bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly Efficient Synergistic Chemotherapy and Magnetic Resonance Imaging for Targeted Ovarian Cancer Therapy Using Hyaluronic Acid‐Coated Coordination Polymer Nanoparticles
Authors: Li Guang , Shi Shengying , Tan Jingxiu , He Lijuan , Liu Qiwen , Fang Feng , Fu Huijiao , Zhong Min , Mai Ziyi , Sun Rui , Liu Kun , Feng Zhenzhen , Liang Peiqin , Yu Zhiqiang , Wang Xuefeng
Published: September 2024

The diagnosis and treatment of ovarian cancer (OC) are still a grand challenge, more than 70% of patients are diagnosed at an advanced stage with a dismal prognosis. Magnetic resonance imaging (MRI) has shown superior results to other examinations in preoperative assessment, while cisplatin‐based chemotherapy is the first‐line treatment for OC. However, few previous studies have brought together the two rapidly expanding fields. Here a technique is presented using cisplatin prodrug (Pt‐COOH), Fe3+, and natural polyphenols (Gossypol) to construct the nanoparticles (HA@PFG NPs) that have a stable structure, controllable drug release behavior, and high drug loading capacity. The acidic pH values in tumor sites facilitate the release of Fe3+, Pt‐COOH, and Gossypol from HA@PFG NPs. Pt‐COOH with GSH consumption and cisplatin‐based chemotherapy plus Gossypol with pro‐apoptotic effects displays a synergistic effect for killing tumor cells. Furthermore, the release of Fe3+ at the tumor sites promotes ferroptosis and enables MRI imaging of OC. In the patient‐derived tumor xenograft (PDX) model, HA@PFG NPs alleviate the tumor activity. RNA sequencing analysis reveals that HA@PFG NPs ameliorate OC symptoms mainly through IL‐6 signal pathways. This work combines MRI imaging with cisplatin‐based chemotherapy, which holds great promise for OC diagnosis and synergistic therapy.
Revealing the Impact of Aging on Perovskite Solar Cells Employing Nickel Phthalocyanine‐Based Hole Transporting Material
Authors: Ans Muhammad , Biyiklioglu Zekeriya , Mahapatra Apurba , Chavan Rohit D. , Kruszyńska Joanna , Unal Muhittin , Fazlı Hilal , Nikiforow Kostiantyn , Yadav Pankaj , Akin Seckin , Güzel Emre , Prochowicz Daniel
Published: September 2024

The enhancement of the photovoltaic performance upon the aging process at particular environment is often observed in perovskite solar cells (PSCs), particularly for the devices with 2,2′,7,7′‐tetrakis(N,N‐di(4‐methoxyphenyl)amino)−9,9′‐spirobifluorene (spiro‐OMeTAD) as hole transporting material (HTM). In this work, for the first time the effect of aging the typical n‐i‐p PSCs employing nickel phthalocyanine (coded as Bis‐PF‐Ni) solely as dopant‐free HTM is investigated and as an additive in spiro‐OMeTAD solution. This study reveals that the prolong aging of these devices at dry air condition (RH = 2%, 25 °C) is beneficial for the improvement of their performances. Various bulk and surface characterization techniques are utilized to understand the factors behind the spontaneous efficiency enhancement of the devices after storage. As a result, the changes in properties of the Bis‐PF‐Ni layer are observed and at perovskite/Bis‐PF‐Ni interface, which ultimately improves the charge transport and reduces non‐radiative recombination. In addition, the devices with Bis‐PF‐Ni HTM reveal enhanced long‐term ambient and thermal stability compared to the PSCs based on doped spiro‐OMeTAD.
Trifunctional Graphene‐Sandwiched Heterojunction‐Embedded Layered Lattice Electrocatalyst for High Performance in Zn‐Air Battery‐Driven Water Splitting
Authors: Kim Dong Won , Kim Jihoon , Choi Jong Hui , Jung Do Hwan , Kang Jeung Ku
Published: September 2024

Zn‐air battery (ZAB)‐driven water splitting holds great promise as a next‐generation energy conversion technology, but its large overpotential, low activity, and poor stability for oxygen reduction reaction (ORR), oxygen evolution reaction (OER), and hydrogen evolution reaction (HER) remain obstacles. Here, a trifunctional graphene‐sandwiched, heterojunction‐embedded layered lattice (G‐SHELL) electrocatalyst offering a solution to these challenges are reported. Its hollow core‐layered shell morphology promotes ion transport to Co3S4 for OER and graphene‐sandwiched MoS2 for ORR/HER, while its heterojunction‐induced internal electric fields facilitate electron migration. The structural characteristics of G‐SHELL are thoroughly investigated using X‐ray absorption spectroscopy. Additionally, atomic‐resolution transmission electron microscopy (TEM) images align well with the DFT‐relaxed structures and simulated TEM images, further confirming its structure. It exhibits an approximately threefold smaller ORR charge transfer resistance than Pt/C, a lower OER overpotential and Tafel slope than RuO₂, and excellent HER overpotential and Tafel slope, while outlasting noble metals in terms of durability. Ex situ X‐ray photoelectron spectroscopy analysis under varying potentials by examining the peak shifts and ratios (Co2+/Co3+ and Mo4+/Mo6+) elucidates electrocatalytic reaction mechanisms. Furthermore, the ZAB with G‐SHELL outperforms Pt/C+RuO2 in terms of energy density (797 Wh kg−1) and peak power density (275.8 mW cm−2), realizing the ZAB‐driven water splitting.
Advanced Crosslinked Solid Polymer Electrolytes: Molecular Architecture, Strategies, and Future Perspectives
Authors: Zeng Xiaoyue , Liu Xuewei , Zhu Huirong , Zhu Jiaxing , Lan Jinle , Yu Yunhua , Lee Young‐Seak , Yang Xiaoping
Published: September 2024

Solid‐state batteries (SSBs) have attracted much attention for high‐energy‐density and high‐safety energy storage devices. Solid polymer electrolytes (SPEs) have emerged as a critical component in the advancement of SSBs, owing to the compelling advantages of strong molecular structure‐designability, low cost, easy manufacturing, and no liquid leakage. However, linear SPEs usually have low room‐temperature ionic conductivity due to crystallization, and melting at high temperature. Thus, crosslinked SPEs have been proposed in that the chemical bonding between internal molecule chains can maintain solid state to expand operational temperature, disrupt regularity of segment, and diminish crystalline degree, leading to an enhancement of room‐temperature ionic conductivity. Furthermore, the integration of functional groups within crosslinked SPE network can significantly augment the electrochemical performance of SPEs. Herein, according to the network structure, crosslinked SPEs are categorized into four types: simple network, AB crosslinked polymers (ABCP), semi‐interpenetrating network (semi‐IPN), and interpenetrating network (IPN), then the structure features and advantages and disadvantages of commonly used polymers for these types of crosslinked SPEs are reviewed. In addition, crosslinked SPEs with self‐healing, flame‐retardant, degradable, and recyclability are introduced. Finally, challenges and prospects of crosslinked SPEs are summarized, hoping to provide guidance for the molecular design of SPEs in the future.
Seven Novel Variants of Weiss‐Kruszka Syndrome and Phenotype Expansion
Authors: Hau Anna , Baxter Anne , Chandler Kate , Fennell Andrew , Hsieh Tzung‐Chien , Krawitz Peter M. , Pinner Jason , Goel Himanshu
Published: September 2024

Weiss‐Kruszka syndrome (WKS) is a rare genetic disorder characterized by metopic ridging, ptosis, arched eyebrows, down slanting palpebral fissures, abnormalities in the corpus callosum, cardiac malformations, and variable neurodevelopmental delay. To date, 32 individuals with a diagnosis of WKS have been reported in the literature. The syndrome is caused by a heterozygous pathogenic variant in the ZNF462 gene or a deletion of the 9p31.2 region involving ZNF462. There is significant phenotypic heterogeneity and intrafamilial variability among these patients. Our study reviewed nine patients from seven unrelated families and identified seven novel heterozygous ZNF462 variants through exome sequencing. GestaltMatcher analysis of our cohort's facial images, alongside previously published images of ZNF462 patients, demonstrated a high degree of facial similarity. Further longitudinal research is needed to delineate this rare condition's long‐term health implications and adult‐onset features.
Rhodium(III)‐Catalyzed (5+2) Annulation Reaction for the Synthesis of Nitro and Cyano Substituted Benzo[b]Oxepines
Authors: Kalita Deep J. , Bhorali Pratiksha , Khundrakpam Supriya , Gogoi Sanjib
Published: September 2024

A Rh(III)‐catalyzed annulation reaction of 2‐(2‐nitrovinyl)phenols and disubstituted alkynes is developed to complete the first synthesis of biologically important 4‐nitro substituted benzo[b]oxepines. The same reaction conditions are also applied for the efficient synthesis of 4‐cyano substituted benzo[b]oxepines which have high biological significance. Some of the synthesized 4‐nitrobenzo[b]oxepines are easily transformed to triazole fused dibenzo[b]oxepines.
Stone toolmaking energy expenditure differs between novice and expert toolmakers
Authors: Pargeter Justin , Cebeiro Adela , Levy Stephanie B.
Published: September 2024

Objectives

This study investigates the energetic costs associated with Oldowan‐style flake production and how skill differences influence these costs.

Materials and Methods

Nine adult participants, including novice and expert toolmakers, underwent a 2‐h experimental session where we measured energy expenditure and flaking outcomes. We measured body mass (kg), percent body fat, and fat‐free mass (kg) and used open‐circuit indirect calorimetry to quantify energy expenditure. The lithic analysis used standard linear and mass measurements on the resulting cores and flakes. Qualitative observations from the video recordings provide insight into the subject's body positions and hand grips.

Results

Results reveal significant differences in energy expenditure between novice and expert toolmakers, with experts demonstrating lower overall energy expenditure. Additionally, experts produced more flakes, reduced greater core mass per unit of energy expenditure, and exhibited distinct body positions, hand grips, and core/flake morphologies compared with novices.

Discussion

The study provides novel insights into the bio‐cultural impacts of stone toolmaking skill acquisition, suggesting that skilled performance reduces the metabolic costs of stone tool production. These findings contribute to debates surrounding the origins of human cultural capacities and highlight the importance of including energy expenditure measures in knapping experiments. Moreover, the results suggest that the presence or absence of expertise in the Paleolithic would have fundamentally altered selective pressures and the reliability of skill reproduction. This study enhances our understanding of differences in stone toolmaking skill and their implications for human energy allocation strategies during early technological evolution.
Pilot implementation of the revised criteria for staging of Alzheimer's disease by the Alzheimer's Association Workgroup in a tertiary memory clinic
Authors: Lu Jiaying , Wang Jing , Wu Jie , Zhang Huiwei , Ma Xiaoxi , Zhu Yuhua , Wang Jie , Yang Yunhao , Xiao Zhenxu , Li Ming , Zhou Xiaowen , Ju Zizhao , Xu Qian , Ge Jingjie , Ding Ding , Yen Tzu‐Chen , Zuo Chuantao , Guan Yihui , Zhao Qianhua ,   the Shanghai Memory Study (SMS)
Published: September 2024

INTRODUCTION

We aimed to evaluate the feasibility of the 2024 Alzheimer's Association Workgroup's integrated clinical‐biological staging scheme in outpatient settings within a tertiary memory clinic.

METHODS

The 2018 syndromal cognitive staging system, coupled with a binary biomarker classification, was implemented for 236 outpatients with cognitive concerns. The 2024 numeric clinical staging framework, incorporating biomarker staging, was specifically applied to 154 individuals within the Alzheimer's disease (AD) continuum.

RESULTS

The 2024 staging scheme accurately classified 95.5% AD. Among these, 56.5% exhibited concordant clinical and biological stages (canonical), 34.7% demonstrated more advanced clinical stages than biologically expected (susceptible), and 8.8% displayed the inverse pattern (resilient). The susceptible group was characterized by a higher burden of neurodegeneration and inflammation than anticipated from tau, whereas the resilient group showed the opposite.

DISCUSSION

The 2024 staging scheme is generally feasible. A discrepancy between clinical and biological stages is relatively frequent among symptomatic patients with AD.

Highlights

The 2024 AA staging scheme is generally feasible in a tertiary memory clinic.

A discrepancy between clinical and biological stages is relatively frequent in AD.

The mismatch may be influenced by a non‐specific pathological process involved in AD.

Individual profiles like aging and lifestyles may contribute to such a mismatch.

Matched and mismatched cases converge toward similar clinical outcomes.
Electrochemical identification and quantification of through‐plane proton channels in graphene oxide membranes
Authors: Wang Yiqing , Eigler Siegfried
Published: September 2024

Stacked graphene oxide (GO) proton membranes are promising candidates for use in energy devices due to their proton conductivity. Identification of through‐plane channels in these membranes is critical but challenging due to their anisotropic nature. Here, we present an electrochemical reduction method for identifying and quantifying through‐plane proton channels in GO membranes. The simplicity lies in the operando optical observation of the change in contrast as GO is electrochemically reduced. Here, we find three proton‐dominated three‐phase interfaces, which are critical for the reduction reactions of GO membranes. Based on these findings, a method is proposed to identify and quantify through‐plane channels in stacked GO proton membranes using a simple three‐electrode device in combination with real‐time imaging of the membrane surface.
Molecular imprinting based sensor system developed using polymeric nanoparticles for detecting 17β‐estradiol in agricultural wastewater
Authors: Yaşar Esra , Özçelik Hilal , Güner Timuçin , Dokuzparmak Emre , Akgöl Sinan
Published: September 2024

Micro pollutants pose a significant issue in water ecosystems. Particularly high concentrations of 17β‐estradiol (E2) have been identified in agricultural wastewater, which poses harmful effects on aquatic organisms and disrupts ecosystem balance. Therefore, effective determination of E2 from water sources is crucial. This study developed a biosensor capable of detecting E2 in wastewater using specific polymer nanoparticle synthesis through molecular imprinting. Est‐imp‐poly(multi‐walled carbon nanotubes‐glycidyl methacrylate [MWCNT‐GMA]) polymer nanoparticles were synthesized using a surfactant‐free emulsion polymerization method, and their characterization was conducted using FTIR and scanning electron microscopy (SEM) technologies. The Qmax value for Est‐imp‐poly(MWCNT‐GMA) nanoparticles in a 1 mg/mL E2 solution was determined to be 140 ppm. Comparing adsorption capacities, the molecularly imprinted nanoparticles (MIP) showed nearly five times higher E2 adsorption compared to non‐imprinted polymers (NIP). The Est‐imp‐poly(MWCNT‐GMA)‐Nafion/screen‐printed electrode (SPE) system was employed for analyzing wastewater samples. The current measurements taken at various concentrations in the wastewater consistently matched the E2 concentration calibration curve. The limit of detection (LoD) and limit of quantification (LoQ) were determined to be 0.042 and 0.12 μM, respectively. The biosensor demonstrated a linear working range from 0.12 to 50 μM, with a high correlation coefficient (R2 = 0.9927). These results highlight the potential of the developed biosensor for detecting E2 in real samples.
Tailoring N, N, N‐trimethyl chitosan nanospheres as an efficient drug carrier to overcome endothelial barrier
Authors: Lu Chao , Tang Howyn , Ouyang Jianying , Zhang Jin
Published: September 2024

Endothelial barriers, integral components of tissue barriers, are densely packed with adherens junction and tight junction proteins, hindering the passage of drugs to target sites. Herein, a novel nanosphere comprising N, N, N‐trimethylated chitosan (TMC), with the size of 51 ± 8 nm and zeta potential of 13.2 ± 5.3 mV, has been engineered as a drug carrier to facilitate the transport of hydrophobic drugs, that is, curcumin, across endothelial barriers efficiently. The effects of pH value and temperature on the release kinetics of curcumin from TMC nanospheres have been studied. In addition, the transportation of TMC nanospheres across an in vitro endothelial barrier was evaluated over a 72‐h period. The integrity of the in vitro endothelial barrier was assessed before and after the transport of TMC nanospheres by using transepithelial electrical resistance measurements and immunofluorescence staining of tight junction proteins. The results reveal that TMC nanospheres significantly enhance the transport of curcumin across the endothelial barrier, with approximately 30% of curcumin released as compared to less than 3.3% across the barrier without the assistance of TMC nanospheres. This investigation underscores the potential of small‐sized TMC nanospheres to enhance the transport of hydrophobic drugs across endothelial barriers.
Constituent compatibility and physical properties of bio‐based EUG/EPDM blends
Authors: Yang Yunyi , Chen Shang , Li Youji , Yang Zhaoxia , Han Zhangying , Xia Haiqin , Shang Jiawei , Shao Yunzhe
Published: September 2024

Eucommia ulmoides gum (EUG)/ethylene propylene diene monomer (EPDM) blends were prepared using EUG with high and low molecular weight, respectively, and their physical properties and constituents compatibility were investigated. The blend exhibited superior physical properties and constituents compatibility when EUG with high molecular weight occupied 10 wt%. When its content increased further, the physical properties deteriorated gradually，the results of SEM, DSC, and DMA diagrams indicated poorer constituents compatibility. The blends prepared from EUG with low molecular weight can achieve better compatibility in a comprehensive range of blending ratio. When the EUG content was 20 wt%, the maximum tensile strength of the blend was observed, which was 49.9% higher than that of pure EPDM, its rebound resilience ascended by 5%, and the wear resistance remained nearly unchanged.
Automated Detection of Hillforts in Remote Sensing Imagery With Deep Multimodal Segmentation
Authors: Canedo Daniel , Fonte João , Dias Rita , do Pereiro Tiago , Gonçalves‐Seco Luís , Vázquez Marta , Georgieva Petia , Neves António J. R.
Published: September 2024

Recent advancements in remote sensing and artificial intelligence can potentially revolutionize the automated detection of archaeological sites. However, the challenging task of interpreting remote sensing imagery combined with the intricate shapes of archaeological sites can hinder the performance of computer vision systems. This work presents a computer vision system trained for efficient hillfort detection in remote sensing imagery. Equipped with an adapted multimodal semantic segmentation model, the system integrates LiDAR‐derived LRM images and aerial orthoimages for feature fusion, generating a binary mask pinpointing detected hillforts. Post‐processing includes margin and area filters to remove edge inferences and smaller anomalies. The resulting inferences are subjected to hard positive and negative mining, where expert archaeologists classify them to populate the training data with new samples for retraining the segmentation model. As the computer vision system is far more likely to encounter background images during its search, the training data are intentionally biased towards negative examples. This approach aims to reduce the number of false positives, typically seen when applying machine learning solutions to remote sensing imagery. Northwest Iberia experiments witnessed a drastic reduction in false positives, from 5678 to 40 after a single hard positive and negative mining iteration, yielding a 99.3% reduction, with a resulting F1 score of 66%. In England experiments, the system achieved a 59% F1 score when fine‐tuned and deployed countrywide. Its scalability to diverse archaeological sites is demonstrated by successfully detecting hillforts and other types of enclosures despite their typical complex and varied shapes. Future work will explore archaeological predictive modelling to identify regions with higher archaeological potential to focus the search, addressing processing time challenges.
Drug Binding and Delivery with Supramolecular System Based on Sodium Carboxymethylcellulose and Viologen Calix[4]resorcinol
Authors: Razuvayeva Yuliya , Kashapov Ruslan , Ziganshina Albina , Salnikov Vadim , Sapunova Anastasiia , Voloshina Alexandra , Zakharova Lucia
Published: September 2024

In the present work, a simple supramolecular approach was used to spontaneously form nanoparticles from sodium carboxymethylcellulose and viologen calix[4]resorcinol as a result of joint self‐assembly in water at room temperature. Supramolecular interactions between them led to the formation of nanoparticles, the morphology and properties of which depend on polymer/macrocycle ratio. When there is excess of macrocycle, the nanoparticles bind lipophilic oleic acid, and when there is excess of polymer, they bind hydrophilic doxorubicin. Interestingly, the solubilization of lipophilic quercetin into these nanoparticles was significantly increased compared to the pure polymer and macrocycle, regardless of their ratio. The nanoparticles of triple composition (polymer/macrocycle/drug) have a more effective penetration ability in tumorcells than those of double composition (polymer/drug). The presented results are the first step towards the creation of new nanotechnologies to improve the bioavailability and delivery of bioactive components.
Regional Shopping Objectives in British Grocery Retail Transactions Using Segmented Topic Models
Authors: Vega Carrasco Mariflor , Musolesi Mirco , O'Sullivan Jason , Prior Rosie , Manolopoulou Ioanna
Published: September 2024

Understanding the customer behaviours behind transactional data has high commercial value in the grocery retail industry. Customers generate millions of transactions every day, choosing and buying products to satisfy specific shopping needs. Product availability may vary geographically due to local demand and local supply, thus driving the importance of analysing transactions within their corresponding store and regional context. Topic models provide a powerful tool in the analysis of transactional data, identifying topics that display frequently‐bought‐together products and summarising transactions as mixtures of topics. We use the segmented topic model (STM) to capture customer behaviours that are nested within stores. STM not only provides topics and transaction summaries but also topical summaries at the store level that can be used to identify regional topics. We summarise the posterior distribution of STM by post‐processing multiple posterior samples and selecting semantic modes represented as recurrent topics, and employ Gaussian process regression to model topic prevalence across British territory while accounting for spatial autocorrelation. We implement our methods on a dataset of transactional data from a major UK grocery retailer and demonstrate that shopping behaviours may vary regionally and nearby stores tend to exhibit similar regional demand.
Integrating biochar production in biorefineries: towards a sustainable future and circular economy
Authors: Chettri Dixita , Boro Deepjyoti , Chirania Manisha , Verma Anil Kumar
Published: September 2024

Biochar, a carbon‐rich material derived from organic biomass under low‐O2 conditions, has gained importance due to its role in mitigating climate change by sequestering carbon. It can be used as an alternative energy source and has applications in nutrient cycling, improving soil properties, and removing heavy metals and organic pollutants, thus contributing to sustainable agriculture and environmental remediation. In the face of alarming climate change, rising energy demand, and increasing pollution, the integration of biochar production into biorefineries is an important strategy to promote a sustainable and circular economy. Adopting a holistic approach to biomass utilization by developing strategies to maximize biochar production along with the production of other value‐added products while improving its quality can increase biorefineries' overall sustainability and efficiency. Fine‐tuning the biorefinery process from feedstock selection to co‐production, optimizing pyrolysis conditions, and integrating it with other technologies can help to achieve this goal while generating zero waste and diversified revenues. With the biochar market growing exponentially, further research into the long‐term impact of biochar on carbon sequestration and its application in the environment is the next step.
Catalytic evaluation of eggshell‐based calcium methoxide over Al2O3 for biodiesel generation from waste cooking oil
Authors: Camacho‐Valencia Fernando , Vázquez‐Rodríguez Gabriela , Tavizón‐Pozos J. Andrés
Published: September 2024

Shell‐derived materials are promising heterogeneous catalysts for biodiesel production due to their nontoxic and renewable nature, but they have the disadvantage of being highly leachable. To overcome this issue, Ca(OCH3)2 formed through the reaction of CaO with methanol, and supported in turn on Al2O3 is proposed as a catalytic system for the transesterification of fresh soybean oil and waste cooking oil (WCO). First, catalysts with several Al/Ca molar ratios (0.2, 0.5, and 0.8‐AC), as well as their precursors (CaO and Al2O3) alone, were tested at 60 °C, catalyst loading 6% wt, methanol‐to‐oil molar ratio (MOR) 10, for 1 h for fresh oil, and 3 h for WCO. The 0.2‐AC catalyst generated the highest biodiesel yield for both oils. The optimum operating conditions for WCO transesterification, determined by using a univariable approach, were 60 °C, 9 wt% catalyst loading, MOR of 12.5, and a reaction time of 3 h. These improved conditions led to yields higher than 90% for pure CaO and the 0.2, 0.5, and 0.8‐AC catalysts. The density, kinematic viscosity, and refractive index of the biodiesel obtained were measured.
Stock market reaction to mandatory sustainability reporting: Does carbon‐intensity and environmental, social, and governance reputation matter?
Authors: Pandey Dharen Kumar , Al‐ahdal Waleed M. , Hashim Hafiza Aishah
Published: September 2024

With a sample of 679 listed firms, integrating the event study method and cross‐sectional analysis, we examine the stock market reaction to mandatory sustainability reporting regulation in India. We find that (1) on average, investors react positively to such announcements; (2) the impact varies across different sectors; (3) affected and unaffected firms do not posit significant differences; (4) carbon‐intensive firms are positively impacted; and (5) high environmental, social, and governance (ESG) performance is negatively associated with the event‐induced cumulative abnormal returns (CAR). One standard deviation change in ESG leads to −0.77%, −0.45%, and −0.61% significant changes in [+1,+5], [−5,+5], and [−7,+7] CAR, respectively. The findings align with the value relevance idea and the reputational risk theory but contradict the reservoir of goodwill hypothesis.
Role of liquid–liquid phase separation in cancer: Mechanisms and therapeutic implications
Authors: Li Xuesong , Yu Zhuo
Published: September 2024

Liquid–liquid phase separation (LLPS) has emerged as a pivotal biological phenomenon involved in various cellular processes, including the formation of membrane‐less organelles and the regulation of biomolecular condensates through precise spatiotemporal coordination of signaling pathways in cells. Dysregulation of LLPSs results in aberrant biomolecular condensates, which are widely implicated in tumorigenesis and cancer progression. Here, we comprehensively summarize the multifaceted roles of LLPS in tumor biology from the perspective of cancer hallmarks, including genomic stability, metabolic reprogramming progression, ferroptosis, and metastasis, to unveil the intricate mechanisms by which LLPS occurs in tumorigenesis. We discuss current discoveries related to therapeutic involvement and potential clinical applications of LLPS in cancer treatment, highlighting the potential of targeting LLPS‐driven processes as novel therapeutic strategies. Additionally, we discuss the challenges associated with new approaches for cancer treatment based on LLPS. This in‐depth discussion of the impact of LLPS on fundamental aspects of tumor biology provides new insights into overcoming cancer.
New Bis(pyrazolo[5,1‐b]quinazolines) and Bis(9H‐xanthenediones) Linked to Alkane Cores: One‐Pot Synthesis, Antibacterial Screening, and SAR Study
Authors: Mekky Ahmed E. M. , Sanad Sherif M. H.
Published: September 2024

Effective one‐pot methods were used to synthesize some new alkane‐linked bis(pyrazolo[5,1‐b]quinazolines) and bis(9H‐xanthenediones). The first series was produced, in 80–88 % yields, via the reaction of one equivalent of the appropriate bis(aldehydes) with two equivalents of 1H‐pyrazole‐3,5‐diamine and dimedone in DMF at 150 °C for 5–6 h. The second series was prepared, in 82–89 % yields, via the reaction one equivalent of the appropriate bis(aldehydes) with four equivalents of dimedone in acetic acid at 120 °C for 4–5 h. The new products displayed a broad range of antibacterial activity against different bacterial strains. Generally, the antibacterial activity of the alkane‐linked bis(pyrazolo[5,1‐b]quinazoline) units is more than 2‐fold their bis(9H‐xanthenedione) analogues. The (p‐tolylthio)methyl)‐linked bis(pyrazolo[5,1‐b]quinazolines) demonstrate the best antibacterial activity with MIC/MBC values up to 3.3/6.6 μM.
Understanding Cytochrome P450 Enzyme Substrate Inhibition and Prospects for Elimination Strategies
Authors: Zhang Yisang , Zhang Guobin , Wang Taichang , Chen Yu , Wang Junqing , Li Piwu , Wang Ruiming , Su Jing
Published: September 2024

Cytochrome P450 (CYP450) enzymes, which are widely distributed and pivotal in various biochemical reactions, catalyze diverse processes such as hydroxylation, epoxidation, dehydrogenation, dealkylation, nitrification, and bond formation. These enzymes have been applied in drug metabolism, antibiotic production, bioremediation, and fine chemical synthesis. Recent research revealed that CYP450 catalytic kinetics deviated from the classic Michaelis–Menten model. A notable substrate inhibition phenomenon that affects the catalytic efficiency of CYP450 at high substrate concentrations was identified. However, the substrate inhibition of various reactions catalyzed by CYP450 enzymes have not been comprehensively reviewed. This review describes CYP450 substrate inhibition examples and atypical Michaelis–Menten kinetic models, and provides insight into mechanisms of these enzymes. We also reviewed 3D structure and dynamics of CYP450 with substrate binding. Outline methods for alleviating substrate inhibition in CYP450 and other enzymes, including traditional fermentation approaches and protein engineering modifications. The comprehensive analysis presented in this study lays the foundation for enhancing the catalytic efficiency of CYP450 by deregulating substrate inhibition.
Predictive action of oncomiR in suppressing TP53 signaling pathway in hypoxia‐conditioned colon cancer cell line HCT‐116
Authors: Susanti R. , Dafip Muchamad , Mustikaningtyas Dewi , Putra Agung
Published: September 2024

Hypoxia‐induced heterogeneity in colorectal cancer (CRC) significantly impacts patient survival by promoting chemoresistance. These conditions alter the regulation of miRNAs, key regulators of crucial processes like proliferation, apoptosis, and invasion, leading to tumor progression. Despite their promising potential as diagnostic and therapeutic targets, the underlying mechanisms by which miRNAs influence hypoxia‐mediated tumorigenesis remain largely unexplored. This study aims to elucidate the action of miRNAs in HCT‐116 colorectal cancer stem cells (CSCs) under hypoxia, providing valuable insights into their role in tumor adaptation and progression. MiRNA expression was determined using Nanostring nCounter, and bioinformatic analysis was performed to explain the molecular pathway. A total of 50 miRNAs were obtained with an average count of ≥ 20 reads for comparative expression analysis. The results showed that hypoxia‐affected 36 oncomiRs were increased in HCT‐116, and 14 suppressor‐miRs were increased in MSCs. The increase in miRNA expression occurred consistently from normoxia to hypoxia and significantly differed between mesenchymal stem cells (MSCs) and HCT‐116. Furthermore, miR‐16‐5p and miR‐29a‐3p were dominant in regulating the p53 signaling pathway, which is thought to be related to the escape mechanism against hypoxia and maintaining cell proliferation. More research with a genome‐transcriptome axis approach is needed to fully understand miRNAs’ role in adapting CRC cells and MSCs to hypoxia. Further research could focus on developing specific biomarkers for diagnosis. In addition, anti‐miR can be developed as a therapy to prevent cancer proliferation or inhibit the adaptation of cancer cells to hypoxia.
Comparative Electrocatalysis of Hydrogen Production and Oxidation: Technetium versus Rhenium Tris(thiolate) Complexes
Authors: Li Xuelian , Wang Yingke , Xu Cheng , Guo Zeyi , Lu Yazhu , Kong Deqing , Wang Junfei , Guan Jia , Tang Hao
Published: September 2024

The development of an efficient catalyst that can selectively activate and generate hydrogen molecules is in urgent demand. Inspired by the 5d rhenium‐tris(thiolate) complex that is capable of catalytically producing and oxidizing H2, the mechanisms of electrocatalytic H2 oxidation (HOR) and evolution (HER) catalyzed by the 4d technetium‐tri(thiolate) analogs, and [TcL3] (L = diphenylphosphinobenzenethiolate, a noninnocent ligand), were investigated by DFT calculations, aiming at elucidating the role of the metal in metal‐ligand cooperativity. DFT calculations anticipate high reactivity in both HOR and HER for [TcL3] beyond that of its Re counterparts. Substituting the Re metal for Tc in metal‐tris(thiolate) complexes results in a greater thiyl‐radical character in the Tc complex compared to that in Re. Even when both complexes evolve H2 with similar [ECEC] mechanisms, the proton relays behave with a distinct disparity, featuring the S ligand in the Tc species as compared to the metal‐hydride in Re. The HOR mechanism also bifurcates as [TcL3]2+ is predicted to mainly occur via the ligand‐based pathway, in contrast to the predominant metal and ligand‐based reactivity for Re. This study established the role of the metal in HER and HOR while emphasizing the utility of such metal‐DPPBT cooperativity in the catalytic process.
Hybrid Nanoparticles: Ni and Au Decorated with [FeFe]‐Hydrogenase Mimics
Authors: Aguado Sergio , Gallego‐Gamo Albert , Vicent Diego J. , Granados Albert , Mallón Laura , Gimbert‐Suriñach Carolina , García‐Antón Jordi , Casarrubios Luis , Vallribera Adelina , Sierra Miguel A.
Published: September 2024

Complexes [(μ‐S₂C₂H₄NHR)Fe₂(CO)₆] (R = p‐C₆H₄‐OCO(CH₂)₉Br (3a); R = p‐C₆H₄‐OCO(CH₂)₈CH₃ (3b)) were used as stabilizing agents in the synthesis of Ni@3 and Au@3 nanoparticles (NPs), which are the first reported stable metallic NPs decorated with [(μ‐S₂C₂H₄NHR)Fe₂(CO)₆] moieties. Electrochemical analysis reveals that incorporating the hydrogenase mimic into the NPs lowers the overpotential and enhances proton reduction electrocatalytic activity in organic media. The NPs act similarly to the [Fe₄S₄] cluster in natural enzymes, functioning as an electron reservoir/relay.
Surface Nanojunction Enabled by Vapor‐Assisted π‐Conjugation Modification of Carbon Nitride for Enhanced Photocatalytic Water Splitting
Authors: Lin Xiaoxue , Peng Xiaoying , Wu Suqin , Ma Chen , Chen Dou , Peng Quanming , Yang Kai , Liu Fan , Yin Shungao , Peng Guiming
Published: September 2024

The unsatisfied visible light harvesting, slow charge separation, and limited practical surface area of carbon nitride (CN) constrain its performance in photocatalytic water splitting and environmental remediation. Herein, the thermal vapor‐assisted π‐conjugation modification of CN by grafting with p‐aminophenoxy groups was developed to tune the photophysical properties of CN to enhance its photocatalytic activity. Besides extending the light absorption, the surface modification constructed a nanojunction across the depth direction, which leads to facilitated charge separation and transfer. In addition, the thermal vapor modification process thermally etches and trims the pristine CN to be a highly holey structure, resulting to >10 times increase in specific surface area. Photocatalysis results showed that the obtained modified CN yielded hydrogen from photocatalytic water splitting at a rate of 7.82 mmol/g/h, over 7‐folds as that of pristine CN, with a quantum yield of 3.28% at 400 nm. The π‐conjugation modified CN also demonstrated enhanced photocatalytic environmental remediation application, exemplified by much faster photodegradation of tetracycline hydrochloride. This work provides the thermal vapor surface chemical modification of CN as a promising integrated pathway of multiple favorable photophysical properties toward efficient photocatalysis application.
Sequential‐Flow Synthesis of Donepezil: A Green and Sustainable Strategy Featuring Heterogeneous Catalysis and Hydrogenation
Authors: Ishitani Haruro , Sogo Hideyuki , Furiya Yuichi , Kobayashi Shu
Published: September 2024

An atom‐economical sequential‐flow synthesis of donepezil, a widely prescribed drug for Alzheimer's disease, was accomplished using inexpensive, commercially available precursors. This achievement was made possible by reconfiguring the synthetic route to include only heterogeneous catalytic addition and condensation reactions, with a particular emphasis on skeletal transformation and bond formation through hydrogenation processes. Notably, water was the sole byproduct in this synthesis. A crucial aspect of this work was the development of appropriate continuous‐flow processes to achieve a one‐flow synthesis. This was accomplished by implementing in‐line treatments of the main reaction stream to eliminate inhibitory factors that could affect catalyst performance in the hydrogenation steps.
Isonitrile Photochemistry: A Functional Group Class Coming in from the Cold
Authors: Giustiniano Mariateresa
Published: September 2024

Starting from a historical background that acknowledges isonitriles as a neglected class of compounds due to their unpleasant smell and hardly controlled reaction conditions with open shell species, the present concept article aims at highlighting the seeds of the modern isonitrile photochemistry. Representative essential transformations achieved via either UV light irradiation or radical initiators at high temperatures are brought into play to draw a parallel with the current literature relying on the exploitation of visible light photochemical methods. Such a comparison points out the potential of this enabling technology to further expand the scope of isonitrile chemistry and the unmet challenges which makes it a very stimulating field.
C−H Activation and Hydrogen Isotope Exchange of Aryl Carbamates Using Iridium(I) Complexes Bearing Chelating NHC‐Phosphine Ligands
Authors: Zorzatto Renan , Mulrainey Paul T. , Reid Marc , Tuttle Tell , Lindsay David M. , Kerr William J.
Published: September 2024

Hydrogen isotope exchange (HIE) via C−H activation constitutes an efficient method for the synthesis of isotopically‐enriched compounds, which are crucial components of the drug discovery process and are extensively employed in mechanistic studies. A series of iridium(I) complexes, bearing a chelating phosphine‐N‐heterocyclic carbene ligand, was designed and synthesized for application in the catalytic HIE of challenging N‐ and O‐aryl carbamates. A broad range of substrates were labeled efficiently, and applicability to biologically‐relevant systems was demonstrated by labeling an ʟ‐tyrosine‐derived carbamate with excellent levels of deuterium incorporation. Combined theoretical and experimental studies unveiled intriguing mechanistic features within this process, in comparison to C−H activation and hydrogen isotope exchange catalyzed by monodentate Ir(I) NHC/phosphine complexes.
Effect of the main components in gasification wastewater on the surface properties of coal water slurry
Authors: Li Dedi , Feng Biao , Luo Yuanlin , Wang Jianbin , Lai Xinjie , Zhao Jun
Published: September 2024

Coal water slurry is an advanced and efficient clean coal technology; using gasification wastewater to prepare coal water slurry can recycle wastewater and improve energy utilization efficiency. As the complex substances in wastewater have a great influence on the slurry properties, the effects of organic matter, metal ions, and ammonia nitrogen in gasification wastewater on the surface properties of coal water slurry are studied in this paper in order to provide new ideas for slurry mechanism of coal water slurry prepared from wastewater. Results show the following: (a) Compared with ordinary coal water slurry, the concentration of coal water slurry prepared from wastewater with high organic content increased by 2.9%, while the concentration of coal water slurry prepared from wastewater with high ammonia nitrogen content decreased by 2.1%. (b) The contact angles of coal water slurry prepared with phenols, alcohols, and urethane are reduced by 2.8°, 6.3°, and 1.5°, respectively, so organic matter can change the hydrophilicity of coal particles and affect slurryability. (c) Mg2+ and Ca2+ have basically no effect on slurry. Fe3+ reduces the absolute value of Zeta potential by 33.1, and Cu3+ increases that by 22.8, as they affect the slurryability by changing the surface potential of coal particles and the absorption of additives. (d) Ammonia nitrogen influences the slurryability by changing the pH value of the slurry. The conclusion of the influence mechanism of organic matter, metal ions, and ammonia nitrogen in wastewater on slurryability can provide a technical reference for the selection of suitable wastewater to prepare coal water slurry.
Synergistic effect of alcohol polyoxyethylene ether sodium sulphate and copper foam on methane hydrate formation
Authors: Wang Hao , Ma Guiyang , Wang Zhongsheng , Yu Jinping , Jiang Xiangchun
Published: September 2024

Natural gas is the cleanest fossil energy source and its consumption is increasing rapidly, so an efficient natural gas way of storing and transporting is urgently needed. Solidified natural gas (SNG) technology is gaining traction because of its higher safety, lower cost, and flexible storage and transportation modes. To improve the methane uptake rate in SNG technology, this work investigated the growth of methane hydrate in fatty alcohol polyoxyethylene ether sodium sulphate (AES) solution with the addition of three different pores per inch (PPI) of copper foam (CF). The results showed that the addition of AES caused the hydrate to grow upwards along the wall, and the methane uptake in the 300 ppm AES solution was increased by 623% compared to pure water. CF not only provided more nucleation sites for hydrate but also transferred the heat generated during hydration. Moreover, there was a synergistic effect between AES and CF and the solution could continuously transport upward along the continuous metal skeleton to increase the gas–liquid contact area. Thus, the formation rate and induction time of methane hydrate improve. Hydrate had the highest methane uptake in the 20 PPI CF system and the lower the pressure, the greater the ability of CF to promote hydrate formation. The methane uptake improved by 27.6% and the induction time was reduced by 59.7% compared to the pure AES system at 6 MPa. This work is aimed at advancing SNG technology (especially at low pressure) and informs the theoretical foundation.
Eutypetides A—E, Structurally Intriguing Polyketides Formed by Intramolecular [4+2] Cycloaddition from Marine‐Derived Fungus Eutypella sp. F0219
Authors: Jiang Zhong‐Ping , Chen Meng‐Ting , Xiang Xiao , Xu Cong‐Jun , Rao Yong , Du Hong‐Zhi , Li Wan‐Shan , Huang Ling
Published: September 2024

Comprehensive Summary

Four polycyclic ten‐membered lactones possessing unprecedented 10/6/5 tricyclic ring skeleton, named eutypetides A—D (1—4), and an intriguing polyketide containing a hexahydroisobenzofuran‐1(3H)‐one motif, named eutypetide E (5) were isolated from the marine‐derived fungus Eutypella sp. F0219, together with three new related biosynthetic polyketides eutypetides F—H (6—8). The absolute configurations of 1—5 were unequivocally determined by single‐crystal X‐ray diffraction analyses (Cu Kα), modified Mosher's method and electronic circular dichroism (ECD) calculations. Eutypetides G (7) showed remarkable anti‐inflammatory activity and could reduce the mRNA expression of proinflammatory cytokines IL‐1β, IL‐6, TNF‐α, and iNOS induced by LPS. Most notably, compounds 1—4 were formed biogenetically from 6—7 via the key intramolecular [4+2] cycloaddition, while compound 5 could be constructed biogenetically from 8 through the intramolecular [4+2] cycloaddition. All the above eight polyketides are proposed to originate from a C10 and a C6 fatty acid.
Bacterial Secondary Metabolites Embedded in Producer Cell Membranes and Antibiotics Targeting Their Biosynthesis
Authors: Xia Zhao , Xiang Hao , Shi Yi‐Ming
Published: September 2024

The bacterial cell membrane primarily houses lipids, carbohydrates, and proteins forming a barrier and interface that maintains cellular integrity, supports homeostasis, and senses environmental changes. Compared to lipid components and excreted secondary metabolites, compounds embedded in the producer cell membrane are often overlooked due to their low abundance and niche‐specific functions. The accumulation of findings has led to an increased appreciation of their crucial roles in bacterial cell biochemistry, physiology, and ecology, as well as their impact on mutualistic and pathogenic bacteria‐eukaryote interactions. This review highlights the structures, biosynthesis, regulation, and ecological functions of membrane‐embedded secondary metabolites. It also discusses antibiotics that target their biosynthetic pathways, aiming to inspire the development of antibiotics specific to pathogenic bacteria without harming human cells.
External Controls to Study Treatment Effects in Rare Diseases: Challenges and Future Directions
Authors: Weberpals Janick , Wang Shirley V.
Published: September 2024

Regulators increasingly rely on real‐world evidence generated from routine‐care health data to evaluate novel therapies. Particularly, external control arms are increasingly used to supplement and contextualize efficacy and safety claims of single arm clinical trials for rare disease therapies. However, there are a number of methodological issues that may affect the validity of results derived from such comparisons. In this mini‐review, we briefly summarize frequently used approaches and outline some of the most important criticisms and paths forward.