bluuebunny/crossref_metadata_2025 huggingface dataset:
Single‐Step Biofabrication of In Situ Spheroid‐Forming Compartmentalized Hydrogel for Clinical‐Sized Cartilage Tissue Formation
Authors: van Loo Bas , Schot Maik , Gurian Melvin , Kamperman Tom , Leijten Jeroen
Published: October 2023

3D cellular spheroids offer more biomimetic microenvironments than conventional 2D cell culture technologies, which has proven value for many tissue engineering applications. Despite beneficiary effects of 3D cell culture, clinical translation of spheroid tissue engineering is challenged by limited scalability of current spheroid formation methods. Although recent adoption of droplet microfluidics can provide a continuous production process, use of oils and surfactants, generally low throughput, and requirement of additional biofabrication steps hinder clinical translation of spheroid culture. Here, the use of clean (e.g., oil‐free and surfactant‐free), ultra‐high throughput (e.g., 8.5 mL min−1, 10 000 spheroids s−1), single‐step, in‐air microfluidic biofabrication of spheroid forming compartmentalized hydrogels is reported. This novel technique can reliably produce 1D fibers, 2D planes, and 3D volumes compartmentalized hydrogel constructs, which each allows for distinct (an)isotropic orientation of hollow spheroid‐forming compartments. Spheroids produced within ink‐jet bioprinted compartmentalized hydrogels outperform 2D cell cultures in terms of chondrogenic behavior. Moreover, the cellular spheroids can be harvested from compartmentalized hydrogels and used to build shape‐stable centimeter‐sized biomaterial‐free living tissues in a bottom‐up manner. Consequently, it is anticipated that in‐air microfluidic production of spheroid‐forming compartmentalized hydrogels can advance production and use of cellular spheroids for various biomedical applications.
Multimodal Imaging‐Guided Photoimmunotherapy of Pancreatic Cancer by Organosilica Nanomedicine
Authors: Zhang Huifeng , Chen Kun , Guo Kai , Tao Jun , Song Lina , Ren Shuai , Zhao Yatong , Teng Zhaogang , Qiu Wenli , Wang Zhongqiu
Published: October 2023

Immune checkpoint blockade (ICB) treatments have contributed to substantial clinical progress. However, challenges persist, including inefficient drug delivery and penetration into deep tumor areas, inadequate response to ICB treatments, and potential risk of inflammation due to over‐activation of immune cells and uncontrolled release of cytokines following immunotherapy. In response, this study, for the first time, presents a multimodal imaging‐guided organosilica nanomedicine (DCCGP) for photoimmunotherapy of pancreatic cancer. The novel DCCGP nanoplatform integrates fluorescence, magnetic resonance, and real‐time infrared photothermal imaging, thereby enhancing diagnostic precision and treatment efficacy for pancreatic cancer. In addition, the incorporated copper sulfide nanoparticles (CuS NPs) lead to improved tumor penetration and provide external regulation of immunotherapy via photothermal stimulation. The synergistic immunotherapy effect is realized through the photothermal behavior of CuS NPs, inducing immunogenic cell death and relieving the immunosuppressive tumor microenvironment. Coupling photothermal stimulation with αPD‐L1‐induced ICB, the platform amplifies the clearance efficiency of tumor cells, achieving an optimized synergistic photoimmunotherapy effect. This study offers a promising strategy for the clinical application of ICB‐based combined immunotherapy and presents valuable insights for applications of organosilica in precise tumor immunotherapy and theranostics.
Engineering Clinically Relevant Probiotics with Switchable “Nano‐Promoter” and “Nano‐Effector” for Precision Tumor Therapy
Authors: Cao Fangfang , Jin Lulu , Zhang Chenyin , Gao Yong , Qian Zhefeng , Wen Hongyang , Yang Sisi , Ye Ziqiang , Hong Liangjie , Yang Huang , Tong Zongrui , Cheng Liang , Ding Yuan , Wang Weilin , Yu Guocan , Mao Zhengwei , Chen Xiaoyuan
Published: October 2023

Probiotics have the potential as biotherapeutic agents for cancer management in preclinical models and human trials by secreting antineoplastic or immunoregulatory agents in the tumor microenvironment (TME). However, current probiotics lack the ability to dynamically respond to unique TME characteristics, leading to limited therapeutic accuracy and efficacy. Although progress has been made in customizing controllable probiotics through synthetic biology, the engineering process is complex and the predictability of production is relatively low. To address this, here, for the first time, this work adopts pH‐dependent peroxidase‐like (POD‐like) artificial enzymes as both an inducible “nano‐promoter” and “nano‐effector” to engineer clinically relevant probiotics to achieve switchable control of probiotic therapy. The nanozyme initially serves as an inducible “nano‐promoter,” generating trace amounts of nonlethal reactive oxygen species (ROS) stress to upregulate acidic metabolites in probiotics. Once metabolites acidify the TME to a threshold, the nanozyme switches to a “nano‐effector,” producing a great deal of lethal ROS to fight cancer. This approach shows promise in subcutaneous, orthotopic, and colitis‐associated colorectal cancer tumors, offering a new methodology for modulating probiotic metabolism in a pathological environment.
Correlative Extinction and Single Fluorophore Bleaching Microscopy for Ligand Quantification on Gold Nanoparticles
Authors: Slesiona Nicole , Payne Lukas , Pope Iestyn , Borri Paola , Langbein Wolfgang , Watson Peter
Published: October 2023

Nanoparticles (NPs) are promising therapeutic delivery agents, with the number and manner of presentation of cell‐binding ligands on the NP affecting the eventual fate of the therapeutic. Whenever NPs are conjugated with biomolecules, a heterogeneous population of decorated NPs will be produced and these subpopulations of particle‐ligand structures need to be characterized for a reliable interpretation of NP‐based data. An optical microscopy method is reported to quantitatively evaluate the conjugation on a single‐particle basis in samples consisting of gold NPs (GNPs) decorated with holo‐transferrin fluorescently labeled with Alexa647 (Tf). Widefield fluorescence and extinction microscopy are employed on NP‐ligand constructs, alongside a correlative analysis that spatially co‐localizes diffraction‐limited sources of fluorescence with the optical extinction by individual GNPs. A photobleaching step analysis estimates the number of fluorophores contributing to the detected emission rate. The method quantifies the number of fluorescent biomolecules attached per GNP, the numbers of unconjugated GNPs and unbound Tf present within the mixed population, and the size and intraparticle clustering propensity of conjugated GNPs. A high variability is found in the number of Tf ligands per GNP within the GNP population, when analyzed at the single‐particle level, unraveling a non‐trivial statistical distribution not accessible in ensemble‐averaged approaches.
Nitrogen‐Doped Carbon Nanotubes with Large Interplanar Distances toward Fast Potassium Storage
Authors: Wang Yun , Keteklahijani Yalda Zamani , Wang Ruishuai , Liu Liang , Jiang Wenfeng , Guo Jia , Yang Dong , Sundararaj Uttandaraman , Arjmand Mohammad , Liu Jian
Published: October 2023

One of the main challenges potassium‐ion batteries (PIBs) face is the lack of structurally stable anodes with high reactivity and fast kinetics for reversible potassium insertion/extraction. Herein, nitrogen‐doped carbon nanotubes (N‐CNTs) are synthesized using a straightforward method assisted by a Co‐based catalyst. The as‐synthesized N‐CNTs possess interlayer distances up to 0.38 nm and nitrogen‐doping content of 2.2 at.%. Compared to the undoped CNTs (U‐CNTs), N‐CNTs exhibit a promising initial specific capacity of 568 mAh g−1 at 0.1 A g−1, as well as excellent long‐term cycling performance of 104, 82, and 76 mAh g−1 at a high current of 0.5, 1, and 2 A g−1 for 500 cycles. The cyclic voltammetry (CV) measurements reveal the potassium storage mechanism of N‐CNTs, which combines the major capacitive mechanisms and the secondary diffusion, and successfully avoids inconspicuous voltage plateau. The kinetic analysis of the galvanostatic intermittent titration technique and ex situ X‐ray photoelectron spectroscopy spectra show fast reaction kinetics and low side effects and degradation for the N‐CNTs anodes during the potassiation/de‐potassiation process. This study provides a straightforward method to synthesize heteroatom‐doped carbonaceous anode materials and achieves superior electrochemical properties with cost‐effectiveness and material sustainability.
Ions‐Silica Percolated Ionic Dielectric Elastomer Actuator for Soft Robots
Authors: Choi Hanbin , Kim Yongchan , Kim Seonho , Kim So Young , Kim Joo Sung , Yun Eseudeo , Kweon Hyukmin , Amoli Vipin , Choi U. Hyeok , Lee Hojin , Kim Do Hwan
Published: October 2023

Soft robotics systems are currently under development using ionic electroactive polymers (i‐EAP) as soft actuators for the human‐machine interface. However, this endeavor has been impeded by the dilemma of reconciling the competing demands of force and strain in i‐EAP actuators. Here, the authors present a novel design called “ions‐silica percolated ionic dielectric elastomer (i‐SPIDER)”, which exhibits ionic liquid‐confined silica microstructures that effectively resolve the chronic issue of conventional i‐EAP actuators. The i‐SPIDER actuator demonstrates remarkable electromechanical conversion capacity at low voltage, thanks to improved ion accumulation facilitated by interpreting electrode polarization at the electrolyte‐electrode interface. This approach concurrently enhances both strain (by approximately 1.52%) and force (by roughly 1.06 mN) even at low Young's modulus (merely 5.9 MPa). Additionally, by demonstrating arachnid‐inspired soft robots endowed with user‐desired tasks through control of various form factors, the development of soft robots using the i‐SPIDER that can concomitantly enhance strain and force holds promise as a compelling avenue for ushering in the next generation of miniaturized, low‐powered soft robotics.
Roles of Blend Morphology and Energy Level Alignment in Determining Open‐Circuit Voltage and Fill Factor of Ternary All‐Polymer Solar Cells
Authors: Liang Zhiyuan , Benten Hiroaki , Hagio Ren , Cho Yongyoon , Pandey Manish , Nakamura Masakazu
Published: October 2023

Tuning the open‐circuit voltage (VOC) and fill factor (FF) without sacrificing the short‐circuit current density is crucial for achieving performance advantages in ternary blend organic solar cells as an alternative to the binary ones. This study investigates ternary all‐polymer solar cells comprised of two polymer donors (D1 and D2) and one polymer acceptor (A), using two types of D2 polymers with different compatibilities with D1. As demonstrated by photoelectron yield spectroscopy, the ionization energy (IE) of the ternary blends continuously shifts between the IEs of D1:A and D2:A binary blends when D2 forms a single indistinguishable domain with D1. In contrast, the IE of the blends does not exhibit any noticeable change when D2 induces distinct phase separation with D1. Models describing the blend composition dependence of the VOC and FF are constructed by correlating the effects of the blend morphology and the shift in the energy level of the hole‐transporting state in the ternary blends. This study demonstrates that a pseudo‐binary blend morphology with a mixed D1 and D2 donor domain and an A acceptor domain is necessary to obtain a broad tunability of VOC and tolerance of FF to the blend composition in ternary all‐polymer solar cells.
Neither lysigenous nor just oil: Demystifying myrtaceous secretory cavities
Authors: Richit José F. , Díaz Shirley V. N. , Dick Luís F. P. , Mariath Jorge E. A.
Published: October 2023

Premise

Leaf subepidermal secretory cavities are a notable trait in Myrtaceae, but their formation is still controversial because of the lack of consensus on their ontogeny among authors. Knowledge about the compounds present in these cavities has grown over the last few years, demonstrating that terpenoid‐rich oils are not their unique content. These two points are the focus of this study on the ontogeny, structure, and contents of secretory cavities in neotropical Myrtaceae.

Methods

We used histochemical tests and Raman analysis to verify the basic chemical composition of the cavity contents of nine species. We studied the ontogeny of glands in one species, comparing aldehyde‐fixed tissues and fresh sections mounted in an inert medium.

Results

We observed schizogenous development and appearance of the secretory cavities and found that sample processing may induce cell breakdown, which can be misinterpreted as lysigeny. The content of these cavities contains putative terpenes, resins, carbonyl groups, and flavonoids.

Conclusions

Our findings support the hypothesis that the lysigenous appearance of the oil glands is a technical artifact. These tissue distortions must be considered when interpreting the development of this type of secretory structure. Moreover, the basic analyses of chemical constituents show for the first time that the glands of neotropical Myrtaceae are potential reservoirs of some compounds such as flavonoids previously reported as novelties for a few other myrtaceous species. Because some of them are non‐lipid compounds, the idea that the glands are just oil repositories is no longer applicable.
Erythropoietin downregulates red blood cell clearance, increasing transfusion efficacy in severely anemic recipients
Authors: Casimir Madeleine , Colard Martin , Dussiot Michael , Roussel Camille , Martinez Anaïs , Peyssonnaux Carole , Mayeux Patrick , Benghiat Samantha , Manceau Sandra , Francois Anne , Marin Nathalie , Pène Frédéric , Buffet Pierre A. , Hermine Olivier , Amireault Pascal
Published: October 2023

Red blood cells (RBC) transfusion is used to alleviate symptoms and prevent complications in anemic patients by restoring oxygen delivery to tissues. RBC transfusion efficacy, that can be measured by a rise in hemoglobin (Hb) concentration, is influenced by donor‐, product‐, and recipient‐related characteristics. In some studies, severe pre‐transfusion anemia is associated with a greater than expected Hb increment following transfusion but the biological mechanism underpinning this relationship remains poorly understood. We conducted a prospective study in critically ill patients and quantified Hb increment following one RBC transfusion. In a murine model, we investigated the possibility that, in conjunction with the host erythropoietic response, the persistence of transfused donor RBC is improved to maintain a highest RBC biomass. We confirmed a correlation between a greater Hb increment and a deeper pre‐transfusion anemia in a cohort of 17 patients. In the mouse model, Hb increment and post‐transfusion recovery were increased in anemic recipients. Post‐transfusion RBC recovery was improved in hypoxic mice or those receiving an erythropoiesis‐stimulating agent and decreased in those treated with erythropoietin (EPO)‐neutralizing antibodies, suggesting that EPO signaling is necessary to observe this effect. Irradiated recipients also showed decreased post‐transfusion RBC recovery. The EPO‐induced post‐transfusion RBC recovery improvement was abrogated in irradiated or in macrophage‐depleted recipients, but maintained in splenectomized recipients, suggesting a mechanism requiring erythroid progenitors and macrophages, but which is not spleen‐specific. Our study highlights a physiological role of EPO in downregulating post‐transfusion RBC clearance, contributing to maintain a vital RBC biomass to rapidly cope with hypoxemia.
Clinical utility of early rapid genome sequencing in the evaluation of patients with differences of sex development
Authors: Aekka Apoorva , Weisman Allison Goetsch , Papadakis Jaclyn , Yerkes Elizabeth , Baker Joshua , Keswani Mahima , Weinstein Joanna , Finlayson Courtney
Published: October 2023

Establishing an early and accurate genetic diagnosis among patients with differences of sex development (DSD) is crucial in guiding the complex medical and psychosocial care they require. Genetic testing routinely utilized in clinical practice for this population is predicated upon physical exam findings and biochemical and endocrine profiling. This approach, however, is inefficient and unstandardized. Many patients with DSD, particularly those with 46,XY DSD, never receive a molecular genetic diagnosis. Rapid genome sequencing (rGS) is gaining momentum as a first‐tier diagnostic instrument in the evaluation of patients with DSD given its ability to provide greater diagnostic yield and timely results. We present the case of a patient with nonbinary genitalia and systemic findings for whom rGS identified a novel variant of the WT1 gene and resulted in a molecular diagnosis within two weeks of life. This timeframe of diagnosis for syndromic DSD is largely unprecedented at our institution. Rapid GS expedited mobilization of a multidisciplinary medical team; enabled early understanding of clinical trajectory; informed planning of medical and surgical interventions; and guided individualized psychosocial support provided to the family. This case highlights the potential of early rGS in transforming the evaluation and care of patients with DSD.
Deep Resequencing of the 1q22 Locus in Non‐Lobar Intracerebral Hemorrhage
Authors: Parodi Livia , Comeau Mary E. , Georgakis Marios K. , Mayerhofer Ernst , Chung Jaeyoon , Falcone Guido J. , Malik Rainer , Demel Stacie L. , Worrall Bradford B. , Koch Sebastian , Testai Fernando D. , Kittner Steven J. , McCauley Jacob L. , Hall Christiana E. , Mayson Douglas J. , Elkind Mitchell S.V. , James Michael L. , Woo Daniel , Rosand Jonathan , Langefeld Carl D. , Anderson Christopher D.
Published: October 2023

Objective

Genome‐wide association studies have identified 1q22 as a susceptibility locus for cerebral small vessel diseases, including non‐lobar intracerebral hemorrhage (ICH) and lacunar stroke. In the present study, we performed targeted high‐depth sequencing of 1q22 in ICH cases and controls to further characterize this locus and prioritize potential causal mechanisms, which remain unknown.

Methods

A total of 95,000 base pairs spanning 1q22, including SEMA4A, SLC25A44, and PMF1/PMF1‐BGLAP were sequenced in 1,055 spontaneous ICH cases (534 lobar and 521 non‐lobar) and 1,078 controls. Firth regression and Rare Variant Influential Filtering Tool analysis were used to analyze common and rare variants, respectively. Chromatin interaction analyses were performed using Hi‐C, chromatin immunoprecipitation followed by sequencing, and chromatin interaction analysis with paired‐end tag databases. Multivariable Mendelian randomization assessed whether alterations in gene‐specific expression relative to regionally co‐expressed genes at 1q22 could be causally related to ICH risk.

Results

Common and rare variant analyses prioritized variants in SEMA4A 5′‐UTR and PMF1 intronic regions, overlapping with active promoter and enhancer regions based on ENCODE annotation. Hi‐C data analysis determined that 1q22 is spatially organized in a single chromatin loop, and that the genes therein belong to the same topologically associating domain. Chromatin immunoprecipitation followed by sequencing and chromatin interaction analysis with paired‐end tag data analysis highlighted the presence of long‐range interactions between the SEMA4A‐promoter and PMF1‐enhancer regions prioritized by association testing. Multivariable Mendelian randomization analyses demonstrated that PMF1 overexpression could be causally related to non‐lobar ICH risk.

Interpretation

Altered promoter–enhancer interactions leading to PMF1 overexpression, potentially dysregulating polyamine catabolism, could explain demonstrated associations with non‐lobar ICH risk at 1q22, offering a potential new target for prevention of ICH and cerebral small vessel disease. ANN NEUROL 2024;95:325–337
Understanding co‐corresponding authorship: A bibliometric analysis and detailed overview
Authors: Tian Wencan , Cai Ruonan , Fang Zhichao , Geng Yu , Wang Xianwen , Hu Zhigang
Published: October 2023

The phenomenon of co‐corresponding authorship is becoming more and more common. To understand the practice of authorship credit sharing among multiple corresponding authors, we comprehensively analyzed the characteristics of the phenomenon of co‐corresponding authorships from the perspectives of countries, disciplines, journals, and articles. This researcher was based on a dataset of nearly 8 million articles indexed in the Web of Science, which provides systematic, cross‐disciplinary, and large‐scale evidence for understanding the phenomenon of co‐corresponding authorship for the first time. Our findings reveal that higher proportions of co‐corresponding authorship exist in Asian countries, especially in China. From the perspective of disciplines, there is a relatively higher proportion of co‐corresponding authorship in the fields of engineering and medicine, while a lower proportion exists in the humanities, social sciences, and computer science fields. From the perspective of journals, high‐quality journals usually have higher proportions of co‐corresponding authorship. At the level of the article, our findings proved that, compared to articles with a single corresponding author, articles with multiple corresponding authors have a significant citation advantage.
Synthesis of Thiophene‐Substituted Ketones via Manganese‐Catalyzed Dehydrogenative Coupling Reaction
Authors: Zhang Xiaoyu , Zhang Yujie , Ding Jiaqiao , Wang Liusheng , Chen Weihua , Li Xinyan , Cui Bing , Zhao Mingqin , Shao Zhihui
Published: October 2023

This study reports an efficient and green one‐step method for synthesizing thiophene‐substituted ketones from 2‐thiophenemethanol and ketones via dehydrogenative coupling using manganese complexes as catalysts. The manganese complex demonstrated a broad applicability under mild conditions and extended the range of usable substrates. Utilizing this strategy, we carried out an efficient and diverse reaction of ketones with 2‐thiophenemethanol, and successfully synthesized a series of thiophene‐substituted saturated ketones and α, β‐unsaturated ketones in good isolated yields.
Reusing wastewater from Coffea arabica processing to produce single‐cell protein using Candida sorboxylosa: Optimizing of culture conditions
Authors: Pillaca‐Pullo Omar Santiago , Lopes André Moreni , Estela‐Escalante Waldir D.
Published: October 2023

Coffee is a crop of significant socioeconomic importance, and the reuse of agri‐food by‐products and biowaste has great potential across several industries. Coffee wastewater (CWW) is a valuable resource containing essential nutrients that can be utilized by Candida sorboxylosa for single‐cell protein (SCP) production. This utilization contributes to mitigating the negative impacts of agro‐industrial waste. The optimization of culture conditions using the design of experiments (DoE) technique is crucial in understanding the environmental factors influencing metabolite production. In our study, the DoE technique was employed to analyze culture conditions, including room temperature, pH 8.4, agitation at 200 rpm, a headspace of 60% (v/v), and an inoculum of 0.75 DO600nm over 28‐h period. This approach resulted in a remarkable SCP yield of 64.4% and dry cell weight (DCW) of 2.26 g/L. It is noteworthy that there is no literature reporting SCP production under alkaline pH conditions in yeast. Interestingly, our work demonstrated that an alkaline pH of 8.4 significantly influenced SCP production by C. sorboxylosa. The DoE technique proved to be an efficient statistical tool for optimizing culture conditions, offering several advantages, such as: (i) conducting cultures at room temperature to minimize unnecessary energy consumption; (ii) reducing the incubation time from 46 to 28 h, thereby enhancing overall productivity; (iii) achieving 1.7‐fold increase in SCP yield compared to previous basal production levels.
Applying active learning by contextualizing robotic applications to historical heritage
Authors: Quesada‐Real Francisco J. , Perez‐Peña Fernando , Morgado‐Estévez Arturo , Ruiz‐Lendínez Juan J.
Published: October 2023

Optional university courses are designed to allow undergraduate students to specialize in relevant fields to enhance their skills and knowledge for their future careers. However, there are some cases in which students prioritize enrolling in courses that are easy to pass. This choice results in having students with low motivation and commitment, who mainly focus on doing just enough to pass the course, missing the opportunity to boost their skills. In this study, an eclectic approach is proposed, applying a mixture of active learning methods together with the theory of multiple intelligences to improve students' performance, motivation, and commitment throughout the course. The study was applied to the 56 students enrolled in the optional Micro‐Robotics Application spring course in the year 2021 at the University of Cádiz (Spain). Results demonstrate that this combination of active learning methodologies increased students' motivation, prompting them to give their best in terms of commitment, performance, and creativity. Furthermore, they were convinced that during the course they not only learned relevant robotic knowledge but also acquired essential skills needed for their future. Finally, this study highlights the benefits and future directions for implementing active learning methodologies in science, technology, engineering, and mathematics courses.
Molecular Docking, Pharmacokinetic and Molecular Simulation Analysis of Novel Mono‐Carbonyl Curcumin Analogs as L858R/T790M/C797S Mutant EGFR Inhibitors
Authors: Bhandari Shashikant V. , Kuthe Pranali V. , Patil Shital M. , Nagras Om G. , Sarkate Aniket P. , Chaudhari Somdatta Y. , Surve Sandip V.
Published: October 2023

Introduction: Curcumin, an anticancer natural compound with multiple pharmacological activities, has a weak pharmacokinetic and instability due to diketone moiety. Curcumin's stability challenges can be overcome by removing the diketone moiety and shortening the 7‐carbon chain, resulting in mono‐carbonyl analogs. Cancer proliferation is caused by the activation of Epidermal Growth Factor (EGFR) pathways. Current available EGFR inhibitors have an issue of resistance. Aim: Thus, we aimed to design new mono‐carbonyl curcumin derivatives and analyse their drug likeness properties. Further, to investigate them on three distinct crystal structures, namely two wild‐type and L858R/T790M/C797S mutant generations for EGFR inhibitory activity. Method: Ten New Molecular Entities (NME's) were designed using literature survey. These molecules were subjected to comparative molecular docking, on the EGFR crystal structures viz. wild‐type (PDB: 1M17 and 4I23) and L858R/T790M/C797S mutant (PDB: 6LUD) using Schrodinger software. The molecules were also tested for Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties. The docked complex of the hit molecule was studied for molecular simulation. Result and Discussion: In molecular docking studies, NMEs 1, 2, and 3 were found to have good binding affinity with 1st, 2nd, and 3rd generation EGFR crystal structures and a greater dock score than standard curcumin. All molecules have shown a good ADMET profile. Since L858R/T790M/C797S is currently being explored more, we decided to take the best molecule, NME 3, for molecular dynamics with 6LUD, and the results were compared with those of the co‐crystallized ligand S4 (Osimertinib). It was found that the Relative mean square standard deviation (RMSD) (1.8 Å), Relative mean standard Fluctuation (RMSF) (1.45 Å) and radius of gyration (4.87 Å) values of NME 3 were much lower than those of reference S4. All these confirm that our designed NME 3 is more stable than reference S4. Conclusion: NME 1 and NME 2 have shown better binding against wild type of EGFR. NME 3 have shown comparable binding and more stability as compared to Osimertinib against L858R/T790M/C797S mutated protein structure. The hit compound can be further explored for its Molecular mechanics with generalised Born and surface area solvation (MM‐GBSA) and discrete Fourier transform (DFT) studies to find out the energy and atomic level study. In the future, this molecule could be taken for wet lab studies and can be tested for mutated EGFR inhibitory activity.
HER‐2‐Targeted Boron Neutron Capture Therapy with Carborane‐integrated Immunoliposomes Prepared via an Exchanging Reaction
Authors: Kawasaki Riku , Oshige Ayano , Yamana Keita , Hirano Hidetoshi , Nishimura Kotaro , Miura Yamato , Yorioka Ryuji , Sanada Yu , Bando Kaori , Tabata Anri , Yasuhara Kazuma , Miyazaki Yusuke , Shinoda Wataru , Nishimura Tomoki , Azuma Hideki , Takata Takushi , Sakurai Yoshinori , Tanaka Hiroki , Suzuki Minoru , Nagasaki Takeshi , Ikeda Atsushi
Published: October 2023

Boron neutron capture therapy (BNCT) is a promising modality for cancer treatment because of its minimal invasiveness. To maximize the therapeutic benefits of BNCT, the development of efficient platforms for the delivery of boron agents is indispensable. Here, carborane‐integrated immunoliposomes were prepared via an exchanging reaction to achieve HER‐2‐targeted BNCT. The conjugation of an anti‐HER‐2 antibody to carborane‐integrated liposomes successfully endowed these liposomes with targeting properties toward HER‐2‐overexpressing human ovarian cancer cells (SK‐OV3); the resulting BNCT activity toward SK‐OV3 cells obtained using the current immunoliposomal system was 14‐fold that of the l‐BPA/fructose complex, which is a clinically available boron agent. Moreover, the growth of spheroids treated with this system followed by thermal neutron irradiation was significantly suppressed compared with treatment with the l‐BPA/fructose complex.
Dual Strategies with Anion/Cation Co‐Doping and Lithium Carbonate Coating to Enhance the Electrochemical Performance of Lithium‐Rich Layered Oxides
Authors: Chen Huai , Ma Jun , Liu Fei , Yao Mengqin
Published: October 2023

Lithium‐rich layered oxides (LLOs, Li1.2Mn0.54Ni0.13Co0.13O2) are widely used as cathode materials for lithium‐ion batteries due to its high specific capacity, high operating voltage and low cost. However, the LLOs are faced with rapid decay of charge/discharge capacity and voltage, as well as interface side reactions, which limit its electrochemical performance. Herein, the dual strategies of sulfite/sodium ion co‐doping and lithium carbonate coating were used to improve it. It founds that modified LLOs achieve 88.74 % initial coulomb efficiency, 295.3 mAh g−1 first turn discharge capacity, in addition to 216.9 mAh g−1 at 1 C, and 87.23 % capacity retention after 100 cycles. Mechanism research indicated that the excellent electrochemical performance benefits from the doping of both Na+ and SO32−, and it could significantly reduce the migration energy barrier of Li+ and promote Li+ migration. Meanwhile, anion and cation are co‐doped greatly reduces the band gap of LLOs and increase its electrical conductivity, and its binding effect on Li+ is weakened, making it easier for Li+ to shuttle through the material. In addition, the lithium carbonate coating significantly inhibits the occurrence of interfacial side reactions of LLOs. This work provides a theoretical basis and practical guidance for the further development of LLOs with higher electrochemical performance.
Power‐to‐X – Nachhaltige Produktionsrouten für eine klimaneutrale Industrie
Authors: Boumrifak Chokri
Published: October 2023

Zahlreiche Industriezweige können erneuerbar erzeugten Strom nicht direkt nutzen oder sind auf fossile Ressourcen zur stofflichen Nutzung angewiesen. Um die Klimaziele trotzdem zu erreichen, müssen die betroffenen Sektoren Alternativen zu den bisher verwendeten fossilen Rohstoffen finden. Die Antwort auf diese Herausforderung heißt Power‐to‐X. Was sich dahinter verbirgt und welches Potenzial in den Technologien steckt, erklärt dieser Trendbericht.
Standardisierung als Wegweiser für Wasserstoff
Authors: Hares Kevin
Published: October 2023

Der Hochlauf einer Wasserstoffwirtschaft ist für die Einhaltung der nationalen Klimaziele essenziell. Damit Abstimmungsprobleme zwischen den Erzeugern und den Abnehmern den Hochlauf nicht verlangsamen, sollen mit der Normungsroadmap flächendeckende Standards über die gesamte Wertschöpfungskette ermöglicht werden.
Präzises Zudosieren von Geruchsstoff
Authors: Richter Walter
Published: October 2023

Da Erdgas selbst geruchlos ist, muss er als Sicherheitsmaßnahme für die öffentliche Gasversorgung gemäß dem Regelwerk DVGW G 280 mit Geruchsstoffen versetzt werden. Ein Energieversorger entschied sich bei dem neuen LNG‐Terminal für den Odorservice der CeH4 technologies, der den Pumpenhersteller Lewa mit der Bereitstellung der Odorieranlagen mit Dosierpumpen beauftragte.
Echtzeiteinblicke in die Methanol‐Synthese
Authors: Schwarz Jörg , Reiff Ellen‐Christine
Published: October 2023

Für viele verfahrenstechnische Anwendungen rund um die aktuellen Power‐to‐X‐Technologien sind faseroptische Sensoren eine gute Lösung, da sie ein lückenloses Temperaturprofil liefern. Die faseroptische Temperaturmessung hilft optimale Katalysatoren und Verfahren für die industrielle Methanol‐Synthese zu entwickeln.
Current Strategies of Modeling Human Trophoblast Using Human Pluripotent Stem Cells in vitro
Authors: Cheung Virginia Chu , Bui Tony , Soncin Francesca , Bai Tao , Kessler John A. , Parast Mana M , Horii Mariko
Published: October 2023

We previously established a trophoblast differentiation protocol from primed human pluripotent stem cells (PSC). To induce this lineage, we use a combination of Bone Morphogenetic Protein‐4 (BMP4) and the WNT inhibitor IWP2. This protocol has enabled us to obtain a pure population of trophectoderm (TE)‐like cells that could subsequently be terminally differentiated into syncytiotrophoblasts (STB) and extravillous trophoblasts (EVT). However, the resulting TE‐like cells could only be terminally differentiated to a variable mixture of STB and EVT, with a bias toward the STB lineage. Recently, methods have been developed for derivation and culture of self‐renewing human trophoblast stem cells (TSC) from human embryos and early gestation placental tissues. These primary TSCs were further able to differentiate into either STB or EVT with high efficiency using the lineage specific differentiation protocols. Based partly on these protocols, we have developed methods for establishing self‐renewing TSC‐like cells from PSC, and for efficient lineage‐specific terminal differentiation. Here, we describe in detail the protocols to derive and maintain PSC‐TSC, from both embryonic stem cells (ESC) and patient‐derived induced pluripotent stem cells (iPSC), and their subsequent terminal differentiation to STB and EVT. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.

This article was corrected on 14 April 2024. See the end of the full text for details.

Basic Protocol 1: Trophoblast Differentiation into TE‐like Cells

Basic Protocol 2: Conversion of PSC‐Derived TE‐like Cells to TSC

Basic Protocol 3: Passaging PSC‐Derived TSC in iCTB Complete Medium

Basic Protocol 4: STB Differentiation from PSC‐derived TSC

Basic Protocol 5: EVT Differentiation from PSC‐derived TSC

Support Protocol 1: Geltrex‐coated tissue culture plate preparation

Support Protocol 2: Collagen IV‐coated tissue culture plate preparation

Support Protocol 3: Fibronectin‐coated tissue culture plate preparation
In‐Cell Arrestin‐Receptor Interaction Assays
Authors: Zheng Chen , Javitch Jonathan A. , Lambert Nevin A. , Donthamsetti Prashant , Gurevich Vsevolod V.
Published: October 2023

G protein‐coupled receptors (GPCRs) represent ∼30% of current drug targets. Ligand binding to these receptors activates G proteins and arrestins, which function in different signaling pathways. Given that functionally selective or biased ligands preferentially activate one of these two groups of pathways, they may be superior medications for certain disease states. The identification of such ligands requires robust drug screening assays for both G protein and arrestin activity. This unit describes protocols for assays that monitor reversible arrestin recruitment to GPCRs in living cells using either bioluminescence resonance energy transfer (BRET) or nanoluciferase complementation (NanoLuc). Two types of assays can be used: one configuration directly measures arrestin recruitment to a GPCR fused to a protein tag at its intracellular C‐terminus, whereas the other configuration detects arrestin translocation to the plasma membrane in response to activation of an unmodified GPCR. Together, these assays are powerful tools for studying dynamic interactions between GPCRs and arrestins. © 2023 Wiley Periodicals LLC.

Basic Protocol 1: Receptor‐arrestin BRET assay to measure ligand‐induced recruitment of arrestin to receptors

Basic Protocol 2: Receptor‐arrestin NANOBIT assay to measure ligand‐induced recruitment of arrestin to receptors

Alternative Protocol 1: BRET assay to measure ligand‐induced recruitment of arrestin to the plasma membrane

Alternative Protocol 2: NANOBIT assay to measure ligand‐induced recruitment of arrestin to the plasma membrane

Support Protocol 1: Optimization of polyethylenimine (PEI) concentration for transfection
Assessing the performance of the Cell Painting assay across different imaging systems
Authors: Tromans‐Coia Callum , Jamali Nasim , Abbasi Hamdah Shafqat , Giuliano Kenneth A. , Hagimoto Mai , Jan Kevin , Kaneko Erika , Letzsch Stefan , Schreiner Alexander , Sexton Jonathan Z. , Suzuki Mahomi , Trask O. Joseph , Yamaguchi Mitsunari , Yanagawa Fumiki , Yang Michael , Carpenter Anne E. , Cimini Beth A.
Published: October 2023

Quantitative microscopy is a powerful method for performing phenotypic screens from which image‐based profiling can extract a wealth of information, termed profiles. These profiles can be used to elucidate the changes in cellular phenotypes across cell populations from different patient samples or following genetic or chemical perturbations. One such image‐based profiling method is the Cell Painting assay, which provides morphological insight through the imaging of eight cellular compartments. Here, we examine the performance of the Cell Painting assay across multiple high‐throughput microscope systems and find that all are compatible with this assay. Furthermore, we determine independently for each microscope system the best performing settings, providing those who wish to adopt this assay an ideal starting point for their own assays. We also explore the impact of microscopy setting changes in the Cell Painting assay and find that few dramatically reduce the quality of a Cell Painting profile, regardless of the microscope used.
Direct diffusion of anti‐Müllerian hormone from both the cranial and caudal regions of the testis during early gonadal development in mice
Authors: Kato Shiori , Yokoyama Toshifumi , Okunishi Nobusuke , Narita Hiroto , Fujikawa Taisei , Kirizuki Yusuke , Mantani Youhei , Miki Takanori , Hoshi Nobuhiko
Published: October 2023

Background

The Müllerian duct (MD), the primordium of the female reproductive tract, is also formed in males during the early stage of development, then regresses due to the anti‐Müllerian hormone (AMH) secreted from the testes. However, the detailed diffusion pathway of AMH remains unclear. We herein investigated the mechanism by which AMH reaches the middle region of the MD using an organ culture system.

Results

Injection of recombinant human AMH into the testis around the start of MD regression induced diffuse immunoreactivity in the mesonephros near the injection site. When the testis and mesonephros were cultured separately, the diameters of both cranial and middle MDs were significantly increased compared to the control. In the testis–mesonephros complex cultured by inhibiting the diffusion of AMH through the cranial region, the cranial MD diameter was significantly increased compared to the control, and there was no difference in middle MD diameter.

Conclusions

These results indicate that AMH, which infiltrates from the testis through the cranial region at physiological concentrations, induces regression of the cranial MD at the start of MD regression. They also indicate that AMH infiltrating through the caudal regions induces regression of the middle MD.
Improving digestibility of sorghum proteins by CRISPR/Cas9‐based genome editing
Authors: Li Xinyu , Liu Wenzhen , Wang Gaoliang , Sun Samuel Sai‐Ming , Yuan Ling , Wang Jingxue
Published: October 2023

Kafirins are the primary storage proteins in sorghum kernels that provide amino acids for seed germination. The highly proteolytic resistant γ‐ and β‐kafirins form the cross‐linked outer layers that encapsulate α‐kafirins to generate protein bodies, resulting in poor digestibility of sorghum grains. The sorghum kafirins thus contribute to the poor quality of the kernels. The nutritional quality and digestibility of sorghum grains can be improved by reducing the contents of kafirin. γ‐Kafirin is encoded by the K2G gene, which is located on sorghum chromosome 2. In this study, we used CRISPR/Cas9 gene editing to target the K2G gene to create new sorghum lines with reduced levels of kafirin. A guide RNA (sgRNA) was designed to introduce mutations in the CDS region that encodes the endoplasmic reticulum signal peptide of γ‐kafirin. The pK2GsgRNA/Cas9 vector was transformed into sorghum using the pollen‐mediated transformation method. Sequencing of the transformants showed that three out of 24 transgenic plants contain genetic mutations in the targeted region. Compared with the wildtype, the γ‐kafirin contents of the mutant plants decreased by 12.75%–19.22%, and the protein digestibility of the mutant kernels increased by 26.91%–74.31% in raw flour. Although the grain weights remained comparable to those of the wildtype, the growth of the mutant plants was more vigorous as the mutant shoots grew taller and thicker compared with those of the wildtype. Our work advances the ability to improve the digestibility of an important crop. The resulting quality improvements can also be rapidly deployed for breeding and generation of transgene‐free, improved cultivars of sorghum, a major crop worldwide.
Effects of food price on nutrition outcomes among women in Nigeria
Authors: Fajobi Deborah Tosin , Ajetomobi Joshua Olusegun , Raufu Mufutau Oyedapo , Fajobi Moses Oluwatobi , Paramasivam Prabhu
Published: October 2023

Nutrition outcomes (undernutrition, overweight, and obesity) among women are growing concerns across the globe. Currently, the rate of undernutrition and overweight among women in Nigeria is ranked among the highest in Africa. A major contributory factor reported is unstable food prices in the country. This study, therefore, examined the effects of food prices on nutrition outcomes among women in Nigeria. Secondary datasets retrieved from two different sources were used for this study. Cross‐sectional data on weight and height for women were obtained from Nigeria Health Demographic Survey (NHDS). Data on monthly prices of the selected food items were obtained from the Nigeria Bureau of Statistics (NBS). The data were categorized into energy dense (yam tuber, garri, rice, and maize) and nutrient dense (egg, beef, and chicken). Multinomial logit regression was used to estimate the relationship between the prices of energy and nutrient‐dense food prices concerning respondents' personal and environmental characteristics such as age, wealth status, and region; as well as the three nutrition outcomes for women (undernutrition, overnutrition, and obesity). This study revealed that the prevalence of overweight and obesity among women was 19.9% and 10.3%, respectively. Nutrition outcomes (obesity and overweight) were positively correlated with the price of energy‐dense food with 0.2% and 0.3%, respectively. Nutrient‐dense food price is negatively correlated with undernutrition with a probability of 0.1%. The study recommends that food policy instruments such as food prices and subsidies can be introduced to favor the consumption of healthier food to stem the prevalence of overweight and obesity in Nigeria.
Felsmechanische Planung in der geotechnischen Werkzeugkiste von morgen: Eurocode 7 – Geotechnische Bauwerke: Böschungen, Flachgründungen und Stützkonstruktionen (EN 1997‐3:2024)
Authors: Stille Håkan , Ashcroft Bruce , Boley Conrad , Labiouse Vincent , Pinto Paulo
Published: October 2023

The second generation of Eurocode 7 includes both soil and rock. In addition to the current practice of ground engineering, this document aims at incorporating rock engineering, improving the ease of use, the harmonization of regulations and covering new developments. This paper provides an overview of some of the significant changes to Eurocode 7 in rock engineering design, taking into consideration limit state design, robustness, durability, and reliability. It focuses on the design of slopes, spread foundations, and retaining structures.

The clauses focus on soil mechanics, but also include special rock mechanical issues such as the influence of discontinuities and strength anisotropy on the limit states. Many matters associated to verification of rock mechanical design are linked to the use of prescriptive rules and shall be given in National Annexes. For geotechnical structures in rock, it is mentioned that geotechnical mapping and documentation is important to verify the limit states. However, the basic issues with partial factor methods for verification of the ground‐structure interaction of reinforced slopes and retaining structures are not fully resolved. This has caused some difficulties in setting up partial factors and obtaining a sufficient overview of the application of partial factor method, especially in rock engineering.

The design of slopes, spread foundations and retaining structures must likewise consider other clauses in the Eurocode. Rock support for slopes and retaining structures is described in Clause 13 ”Rock Bolts and Surface Support“. Groundwater‐related issues are described in clause 12 ”Ground water control“ which influence the design and limit states for the actual geotechnical structure. Dams and levees are featured in Clause 4 ”Slopes, Cuttings and Embankments“.
Felsbauplanung im geotechnischen Werkzeugkasten von morgen: Eurocode 7 – Geotechnische Bauwerke: Anker, Felsnägel, Bodennägel und Grundwasserkontrolle (EN 1997‐3:2024)
Authors: Maca Natalia , Dietz Klaus , Stille Håkan , Virely Didier
Published: October 2023

In 2025 the new generation of the Eurocode 7 will be introduced and set a framework for geotechnical design for the next 20 years. As Eurocode 7 is an essential design code, the changes will affect numerous practising geotechnical Engineers. The paper provides an overview of significant changes in rock engineering design introduced in the new EN 1997 part 3, considering limit state design, durability, reliability, testing and other crucial design aspects. It focuses on the anchor clause revision and first introduced design rules for rock bolts and soil‐nailed structures. The improvements described include distinguishing between different tension supporting elements that have often been confused. Furthermore, the provisions for groundwater control measures influencing the working condition and limit states for all other geotechnical systems that have not yet been comprehensively addressed in the current Eurocode 7 are also clarified. Finally, the design of the described geotechnical structure will also be strongly affected by changes in the overall philosophy of the Eurocodes, which is also explained.