bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling three‐dimensional cancer‐associated cachexia and therapy: The molecular basis and therapeutic potential of interleukin‐6 transignalling blockade
Authors: Cosentino Marianna , Forcina Laura , Zouhair Mariam , Apa Ludovica , Genovese Desirèe , Boccia Caterina , Rizzuto Emanuele , Musarò Antonio 
Published: September 2023

AbstractBackgroundCauses and mechanisms underlying cancer cachexia are not fully understood, and currently, no therapeutic approaches are available to completely reverse the cachectic phenotype. Interleukin‐6 (IL‐6) has been extensively described as a key factor in skeletal muscle physiopathology, exerting opposite roles through different signalling pathways.MethodsWe employed a three‐dimensional ex vivo muscle engineered tissue (X‐MET) to model cancer‐associated cachexia and to study the effectiveness of selective inhibition of IL‐6 transignalling in counteracting the cachectic phenotype. Conditioned medium (CM) derived from C26 adenocarcinoma cells was used as a source of soluble factors contributing to the establishment of cancer cachexia in the X‐MET model. A dose of 1.2 ng/mL of glycoprotein‐130 fused chimaera (gp130Fc) was added to cachectic culture medium to neutralize IL‐6 transignalling.ResultsC26‐conditioned medium induced a cachectic‐like phenotype in the X‐MET, leading to a decline of muscle mass (−60%; P < 0.001), a reduction in myosin expression (−92.4%; P < 0.005) and a reduction of the contraction frequency spectrum (−94%). C26‐conditioned medium contains elevated amounts of IL‐6 (8.61 ± 4.09 pg/mL) and IL6R (56.85 ± 10.96 pg/mL). These released factors activated the signal transducer and activator of transcription 3 (STAT3) signalling in the C26_CM X‐MET system (phosphorylated STAT3/TOTAL +54.6%; P < 0.005), which in turn promote an enhancement of Il‐6 (+69.2%; P < 0.05) and Il6r (+43%; P < 0.05) gene expression, suggesting the induction of a feed‐forward loop. The selective neutralization of IL‐6 transignalling, by gp130Fc, in C26_CM X‐MET prevented the hyperactivation of STAT3 (−55.8%; P < 0.005), countered the reduction of cross‐sectional area (+28.2%; P < 0.05) and reduced the expression of proteolytic factors including muscle ring finger‐1 (−88%; P < 0.005) and ATROGIN1 (−92%; P < 0.05), thus preserving the robustness and increasing the contractile force (+20%) of the three‐dimensional muscle system. Interestingly, the selective inhibition of IL‐6 transignalling modulated gene regulatory networks involved in myogenesis and apoptosis, normalizing the expression of pro‐apoptotic miRNAs, including miR‐31 (−53.2%; P < 0.05) and miR‐34c (−65%; P < 0.005), and resulting in the reduction of apoptotic pathways highlighted by the sensible reduction of cleaved caspase 3 (−92.5%; P < 0.005) in gp130Fc‐treated C26_CM X‐MET.ConclusionsIL‐6 transignalling appeared as a promising target to counter cancer cachexia‐related alterations. The X‐MET model has proven to be a reliable drug‐screening tool to identify novel therapeutic approaches and to test them in preclinical studies, significantly reducing the use of animal models.
Skeletal muscle adaptations in patients with lung cancer: Longitudinal observations from the whole body to cellular level
Authors: Snoke Deena B. , Bellefleur Emma , Rehman Hibba Tul , Carson James A. , Poynter Matthew E. , Dittus Kim L. , Toth Michael J. 
Published: September 2023

AbstractBackgroundCancer and its treatment can adversely affect skeletal muscle, impacting physical function, treatment response and survival. No studies, however, have comprehensively characterized these muscle adaptations longitudinally in human patients at the cellular level.MethodsWe examined skeletal muscle size and function from the whole body to the sub‐cellular level in 11 patients with non‐small cell lung cancer (NSCLC; 6 male/5 female, mean age 58 ± 3 years) studied over a 2‐month observation period starting during their first cycle of standard of care cancer treatment and in 11 age‐ and sex‐matched healthy controls (HC) without a current or past history of cancer. Biopsies of the vastus lateralis were performed to assess muscle fibre size, contractility and mitochondrial content, along with assessments of physical function, whole muscle size and function, and circulating cytokines.ResultsBody weight, composition and thigh muscle area and density were unaltered over time in patients with NSCLC, while muscle density was lower in patients with NSCLC versus HC (P = 0.03). Skeletal muscle fibre size decreased by 18% over time in patients (all P = 0.02) and was lower than HC (P = 0.02). Mitochondrial fractional area and density did not change over time in patients, but fractional area was lower in patients with NSCLC compared with HC (subsarcolemmal, P = 0.04; intermyofibrillar, P = 0.03). Patients with NSCLC had higher plasma concentrations of IL‐6 (HC 1.40 ± 0.50; NSCLC 4.71 ± 4.22; P < 0.01), GDF‐15 (HC 569 ± 166; NSCLC 2071 ± 1168; P < 0.01) and IL‐8/CXCL8 (HC 4.9 ± 1.8; NSCLC 10.1 ± 6.0; P = 0.02) compared with HC, but there were no changes in inflammatory markers in patients with NSCLC over time. No changes were observed in markers of satellite cell activation or DNA damage in patients and no group differences were noted with HC. Whole‐muscle strength was preserved over time in patients with NSCLC coincident with improved single fibre contractility.ConclusionsThis study is the first to comprehensively examine longitudinal alterations in skeletal muscle fibre size and function in patients with NSCLC and suggests that muscle fibre atrophy occurs during cancer treatment despite weight stability and no changes in conventional clinical measurements of whole body or thigh muscle size over this period.
Mesenchymal stem cell‐derived exosomes in myocardial infarction: Therapeutic potential and application
Authors: Li Jing , Tang Yuting , Yin Leijing , Lin Xiaofang , Luo Zhengyang , Wang Shuxin , Yuan Ludong , Liang Pengfei , Jiang Bimei 
Published: September 2023

AbstractMyocardial infarction refers to the irreversible impairment of cardiac function resulting from the permanent loss of numerous cardiomyocytes and the formation of scar tissue. This condition is caused by acute and persistent inadequate blood supply to the heart's arteries. In the treatment of myocardial infarction, Mesenchymal stem cells (MSCs) play a crucial role because of their powerful therapeutic effects.These effects primarily stem from the paracrine secretion of multiple factors by MSCs, with exosome‐carried microRNAs being the most effective component in promoting cardiac function recovery after infarction. Exosome therapy has emerged as a promising cell‐free treatment for myocardial infarction as a result of its relatively simple composition, low immunogenicity and controlled transplantation dose. Despite these advantages, maintaining the stability of exosomes after transplantation and enhancing their targeting effect remain significant challenges in clinical applications. In recent developments, several approaches have been designed to optimize exosome therapy. These include enhancing exosome retention, improving their ability to target specific effects, pretreating MSC‐derived exosomes and employing transgenic MSC‐derived exosomes. This review primarily focuses on describing the biological characteristics of exosomes, their therapeutic potential and their application in treating myocardial infarction.
Synthesis, characterization, antibacterial activity and cytotoxicity of (1′R,2′S,7a′S)‐2′‐(2,5‐dichlorothiophene‐3‐carbonyl)‐1′‐(aryl)‐1′,2′,5′,6′,7′,7a′‐hexahydrospiro[indoline‐3,3′‐pyrrolizin]‐2‐one derivatives
Authors: Al‐Refai Mahmoud , Ali Basem F. , Al‐Masri Eman K. , Mansi Iman A. , Aljaar Nayyef , Abu‐Irmaileh Bashaer , Geyer Armin , Ivlev Sergei I. 
Published: September 2023

AbstractThe synthesis and bioactivity studies of a series of (1′R,2′S,7a′S)‐2′‐(2,5‐dichlorothiophene‐3‐carbonyl)‐1′‐(aryl)‐1′,2′,5′,6′,7′,7a′‐hexahydrospiro[indoline‐3,3′‐pyrrolizin]‐2‐one derivatives are described here. The spirooxindole title compounds were obtained from the regio‐ and diastereoselective 1,3‐dipolar cycloaddition reaction between an intermediate azomethine ylide and different chalcones. The structures of all compounds were proposed based on elemental analysis, ATR‐FTIR, 1H NMR, 13C NMR, ESIMS, and HRESIMS. Single crystal x‐ray structure determinations for some derivatives confirm the proposed structures. All synthesized compounds showed high cytotoxicity toward A549, HCT116, MCF7, DU145, and K562 but eight of them were also toxic toward normal skin fibroblast cell lines. Compound 4b showed moderate cytotoxicity toward A549 and MCF7 while 4c was highly cytotoxic toward DU145 and K562 and moderately toxic toward other cell lines. Both compounds were nontoxic toward normal skin fibroblast which makes them good drug candidates.
Correlates of postnatal human cytomegalovirus transmission in term babies in the first year
Authors: d'Angelo Piera , Zelini Paola , Zavaglio Federica , Piccini Stefania , Cirasola Daniela , Arossa Alessia , Spinillo Arsenio , Lilleri Daniele , Baldanti Fausto 
Published: September 2023

AbstractPostnatal human cytomegalovirus (HCMV) infection in newborns is well characterized for preterm infants but less so for term infants. We sought to analyze the rates and routes of HCMV transmission in full‐term infants during the first year of life. A cohort of 120 HCMV seropositive mothers and their 122 newborns were tested after delivery for HCMV‐DNA shedding in different bodily fluids. Postnatal HCMV infection was defined as the detection of >2.5 × 102 HCMV‐DNA copies/mL in infants' saliva swabs. Maternal neutralizing antibody serum titer, HCMV‐specific T‐cell response, and HCMV glycoprotein B immunoglobulin G on breastmilk were analyzed. HCMV shedding was detected in 67 of 120 mothers (55.8%), and 20 of 122 infants (16.4%) developed HCMV infection within the first 3 months of life. Six additional infants were infected during the first year, for a postnatal infection rate of 21.3%. Viral shedding was more frequent in breastmilk than saliva, urine, and vaginal secretions, and the mothers of infected infants showed higher levels of HCMV‐DNA in milk. No association was found between the antibody levels in serum or milk and maternal viral shedding, whereas a slightly lower frequency of HCMV‐specific CD4+ T‐cells with long‐term memory phenotype was observed in women with HCM‐DNA‐positive milk. About one out of five infants develop HCMV infection within the first year of life. Breastmilk appears the major route of transmission of the infection, maternal saliva has a minor role whereas the role of vaginal secretions is negligible.
Influence of pre‐treatment methods on quality indicators and mineral composition of plant milk from different sources of raw materials
Authors: Lavrentev Filipp V. , Baranovskaia Darina A. , Shiriaev Valerii A. , Fomicheva Daria A. , Iatsenko Viktotiia A. , Ivanov Maksim S. , Ashikhmina Mariia S. , Morozova Olga V. , Iakovchenko Natalia V. 
Published: September 2023

AbstractBACKGROUNDPre‐treatment of plant materials is essential in producing plant‐based products and can affect their various organoleptic and physicochemical characteristics. This work aimed to study the effect of pre‐treatment of vegetable raw materials, namely ultrasonic processing and freezing of raw materials under various low‐temperature conditions, to obtain multiple types of vegetable milk and determine their characteristics.RESULTSIt is shown that by applying a certain kind of pre‐treatment of vegetable raw materials it is possible to adjust organoleptic parameters and the content of solids, protein, fat, carbohydrates, fiber and mineral composition of various types of vegetable milk from soy, rice, oats, wheat, peas, buckwheat, pumpkin seeds and lentils. Ultrasound pre‐treatment allows increasing of polyphenol content by an average of 15–20% for all types of plant milk, except for lentil milk. The results showed that ultrasound treatment for 3 min had the most significant effect on the overall acceptability for lentils, pumpkin, rice and pea milk. Pre‐freezing at a temperature regime of −17 and –85 °C contributed to an increase in Fe, K, Zn, Ca, Mg, Si and P by an average of 30–100%, depending on the plant material.CONCLUSIONPre‐treatment of vegetable raw materials, including freezing and ultrasonic treatment, can positively affect the macro‐ and micronutrient composition of plant milk. However, the effect may vary depending on the type of raw material and processing conditions. © 2023 Society of Chemical Industry.
Soy protein isolate–guar gum–goose liver oil O/W Pickering emulsions that remain stable under accelerated oxidation at high temperatures
Authors: Fan Xiankang , Li Chunwei , Shi Zihang , Xia Qiang , Du Lihui , Zhou Changyu , Pan Daodong 
Published: September 2023

AbstractBackgroundGoose liver oil (GLO) is a solid–liquid mixture, rich in polyunsaturated fatty acids and high in nutritional value, but poor in fluidity and easily oxidized. Therefore, oil‐in‐water (O/W) Pickering emulsions of three polysaccharides and soy protein isolate (SPI) with GLO were prepared to improve the stability of it.ResultsSodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE), Fourier‐transform infrared spectroscopy, and zeta potential revealed that the SPI and complexes with konjac glucomannan, pectin, and guar gum (GG) ranged from 17 to 75 kDa, with the site of action being the –OH stretch and the amide group, and bound by hydrogen bonding. Adding konjac glucomannan and GG significantly increased the water contact angle of the SPI to 74.1° and 59.0°, respectively. Therefore, the protein–polysaccharide complexes could enhance the emulsion stability. In addition, the O/W Pickering emulsions with GLO had near‐Newtonian fluid rheological properties with a significant increase in apparent viscosity and viscoelasticity, forming a dual network structure consisting of a ductile and flexible protein network and a rigid and brittle polysaccharide network. The microstructure observation indicated that the O/W emulsions were spherical and homogeneous. The highest emulsification activity was observed for the SPI–GG–GLO emulsions, without significant delamination or flocculation and high oxidative stability after 7 days in storage.ConclusionThese results demonstrate that the construction of SPI–GG–GLO O/W Pickering emulsions can stabilize GLO even at high temperatures that promote oxidation. © 2023 Society of Chemical Industry.
Assessing the effects of drought on rainfed maize water footprints based on remote sensing approaches
Authors: Li Bo , Qin Lijie , Qi Hang , Wang Jianqin , Dang Yongcai , Lv Mingzhu , He Hongshi 
Published: September 2023

AbstractBACKGROUNDDrought affects the characteristics of water use during crop production and so quantitatively evaluating the impacts is important. However, it remains unclear how crop water use responds to drought. To address this gap, water footprint (WF) and standardized precipitation evapotranspiration index (SPEI) were calculated by remote sensing approaches to assess the effects of drought on crop water use. Rainfed maize is the most important crop in Jilin Province, and its growth and water use are more susceptible to drought. The present study explored not only the impact of growing season drought on the maize WF values in Jilin Province, but also the response of WF values to drought at different time scales.RESULTSSpatially, 72.94% of the WFblue pixels showed a non‐significant increase, and the WFgreen in 68% pixels decreased significantly, being mainly concentrated in the middle region. Furthermore, the pixels affected by monthly time scale drought were mainly in the middle region, whereas the pixels affected by annual time scale drought were mainly in the western region.CONCLUSIONDrought not only affected on the source and structure of agricultural water consumption, but also had different effects on WF values at different time scale. These effects had obvious spatial differences. The present study systematically explored the effects of drought on the WF values for rainfed maize in different climate regions and a consideration of these effects could provide valuable information on rainfed maize growth and the agricultural water use response to a changing climate. © 2023 Society of Chemical Industry.
Novel Linear Piezo‐resistive Auxetic Meta‐Sensors with Low Young's Modulus by a Core–Shell Conceptual Design and Electromechanical Modelling
Authors: Taherkhani Bahman , Bodaghi Mahdi , Mousavi Nejad Souq Seyyed Sajad , Malmir Chegini Motaleb , Nemati Mohammad 
Published: September 2023

AbstractProduction of piezo‐resistive auxetic sensors is usually carried out through mixing and coating methods. Although these methods are beneficial, Young's modulus of mixed sensors becomes high because of using a high percentage of sensing elements while the durability of coated sensors gets low due to the separation of sensing elements from the sensor surface. This article presents a new core–shell metamaterial model to address the mentioned problems. The shell and the core are produced of polydimethylsiloxane (PDMS) rubber and a mixture of PDMS/graphite powders (73.45 wt% graphite powders), respectively. A finite element model is developed via COMSOL software to predict the electromechanical behaviors of the created sensor and verified by an experimental study. Scanning electron microscope imaging is conducted to detect the separations of the graphite particles. The main important feature of this meta‐sensor is to possess a linear sensitivity due to having zero Poisson's ratio. The advantage of this method is that Young's modulus of the sensor does not decrease (unlike the mixing method), and the sensor‐coated particles do not separate from the sensor after a while (unlike the coating method). The introduced model has advantages that promote potential applications such as using sensory gloves to detect, for instance, human hand movements.
DDR1/2 enhance KIT activation and imatinib resistance of primary and secondary KIT mutants in gastrointestinal stromal tumors
Authors: Liu Anbu , Zhang Shaoting , Wang Ming , Zhang Liangying , Xu Shidong , Nasimian Ahmad , Li Shujing , Zhao Sien , Cao Xu , Tian Jinhai , Yu Yuanyuan , Fan Zhaoyang , Xiao Kun , Zhao Hui , Kazi Julhash U. , Ma Lijun , Sun Jianmin 
Published: September 2023

AbstractGastrointestinal stromal tumors (GISTs) are predominantly initiated by KIT mutations. In this study, we observed that discoidin domain receptors 1 and 2 (DDR1 and DDR2) exhibited high expression in GISTs, were associated with KIT, and enhanced the activation of both wild‐type KIT and primary KIT mutants. Inhibition of DDR1/2 led to a reduction in the activation of KIT and its downstream signaling molecules, ultimately impairing GIST cell survival and proliferation in vitro. Consequently, treatment of mice carrying germline KIT/V558A mutation with DDR1/2 inhibitor significantly impeded tumor growth, and the combined use of DDR1/2 inhibitor and imatinib, the first‐line targeted therapeutic agent for GISTs, markedly enhanced tumor growth suppression. In addition, DDR1/2 inhibition resulted in decreased KIT expression, while KIT inhibition led to upregulation of DDR1/2 expression in GISTs. The presence of DDR1/2 also decreased the sensitivity of wild‐type KIT or primary KIT mutants to imatinib, indicating a possible role for DDR1/2 in promoting GIST survival during KIT‐targeted therapy. The development of drug‐resistant secondary KIT mutations is a primary factor contributing to GIST recurrence following targeted therapy. Similar to primary KIT mutants, DDR1/2 can associate with and enhance the activation of secondary KIT mutants, further diminishing their sensitivity to imatinib. In summary, our data demonstrate that DDR1/2 contribute to KIT activation in GISTs and strengthen resistance to imatinib for both primary and secondary KIT mutants, providing a rationale for further exploration of DDR1/2 targeting in GIST treatment.
Asymmetrically Substituted s‐Triazine Phosphonates by One‐Step Synthesis
Authors: Vogt Claudia , Höhne Carl‐Christoph , Limburger Jennifer , König Alexander , Wagener Tobias , Kroke Edwin 
Published: September 2023

AbstractAsymmetrically substituted s‐triazine phosphonates with up to three different phosphonate groups C3N3RR'R” with R, R’, R”=PO(OR”’) and R”’=for example, methyl, ethyl, isopropyl or n‐butyl are interesting as polymer additives like flame retardants. Typically, these compounds are obtained by multiple synthesis steps. However, this leads to high production costs, which are a disadvantage for commercial use. Here we report the one‐step synthesis of mixtures of asymmetrical s‐triazine phosphonates which is an easy way to adjust the thermal behaviour and other properties such as viscosities of the compounds. The synthesis is based on a Michaelis–Arbuzov reaction. A complete conversion of the reactants to the target compounds is observed which was proofed by detailed 1H, 13C and 31P NMR investigations and elemental analysis. The thermal behaviour was compared with thermogravimetric analysis (TGA).
Targeting a faster time‐to‐solution of mortar‐based contact problems
Authors: Steimer Christopher , Mayr Matthias , Popp Alexander 
Published: September 2023

AbstractWhile mortar methods are undoubtedly among the most prominent and accurate approaches in computational contact mechanics, they come with considerable cost. The required numerical effort originates not only from the evaluation of the mortar integrals but also from the solution of the system of linear equations within Newton‐type solvers. While each of these cost factors has been analyzed and addressed individually in the past, this contribution outlines approaches and first results to comprehensively reduce the time to solution by combining dynamic load balancing techniques with algebraic multigrid preconditioners. We present a proof of concept for a three‐dimensional unilateral contact simulation with an evolving contact zone.
Multifield computational model for human brain development: Explicit numerical stabilization
Authors: Zarzor Mohammad Saeed , Steinmann Paul , Budday Silvia 
Published: September 2023

AbstractThe morphological surface of the human brain is still puzzling to scientists. During the last few decades, studies have addressed different aspects of this phenomenon. The underlying cellular processes occurring at the microscopic scale are certainly important for the folding process. However, there is also an essential contribution from mechanical forces generated at the macroscopic scale during these processes. Many previous studies confirmed this fact, but still, most of them have not considered the link between cellular processes and mechanical forces. Recently, we have explained how the proliferation in different zones of the brain, cell migration, and neuronal connectivity affect the folding through a multifield computational model coupling an advection‐diffusion model with the theory of finite growth. We mathematically describe the cellular behavior of cells to control mechanical growth in both radial and circumferential directions. To deal with issues regarding numerical stability of the advection‐diffusion equation, which lead to temporal and spatial numerical oscillations, reduced efficiency of the numerical solver, and inaccurate results, we introduce an artificial diffusivity, which we apply only when the actual cell density does not satisfy the balance equation. The proposed method stabilizes the numerical solution and significantly improves the simulation results without additional numerical cost. It allows us to study brain development in 2D and 3D.