bluuebunny/crossref_metadata_2025 huggingface dataset:
Multifunctional Antibacterial Nanonets Attenuate Inflammatory Responses through Selective Trapping of Endotoxins and Pro‐Inflammatory Cytokines
Authors: Tram Nhan Dai Thien , Tran Quy Thi Ngoc , Xu Jian , Su Jeannie Ching Ting , Liao Wupeng , Wong Wai Shiu Fred , Ee Pui Lai Rachel
Published: March 2023

Extracellular lipopolysaccharide (LPS) released from bacteria cells can enter the bloodstream and cause septic complications with excessive host inflammatory responses. Target‐specific strategies to inactivate inflammation mediators have largely failed to improve the prognosis of septic patients in clinical trials. By utilizing their high density of positive charges, de novo designed peptide nanonets are shown to selectively entrap the negatively charged LPS and pro‐inflammatory cytokines tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6). This in turn enables the nanonets to suppress LPS‐induced cytokine production by murine macrophage cell line and rescue the antimicrobial activity of the last‐resort antibiotic, colistin, from LPS binding. Using an acute lung injury model in mice, it is demonstrated that intratracheal administration of the fibrillating peptides is effective at lowering local release of TNF‐α and IL‐6. Together with previously shown ability to simultaneously trap and kill pathogenic bacteria, the peptide nanonets display remarkable potential as a holistic, multifunctional anti‐infective, and anti‐septic biomaterial.
Injury Site Specific Xenon Delivered by Platelet Membrane‐Mimicking Hybrid Microbubbles to Protect Against Acute Kidney Injury via Inhibition of Cellular Senescence
Authors: Yang Jing , Chen Chaojin , Miao Xiaoyan , Wang Tienan , Guan Yu , Zhang Linan , Chen Sufang , Zhang Zheng , Xia Zhengyuan , Kang Jiayi , Li Haobo , Yin Tinghui , Hei Ziqing , Yao Weifeng
Published: March 2023

Inhalation of xenon gas improves acute kidney injury (AKI). However, xenon can only be delivered through inhalation, which causes non‐specific distribution and low bioavailability of xenon, thus limiting its clinical application. In this study, xenon is loaded into platelet membrane‐mimicking hybrid microbubbles (Xe‐Pla‐MBs). In ischemia‐reperfusion‐induced AKI, intravenously injected Xe‐Pla‐MBs adhere to the endothelial injury site in the kidney. Xe‐Pla‐MBs are then disrupted by ultrasound, and xenon is released to the injured site. This release of xenon reduced ischemia‐reperfusion‐induced renal fibrosis and improved renal function, which are associated with decreased protein expression of cellular senescence markers p53 and p16, as well as reduced beta‐galactosidase in renal tubular epithelial cells. Together, platelet membrane‐mimicking hybrid microbubble‐delivered xenon to the injred site protects against ischemia‐reperfusion‐induced AKI, which likely reduces renal senescence. Thus, the delivery of xenon by platelet membrane‐mimicking hybrid microbubbles is a potential therapeutic approach for AKI.
Intravascularly Deliverable Biomaterial Platforms for Tissue Repair and Regeneration Post‐Myocardial Infarction
Authors: Chen Alexander , Mesfin Joshua M. , Gianneschi Nathan C. , Christman Karen L.
Published: March 2023

Each year, nearly 19 million people die of cardiovascular disease with coronary heart disease and myocardial infarction (MI) as the leading cause of the progression of heart failure. Due to the high risk associated with surgical procedures, a variety of minimally invasive therapeutics aimed at tissue repair and regeneration are being developed. While biomaterials delivered via intramyocardial injection have shown promise, there are challenges associated with delivery in acute MI. In contrast, intravascularly injectable biomaterials are a desirable category of therapeutics due to their ability to be delivered immediately post‐MI via less invasive methods. In addition to passive diffusion into the infarct, these biomaterials can be designed to target the molecular and cellular characteristics seen in MI pathophysiology, such as cells and proteins present in the ischemic myocardium, to reduce off‐target localization. These injectable materials can also be stimuli‐responsive through enzymes or chemical imbalances. This review outlines the natural and synthetic biomaterial designs that allow for retention and accumulation within the infarct via intravascular delivery, including intracoronary infusion and intravenous injection.
Space‐Confined Metal Ion Strategy for Carbon Materials Derived from Cobalt Benzimidazole Frameworks with High Desalination Performance in Simulated Seawater
Authors: Cao Shuai , Li Yong , Tang Yijian , Sun Yangyang , Li Wenting , Guo Xiaotian , Yang Feiyu , Zhang Guangxun , Zhou Huijie , Liu Zheng , Li Qing , Shakouri Mohsen , Pang Huan
Published: March 2023

Various metal ions with different valence states (Mg2+, Al3+, Ca2+, Ti4+, Mn2+, Fe3+, Ni2+, Zn2+, Pb2+, Ba2+, Ce4+) are successfully confined in quasi‐microcube shaped cobalt benzimidazole frameworks using a space‐confined synthesis strategy. More importantly, a series of derived carbon materials that confine metal ions are obtained by high‐temperature pyrolysis. Interestingly, the derived carbon materials exhibited electric double‐layer and pseudocapacitance properties because of the presence of metal ions with various valence states. Moreover, the presence of additional metal ions within carbon materials may create new phases, which can accelerate Na+ insertion/extraction and thus increase electrochemical adsorption. Density functional theory results showed that carbon materials in which Ti ions are confined exhibit enhanced insertion/extraction of Na+ resulting from the presence of the characteristic anatase crystalline phases of TiO2. The Ti‐containing materials have an impressive desalination capacity (62.8 mg g−1) in capacitive deionization (CDI) applications with high cycling stability. This work provides a facile synthetic strategy for the confinement of metal ions in metal–organic frameworks and thus supports the further development of derived carbon materials for seawater desalination by CDI.
Identifying the Internal Network Structure of a New Copper Isonicotinate Thin‐Film Polymorph Obtained via Chemical Vapor Deposition
Authors: Legenstein Lukas , Rodríguez‐Hermida Sabina , Rubio‐Giménez Víctor , Stassin Timothée , Hofer Sebastian , Kainz Manuel P. , Fratschko Mario , Carraro Francesco , Falcaro Paolo , Ameloot Rob , Resel Roland
Published: March 2023

The preparation of thin films is often associated with the appearance of unknown polymorphs, as both the substrate and deposition method can heavily influence crystallization processes. Here, chemical vapor deposition is used to obtain thin films of a copper‐isonicotinate (Cu‐INA) metal–organic framework (MOF). Starting from copper‐based precursor layers (copper oxide and hydroxide), a solid‐vapor conversion with vaporized isonicotinic acid in either a dry or humidified atmosphere, yields a new Cu‐INA MOF polymorph. It is found that the crystalline order of the precursor layer has a strong impact on the texture of Cu‐INA thin films. Furthermore, a novel methodology is introduced to determine the structure of a previously unknown thin‐film phase of Cu‐INA. Although only a few diffraction peaks are found via synchrotron grazing incidence X‐ray diffraction (GIXRD), a triclinic unit cell can be determined, and Patterson functions can be calculated. The latter reveals the position of the copper atoms within the unit cell and the alignment of the INA linkers defining the coordination network structure. This work introduces how the combination of GIXRD data with Patterson functions can be used to identify the structure of an unknown thin‐film MOF polymorph.
Synthesis of Chiral Diaryl Methanols via RuPHOX‐Ru Catalyzed Asymmetric Hydrogenation
Authors: Zhou Jiayu , Ye Jianxun , Zhang Yang , Li Zhaodi , Li Jingjing , Liu Delong , Zhang Wanbin
Published: March 2023

The RuPHOX‐Ru catalyzed asymmetric hydrogenation of diaryl ketones has been established, providing the corresponding chiral diaryl methanols in up to 99% yield and 99% ee. The protocol could be performed on a gram‐scale with a relatively low catalyst loading (2000 S/C) and the resulting products allow for several useful transformations, in particular for the synthesis of chiral drugs, such as, (S)‐Orphenadrine and (S)‐Neobenodine. Deuterium labeling and control experiments revealed that the RuPHOX‐Ru‐catalyzed asymmetric hydrogenation is fully subject to hydrogenation with H2 as the sole hydrogen source.

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Functional Carbon from Nature: Biomass‐Derived Carbon Materials and the Recent Progress of Their Applications
Authors: He Hongzhe , Zhang Ruoqun , Zhang Pengcheng , Wang Ping , Chen Ning , Qian Binbin , Zhang Lian , Yu Jianglong , Dai Baiqian
Published: March 2023

Biomass is considered as a promising source to fabricate functional carbon materials for its sustainability, low cost, and high carbon content. Biomass‐derived‐carbon materials (BCMs) have been a thriving research field. Novel structures, diverse synthesis methods, and versatile applications of BCMs have been reported. However, there has been no recent review of the numerous studies of different aspects of BCMs‐related research. Therefore, this paper presents a comprehensive review that summarizes the progress of BCMs related research. Herein, typical types of biomass used to prepare BCMs are introduced. Variable structures of BCMs are summarized as the performance and properties of BCMs are closely related to their structures. Representative synthesis strategies, including both their merits and drawbacks are reviewed comprehensively. Moreover, the influence of synthetic conditions on the structure of as‐prepared carbon products is discussed, providing important information for the rational design of the fabrication process of BCMs. Recent progress in versatile applications of BCMs based on their morphologies and physicochemical properties is reported. Finally, the remaining challenges of BCMs, are highlighted. Overall, this review provides a valuable overview of current knowledge and recent progress of BCMs, and it outlines directions for future research development of BCMs.
Engineering the MoS2/MXene Heterostructure for Precise and Noninvasive Diagnosis of Prostate Cancer with Clinical Specimens
Authors: Xie Shaowei , Fei Xiaochen , Wang Jiayi , Zhu Yi‐Cheng , Liu Jiazhou , Du Xinxing , Liu Xuesong , Dong Liang , Zhu Yinjie , Pan Jiahua , Dong Baijun , Sha Jianjun , Luo Yu , Sun Wenshe , Xue Wei
Published: March 2023

High‐throughput metabolic fingerprinting has been deemed one of the most promising strategies for addressing the high false positive rate of prostate cancer (PCa) diagnosis in the prostate‐specific antigen (PSA) gray zone. However, the current metabolic fingerprinting remains challenging in achieving high‐precision metabolite detection in complex biological samples (e.g., serum and urine). Herein, a novel self‐assembly MoS2/MXene heterostructure nanocomposite with a tailored doping ratio of 10% is presented as a matrix for laser desorption ionization mass spectrometry analysis in clinical biosamples. Notably, owing to the two‐dimensional architecture and doping effect, MoS2/MXene demonstrates favorable laser desorption ionization performance with low adsorption energy, which is evidenced by efficient urinary metabolic fingerprinting with an enhanced area under curve (AUC) diagnosis capability of 0.959 relative to that of serum metabolic fingerprinting (AUC = 0.902) for the diagnosis of PCa in the PSA gray zone. Thus, this MoS2/MXene heterostructure is anticipated to offer a novel strategy to precisely and noninvasively diagnose PCa in the PSA gray zone.
Raman spectroscopic assessment of fibers and seeds of six cotton genotypes
Authors: He Zhongqi , Nam Sunghyun , Fang David
Published: March 2023

Raman spectroscopy (RS) is a vibrational spectroscopy. This work reported the RS spectral characteristics of fiber and seed of six cotton (Gossypium sp.) genotypes differing in fiber length. While the RS spectra of fiber samples were dominated by the cellulose‐related peaks, the spectra of cottonseed samples were featured by the bands related to oil, protein, carbohydrate, and lignin components. Principal component analysis (PCA) revealed that the first two principal components (PCs) accounted for >87% of the total variation of the two types of samples. The PC1 versus PC2 plot classified the six fiber samples into three groups, but their cottonseeds into four groups. This experimental evidence implied the possibility of RS combined with PCA for rapid fiber phenotyping of cotton as well as for evaluating cottonseed nutrient information.
A density functional theory insight into the extraction mechanism of lithium recovery from alkaline brine by β‐diketones
Authors: Sun Qing , Chen Hang , Yu Jianguo
Published: March 2023

In this study, the mechanism of lithium extraction with β‐diketones was investigated by resolving the reaction mechanism, thermodynamic property, and molecular interaction through density functional theory approach. Before the selective extraction of lithium, the β‐diketones had tautomerism with the product of enol. The enol structure was unsteady in alkaline environment so that Li+can be selectively extracted by taking the place of hydroxyl hydrogen. Meanwhile, the synergistic effect of TOPO intensified the extraction ability by the generation of strong electrostatic. Based on the calculated Gibbs energy changes, the parameters of extraction efficiency and separation factor were analyzed and they had qualitative consistence with the experimental results. Meanwhile, it was determined that the electron‐withdrawing effect of the subsistent group in the β‐diketones had a critical influence on the extraction separation performance. Besides, the theoretical model predicted successfully the transition of extraction complex from hydrophilicity to lipophilicity after the combination with synergistic reagent.
Hydrogen bond induced acidic liquids for efficient biodiesel production
Authors: Zhou Zijing , Chen Xiaoyan , Worth John , Ye Changshen , Chen Jie , Qiu Ting
Published: March 2023

In chemical engineering, the Fischer–Speier esterification shows incredible value for biofuel production. However, the transformation suffers from challenges including necessary catalysts that cause corrosion issues in addition to a complex synthesis. Herein, we report a green acidic liquid, [N,N,N‐tris(propanesulfonic)aniline][ethanol]3, which is induced by hydrogen bonding interactions between a hydrogen bond acceptor (HBA) of [N,N,N‐tris(propanesulfonic)aniline] and three hydrogen bond donators (HBD) of ethanol, through a one‐step reaction. This liquid demonstrates strong Bronsted acidity and hydrogen bond networking to mimic ionic liquids (ILs) or deep‐eutectic solvents (DESs). Even under mild conditions, biodiesel was produced with 97.65% of esterification conversion. Exploiting distinguished molecular geometry with a singular methodology, made possible by contributions from HBD, allows for a further reaction of 1,3‐propanesulfonate with positively charged amines. This discovery is feasible with a wide range of HBDs as a solvent resulting more commercially accessible products owing to a much greener synthesis when compared with ILs and DESs.
H4C5 missense variant leads to a neurodevelopmental phenotype overlapping with Angelman syndrome
Authors: Borja Nicholas , Borjas‐Mendoza Paulo , Bivona Stephanie , Peart LéShon , Gonzalez Joanna , Johnson Brittney Keira , Guo Shengru , Yusupov Roman ,   Undiagnosed Diseases Network, Bademci Guney , Tekin Mustafa
Published: March 2023

Recurrent de novo missense variants in H4 histone genes have recently been associated with a novel neurodevelopmental syndrome that is characterized by intellectual disability and developmental delay as well as more variable findings that include short stature, microcephaly, and facial dysmorphisms. A 4‐year‐old male with autism, developmental delay, microcephaly, and a happy demeanor underwent evaluation through the Undiagnosed Disease Network. He was clinically suspected to have Angelman syndrome; however, molecular testing was negative. Genome sequencing identified the H4 histone gene variant H4C5 NM_003545.4: c.295T>C, p.Tyr99His, which parental testing confirmed to be de novo. The variant met criteria for a likely pathogenic classification and is one of the seven known disease‐causing missense variants in H4C5. A comparison of our proband's findings to the initial description of the H4‐associated neurodevelopmental syndrome demonstrates that his phenotype closely matches the spectrum of those reported among the 29 affected individuals. As such, this report corroborates the delineation of neurodevelopmental syndrome caused by de novo missense H4 gene variants. Moreover, it suggests that cases of clinically suspected Angelman syndrome without molecular confirmation should undergo exome or genome sequencing, as novel neurodevelopmental syndromes with phenotypes overlapping with Angelman continue to be discovered.
Scope and Limitations in the Synthesis of Glucosamine‐based Ionic Liquids
Authors: Komabayashi Mirai , Okushiba Shoma , Nokami Toshiki , Jopp Stefan
Published: March 2023

This research article focuses on the synthesis of ionic liquids from glucosamine, a renewable material obtained from chitin. Our group previously experienced some obstacles in the synthesis of these glucosamine‐based ionic liquids, often due to the sterical hindrance induced by the dimethylated amino‐group. In this work we present a method using Borch reductive amination to overcome these limitations to achieve a dimethylethylamino‐group. We furthermore expanded upon the library of glucosamine‐based ionic liquids with new glycosidic groups, discovered a new shortened reaction procedure by skipping a deprotection step and finally compared the thermal properties of the ionic products to get an insight into structure‐property relationships.
An Iridium/Aluminum Cooperative Strategy for the β‐C(sp3)‐H Borylation of Saturated Cyclic Amines
Authors: Kuroda Yusuke , Park Kyungho , Shimazaki Yuto , Zhong Rong‐Lin , Sakaki Shigeyoshi , Nakao Yoshiaki
Published: March 2023

Despite the widespread success in the functionalization of C(sp2)−H bonds, the deliberate functionalization of C(sp3)−H bonds in a highly site‐ and stereoselective manner remains a longstanding challenge. Herein, we report an iridium/aluminum cooperative catalytic system that enables the β‐selective C−H borylation of saturated cyclic amines and lactams. Furthermore, we have accomplished an enantioselective variant using binaphthol‐derived chiral aluminum catalysts to forge C−B bonds with high levels of stereocontrol. Computational studies suggest that the formation of a Lewis pair with the substrates is crucial to lower the energy of the transition state for the rate‐determining reductive elimination step.
Photoelectromagnetic Responsive Adaptive Porous Frameworks through Dynamic Covalent Chemistry of Tetraarylethylene‐backboned Aryldicyanomethyl Radicals
Authors: Wang Xinhao , Zhang Hui , Liu Haohao , Xu Gaoqiang , Lai Weiming , Zhang Yang , Ni Xinlong , Xie Sheng , Tang Ben Zhong , Zeng Zebing
Published: March 2023

Dynamic materials undergoing adaptive solid‐state transitions are attractive for soft mechanics and information technology. Here, we report a novel porous framework system based on macrocyclic trimers assembled from open‐shell tetraarylethylene building blocks with aryldicyanomethyl radicals as coupling linkers. Under mechanical, thermal, or chemical stimuli, the framework showed adaptability by activating conformational dynamics and radical‐based transformations, thus displaying macroscopic responsiveness in terms of light absorption, luminescence, and magnetism. We studied the dynamic processes by variable‐temperature nuclear magnetic resonance (VT‐NMR), variable‐temperature electron spin resonance (VT‐ESR), and superconducting quantum interference device (SQUID) measurement and further established a proof‐of‐concept application for multi‐modal information encryption. The strategy may open avenues for rational design of solid‐state photoelectromagnetic dynamic materials by merging dynamic covalent coupling chemistry and functional aggregation principles.
Photo‐RAFT Polymerization for Hydrogel Synthesis through Barriers and Development of Light‐Regulated Healable Hydrogels under NIR Irradiation
Authors: Wu Zilong , Zhang Tong , Shi Xiaobing , Corrigan Nathaniel , Ng Gervase , Boyer Cyrille
Published: March 2023

We report an aqueous and near‐infrared (NIR) light mediated photoinduced reversible addition–fragmentation chain transfer (photo‐RAFT) polymerization system catalyzed by tetrasulfonated zinc phthalocyanine (ZnPcS4−) in the presence of peroxides. Taking advantage of its fast polymerization rates and high oxygen tolerance, this system is successfully applied for the preparation of hydrogels. Exploiting the enhanced penetration of NIR light, photoinduced gelation is effectively performed through non‐transparent biological barriers. Notably, the RAFT agents embedded in these hydrogel networks can be reactivated on‐demand, enabling the hydrogel healing under NIR light irradiation. In contrast to the minimal healing capability (<15 %) of hydrogels prepared by free radical polymerization (FRP), RAFT‐mediated networks display more than 80 % recovery of tensile strength. Although healable polymer networks under UV and blue lights have already been established, this work is the first photochemistry system using NIR light, facilitating photoinduced healing of hydrogels through thick non‐transparent barriers.
Genetic Fusion of Thermoresponsive Polypeptides with UCST‐type Behavior Mediates 1D Assembly of Coiled‐Coil Bundlemers
Authors: Patkar Sai S. , Tang Yao , Bisram Arriana M. , Zhang Tianren , Saven Jeffery G. , Pochan Darrin J. , Kiick Kristi L.
Published: March 2023

Thermoresponsive resilin‐like polypeptides (RLPs) of various lengths were genetically fused to two different computationally designed coiled coil‐forming peptides with distinct thermal stability, to develop new strategies to assemble coiled coil peptides via temperature‐triggered phase separation of the RLP units. Their successful production in bacterial expression hosts was verified via gel electrophoresis, mass spectrometry, and amino acid analysis. Circular dichroism (CD) spectroscopy, ultraviolet‐visible (UV/Vis) turbidimetry, and dynamic light scattering (DLS) measurements confirmed the stability of the coiled coils and showed that the thermosensitive phase behavior of the RLPs was preserved in the genetically fused hybrid polypeptides. Cryogenic‐transmission electron microscopy and coarse‐grained modeling revealed that functionalizing the coiled coils with thermoresponsive RLPs leads to their thermally triggered noncovalent assembly into nanofibrillar assemblies.
Bicyclo[1.1.1]pentane Embedded in Porphyrinoids**
Authors: Grover Nitika , Cheveau Maxime , Twamley Brendan , Kingsbury Christopher J. , Mattern Cornelia M. , Senge Mathias O.
Published: March 2023

We report a two‐step approach to obtain synthetically versatile bicyclo[1.1.1]pentane (BCP) derivatives using Grignard reagents. This method allows the incorporation of BCP units in tetrapyrrolic macrocycles and the synthesis of a new class of calix[4]pyrrole analogues by replacing two bridging methylene groups with two BCP units. In addition, a doubly N‐confused system was also formed in the presence of electron‐withdrawing substituents at the BCP bridgeheads. The pyrrole rings in BCP containing macrocycles exist in 1,3‐alternate or αβαβ conformations, as observed from single‐crystal X‐ray diffraction analyses and 2D NMR spectroscopy.
Solid‐State Luminescence Stimulus‐Responsive Property and Doped RTP Emission of Novel 7a,8,10,11‐Tetrahydro‐9H‐ pyrido[2′,1′:2,3][1,3]oxazino[6,5,4‐ij]isoquinoline Derivative
Authors: Wang Yuzhe , Liu Miaochang , Zhang Weijing , Lei Yunxiang , Zhou Yunbing , Gao Wenxia , Ding Qiuping , Wu Huayue , Huang Xiaobo
Published: March 2023

A novel 7a,8,10,11‐tetrahydro‐9H‐pyrido[2′,1′:2,3][1,3]‐oxazino[6,5,4‐ij]isoquinoline derivative (POIQ) is accidentally obtained from an isoquinoline derivative and iodine in dimethyl sulfoxide, which is demonstrated to undergo a mechanism of demethylation and thus intramolecular nucleophilic substitution. POIQ with twisted molecular conformation and loose stacking arrangement shows multifunctional optical properties including dual‐state emission, mechanochromic, and solid‐state acidochromic activities. Furthermore, an organic room temperature phosphorescence (RTP) doped system with green afterglow of 2 s is constructed using POIQ as the guest and easily available phenyl benzoate as the host, in which the host molecules assist in the transfer of the triplet excitons of the guest molecules. Rewritable optical recording media and information encryption are also realized based on multifunctional optical properties of this compound. This work provides inspiration for the development of N,O‐containing fused‐ring compounds with fluorescence/RTP properties.
Two‐channel false data injection attacks on multi‐sensor remote state estimation
Authors: Hua Jinxing , Liu Ruirui , Hao Fei
Published: March 2023

This paper investigates a security problem in cyber‐physical systems (CPSs) under multisensory framework. In the considered system, the feedback and feed‐forward channels may suffer from false data injection (FDI) attacks. The attacker aims at disturbing the systems by modifying the sensors' measurements and injecting external control inputs while keep (
)‐stealthiness. Two types of multi‐sensor fusion Kalman filters, which are equivalent in the absence of attacks, are adopted by the remote state estimator. When the system is maliciously attacked, the necessary and sufficient condition is obtained to guarantee the equivalence of the sequential Kalman filter and data compression Kalman filter under two‐channel attacks. Moreover, suboptimal (
)‐stealthiness attack strategies for these Kalman filters are obtained by applying two‐stage optimization method, convex analysis and monotonic optimization techniques. Finally, simulations on a numerical example of a quadrotor are carried out to validate the feasibility of theoretical results.
A CHO stable pool production platform for rapid clinical development of trimeric SARS‐CoV‐2 spike subunit vaccine antigens
Authors: Joubert Simon , Stuible Matthew , Lord‐Dufour Simon , Lamoureux Linda , Vaillancourt François , Perret Sylvie , Ouimet Manon , Pelletier Alex , Bisson Louis , Mahimkar Rohan , Pham Phuong Lan , L′Ecuyer‐Coelho Helene , Roy Marjolaine , Voyer Robert , Baardsnes Jason , Sauvageau Janelle , St‐Michael Frank , Robotham Anna , Kelly John , Acel Andrea , Schrag Joseph D. , El Bakkouri Majida , Durocher Yves
Published: March 2023

Protein expression from stably transfected Chinese hamster ovary (CHO) clones is an established but time‐consuming method for manufacturing therapeutic recombinant proteins. The use of faster, alternative approaches, such as non‐clonal stable pools, has been restricted due to lower productivity and longstanding regulatory guidelines. Recently, the performance of stable pools has improved dramatically, making them a viable option for quickly producing drug substance for GLP‐toxicology and early‐phase clinical trials in scenarios such as pandemics that demand rapid production timelines. Compared to stable CHO clones which can take several months to generate and characterize, stable pool development can be completed in only a few weeks. Here, we compared the productivity and product quality of trimeric SARS‐CoV‐2 spike protein ectodomains produced from stable CHO pools or clones. Using a set of biophysical and biochemical assays we show that product quality is very similar and that CHO pools demonstrate sufficient productivity to generate vaccine candidates for early clinical trials. Based on these data, we propose that regulatory guidelines should be updated to permit production of early clinical trial material from CHO pools to enable more rapid and cost‐effective clinical evaluation of potentially life‐saving vaccines.
Thirteen‐year trends in risk scores predictive values for subsequent stroke in patients with acute ischemic event
Authors: Xiong Yunyun , Wang Shang , Li Zixiao , Fisher Marc , Wang Liyuan , Jiang Yong , Huang Xinying , Zhao Xing‐Quan , Meng Xia , Wang Yongjun
Published: March 2023

Introduction

A high residual risk of subsequent stroke suggested that the predictive ability of Stroke Prognosis Instrument‐II (SPI‐II) and Essen Stroke Risk Score (ESRS) may have changed over the years.

Aim

To explore the predictive values of the SPI‐II and ESRS for 1‐year subsequent stroke risk in a pooled analysis of three consecutive national cohorts in China over 13 years.

Results

In the China National Stroke Registries (CNSRs), 10.7% (5297/50,374) of the patients had a subsequent stroke within 1 year; area under the curve (AUC) of SPI‐II and ESRS was .60 (95% confidence interval [CI]: .59–.61) and .58 (95% CI: .57–.59), respectively. For SPI‐II, the AUC was .60 (95% CI: .59–.62) in CNSR‐I, .60 (95% CI: .59–.62) in CNSR‐II, and .58 (95% CI: .56–.59) in CNSR‐III over the past 13 years. The declining trend was also found in ESRS scale (CNSR‐I: .60 [95% CI: .59–.61]; CNSR‐II: .60 [95% CI: .59–.62]; and CNSR‐III: .56 [95% CI: .55–.58]).

Conclusions

The predictive power of the traditional risk scores SPI‐II and ESRS was limited and gradually decreased over the past 13 years, thus the scales may not be useful for current clinical practice. Further derivation of risk scales with additional imaging features and biomarkers may be warranted.
Structural alterations of the salience network in patients with insular glioma
Authors: Hu Guanjie , Wu Zhiqiang , Cao Bowen , Shi Qinyu , Zhang Zifeng , Fan Xiao , Tang Yao , Cheng Zhangchun , Wang Xiefeng , Jing Shenqi , Li Tao , Zhang Junxia , You Yongping
Published: March 2023

Objective

The structural alteration that occurs within the salience network (SN) in patients with insular glioma is unclear. Therefore, we aimed to investigate the changes in the topological network and brain structure alterations within the SN in patients with insular glioma.

Methods

We enrolled 46 patients with left insular glioma, 39 patients with right insular glioma, and 21 demographically matched healthy controls (HCs). We compared the topological network, gray matter (GM) volume, and fractional anisotropy (FA) between HCs and patients after controlling for the effects of age and gender.

Results

Patients with insular glioma showed topological network decline mainly in the insula, basal ganglia region, and anterior cingulate cortex (ACC). Compared with HCs, patients primarily showed GM volume increased in the ACC, inferior temporal gyrus (ITG), superior temporal gyrus (STG), temporal pole: middle temporal gyrus (TPOmid), insula, middle temporal gyrus (MTG), middle frontal gyrus, and superior occipital gyrus (SOG), but decreased in TPOmid, ITG, temporal pole: superior temporal gyrus, and SOG. FA declined mainly in the STG, MTG, ACC, superior frontal gyrus, and SOG, and also showed an increased cluster in SOG.

Conclusions

FA represents the integrity of the white matter. In patients with insular glioma, decreased FA may lead to the destruction of the topological network within the SN, which in turn may lead to the decrease of network efficiency and brain function, and the increase of GM volume may compensate for these changes. Overall, this pattern of structural changes provides new insight into the compensation model of insular glioma.
JNK‐IN‐8 treatment improves ARDS‐induced cognitive impairment by inhibiting JNK/NF‐κB‐mediated NLRP3 inflammasome
Authors: Shi Yunchao , Fang Ying , Shen Peng , Liu He , Xu Longsheng , Wang Liyan , Yang Maoxian
Published: March 2023

Purpose

Cognitive impairment is a critical complication of acute respiratory distress syndrome (ARDS). However, effective interventions are lacking. Growing evidence demonstrates that c‐Jun N‐terminal kinase (JNK)‐mediated neuroinflammation is involved in the development of ARDS. Therefore, we hypothesized that the JNK pathway is involved in ARDS‐induced cognitive impairment.

Methods

An in vivo rat model of ARDS was established by treating it with lipopolysaccharide. The cognitive function was assessed by behavioral tests. The levels of pro‐inflammatory cytokines, JNK and NOD‐, LRR‐, and pyrin domain‐containing protein 3 (NLRP3) were analyzed by enzyme‐linked immunosorbent assay, western blot, or immunohistochemical analysis.

Results

We found that JNK inhibitor 8 (JNK‐IN‐8) alleviated cognitive impairment, neuroinflammation, and NLRP3 inflammasome activation in the ARDS rat model. Additionally, an in vivo study showed that the protective effect of JNK‐IN‐8 on cognitive impairment was blocked by nigericin, an NLRP3 activator.

Conclusions

Our data suggest that JNK‐IN‐8 treatment improves ARDS‐induced cognitive impairment by inhibiting the JNK/nuclear factor‐κB‐mediated NLRP3 inflammasome.
How Does Brazilian Green Propolis Act in Normal and Tumor Cells? Identification of Compounds in or out Monocytes or HEp‐2 Cells
Authors: Farlow Anthony , José Crevelin Eduardo , Basso Santiago Karina , de Oliveira Cardoso Eliza , Matsumoto da Silva Livia , Kenupp Bastos Jairo , Maurício Sforcin José
Published: March 2023

The aim of this study was to identify propolis compounds after incubation of normal and tumor cells (monocytes and HEp‐2 cells, respectively) with Brazilian green propolis, in the lysate and supernatant of cell cultures and within these cells by gas chromatography‐mass spectrometry (GC/MS). Cinnamic acid derivatives were generally localized in the lysate of both cell lines after incubation, suggesting these compounds are actively transported across the membrane into the cytoplasm. Terpenes were also found in the lysate. Artepillin C, in contrast, was localised only in the supernatant. Some constituents were unobservable after incubation, especially in monocytes, suggesting the compounds had been degraded. Our findings shed light on the possible sites of action (intracellular or via a cell membrane protein) and the bioavailability of various constituents of propolis, as well as possible modes of delivery of bioactive constituents.
Deconstructing the Potency and Cell‐Line Selectivity of Membranolytic Anticancer Peptides**
Authors: Martinez‐Hernandez Cristina , del Carmen Aguilera‐Puga Mariana , Plisson Fabien
Published: March 2023

Current cancer treatments damage healthy cells and tissues, causing short‐term and long‐term side effects. New treatments are desired that show greater selectivity toward cancer cells and evade the common mechanisms of multidrug resistance. Membranolytic anticancer peptides (mACPs) hold promise against cancer and multidrug resistance. Amphipathicity, hydrophobicity, and net charge of mACPs participate in their respective interactions with cell membranes and their overall inhibition of cancer cells. To support the design of cell‐line selective mACPs, we investigated the relationships that amino acid composition, physicochemical properties, sequence motifs, and sequence homology could have with their potency and selectivity towards several healthy and cancer cell lines. Sequence length and net charge are known to affect the selectivity of mACPs between cancer and healthy cell lines. Our study reveals that increasing the net charge or flexibility (i. e., small and aliphatic residues) influences their selectivity between cancer cell lines with comparable lipid compositions.
Bufalin induces apoptosis and autophagy via the Ca2+/CaMKKβ/AMPK/Beclin1 signaling pathway in osteosarcoma cells
Authors: Zheng Ya‐Dong , He Zhen , Su Zhu‐Cheng , Wang Hui , Jiang Xiao‐Hong , Fang Xu , Lu Sheng‐Lin , Li Yuan
Published: March 2023

Bufalin, a major cardiotonic compound of the traditional Chinese medicine Chanshu has been used for cancer treatment for several years. However, the molecular mechanisms of Bufalin‐induced autophagy in osteosarcoma (OS) is not fully understood. In the present study, it was shown that Bufalin induced crosstalk between apoptosis and autophagy, which resulted in OS cell death. Mechanistically, Bufalin induced autophagy by increased the ratio of microtubule‐associated protein 1A/1B‐light chain 3 (LC3)‐II/LC3‐I, and inducing apoptosis via the caspase‐dependent pathway. Inhibition of autophagy promoted Bufalin‐induced cell death. In contrast, suppression of apoptosis enhanced Bufalin‐induced autophagy. In addition, it was found that Bufalin activated the Ca2+/calmodulin‐dependent protein kinase β/AMPK/Beclin1 pathway, which resulted in induction of autophagy. These findings provide a mechanistic understanding of the means by which Bufalin mediates autophagy and apoptosis in OS cells.
Selective, Aerobic Oxidation of Methane to Formaldehyde over Platinum ‐ a Perspective
Authors: van Steen Eric , Guo Junfeng , Hytoolakhan Lal Mahomed Nasseela , Leteba Gerard M. , Mahlaba Sinqobile V. L.
Published: March 2023

The direct formation of formaldehyde in the selective, aerobic oxidation of methane in the presence of liquid water at ca. 498 K has recently been described. One of the intriguing observations in the aerobic oxidation of methane over platinum in the presence of water is the absence of the typically observed negative selectivity‐conversion dependency (up to a methane conversion of 1 %). In this perspective, the main differences between this route and other methods for the selective oxidation of methane are being described. Possible reaction pathways for the formation of formaldehyde are discussed. Further developments for this newly developed methane activation route are highlighted.
Differential Evolution‐Based Optimization in Dimethyl Oxalate Hydrogenation
Authors: Rohman Fakhrony Sholahudin , Muhammad Dinie , Zahan Khairul Azly , Aziz Norashid , Murat Muhamad Nazri
Published: March 2023

Multi‐objective optimization of dimethyl oxalate (DMO) hydrogenation to produce ethylene glycol (EG) is performed for three problems with four different objectives: maximization of DMO conversion and minimization of energy cost for problem 1; maximization of productivity and minimization of energy cost for problem 2; maximization of productivity and minimization of side product for problem 3; minimization of bare module and energy cost for problem 4; maximization of productivity and minimization of bare module for problem 5, and maximization of productivity and minimization of bare module and energy cost for problem 6. Multi‐objective differential evolution with ranking‐based mutation operator is applied to tackle the optimization problem with ASPEN simulator as model‐based optimization for EG production. The plots of decision variables denote that the optimal solution is strongly dependent on temperature.
Trumpet‐Like ZnS@C Composite for High‐Performance Potassium Ion Battery Anode
Authors: Gan Yunfei , Mu Meiqi , Li Mingquan , Ma Xiangdong , Yuan Jujun , He Haishan , Li Xiaokang , Mou Jirong , Zhang Chao , Zhang Xianke , Liu Jun
Published: March 2023

ZnS has acquired increasing attention for high‐performance PIBs anode because of its remarkable theoretical capacity, and redox reversibility for conversion reaction. However, the larger volume variation and delayed reaction kinetics for the ZnS in the discharge/charge processes lead to pulverization and severe capacity degradation. Herein, the trumpet‐like ZnS@C composite was synthesized by template method by using sodium citrate as carbon source followed by vulcanization process. As potassium ion batteries (PIB) anode, ZnS@C composite exhibits good rate performance and long life (stable reversible capacity of 107.8 mAh/g over 2000 charge‐discharge cycles at 5 A/g and high reversible capacity of 310 mAh/g at 0.1 A/g). The outstanding electrochemical performance of the ZnS@C composite is ascribed to its unique structure, which can mitigate the volume expansion of ZnS in the charge discharge process, expand the contact area between the electrode and electrolyte, and improve the conductivity of electrode materials by the introduction of carbon layer. This method of synthesizing trumpet‐like ZnS@C composite provides an important strategy for obtaining potassium ion batteries anode with long cycle.
Redox Reporter ‐ Ligand Competition to Support Signaling in the Cocaine‐Binding Electrochemical Aptamer‐Based Biosensor
Authors: Dauphin‐Ducharme Philippe , Churcher Zachary R. , Shoara Aron A. , Rahbarimehr Erfan , Slavkovic Sladjana , Fontaine Nicolas , Boisvert Olivia , Johnson Philip E.
Published: March 2023

Electrochemical aptamer‐based (E‐AB) biosensors have demonstrated capabilities in monitoring molecules directly in undiluted complex matrices and in the body with the hopes of addressing personalized medicine challenges. This sensing platform relies on an electrode‐bound, redox‐reporter‐modified aptamer. The electrochemical signal is thought to originate from the aptamer undergoing a binding‐induced conformational change capable of moving the redox reporter closer to the electrode surface. While this is the generally accepted mechanism, it is notable that there is limited evidence demonstrating conformational change or distance‐dependent change in electron transfer rates in E‐AB sensors. In response, we investigate here the signal transduction of the well‐studied cocaine‐binding aptamer with different analytical methods and found that this sensor relies on a redox‐reporter ‐ ligand competition mechanism rather than a ligand‐induced structure formation mechanism. Our results show that the covalently bound redox reporter, methylene blue, binds at or near the ligand binding site on the aptamer resulting in a folded conformation of the cocaine‐binding aptamer. Addition of ligand then competes with the redox reporter for binding, altering its electron transfer rate. While we show this for the cocaine‐binding aptamer, given the prevalence of methylene blue in E‐AB sensors, a similar competition‐based may occur in other systems.
Calculating porosity and permeability from synthetic micro‐CT scan images based on a hybrid artificial intelligence
Authors: Mohyeddini Amir , Rasaei Mohammad Reza
Published: March 2023

Nowadays, lattice Boltzmann is one of the standard and exact methods of simulation in micro‐CT images of rock. However, it has a high weakness in run time. Therefore, the effort in this article is to reach a comprehensive substitute method for permeability calculation with less run time than the lattice Boltzmann method. The other purposes are the automation of processing operations, preparation of images, and in the end, the calculation of porosity. The best way to achieve these outcomes is to use hybrid artificial intelligence. In this research work, comprehensive model architecture has been used to design a hybrid artificial intelligence to be able to calculate permeability and porosity in complex images. A thousand images were randomly generated with high complexity, which makes the model comprehensive and extensible, and image processing was applied. After that, the lattice Boltzmann method as the direct simulation was selected. Finally, the convolutional neural network and multilayer perceptron based on a new and comprehensive model were evaluated for the first time; the mean squared error resulting from the evaluation of training data is 0.01, and the test data is 0.03. Expert systems have been used as a subset of artificial intelligence for automated image processing and porosity calculation. In this way, problems related to the direct implementation of classical algorithms for image processing, models, and patterns related to machine learning and needing an expert were solved to an acceptable extent, and an error of less than 5% was achieved.
The impact of antihypertensive treatment of mild to moderate hypertension during pregnancy on maternal and neonatal outcomes: An updated meta‐analysis of randomized controlled trials
Authors: Attar Armin , Hosseinpour Alireza , Moghadami Mana
Published: March 2023

Currently, there is controversy regarding the treatment of pregnant patients with mild hypertension (blood pressure 140–159/90–109 mm Hg). While guidelines do not recommend this treatment, results from recent clinical trials are supportive of the treatment. This meta‐analysis aimed to clarify if active treatment of mild hypertension during pregnancy results in better maternal and fetal outcomes. All of the potentially eligible randomized controlled trials were retrieved through a systematic database search investigating the impact of pharmacological treatment in mild hypertensive patients on maternal, fetal, and neonatal outcomes. Relative risk (RR) and 95% confidence interval (CI) were calculated using a random‐effects model. Data from 12 trials comprising 4461 pregnant women diagnosed with mild to moderate hypertension (2395 in the intervention group and 2066 in the control group) were extracted for quantitative synthesis. Antihypertensive treatment was associated with better outcomes in seven out of the 19 analyzed outcomes: Severe hypertension (RR = 0.53; 95% CI = [0.38;0.75]), preeclampsia (RR = 0.71; 95% CI = [0.54; 0.93]), placental abruption (RR = 0.48; 95% CI = [0.26; 0.87]), changes in electrocardiogram (RR = 0.43; 95% CI = [0.25; 0.72]), renal impairment (RR = 0.42; 95% CI = [0.34; 0.51]), pulmonary edema (RR = 0.46; 95% CI = [0.25; 0.84]), and neonatal mortality (RR = 0.72; 95% CI = [0.57; 0.92]). The primary safety outcome of small for gestational age was not different between the treatment group and the control group (RR = 1.12; 95% CI = [0.80; 1.57]). The results of this meta‐analysis are in favor of the beneficial impact of pharmacological treatment of mild hypertension on both maternal and neonatal outcomes and without significant adverse events for the fetus.
A real‐world data analysis of predictors of early mortality after a diagnosis of multiple myeloma
Authors: Grant Shakira J. , Wildes Tanya M. , Rosko Ashley E. , Silberstein Juliet , Giri Smith
Published: March 2023

Background

Despite the increased availability and use of novel therapies for multiple myeloma, early mortality is a pervasive challenge with a significant impact on older adults. Reported rates and predictors of early mortality have varied in the literature, with most studies seldom focusing on community‐treated patients.

Methods

In this retrospective cohort analysis of a real‐world electronic health record–derived deidentified database of 7512 patients newly diagnosed with multiple myeloma between January 1, 2011, and February 2, 2021, and treated primarily in US‐based community oncology practices, factors associated with early mortality (defined as death within 6 months after the multiple myeloma diagnosis) were examined with the use of binary logistic regression.

Results

The median age was 70 years overall. We found an overall early mortality rate of 8.3%, with 73% of early deaths occurring in those aged ≥70 years. Among the early deaths, only 49 patients (8.7%) had documented disease progression before death (median time to progression, 30 days [interquartile range, 7–53 days]). Baseline factors associated with higher odds of early mortality included an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2, Revised International Staging System (R‐ISS) stage III, an age ≥ 70 years, receipt of proteasome inhibitor–doublet therapy, a light‐chain isotype, and the presence of renal dysfunction (estimated glomerular filtration rate < 30 mL/min). Among those aged ≥70 years, ECOG PS ≥ 2 and R‐ISS stage III remained the strongest predictors of early mortality.

Conclusions

Early mortality disproportionately affects older adults (aged ≥70 years) with multiple myeloma. Interventions to support this population are needed to reduce disparate survival outcomes.

Plain language summary

Factors associated with an increased risk of dying within 6 months (early mortality) of a new diagnosis of multiple myeloma (MM) among 7512 mostly community‐treated patients with MM were evaluated.

The early mortality rate was 8.3%; among those deaths, 49 patients (8.7%) had documented evidence of MM progression before death.

The risk of early mortality was greatest for older patients (aged ≥70 years) and those with a poor performance status, poor kidney function, a higher disease stage, and light‐chain MM and those receiving two‐drug MM therapies.

These findings highlight the need for supportive interventions geared toward older adults with MM.