bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Smart Near‐Infrared Carbon Dot‐Metal Organic Framework Assemblies for Tumor Microenvironment‐Activated Cancer Imaging and Chemodynamic‐Photothermal Combined Therapy
Authors: Bai Yulong , Zhao Jingjin , Zhang Liangliang , Wang Shulong , Hua Jing , Zhao Shulin , Liang Hong 
Published: February 2022

AbstractTumor microenvironment (TME)‐activated cancer imaging and therapy is a key to achieving accurate diagnosis and treatment of cancer and reducing the side effects. Herein, smart near‐infrared carbon dot‐metal organic framework MIL‐100 (Fe) assemblies are constructed to achieve TME‐activated cancer imaging and chemodynamic‐photothermal combined therapy. First, a near‐infrared emission carbon dot (RCDs) is developed using glutathione (GSH) as the precursor. Then, the RCDs@MIL‐100 self‐assemblies are obtained using RCDs, FeCl3, and trimesic acid solutions as raw materials. After the RCDs@MIL‐100 enters the TME, a high concentration of GSH reduces Fe3+ to Fe2+ and drains the GSH, triggering the collapse of RCDs@MIL‐100 skeleton and the release of RCDs and Fe2+, at which time the RCDs fluorescence is restored and in an “on” state to illuminate the tumor cells, which achieved cancer imaging. The released Fe2+ reacts with H2O2 in the TME to form highly reactive hydroxyl radicals (•OH) by Fenton reaction, which achieves the chemodynamic therapy of tumors. Thus, efficient synergistic chemodynamic‐photothermal dual mode therapy is achieved under fluorescence imaging guidance with TME response.
Predicting the Effects of Waning Vaccine Immunity Against COVID‐19 through High‐Resolution Agent‐Based Modeling
Authors: Truszkowska Agnieszka , Zino Lorenzo , Butail Sachit , Caroppo Emanuele , Jiang Zhong‐Ping , Rizzo Alessandro , Porfiri Maurizio 
Published: February 2022

AbstractThe potential waning of the vaccination immunity to COVID‐19 could pose threats to public health, as it is tenable that the timing of such waning would synchronize with the near‐complete restoration of normalcy. Should also testing be relaxed, a resurgent COVID‐19 wave in winter 2021/2022 might be witnessed. In response to this risk, an additional vaccine dose, the booster shot, is being administered worldwide. A projected study with an outlook of 6 months explores the interplay between the rate at which boosters are distributed and the extent to which testing practices are implemented, using a highly granular agent‐based model tuned on a medium‐sized US town. Theoretical projections indicate that the administration of boosters at the rate at which the vaccine is currently administered could yield a severe resurgence of the pandemic. Projections suggest that the peak levels of mid‐spring 2021 in the vaccination rate may prevent such a scenario to occur, although exact agreement between observations and projections should not be expected due to the continuously evolving nature of the pandemic. This study highlights the importance of testing, especially to detect asymptomatic individuals in the near future, as the release of the booster reaches full speed.
A Bionic‐Homodimerization Strategy for Optimizing Modulators of Protein–Protein Interactions: From Statistical Mechanics Theory to Potential Clinical Translation
Authors: Yan Jin , Zheng Xiaoqiang , You Weiming , He Wangxiao , Xu Guang‐Kui 
Published: February 2022

AbstractEmerging protein–protein interaction (PPI) modulators have brought out exciting ability as therapeutics in human diseases, but its clinical translation has been greatly hampered by the limited affinity. Inspired by the homodimerize structure of antibody, the homodimerization contributes hugely to generating the optimized affinity is conjectured. Herein, a statistical‐mechanics‐theory‐guided method is established to quantize the affinity of ligands with different topologies through analyzing the change of enthalpy and the loss of translational and rotational entropies. A peptide modulator for p53‐MDM2 termed CPAP is used to homodimerize connecting, and this simple homodimerization can significantly increase the affinity. To realize the cellular internalization and tumor accumulation, DimerCPAP and MonoCPAP are nanoengineered into gold(I)‐CPAP supermolecule by the aurophilic interaction‐driven self‐assembly. Nano‐DimerCPAP potently suppressed tumor growth in lung cancer allograft model and a patient‐derived xenograft model in more action than Nano‐MonoCPAP, while keeping a favorable drug safety profile. This work not only presents a physico‐mechanical method for calculating the affinity of PPI modulators, but also provides a simple yet robust homodimerization strategy to optimize the affinity of PPI modulators.
Influence of thermal runaway in styrene–acrylonitrile bulk copolymerization revealed by computational fluid dynamics modeling
Authors: Yang Ya‐Nan , Zhou Yin‐Ning , Ouyang Bo , Wu Yi‐Yang , Zhang Xi‐Bao , Luo Zheng‐Hong 
Published: February 2022

AbstractThe computational fluid dynamics (CFD) and kinetic‐based moment methods coupled approach is adopted to simulate the bulk copolymerization of styrene–acrylonitrile (SAN) in a stirred tank reactor. Numerical simulations are carried out to investigate the impacts of impeller speed, monomer ratio, initiator ratio, and initial reaction temperature on the copolymerization process and product properties. Particularly, the Chaos theory is selected as a criterion for evaluating the occurrence of the thermal runaway. The Flory's and Stockmayer's distributions are employed to calculate chain length distribution and copolymer composition distribution of copolymer. The simulation results highlight that the appearance of thermal runaway can be postponed by properly increasing the rotation speed, decreasing the initiator loadings, initial acrylonitrile contents and initial reactor temperature. Furthermore, significant differences exist in the product properties that predicted by the ideal and non‐ideal models, which demonstrates that the temperature heterogeneity plays a crucial role in SAN copolymerization. This study could offer references for the safe operation and design of polymerization processes.
Personalizing Deep Brain Stimulation Using Advanced Imaging Sequences
Authors: Neudorfer Clemens , Kroneberg Daniel , Al‐Fatly Bassam , Goede Lukas , Kübler Dorothee , Faust Katharina , van Rienen Ursula , Tietze Anna , Picht Thomas , Herrington Todd M. , Middlebrooks Erik H. , Kühn Andrea , Schneider Gerd‐Helge , Horn Andreas 
Published: February 2022

ObjectiveWith a growing appreciation for interindividual anatomical variability and patient‐specific brain connectivity, advanced imaging sequences offer the opportunity to directly visualize anatomical targets for deep brain stimulation (DBS). The lack of quantitative evidence demonstrating their clinical utility, however, has hindered their broad implementation in clinical practice.MethodsUsing fast gray matter acquisition T1 inversion recovery (FGATIR) sequences, the present study identified a thalamic hypointensity that holds promise as a visual marker in DBS. To validate the clinical utility of the identified hypointensity, we retrospectively analyzed 65 patients (26 female, mean age = 69.1 ± 12.7 years) who underwent DBS in the treatment of essential tremor. We characterized its neuroanatomical substrates and evaluated the hypointensity's ability to predict clinical outcome using stimulation volume modeling and voxelwise mapping. Finally, we determined whether the hypointensity marker could predict symptom improvement on a patient‐specific level.ResultsAnatomical characterization suggested that the identified hypointensity constituted the terminal part of the dentatorubrothalamic tract. Overlap between DBS stimulation volumes and the hypointensity in standard space significantly correlated with tremor improvement (R2 = 0.16, p = 0.017) and distance to hotspots previously reported in the literature (R2 = 0.49, p = 7.9e‐4). In contrast, the amount of variance explained by other anatomical atlas structures was reduced. When accounting for interindividual neuroanatomical variability, the predictive power of the hypointensity increased further (R2 = 0.37, p = 0.002).InterpretationOur findings introduce and validate a novel imaging‐based marker attainable from FGATIR sequences that has the potential to personalize and inform targeting and programming in DBS for essential tremor. ANN NEUROL 2022;91:613–628
RGMa Signal in Macrophages Induces Neutrophil‐Related Astrocytopathy in NMO
Authors: Iwamoto Shosuke , Itokazu Takahide , Sasaki Atsushi , Kataoka Hirotoshi , Tanaka Shinji , Hirata Takeshi , Miwa Keiko , Suenaga Toshihiko , Takai Yoshiki , Misu Tatsuro , Fujihara Kazuo , Yamashita Toshihide 
Published: February 2022

ObjectiveRepulsive guidance molecule‐a (RGMa) is a glycosylphosphatidylinositol‐linked glycoprotein which has multiple functions including axon growth inhibition and immune regulation. However, its role in the pathophysiology of neuromyelitis optica (NMO) is poorly understood. Perivascular astrocytopathy, which is induced by the leakage of aquaporin‐4 (AQP4)‐specific IgG into the central nervous system parenchyma, is a key feature of NMO pathology. We investigated the RGMa involvement in the pathology of NMO astrocytopathy, and tested a therapeutic potential of humanized anti‐RGMa monoclonal antibody (RGMa‐mAb).MethodsUsing a clinically relevant NMO rat model, we evaluated the therapeutic effect of a RGMa‐mAb by behavioral testing, immunohistochemistry, and gene expression assay. We further performed in vitro experiments to address the RGMa‐signaling in macrophages.ResultsIn both NMO rats and an NMO‐autopsied sample, RGMa was expressed by the spared neurons and astrocytes, whereas its receptor neogenin was expressed by infiltrating macrophages. AQP4‐IgG‐induced astrocytopathy and clinical exacerbation in NMO rats were ameliorated by RGMa‐mAb treatment. RGMa‐mAb treatment significantly suppressed neutrophil infiltration, and decreased the expression of neutrophil chemoattractants. Interestingly, neogenin‐expressing macrophages accumulated in the lesion expressed CXCL2, a strong neutrophil chemoattractant, and further analysis revealed that RGMa directly regulated CXCL2 expression in macrophages. Finally, we found that our NMO rats developed neuropathic pain, and RGMa‐mAb treatment effectively ameliorated the severity of neuropathic pain.InterpretationRGMa signaling in infiltrated macrophages is a critical driver of neutrophil‐related astrocytopathy in NMO lesions, and RGMa‐mAb may provide an efficient therapeutic strategy for NMO‐associated neuropathic pain and motor deficits in patients with NMO. ANN NEUROL 2022;91:532–547
Ultra‐Tough Elastomers from Stereochemistry‐Directed Hydrogen Bonding in Isosorbide‐Based Polymers
Authors: Petersen Shannon R. , Prydderch Hannah , Worch Joshua C. , Stubbs Connor J. , Wang Zilu , Yu Jiayi , Arno Maria C. , Dobrynin Andrey V. , Becker Matthew L. , Dove Andrew P. 
Published: February 2022

AbstractThe remarkable elasticity and tensile strength found in natural elastomers are challenging to mimic. Synthetic elastomers typically feature covalently cross‐linked networks (rubbers), but this hinders their reprocessability. Physical cross‐linking via hydrogen bonding or ordered crystallite domains can afford reprocessable elastomers, but often at the cost of performance. Herein, we report the synthesis of ultra‐tough, reprocessable elastomers based on linear alternating polymers. The incorporation of a rigid isohexide adjacent to urethane moieties affords elastomers with exceptional strain hardening, strain rate dependent behavior, and high optical clarity. Distinct differences were observed between isomannide and isosorbide‐based elastomers where the latter displays superior tensile strength and strain recovery. These phenomena are attributed to the regiochemical irregularities in the polymers arising from their distinct stereochemistry and respective inter‐chain hydrogen bonding.
Short Synthesis of (+)‐Actinobolin: Simple Entry to Complex Small‐Molecule Inhibitors of Protein Synthesis
Authors: Tharra Prabhakara R. , Mikhaylov Andrey A. , Švejkar Jiří , Gysin Marina , Hobbie Sven N. , Švenda Jakub 
Published: February 2022

AbstractWe report a concise synthesis of the naturally occurring protein synthesis inhibitor (+)‐actinobolin (1). The densely functionalized and stereochemically complex molecular structure of 1 was assembled from (−)‐quinic acid, L‐threonine, and L‐alanine as the principal components. Our route is based around a convergent strategy that features conjugate addition of an α‐amino radical in the key fragment‐coupling step. The dramatically simplified synthesis of (+)‐actinobolin proceeding in 9 steps with 18 % overall yield has practical implications for analog preparation, as demonstrated herein.
Synthesis of Cyclophenacene‐ and Chiral‐Type Cyclophenylene‐Naphthylene Belts
Authors: Nogami Juntaro , Nagashima Yuki , Sugiyama Haruki , Miyamoto Kazunori , Tanaka Yusuke , Uekusa Hidehiro , Muranaka Atsuya , Uchiyama Masanobu , Tanaka Ken 
Published: February 2022

AbstractWe report the synthesis of a [20]cyclophenacene‐type cyclophenylene‐naphthylene (CPN) belt and the enantioselective synthesis of chiral‐type CPN belts (up to >99 %ee) by the cationic rhodium(I)‐catalyzed intramolecular [2+2+2] cycloaddition of naphthalene‐embedded cyclic polyynes. The synthesis of a depth‐expanded CPN belt was also attempted, but the final intramolecular [2+2+2] cycloaddition was unsuccessful. Theoretical calculations clarified that the reactivity depends on the stability of the transition state in the initial oxidative cycloaddition step which is subject to molecular strain. The cylindrical structures of these CPN belts were confirmed by X‐ray crystallographic analyses. As a result of π‐extension through the introduction of naphthalenes in the chiral‐type CPN belts, the anisotropy dissymmetry factors of electronic circular dichroism and circularly polarized luminescence are amplified compared with the corresponding zigzag‐type chiral cyclophenylene belts.
Shape‐Shifting Molecules: Unveiling the Valence Tautomerism Phenomena in Bare Barbaralones
Authors: Sanz‐Novo Miguel , Mato Mauro , León Íker , Echavarren Antonio M. , Alonso José L. 
Published: February 2022

AbstractWe report a state‐of‐the‐art spectroscopic study of an archetypical barbaralone, conclusively revealing the valence tautomerism phenomena for this bistable molecular system. The two distinct 1‐ and 5‐substituted valence tautomers have been isolated in a supersonic expansion for the first time and successfully characterized by high‐resolution rotational spectroscopy. This work provides irrefutable experimental evidence of the [3,3]‐rearrangement in barbaralones and highlights the use of rotational spectroscopy to analyze shape‐shifting mixtures. Moreover, this observation opens the window toward the characterization of new fluxional systems in the isolation conditions of the gas phase and should serve as a reference point in the general understanding of valence tautomerism.
Overcoming Spectral Dependence: A General Strategy for Developing Far‐Red and Near‐Infrared Ultra‐Fluorogenic Tetrazine Bioorthogonal Probes
Authors: Mao Wuyu , Chi Weijie , He Xinyu , Wang Chao , Wang Xueyi , Yang Haojie , Liu Xiaogang , Wu Haoxing 
Published: February 2022

AbstractBioorthogonal fluorogenic dyes are indispensable tools in wash‐free bioimaging of specific biological targets. However, the fluorogenicity of existing tetrazine‐based bioorthogonal probes deteriorates as the emission wavelength shifts towards the NIR window, greatly limiting their applications in live cells and tissues. Herein, we report a generalizable molecular design strategy to construct ultra‐fluorogenic dyes via a simple substitution at the meso‐positions of various far‐red and NIR fluorophores. Our probes demonstrate significant fluorescence turn‐on ratios (102–103‐fold) in the range 586–806 nm. These results will greatly expand the applications of bioorthogonal chemistry in NIR bioimaging and biosensing.
Evaluation of mechanical properties of poly(L‐lactic acid) braided stents with axial stiffeners
Authors: Zhao Gutian , Liu Qingwei , Tian Yuan , Liu Jinbo , Cheng Jie , Ni Zhonghua 
Published: February 2022

AbstractPoly(l‐lactic acid) (PLLA) has been widely used in constructing biodegradable braided stents due to high biocompatibility and biodegradability. However, poor mechanical properties of this stent are main weaknesses. In this paper, the mechanical properties of PLLA braided stents containing axial stiffeners were evaluated. The stents with stiffener diameters of 0.11, 0.19 and 0.28 mm are named SS11, SS19 and SS28, respectively, and the stent without stiffener is named SS00 as control. The results show that compared with SS00, the bending stiffness of SS11, SS19 and SS28 is increased by 0.77, 1.76, and 2.70 times, respectively. Meanwhile, chronic outward force at an indicated use diameter of 5 mm is increased by 0.83, 0.50, and 0.21 times, but elastic recovery rate is decreased by 5.6%, 14.6%, 22.5%. In addition, radial stiffness of SS11, SS19, and SS28 are increased by 2.81, 2.08 and 1.62 times, respectively. Therefore, the radial support performance is improved and the bending flexibility is weakened by adding stiffeners. Taken together, SS11 can provide sufficient radial support force and low axial force in clinical applications. This study may provide a reference for optimizing the mechanical properties of the biodegradable braided stents.
Improving of the structures and properties of functional polyimide films by direct blend method
Authors: Niu Yongan , Shi Zenghui , Pei Yingjin , Lu Xinyu , Feng Jianming , Zhang Xin 
Published: February 2022

AbstractTriphenylamine (TPA)‐based polyimides (PIs) have excellent discoloration characteristics and widely used as functional films. However, these PIs usually exhibit lower mechanical and thermal properties, and TPA units as the electron donor also weaken the optical transmittance of PIs. Utilized blending with diaminodiphenyl ether (ODA)‐based PIs, we successfully prepared the blend polyimide (BPI) films containing ODA/TPA units, to realize complementary advantages of excellent mechanical, thermal, optical, and electrochemical properties. Among them, the tensile strength of BPI‐53 film (mole ratio of TPA/ODA = 5:3) is reached up to 105.5 MPa, which is 641.9% much higher than 14.22 MPa of TPA‐PI film. Moreover, the thermal stability of BPI‐53 film is also significantly improved. T5 (temperature of 5% weight loss) can be increased to 548.26°C for BPI‐53 film, and the weight residual rate at 800°C in N2 atmosphere is increased by an addition of 4%. Besides, BPI‐53 film also has good transmittance property in district of 400–700 nm, and the variation range of transmittance under 1.0 V positive bias voltage is of 36.61%. For the electrochromics, the discoloration properties of blend polyamide acid (BPAA) dry film can be well maintained.
Bis‐Iridoids from Pterocephalus hookeri and Evaluation of Their Anti‐Inflammatory Activity
Authors: Xu De‐Feng , Miao Lei , Zhang Jun‐Sheng , Zhang Hua 
Published: February 2022

AbstractFour new secoiridoid‐iridoid heterodimers, pterocenoids E–H (1–4), together with a known analog (5), were separated from the whole plants of Pterocephalus hookeri. Their structures were characterized by detailed spectroscopic analyses and NMR comparison with reported data for known analogs. Pterocenoid E (1) represents the first bis‐iridoid example incorporating a rare trans‐fused monomeric unit, and the C(8) configuration in 5 was corrected to be reversed to the original assignment. Among all the isolates, compound 5 not only showed moderate inhibition against the nitric oxide production (IC50=36.0±4.3 μM) but also dose‐dependently suppressed the secretion of an important pro‐inflammatory cytokine TNF‐α, in lipopolysaccharide‐induced RAW264.7 cells.
The patient experience of relapsed refractory multiple myeloma and perspectives on emerging therapies
Authors: Crawford Rebecca , Gries Katharine S. , Valluri Satish , Fastenau John , Morrison Ross , Yeh Tzu‐Min , Olyslager Yunsi , Goldberg Jenna D. , Schecter Jordan M. , Jackson Carolyn C. , Deraedt William , Doward Lynda 
Published: February 2022

AbstractBackgroundRelapsed refractory multiple myeloma (RRMM) is a disease that is nonresponsive or progressive on therapy, and although patients can achieve remission, relapse is common. As more treatment options become available for multiple myeloma (MM), it is important to understand patients' experiences of current and emerging therapies.AimsThis study aimed to better understand patient experiences with treatment and therapies for MM using qualitative interviews and patient‐reported information (PRI) shared on social media.MethodsSemistructured qualitative interviews were conducted with adults with RRMM who resided in the United States. In addition to the interviews, PRI was collected from YouTube and a patient advocacy website. Key themes from the interviews and PRI were summarized, and illustrative quotes were extracted.ResultsTwenty participants were interviewed; 11 were female, and mean (standard deviation) age was 60 (7.0) years. The PRI included 14 posts and 19 unique contributors (10 were female). Similar treatment‐related symptoms were reported in the interviews and PRI. Fatigue and pain were the most frequently reported symptoms while receiving treatment in both the interviews and PRI. These symptoms had a meaningful impact on health‐related quality of life (HRQOL); being off treatment and returning to normal living was described as an ideal treatment outcome. Nearly all interview participants (n = 18) preferred a treatment that would allow for a treatment‐free interval, if it had the same efficacy and safety profile as a continuous treatment.ConclusionThe symptom experience reported in this study is consistent with known RRMM symptoms and HRQOL impacts. Additionally, this study highlighted that patients' treatment expectations are changing relative to their past treatment experience. Individuals living with RRMM strongly desire therapies with a treatment‐free interval and minimal impact on their HRQOL.