bluuebunny/crossref_metadata_2025 huggingface dataset:
Layout Design of Strapdown Array Seeker and Extraction Method of Guidance Information
Authors: Yang Hao , Bai Xibin , Zhang Shifeng
Published: July 2022

This paper proposed a multi-view surface array to enlarge the field-of-view (FOV) from 45° × 45° to 72° × 75° and improve the estimation precision of guidance information. First, based on circular and rectangular FOV sensors, the superposition characteristics of FOV in the +-shaped layout and the X-shaped layout were explored and analyzed. Secondly, normalization processing was applied to obtain the equivalent measurement value of the central sensor and the corresponding error distribution. Based on such measurement value and error distribution, the filtering model could be constructed, which could effectively solve the problem of observation number variation caused by multiple sensors. Thirdly, a multivariate iterated extended Kalman filter (MIEKF) was proposed to make full use of multiple measurements. By iterating multiple unequal observations and making full use of the known error distribution information, the noise of filtered data was found to be effectively reduced and the estimation precision of guidance information was improved. Finally, based on a 6-DOF trajectory simulation, the correctness and effectiveness of the proposed method were verified. Simulation results show that MIEKF can improve the estimation accuracy of the line-of-sight (LOS) angle by at least 30% and the estimation accuracy of the LOS angle rate by nearly 80% compared with EKF.
Transcriptome Sequencing of Agave angustifolia Reveals Conservation and Diversification in the Expression of Cinnamyl Alcohol Dehydrogenase Genes in Agave Species
Authors: Huang Xing , Xu Bochao , Tan Shibei , Huang Yanlei , Xi Jingen , Qin Xu , Chen Tao , Chen Helong , Yang Xiaohan , Yi Kexian
Published: July 2022

Agave angustifolia is an important crassulacean acid metabolism plant species, with wide applications in beverage and sisal fiber production. In this study, we carried out a transcriptome analysis of A. angustifolia leaves, generating a total of 58,482,436 clean reads through Illumina paired-end sequencing. De novo transcriptome assembly generated 67,314 unigenes, with about half of them having homologs in four public databases. In the Nr database, Asparagus officinalis was shown to be most closely related to agave, and the early angiosperm Amborella trichopoda was selected as an outgroup species. We further identified five, two, seven, seven, seven, six and six CAD genes in asparagus, amborella, A. deserti, A. tequilana, A. americana, A. hybrid H11648 and A. angustifolia, respectively. The maximum likelihood phylogenetic tree revealed the species-specific expansion of CAD genes in arabidopsis, rice and agave. The expression analysis indicated the conservatively expressed CAD1/2/4/6, providing candidate targets for manipulation to improve lignin traits. The species-specific expression of CAD3/5/7 indicates the existence of different regulatory mechanisms controlling the expression of these genes in agave species. This study presents the first transcriptome dataset of A. angustifolia, facilitating future studies on lignin biosynthesis in agave.
Sedation of Wild Pyrenean Capercaillie (Tetrao urogallus aquitanicus) Using Intramuscular Midazolam
Authors: Nicolás Francisco Olga , Afonso Jordana Ivan , Garcia Ferré Diego , Roig Simón Job , Ewbank Ana Carolina , Margalida Antoni , Sacristán Irene , Foulché Kévin , Ménoni Emmanuel , Sacristán Carlos
Published: July 2022

Global Positioning System (GPS) tracking offers key information in the study of movement ecology of threatened species. Nevertheless, the placement of GPS devices requires animal capture and handling, which may represent a challenge to the individual’s survival after release, mainly due to capture myopathy. The Pyrenean Capercaillie (Tetrao urogallus aquitanicus) is a threatened galliform especially sensitive to handling, extremely elusive, and challenging to capture. Our goal was to adapt a sedation protocol for Pyrenean Capercaillies undergoing GPS tagging, in order to increase their welfare and safety during the procedure. From 2018 to 2021, 23 wild Pyrenean Capercaillies were captured and sedated for GPS tagging as part of a European conservation project of emblematic Pyrenean avian species. The birds received intramuscular (IM) sedation with midazolam (ranging from 1.9 mg/kg to 8.08 mg/kg) and were handled for 20 to 40 min. Sedation was reversed with flumazenil (0.1 mg/mL IM). The sedated capercaillies were less responsive to stimuli (i.e., closed eyes and recumbency), showing discrete to no response to handling (i.e., placement of the GPS device, physical examination, cloacal temperature measurement, or reflex tests). Such response was compared in birds with sedation doses above and below the average dose (5.17 mg/kg). Only one clinical sign showed statistically significant differences between the two groups (“open-mouth breathing” sign, p = 0.02). A mortality rate of 4.35% was registered (one individual died during handling). Sedation facilitated the handling of the birds and faster interventions in the field, without increasing mortality when compared to handling without sedation. Therefore, sedation was shown to be a useful tool to reduce stress related to capture and handling of the threatened Pyrenean Capercaillie.
The Differences in Histoarchitecture of Hoof Lamellae between Obese and Lean Draft Horses
Authors: Senderska-Płonowska Magdalena , Siwińska Natalia , Zak-Bochenek Agnieszka , Rykała Marta , Słowikowska Malwina , Madej Jan P. , Kaleta-Kuratewicz Katarzyna , Niedźwiedź Artur
Published: July 2022

Obesity is a common problem in horses. The associations between obesity and equine metabolic syndrome (EMS) and between EMS and laminitis are known. However, there is a lack of data on whether obesity itself can affect hoof lamellae. Forelimbs and blood from 12 draft horses (six obese and six lean) from a slaughterhouse were acquired. To exclude laminitis and EMS horses, insulin concentration was measured, and hooves were radiographed. Histological evaluation was performed. The shape of the primary and secondary epidermal lamellae (PEL and SEL) was evaluated, and the length of the keratinized and total primary epidermal lamellae was measured (KPEL and TEL). All horses showed pathological changes in lamellae. In the lean group, the changes were longer SELs, more proliferated and separated PDLs, and less standard PDLs. In the obese group, the changes were a lower number of club-shaped and standard SELs and significantly more tapered SELs. No difference in the shape of PELs and the length of KPELs was noticed. The research did not confirm the effects of obesity on lamellar failure. The measurements taken indicate that the lamellae are much longer compared to other research studies; this could indicate that the length of the PEL depends on the hoof size.
Comparative Transcriptome Analysis Provides Novel Insights into the Effect of Lipid Metabolism on Laying of Geese
Authors: Ouyang Qingyuan , Hu Shenqiang , Tang Bincheng , Hu Bo , Hu Jiwei , He Hua , Li Liang , Wang Jiwen
Published: July 2022

The lower egg production of geese (20~60 eggs per year) compared with chicken and duck limits the development of the industry, while the yolk weight and fatty liver susceptibility of geese was higher than that of other poultry. Therefore, the relationship between lipid metabolism and the laying performance of geese remains to be explored. Phenotypically, we observed that the liver fat content of the high-, low-, and no-egg production groups decreased in turn, while the abdominal fat weight increased in turn. For transcriptional regulation, the KEGG pathways related to lipid metabolism were enriched in all pairwise comparisons of abdominal fat and liver through functional analysis. However, some KEGG pathways related to inflammation and the circadian rhythm pathway were enriched by DEGs only in abdominal fat and the liver, respectively. The DEGs in ovarian stroma among different groups enriched some KEGG pathways related to ovarian steroidogenesis and cell adhesion. Our research reveals that lipid metabolism regulated by the circadian rhythm of the liver may directly or indirectly affect ovarian function through the inflammation and hormone secretion of abdominal fat. These results offer new insights into the regulation mechanisms of goose reproductive traits.
Ebselen Interferes with Alzheimer’s Disease by Regulating Mitochondrial Function
Authors: Li Xuexia , Shi Qingqing , Xu Hao , Xiong Yufang , Wang Chao , Le Linfeng , Lian Junliang , Wu Guoli , Peng Feiyuan , Liu Qiong , Du Xiubo
Published: July 2022

(1) Background: With unknown causes and no effective treatment available, Alzheimer’s disease (AD) places enormous pressure on families and society. Our previous study had shown that Ebselen at a high concentration (10.94 μM) improved the cognition of triple-transgenic AD (3×Tg-AD) mice and alleviated the related pathological indicators but showed toxicity to the mice. Here, we dedicated to study the therapeutic effect and molecular mechanism of Ebselen at a much lower concentration on 3×Tg-AD mice. (2) Methods: Various behavioral experiments were applied to detect the behavioral ability of mice. Western blot, thioflavin T staining and a transmission electron microscope were used to evaluate the pathology of AD mice. The mitochondrial membrane potential and respiration were assessed with the corresponding assay kit. (3) Results: Ebselen remarkably increased cognitive ability of AD mice, eliminated β-Amyloid (Aβ) oligomers and recovered the synaptic damage in AD mice brain. In addition, the destroyed mitochondrial morphologies and function were repaired by Ebselen through ameliorating mitochondrial energy metabolism, mitochondrial biogenesis and mitochondrial fusion/fission balance in N2a-SW cells and brain tissues of AD mice. (4) Conclusions: This research indicated that Ebselen might exert its therapeutic effect via protecting mitochondria in AD.
Phenolic Characterization Using cLC-DAD Analysis and Evaluation of In Vitro and In Vivo Pharmacological Activities of Ruta tuberculata Forssk
Authors: Saidi Asma , Hambaba Leila , Bensaad Mohamed Sabri , Melakhessou Mohamed Akram , Bensouici Chawki , Ferhat Nouicer , Kahoul Mohamed Amine , Helal Mahmoud , Sami Rokayya , Alharthy Saif A. , Baty Roua S. , Alsubhi Nouf H. , Alrefaei Ghadeer I. , Elhakem Abeer , Alharthi Sarah , Elsaid Fahmy G. , Shati Ali A.
Published: July 2022

The perennial aromatic plant Ruta tuberculata Forssk (Rutaceae) has been traditionally used by Mediterranean peoples as folk medicine against several types of disease to treat diverse illness. The objective of this work is to evaluate the in vitro and in vivo pharmacological activities of the aqueous (RAE) and methanolic (MeOH) 80% (RME) extracts of Algerian R. tuberculata aerial parts. Antioxidant potential, neuro-protective and anti-arthritic activities were investigated in vitro using six antioxidant approaches and by determining acetyl-cholinesterase and bovine albumin denaturation inhibitory capacities, respectively. Furthermore, in vivo anti-ulcer and anti-inflammatory activities were evaluated on EtOH-induced gastric mucosal damage and carrageenan-induced paw edema models in mice. Moreover, bio-compounds’ contents were also quantified using spectrophotometric and cLC-DAD methods. Both in vivo and in vitro investigations showed remarkable antioxidant activity of Ruta tuberculata Forssk, while methanolic extract (RME) of Ruta tuberculata Forssk exhibited more significant neuro-protective and anti-inflammatory effects. However, the antiulcer activity was more pronounced with RAE of R. tuberculata, which suggests that this plant can be considered as a natural resource of potent bioactive compounds that may act as antioxidant and anti-inflammatory agents, which underlines the importance of incorporating them in therapies in order to treat various diseases linked to oxidative stress, and they may also provide crucial data for the development of new anticholinesterase drugs to improve neurodegenerative diseases, such as Alzheimer’s.
Physapruin A Induces Reactive Oxygen Species to Trigger Cytoprotective Autophagy of Breast Cancer Cells
Authors: Yu Tzu-Jung , Shiau Jun-Ping , Tang Jen-Yang , Yen Chia-Hung , Hou Ming-Feng , Cheng Yuan-Bin , Shu Chih-Wen , Chang Hsueh-Wei
Published: July 2022

Physalis peruviana-derived physapruin A (PHA) is a potent compound that selectively generates reactive oxygen species (ROS) and induces cancer cell death. Autophagy, a cellular self-clearance pathway, can be induced by ROS and plays a dual role in cancer cell death. However, the role of autophagy in PHA-treated cancer cells is not understood. Our study initially showed that autophagy inhibitors such as bafilomycin A1 enhanced the cytotoxic effects of PHA in breast cancer cell lines, including MCF7 and MDA-MB-231. PHA treatment decreased the p62 protein level and increased LC3-II flux. PHA increased the fluorescence intensity of DAPGreen and DALGreen, which are used to reflect the formation of autophagosome/autolysosome and autolysosome, respectively. ROS scavenger N-acetylcysteine (NAC) decreased PHA-elevated autophagy activity, implying that PHA-induced ROS may be required for autophagy induction in breast cancer cells. Moreover, the autophagy inhibitor increased ROS levels and enhanced PHA-elevated ROS levels, while NAC scavenges the produced ROS resulting from PHA and autophagy inhibitor. In addition, the autophagy inhibitor elevated the PHA-induced proportion of annexin V/7-aminoactinmycin D and cleavage of caspase-3/8/9 and poly (ADP-ribose) polymerase. In contrast, NAC and apoptosis inhibitor Z-VAD-FMK blocked the proportion of annexin V/7-aminoactinmycin D and the activation of caspases. Taken together, PHA induced ROS to promote autophagy, which might play an antioxidant and anti-apoptotic role in breast cancer cells.
A State of the Art Review on Sensible and Latent Heat Thermal Energy Storage Processes in Porous Media: Mesoscopic Simulation
Authors: Mabrouk Riheb , Naji Hassane , Benim Ali Cemal , Dhahri Hacen
Published: July 2022

Sharing renewable energies, reducing energy consumption and optimizing energy management in an attempt to limit environmental problems (air pollution, global warming, acid rain, etc.) has today become a genuine concern of scientific engineering research. Furthermore, with the drastic growth of requirements in building and industrial worldwide sectors, the need for proper techniques that allow enhancement in the thermal performance of systems is increasingly being addressed. It is worth noting that using sensible and latent heat storage materials (SHSMs and phase change materials (PCMs)) for thermal energy storage mechanisms can meet requirements such as thermal comfort in buildings when selected correctly. However, as the operating temperature changes, a series of complex technical issues arise, such as heat transfer issues, leaks, corrosion, subcooling, supercooling, etc. This paper reviews the most recent research advances in the area of sensible and latent heat storage through the porous media as potential technology while providing useful information for researchers and engineers in the energy storage domain. To this end, the state and challenges of PCMs incorporation methods are drawn up, and an updated database of various research is provided while discussing the conclusions concerning the sensible and latent heat storage in porous media, their scopes of application and impact on energy consumption. In the light of this non-exhaustive review, it turns out that the adoption of porous matrices improves the thermal performance of systems, mitigates energy consumption and drops CO2 emissions while ensuring thermal comfort within buildings. In addition, at the representative elementary volume (REV) and pore scales, the lattice Boltzmann method (LBM) is examined as an alternative method to the commonly used, traditional numerical methods. These two approaches are compared based on results available in the literature. Through these means, their ability to handle latent and sensible heat storage process in a porous medium is demonstrated. To sum up, to be more complete, perspectives of sensible and latent energy storage technologies are covered.
Application of Particle Swarm Optimization for Improvement of Peel Strength in a Laminated Double-Lap Composite Joint
Authors: Arjomandi Mohammad Ali , Shishehsaz Mohammad , Ghanbarzadeh Afshin , Mosallanezhad Behzad , Akrami Mohammad
Published: July 2022

A double lap joint is commonly used in thin structures under low running loads. Peel and inter-laminar stresses are among the major limitations of this type of joint, which may cause delamination failure. These stresses should be determined for designing a stronger structure. This study presents a method based on particle swarm optimization to find the best layup for a classic double lap joint under horizontal constant tensile forces. The peel stress equation is analytically obtained and utilized as the objective function for the algorithm. The method’s accuracy is explored by assessing the algorithm’s ability. This helps to find the best arrangement with the highest strength delamination against considering four initial layups. The results show that the optimized layups, on average, can reduce peel stress by about 96%. Additionally, the effects of different parameters on joint strength are investigated.
A Deformation Force Monitoring Method for Aero-Engine Casing Machining Based on Deep Autoregressive Network and Kalman Filter
Authors: Guo Haonan , Li Yingguang , Liu Changqing , Ni Yang , Tang Kai
Published: July 2022

Aero-engine casing is a kind of thin-walled rotary part for which serious deformation often occurs during its machining process. As deformation force is an important physical quantity associated with deformation, the utilization of deformation force to control the deformation has been suggested. However, due to the complex machining characteristics of an aero-engine casing, obtaining a stable and reliable deformation force can be quite difficult. To address this issue, this paper proposes a deformation force monitoring method via a pre-support force probabilistic decision model based on deep autoregressive neural network and Kalman filter, for which a set of sophisticated clamping devices with force sensors are specifically developed. In the proposed method, the pre-support force is determined by the predicted value of the deformation force and the equivalent flexibility of the part, while the measurement errors and the reality gaps are reduced by Kalman filter via fusing the predicted and measured data. Both computer simulation and physical machining experiments are carried out and their results give a positive confirmation on the effectiveness of the proposed method. The results are as follows. In the simulation experiments, when the confidence is 84.1%, the success rate of deformation force monitoring is increased by about 30% compared with the traditional approach, and the final impact of clamping deformation of the proposed method is less than 0.003 mm. In the real machining experiments, the results show that the calculation error of deformation by the proposed method based on monitoring the deformation force is less than 0.008 mm.
Theoretical and Observational Constraints on Lunar Orbital Evolution in the Three-Body Earth-Moon-Sun System
Authors: Hofmeister Anne M. , Criss Robert E. , Criss Everett M.
Published: July 2022

Extremely slow recession of the Moon from the Earth has been recently proposed and attributed to conversion of Earth’s axial spin to lunar orbital momentum. This hypothesis is inconsistent with long-standing recognition that the Moon’s orbit involves three-body interactions. This and other short-comings, such as Earth’s spin loss being internal, are summarized here. Considering point-masses is justified by theory and observational data on other moons. We deduce that torque in the Earth-Moon-Sun system increases eccentricity of the lunar orbit but decreases its inclination over time. Consequently, the average lunar orbital radius is decreasing. We also show that lunar drift is too small to be constrained through lunar laser ranging measurements, mainly because atmospheric refraction corrections are comparatively large and variations in lunar cycles are under-sampled. Our findings support co-accretion and explain how orbits evolve in many-body point-mass systems.
Large-Scale Meteorological Drivers of the Extreme Precipitation Event and Devastating Floods of Early-February 2021 in Semarang, Central Java, Indonesia
Authors: Hermawan Eddy , Lubis Sandro W. , Harjana Teguh , Purwaningsih Anis , Risyanto Risyanto , Ridho Ainur , Andarini Dita Fatria , Ratri Dian Nur , Widyaningsih Retno
Published: July 2022

Unusually long duration and heavy rainfall from 5 to 6 February 2021 caused widespread and devastating floods in Semarang, Central Java, Indonesia. The heavy rainfall was produced by two mesoscale convective systems (MCSs). The first MCS developed at 13Z on 5 February 2021 over the southern coast of Sumatra and propagated towards Semarang. The second MCS developed over the north coast of Semarang at 18Z on 5 February 2021 and later led to the first peak of precipitation at 21Z on 5 February 2021. These two MCSs eventually merged into a single MCS, producing the second peak of precipitation at 00Z on 6 February 2021. Analysis of the moisture transport indicates that the strong and persistent north-westerly wind near the surface induced by CENS prior to and during the event created an intensive meridional (southward) tropospheric moisture transport from the South China Sea towards Semarang. In addition, the westerly flow induced by low-frequency variability associated with La Nina and the tropical depression over the North of Australia produced an intensive zonal (eastward) tropospheric moisture transport from the Indian Ocean towards Semarang. The combined effects of the zonal and meridional moisture transport provided favorable conditions for the development of MCSs, and hence extreme rainfall over Semarang. These results provide useful precursors for extreme weather-driven hazard prediction in Semarang and the surrounding regions in the future.
Magnetic Sublevel Independent Magic and Tune-Out Wavelengths of the Alkaline-Earth Ions
Authors: Jyoti  , Kaur Harpreet , Arora Bindiya , Sahoo Bijaya Kumar
Published: July 2022

Light shift in a state due to the applied laser in an atomic system vanishes at tune-out wavelengths (λTs). Similarly, differential light shift in a transition vanishes at the magic wavelengths (λmagics). In many of the earlier studies, values of the electric dipole (E1) matrix elements were inferred precisely by combining measurements and calculations of λmagic. Similarly, the λT values of an atomic state can be used to infer the E1 matrix element, as it involves dynamic electric dipole (α) values of only one state whereas the λmagic values require evaluation of α values for two states. However, both the λmagic and λT values depend on angular momenta and their magnetic components (M) of states. Here, we report the λmagic and λT values of many S1/2 and D3/2,5/2 states, and transitions among these states of the Mg+, Ca+, Sr+ and Ba+ ions that are independent of M values. It is possible to infer a large number of E1 matrix elements of the above ions accurately by measuring these values and combining with our calculations.
On Some Generalizations of Reverse Dynamic Hardy Type Inequalities on Time Scales
Authors: El-Deeb Ahmed A. , Cesarano Clemente
Published: July 2022

In the present paper, we prove some new reverse type dynamic inequalities on T. Our main inequalities are proved by using the chain rule and Fubini’s theorem on time scales T. Our results extend some existing results in the literature. As special cases, we obtain some new discrete inequalities, quantum inequalities and integral inequalities.
Enhancing Marketing Provision through Increased Online Safety That Imbues Consumer Confidence: Coupling AI and ML with the AIDA Model
Authors: Lee Yang-Im , Trim Peter R. J.
Published: July 2022

To enhance the effectiveness of artificial intelligence (AI) and machine learning (ML) in online retail operations and avoid succumbing to digital myopia, marketers need to be aware of the different approaches to utilizing AI/ML in terms of the information they make available to appropriate groups of consumers. This can be viewed as utilizing AI/ML to improve the customer journey experience. Reflecting on this, the main question to be addressed is: how can retailers utilize big data through the implementation of AI/ML to improve the efficiency of their marketing operations so that customers feel safe buying online? To answer this question, we conducted a systematic literature review and posed several subquestions that resulted in insights into why marketers need to pay specific attention to AI/ML capability. We explain how different AI/ML tools/functionalities can be related to different stages of the AIDA (Awareness, Interest, Desire, and Action) model, which in turn helps retailers to recognize potential opportunities as well as increase consumer confidence. We outline how digital myopia can be reduced by focusing on human inputs. Although challenges still exist, it is clear that retailers need to identify the boundaries in terms of AI/ML’s ability to enhance the company’s business model.
Atherosclerosis Plaque Reduction by Lycopene Is Mediated by Increased Energy Expenditure through AMPK and PPARα in ApoE KO Mice Fed with a High Fat Diet
Authors: Mannino Federica , Pallio Giovanni , Altavilla Domenica , Squadrito Francesco , Vermiglio Giovanna , Bitto Alessandra , Irrera Natasha
Published: July 2022

Lycopene is a carotenoid found in tomatoes that has potent antioxidant activity. The Mediterranean diet is particularly rich in lycopene, which has well-known beneficial effects on cardiovascular health. We tested the effects of lycopene extract in a group of 20 ApoE knockout mice, fed with a high fat western diet for 14 weeks. Starting from week 3 and up to week 14, the mice were randomly divided into two groups that received lycopene (n = 10) by oral suspension every day at the human equivalent dose of 60 mg/day (0.246 mg/mouse/day), or the vehicle solution (n = 10). The lycopene administration reduced triglycerides and cholesterol blood levels starting from week 6 and continuing through to the end of the experiment (p < 0.001). This reduction was mediated by an enhanced liver expression of PPAR-α and AMPK-α and reduced SREBP levels (p < 0.0001). As a histological red-out, the extent of atherosclerotic plaques and the intima–media thickness in the aorta were significantly reduced by lycopene. In this context, lycopene augmented the Nrf-2 positivity staining in the endothelium, thereby confirming that its antioxidant activity was mediated by this nuclear factor. The positive results obtained in this pre-clinical model further support the use of lycopene extracts to reduce atherosclerosis.
Bone Mineral Density Is a Predictor of Mortality in Female Patients with Cholangiocellular Carcinoma Undergoing Palliative Treatment
Authors: Jördens Markus S. , Wittig Linda , Loberg Christina , Heinrichs Lisa , Keitel Verena , Schulze-Hagen Maximilian , Antoch Gerald , Knoefel Wolfram T. , Fluegen Georg , Loosen Sven H. , Roderburg Christoph , Luedde Tom
Published: July 2022

Background: Cholangiocellular adenocarcinoma (CCA) is a rare and aggressive malignancy originating from the bile ducts. Its general prognosis is poor as therapeutic options are limited. Many patients present with advanced stages of disease, and palliative chemotherapy remains the only treatment option. Prognostic markers to assess the outcome of chemotherapeutic treatment in CCA are limited. We therefore evaluated bone mineral density (BMD) as a prognostic tool in patients with advanced CCA. Patients and Methods: We included 75 patients with advanced CCA that were treated at our academic tumor center. Prior to treatment, bone mineral density was analyzed at the first lumbar vertebra using routine CT scans in the venous phase and the local PACS (IntelliSpace PACS, Philips, Amsterdam, The Netherlands). Results: BMD was not significantly different between male and female patients but decreased with age. Patients with BMD above 167 HU have a significantly improved overall survival (474 days vs. 254 days; log-rank X2(1) = 6.090; p = 0.014). The prognostic value of BMD was confirmed using univariate (HR 2.313 (95%CI: 1.170–4.575); p = 0.016) and multivariate (HR 4.143 (95%CI: 1.197–14.343); p = 0.025) Cox regression analyses. Subgroup analysis revealed that the prognostic value of BMD was only present in female patients and not in male patients, suggesting sex-specific differences. Conclusions: Our data suggest that BMD is a valuable, easily accessible, and independent prognostic marker for overall survival in patients with advanced CCA. Furthermore, subgroup analysis showed the sex specificity of this marker, which demonstrated relevance only in female patients.
Nephroprotective Effects of Semaglutide as Mono- and Combination Treatment with Lisinopril in a Mouse Model of Hypertension-Accelerated Diabetic Kidney Disease
Authors: Dalbøge Louise S. , Christensen Michael , Madsen Martin Rønn , Secher Thomas , Endlich Nicole , Drenic’ Vedran , Manresa-Arraut Alba , Hansen Henrik H. , Rune Ida , Fink Lisbeth N. , Østergaard Mette V.
Published: July 2022

Background: Obesity, hyperglycemia and hypertension are critical risk factors for development of diabetic kidney disease (DKD). Emerging evidence suggests that glucagon-like peptide-1 receptor (GLP-1R) agonists improve cardiovascular and renal outcomes in type 2 diabetes patients. Here, we characterized the effect of the long-acting GLP-1R agonist semaglutide alone and in combination with an ACE inhibitor (lisinopril) in a model of hypertension-accelerated, advanced DKD facilitated by adeno-associated virus-mediated renin overexpression (ReninAAV) in uninephrectomized (UNx) female diabetic db/db mice. Methods: Female db/db mice received a single intravenous injection of ReninAAV 1 week prior to UNx. Six weeks post-nephrectomy, db/db UNx-ReninAAV mice were administered (q.d.) vehicle, semaglutide (30 nmol/kg, s.c.) or semaglutide (30 nmol/kg, s.c.) + lisinopril (30 mg/kg, p.o.) for 11 weeks. Endpoints included blood pressure, plasma/urine biochemistry, kidney histopathology and RNA sequencing. Results: Vehicle-dosed db/db UNx-ReninAAV mice developed hallmarks of DKD characterized by severe albuminuria and advanced glomerulosclerosis. Semaglutide robustly reduced hyperglycemia, hypertension and albuminuria concurrent with notable improvements in glomerulosclerosis severity, podocyte filtration slit density, urine/renal kidney injury molecule-1 (KIM-1) levels and gene expression markers of inflammation and fibrogenesis in db/db UNx-ReninAAV mice. Co-administration of lisinopril further ameliorated hypertension and glomerulosclerosis. Conclusions: Semaglutide improves disease hallmarks in the db/db UNx-ReninAAV mouse model of advanced DKD. Further benefits on renal outcomes were obtained by adjunctive antihypertensive standard of care. Collectively, our study supports the development of semaglutide for management of DKD.
Near-Infrared Photoimmunotherapy for Thoracic Cancers: A Translational Perspective
Authors: Matsuoka Kohei , Yamada Mizuki , Sato Mitsuo , Sato Kazuhide
Published: July 2022

The conventional treatment of thoracic tumors includes surgery, anticancer drugs, radiation, and cancer immunotherapy. Light therapy for thoracic tumors has long been used as an alternative; conventional light therapy also called photodynamic therapy (PDT) has been used mainly for early-stage lung cancer. Recently, near-infrared photoimmunotherapy (NIR-PIT), which is a completely different concept from conventional PDT, has been developed and approved in Japan for the treatment of recurrent and previously treated head and neck cancer because of its specificity and effectiveness. NIR-PIT can apply to any target by changing to different antigens. In recent years, it has become clear that various specific and promising targets are highly expressed in thoracic tumors. In combination with these various specific targets, NIR-PIT is expected to be an ideal therapeutic approach for thoracic tumors. Additionally, techniques are being developed to further develop NIR-PIT for clinical practice. In this review, NIR-PIT is introduced, and its potential therapeutic applications for thoracic cancers are described.
Interaction Interface of Aβ42 with Human Na,K-ATPase Studied by MD and ITC and Inhibitor Screening by MD
Authors: Adzhubei Alexei A. , Tolstova Anna P. , Strelkova Maria A. , Mitkevich Vladimir A. , Petrushanko Irina Yu. , Makarov Alexander A.
Published: July 2022

Alzheimer’s disease (AD) is a neurodegenerative disease accompanied by progressive cognitive and memory dysfunction due to disruption of normal electrotonic properties of neurons and neuronal loss. The Na,K-ATPase interaction with beta amyloid (Aβ) plays an important role in AD pathogenesis. It has been shown that Na,K-ATPase activity in the AD brain was significantly lower than those in age-matched control brain. The interaction of Aβ42 with Na,K-ATPase and subsequent oligomerization leads to inhibition of the enzyme activity. In this study interaction interfaces between three common Aβ42 isoforms, and different conformations of human Na,K-ATPase (α1β1) have been obtained using molecular modeling, including docking and molecular dynamics (MD). Interaction sites of Na,K-ATPase with Aβ42 are localized between extracellular parts of α- and β- subunits and are practically identical for Na,K-ATPase at different conformations. Thermodynamic parameters for the formation of Na,K-ATPase:Aβ42 complex at different conformations acquired by isothermal titration calorimetry (ITC) are similar, which is in line with the data of molecular modeling. Similarity of Na,K-ATPase interaction interfaces with Aβ in all conformations allowed us to cross-screen potential inhibitors for this interaction and find pharmaceutical compounds that could block it.
NO-Dependent Mechanisms of p53 Expression and Cell Death in Rat’s Dorsal Root Ganglia after Sciatic-Nerve Transection
Authors: Rodkin Stanislav , Dzreyan Valentina , Bibov Mikhail , Ermakov Alexey , Derezina Tatyana , Kirichenko Evgeniya
Published: July 2022

Peripheral-nerve injury is a frequent cause of disability. Presently, no clinically effective neuroprotectors have been found. We have studied the NO-dependent expression of p53 in the neurons and glial cells of the dorsal root ganglia (DRG) of a rat’s spinal cord, as well as the role of NO in the death of these cells under the conditions of axonal stress, using sciatic-nerve axotomy as a model. It was found out that axotomy led to the nuclear–cytoplasmic redistribution of p53 in neurons, 24 h after trauma. The NO donor led to a considerable increase in the level of p53 in nuclei and, to a smaller degree, in the cytoplasm of neurons and karyoplasm of glial cells 4 and 24 h after axotomy. Application of a selective inhibitor of inducible NO-synthase (iNOS) provided the opposite effect. Introduction of the NO donor resulted in a significant increase in cell death in the injured ipsilateral DRG, 24 h and 7 days after trauma. The selective inhibitor of iNOS demonstrated a neuroprotective effect. Axotomy was shown to upregulate the iNOS in nuclei and cytoplasm of DRG cells. The NO-dependent expression of p53, which is particularly achieved through iNOS activation, is believed to be a putative signaling mechanism of neural and glial-cell death after axotomy.
Glutamate-Induced Deregulation of Krebs Cycle in Mitochondrial Encephalopathy Lactic Acidosis Syndrome Stroke-Like Episodes (MELAS) Syndrome Is Alleviated by Ketone Body Exposure
Authors: Belal Sophie , Goudenège David , Bocca Cinzia , Dumont Florent , Chao De La Barca Juan Manuel , Desquiret-Dumas Valérie , Gueguen Naïg , Geffroy Guillaume , Benyahia Rayane , Kane Selma , Khiati Salim , Bris Céline , Aranyi Tamas , Stockholm Daniel , Inisan Aurore , Renaud Aurélie , Barth Magalie , Simard Gilles , Reynier Pascal , Letournel Franck , Lenaers Guy , Bonneau Dominique , Chevrollier Arnaud , Procaccio Vincent
Published: July 2022

(1) Background: The development of mitochondrial medicine has been severely impeded by a lack of effective therapies. (2) Methods: To better understand Mitochondrial Encephalopathy Lactic Acidosis Syndrome Stroke-like episodes (MELAS) syndrome, neuronal cybrid cells carrying different mutation loads of the m.3243A > G mitochondrial DNA variant were analysed using a multi-omic approach. (3) Results: Specific metabolomic signatures revealed that the glutamate pathway was significantly increased in MELAS cells with a direct correlation between glutamate concentration and the m.3243A > G heteroplasmy level. Transcriptomic analysis in mutant cells further revealed alterations in specific gene clusters, including those of the glutamate, gamma-aminobutyric acid pathways, and tricarboxylic acid (TCA) cycle. These results were supported by post-mortem brain tissue analysis from a MELAS patient, confirming the glutamate dysregulation. Exposure of MELAS cells to ketone bodies significantly reduced the glutamate level and improved mitochondrial functions, reducing the accumulation of several intermediate metabolites of the TCA cycle and alleviating the NADH-redox imbalance. (4) Conclusions: Thus, a multi-omic integrated approach to MELAS cells revealed glutamate as a promising disease biomarker, while also indicating that a ketogenic diet should be tested in MELAS patients.
HDL-apoA-II Is Strongly Associated with 1-Year Mortality in Acute Heart Failure Patients
Authors: Klobučar Iva , Degoricija Vesna , Potočnjak Ines , Trbušić Matias , Pregartner Gudrun , Berghold Andrea , Fritz-Petrin Eva , Habisch Hansjörg , Madl Tobias , Frank Saša
Published: July 2022

The prognostic value of the subset of high-density lipoprotein (HDL) particles containing apolipoprotein (apo)A-II (HDL-apoA-II) in acute heart failure (AHF) remains unexplored. In this study, baseline serum levels of HDL-apoA-II (total and subfractions 1–4) were measured in 315 AHF patients using NMR spectroscopy. The mean patient age was 74.2 ± 10.5 years, 136 (43.2%) were female, 288 (91.4%) had a history of cardiomyopathy, 298 (94.6%) presented as New York Heart Association class 4, and 118 (37.5%) patients died within 1 year after hospitalization for AHF. Multivariable Cox regression analyses, adjusted for age and sex as well as other clinical and laboratory parameters associated with 1-year mortality in the univariable analyses, revealed a significant inverse association of HDL-apoA-II (hazard ratio (HR) 0.67 per 1 standard deviation (1 SD) increase, 95% confidence interval (CI) 0.47–0.94, p = 0.020), HDL2-apoA-II (HR 0.72 per 1 SD increase, 95% CI 0.54–0.95, p = 0.019), and HDL3-apoA-II (HR 0.59 per 1 SD increase, 95% CI 0.43–0.80, p < 0.001) with 1-year mortality. We conclude that low baseline HDL-apoA-II, HDL2-apoA-II, and HDL3-apoA-II serum levels are associated with increased 1-year mortality in AHF patients and may thus be of prognostic value in AHF.
2-Arachidonoylglycerol Reduces the Production of Interferon-Gamma in T Lymphocytes from Patients with Systemic Lupus Erythematosus
Authors: Navarini Luca , Vomero Marta , Di Donato Stefano , Currado Damiano , Berardicurti Onorina , Marino Annalisa , Bearzi Pietro , Biaggi Alice , Ferrito Matteo , Ruscitti Piero , Fava Marina , Leuti Alessandro , Cipriani Paola , Maccarrone Mauro , Giacomelli Roberto
Published: July 2022

Background: the endocannabinoid 2-arachidonoylglycerol (2-AG) plays a pivotal role in immune cells regulation. The plasma levels of 2-AG are increased in patients with systemic lupus erythematosus (SLE) and correlate with disease activity. Moreover, in plasmacytoid dendritic cells from SLE patients, 2-AG is able to control the production of type 1 interferon (IFN) through CB2 activation. The aim of this study was to evaluate the potential role of 2-AG on T lymphocytes from SLE patients. Methods: peripheral blood mononuclear cells (PBMCs) from SLE participants and age- and sex-matched healthy donors (HD) were isolated by Ficoll–Hypaque density-gradient centrifugation. The PBMCs were treated with increasing concentrations of 2-AG, and AM251 and AM630 were used to antagonize CB1 and CB2, respectively. Flow cytometry was used to assess the expression of CD3, CD4, CD8, CD25, IFN-ɣ, IL-4, and IL-17A. Results: 2-AG (1 μM) decreased IFN-ɣ expression (p = 0.0005) in the Th1 lymphocytes of SLE patients. 2-AG did not modulate the cytokine expression of any other T lymphocyte population from either SLE or HD. Treatment with both 2-AG and AM630 increased the IFN-ɣ expression in Th1 lymphocytes of SLE patients (p = 0.03). Discussion: 2-AG is able to modulate type 2 IFN production from CD4+ T lymphocytes from SLE patients through CB2 activation.
Simultaneous Detection of Salmonella typhimurium and Escherichia coli O157:H7 in Drinking Water and Milk with Mach–Zehnder Interferometers Monolithically Integrated on Silicon Chips
Authors: Angelopoulou Michailia , Petrou Panagiota , Misiakos Konstantinos , Raptis Ioannis , Kakabakos Sotirios
Published: July 2022

The consumption of water and milk contaminated with bacteria can lead to foodborne disease outbreaks. For this reason, the development of rapid and sensitive analytical methods for bacteria detection is of primary importance for public health protection. Here, a miniaturized immunosensor based on broadband Mach–Zehnder Interferometry for the simultaneous determination of S. typhimurium and E. coli O157:H7 in drinking water and milk is presented. For the assay, mixtures of bacteria solutions with anti-bacteria-specific antibodies were run over the chip, followed by solutions of biotinylated anti-species-specific antibody and streptavidin. The assay was fast (10 min for water, 15 min for milk), accurate, sensitive (LOD: 40 cfu/mL for S. typhimurium; 110 cfu/mL for E. coli) and reproducible. The analytical characteristics achieved combined with the small chip size make the proposed biosensor suitable for on-site bacteria determination in drinking water and milk samples.
Progress and Prospects of Electrochemiluminescence Biosensors Based on Porous Nanomaterials
Authors: Li Chenchen , Yang Jinghui , Xu Rui , Wang Huan , Zhang Yong , Wei Qin
Published: July 2022

Porous nanomaterials have attracted much attention in the field of electrochemiluminescence (ECL) analysis research because of their large specific surface area, high porosity, possession of multiple functional groups, and ease of modification. Porous nanomaterials can not only serve as good carriers for loading ECL luminophores to prepare nanomaterials with excellent luminescence properties, but they also have a good electrical conductivity to facilitate charge transfer and substance exchange between electrode surfaces and solutions. In particular, some porous nanomaterials with special functional groups or centered on metals even possess excellent catalytic properties that can enhance the ECL response of the system. ECL composites prepared based on porous nanomaterials have a wide range of applications in the field of ECL biosensors due to their extraordinary ECL response. In this paper, we reviewed recent research advances in various porous nanomaterials commonly used to fabricate ECL biosensors, such as ordered mesoporous silica (OMS), metal–organic frameworks (MOFs), covalent organic frameworks (COFs) and metal–polydopamine frameworks (MPFs). Their applications in the detection of heavy metal ions, small molecules, proteins and nucleic acids are also summarized. The challenges and prospects of constructing ECL biosensors based on porous nanomaterials are further discussed. We hope that this review will provide the reader with a comprehensive understanding of the development of porous nanomaterial-based ECL systems in analytical biosensors and materials science.
Microsensor in Microbioreactors: Full Bioprocess Characterization in a Novel Capillary-Wave Microbioreactor
Authors: Viebrock Kevin , Rabl Dominik , Meinen Sven , Wunder Paul , Meyer Jan-Angelus , Frey Lasse Jannis , Rasch Detlev , Dietzel Andreas , Mayr Torsten , Krull Rainer
Published: July 2022

Microbioreactors (MBRs) with a volume below 1 mL are promising alternatives to established cultivation platforms such as shake flasks, lab-scale bioreactors and microtiter plates. Their main advantages are simple automatization and parallelization and the saving of expensive media components and test substances. These advantages are particularly pronounced in small-scale MBRs with a volume below 10 µL. However, most described small-scale MBRs are lacking in process information from integrated sensors due to limited space and sensor technology. Therefore, a novel capillary-wave microbioreactor (cwMBR) with a volume of only 7 µL has the potential to close this gap, as it combines a small volume with integrated sensors for biomass, pH, dissolved oxygen (DO) and glucose concentration. In the cwMBR, pH and DO are measured by established luminescent optical sensors on the bottom of the cwMBR. The novel glucose sensor is based on a modified oxygen sensor, which measures the oxygen uptake of glucose oxidase (GOx) in the presence of glucose up to a concentration of 15 mM. Furthermore, absorbance measurement allows biomass determination. The optical sensors enabled the characterization of an Escherichia coli batch cultivation over 8 h in the cwMBR as proof of concept for further bioprocesses. Hence, the cwMBR with integrated optical sensors has the potential for a wide range of microscale bioprocesses, including cell-based assays, screening applications and process development.
Homo and Heterotypic Cellular Cross-Talk in Epithelial Ovarian Cancer Impart Pro-Tumorigenic Properties through Differential Activation of the Notch3 Pathway
Authors: Mukherjee Souvik , Sakpal Asmita , Mehrotra Megha , Phadte Pratham , Rekhi Bharat , Ray Pritha
Published: July 2022

An active fluidic microenvironment governs peritoneal metastasis in epithelial ovarian cancer (EOC), but its critical functional/molecular cues are not fully understood. Utilizing co-culture models of NIH3T3 cells (differentially overexpressing Jagged1) and SKOV3 cells expressing a Notch3 luciferase reporter-sensor (SNFT), we showed that incremental expression of Jagged1 led to proportional Notch3 activation in SNFT. With no basal luciferase activity, this system efficiently recorded dose-dependent Notch3 activation by rh-Jag1 peptide and the non-appearance of such induction in co-culture with NIH3T3Δjag1 cells indicates its sensitivity and specificity. Similar Notch3 modulation was shown for the first time in co-cultures with HGSOC patients’ ascites-derived cancer-associated fibroblasts and Jagged1-expressing EOC cell lines. NIH3T3J1-A and OVCAR3 co-cultured SNFT cells showed maximum proliferation, invasion, and cisplatin resistance among all the heterotypic/homotypic cellular partners. VEGFA and CDKN1A are the two most upregulated genes identified across co-cultures by the gene profiler array. Co-culture induced VEGFA secretion from SNFT cells which also reduced cancer stem cell differentiation in platinum-resistant A2780 cells. rh-Jag1-peptide promoted enhanced nuclear-cytoplasmic p21 expression. Additionally, metastatic HGSOC tumors had higher VEGFA than corresponding primary tumors. This study thus demonstrates the tumoral and non-tumoral cell-mediated differential Notch3 activation imparting its tumorigenic effects through two critical molecular regulators, VEGFA and p21, during EOC progression.