bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-Assembly of Amyloid Fibrils into 3D Gel Clusters versus 2D Sheets
Authors: Karunarathne Kanchana , Bushra Nabila , Williams Olivia , Raza Imad , Tirado Laura , Fakhre Diane , Fakhre Fadia , Muschol Martin
Published: January 2023

The deposition of dense fibril plaques represents the pathological hallmark for a multitude of human disorders, including many neurodegenerative diseases. Fibril plaques are predominately composed of amyloid fibrils, characterized by their underlying cross beta-sheet architecture. Research into the mechanisms of amyloid formation has mostly focused on characterizing and modeling the growth of individual fibrils and associated oligomers from their monomeric precursors. Much less is known about the mechanisms causing individual fibrils to assemble into ordered fibrillar suprastructures. Elucidating the mechanisms regulating this “secondary” self-assembly into distinct suprastructures is important for understanding how individual protein fibrils form the prominent macroscopic plaques observed in disease. Whether and how amyloid fibrils assemble into either 2D or 3D supramolecular structures also relates to ongoing efforts on using amyloid fibrils as substrates or scaffolds for self-assembling functional biomaterials. Here, we investigated the conditions under which preformed amyloid fibrils of a lysozyme assemble into larger superstructures as a function of charge screening or pH. Fibrils either assembled into three-dimensional gel clusters or two-dimensional fibril sheets. The latter displayed optical birefringence, diagnostic of amyloid plaques. We presume that pH and salt modulate fibril charge repulsion, which allows anisotropic fibril–fibril attraction to emerge and drive the transition from 3D to 2D fibril self-assembly.
Antibiotic Resistance Genes in Interconnected Surface Waters as Affected by Agricultural Activities
Authors: Zhao Beilun , van Bodegom Peter M. , Trimbos Krijn B.
Published: January 2023

Pastures have become one of the most important sources of antibiotic resistance genes (ARGs) pollution, bringing risks to human health through the environment and the food that is grown there. Another significant source of food production is greenhouse horticulture, which is typically located near pastures. Through waterways, pasture-originated ARGs may transfer to the food in greenhouses. However, how these pasture-originated ARGs spread to nearby waterways and greenhouses has been much less investigated, while this may pose risks to humans through agricultural products. We analyzed 29 ARGs related to the most used antibiotics in livestock in the Netherlands at 16 locations in an agricultural area, representing pastures, greenhouses and lakes. We found that ARGs were prevalent in all surface waters surrounding pastures and greenhouses and showed a similar composition, with sulfonamide ARGs being dominant. This indicates that both pastures and greenhouses cause antibiotic resistance pressures on neighboring waters. However, lower pressures were found in relatively larger and isolated lakes, suggesting that a larger water body or a non-agricultural green buffer zone could help reducing ARG impacts from agricultural areas. We also observed a positive relationship between the concentrations of the class 1 integron (intl1 gene)—used as a proxy for horizontal gene transfer—and ARG concentration and composition. This supports that horizontal gene transfer might play a role in dispersing ARGs through landscapes. In contrast, none of the measured four abiotic factors (phosphate, nitrate, pH and dissolved oxygen) showed any impact on ARG concentrations. ARGs from different classes co-occurred, suggesting simultaneous use of different antibiotics. Our findings help to understand the spatial patterns of ARGs, specifically the impacts of ARGs from pastures and greenhouses on each other and on nearby waterways. In this way, this study guides management aiming at reducing ARGs′ risk to human health from agricultural products.
Does TRODAT-1 SPECT Uptake Correlate with Cerebrospinal Fluid α-Synuclein Levels in Mid-Stage Parkinson’s Disease?
Authors: Coutinho Artur M. , Ghilardi Maria Gabriela , Campos Ana Carolina P. , Etchebehere Elba , Fonoff Fernanda C. , Cury Rubens G. , Pagano Rosana L. , Martinez Raquel C. R. , Fonoff Erich T.
Published: January 2023

Background: Parkinson’s disease (PD) is characterized by a progressive loss of nigrostriatal dopaminergic neurons with impaired motor and non-motor symptoms. It has been suggested that motor asymmetry could be caused due to an imbalance in dopamine levels, as visualized by dopamine transporter single emission computed tomography test (DAT-SPECT), which might be related to indirect measures of neurodegeneration, evaluated by the Montreal Cognitive Assessment (MOCA) and α-synuclein levels in the cerebrospinal fluid (CSF). Therefore, this study aimed to understand the correlation between disease laterality, DAT-SPECT, cognition, and α-synuclein levels in PD. Methods: A total of 28 patients in the moderate-advanced stage of PD were subjected to neurological evaluation, TRODAT-1-SPECT/CT imaging, MOCA, and quantification of the levels of α-synuclein. Results: We found that α-synuclein in the CSF was correlated with global cognition (positive correlation, r2 = 0.3, p = 0.05) and DAT-SPECT concentration in the putamen (positive correlation, r2 = 0.4, p = 0.005), and striatum (positive correlation, r2 = 0.2, p = 0.03), thus working as a neurodegenerative biomarker. No other correlations were found between DAT-SPECT, CSF α-synuclein, and cognition, thus suggesting that they may be lost with disease progression. Conclusions: Our data highlight the importance of understanding the dysfunction of the dopaminergic system in the basal ganglia and its complex interactions in modulating cognition.
The Imbalance of Astrocytic Mitochondrial Dynamics Following Blast-Induced Traumatic Brain Injury
Authors: Guilhaume-Correa Fernanda , Pickrell Alicia M. , VandeVord Pamela J.
Published: January 2023

Mild blast-induced traumatic brain injury (bTBI) is a modality of injury that has been of major concern considering a large number of military personnel exposed to explosive blast waves. bTBI results from the propagation of high-pressure static blast forces and their subsequent energy transmission within brain tissue. Exposure to this overpressure energy causes a diffuse injury that leads to acute cell damage and, if chronic, leads to detrimental long-term cognitive deficits. The literature presents a neuro-centric approach to the role of mitochondria dynamics dysfunction in bTBI, and changes in astrocyte-specific mitochondrial dynamics have not been characterized. The balance between fission and fusion events is known as mitochondrial dynamics. As a result of fission and fusion, the mitochondrial structure is constantly altering its shape to respond to physiological stimuli or stress, which in turn affects mitochondrial function. Astrocytic mitochondria are recognized to play an essential role in overall brain metabolism, synaptic transmission, and neuron protection. Mitochondria are vulnerable to injury insults, leading to the increase in mitochondrial fission, a mechanism controlled by the GTPase dynamin-related protein (Drp1) and the phosphorylation of Drp1 at serine 616 (p-Drp1s616). This site is critical to mediate the Drp1 translocation to mitochondria to promote fission events and consequently leads to fragmentation. An increase in mitochondrial fragmentation could have negative consequences, such as promoting an excessive generation of reactive oxygen species or triggering cytochrome c release. The aim of the present study was to characterize the unique pattern of astrocytic mitochondrial dynamics by exploring the role of DRP1 with a combination of in vitro and in vivo bTBI models. Differential remodeling of the astrocytic mitochondrial network was observed, corresponding with increases in p-Drp1S616 four hours and seven days post-injury. Further, results showed a time-dependent reactive astrocyte phenotype transition in the rat hippocampus. This discovery can lead to innovative therapeutics targets to help prevent the secondary injury cascade after blast injury that involves mitochondria dysfunction.
Wearable Localized Surface Plasmon Resonance-Based Biosensor with Highly Sensitive and Direct Detection of Cortisol in Human Sweat
Authors: Nan Minghui , Darmawan Bobby Aditya , Go Gwangjun , Zheng Shirong , Lee Junhyeok , Kim Seokjae , Lee Taeksu , Choi Eunpyo , Park Jong-Oh , Bang Doyeon
Published: January 2023

Wearable biosensors have the potential for developing individualized health evaluation and detection systems owing to their ability to provide continuous real-time physiological data. Among various wearable biosensors, localized surface plasmon resonance (LSPR)-based wearable sensors can be versatile in various practical applications owing to their sensitive interactions with specific analytes. Understanding and analyzing endocrine responses to stress is particularly crucial for evaluating human performance, diagnosing stress-related diseases, and monitoring mental health, as stress takes a serious toll on physiological health and psychological well-being. Cortisol is an essential biomarker of stress because of the close relationship between cortisol concentration in the human body and stress level. In this study, a flexible LSPR biosensor was manufactured to detect cortisol levels in the human body by depositing gold nanoparticle (AuNP) layers on a 3-aminopropyltriethoxysilane (APTES)-functionalized poly (dimethylsiloxane) (PDMS) substrate. Subsequently, an aptamer was immobilized on the surface of the LSPR substrate, enabling highly sensitive and selective cortisol capture owing to its specific cortisol recognition. The biosensor exhibited excellent detection ability in cortisol solutions of various concentrations ranging from 0.1 to 1000 nM with a detection limit of 0.1 nM. The flexible LSPR biosensor also demonstrated good stability under various mechanical deformations. Furthermore, the cortisol levels of the flexible LSPR biosensor were also measured in the human epidermis before and after exercise as well as in the morning and afternoon. Our biosensors, which combine easily manufactured flexible sensors with sensitive cortisol-detecting molecules to measure human stress levels, could be versatile candidates for human-friendly products.
Changes in Apathy, Depression, and Anxiety in Parkinson’s Disease from before to during the COVID-19 Era
Authors: Kinger Shraddha B. , Juneau Truley , Kaplan Rini I. , Pluim Celina F. , Fox-Fuller Joshua T. , Wang Timothy , Mukadam Nishaat , Neargarder Sandy , Salazar Robert D. , Cronin-Golomb Alice
Published: January 2023

Apathy, depression, and anxiety are common non-motor symptoms of Parkinson’s disease (PD). Tracking the changes in such symptoms over time would be valuable not only to determine their natural course during the disease, but also to establish the effects of unusual historical events interacting with the natural course. Having collected data on apathy (Apathy Scale), depression (Beck Depression Inventory-II), and anxiety (Parkinson’s Anxiety Scale) in a large sample of persons with PD (PwPD) before the beginning of the COVID-19 era, we followed up with these individuals to investigate the changes in their prevalence of apathy, depression, and anxiety across two timepoints (T1 and T2). Of the original 347 participants, 111 responded and provided complete data at T2. The data collection at T1, before COVID-19, occurred between 2017–2018. The data collection at T2 occurred in 2021 and included the same measures, with the addition of the Coronavirus Impact Scale to assess the effects of the pandemic on the individual participants. Over this period, there was a significant increase in apathy, but not in depression or anxiety. Anxiety and depression, but not apathy, were correlated with the impact of COVID-19.
Low Levels of Adenosine and GDNF Are Potential Risk Factors for Parkinson’s Disease with Sleep Disorders
Authors: Wang Li , Gao Zheng , Chen Gang , Geng Deqin , Gao Dianshuai
Published: January 2023

Sleep disturbances are the most prevalent non-motor symptoms in the preclinical stage of Parkinson’s disease (PD). Adenosine, glial-derived neurotrophic factor (GDNF), and associated neurotransmitters are crucial in the control of sleep arousal. This study aimed to detect the serum levels of adenosine, GDNF, and associated neurotransmitters and explored their correlations with PD with sleep disorders. Demographic characteristics and clinical information of PD patients and healthy participants were assessed. Serum concentrations of adenosine, GDNF, and related neurotransmitters were detected by ELISA and LC-MS. The correlation between serum levels of adenosine, GDNF, and associated neurotransmitters and sleep disorders was explored using logistic regression. PD patients with sleep disorders had higher scores of HAMA, HAMD, ESS, UPDRS-III, and H-Y stage. Lower levels of adenosine, GDNF, and γ-GABA were observed in PD patients who had sleep problems. Logistic regression analysis showed adenosine and GDNF were protective factors for preventing sleep disorders. Adenosine combined with GDNF had a higher diagnostic efficiency in predicting PD with sleep disorders by ROC analysis. This study revealed low adenosine and GDNF levels may be risk factors for sleep disorders in PD. The decrease of serum adenosine and GDNF levels may contribute to the diagnosis of PD with sleep disturbances.
Implicit Knowledge Acquisition and Potential Challenges for Advanced Chinese and Spanish EFL Learners: A Word Monitoring Test on English Questions
Authors: He Qiaoling , Oltra-Massuet Isabel
Published: January 2023

This study aims to explore whether advanced EFL learners can acquire implicit knowledge of basic sentence structures, such as English questions. We ran a reaction-time experiment, a word monitoring test experiment to test learners’ implicit knowledge by checking advanced EFL learners’ grammatical sensitivity to English questions with five types of grammatical errors. The study recruited three groups of participants: native English speakers (n = 12), advanced Chinese EFL learners (n = 32), and advanced Spanish EFL learners (n = 37). Our results revealed that advanced EFL learners had not yet attained native-equivalent implicit grammar knowledge in English questions, despite their English proficiency level. The results also indicated that the learners’ different L1 languages do not impact advanced learners’ overall implicit knowledge acquisition but constitute influential factors for particular morphosyntactic inflections in English question formation.
Study of the Correlation among Luminous Properties of Smart Glazing for Adaptive Energy Saving Buildings
Authors: Piccolo Antonio , Prestipino Mauro , Panzera Maria Francesca , Baccoli Roberto
Published: January 2023

A smart window, such as electrochromic or thermochromic windows, may not be able to accomplish at the same time energy efficiency and visual comfort functions, since satisfying one criterium interferes with the other. This recalls to the important issue of establishing precise relationships among parameters affecting energy, glare control, and color rendering tasks and the influence on them of glazing material composition and preparation technique. With this aim, the luminous properties of a number of advanced glazings found in literature and of three home-made electrochromic devices differing by material composition and/or preparation technique are analyzed in this study. The investigation has involved the determination of the CIE (Commission International de l’Eclairage) Color Rendering Index (CIE CRI), the Correlated Color Temperature (CCT), and the luminous transmittance coefficient (τV) of the devices which are discussed with regard to their potential in absolving to energy and visual comfort tasks. Results lead to the main conclusion that the CIE CRI, CCT, and τV indexes are clearly linked by an exponential correlation. At low τV values (τV< 0.5), however, the correlation weakens and the variation of the CIE CRI and CCT indexes becomes entirely material dependent. The influence of preparation technique appears to be irrelevant since the color rendering indexes appear to be well correlated to τV over all the investigated τV range.
Sewage Sludge Valorization for Collapsible Soil Improvement
Authors: Feitosa Maria C. A. , Ferreira Sílvio R. M. , Delgado João M. P. Q. , Silva Fernando A. N. , Oliveira Joaquim T. R. , Oliveira Pedro E. S. , Azevedo António C.
Published: January 2023

The environmental problems caused by sewage sludge generated by the growth of the global population and urbanization are drawing the attention of the scientific community worldwide to the need of developing sustainable solutions to use that material. This work investigated the possibilities of using sewage sludge, generated in wastewater treatment plants, as a strategy to improve and stabilize collapsible soils. Different soil–sludge mixtures, with 5%, 10%, and 15% of sludge, were analyzed. For the characterization and analysis of the soil–sludge interaction, physical, chemical, and edometric experiments were performed. The results showed that the addition of sludge to the soil causes a void index reduction, improves particle packaging, and reduces soil collapsibility to the same specific dry apparent weights, i.e., showed to be a promising method for the improvement of collapsible soils.
Investigating the Influence of Age-Friendly Community Infrastructure Facilities on the Health of the Elderly in China
Authors: Chen Qingwen , Zhang Zhao , Mao Yihua , Deng Ruyu , Shui Yueyao , Wang Kai , Hu Yuchen
Published: January 2023

Global population aging has become a continuous and irreversible trend. Most of the elderly in China prefer “aging in place” owing to the influence of traditional concepts and social welfare, but many communities, as a basic place for the elderly to live, generally lack age-friendly infrastructure facilities. Based on the 2018 China Health and Retirement Longitudinal Study database, this study applies the propensity score matching method to empirically investigate the influence of the infrastructure facilities on the health of the elderly in China. The results show that adding elevators, installing bathing facilities, supplying gas or natural gas, and changing squatting toilets into sitting toilets, positively influence the health of the elderly, but there are some differences. The order of the degree of impact on self-rated health (SRH) was elevator > toilet type > kitchen gas supply > bathing facility, while that of activities of daily living (ADL) was bathing facility > toilet type > elevator > kitchen gas supply. Elderly people with different personal characteristics and family status have different degrees of ownership for the infrastructure facilities. It is suggested that age-friendly regeneration schemes be developed according to the different impacts and demands of the facilities.
Deletion of Glycogen Synthase Kinase 3 Beta Reprograms NK Cell Metabolism
Authors: Pereira Marcelo S. F. , Sorathia Kinnari , Sezgin Yasemin , Thakkar Aarohi , Maguire Colin , Collins Patrick L. , Mundy-Bosse Bethany L. , Lee Dean A. , Naeimi Kararoudi Meisam
Published: January 2023

Loss of cytotoxicity and defective metabolism are linked to glycogen synthase kinase 3 beta (GSK3β) overexpression in natural killer (NK) cells from patients with acute myeloid leukemia or from healthy donors after expansion ex vivo with IL-15. Drug inhibition of GSK3β in these NK cells improves their maturation and cytotoxic activity, but the mechanisms of GSK3β-mediated dysfunction have not been well studied. Here, we show that expansion of NK cells with feeder cells expressing membrane-bound IL-21 maintained normal GSK3β levels, allowing us to study GSK3β function using CRISPR gene editing. We deleted GSK3B and expanded paired-donor knockout and wild-type (WT) NK cells and then assessed transcriptional and functional alterations induced by loss of GSK3β. Surprisingly, our data showed that deletion of GSK3B did not alter cytotoxicity, cytokine production, or maturation (as determined by CD57 expression). However, GSK3B-KO cells demonstrated significant changes in expression of genes related to rRNA processing, cell proliferation, and metabolic function, suggesting possible metabolic reprogramming. Next, we found that key genes downregulated in GSK3B-KO NK cells were upregulated in GSK3β-overexpressing NK cells from AML patients, confirming this correlation in a clinical setting. Lastly, we measured cellular energetics and observed that GSK3B-KO NK cells exhibited 150% higher spare respiratory capacity, a marker of metabolic fitness. These findings suggest a role for GSK3β in regulating NK cell metabolism.
The Use of Artificial Intelligence in the Diagnosis and Classification of Thyroid Nodules: An Update
Authors: Ludwig Maksymilian , Ludwig Bartłomiej , Mikuła Agnieszka , Biernat Szymon , Rudnicki Jerzy , Kaliszewski Krzysztof
Published: January 2023

The incidence of thyroid nodules diagnosed is increasing every year, leading to a greater risk of unnecessary procedures being performed or wrong diagnoses being made. In our paper, we present the latest knowledge on the use of artificial intelligence in diagnosing and classifying thyroid nodules. We particularly focus on the usefulness of artificial intelligence in ultrasonography for the diagnosis and characterization of pathology, as these are the two most developed fields. In our search of the latest innovations, we reviewed only the latest publications of specific types published from 2018 to 2022. We analyzed 930 papers in total, from which we selected 33 that were the most relevant to the topic of our work. In conclusion, there is great scope for the use of artificial intelligence in future thyroid nodule classification and diagnosis. In addition to the most typical uses of artificial intelligence in cancer differentiation, we identified several other novel applications of artificial intelligence during our review.
Mechanisms of ADC Toxicity and Strategies to Increase ADC Tolerability
Authors: Nguyen Toan D. , Bordeau Brandon M. , Balthasar Joseph P.
Published: January 2023

Anti-cancer antibody-drug conjugates (ADCs) aim to expand the therapeutic index of traditional chemotherapy by employing the targeting specificity of monoclonal antibodies (mAbs) to increase the efficiency of the delivery of potent cytotoxic agents to malignant cells. In the past three years, the number of ADCs approved by the Food and Drug Administration (FDA) has tripled. Although several ADCs have demonstrated sufficient efficacy and safety to warrant FDA approval, the clinical use of all ADCs leads to substantial toxicity in treated patients, and many ADCs have failed during clinical development due to their unacceptable toxicity profiles. Analysis of the clinical data has demonstrated that dose-limiting toxicities (DLTs) are often shared by different ADCs that deliver the same cytotoxic payload, independent of the antigen that is targeted and/or the type of cancer that is treated. DLTs are commonly associated with cells and tissues that do not express the targeted antigen (i.e., off-target toxicity), and often limit ADC dosage to levels below those required for optimal anti-cancer effects. In this manuscript, we review the fundamental mechanisms contributing to ADC toxicity, we summarize common ADC treatment-related adverse events, and we discuss several approaches to mitigating ADC toxicity.
Effects of Tumor Localization, Age, and Stage on the Outcomes of Gastric and Colorectal Signet Ring Cell Adenocarcinomas
Authors: Benesch Matthew G. K. , Mathieson Alexander , O’Brien Shalana B. L.
Published: January 2023

Signet ring cell adenocarcinomas (SRCCs) are a rare histological adenocarcinoma subtype, classically thought to have a worse prognosis than conventional adenocarcinomas. The majority of these cancers occur in the stomach, colon, and rectum. Their rarity means that most epidemiological studies into their pathology are often underpowered, and interpretations from these reports are mixed. In this study, we use the Surveillance, Epidemiology, and End Results Program (SEER) database to examine the effects of tumor localization, age, and stage on gastric and colorectal cancer outcomes. For early onset localized and regional gastric cancers, SRCCs have the same overall risk of mortality compared to conventional adenocarcinomas. Over the age of 50 years, SRCCs have worse outcomes across all stages. Gastric SRCCs are 2–3-fold more likely in younger patients, and more heavily favor the distal stomach. Like conventional adenocarcinomas, proximal gastric SRCCs have decreased survival. Across all ages, stages, and locations, colorectal SRCCs have worse outcomes. SRCCs favor the right colon, but outcomes are significantly worse for the left colon and rectal cancers. Relative to adenocarcinomas, colorectal SRCCs have the worst outcomes in younger patients. Overall, these results provide insights into SRCC disease patterns that cannot be surmised outside of population-level data.
Important Requirements for Desorption/Ionization Mass Spectrometric Measurements of Temozolomide-Induced 2′-Deoxyguanosine Methylations in DNA
Authors: Fresnais Margaux , Jung Ina , Klein Uli B. , Miller Aubry K. , Turcan Sevin , Haefeli Walter E. , Burhenne Jürgen , Longuespée Rémi
Published: January 2023

In clinical pharmacology, drug quantification is mainly performed from the circulation for pharmacokinetic purposes. Finely monitoring the chemical effect of drugs at their chemical sites of action for pharmacodynamics would have a major impact in several contexts of personalized medicine. Monitoring appropriate drug exposure is particularly challenging for alkylating drugs such as temozolomide (TMZ) because there is no flow equilibrium that would allow reliable conclusions to be drawn about the alkylation of the target site from plasma concentrations. During the treatment of glioblastoma, it appears, therefore, promising to directly monitor the alkylating effect of TMZ rather than plasma exposure, ideally at the site of action. Mass spectrometry (MS) is a method of choice for the quantification of methylated guanines and, more specifically, of O6-methylguanines as a marker of TMZ exposure at the site of action. Depending on the chosen strategy to analyze modified purines and 2′-deoxynucleosides, the analysis of methylated guanines and 2′-deoxyguanosines is prone to important artefacts due to the overlap between masses of (i) guanines from DNA and RNA, and (ii) different methylated species of guanines. Therefore, the specific analysis of O6-methyl-2′deoxyguanosine, which is the product of the TMZ effect, is highly challenging. In this work, we report observations from matrix-assisted laser desorption/ionization (MALDI), and desorption electrospray ionization (DESI) MS analyses. These allow for the construction of a decision tree to initiate studies using desorption/ionization MS for the analysis of 2′-deoxyguanosine methylations induced by TMZ.
Drug Resistance and Novel Therapies in Cancers in 2020
Authors: Wang Zhixiang
Published: January 2023

After a very successful year in 2019 with 34 publications, our Topic collection “Drug Resistance and Novel Therapies in Cancers” guaranteed another productive year with the publication of 17 research articles and 4 review articles in 2020 [...]
Prognostic Impact of Sarcopenia’s Occurrence during Radiotherapy in Oropharyngeal Cancer Patients
Authors: Bergamaschi Luca , Marvaso Giulia , Zaffaroni Mattia , Vincini Maria Giulia , D’Ecclesiis Oriana , Volpe Stefania , Ferrari Annamaria , Zorzi Stefano Filippo , Rocca Maria Cossu , Sabbatini Annarita , Cannillo Giulia , Zagallo Emanuela , Starzyńska Anna , Ansarin Mohssen , Cattani Federica , Gandini Sara , Orecchia Roberto , Alterio Daniela , Jereczek-Fossa Barbara Alicja
Published: January 2023

The current study aims to profile sarcopenic condition (both at baseline and developed during treatment) in oropharyngeal carcinoma (OPC) patients treated with curative radiotherapy (RT) +/− chemotherapy and to evaluate its impact on oncological outcomes and toxicity. A total of 116 patients were included in this retrospective single-center study. Sarcopenia assessment at baseline and at 50 Gy re-evaluation CT was obtained from two different methodologies: (i) the L3-skeletal muscle index (SMI) derived from the contouring of the cross-sectional area (CSA) of the masticatory muscles (CSA-MM); and (ii) the paravertebral and sternocleidomastoid muscles at the level of the third cervical vertebra (CSA-C3). Based on L3-SMI from CSA-MM, developing sarcopenic condition during RT (on-RT sarcopenia) was associated with worse progression-free survival (PFS) (p = 0.03) on multivariable analysis and a trend of correlation with overall survival (OS) was also evident (p = 0.05). According to L3-SMI derived from CSA-C3, on-RT sarcopenia was associated with worse PFS (p = 0.0096) and OS (p = 0.013) on univariate analysis; these associations were not confirmed on multivariable analysis. A significant association was reported between becoming on-RT sarcopenia and low baseline haemoglobin (p = 0.03) and the activation of nutritional counselling (p = 0.02). No significant associations were found between sarcopenia and worse RT toxicity. Our data suggest that the implementation of prompt nutritional support to prevent the onset of sarcopenia during RT could improve oncological outcomes in OPC setting.
Therapeutic Strategies to Overcome Fibrotic Barriers to Nanomedicine in the Pancreatic Tumor Microenvironment
Authors: Tanaka Hiroyoshi Y. , Nakazawa Takuya , Enomoto Atsushi , Masamune Atsushi , Kano Mitsunobu R.
Published: January 2023

Pancreatic cancer is notorious for its dismal prognosis. The enhanced permeability and retention (EPR) effect theory posits that nanomedicines (therapeutics in the size range of approximately 10–200 nm) selectively accumulate in tumors. Nanomedicine has thus been suggested to be the “magic bullet”—both effective and safe—to treat pancreatic cancer. However, the densely fibrotic tumor microenvironment of pancreatic cancer impedes nanomedicine delivery. The EPR effect is thus insufficient to achieve a significant therapeutic effect. Intratumoral fibrosis is chiefly driven by aberrantly activated fibroblasts and the extracellular matrix (ECM) components secreted. Fibroblast and ECM abnormalities offer various potential targets for therapeutic intervention. In this review, we detail the diverse strategies being tested to overcome the fibrotic barriers to nanomedicine in pancreatic cancer. Strategies that target the fibrotic tissue/process are discussed first, which are followed by strategies to optimize nanomedicine design. We provide an overview of how a deeper understanding, increasingly at single-cell resolution, of fibroblast biology is revealing the complex role of the fibrotic stroma in pancreatic cancer pathogenesis and consider the therapeutic implications. Finally, we discuss critical gaps in our understanding and how we might better formulate strategies to successfully overcome the fibrotic barriers in pancreatic cancer.
Is Reflex Germline BRCA1/2 Testing Necessary in Women Diagnosed with Non-Mucinous High-Grade Epithelial Ovarian Cancer Aged 80 Years or Older?
Authors: Morgan Robert D. , Burghel George J. , Flaum Nicola , Bulman Michael , Smith Philip , Clamp Andrew R. , Hasan Jurjees , Mitchell Claire L. , Salih Zena , Woodward Emma R. , Lalloo Fiona , Crosbie Emma J. , Edmondson Richard J. , Schlecht Helene , Jayson Gordon C. , Evans D. Gareth R.
Published: January 2023

Women diagnosed with non-mucinous high-grade epithelial ovarian cancer (EOC) in England are often reflex-tested for germline and tumour BRCA1/2 variants. The value of germline BRCA1/2 testing in women diagnosed aged ≥80 is questionable. We performed an observational study of all women diagnosed with non-mucinous high-grade EOC who underwent germline and tumour BRCA1/2 testing by the North West of England Genomic Laboratory Hub. A subgroup of women also underwent germline testing using a panel of homologous recombination repair (HRR) genes and/or tumour testing for homologous recombination deficiency (HRD) using Myriad’s myChoice® companion diagnostic. Seven-hundred-two patients successfully underwent both germline and tumour BRCA1/2 testing. Of these, 48 were diagnosed with non-mucinous high-grade EOC aged ≥80. In this age group, somatic BRCA1/2 pathogenic/likely pathogenic variants (PV/LPVs) were detected nine times more often than germline BRCA1/2 PV/LPVs. The only germline PV reported in a patient aged ≥80 was detected in germline and tumour DNA (BRCA2 c.4478_4481del). No patient aged ≥80 had a germline PV/LPVs in a non-BRCA1/2 HRR gene. Thirty-eight percent of patients aged ≥80 had a tumour positive for HRD. Our data suggest that tumour BRCA1/2 and HRD testing is adequate for patients diagnosed with non-mucinous high-grade EOC aged ≥80, with germline BRCA1/2 testing reserved for women with a tumour BRCA1/2 PV/LPVs.
The PtM/C (M = Co, Ni, Cu, Ru) Electrocatalysts: Their Synthesis, Structure, Activity in the Oxygen Reduction and Methanol Oxidation Reactions, and Durability
Authors: Belenov Sergey , Pavlets Angelina , Paperzh Kirill , Mauer Dmitry , Menshikov Vladislav , Alekseenko Anastasia , Pankov Ilia , Tolstunov Mikhail , Guterman Vladimir
Published: January 2023

PtM/C (M = Co, Ni, Cu, Ru) catalysts were prepared by wet-synthesis methods. The composition and structure of the synthesized materials were estimated by TXRF, XRD, TEM, HAADF-STEM, EDX, and TGA/DSC methods. According to the CV and LSV methods, the PtCu/C material is characterized by the highest activity in the ORR compared to the other materials studied. The PtRu/C catalysts also exhibit the highest activity in the MOR. Studying the durability of the obtained bimetallic catalysts using accelerated stress testing has allowed for the detection of the most promising materials, whose characteristics would be superior to those of the commercial Pt/C analog. This study has shown that wet-synthesis methods allow obtaining bimetallic catalysts characterized by higher activity and enhanced durability. This research also indicates that special attention should be given to the possibility of scaling these synthesis techniques, which makes the aforementioned catalysts promising for commercial applications.
Surfactant- and Ligand-Free Synthesis of Platinum Nanoparticles in Aqueous Solution for Catalytic Applications
Authors: Charde Rashmi P. , Devener Brian van , Nigra Michael M.
Published: January 2023

The synthesis of surfactant-free and organic ligand-free metallic nanoparticles in solution remains challenging due to the nanoparticles’ tendency to aggregate. Surfactant- and ligand-free nanoparticles are particularly desirable in catalytic applications as surfactants, and ligands can block access to the nanoparticles’ surfaces. In this contribution, platinum nanoparticles are synthesized in aqueous solution without surfactants or bound organic ligands. Pt is reduced by sodium borohydride, and the borohydride has a dual role of reducing agent and weakly interacting stabilizer. The 5.3 nm Pt nanoparticles are characterized using UV-visible spectroscopy and transmission electron microscopy. The Pt nanoparticles are then applied as catalysts in two different reactions: the redox reaction of hexacyanoferrate(III) and thiosulfate ions, and H2O2 decomposition. Catalytic activity is observed for both reactions, and the Pt nanoparticles show up to an order of magnitude greater activity over the most active catalysts reported in the literature for hexacyanoferrate(III)/thiosulfate redox reactions. It is hypothesized that this enhanced catalytic activity is due to the increased electron density that the surrounding borohydride ions give to the Pt nanoparticle surface, as well as the absence of surfactants or organic ligands blocking surface sites.
Catalytic Etching and Oxidation of Platinum Group Metals: Morphology, Chemical Composition and Structure of Pt, Pd and Rh Foils in the O2 Atmosphere and during NH3 Oxidation with Air at 1133 K
Authors: Salanov Aleksei , Serkova Alexandra , Isupova Lyubov , Tsybulya Sergey , Parmon Valentin
Published: January 2023

Platinum alloy gauzes are employed for the high-temperature oxidation of NH3 to NO used in the industrial production of HNO3 for application in agricultural fertilizers. To enhance the efficiency of NH3 oxidation, various Pt–Pd–Rh alloys are employed for the production of such catalytic gauzes. To understand the role of these metals in NH3 oxidation, scanning electron microscopy, energy-dispersive spectroscopy and X-ray diffraction were applied to investigate the morphology, composition and structure of Pt, Pd and Rh foils after annealing in O2 and oxidation of NH3 with air at 1133 K. After annealing in O2 and NH3 oxidation, the metallic microgranular structure was detected on Pt(poly), whereas oxide layers of Rh2O3 and PdO were observed on Rh(poly) and Pd(poly). At the onset of NH3 oxidation (t = 1 h), fibrous metal-oxide agglomerates of nanofibers formed on these oxide layers. The long-term (5–10 h) oxidation of NH3 led to the formation of a continuous layer of pyramidal crystals on Rh(poly) and palladium “cauliflowers” on Pd(poly). The highly exothermic reaction of NH3 with oxygen on metals and PdO or Rh2O3 initiates strong catalytic etching forming grains and facets on Pt, fibrous metal-oxide agglomerates, pyramidal crystals and metallic “cauliflowers” on Rh and Pd.
Role and Application of Biocatalysts in Cancer Drug Discovery
Authors: Sengupta Sounok , Das Prathama , Sharma Samridhi , Shukla Monu Kumar , Kumar Rajesh , Kumar Tonk Rajiv , Pandey Sadanand , Kumar Deepak
Published: January 2023

A biocatalyst is an enzyme that speeds up or slows down the rate at which a chemical reaction occurs and speeds up certain processes by 108 times. It is used as an anticancer agent because it targets drug activation inside the tumor microenvironment while limiting damage to healthy cells. Biocatalysts have been used for the synthesis of different heterocyclic compounds and is also used in the nano drug delivery systems. The use of nano-biocatalysts for tumor-targeted delivery not only aids in tumor invasion, angiogenesis, and mutagenesis, but also provides information on the expression and activity of many markers related to the microenvironment. Iosmapinol, moclobemide, cinepazide, lysine dioxygenase, epothilone, 1-homophenylalanine, and many more are only some of the anticancer medicines that have been synthesised using biocatalysts. In this review, we have highlighted the application of biocatalysts in cancer therapies as well as the use of biocatalysts in the synthesis of drugs and drug-delivery systems in the tumor microenvironment.
Titanium Carbide Composite Hollow Cobalt Sulfide Heterojunction with Function of Promoting Electron Migration for Efficiency Photo-Assisted Electro-Fenton Cathode
Authors: Chen Fengjiang , Yang Fan , Che Sai , Liu Hongchen , Chen Neng , Wu Zhijie , Li Yongfeng
Published: January 2023

Constructing heterostructure within electrocatalysts proves to be an attractive approach to adjust the interfacial charge redistribution to promote the adsorption of reactive species and accelerate the charge transfer. Herein, we present the one-pot solvothermal synthesis of Ti3C2 supported hollow CoS2/CoS microsphere heterostructure with uneven charge distribution as the cathodic catalyst, which displays a superior quasi-first-order degradation rate (0.031 min−1) for sulfamethazine (SMT) in photo-assisted electric–Fenton (EF) process. CoS2/CoS/Ti3C2 is proven to favor the 2e− oxygen reduction reaction (ORR), with H2O2 selectivity up to 76%. The built-in potential present in the heterojunction helps to accelerate electron transfer, thus promoting the production of H2O2. Subsequently, H2O2 is rapidly activated to produce ∙OH due to the synergistic effect of Co and S. Notably, CoS2/CoS/Ti3C2 exhibits enhanced photo-assisted EF (PEF) performance under light. The excellent photocatalysis properties of CoS2/CoS/Ti3C2 are attributed to that the unique hollow microsphere structure of catalyst improves the light absorption, and the uneven charge distribution of CoS2/CoS heterojunctions promotes the separation of photo-generated holes and electrons. Given the above advantages, CoS2/CoS/Ti3C2 cathode delivers a high degradation rate of 98.5%, 91.8%, and 94.5% for SMT, bisphenol A, and sulfadiazine, respectively, with TOC removal efficiency of 76% for SMT with 120 min. This work provides a novel light of the design and construction of efficient PEF cathodes for the treatment of antibiotic wastewater.
Sol-Gel Obtaining of TiO2/TeO2 Nanopowders with Biocidal and Environmental Applications
Authors: Bachvarova-Nedelcheva Albena , Iordanova Reni , Naydenov Anton , Stoyanova Angelina , Georgieva Nelly , Nemska Veronica , Foteva Tsvetelina
Published: January 2023

TiO2/TeO2 powders were obtained by an aqueous sol-gel method. Telluric acid (H6TeO6) and titanium butoxide were used as precursors. The as-prepared gel was step-wisely heated in the temperature range 200–700 °C and subsequently characterized by XRD, IR, and UV-Vis analysis and SEM. Mixtures containing TiO2 (anatase), α-TeO2 (paratellurite), and TiTe3O8 were established by XRD as final products, depending on heating temperature. The thermal stability of the obtained gels in the temperature range 100–400 °C was investigated. It was found by IR spectroscopy that the samples heated up to 300–400 °C consist mainly of an organic–inorganic amorphous phase which is transformed into an inorganic one above these temperatures. The microstructure of the gels was verified by scanning electron microscopy (SEM). The photocatalytic degradation of the synthesized nanopowders toward Malachite green organic dye (MG) was examined in order to evaluate the potential applications for environmental remediation. The prepared TiO2/TeO2 samples showed up to 60% decoloration efficiency after 120 min exposure to UV-light. The composition exhibited good antimicrobial activity against E. coli K12. The properties of the obtained material were investigated by the reactions of complete catalytic oxidation of different alkanes and toluene, and it could be suggested that TiO2/TeO2 powders are promising material for use as an active phase in environmental catalysts.
Enhanced Photodegradation of Organic Pollutants by Novel Samarium-Doped Zinc Aluminium Spinel Ferrites
Authors: Grecu Ionela , Samoila Petrisor , Pascariu Petronela , Cojocaru Corneliu , Ignat Maria , Dascalu Ioan-Andrei , Harabagiu Valeria
Published: January 2023

ZnAlFe1−xSmxO4 (x = 0, 0.02, 0.04, 0.06, 0.08) spinel ferrites were successfully obtained for the first time via a sol–gel autocombustion technique using citric acid as the combustion/chelating agent. These materials were then employed as photocatalysts for the degradation of Evans Blue, considered herein as a model organic pollutant. The XRD and FTIR analysis confirmed the achievement of pure spinel ferrite structures for all the materials. TEM analysis showed that the average particle sizes decline from about 27 for the undoped material to 17 nm for samarium-doped materials, and the magnetic characterization at room temperature indicated the paramagnetic conduct for the studied samples. All the photocatalysts were active in Evans Blue photodegradation. The best photocatalytic performances were observed for the ZnAlFe0.94Sm0.06O4 formulation and explained by the smallest values calculated for lattice parameter, interplanar distance, and particle-size values. By adding H2O2 and applying the modelling and optimization of the photocatalytic process for the best material, the half-life of the pollutant decreased significantly from 115 min to about 7 min (about 16-times), and the colour-removal efficiency was almost 100%.
One-Pot Synthesis of β-Alanine from Maleic Acid via Three-Enzyme Cascade Biotransformation
Authors: Wu Jia , Ma Bao-Di , Xu Yi
Published: January 2023

A novel and efficient one-pot three-enzyme cascade method for the synthesis of β-alanine from maleic acid was developed. Two recombinant E. coli strains were constructed. The E. coli (MaiA-AspA) co-expressing maleic cis-trans isomerase (MaiA) and L-aspartase (AspA) catalyzed the biotransformation of maleic acid to L-aspartate via fumaric acid, and E. coli (ADC) expressing L-aspartate-α-decarboxylase (ADC) catalyzed the bioconversion of L-aspartate to β-alanine. After systematic optimization of reaction conditions for each strain, the whole cells of two strains were combined for one-pot synthesis of β-alanine. It was found that the ratio of the two kinds of cells as well as the cell amount play critical roles in the reaction rate and yield of β-alanine. Adding two kinds of cells in one-pot at the beginning of the reaction was better than adding step by step. Under optimal conditions, the concentration of β-alanine reached 751 mM after a 9 h reaction, corresponding to a 93.9% yield and 178 g/L/d space-time yield. The developed new route showed application potential for green and efficient biosynthesis of β-alanine from a cheap substrate by tandem biocatalysts.
Interstitial Macrophages Lead Early Stages of Bleomycin-Induced Lung Fibrosis and Induce Fibroblasts Activation
Authors: Libório-Ramos Sofia , Barbosa-Matos Catarina , Fernandes Raquel , Borges-Pereira Caroline , Costa Sandra
Published: January 2023

A progressive fibrosing phenotype is critical in several lung diseases. It is irreversible and associated with early patient mortality. Growing evidence has revealed pulmonary macrophages’ role as modulators of the fibrotic processes. The proportion, phenotype, and function of alveolar (AM) and interstitial macrophages (IM) at the early stages of bleomycin-induced pulmonary fibrosis have not been clearly described. In this way, our study aimed to characterize these macrophage populations and investigate the effect on fibroblast activation. C57BL/6 mice were intratracheally injected with bleomycin and were sacrificed at day 3, 5, and 7 for the performance of flow cytometry and fluorescent-activated cell sorting analysis for protein and gene expression quantification. After bleomycin administration, the proportion of IM was significantly higher than that of AM, which showed a decay during the inflammatory phase, and peaked at day 7. At day 7 of the inflammatory phase, AM started shifting their phenotype from M1-like towards M2, while IM showed a M2-like phenotype. Conditioned medium derived from IM sorted at day 7 induced fibroblast activation and differentiation in myofibroblasts in vitro. Our findings indicate that IM are the largest macrophage population at the early stages of experimental pulmonary fibrosis and are secreted mediators able to activate fibroblasts, pointing to macrophage modulation as a potential therapeutic strategy to restrain progressive fibrosing lung disorders.
Calnexin, More Than Just a Molecular Chaperone
Authors: Paskevicius Tautvydas , Farraj Rabih Abou , Michalak Marek , Agellon Luis B.
Published: January 2023

Calnexin is a type I integral endoplasmic reticulum (ER) membrane protein with an N-terminal domain that resides in the lumen of the ER and a C-terminal domain that extends into the cytosol. Calnexin is commonly referred to as a molecular chaperone involved in the folding and quality control of membrane-associated and secreted proteins, a function that is attributed to its ER- localized domain with a structure that bears a strong resemblance to another luminal ER chaperone and Ca2+-binding protein known as calreticulin. Studies have discovered that the cytosolic C-terminal domain of calnexin undergoes distinct post-translational modifications and interacts with a variety of proteins. Here, we discuss recent findings and hypothesize that the post-translational modifications of the calnexin C-terminal domain and its interaction with specific cytosolic proteins play a role in coordinating ER functions with events taking place in the cytosol and other cellular compartments.