bluuebunny/crossref_metadata_2025 huggingface dataset:
Viral Transduction Enhancing Effect of EF‐C Peptide Nanofibrils Is Mediated by Cellular Protrusions
Authors: Schütz Desiree , Rode Sascha , Read Clarissa , Müller Janis A. , Glocker Bernhard , Sparrer Konstantin M. J. , Fackler Oliver T. , Walther Paul , Münch Jan
Published: July 2021

Self‐assembling peptide nanofibrils (PNF) have gained increasing attention as versatile molecules in material science and biomedicine. One important application of PNF is to enhance retroviral gene transfer, a technology that has been central for gene therapy approaches. The best‐investigated and commercially available PNF is derived from a 12‐mer peptide termed EF‐C. The mechanism of transduction enhancement depends on the polycationic surface of EF‐C PNF, which bind to the negatively charged membranes of viruses and cells, thereby overcoming electrostatic repulsions and increasing virion attachment and fusion. To better understand how EF‐C PNF interact with the cell surface, scanning electron and time‐lapse confocal microscopy were performed. The fibrils are found to be actively engaged by cellular protrusions such as filopodia. Consequently, chemical suppression of protrusion formation abrogates fibril binding and virion delivery to the cell surface of immortalized and primary T cells. Vice versa, induction of plasma membrane blebs result in increased fibril binding. Thus, the mechanism of PNF‐mediated viral transduction enhancement involves an active engagement of virus‐loaded fibrils by cellular protrusions, which may explain its superior performance over soluble transduction enhancers.
Localized Chemotherapy Based on Injectable Hydrogel Boosts the Antitumor Activity of Adoptively Transferred T Lymphocytes In Vivo
Authors: Cao Yue , Zhou Yuhao , Chen Zhixiong , Zhang Zhen , Chen Xuesi , He Chaoliang
Published: July 2021

The adoptive transfer of antigen‐specific T cells has been successfully applied in the treatment of hematological malignancies. However, its application in the treatment of solid tumors has been overshadowed by the immunosuppressive tumor microenvironment. In this context, a preprocessing strategy is developed to reprogram the immunosuppressive tumor microenvironment using a thermoresponsive hydrogel loaded with doxorubicin (DOX@Gel). Compared with hydrogel‐based chemotherapy alone or adoptive T cell therapy alone, this combination exhibits enhanced anti‐tumor efficacy. In addition to the direct killing of tumor cells, the local chemotherapy releases tumor‐associated antigens which enhance the proliferation and effector function of endogenous and adoptively transferred T cells. Moreover, DOX@Gel significantly reduces the numbers of both myeloid derived suppressor cells and Tregs in tumor microenvironment. It is suggested that DOX@Gel promotes the efficacy of adoptively transferred T cells against solid tumors, overcoming the key limitations of adoptive T cell therapy.
Triarylamine‐Pyridine‐Carbonitriles for Organic Light‐Emitting Devices with EQE Nearly 40%
Authors: Chen Yi‐Kuan , Jayakumar Jayachandran , Hsieh Chia‐Min , Wu Tien‐Lin , Liao Chun‐Cheng , Pandidurai Jayabalan , Ko Chang‐Lun , Hung Wen‐Yi , Cheng Chien‐Hong
Published: July 2021

Highly efficient thermally activated delayed fluorescence (TADF) molecules are in urgent demand for solid‐state lighting and full‐color displays. Here, the design and synthesis of three triarylamine‐pyridine‐carbonitrile‐based TADF compounds, TPAPPC, TPAmPPC, and tTPAmPPC, are shown. They exhibit excellent photoluminescence quantum yields of 79−100% with small ΔEST values, fast reverse intersystem crossing (RISC), and high horizontal dipole ratios (Θ// = 86−88%) in the thin films leading to the enhancement of device light outcoupling. Consequently, a green organic light‐emitting diode (OLED) based on TPAmPPC shows a high average external quantum efficiency of 38.8 ± 0.6%, a current efficiency of 130.1 ± 2.1 cd A–1, and a power efficiency of 136.3 ± 2.2 lm W–1. The highest device efficiency of 39.8% appears to be record‐breaking among TADF‐based OLEDs to date. In addition, the TPAmPPC‐based device shows superior operation lifetime and high‐temperature resistance. It is worth noting that the TPA‐PPC‐based materials have excellent optical properties and the potential for making them strong candidates for TADF practical application.
A Robust Narrow Bandgap Vanadium Tetrasulfide Sonosensitizer Optimized by Charge Separation Engineering for Enhanced Sonodynamic Cancer Therapy
Authors: Liang Shuang , Liu Bin , Xiao Xiao , Yuan Meng , Yang Ling , Ma Ping'an , Cheng Ziyong , Lin Jun
Published: July 2021

The development and optimization of sonosensitizers for elevating intratumoral reactive oxygen species (ROS) are definitely appealing in current sonodynamic therapy (SDT). Given this, branched vanadium tetrasulfide (VS4) nanodendrites with a narrower bandgap (compared with the most extensively explored sonosensitizers) are presented as a new source of sonosensitizer, which allows a more effortless separation of sono‐triggered electron–hole pairs for ROS generation. Specifically, platinum (Pt) nanoparticles and endogenous high levels of glutathione (GSH) are rationally engineered to further optimize its sono‐sensitized performance. As cocatalyst, Pt is conducive to trapping electrons, whereas GSH, as a natural hole‐scavenger, tends to capture holes. Compared with the pristine VS4 sonosensitizer, the GSH‐Pt‐VS4 nanocomposite can greatly prolong the lifetime of the charge and confer a highly efficacious ROS production activity. Furthermore, such nanoplatforms are capable of reshaping tumor microenvironments to realize ROS overproduction, contributed by overcoming tumor hypoxia to improve SDT‐triggered singlet oxygen production, catalyzing endogenic hydrogen peroxide into destructive hydroxyl radicals for chemodynamic therapy, and depleting GSH to amplify intratumoral oxidative stress. All these combined effects result in a significantly efficient tumor suppression outcome. This study enriches sonosensitizer research and proves that sonosensitizers can be rationally optimized by charge separation engineering strategy.
Emerging Dual‐Atomic‐Site Catalysts for Efficient Energy Catalysis
Authors: Zhang Weiyu , Chao Yuguang , Zhang Wenshu , Zhou Jinhui , Lv Fan , Wang Kai , Lin Fangxu , Luo Heng , Li Jing , Tong Meiping , Wang Erkang , Guo Shaojun
Published: July 2021

Atomically dispersed metal catalysts with well‐defined structures have been the research hotspot in heterogeneous catalysis because of their high atomic utilization efficiency, outstanding activity, and selectivity. Dual‐atomic‐site catalysts (DASCs), as an extension of single‐atom catalysts (SACs), have recently drawn surging attention. The DASCs possess higher metal loading, more sophisticated and flexible active sites, offering more chance for achieving better catalytic performance, compared with SACs. In this review, recent advances on how to design new DASCs for enhancing energy catalysis will be highlighted. It will start with the classification of marriage of two kinds of single‐atom active sites, homonuclear DASCs and heteronuclear DASCs according to the configuration of active sites. Then, the state‐of‐the‐art characterization techniques for DASCs will be discussed. Different synthetic methods and catalytic applications of the DASCs in various reactions, including oxygen reduction reaction, carbon dioxide reduction reaction, carbon monoxide oxidation reaction, and others will be followed. Finally, the major challenges and perspectives of DASCs will be provided.
First‐Principles Multiscale Modeling of Mechanical Properties in Graphene/Borophene Heterostructures Empowered by Machine‐Learning Interatomic Potentials
Authors: Mortazavi Bohayra , Silani Mohammad , Podryabinkin Evgeny V. , Rabczuk Timon , Zhuang Xiaoying , Shapeev Alexander V.
Published: July 2021

Density functional theory calculations are robust tools to explore the mechanical properties of pristine structures at their ground state but become exceedingly expensive for large systems at finite temperatures. Classical molecular dynamics (CMD) simulations offer the possibility to study larger systems at elevated temperatures, but they require accurate interatomic potentials. Herein the authors propose the concept of first‐principles multiscale modeling of mechanical properties, where ab initio level of accuracy is hierarchically bridged to explore the mechanical/failure response of macroscopic systems. It is demonstrated that machine‐learning interatomic potentials (MLIPs) fitted to ab initio datasets play a pivotal role in achieving this goal. To practically illustrate this novel possibility, the mechanical/failure response of graphene/borophene coplanar heterostructures is examined. It is shown that MLIPs conveniently outperform popular CMD models for graphene and borophene and they can evaluate the mechanical properties of pristine and heterostructure phases at room temperature. Based on the information provided by the MLIP‐based CMD, continuum models of heterostructures using the finite element method can be constructed. The study highlights that MLIPs were the missing block for conducting first‐principles multiscale modeling, and their employment empowers a straightforward route to bridge ab initio level accuracy and flexibility to explore the mechanical/failure response of nanostructures at continuum scale.
Preparation of Ultrablack Composite Sheets with Excellent Mechanical and Chemical Stability from Sandpaper‐Based Template‐Imprinting
Authors: Chen Hai Tao , Li Chao Qun , Zhan Hang , Mo Run Wei , Zhang Yu , Wang Jian Nong
Published: July 2021

Ultrablack materials have applications in wide areas such as visible stealth, solar cells, and sea water evaporation. However, their high production cost, low mechanical property, and poor chemical stability have restricted their wide applications. Herein, a low‐cost method is reported for preparing large‐area ultrablack composite sheets with excellent mechanical and chemical stability. This is achieved by mixing a light absorber and transparent resin, and then copying and molding microconvex structures of sandpaper. The result shows that the absorption rate of the prepared composite sheet can reach more than 99% in the visible light range. More importantly, its performance remains almost unchanged after many cycles of mechanical stretching and long‐term chemical soaking. This excellent ultrablack performance is mainly attributed to the light‐trap effect of the subwavelength convex structure with the light absorber embedded in the resilient resin. Such composite sheets open a new pathway to developing high‐performance ultrablack materials with practical applications.
1,3‐Difunctionalization of Imino‐Carbenes via Rhodium‐Catalyzed Reactions of Triazoles with Acyl Selenides
Authors: Li Fang , Pei Chao , Quaranta Calogero , Koenigs Rene M.
Published: July 2021

Herein, we report on the rhodium‐catalyzed reaction of triazoles with acyl selenides. Under thermal reaction conditions and in the presence of a rhodium catalyst, a rapid 1,3‐difunctionalization reaction occurs to provide valuable α‐seleno enamides with high stereoselectivity and broad functional group tolerance, which was demonstrated in 35 examples with up to 95% yield. Computational calculations suggest a reaction pathway that gives a direct access to the 1,3‐difunctionalization without intermittent formation of ylide intermediates.

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MRI‐Active Metal‐Organic Frameworks: Concepts for the Translation from Lab to Clinic
Authors: Peller Michael , Lanza Arianna , Wuttke Stefan
Published: July 2021

Metal‐organic frameworks (MOFs) are an emerging class of synthetic materials obtained by combining organic and inorganic chemistry. MOFs show peculiar properties such as well‐defined crystalline structures, systematic structural variation, high porosity and the possibility to chemically functionalize the pores. These properties are especially promising for designing MOF nanoparticles (NPs) with special functions. The desired functions can be introduced and modified with a chemical approach, by the choice of the inorganic and organic building blocks. All these features and the highest surface area of any porous material make MOF NPs ideal for the use as nanocarrier in biomedicine. So far, a wide variety of biomedical applications of MOF NPs have been already envisioned being supported by promising first in vitro and in vivo results. The ongoing development of MOF NPs is at the edge of basic science to biomedical applications. A major focus of biomedical research is already in cancer therapy using MOF NPs as theranostic nanocarrier. In this article, NP designs and MRI‐labelling concepts are pointed out and discussed in the perspective of facilitating their translation to clinical use. Clinical application is envisioned with a major focus on theranostic MOF NPs and MRI as the most promising imaging method.
TLR7/8 Agonist and SHP2 Inhibitor Loaded Nanoparticle Enhances Macrophage Immunotherapy Efficacy
Authors: Malik Vaishali , Ramesh Anujan , Kulkarni Ashish A.
Published: July 2021

Tumor‐associated macrophages (TAMs) are among the most abundant immune cells in the solid tumor microenvironment, making them an attractive target for cancer immunotherapy. However, there are two important challenges. First, tumors repolarize the TAMs predominantly to M2 tumor‐aiding phenotype by secreting various immunosuppressive cytokines. Second, CD47 on cancer cells interacts with signal‐regulating protein a (SIRPa) expressed on macrophages. This crosstalk provides a downregulatory signal in the form of activation of SHP1/2 that inhibits cancer cell phagocytosis. These challenges can be overcome by engineering a nanoparticle that can deliver a rationale combination of immunomodulatory agents to the TAMs that can repolarize the M2 macrophages to M1 phenotype efficiently and concurrently block CD47‐SIRPa interactions by inhibiting SHP2 signaling. A lipid nanoparticle (LNP) system loaded with amphiphilic R848‐cholesterol (TLR7/8 agonist) and SHP099 (SHP2 inhibitor) in a predefined ratio has been designed. In vitro studies show that the LNPs system repolarized to M2 macrophages to M1 phenotype and expressed co‐stimulatory molecules while enhancing phagocytic potential. In vivo efficacy studies in 4T1 tumor‐bearing mice show that LNPs exhibit superior anti‐tumor efficacy than other treatments. Thus, the lipid nanoparticle‐mediated co‐delivery of a rational combination of TLR7/8 agonist and SHP2 inhibitor in the TAMs can enhance macrophage immunotherapy.
Harnessing CURATE.AI for N‐of‐1 Optimization Analysis of Combination Therapy in Hypertension Patients: A Retrospective Case Series
Authors: Truong Anh T. L. , Tan Lester W. J. , Chew Kimberly A. , Villaraza Steven , Siongco Paula , Blasiak Agata , Chen Christopher , Ho Dean
Published: July 2021

Hypertension is a global public health challenge that imposes a significant burden on patients and healthcare systems. Conventional treatment involves dose escalation of an antihypertensive drug, and if the desired response is not achieved, patients are prescribed another drug, often in combination with other therapies. Importantly, drug synergy is dose‐, time‐ and patient‐dependent. Coupled with the challenges of intra‐ and inter‐individual variability, standard care can lead to sub‐optimal outcomes, additional visits, and adherence issues. Furthermore, these factors can cause the additional complication of patients being misperceived as refractory to regimens that are sub‐optimally administered. A scalable strategy that can longitudinally optimize patient response would be a powerful advance for chronic disease management. This four‐patient case series reports the application of CURATE.AI as a mechanism‐independent and disease‐agnostic platform for a retrospective N‐of‐1 (personalized) dose optimization using each patient's own data, including drug doses and corresponding changes in blood pressures. This approach may enable the rapid prediction of treatment response and the identification of optimal doses that may yield improved outcomes. CURATE.AI can be implemented in clinical workflows without creating additional burden of extensive data collection. The findings from this study support the prospective validation of CURATE.AI to optimize hypertension management.
Self‐Assembled Peptide Amphiphile Nanofibers for Controlled Therapeutic Delivery to the Atherosclerotic Niche
Authors: Peters Erica B. , Karver Mark R. , Sun Kui , Gillis David C. , Biswas Suvendu , Clemons Tristan D. , He Wenhan , Tsihlis Nick D. , Stupp Samuel I. , Kibbe Melina R.
Published: July 2021

Atherosclerotic plaque remains the leading contributor to cardiovascular disease and requires invasive surgical procedures for its removal. Nanomedicine offers a minimally invasive approach to alleviate plaque burden by targeted therapeutic delivery. However, nanocarriers are limited without the ability to sense and respond to the diseased microenvironment. In this study, targeted self‐assembled peptide amphiphile (PA) nanofibers are developed that cleave in response to biochemical cues expressed in atherosclerotic lesions—reactive oxygen species (ROS) and intracellular glutathione—to deliver a liver X receptor agonist (LXR) to enhance macrophage cholesterol efflux. The PAs release LXR in response to physiological levels of ROS and reducing agents and can be co‐assembled with plaque‐targeting PAs to form nanofibers. The resulting LXR PA nanofibers promoted cholesterol efflux from macrophages in vitro as well as LXR alone and with lower cytotoxicity. Further, the ApoA1‐LXR PA nanofibers target plaque within an atherosclerotic mouse model in vivo and activate ATP‐binding cassette A1 (ABCA1) expression as well as LXR alone with reduced liver toxicity. Taken together, these results demonstrate the potential of self‐assembled PA nanofibers for controlled therapeutic delivery to the atherosclerotic niche.
Fiber‐Shaped Electronic Devices
Authors: Fakharuddin Azhar , Li Haizeng , Di Giacomo Francesco , Zhang Tianyi , Gasparini Nicola , Elezzabi Abdulhakem Y. , Mohanty Ankita , Ramadoss Ananthakumar , Ling JinKiong , Soultati Anastasia , Tountas Marinos , Schmidt‐Mende Lukas , Argitis Panagiotis , Jose Rajan , Nazeeruddin Mohammad Khaja , Mohd Yusoff Abd Rashid Bin , Vasilopoulou Maria
Published: July 2021

Textile electronics embedded in clothing represent an exciting new frontier for modern healthcare and communication systems. Fundamental to the development of these textile electronics is the development of the fibers forming the cloths into electronic devices. An electronic fiber must undergo diverse scrutiny for its selection for a multifunctional textile, viz., from the material selection to the device architecture, from the wearability to mechanical stresses, and from the environmental compatibility to the end‐use management. Herein, the performance requirements of fiber‐shaped electronics are reviewed considering the characteristics of single electronic fibers and their assemblies in smart clothing. Broadly, this article includes i) processing strategies of electronic fibers with required properties from precursor to material, ii) the state‐of‐art of current fiber‐shaped electronics emphasizing light‐emitting devices, solar cells, sensors, nanogenerators, supercapacitors storage, and chromatic devices, iii) mechanisms involved in the operation of the above devices, iv) limitations of the current materials and device manufacturing techniques to achieve the target performance, and v) the knowledge gap that must be minimized prior to their deployment. Lessons learned from this review with regard to the challenges and prospects for developing fiber‐shaped electronic components are presented as directions for future research on wearable electronics.
Evaluating agronomic factors for maize production in a semi‐arid Loess Plateau
Authors: Liang Gaimei , Chi Baoliang , Li Nana , Chen Wenliang , Qin Wei , Wu Xueping , Huang Xuefang
Published: July 2021

Crop production is often affected by multiple agronomic factors. However, little has been reported on the synergistic effects of multiple factors on crop production. Here, we reported the effects of five factors (i.e., variety, planting density, nitrogen application, supplemental irrigation, and plastic mulching) on crop yields, using data from a 5‐yr experiment at Dongyang, Shanxi province of China. An incomplete factorial design with these factors comprised 12 treatments, including two controls: optimized technology (OT) and conventional technology (CT), comprising all five factors applied at the added or subtracted level, respectively. The result showed that, on 5‐yr average, OT significantly increased maize yield by 3.5 Mg ha–1 (44.3% more) as compared to CT (7.9 Mg ha–1), showing a huge potential for increasing yields. Among the five factors, plastic mulching contributed the most in yield increase (11.5%), and high density, improved variety, and irrigation contributed 9.9, 6.9, and 5.1% increases in yield, respectively. There were no significant differences in yield between two N input levels (i.e., 225 and 300 kg N ha–1), suggesting the N input of 225 kg N ha–1 was sufficient to realize a yield level of 8–11 Mg ha–1 in the studied area. In conclusion, reducing the yield gap can only be achieved by optimizing multiple factors simultaneously because the effects of single measure are relatively small and inconsistent among years. The results of our study will help develop adaptive management practices for increasing crop yield stability in other semi‐arid regions.
Microwave‐Assisted Synthesis of d/l‐Agrimonolide
Authors: Cui Yu‐Ang , Zhang Guang‐Yu , Li Yun‐Zhi , Li Wei , Tanabe Genzoh , Osamu Muraoka , Xie Wei‐Jia
Published: July 2021

In this study, we reported an improved approach for the synthesis of d/l Agrimonolide from 4‐Chlororesorcinol. It was found that a microwave assisted intramolecular esterification is an effective way to construct the 3,4‐dihydroisocoumarin core structure. The target d/l Agrimonolide is obtained in 7 steps with the overall yields of 20.7%.
External Catalyst‐Free Oxidation of Benzyl Halides to Benzoic Acids Using NaOH/TBHP in Water
Authors: Saini Parul , Krishnan Anandhu , Yadav Deepak , Hazra Susanta , Elias Anil J.
Published: July 2021

An efficient and metal‐free methodology for the oxidation of benzyl halides to benzoic acids using an inexpensive and green oxidant (TBHP) in aqueous basic medium has been developed. This protocol offers an excellent way to avoid adding catalysts and involves the use of an in‐situ generated halide ion as catalyst. It is also the first report on the oxidation of benzyl iodides to benzoic acids. A series of carboxylic acids were prepared from benzyl halides in high yields under mild reaction conditions by this method which does not require chromatographic purification. Gram scale reactions for the synthesis of the carboxylic acids in good yields have been successfully carried out using benzyl chloride, bromide and iodide. As an industrial application, the synthesis of a key monomer used for the synthesis of polyethylene terephthalate (PET), i. e., terephthalic acid (PTA), has also been accomplished in good yields.
Is craniofacial morphology and body composition related by common genes: Comparative analysis of two ethnically diverse populations
Authors: Ghosh Sudipta , Kasher Melody , Malkina Ida , Livshits Gregory
Published: July 2021

Objectives

The overarching hypothesis of the present paper is that ethnically and/or genetically diverse human populations may exhibit similarity in correlations between various aspects of human phenotypes due to the morphological integration process during the ontogenetic stages. To test this we investigated whether an association between craniofacial (CF) features and body composition (BC) variations is present in humans and the extent to which such possible associations are comparable in different populations. Furthermore, the paper examines the contribution of common genetic (additive) and shared familial environmental factors in assessing the correlation between CF and BC characteristics in humans.

Materials and Methods

Two pedigree‐based samples were collected from two distinct populations, including India (Santhal) and Europe (Chuvash). Canonical correlation analysis was used to compare the association between CF and BC characteristics in the two studied samples. The contribution of genetic and familial environmental factors on the correlation between CF and BC features was analyzed through variance decomposition analysis by implementing the Mendelian Analysis package (MAN).

Results

Our study suggests that CF morphology is significantly (p < 0.001) associated with BC variation in both samples. CF characteristics and BC phenotypes revealed a consistent trend in both samples where condensed and broad CF morphology was significantly associated with increased fat accumulation, with slight variations between the Santhal and Chuvash samples. Despite the variations observed between the samples, the heritability estimates were impressively equivalent for traits like total facial height (55.6%Santhalvs.56.1%Chuvash) and nasal index (42.8%Santhalvs. 43.3%Chuvash).

Discussion

The genetic contribution of CF morphology appeared to be extensive and the contribution of common genetic and shared family environmental correlations between CF and BC measures were suggestively substantial. Accordingly, these correlations were consistently observed across ethnically diverse populations, despite drastic morphological differences between the samples under comparison.
Recruitment of a multi‐site randomized controlled trial of aerobic exercise for older adults with amnestic mild cognitive impairment: The EXERT trial
Authors: Shadyab Aladdin H. , LaCroix Andrea Z. , Feldman Howard H. , van Dyck Christopher H. , Okonkwo Ozioma C. , Tam Steven P. , Fairchild J. Kaci , Welsh‐Bohmer Kathleen A. , Matthews Genevieve , Bennett Daniel , Shadyab Alexandre A. , Schafer Kimberly A. , Morrison Rosemary H. , Kipperman Sean A. , Mason Jennifer , Tan Donna , Thomas Ronald G. , Cotman Carl W. , Baker Laura D. ,   for the ADCS EXERT Study Group
Published: July 2021

Introduction

Effective strategies to recruit older adults with mild cognitive impairment (MCI) into nonpharmacological intervention trials are lacking.

Methods

Recruitment for EXERT, a multisite randomized controlled 18‐month trial examining the effects of aerobic exercise on cognitive trajectory in adults with amnestic MCI, involved a diverse portfolio of strategies to enroll 296 participants.

Results

Recruitment occurred September 2016 through March 2020 and was initially slow. After mass mailings of 490,323 age‐ and geo‐targeted infographic postcards and brochures, recruitment rates increased substantially, peaking at 16 randomizations/month in early 2020. Mass mailings accounted for 52% of randomized participants, whereas 25% were recruited from memory clinic rosters, electronic health records, and national and local registries. Other sources included news broadcasts, public service announcements (PSA), local advertising, and community presentations.

Discussion

Age‐ and geo‐targeted mass mailing of infographic materials was the most effective approach in recruiting older adults with amnestic MCI into an 18‐month exercise trial.
Specialty chemicals production case study: Economic analysis of modular chemical process intensification versus conventional stick‐built approaches
Authors: O'Connor James T. , Kowall Cliff P. , Haapala Karl R. , Agrawal Naman V. , Paul Brian K.
Published: July 2021

The beneficial synergies of chemical process intensification and plant modularization present a unique step‐wise advancement opportunity for many chemical manufacturers, but economic case studies are needed to raise awareness of such opportunities. The primary objective of this case study is to better understand the business case economics of a specialty chemical plant using modular chemical process intensification (MCPI), by comparing it with that of a conventional stick‐built (CSB) plant that produces the same product at the same production capacity. When comparing MCPI against CSB approaches for a plant project strategy decision, analysts should thoroughly understand and model the differences and similarities in scope bases. The MCPI approach for this case study benefitted from dramatic reductions in capital expenditures (CAPEX). A sizeable reduction in plant spatial volume likely explains some of these reductions. Sizeable operational expenditure (OPEX) reductions with the MCPI plant appear to be associated with the reduced operator staffing required from converting a labor‐intensive batch process into an automated, continuous flow process. Traditional project investment economic measures strongly favored the MCPI case for the design, construction, and operation of the specialty chemical plant. The net present value for the MCPI case was nearly twice that for the CSB case over a ten‐year period, and the payback period for the CSB case was nearly five times longer than that of the MCPI case. The opinion‐based perspective of the study participant identified significant contributors to superior MCPI economic performance for this case study. With the two conditions of low MCPI CAPEX and high product profit margin, economic analysis indicates that incorporation of a backup MCPI train, for operational redundancy when downtime occurs, is a very beneficial strategy.
Advection‐Enhanced Kinetics in Microtiter Plates for Improved Surface Assay Quantitation and Multiplexing Capabilities
Authors: Pereiro Iago , Fomitcheva Khartchenko Anna , Lovchik Robert D. , Kaigala Govind V.
Published: July 2021

Surface assays such as ELISA are pervasive in clinics and research and predominantly standardized in microtiter plates (MTP). MTPs provide many advantages but are often detrimental to surface assay efficiency due to inherent mass transport limitations. Microscale flows can overcome these and largely improve assay kinetics. However, the disruptive nature of microfluidics with existing labware and protocols has narrowed its transformative potential. We present WellProbe, a novel microfluidic concept compatible with MTPs. With it, we show that immunoassays become more sensitive at low concentrations (up to 9× signal improvement in 12× less time), richer in information with 3–4 different kinetic conditions, and can be used to estimate kinetic parameters, minimize washing steps and non‐specific binding, and identify compromised results. We further multiplex single‐well assays combining WellProbe's kinetic regions with tailored microarrays. Finally, we demonstrate our system in a context of immunoglobulin subclass evaluation, increasingly regarded as clinically relevant.
Mycosynthesis of silver nanoparticles using Aspergillus caespitosus: Characterization, antimicrobial activities, cytotoxicity, and their performance as an antimicrobial agent for textile materials
Authors: El‐Bendary Magda A. , Moharam Maysa E. , Hamed Shimaa R. , Abo El‐Ola Samiha M. , Khalil Safaa K. H. , Mounier Marwa M. , Roshdy Amira M. , Allam Mousa A.
Published: July 2021

Mycosynthesis of stable silver nanoparticles (AgNPs) using Aspergillus caespitosus exo‐ and endo‐filtrates were obtained. Both exo‐ and endo‐AgNPs showed an absorbance peak at 410 nm, spherical, hexagonal, and anisotropic crystalline nanoparticles with 22–57 nm in size. FTIR analysis of mycosynthesized AgNPs showed presence of amide and carbonyl functional groups, which depicts the presence of peptides that involved in the synthesis and stability of AgNPs. Nitrate reductase activity was found to be 0.71 and 0.36 μM/min/ml for exo‐ and endo‐filtrates, respectively. The optimum conditions for the synthesis of exo‐ and endo‐AgNPs were at 6:4 and 8:2 filtrate:double distilled water dilution, respectively. Also, both AgNPs syntheses were the maximum at using one mM AgNO3 in aqueous solution, 24‐h incubation at 30°C under static and illuminating conditions. Aspergillus caespitosus‐synthesized AgNPs showed antimicrobial activities against Gram‐positive and Gram‐negative bacteria and Candida albicans. They showed non‐cytotoxic effect with exception of endo‐AgNPs on MCF‐7 breast carcinoma cells. Different textile samples treated with these nanoparticles exhibited antimicrobial activities against the tested pathogenic microorganisms. Finally, Aspergillus caespitosus is a promising nano‐factory for simple, green, and cost‐effective biosynthesis of AgNPs using extracellular and intracellular filtrates.
Evolutionary treasures hidden in the West Indies: Comparative osteology and visceral morphology reveals intricate miniaturization in the insular generaMitophisHedges, Adalsteinsson, & Branch, 2009 andTetracheilostomaJan, 1861 (Leptotyphlopidae: Epictinae: Tetracheilostomina)
Authors: Martins Angele , Koch Claudia , Joshi Mitali , Pinto Roberta , Machado Alessandra , Lopes Ricardo , Passos Paulo
Published: July 2021

The generaMitophisandTetracheilostomacomprise two extant lineages of small‐sized threadsnakes that exclusively inhabit several islands of the West Indies. Even though leptotyphlopids are known for their extremely reduced size, miniaturization has only been hypothesized to reflect insular dwarfism for the genusTetracheilostoma. Herein, we aim to describe the comparative osteology and visceral morphology of both genera, investigating and discussing their several internal morphological simplifications and novelties. Our results indicate that these taxa exhibit several autapomorphies mostly concentrated in the dorsoposterior skull elements and maxillae, as well as in their axial skeleton and viscera. These novelties and simplifications are most likely a result of extreme miniaturization driven by the evolutionary constraints or ecological opportunities possibly imposed by the “island rule.” BothMitophisandTetracheilostomadistinguish from all other Epictinae in lacking a dentigerous process in the maxillae, by having the prootic fused to the otooccipital, and by the lack (except in comparison to a fewEpictia) of a cervical vertebrae intercentrum I. Additionally,Mitophiscan be distinguished from other Epictinae by the participation of the unpaired supraoccipital in the dorsal border of the foramen magnum, by the absence of the pleurapophyses in the caudal vertebrae, by a higher number of liver segments, and by the extreme degeneration of the pelvic rudiments.Tetracheilostomadiffers from other Epictinae by lacking a distinct supraoccipital, which is fused to the parietal. Thus, our results reinforce that morphological characters are extremely valuable for leptotyphlopid systematics given their extremely conserved external morphology.
Hexanuclear Co4Dy2, Zn4Dy2, and Co4Y2 Complexes with Defect Tetracubane Cores: Syntheses, Structures, and Magnetic Properties
Authors: Li Dawei , Li Yafei , Tello Yepes David Felipe , Zhang Xiamei , Li Yahong , Yao Jin‐lei
Published: July 2021

A hexanuclear heterometallic cluster of composition [Dy2Co4(L)4(NO3)2(OH)4(C2H5OH)2] ⋅ 2 C2H5OH (1) was synthesized by employing a Schiff base 2‐(((2‐hydroxy‐3‐methoxybenzyl) imino)methyl)‐4‐methoxyphenol (H2L) as ligand and utilizing Dy(NO3)3 ⋅ 6H2O and Co(NO3)2 ⋅ 6H2O as metal ion sources. X‐ray single‐crystal diffraction analysis indicated that complex 1 contains a defect tetracubane core and possesses central symmetric structure, with two DyIII ions being in the central body position of the molecule and four CoII ions being arranged at the outer sites. Magnetic studies reveal that complex 1 behaves as single‐molecule magnet (SMM) with energy barrier of 27.50 K. To investigate the individual contribution of DyIII and CoII ions to the SMM behavior, another two complexes of formulae [Dy2Zn4(L)4(NO3)2(OH)4] ⋅ 4CH3OH (2) and [Y2Co4(L)4(NO3)2(OH)4(C2H5OH)2] ⋅ 2 C2H5OH (3) were prepared. Complexes 1 and 3 are isomorphous. The coordination geometries of DyIII ions in 1 and 2 are different. The DyIII ions are eight‐coordinated in 2 and nine‐coordinated in 1. Complex 2 exhibits SMM behavior with energy barrier of 69.67 K, but complex 3 does not display SMM property. These results reveal that the SMM behaviors of 1 and 2 are mainly originated from DyIII ions. It might be the higher symmetry of DyIII ions in 2 that results in the higher energy barrier.
Stochastic comparison on load‐sharing systems with one statistically dependent redundancy
Authors: Li Chen , Fang Rui , Li Xiaohu
Published: July 2021

In this article, we study a load‐sharing redundancy system in the presence of statistical dependence between base and redundancy component lifetimes when they are under partial workload. We derive the system reliability function in terms of reliability functions and the copula function of the base and redundancy component lifetimes. Further, in the setting of some aging properties, the base component and absolute continuous copula, we develop the hazard rate order, the reversed hazard rate order, and the likelihood ratio order between the system lifetime and the base component lifetimes. Two typical scenarios with independence between the base and redundancy component lifetimes are discussed in particular. Several numerical examples are presented to illustrate the theoretical findings as well.
Comparison of UV‐ and Raman‐based monitoring of the Protein A load phase and evaluation of data fusion by PLS models and CNNs
Authors: Rolinger Laura , Rüdt Matthias , Hubbuch Jürgen
Published: July 2021

A promising application of Process Analytical Technology to the downstream process of monoclonal antibodies (mAbs) is the monitoring of the Protein A load phase as its control promises economic benefits. Different spectroscopic techniques have been evaluated in literature with regard to the ability to quantify the mAb concentration in the column effluent. Raman and Ultraviolet (UV) spectroscopy are among the most promising techniques. In this study, both were investigated in an in‐line setup and directly compared. The data of each sensor were analyzed independently with Partial‐Least‐Squares (PLS) models and Convolutional Neural Networks (CNNs) for regression. Furthermore, data fusion strategies were investigated by combining both sensors in hierarchical PLS models or in CNNs. Among the tested options, UV spectroscopy alone allowed for the most precise and accurate prediction of the mAb concentration. A Root Mean Square Error of Prediction (RMSEP) of 0.013 g L−1 was reached with the UV‐based PLS model. The Raman‐based PLS model reached an RMSEP of 0.232 g L−1. The different data fusion techniques did not improve the prediction accuracy above the prediction accuracy of the UV‐based PLS model. Data fusion by PLS models seems meritless when combining a very accurate sensor with a less accurate signal. Furthermore, the application of CNNs for UV and Raman spectra did not yield significant improvements in the prediction quality. For the presented application, linear regression techniques seem to be better suited compared with advanced nonlinear regression techniques, like, CNNs. In summary, the results support the application of UV spectroscopy and PLS modeling for future research and development activities aiming to implement spectroscopic real‐time monitoring of the Protein A load phase.
The protective effects of Ramelteon against 6‐OHDA‐induced cellular senescence in human SH‐SY5Y neuronal cells
Authors: Liu Dan , Gu Xinyi , Han Fang , Cai Ming , Liu Weijie , Han Li , Ma Qiang
Published: July 2021

Background and purpose

Parkinson's disease (PD) is a severe neurodegenerative disease with high morbidity in the elderly population. 6‐OHDA‐induced cell senescence is reported to be involved in the pathogenesis of PD. Ramelteon is an oral hypnotic agent that specifically targets the receptors of the suprachiasmatic nucleus in the human hypothalamus. Here, an investigation is made to see whether Ramelteon possesses a beneficial effect against 6‐OHDA‐induced cellular senescence in human SH‐SY5Y neuronal cells.

Methods

The release of LDH was detected to assess cytotoxicity and flow cytometry was conducted to evaluate the cell cycle. The telomerase activity and the SA‐β‐Gal assay were performed to determine the state of cell senescence. Oxidative stress was evaluated by detecting the release of H2O2. The expressions of p21, p53, and Nrf2 were measured using the qRT‐PCR and Western blotting assay. siRNA technology was used to knock down the expression level of Nrf2 in SH‐SY5Y neuronal cells.

Results

First, it was found that Ramelteon mitigated cell cycle arrest in the G0/G1 phase in 6‐OHDA‐challenged SH‐SY5Y neuronal cells. Second, treatment with Ramelteon alleviated cellular senescence in 6‐OHDA‐treated SH‐SY5Y neuronal cells by increasing telomerase activity and reducing the activity of SA‐β‐gal. It was also found that Ramelteon reduced the expressions of p21 and p53. Notably, Ramelteon attenuated 6‐OHDA‐induced oxidative stress by increasing the expression of Nrf2. Silencing of Nrf2 abolished the protective effects of Ramelteon against 6‐OHDA‐induced cellular senescence. Based on these findings, it was concluded that Ramelteon alleviated 6‐OHDA‐induced cellular senescence by increasing the expression of Nrf2 in human SH‐SY5Y neuronal cells.

Conclusion

Ramelteon protected against 6‐OHDA‐induced cellular senescence in human SH‐SY5Y neuronal cells through activating the Nrf2 signaling pathway.
Community resilience and anxiety among Chinese older adults during COVID‐19: The moderating role of trust in local government
Authors: Zhang Jinfeng , Wang Yan , Zhou Mingjie , Ke Jihong
Published: July 2021

The worldwide spread of COVID‐19 has resulted in an enormous threat to public health, causing global panic, especially older adults suffering severe anxiety due to their vulnerability. With a questionnaire survey on 213 Chinese older adults in April 2020, we examined the role of community resilience in protecting older adults from anxiety during the COVID‐19 pandemic, and simultaneously considered the moderating role of trust in local government. The results indicated that community resilience was negatively associated with older adults' anxiety, and this association was weakened for older adults with low trust in local government. This study has implications for intervention designs that combine resilient factors related to communities and local governments to relieve older adults' anxiety during the pandemic. Please refer to the Supplementary Material section to find this article's Community and Social Impact Statement.
Chemically Sulfated Polysaccharides from Agaricus blazei Murill: Synthesis, Characterization and Anti‐HIV Activity
Authors: Zhao Yanping , Tian Nana , Wang Hongjun , Yan Hong
Published: July 2021

AIDS, caused by HIV‐1, is one of the most dangerous infectious diseases in the world. Therefore, it is necessary to develop new drugs with more potent bioactivities, less toxicity and higher tolerability for controlling the viral load, particularly by using the raw materials that are widely available. Agaricus blazei Murill (AbM), known in China as jisongrong, is of great importance as a food source and as a health‐promoting supplement for immunomodulation. The polysaccharides of AbM exhibit various biological activities, such as regulating cellular immunity and providing anti‐oxidative, anti‐infective, and anti‐inflammatory effects. At present, to our knowledge, no report has explored the chemically sulfated and anti‐HIV‐1 activity of AbM polysaccharides. Herein, the sulfated AbM polysaccharides with different sulfur contents were prepared by the chlorosulfonic acid‐pyridine method. The characteristics of sulfated derivatives were established by the determination of the sulfur content, the relative molecular weight, and the Fourier‐transform infrared spectroscopy. The anti‐HIV activities of the sulfated AbM polysaccharides were evaluated by CCK‐8 and the single‐cycle pseudovirus infection (TZM‐bl) assay. The sulfated AbM polysaccharides had strong antiviral properties, and the half‐maximal inhibitory concentrations approached that of the positive control, azidothymidine. Sulfated modification of AbM polysaccharides can increase their anti‐HIV pharmacological activity, which makes them promising alternative candidates as bioactive macromolecules for biomedical applications in HIV/AIDS.
Ectopic pregnancy of the fundal myometrium in a patient with tuberous sclerosis
Authors: Sharma Neha , Agustin Michele , Polonsky Ariel , Bruck Lance
Published: July 2021

A myometrial ectopic pregnancy is a rare and potentially fatal diagnosis. This diagnosis should be considered when presented with large increases in serum beta‐hCG with no evidence of an intrauterine pregnancy, particularly with altered myometrium.
Successful treatment of acute promyelocytic leukemia in a patient under hemodialysis with arsenic trioxide
Authors: Hashimoto Akiko , Tanaka Yasuhiro , Ishikawa Takayuki , Shinzato Isaku
Published: July 2021

A man with chronic kidney disease (CKD) under hemodialysis was diagnosed with acute promyelocytic leukemia (APL). He received arsenic trioxide as a single agent and achieved complete molecular remission without severe adverse events. Arsenic trioxide (ATO) can be used safely and effectively for APL with CKD.
Diagnostic Fleischner’s sign in atrial septal defect
Authors: Chen Bailang , Lan Zhibin
Published: July 2021

Fleischner sign is very rare in patients with ASD unless the defect remains undiagnosed till the elderly. For adulthood people with Fleischner sign, we should think about the possibility of congenital heart disease.
Response to gefitinib/crizotinib combination in a pulmonary sarcomatoid carcinoma patient harboring concurrent EGFR mutation and MET amplification
Authors: Wang Xiaomeng , Cao Jie , Du Weijiao , Zhang Weihong , Cao Shui
Published: July 2021

Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non‐small cell lung cancer (NSCLC) with an extremely poor prognosis making it a therapeutic challenge. However, the development of genetic variation molecular diagnosis and targeted agents has brought the treatment of such malignancies to the precision era. Co‐existing mutations of EGFR and MET have been reported in NSCLC, but rarely found in PSC. We herein present a rare case of a 74‐year‐old female patient diagnosed with PSC, carrying an activating mutation in exon 21 L858R of EGFR and a concurrent MET amplification prior to treatment. Combined application of gefitinib and crizotinib, inhibitors targeting EGFR and MET, respectively, was prescribed. The patient experienced a partial response and was stable for 9.7 months off therapy. The observation stresses the importance of genetic testing and paves the way for combined targeted strategies in PSC.
Severe peripartum cardiomyopathy complicated by COVID‐19 infection and small intestinal obstruction
Authors: Abdulraheem Ekhlas , Shaikhoun Mazin , Kung David
Published: July 2021

COVID‐19 infection can be a possible trigger for peripartum cardiomyopathy. Multidisciplinary teamwork was crucial for the favorable outcome in our patient. Small bowel strangulation is a rare complication post‐cesarean section.
Mild‐to‐severe poisoning due to Coniummaculatum as toxic herb: A case series
Authors: Boskabadi Javad , Askari Zahra , Zakariaei Zakaria , Fakhar Mahdi , Tabaripour Rabeeh
Published: July 2021

Conium maculatum toxicity may occur by mistakenly or intentionally eating this plant. Due to muscarinic or nicotinic symptoms associated with this plant toxicity, supportive care and treatment with atropine are urgently important.
Pregnancy complicated by HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP): a case report
Authors: Mori Hiroshi , Shibata Eiji , Kuwazuru Tomoichiro , Uchimura Takayuki , Kondo Emi , Iwanaka Yukio , Yoshino Kiyoshi
Published: July 2021

Pregnancy was not associated with deterioration of HAM nor was HAM associated with adverse pregnancy outcome in this case. These findings suggest that women with HAM/TSP, even those who use a wheelchair, should not be discouraged from pregnancy.
3‐Hydroxyisobutyryl‐CoA hydrolase deficiency in an infant with developmental delay and high anion gap acidosis
Authors: Saneifard Hedyeh , Mosallanejad Asieh , Fallahzadeh Aida , Sheikhy Ali
Published: July 2021

Due to the rarity of this disorder, paying attention to diagnostic clues is important. Low valine formula seems to be effective in improvement of patient's symptoms. Prevention of consanguineous marriage is the best way to prevent this disease.