bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Study of Single-Trait and Multi-Trait Genomic Prediction Models
Authors: Tang Xi , Xiao Shijun , Ding Nengshui , Zhang Zhiyan , Huang Lusheng
Published: October 2024

Conventional genomic selection models trait individually, neglecting complex trait interactions. Multi-trait models address this by considering genetic correlations, thus improving breeding value accuracy. Despite their theoretical benefits, quantifying these models’ breeding advantages across genetic backgrounds is essential. This study evaluates the benefits of multi-trait models under varying population sizes and three levels of genetic correlations (low, medium, high) using simulations based on 50 K chip data from 5000 individuals. In equal heritability scenarios, the multi-trait GBLUP model consistently outperforms single-trait models, with breeding advantages increasing with heritability. For example, with a reference population of 4500, improvements range from 0.3% to 4.1%. Notably, trait combinations with low heritability are insensitive to changes in genetic correlation, with gains remaining ≤ 0.1% across different genetic correlations under low heritability conditions. In differing heritability scenarios, the multi-trait model’s benefits vary, particularly enhancing low-heritability traits when paired with high-heritability ones. Additionally, modeling time increases as genetic correlation decreases. The results of this study indicate that multi-trait models improve breeding accuracy but require more modeling time and place higher demands on algorithms and software. We recommend breeding strategies tailored to different phenotypes and genetic backgrounds to balance efficiency and accuracy.
The Effects of Dietary Orange Peel Fragments Enriched with Zinc and Vitamins C and E on the Antioxidant and Immune Responses of Nile Tilapia under Stress Conditions
Authors: Vicente Igor Simões Tiagua , Fleuri Luciana Francisco , Xavier William dos Santos , Guimarães Matheus Gardim , de Carvalho Pedro Luiz Pucci Figueiredo , Rodrigues Edgar Junio Damasceno , Fonseca Alves Carlos Eduardo , Nunes Aline , Lima Giuseppina Pace Pereira , Kadri Samir Moura , Pezzato Luiz Edivaldo , Barros Margarida Maria
Published: October 2024

This study aimed to evaluate the effect of dietary orange peel fragments (OPFs) enriched with vitamins C (C) and E (E), as well as zinc (Zn) on the growth performance, hematological profile, immunological parameters, antioxidant capacity, and fillet lipid peroxidation of Nile tilapia subjected to heat/dissolved oxygen-induced stress (HDOIS), transport-induced stress (TIS), and Aeromonas hydrophila infection (BC). A group of 500 male Nile tilapia (2.7 ± 0.03 g) was randomly distributed in twenty-five 250 L aquaria (20 fish/aquarium) and fed diets containing OPFs (6 g kg−1), OPFs/C (6 g kg−1/1.8 g kg−1), OPFs/E (6 g kg−1/0.4 g kg−1), OPFs/Zn (6 g kg−1/0.21 g kg−1), or OPFs/C/E/Zn (6 g kg−1/1.8 g kg−1/0.4 g kg−1/0.21 g kg−1) for 100 days. The diets were formulated to contain 30% crude protein and 17 MJ kg−1 gross energy. After the feeding period, three groups of fish were independently subjected to a different type of stress: HDOIS (34 °C) for two days; TIS for four hours, or BC for 15 days. The hematological profile, antioxidant capacity, and fillet lipid peroxidation were determined before and after all the stress treatments, along with immunological parameters, which were investigated only for the fish subjected to bacterial infection. In summary, the results showed that growth was not affected by the OPFs, nor by the OPFs enriched with C, E, and Zn; bacterial infection determined anemia for the fish fed any of the experimental diets; the OPFs did not prevent lipid peroxidation under TIS and BC; on the other hand, when enriched with C/E/Zn, lipid peroxidation decreased under HDOIS and TIS. In conclusion, the OPFs enriched with C/E/Zn showed a synergistic effect that promoted an increase in antioxidant enzyme activity, a decrease in lipid peroxidation, and the maintenance of the hematological profile under HDOIS and TIS, but they were not able to maintain the health status under BC.
Effect of Dietary Supplementation of Glycerol Monolaurate on Growth Performance, Digestive Enzymes, Serum Immune and Antioxidant Parameters, and Intestinal Morphology in Black Sea Bream
Authors: Ullah Sami , Zhang Jinzhi , Feng Fengqin , Shen Fei , Qiufen Mo , Wang Jing , Ur Rahman Tanzil , Haleem Abdul , Zhao Minjie , Shao Qingjun
Published: October 2024

An eight-week feeding trial was conducted to examine the impact of dietary supplementation with glycerol monolaurate (GML) on juvenile black sea bream. A basal diet was formulated containing 24% fish meal, while five additional diets were prepared, each supplemented with varying levels of GML: GML1 (0.01%), GML2 (0.02%), GML3 (0.04%), GML4 (0.08%), and GML5 (0.16%). Triplicate tanks were randomly allocated to each diet, each containing 20 fish with an initial weight of 1.55 ± 0.05 g. By the trial’s end, the GML3 group displayed a notably higher final body weight (FBW), weight gain (WG), specific growth rate (SGR), and protein efficiency ratio (PER) compared to the other groups (p < 0.05), but the FCR was significantly higher in the control group. However, no significant differences were observed in the MFI, PPV, CF, HSI, IPF, VSI, or SR among the groups (p > 0.05). Regarding the proximate compositions of the dorsal muscle and whole body, no substantial differences were observed across the groups (p > 0.05). Additionally, there were no significant variations in digestive enzyme activity (p > 0.05), serum immune, or biochemical parameters in the midgut and hindgut among the treatment groups. But in the serum immune response IgM, C3 and C4 were significantly higher in the GML3 group as compared to the other groups (p < 0.05). However, the GML3 group exhibited significantly greater fore-intestinal villus height, crypt depth, villus height per crypt depth, and the number of goblet cells per villus compared to the other groups (p < 0.05). Overall, GML supplementation, particularly GML3, significantly improved growth indicators like the final body weight and intestinal morphology. While certain parameters remained unaffected, these findings suggest GML’s potential as a beneficial dietary supplement in fish diets.
Prevalence, Virulence Genes, Drug Resistance and Genetic Evolution of Trueperella pyogenes in Small Ruminants in Western China
Authors: Wei Yuchen , Wang Bin , Wu Ke , Wang Chenxiao , Bai Xindong , Wang Juan , Yang Zengqi
Published: October 2024

Trueperella pyogenes is a significant opportunistic pathogen that causes substantial economic losses in animal agriculture due to its ability to infect various animal tissues and organs. Limited research has been conducted on the prevalence and biological characteristics of T. pyogenes isolated from sheep and goats. This study aimed to isolate T. pyogenes from clinical samples of sheep and goats in western China, examining genetic evolutionary relationships, antibiotic resistance, and virulence genes. Between 2021 and 2023, standard bacteriological methods were used to isolate and identify T. pyogenes from 316 samples (209 from goats and 107 from sheep) collected from 39 farms. Susceptibility to 14 antibiotics was tested using broth microdilution per CLSI guidelines, and PCR detected eight virulence genes. Whole-genome sequencing analyzed genetic relationships and gene carriage status in 39 isolates. The results indicated that 86 strains of T. pyogenes were isolated from 316 samples, yielding an isolation rate of 27.2% (goats n = 47, 22.5%; sheep n = 39, 36.4%). The virulence genes plo, cbpA, nanH, nanP, fimA, fimC, and fimE were present in 100%, 66.7%, 64.1%, 71.8%, 69.2%, 59.0%, and 82.1% of isolates, respectively, with none carrying the fimG gene. The dominant virulence genotype was plo/nanH/nanP/fimA/fimC/fimE. The isolates exhibited resistance to erythromycin (44.2%, 38/86), gentamicin (38.4%, 33/86), sulfamethoxazole/trimethoprim (37.2%, 32/86), tetracycline (32.6%, 28/86), and streptomycin (32.6%, 28/86), and low resistance to chloramphenicol (14.0%, 12/86), ciprofloxacin (7.0%, 6/86), penicillin (5.8%, 5/86), and clindamycin (4.7%, 4/86). All isolates were susceptible to cefotaxime, vancomycin, and linezolid. Among the 86 isolates, 37 (43.0%) displayed multidrug resistance (MDR) characteristics. The whole genome sequencing of 39 isolates identified eight types of resistance genes, including ant(2″)-Ia, ant(3″)-Ia, cmlA1, cmx, erm(X), lnu(A), sul1, and tet(W). Except for tet(W), erm(X), and sul1, the other resistance genes were reported for the first time in T. pyogenes isolated in China. The drug susceptibility test results and resistance gene detection for the isolated strains were consistent for tetracycline, erythromycin, gentamicin, and sulfisoxazole. Similar allelic profiles and genetic evolutionary relationships were found among isolates from different farms. This study highlights the antibiotic resistance status and virulence gene-carrying rate of Trueperella pyogenes, providing a basis for clinical medication.
The Impact of Biotechnologically Produced Lactobionic Acid on Laying Hens’ Productivity and Egg Quality during Early Laying Period
Authors: Zagorska Jelena , Ruska Diana , Radenkovs Vitalijs , Juhnevica-Radenkova Karina , Kince Tatjana , Galoburda Ruta , Gramatina Ilze
Published: October 2024

Lactobionic acid (Lba), an oligosaccharide aldonic acid, has demonstrated various health-promoting benefits and applications in diverse areas. Lba has been recognized for its multifunctional properties, such as metal ion chelation and calcium sequestration. This study aimed to evaluate the effects of supplementing the diet of early-laying hens with Lba (EXP group) on their performance and the physical–chemical properties, and nutritional quality of eggs. The 12-week study involved 700 Sonja breed hens per group, with the EXP group’s diet enriched with 2% of biotechnologically produced Lba, while the control group (CON) received no Lba supplementation. Lba supplementation influenced both the hen’s performance and egg quality, particularly in terms of egg production and fatty acid accumulation. Performance in the EXP group was significantly improved (p < 0.05), showing a 4.6–8.9% increase compared to the CON group at all experiment stages. Lba also promoted an increase in monounsaturated fatty acid (MUFA) content, particularly palmitoleic and vaccenic acids. Overall, Lba supplementation enhanced both the productivity of laying hens and the nutritional value of eggs during the early laying period.
Exploring Sound Frequency Detection in the Golden Rabbitfish, Siganus guttatus: A Behavioral Study
Authors: Zhang Shenwei , Zhang Xuguang , Tang Xianming , Zhang Shouyu
Published: October 2024

This study investigates the auditory capabilities of Golden Rabbitfish (Siganus guttatus) and the potential efficacy of sound-based deterrent methods for behavior control. Behavioral experiments were conducted on Golden Rabbitfish to assess their responses to sound stimuli. Sinusoidal pulses in the range of 100~800 Hz, based on previous research on auditory evoked potentials (AEPs), were utilized. An analysis of behavioral trajectories, swimming speed, and acceleration changes revealed the fish’s reactions to varying frequency sound stimuli. The results indicate that Golden Rabbitfish exhibited increased swimming activity and speed when stimulated by sound and notably moved away from the source under prolonged exposure to low-frequency acoustic signals. Specifically, the fish displayed the most significant response to 200 Hz sinusoidal pulses with a response threshold of 113~126 dB. These findings suggest that Golden Rabbitfish are particularly sensitive to low-frequency noise, aligning with AEP study outcomes. This study concludes that employing sound stimuli to deter Golden Rabbitfish in practical settings holds promise for mitigating economic losses in seaweed farming due to Golden Rabbitfish grazing.
PET Imaging with [18F]ROStrace Detects Oxidative Stress and Predicts Parkinson’s Disease Progression in Mice
Authors: Zhu Yi , Kohli Neha , Young Anthony , Sheldon Malkah , Coni Jani , Rajasekaran Meera , Robinson Lozen , Chroneos Rea , Riley Shaipreeah , Guarnieri Joseph W. , Jose Joshua , Patel Nisha , Wallace Douglas C. , Li Shihong , Lee Hsiaoju , Mach Robert H. , McManus Meagan J.
Published: October 2024

Although the precise molecular mechanisms responsible for neuronal death and motor dysfunction in late-onset Parkinson’s disease (PD) are unknown, evidence suggests that mitochondrial dysfunction and neuroinflammation occur early, leading to a collective increase in reactive oxygen species (ROS) production and oxidative stress. However, the lack of methods for tracking oxidative stress in the living brain has precluded its use as a potential biomarker. The goal of the current study is to address this need through the evaluation of the first superoxide (O2•−)-sensitive radioactive tracer, [18F]ROStrace, in a model of late-onset PD. To achieve this goal, MitoPark mice with a dopaminergic (DA) neuron-specific deletion of transcription factor A mitochondrial (Tfam) were imaged with [18F]ROStrace from the prodromal phase to the end-stage of PD-like disease. Our data demonstrate [18F]ROStrace was sensitive to increased oxidative stress during the early stages of PD-like pathology in MitoPark mice, which persisted throughout the disease course. Similarly to PD patients, MitoPark males had the most severe parkinsonian symptoms and metabolic impairment. [18F]ROStrace retention was also highest in MitoPark males, suggesting oxidative stress as a potential mechanism underlying the male sex bias of PD. Furthermore, [18F]ROStrace may provide a method to identify patients at risk of Parkinson’s before irreparable neurodegeneration occurs and enhance clinical trial design by identifying patients most likely to benefit from antioxidant therapies.
Bioactivities of Quinic Acids from Vitex rotundifolia Obtained by Supercritical Fluid Extraction
Authors: Le Duc Dat , Jang Young Su , Truong Vinhquang , Yu Soojung , Dinh Thientam , Lee Mina
Published: October 2024

Acyl-quinic acids (AQAs), present in various plants with many health benefits, are regarded as therapeutic agents in the prevention and treatment of chronic and cardiovascular diseases. The molecular network-guided identification of ten AQA compounds, two new (5 and 7) and eight known compounds, were isolated from V. rotundifolia L. f. by using a newly applied extraction method. Their structures were determined through spectroscopic means, reaction mixtures, and modified Mosher and PGME techniques. These compounds were assessed for their anti-inflammatory and antioxidant capabilities. Notably, compounds 1, 3, 4, 6, 8, and 9 exhibited notable DPPH radical scavenging activity. In LPS-induced HT-29 cells, compounds 2–7 significantly inhibited IL-8 production. Furthermore, compounds 3–5 and 7 markedly suppressed NO production, while compounds 1–10 effectively inhibited IL-6 production in LPS-induced RAW264.7 cells. Western blot analyses revealed that compounds 3–5, and 7 reduced iNOS and COX-2 expression, and compounds 2–5, 7, and 8 also diminished the expression levels of p38 MAPK phosphorylation. Docking studies demonstrated the active compounds’ binding affinity with the IL-8, iNOS, COX-2, and p38 MAPK proteins through interactions with essential amino acids within the binding pockets of complexes. The findings suggest that compounds 1, 3, 4, 6, 8, and 9, and compounds 3–5, and 7, hold promise as potential therapeutic agents for treating antioxidative and inflammatory diseases, respectively.
Nannochloropsis oceanica Lipid Extract Moderates UVB-Irradiated Psoriatic Keratinocytes: Impact on Protein Expression and Protein Adducts
Authors: Wroński Adam , Gęgotek Agnieszka , Conde Tiago , Domingues Maria Rosário , Domingues Pedro , Skrzydlewska Elżbieta
Published: October 2024

Psoriasis is characterized by excessive exfoliation of the epidermal layer due to enhanced pro-inflammatory signaling and hyperproliferation of keratinocytes, further modulated by UV-based anti-psoriatic treatments. Consequently, this study aimed to evaluate the impact of a lipid extract derived from the microalgae Nannochloropsis oceanica on the proteomic alterations induced by lipid derivatives in non-irradiated and UVB-irradiated keratinocytes from psoriatic skin lesions compared to keratinocytes from healthy individuals. The findings revealed that the microalgae extract diminished the viability of psoriatic keratinocytes without affecting the viability of these cells following UVB exposure. Notably, the microalgae extract led to an increased level of 4-HNE-protein adducts in non-irradiated cells and a reduction in 4-hydroxynonenal (4-HNE)-protein and 15-deoxy-12,14-prostaglandin J2 (15d-PGJ2)-protein adducts in UVB-exposed keratinocytes from psoriasis patients. In healthy skin cells, the extract decreased the UV-induced elevation of 4-HNE-protein and 15d-PGJ2-protein adducts. The antioxidant/anti-inflammatory attributes of the lipid extract from the Nannochloropsis oceanica suggest its potential as a protective agent for keratinocytes in healthy skin against UVB radiation’s detrimental effects. Moreover, it could offer therapeutic benefits to skin cells afflicted with psoriatic lesions by mitigating their proliferation and inflammatory responses during UV radiation treatment.
Determining the Axial Orientations of a Large Number of Flux Transfer Events Sequentially Observed by Cluster during a High-Latitude Magnetopause Crossing
Authors: Li Zhaoyu , Chen Tao , Li Lei
Published: October 2024

Flux transfer events (FTEs) are magnetic structures generally believed to originate from time-varying magnetic reconnection at the Earth’s magnetopause. Despite years of research, the mechanism of how FTEs are formed through reconnection remains controversial. In various models, FTEs exhibit different global configurations. Studying the FTE axial orientation can provide insights into their global shape, thereby helping to distinguish the generation mechanisms. In this paper, taking advantage of the orbital characteristics of the four Cluster spacecraft, we devised a multi-spacecraft timing method to determine the axes of a total of 57 FTEs observed sequentially by Cluster during a high-latitude duskside magnetopause crossing. During the nearly five-hour observation, the interplanetary magnetic field (IMF) experienced a large rotation, leading to a substantial rotation of the magnetosheath magnetic field. The analysis results show two new features of the FTE axis that have not been reported before: (1) the axes of the FTEs gradually rotate in response to the turning of the IMF and the magnetosheath magnetic field; (2) the axes of the FTEs vary between the direction of the magnetosheath magnetic field and the direction of the reconnection X-line. These features indicate that FTEs may have a more complex global configuration than depicted by traditional FTE models.
On the Possible Climatic Consequences of the Large Oil Spills in Oceans
Authors: Prokopciuk Nina , Tarasiuk Nikolaj , Franck Ulrich , Schraufnagel Dean Ernest , Valiulis Algirdas , Kostantinova Marina , Zielinski Tymon , Valiulis Arunas
Published: October 2024

In the North Atlantic and the Northern Ocean, from the second half of 2010 to 2014, satellite imagery data showed increased surface water temperatures (in the Icelandic Depression area in September–October 2010, it was 1.3 °C higher than in 2009). The peak of the annual sum of mean monthly ocean surface temperatures near the Icelandic Depression in 2010 (109.3 °C), as well as the negative values of the monthly averaged North Atlantic Oscillation (NAO) indices, estimated in the second half of 2010 and until March 2011, can be explained by the appearance of an additional film of oil origin on the water surface, formed after an oil spill accident at the Deepwater Horizon drilling rig in the Gulf of Mexico. Insufficient evaporative cooling of surface waters near the Icelandic Depression related to the formation of an additive film due to the influence of pollution of the North Sea by oil can explain the earlier peak in the annual sum of mean monthly ocean surface temperatures near the Icelandic Depression in 2003 (107.2 °C). Although global warming is usually ascribed to increased greenhouse gases in the atmosphere, ocean surface water pollution could increase the heat content of the ocean and explain the steady temperature stratification and desalination of these waters due to the melting of Greenland’s glaciers. Thus, when analyzing the concept of global warming, it is necessary to take into account the aspects of pollution of the ocean surface waters to assess the changes in their capacity to accumulate solar radiation, as well as the changes in the heat content of the ocean mixing zone (~200 m).
Multiple-Win Effects and Beneficial Implications from Analyzing Long-Term Variations of Carbon Exchange in a Subtropical Coniferous Plantation in China
Authors: Bai Jianhui , Yang Fengting , Wang Huimin , Yao Lu , Xu Mingjie
Published: October 2024

To improve our understanding of the carbon balance, it is significant to study long-term variations of all components of carbon exchange and their driving factors. Gross primary production (GPP), respiration (Re), and net ecosystem productivity (NEP) from the hourly to the annual sums in a subtropical coniferous forest in China during 2003–2017 were calculated using empirical models developed previously in terms of PAR (photosynthetically active radiation), and meteorological parameters, GPP, Re, and NEP were calculated. The calculated GPP, Re, and NEP were in reasonable agreement with the observations, and their seasonal and interannual variations were well reproduced. The model-estimated annual sums of GPP and Re over 2003–2017 were larger than the observations of 11.38% and 5.52%, respectively, and the model-simulated NEP was lower by 34.99%. The GPP, Re, and NEP showed clear interannual variations, and both the calculated and the observed annual sums of GPPs increased on average by 1.04% and 0.93%, respectively, while the Re values increased by 4.57% and 1.06% between 2003 and 2017. The calculated and the observed annual sums of NEPs/NEEs (net ecosystem exchange) decreased/increased by 1.04%/0.93%, respectively, which exhibited an increase of the carbon sink at the experimental site. During the period 2003–2017, the annual averages of PAR and the air temperature decreased by 0.28% and 0.02%, respectively, while the annual average water vapor pressure increased by 0.87%. The increase in water vapor contributed to the increases of GPP, Re, and NEE in 2003–2017. Good linear and non-linear relationships were found between the monthly calculated GPP and the satellite solar-induced fluorescence (SIF) and then applied to compute GPP with relative biases of annual sums of GPP of 5.20% and 4.88%, respectively. Large amounts of CO2 were produced in a clean atmosphere, indicating a clean atmospheric environment will enhance CO2 storage in plants, i.e., clean atmosphere is beneficial to human health and carbon sink, as well as slowing down climate warming.
Analyzing the Spatiotemporal Changes in Climatic Extremes in Cold and Mountainous Environment: Insights from the Himalayan Mountains of Pakistan
Authors: Zafar Usama , Anjum Muhammad Naveed , Hussain Saddam , Sultan Muhammad , Rasool Ghulam , Riaz Muhammad Zain Bin , Shoaib Muhammad , Asif Muhammad
Published: October 2024

This study assessed the past changes in extreme precipitation and temperature events across the Himalayan Mountains of Pakistan. This cold and mountainous environmental region has witnessed a significant increase in climate-related disasters over the past few decades. Spatiotemporal changes in extreme temperature and precipitation events were analyzed using 24 indices developed by the Expert Team on Climate Change Detection and Indices (ETCCDI). For this study, in situ data of 16 national meteorological stations were obtained from the Pakistan Meteorological Department (PMD) for the past three decades (1991–2020). The significance of the trends was assessed using the modified Mann–Kendall (MMK) test, and the Theil–Sen (TS) slope estimator was used to estimate the slope of the trend. The results showed that there has been a consistent decline in the total precipitation amount across the Himalayan Mountains of Pakistan. The trend exhibited a decrease in the annual average precipitation at a rate of −6.56 mm/year. Simultaneously, there was an increasing trend in the annual average minimum and maximum temperatures at rates of 0.02 °C/year and 0.07 °C/year, respectively. The frequencies of consecutive wet days (CWDs) and maximum 5-day precipitation (RX5day) have decreased significantly, with decreasing rates of −0.40 days/year and −1.18 mm/year, respectively. The amount of precipitation during very wet days (R95p) and extremely wet days was decreased by −19.20 and −13.60 mm/decade, respectively. The warm spell duration (WSDI) and the frequency of warm days (TX90p) across the Himalayan Range both increased by 1.5 and 1.4 days/decade. The number of cold days (TX10p) and cold nights (TN10p) decreased by 2.9 and 3.4 days/decade. The average temperature of the hottest nights (TXn) and the diurnal temperature range (DTR) were increased by 0.10 and 0.30 °C/decade. The results indicated an increasing tendency of dry and warm weather in the Himalayan region of Pakistan, which could have adverse consequences for water resources, agriculture, and disaster management in the country. Therefore, it is essential to prioritize the implementation of localized adaptation techniques in order to enhance sustainable climate resilience and effectively address the emerging climate challenges faced by these mountainous regions.
Modulating OCA2 Expression as a Promising Approach to Enhance Skin Brightness and Reduce Dark Spots
Authors: Cho Eunbyul , Hyung Kyong Eun , Choi Yun-Ho , Chun Hyeyeon , Kim Daehyun , Jun Seung-Hyun , Kang Nae-Gyu
Published: October 2024

The oculocutaneous albinism II (OCA2) gene encodes a melanosomal transmembrane protein involved in melanogenesis. Recent genome-wide association studies have identified several single nucleotide polymorphisms within OCA2 genes that are involved in skin pigmentation. Nevertheless, there have been no attempts to modulate this gene to improve skin discoloration. Accordingly, our aim was to identify compounds that can reduce OCA2 expression and to develop a formula that can improve skin brightness and reduce hyperpigmented spots. In this study, we investigated the effects of OCA2 expression reduction on melanin levels, melanosome pH, and autophagy induction through siRNA knockdown. Additionally, we identified several bioactives that effectively reduce OCA2 expression. Ultimately, in a clinical trial, we demonstrated that topical application of those compounds significantly improved skin tone and dark spots compared to vitamin C, a typical brightening agent. These findings demonstrate that OCA2 is a promising target for the development of efficacious cosmetics and therapeutics designed to treat hyperpigmentation.
Chemical and Biological Characterization of Metabolites from Silene viridiflora Using Mass Spectrometric and Cell-Based Assays
Authors: Mamadalieva Nilufar Z. , Koval Alexey , Dusmuratov Maksud M. , Hussain Hidayat , Katanaev Vladimir L.
Published: October 2024

A comprehensive metabolite profiling of the medicinal plant Silene viridiflora using an UHPLC-ESI-MS/MS method is described for the first time. A total of 71 compounds were identified and annotated, the most common of which were flavonoids, triterpene glycosides, and ecdysteroids. The three major compounds schaftoside, 26-hydroxyecdysone, and silviridoside can be chosen as the markers for the assessment of the quality of S. viridiflora preparations. The methanol extract and a variety of metabolites identified in S. viridiflora were screened for their cytotoxic and Wnt pathway-inhibiting activities against triple-negative breast cancer (TNBC), the deadliest form of cancer in women. 2-Deoxy-20-hydroxyecdysone with submicromolar IC50 was identified as a result. The structure–activity relationship derived from the data from the in vitro proliferation assay showed that the hydroxyl group present at position C-2 of steroid core reduces the ecdysteroids’ cytotoxicity against cancer cells.
Design and Synthesis of Small Molecule Probes of MDA-9/Syntenin
Authors: Sankaranarayanan Nehru Viji , Villuri Bharath Kumar , Nagarajan Balaji , Lewicki Sarah , Das Swadesh K. , Fisher Paul B. , Desai Umesh R.
Published: October 2024

MDA-9/Syntenin, a key scaffolding protein and a molecular hub involved in a diverse range of cell signaling responses, has proved to be a challenging target for the design and discovery of small molecule probes. In this paper, we report on the design and synthesis of small molecule ligands of this key protein. Genetic algorithm-based computational design and the five–eight step synthesis of three molecules led to ligands with affinities in the range of 1–3 µM, a 20–60-fold improvement over literature reports. The design and synthesis strategies, coupled with the structure-dependent gain or loss in affinity, afford the deduction of principles that should guide the design of advanced probes of MDA-9/Syntenin.
The Formation of Stable Lung Tumor Spheroids during Random Positioning Involves Increased Estrogen Sensitivity
Authors: Barkia Balkis , Sandt Viviann , Melnik Daniela , Cortés-Sánchez José Luis , Marchal Shannon , Baselet Bjorn , Baatout Sarah , Sahana Jayashree , Grimm Daniela , Wehland Markus , Schulz Herbert , Infanger Manfred , Kraus Armin , Krüger Marcus
Published: October 2024

The formation of tumor spheroids on the random positioning machine (RPM) is a complex and important process, as it enables the study of metastasis ex vivo. However, this process is not yet understood in detail. In this study, we compared the RPM-induced spheroid formation of two cell types of lung carcinoma (NCI-H1703 squamous cell carcinoma cells and Calu-3 adenocarcinoma cells). While NCI-H1703 cells were mainly present as spheroids after 3 days of random positioning, Calu-3 cells remained predominantly as a cell layer. We found that two-dimensional-growing Calu-3 cells have less mucin-1, further downregulate their expression on the RPM and therefore exhibit a higher adhesiveness. In addition, we observed that Calu-3 cells can form spheroids, but they are unstable due to an imbalanced ratio of adhesion proteins (β1-integrin, E-cadherin) and anti-adhesion proteins (mucin-1) and are likely to disintegrate in the shear environment of the RPM. RPM-exposed Calu-3 cells showed a strongly upregulated expression of the estrogen receptor alpha gene ESR1. In the presence of 17β-estradiol or phenol red, more stable Calu-3 spheroids were formed, which was presumably related to an increased amount of E-cadherin in the cell aggregates. Thus, RPM-induced tumor spheroid formation depends not solely on cell-type-specific properties but also on the complex interplay between the mechanical influences of the RPM and, to some extent, the chemical composition of the medium used during the experiments.
Comprehensive Analysis of the 5xFAD Mouse Model of Alzheimer’s Disease Using dMRI, Immunohistochemistry, and Neuronal and Glial Functional Metabolic Mapping
Authors: Westi Emil W. , Molhemi Saba , Hansen Caroline Termøhlen , Skoven Christian Stald , Knopper Rasmus West , Ahmad Dashne Amein , Rindshøj Maja B. , Ameen Aishat O. , Hansen Brian , Kohlmeier Kristi A. , Aldana Blanca I.
Published: October 2024

Alzheimer’s disease (AD) is characterized by complex interactions between neuropathological markers, metabolic dysregulation, and structural brain changes. In this study, we utilized a multimodal approach, combining immunohistochemistry, functional metabolic mapping, and microstructure sensitive diffusion MRI (dMRI) to progressively investigate these interactions in the 5xFAD mouse model of AD. Our analysis revealed age-dependent and region-specific accumulation of key AD markers, including amyloid-beta (Aβ), GFAP, and IBA1, with significant differences observed between the hippocampal formation and upper and lower regions of the cortex by 6 months of age. Functional metabolic mapping validated localized disruptions in energy metabolism, with glucose hypometabolism in the hippocampus and impaired astrocytic metabolism in the cortex. Notably, increased cortical glutaminolysis suggested a shift in microglial metabolism, reflecting an adaptive response to neuroinflammatory processes. While dMRI showed no significant microstructural differences between 5xFAD and wild-type controls, the study highlights the importance of metabolic alterations as critical events in AD pathology. These findings emphasize the need for targeted therapeutic strategies addressing specific metabolic disturbances and underscore the potential of integrating advanced imaging with metabolic and molecular analyses to advance our understanding of AD progression.
Unveiling the Potential of Phytocannabinoids: Exploring Marijuana’s Lesser-Known Constituents for Neurological Disorders
Authors: Basavarajappa Balapal S. , Subbanna Shivakumar
Published: October 2024

Cannabis sativa is known for producing over 120 distinct phytocannabinoids, with Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) being the most prominent, primarily in their acidic forms. Beyond Δ9-THC and CBD, a wide array of lesser-known phytocannabinoids, along with terpenes, flavonoids, and alkaloids, demonstrate diverse pharmacological activities, interacting with the endocannabinoid system (eCB) and other biological pathways. These compounds, characterized by phenolic structures and hydroxyl groups, possess lipophilic properties, allowing them to cross the blood–brain barrier (BBB) effectively. Notably, their antioxidant, anti-inflammatory, and neuro-modulatory effects position them as promising agents in treating neurodegenerative disorders. While research has extensively examined the neuropsychiatric and neuroprotective effects of Δ9-THC, other minor phytocannabinoids remain underexplored. Due to the well-established neuroprotective potential of CBD, there is growing interest in the therapeutic benefits of non-psychotropic minor phytocannabinoids (NMPs) in brain disorders. This review highlights the emerging research on these lesser-known compounds and their neuroprotective potential. It offers insights into their therapeutic applications across various major neurological conditions.
Identification and Characterization of a Novel Insulin-like Receptor (LvRTK2) Involved in Regulating Growth and Glucose Metabolism of the Pacific White Shrimp Litopenaeus vannamei
Authors: Liu Zijian , Liu Jiawei , Liu Zijie , Song Xiaowei , Liu Su , Liu Fei , Song Lin , Gao Yi
Published: October 2024

The insulin receptor (IR) plays a crucial role in the growth and metabolism of animals. However, there are still many questions regarding the IR in crustaceans, particularly their role in shrimp growth and glucose metabolism. In this study, we identified a novel insulin-like receptor gene in Litopenaeus vannamei and cloned its full length of 6439 bp. This gene exhibited a highly conserved sequence and structural characteristics. Phylogenetic analysis confirmed it as an unreported RTK2-type IR, namely, LvRTK2. Expression pattern analysis showed that LvRTK2 is primarily expressed in female reproductive and digestive organs. Through a series of in vivo and in vitro experiments, including glucose treatment, exogenous insulin treatment, and starvation treatment, LvRTK2 was confirmed to be involved in the endogenous glucose metabolic pathway of shrimp under different glucose variations. Moreover, long-term and short-term interference experiments with LvRTK2 revealed that the interference significantly reduced the shrimp growth rate and serum glucose clearance rate. Further studies indicated that LvRTK2 may regulate shrimp growth by modulating the downstream PI3K/AKT signaling pathway and a series of glucose metabolism events, such as glycolysis, gluconeogenesis, glycogen synthesis, and glycogenolysis. This report on the characteristics and functions of LvRTK2 confirms the important role of RTK2-type IRs in regulating shrimp growth and glucose metabolism.
Treatment of Parkinson’s Disease Psychosis—A Systematic Review and Multi-Methods Approach
Authors: Rose Olaf , Huber Sophia , Trinka Eugen , Pachmayr Johanna , Clemens Stephanie
Published: October 2024

Objectives: Parkinson’s disease psychosis (PDP) is a prevalent non-motor symptom associated with Parkinson’s disease. The treatment options for PDP are limited, and its pharmacological management remains ambiguous. This study aimed to evaluate the existing evidence in relation to clinical practice. Methods: This multi-methods study consisted of a systematic review of reviews, adhering to the PRISMA guidelines. The review was registered with PROSPERO. Following data extraction and assessment using the AMSTAR 2 tool, a narrative synthesis was performed. In the second phase of the study, a questionnaire was developed, validated, piloted, and distributed to the heads of specialized PD clinics in Germany and Austria. Results: The search resulted in the inclusion of eleven reviews. The quality of eight of these reviews was rated as high (n = 7) or moderate (n = 1). The reviews indicated that clozapine and pimavanserin demonstrated the highest efficacy and tolerability. Other antipsychotic medications either failed to alleviate PDP symptoms or resulted in distinct motor complications. The survey findings also favored clozapine for its efficacy in managing PDP and improving quality of life, although quetiapine was regarded as effective and pimavanserin was not available. Clinicians reported initiating antipsychotic treatment at various stages of PDP, with a tendency to reduce the dosage or discontinue D2 agonists or anticholinergics. Conclusions: The reviewed literature and the survey results consistently favored clozapine for its efficacy and tolerability in treating PDP. It may be considered the first-line treatment, with pimavanserin as an alternative option.
Survival Determinants in Glioblastoma: An Insight into Biopsy-Only Patient Outcomes
Authors: Gonçalves João Meira , Ferreira Francisca , Carvalho Bruno , Polónia Patrícia , Linhares Paulo
Published: October 2024

Background: Glioblastoma is a challenge in neuro-oncology, with survival significantly influenced mainly by the extent of resection and molecular markers. Despite advancements, the prognosis for IDH-wildtype glioblastoma remains poor, particularly when surgical resection is not possible. However, some patients exhibit unexpectedly extended survival despite the extent of resection. This study aims to analyze the determinants that contribute to these atypical survival rates among glioblastoma patients who have had solely biopsy procedures. Methods: We conducted a retrospective analysis of patients diagnosed with IDH-wildtype glioblastomas at our institution from 2017 to 2021, who underwent biopsy only. This study focused on evaluating the impact of demographic characteristics, clinical features, molecular markers, and treatment modalities on survival outcomes (overall survival (OS) and progression-free survival (PFS)). Statistical analyses included survival analysis and logistic regression for evaluating associations between OS and pre-operative characteristics and post-operative treatments. Results: The cohort included 99 patients, with a median age at diagnosis of 65.5 years. Median OS and PFS were 6.0 and 3.6 months, respectively. The multivariate analysis revealed that higher Karnofsky Performance Status (KPS) scores before biopsy, no contrast uptake on imaging, and any adjuvant therapy, particularly the use of bevacizumab, were independently associated to increased OS (HR = 0.97, p = 0.009. HR = 0.7, p = 0.015; HR = 0.27, p = 0.002, respectively). Out of 99 patients, 77.8% survived past the 3-month threshold, with 87.0% of this receiving adjuvant treatment. Only 8% of patients survived past 24 months, and in this group of patients, MGMT methylation was observed in just 25% of cases. Kaplan–Meier analysis indicated a better prognosis with any type of adjuvant therapy across all patients, particularly so in those with KPS ≥ 70. Age did not significantly affect survival outcomes (OR = 1.00, p = 0.835). Conclusion: Our findings reveal that any adjuvant treatment (whether chemotherapy and radiotherapy combined, chemotherapy alone, or bevacizumab), no contrast uptake on imaging, and higher pre-operative KPS are key determinants of survival in IDH-wildtype glioblastoma and should therefore be considered when deciding whether to perform a biopsy.
Evaluating Synergistic Effects of Hyaluronic Acid, Human Umbilical Cord-Derived Mesenchymal Stem Cells, and Growth Hormones in Knee Osteoarthritis: A Multi-Arm Randomized Trial
Authors: Dilogo Ismail Hadisoebroto , Canintika Anissa Feby , Hartanto Bernadus Riyan , Pandelaki Jacub , Himantoko Irsa Gagah
Published: October 2024

Background: Knee osteoarthritis (OA) significantly affects quality of life and imposes economic burdens due to its prevalence and the disability it causes. The efficacy of current treatments is limited to alleviating the symptoms, and they cannot be used for regenerative purposes. This study aims to evaluate the efficacy and safety of combining hyaluronic acid (HA), human umbilical cord-derived mesenchymal stem cells (hUC-MSCs), and synthetic human growth hormone (somatotropin) in the treatment of knee OA, assessing pain relief, functional improvement, and cartilage regeneration. Methods: A four-arm, double-blind randomized trial was conducted with 51 knees from 28 subjects aged ≥50 with primary knee OA. The treatments involved were HA alone, HA with hUC-MSCs, HA with somatotropin, and a combination of all three. Efficacy was measured through the International Knee Documentation Committee (IKDC) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and visual analog score (VAS), and MRI T2 mapping of cartilage was conducted on pre-implantation at the 6th and 12th month. Results: All treatment arms showed improvements in the VAS and WOMAC scores over 12 months, suggesting some pain relief and functional improvement. However, MRI T2 mapping showed no significant cartilage regeneration across the groups. Conclusions: While the combined use of HA, hUC-MSCs, and somatotropin improved symptoms of knee OA, it did not enhance cartilage regeneration significantly. This study highlights the potential of these combinations for symptom management but underscores the need for further research to optimize these therapies for regenerative outcomes.
Metal–Organic Framework-Based Nanostructures for Electrochemical Sensing of Sweat Biomarkers
Authors: Meng Jing , Zahran Moustafa , Li Xiaolin
Published: October 2024

Sweat is considered the most promising candidate to replace conventional blood samples for noninvasive sensing. There are many tools and optical and electrochemical methods that can be used for detecting sweat biomarkers. Electrochemical methods are known for their simplicity and cost-effectiveness. However, they need to be optimized in terms of selectivity and catalytic activity. Therefore, electrode modifiers such as nanostructures and metal–organic frameworks (MOFs) or combinations of them were examined for boosting the performance of the electrochemical sensors. The MOF structures can be prepared by hydrothermal/solvothermal, sonochemical, microwave synthesis, mechanochemical, and electrochemical methods. Additionally, MOF nanostructures can be prepared by controlling the synthesis conditions or mixing bulk MOFs with nanoparticles (NPs). In this review, we spotlight the previously examined MOF-based nanostructures as well as promising ones for the electrochemical determination of sweat biomarkers. The presence of NPs strongly improves the electrical conductivity of MOF structures, which are known for their poor conductivity. Specifically, Cu-MOF and Co-MOF nanostructures were used for detecting sweat biomarkers with the lowest detection limits. Different electrochemical methods, such as amperometric, voltammetric, and photoelectrochemical, were used for monitoring the signal of sweat biomarkers. Overall, these materials are brilliant electrode modifiers for the determination of sweat biomarkers.
Synthetic Microwave Focusing Techniques for Medical Imaging: Fundamentals, Limitations, and Challenges
Authors: Abbosh Younis M. , Sultan Kamel , Guo Lei , Abbosh Amin
Published: October 2024

Synthetic microwave focusing methods have been widely adopted in qualitative medical imaging to detect and localize anomalies based on their electromagnetic scattering signatures. This paper discusses the principles, challenges, and limitations of synthetic microwave-focusing techniques in medical applications. It is shown that the various focusing techniques, including time reversal, confocal imaging, and delay-and-sum, are all based on the scalar solution of the electromagnetic scattering problem, assuming the imaged object, i.e., the tissue or object, is linear, reciprocal, and time-invariant. They all aim to generate a qualitative image, revealing any strong scatterer within the imaged domain. The differences among these techniques lie only in the assumptions made to derive the solution and create an image of the relevant tissue or object. To get a fast solution using limited computational resources, those methods assume the tissue is homogeneous and non-dispersive, and thus, a simplified far-field Green’s function is used. Some focusing methods compensate for dispersive effects and attenuation in lossy tissues. Other approaches replace the simplified Green’s function with more representative functions. While these focusing techniques offer benefits like speed and low computational requirements, they face significant ongoing challenges in real-life applications due to their oversimplified linear solutions to the complex problem of non-linear medical microwave imaging. This paper discusses these challenges and potential solutions.
Ultrasensitive Electrochemical Detection of Salmonella typhimurium in Food Matrices Using Surface-Modified Bacterial Cellulose with Immobilized Phage Particles
Authors: Hussain Wajid , Wang Huan , Yang Xiaohan , Ullah Muhammad Wajid , Hussain Jawad , Ullah Najeeb , Ul-Islam Mazhar , Awad Mohamed F. , Wang Shenqi
Published: October 2024

The rapid and sensitive detection of Salmonella typhimurium in food matrices is crucial for ensuring food safety. This study presents the development of an ultrasensitive electrochemical biosensor using surface-modified bacterial cellulose (BC) integrated with polypyrrole (Ppy) and reduced graphene oxide (RGO), further functionalized with immobilized S. typhimurium-specific phage particles. The BC substrate, with its ultra-fibrous and porous structure, was modified through in situ oxidative polymerization of Ppy and RGO, resulting in a highly conductive and flexible biointerface. The immobilization of phages onto this composite was facilitated by electrostatic interactions between the polycationic Ppy and the negatively charged phage capsid heads, optimizing phage orientation and enhancing bacterial capture efficiency. Morphological and chemical characterization confirmed the successful fabrication and phage immobilization. The biosensor demonstrated a detection limit of 1 CFU/mL for S. typhimurium in phosphate-buffered saline (PBS), with a linear detection range spanning 100 to 107 CFU/mL. In real samples, the sensor achieved detection limits of 5 CFU/mL in milk and 3 CFU/mL in chicken, with a linear detection range spanning 100 to 106 CFU/mL, maintaining high accuracy and reproducibility. The biosensor also effectively discriminated between live and dead bacterial cells, demonstrating its potential in real-world food safety applications. The biosensor performed excellently over a wide pH range (4–10) and remained stable for up to six weeks. Overall, the developed BC/Ppy/RGO–phage biosensor offers a promising tool for the rapid, sensitive, and selective detection of S. typhimurium, with robust performance across different food matrices.