabricated and measured, and the result shows the filter with the center frequency f0 1.185 GHz has 151% 3‐dB fractional bandwidth. Its upper stopband is extended to 9.18 GHz (7.75 f0) and the 20‐dB roll off rate is 212.5 dB/GHz. What's more, the size of the proposed filter is 0.175 λg × 0.18 λg, where λg is the guided wavelength at the center frequency f0.
Design of planar wideband surface‐wave excited substrate integrated waveguide horn antenna loaded with metamaterials
Authors: Cai Yang , Han Wenting , Song Wenke , Li Sen , Cao Yufan
Published: December 2022

In this paper, a wideband planar substrate integrated waveguide (SIW) horn antenna based on surface wave excitation through loading metamaterials is designed. Strong coupling effect is realized between the employed bilayer metamaterial unit with the top layer as a π‐shaped‐slotted patch while the bottom layer as the complementary cross‐shaped‐slotted patch. The equivalent permittivity of the extended substrate in front of the planar horn aperture can be effectively reduced to unity and impedance mismatching for conventional planar SIW horn antenna can be reduced in a wide bandwidth. Results indicate that the working frequency of the antenna is 12.3–15.8 GHz with the relative impedance bandwidth of 24.6%.
Q‐factor enhanced resonator biosensor optimized by adaptive genetic algorithm for glucose detection
Authors: Xie Bingfang , Wang Cong , Meng Fanyi , Li Xiao , Wu Qun
Published: December 2022

This paper presents three devices of biosensors for glucose concentrations. A resonator based on the defected ground structure (DGS) was designed and the optimizations for the single square and both squares of the DGS via adaptive genetic algorithm were applied to enhance the performance of the sensors including the Q‐factor and the electric field distribution. The fabricated devices of the best optimized one exhibited an enhanced Q‐factor of 442 and a sensitivity of 142.2 MHz/mgml−1, which is more than 2.37 times than the basic structure.
Wideband filtering phase shifters using vertically installed planar structure
Authors: Dai Yong , Wang Da‐Yang , Jiang Song , Liu Lei
Published: December 2022

In this letter, A wideband filtering phase shifter is proposed based on vertically installed planar (VIP) circuit structures, where the VIP circuit is used to realize a tight coupling. The even‐odd mode analysis is adopted to analyze the whole structure. Then, a 45° filtering phase shifter is designed to verify the validity of the design methodology. The simulated and measured results demonstrate that the proposed phase shifter has low insertion losses (<0.5 dB) and excellent return losses (<−15 dB). The 3°‐phase shift bandwidth is more than 64.31%.
‘Optimal’ cutoff selection in studies of depression screening tool accuracy using the PHQ‐9, EPDS, or HADS‐D: A meta‐research study
Authors: Brehaut Eliana , Neupane Dipika , Levis Brooke , Wu Yin , Sun Ying , Ioannidis John P. A. , Markham Sarah , Cuijpers Pim , Patten Scott B. , Benedetti Andrea , Thombs Brett D.
Published: December 2022

Objectives

Optimal cutoff thresholds are selected to separate ‘positive’ from ‘negative’ screening results. We evaluated how depression screening tool studies select optimal cutoffs.

Methods

We included studies from previously conducted meta‐analyses of Patient Health Questionnaire‐9, Edinburgh Postnatal Depression Scale, or Hospital Anxiety and Depression Scale—Depression accuracy. Outcomes included whether an optimal cutoff was selected, method used, recommendations made, and reporting guideline and protocol citation.

Results

Of 212 included studies, 172 (81%) attempted to identify an optimal cutoff, and 147 of these 172 (85%) reported one or more methods. Methods were heterogeneous with Youden's J (N = 35, 23%) most common. Only 23 of 147 (16%) studies described a rationale for their method. Rationales focused on balancing sensitivity and specificity without describing why desirable. 131 of 172 studies (76%) identified an optimal cutoff other than the standard; most did not make use recommendations (N = 56; 43%) or recommended using a non‐standard cutoff (N = 53; 40%). Only 4 studies cited a reporting guideline, and 4 described a protocol with optimal cutoff selection methods, but none used the protocol method in the published study.

Conclusions

Research is needed to guide how selection of cutoffs for depression screening tools can be standardized and reflect clinical considerations.
Targeting peptide‐mediated interactions in omics
Authors: Lin Jing , Wang Shaozhou , Wen Li , Ye Haiyang , Shang Shuyong , Li Juelin , Shu Jianping , Zhou Peng
Published: December 2022

Peptide‐mediated interactions (PMIs) play a crucial role in cell signaling network, which are responsible for about half of cellular protein–protein associations in the human interactome and have recently been recognized as a new kind of promising druggable target for drug development and disease therapy. In this article, we give a systematic review regarding the proteome‐wide discovery of PMIs and targeting druggable PMIs (dPMIs) with chemical drugs, self‐inhibitory peptides (SIPs) and protein agents, particularly focusing on their implications and applications for therapeutic purpose in omics. We also introduce computational peptidology strategies used to model, analyze, and design PMI‐targeted molecular entities and further extend the concepts of protein context, direct/indirect readout, and enthalpy/entropy effect involved in PMIs. Current issues and future perspective on this topic are discussed. There is still a long way to go before establishment of efficient therapeutic strategies to target PMIs on the omics scale.
Extinction risk to the endemic trees of Papua New Guinea
Authors: Barstow Megan , Jimbo Tiberius , Davies Katharine
Published: December 2022

Societal Impact Statement

Papua New Guinea has a diverse tree flora. Now for the first time we know that 460 (36%) of its endemic tree species are threatened with extinction in the wild. These trees require immediate conservation action, through a variety of methods. Protection of trees is essential in Papua New Guinea as many people across the country rely on them for their livelihoods. Additionally, the extinction of these species would mean the loss of unique biodiversity. With the majority of forest cover still remaining in Papua New Guinea, it presents an almost unique opportunity to save tree diversity at a large scale and should therefore be at the forefront of the conservation agenda.

Papua New Guinea is one of the world's most tree diverse countries, with over 1,200 endemic tree species. However, forests within the country face a range of threats but the impact of these threats on individual tree species has yet to be studied. Without identifying which species are threatened, where they are and their major threats it is not possible to effectively prioritise conservation actions for the trees of Papua New Guinea.

The Global Tree Assessment for Papua New Guinea produced International Union for Conservation of Nature (IUCN) Red List assessments for over 90% of tree species endemic to Papua New Guinea. The assessments compiled information on extinction risk, major threats, conservation and research needs for the country's tree flora.

Four hundred and sixty tree species are threatened with extinction, including 143 Critically Endangered species. This is 36% of the country's endemic tree flora. The majority of tree species are threatened by annual‐perennial non‐timber crop farming, logging and establishment of wood and pulp plantations. The change in land use instigated by these threats causes lowland tropical/sub‐tropical forest to be the most threatened habitat types for trees.

To protect Papua New Guinea's diverse tree flora, a range of conservation activities are required. Both in situ and ex situ conservation efforts, which are species specific, are needed and activities should be supported on a local, national and international level with continued and expanded collaboration between international NGOs and botanists and specialists working in Papua New Guinea.
Endothelial β‐arrestins regulate mechanotransduction by the type II bone morphogenetic protein receptor in primary cilia
Authors: Park Saejeong , Ma Zhiyuan , Zarkada Georgia , Papangeli Irinna , Paluri Sarin , Nazo Nour , Rivera‐Molina Felix , Toomre Derek , Rajagopal Sudarshan , Chun Hyung J.
Published: December 2022

Modulation of endothelial cell behavior and phenotype by hemodynamic forces involves many signaling components, including cell surface receptors, intracellular signaling intermediaries, transcription factors, and epigenetic elements. Many of the signaling mechanisms that underlie mechanotransduction by endothelial cells are inadequately defined. Here we sought to better understand how β‐arrestins, intracellular proteins that regulate agonist‐mediated desensitization and integration of signaling by transmembrane receptors, may be involved in the endothelial cell response to shear stress. We performed both in vitro studies with primary endothelial cells subjected to β‐arrestin knockdown, and in vivo studies using mice with endothelial specific deletion of β‐arrestin 1 and β‐arrestin 2. We found that β‐arrestins are localized to primary cilia in endothelial cells, which are present in subpopulations of endothelial cells in relatively low shear states. Recruitment of β‐arrestins to cilia involved its interaction with IFT81, a component of the flagellar transport protein complex in the cilia. β‐arrestin knockdown led to marked reduction in shear stress response, including induction of NOS3 expression. Within the cilia, β‐arrestins were found to associate with the type II bone morphogenetic protein receptor (BMPR‐II), whose disruption similarly led to an impaired endothelial shear response. β‐arrestins also regulated Smad transcription factor phosphorylation by BMPR‐II. Mice with endothelial specific deletion of β‐arrestin 1 and β‐arrestin 2 were found to have impaired retinal angiogenesis. In conclusion, we have identified a novel role for endothelial β‐arrestins as key transducers of ciliary mechanotransduction that play a central role in shear signaling by BMPR‐II and contribute to vascular development.
Efficacy and safety of oral pulmonary vasodilators in pulmonary veno‐occlusive disease
Authors: Nakamura Junichi , Tsujino Ichizo , Shima Hideki , Nakaya Toshitaka , Sugimoto Ayako , Sato Takahiro , Watanabe Taku , Ohira Hiroshi , Suzuki Masaru , Tsuneta Satonori , Hisada Ryo , Kato Masaru , Konno Satoshi
Published: December 2022

Pulmonary veno‐occlusive disease (PVOD) or pulmonary capillary hemangiomatosis (PCH) is a rare subtype of pulmonary hypertension with dismal prognosis. Limited data are available on the efficacy and safety of orally administered pulmonary vasodilators for PVOD/PCH. Whether and how systemic sclerosis (SSc) affects the clinical outcomes of PVOD/PCH is also unknown. This study aimed to determine the clinical and hemodynamic efficacy and safety of oral pulmonary vasodilators for PVOD/PCH and clarify the possible effects of SSc on the clinical presentation of PVOD/PCH. We retrospectively analyzed the clinical data of 15 patients with PVOD/PCH treated with oral pulmonary vasodilators in our department since 2001. Six of them had SSc. Oral pulmonary vasodilators were administered either as single agents (n = 10) or in combination (n = 5). Treatment improved the functional class of five patients, and pulmonary arterial pressure and pulmonary vascular resistance decreased by 10 ± 12 mmHg and 36 ± 19%, respectively (p < 0.05 for both, n = 13), whereas pulmonary edema developed in three patients. The mean survival was 3.9 years, and the 1‐ and 3‐year survival rates were 93% and 65%, respectively. The clinical presentation, including survival, was similar between patients with and without SSc. In our PVOD/PCH cohort, oral pulmonary vasodilators caused pulmonary edema in 20% of patients, but more than 80% of patients experienced significant pulmonary vasodilatory effects, and the overall prognosis was better than that previously reported. SSc does not adversely affect the clinical outcomes of PVOD/PCH.
Failure mode and effect analysis using the hesitant intuitionistic fuzzy hybrid GRP approach with ordered comprehensive weights
Authors: Yu Jianxing , Xu Ya , Yu Yang , Wu Shibo
Published: December 2022

Failure mode and effect analysis (FMEA), a multidisciplinary reliability analysis tool based on team evaluations, has been widely used in various industries. There are three critical issues in FMEA: the conversion of linguistic evaluations, the weights of risk factors, and the ranking mechanism of failure modes. Scholars have used various fuzzy theories and multi‐attribute decision‐making (MADM) methods to improve traditional FMEA, but there are still deficiencies. In this paper, the hesitant intuitionistic fuzzy set (HIFS), a concept that combines the intuitionistic fuzzy set (IFS) and the hesitant fuzzy set (HFS), is introduced into FMEA to convert linguistic evaluations. Some operators based on HIFS are proposed to process the converted data. Among them, a hesitant intuitionistic fuzzy comprehensive weighted Hamming distance (HIFCWHD) operator is proposed to compute the ordered comprehensive weight, effectively weakening the effect of extreme scores on results. The gray relational projection (GRP) method is adopted to determine the risk priority order of the failure modes. Finally, we give an illustrative case to demonstrate the effectiveness of the proposed FMEA method.
Ammonium Hexafluorosilicate (AHFS) Modified HMCM‐22 As Efficient Catalysts for Alkylation of Phenol with Methanol
Authors: Liu Zonghui , Xie Dehua , Ran Jianzhou , Wu Jing , Liu Na , Xue Bing
Published: December 2022

A series of xAHFS/HMCM‐22 (x denotes the amount of AHFS treatment on HMCM‐22, AHFS is the abbreviation for ammonium hexafluorosilicate) were prepared and evaluated in the catalytic synthesis of p‐cresol by alkylation of phenol with methanol. Several characterization techniques including N2 adsorption‐desorption, XRD, FT‐IR, 27Al MAS NMR, Pyridine‐IR, and NH3‐TPD have been used to analyze the physicochemical properties of the xAHFS/HMCM‐22 catalyst. The conversion of phenol decreased with increasing x of xAHFS/HMCM‐22 catalyst; while the selectivity for p‐cresol maximized at x=0.07. The 0.07AHFS/HMCM‐22 catalyst was identified as the most efficient catalyst, showing the highest p‐cresol selectivity (53.3 %) for longer than 24 h under optimized reaction conditions (325 °C, WHSV=2 h−1), which is much higher than that of parent HMCM‐22 catalyst (37.1 %). The high p‐cresol selectivity of the catalyst is attributed to AHFS removing part of the acid sites on the external surface of the HMCM‐22, and preserving the acid sites in the micropores of zeolite. By contrast, the decrease in catalyst activity is due to the decrease in total acid sites.
Selective Adsorption and Removal of Congo Red Based on Ethylenediamine Functionalized Mesoporous Silica
Authors: Zhou Yunpeng , Wang Jing , Zhao Qian , Cai Honghui , Zhang Hao
Published: December 2022

Five types of mesoporous silica‐based adsorbents were prepared by rationally implementing five diverse amine‐containing functional units into the mesoporous SBA‐15 structures. The prepared materials were characterized by Fourier transform infrared spectroscopy, X‐ray diffraction, scanning electron microscopy, transmission electron microscopy, N2 adsorption−desorption isotherms and thermogravimetric analysis. Among the five adsorbents, the ethylenediamine functionalized SBA‐15, namely, AAPTMS‐SBA‐15, achieved the complete adsorption of Congo red (CR) at pH 6.0, with the maximum adsorption capacity of 4608 mg/g. The AAPTMS‐SBA‐15 material was used effectively for CR adsorption from the individual and binary dye aqueous solutions, indicating that AAPTMS‐SBA‐15 can selectively remove and separate CR from wastewater. The hydrogen bonding interactions between AAPTMS‐SBA‐15 and CR were beneficial to the high selectivity and excellent adsorption capacity of AAPTMS‐SBA‐15 toward CR. Moreover, the selective adsorption and efficient separation of CR realized the recovery and reusability of AAPTMS‐SBA‐15 and CR, which can not only avoid secondary environmental pollution, but also save economic costs.
Complexation of N‐Heterocyclic Substituted 1,10‐Phenanthroline‐2,9‐diamide with Am3+/Eu3+ Ions for Nuclear Waste Water Treatment
Authors: Ebenezer Cheriyan , Solomon Rajadurai Vijay
Published: December 2022

Designing organic ligands is a popular strategy in removing hazardous radioactive substances from nuclear wastewater which has been a major environmental concern. In this regard, a new family of alicyclic substituted 1, 10‐ phenanthroline‐2, 9‐diamide ligands has been reported recently for efficient extraction of Am3+ over Eu3+ ions. Thus, a series of 1, 10‐ phenanthroline‐2, 9‐diamide ligands with heterocyclic substituents (Pyrrolidine, Piperidine, Pyrrole and Dihydropyridine) and their 1 : 1 complexes (ML(NO3)3) have been considered for this investigation to understand the role of substitution of heterocycles in selective extraction process in nuclear waste management. An attempt has been made to unveil the complexation behaviour of these ligands with Am3+ and Eu3+ ions from DFT calculations. Electronic structure, Mulliken Population Analysis, Bond Order Analysis, QTAIM (Quantum Theory of Atoms in Molecules) Analysis, and EDA (Energy Decomposition Analysis) were all performed. We addressed the feasibility of ML(NO3)3 complex formation from thermodynamics perspective where Pyrrolidine moiety has been found to show highest selectivity for Am3+ ion. M−O bonds contribute more to the coordinating ability of the ligands than M−N bonds in each complex, according to the findings. Orbital interactions hold the key between M(NO3)3 and the ligand in stabilizing the complexes. The weak covalent character of Metal‐Ligand bonds is addressed from QTAIM analysis. In short, this study offers guidelines to use heterocycles efficiently to design better ligands for selective partitioning of trivalent Am over Eu ions in the spent nuclear fuel processing.
Effect of Alkyl Chain Length on Current‐Voltage Characteristics of BODIPY Molecules Deposited on Si(n++) Substrates
Authors: Shivran Neelam , Koiry Shankar P. , Kushwah Nisha , Chauhan Anil K. , Aswal Dinesh K. , Chattopadhyay Subrata , Mula Soumyaditya
Published: December 2022

Despite having good electronic properties, BODIPY (boron dipyrromethene) and its derivatives attract less research attention towards the development of BODIPY based molecular electronics. Here we have investigated the effect of alkyl chain length attached to BODIPY molecule on its diode and negative differential behaviour. An undecenyl‐BODIPY dye (BODIPY‐C11) was designed, synthesized and deposited on Si (111) surface which was further converted into a bilayer using another BODIPY dye, PM567. Various techniques were used to check the arrangement and thickness of the layers which established that the designed molecule is suitable for compact grafting on Si surface. Electrical behaviour of BODIPY‐C11 monolayer and bilayer showed rectification (rectification ratio=500) and NDR property (peak‐to‐valley ratio=1000), respectively with improved device performances as compared to the electrical characteristics shown by 2,6‐diethyl‐4,4‐difluoro‐1,3,5,7‐tetramethyl‐8‐(4’‐(4”‐penteneoxyphenyl)‐4‐bora‐3a,4a‐diaza‐s‐indecene (BODIPY‐C5) grafted on Si. This study established that the electrical behaviour of BODIPY can be modulated by simply changing the alkyl chain length, which will be useful for the development of BODIPY‐based electronic materials.
Atomic Horizons Interpretation on Enhancing Electrochemical Performance of Ni‐Rich NCM Cathode via W Doping: Dual Improvements in Electronic and Ionic Conductivities from DFT Calculations and Experimental Confirmation
Authors: Gao Daichao , Huang Yanwei , Dong Hongliang , Li Chunyu , Chang Chengkang
Published: December 2022

The rapid capacity degradation and poor rate capability hinder the application of Rich‐Ni layered LiNixCoyMnzO2 (NCM) as cathode materials for high‐energy lithium‐ion batteries. In this study, density functional theory (DFT) calculations, combined with conventional electrochemical measurements, reveal from the atomic view that the dual improvements in electronic and ionic conductivities are the main facts for the property enhancement. The bandgap of the cathode material is reduced to 1.1623 eV due to the increased number of electrons near the Fermi level after W intercalation. Such improved electronic conductivity subsequently leads to a suppressed polarization and reduced resistance, enabling an improved cycle life of up to 93.97% after 100 cycles at 0.5 C. Furthermore, the doping with W6+ also introduced a strong WO bond into the layered structure so that the thickness of the Li slab is expanded to 2.6476 Å, which reduces the energy barrier from 0.355 to 0.308 eV for the migration of Li+ within the Li slab, as confirmed by the DFT calculation. Consequently, the rate performance is greatly improved due to the reduced diffusion energy, with a specific capacity of 159.11 mAg−1 even at 5 C rate, indicating high potential for future applications.
Creating Highly Active Iron Sites in Electrochemical N2 Reduction by Fabricating Strongly‐Coupled Interfaces
Authors: Zhao Meng , Wang Jing , Wang Xiao , Xu Jing , Liu Li , Yang Weiting , Feng Jing , Song Shuyan , Zhang Hongjie
Published: December 2022

Electrochemical Nc reduction has been regarded as one of the most promising approaches to producing ammonia under mild conditions, but there are remaining pressing challenges in improving the reaction rate and efficiency. Herein, an unconventional galvanic replacement reaction is reported to fabricate a unique hierarchical structure composed of Fe3O4‐CeO2 bimetallic nanotubes covered by Fe2O3 ultrathin nanosheets. Control experiments reveal that CeO2 species play the essential role of stabilizer for Fe2+ cations. Compared with bare CeO2 and Fe2O3 nanotubes, the as‐obtained Fe2O3/Fe3O4‐CeO2 possesses a remarkably enhanced NH3 yield rate (30.9 µg h−1 mgcat−1) and Faradaic efficiency (26.3%). The enhancement can be attributed to the hierarchical feature that makes electrodes more easily to contact with electrolytes. More importantly, as verified by density functional theory calculations, the generation of Fe2O3‐Fe3O4 heterogeneous junctions can efficiently optimize the reaction pathways, and the energy barrier of the potential determining step (the *N2 hydrogenates into *N*NH) is significantly decreased.
Phase Transition Induced via the Template Enabling Cocoon‐like MoS2 an Exceptionally Electromagnetic Absorber
Authors: Fang Jiefeng , You Wenbin , Xu Chunyang , Yang Bintong , Wang Min , Zhang Jincang , Che Renchao
Published: December 2022

Structural engineering via the template method is efficient for micro‐nano assembling. However, only structural design and lack of composition control restrict their advanced application. To overcome this issue, applying a template to simultaneously realize the structural design and fine component control is highly desired, which has been ignored. In this study, a spinel‐shaped MoS2 heterostructure with controlled phase ratios of 1H and 2H phase is developed using the AlOOH template method. This work demonstrates that the MoS2 phase transition mechanism from 2H to 1T is substantially attributed to the close exposed crystal's surface and approximately accordant surface energy. The superiority and additional proof are provided based on density‐functional theory simulation, transmission electron microscope holography, etc. With an effective absorptance region of 6.3 GHz under a thickness of 1.4 mm, the reported samples present outstanding microwave absorption capacity. This is attributed to the beneficial coupled effect between the well‐designed structure and phase regulation. This work offers valuable insights into structural engineering and component regulation template methods.
Functional Carbon Quantum Dots for Ocular Imaging and Therapeutic Applications
Authors: Kumar Vijay Bhooshan , Sher Ifat , Rencus‐Lazar Sigal , Rotenstreich Ygal , Gazit Ehud
Published: December 2022

Carbon quantum dots (CDs) are a class of emerging carbonaceous nanomaterials that have received considerable attention due to their excellent fluorescent properties, extremely small size, ability to penetrate cells and tissues, ease of synthesis, surface modification, low cytotoxicity, and superior water dispersion. In light of these properties, CDs are extensively investigated as candidates for bioimaging probes, efficient drug carriers, and disease diagnostics. Functionalized CDs represent a promising therapeutic candidate for ocular diseases. Here, this work reviews the potential use of functionalized CDs in the diagnosis and treatment of eye‐related diseases, including the treatment of macular and anterior segment diseases, as well as targeting Aβ amyloids in the retina.
One‐Pot Controllable Assembly of a Baicalin‐Condensed Aptamer Nanodrug for Synergistic Anti‐Obesity
Authors: Tian Jingjing , He Xiaoyun , Lan Xinyue , Liang Xingxing , Zhong Zhaobin , Zhu Longjiao , Chen Keren , Chang Qiaoying , Xu Wentao
Published: December 2022

The rapid, simple and low‐cost preparation of DNA micro‐nano‐architectures remain challenging in biosensing and therapy. Polymerase chain reaction (PCR)‐driven DNA micro‐nano‐flowers are used to construct a nanosized baicalin‐compressed‐aptamer‐nanodrug (bcaND) via one‐pot assembly for targeted and synergistic anti‐obesity. In the design, the tailored Adipo‐8 (tAdi‐8) overhang in the PCR amplicon displays anti‐obesity targeting activity, while the baicalin loaded in the bcaND by embedding the amplicon plays a three‐fold role as a lipid‐lowering factor, bcaND size compressor, and uncoupling protein‐1 (UCP1)‐raised thermogenic activator. The ingenious bcaND represents an advanced multifunctional nanomaterial capable of adjusting the morphology at an optimal 400/1 molar ratio of Mg2+ to phosphate groups, compressing the size from 2.699 µm to 214.76 nm using 1 mg/mL baicalin at a temperature of 70 °C, an effective payload with amplicons of up to 98.94%, and a maximum baicalin load of 86.21 g/g DNA. Responsive release in acidic conditions (pH 5.0) occurs within 72 h, accelerating thermogenesis via UCP1 up‐regulation by 2.5‐fold in 3T3‐L1‐preadipocytes and 13.7‐fold in the white‐adipose‐tissue (WAT) of mice, targeting adipocytes and visceral white adipose tissue. It plays an efficient synergistic role in obesity therapy in vitro and in vivo, providing a new direction for DNA self‐assembly nanotechnology.
Maneuvering the Peroxidase‐Like Activity of Palladium‐Based Nanozymes by Alloying with Oxophilic Bismuth for Biosensing
Authors: Xia Shiyu , Wu Fengxia , Cheng Lu , Bao Haibo , Gao Wenping , Duan Jin , Niu Wenxin , Xu Guobao
Published: December 2022

Engineering the catalytic performance of nanozymes is of vital importance for their broad applications in biological analysis, cancer treatment, and environmental management. Herein, a strategy to boost the peroxidase‐like activity of Pd‐based nanozymes with oxophilic metallic bismuth (Bi) is demonstrated, which is based on the incorporation of oxophilic Bi in the Pd‐based alloy nanocrystals (NCs). To synthesize PdBi alloy NCs, a seed‐mediated method is employed with the assistance of underpotential deposition (UPD) of Bi on Pd. The strong interaction of Bi atoms with Pd surfaces favors the formation of alloy structures with controllable shapes and excellent monodispersity. More importantly, the PdBi NCs show excellent peroxidase‐like activities compared with pristine Pd NCs. The structure–function correlations for the PdBi nanozymes are elucidated, and an indirect colorimetric method based on cascade reactions to determine alkaline phosphatase (ALP) is established. This method has good linear range, low detection limit, excellent selectivity, and anti‐interference. Collectively, this work not only provides new insights for the design of high‐efficiency nanozymes, expands the colorimetric sensing platform based on enzyme cascade reactions, but also represents a new example for UPD‐directed synthesis of alloy NCs.