Background and Aim: Multiple sclerosis (MS) is known as an autoimmune disease and a chronic inflammatory condition, inducing a wide variety of mood affective disorders, including depression and feelings of hopelessness in many aspects of patients’ quality of life (QoL). In view of the positive side effects of spirituality and spiritual care on finding appropriate strategies for further adaptation, this study aimed to determine the impact of group spiritual care (GSC) on levels of hope in patients suffering from MS. Materials and Methods: This clinical trial was conducted on a total number of 96 patients with MS, referring to the National Multiple Sclerosis Society (NMSS) in the city of Zahedan, Iran. Following sample selection via the convenience sampling technique, the patients meeting the inclusion criteria were randomized into two groups, i.e., intervention and control. The data collection tools for this purpose included a demographic information form and the Adult Hope Scale (AHS, Snyder et al. 1991), completed by the subjects at the pre- and post-intervention stages. As well, the intervention group received five sessions of GSC during three weeks but the control group members only talked over daily issues along with their mental health problems. The data were also analyzed using the SPSS Statistics software (ver. 14). Results: The Kruskal-Wallis test results revealed that the GSC intervention could have a significant positive effect on raising hope in the patients with MS (p<0.001). Moreover, a significant growth was observed in the scores of hope dimensions including agency and pathway (p<0.001). Conclusion: GSC can effectively boost levels of hope in patients suffering from MS in all dimensions. Therefore, it is recommended to utilize this type of care in order to nurture hope in such individuals.

Introduction: multiple sclerosis (MS) is the most common immune-mediated chronic neurodegenerative disease of the central nervous system (CNS), affecting young people. Due to the permanent disability, cognitive impairment, and the enormous detrimental impact MS can exert on the patients’ health-related quality of life. It is of great importance to recognise it in time and commence adequate treatment at an early stage. The currently used disease-modifying therapies (DMT) aim to reduce disease activity and thus halt disability development, which in current clinical practice are monitored by clinical and imaging parameters but not by biomarkers found in blood and/or the cerebrospinal fluid (CSF). Both clinical and radiological measures routinely used to monitor disease activity lack information on the fundamental pathophysiological features and mechanisms of MS. Furthermore, they lag behind the disease process itself. By the time a clinical relapse becomes evident or a new lesion appears on the MRI scan, potentially irreversible damage has already occurred in the CNS. In recent years several biomarkers that previously have been linked to other neurological and immunological diseases have received increased attention in MS. Additionally, other novel, potential biomarkers with prognostic and diagnostic properties have been detected in the CSF and blood of MS patients. Areas covered: in this review, we summarise the most up to date knowledge and research conducted on the already known and most promising new biomarker candidates found in the CSF and blood of MS patients. Author commentary: the current diagnostic criteria of MS rely on three pillars; MRI imaging, clinical events and the presence of oligoclonal bands in the CSF (which was reinstated into the diagnostic criteria by the most recent revision). Even though the most recent McDonald criteria made the diagnosis of MS faster than the prior iteration, it is still not an infallible diagnostic toolset, especially at the very early stage of clinically isolated syndrome. Together with the gold standard MRI and clinical measures, ancillary blood and CSF biomarkers may not just improve diagnostic accuracy and speed but very well may become agents to monitor therapeutic efficacy and make even more personalised treatment in MS a reality in the near future. The major disadvantage of these biomarkers in the past has been the need to obtain CSF to measure them. However, the recent advances in extremely sensitive immunoassays made their measurement possible from peripheral blood even when present only in minuscule concentrations. This should mark the beginning of a new biomarker research and utilisation era in MS.

Pyrethroid pesticides (PYRs) as the third most widely used pesticides, following organophosphorus and carbamate pesticides, which are of significant importance in the analysis and detection of vegetables. However, the current pretreatment technology for PYRs confronts challenges of difficult separation and low enrichment efficiency, resulting in a cumbersome and time-consuming pretreatment process with poor selectivity. Here, a simple and efficient magnetic solid-phase extraction (MSPE) strategy was developed to simultaneously purify and enrich five PYRs in vegetables, with the magnetic covalent organic framework nanomaterial COF-SiO2@Fe3O4 as an adsorbent. The COF-SiO2@Fe3O4 was prepared by a simple solvothermal conditions method, using Fe3O4 as magnetic core, benzidine and 3,3,5,5-tetraaldehyde biphenyl as two building units. COF-SiO2@Fe3O4 could effectively capture the targeted PYRs by virtue of its abundant π-electron system and hydroxyl groups. The impact of various experimental parameters on extraction efficiency was investigated to optimize the MSPE conditions, including adsorbent amount, extraction time, elution solvent type and elution time. Subsequently, method validation was conducted under the optimal conditions in conjunction with gas chromatography-mass spectrometry (GC-MS). Within the range of 5.00–100 μg·kg-1 (1.00–100 μg·kg-1 for bifenthrin and 2.5–100 μg·kg-1 for fenpropathrin), the five PYRs exhibited a strong linear relationship, with determination coefficients ranging from 0.9990 to 0.9997. The limits of detection (LODs) were 0.3–1.5 μg·kg-1, and the limits of quantification (LOQs) were 0.9–4.5 μg·kg-1. The recoveries were 80.2–116.7% with relative standard deviations (RSDs) below 7.0%. Finally, COF-SiO2@Fe3O4, NH2-SiO2@Fe3O4 and Fe3O4 were compared as MSPE adsorbents for PYRs. The results indicated that COF-SiO2@Fe3O4 was an efficient and rapid selective adsorbent for PYRs. This method holds promising prospects for the determination of PYRs in real samples.

Gradual disability worsening in Multiple Sclerosis (MS) is indicative of confirmed progression that mostly involves progression independent of relapse activity (PIRA) and is associated with neurodegeneration. Insights from pathology reveal grey matter involvement (neocortex, hippocampus, spinal cord, and deep grey matter structures) and microglia activation in early stages of MS. Cortical lesions result in thinning and atrophy and are considered accurate predictors of disability progression and cognitive decline.Neuroimaging biomarkers, such as high-resolution 7T MR images and TSPO-PET, have been examined for the detection of cortical pathology linked to cognitive deficits and thus progression, but are limited in clinical practice due to availability, time constraints, and cost.Electroencephalography (EEG) emerges as a non-invasive, cost-effective tool that reflects cortical activity in MS. Its potential in monitoring cognitive impairment is explored by focusing on nonlinear EEG analysis. The MuST PREDICT^TM project aims to extract linear and nonlinear EEG features, investigating their role in predicting disease progression and optimizing treatment. The study employs retrospective, cross-sectional, and prospective designs, utilizing EEGs from various MS forms, cognitive assessments, serum/cerebrospinal fluid biomarkers and neuroimaging. The methodology involves time-based and spectral feature extraction, employing artificial intelligence classifiers and brain criticality-based approaches.The conceptual framework of an innovative modality is herein presented, that would EEG for early MS progression detection. Standardization of the methodology could lead to the creation of a digital tool for better prognostication and treatment strategy optimization.

We previously reported that in multiple sclerosis (MS) patients with a progressive form of the disease, spinal cord periplaques extend distance away from plaque borders and are characterized by the co-occurrence of partial demyelination, astrocytosis and low-grade inflammation. However, transcriptomic analyses comparing periplaques to adjacent normal-appearing white matter (NAWM) areas did not allow providing a comprehensive view of molecular events in astrocytes vs oligodendrocytes. Here, we re-assessed our transcriptomic data with the aim of identifying functionally-relevant co-expression networks that would reflect astrocyte vs oligodendrocyte molecular signatures in periplaques. We identified an astrocytosis-related gene module comprising GFAP, the hub gene CX43/GJA1 and a set of transcripts forming a TGFB/SMAD1/SMAD2 genomic signature. Partial demyelination was characterized by a co-expression network which, besides myelin genes, comprised a highly significant number of translation/elongation-related genes. Interestingly, the main oligodendrocyte-related hub we identified was NDRG1, a gene previously shown to be specifically silenced in the NAWM of MS patients. This result indicated that NDRG1 down-regulation could be an important event in the process of periplaque partial demyelination. To establish a putative link between NDRG1 down-regulation and a cytokine/chemokine signature, we then sought to identify cytokine/chemokine genes whose mRNA levels inversely correlated with those of NDRG1. Following this approach we found 5 candidate immune-related genes whose up-regulation associated with NDRG1 down-regulation: TGFB1, PDGFC, IL-17D, IL-33, and IL-12A. From these results we propose that in the spinal cord of MS patients with progressive forms of the disease, TGFB1 may limit acute inflammation but concurrently induce astrocytosis and an alteration of oligodendrocytes terminal differentiation.

By repeated unloading and loading of the excavation dynamic and static loads, repeated train dynamic and static loads of multi-factors, the underpass tunnel, cross tunnel engineering influence area rock layer, the existing tunnel structure of the three constitutes a multifaceted structure, multi-factor interaction system. Existing tunnels into the prediction theory model of the new tunnel excavation process of dynamic and static loads, dynamic and static loads of existing tunnels are mostly analyzed individually, the results of synergistic analysis needs to be improved. Based on the theory of the current layer method, the paper comprehensively considers the stiffness of the existing tunnel, the stiffness of the new tunnel, the excavation method load and the existing tunnel load, coupled with Peck's empirical formula, the theoretical model of deformation prediction for excavation of a two-lane highway tunnel under the tunnel through the existing railroad is proposed, and verified and optimized by numerical calculations and monitoring data, which proves the applicability and reliability of the theoretical model in the similar strata and the project promotion.

Bioprospecting native Australian plants offers potential discovery of latent and novel bioactive compounds. Promising cytotoxic and antibacterial activity of methanolic extracts of Pittosporum angustifolium and Terminalia ferdinandiana led to further fractionation and isolation using our laboratory’s bioassay guided fractionation protocol. Hence, the aim of this study was to further evaluate the bioactivity of the fractions and subfractions and characterize bioactive compounds using liquid chromatography mass spectroscopy (LC-MS/MS) and gas chromatography MS (GC-MS). Compounds tentatively identified in P. angustifolium Fraction 1 using LC-ESI-QTOF-MS/MS were chlorogenic acid and/or neochlorogenic acid, bergapten, berberine, 8’-epitanegool and rosmarinic acid. GC-MS analysis data showed the presence of around 100 compounds, mainly comprising of carboxylic acids, sugars, sugar alcohols, amino acids, and monoalkylglycerols. Furthermore, the fractions obtained from T. ferdinandiana flesh extracts showed no cytotoxicity, except against HT29 cell lines, and only Fraction 2 exhibited some antibacterial activity. The reduced bioactivity observed in the T. ferdinandiana fractions could be attributed to the potential loss of synergy as compounds become separated within the fractions. As a result, further fractionation, and separation of compounds in these samples were not pursued. However, additional dose-dependent studies are warranted to validate the bioactivity of T. ferdinandiana flesh fractions, particularly since this is an understudied species. Moreover, LC-MS/GC-MS studies confirm the presence of bioactive compounds in P. angustifolium Fraction 1/subfractions which helps to explain the significant acute anti-cancer activity of this plant. The screening process designed in this study has the potential to pave the way for developing scientifically validated phytochemical/bioactivity information on ethnomedicinal plants, thereby facilitating further bioprospecting efforts, and supporting the discovery of novel drugs in modern medicine.

Background and objectives: Lipoid proteinosis (LP) is an autosomal recessive transfer lysosomal storage disease, characterised by the accumulation of hyalin substance in the mucous membranes, skin, internal organs and brain, for which there is no biochemical diagnostic method. The aim of this study was to determine the carnitine and acylcarnitine metabolic profile with LC-MS/MS in LP patients and thereby examine the potential of this as a new biochemical method in the determination of biochemical markers in LP patients. Materials and Methods: In this study, 27 carnitine and acylcarnitine esters were measured with LC-MS/MS in serum samples taken from 14 healthy control subjects and 14 patients who presented at the Skin and Venereal Diseases Polyclinic and were diagnosed with LP as a result of clinical, radiological and histopathological examinations. Results: The results of the study showed that C0 (free carnitine) C3, C4, C4:DC, C5DC, C6, C8, C14:1, C14:2, C16 and C18 acylcarnitines were statistically significantly reduced in the LP patients (p<0.05, p<0.01). Conclusions: It was concluded that the application of carnitine profile screening, which is an inexpensive, rapid and reliable method, could make a contribution to the differential diagnosis as aa supporting laboratory test in individuals with suspected LP.

Background and objectives: TSC1 is a crucial component of the mTOR pathway, impacting cell growth, proliferation, and autophagy, while TSC2 is a tumor suppressor gene that regulates cell growth and is associated with the mTOR signaling pathway. In the present study, we analyzed TSC1 and TSC2 mRNA expression levels in rectal cancer, and evaluated the clinicopathological and prognostic characteristics of TSC1 and TSC2. Materials and Methods: TSC1 and TSC2 mRNA expression was examined in various cancer types. We further evaluated survival to determine the prognostic significance of TSC1 and TSC2 mRNA in CRC using The Cancer Genome Atlas (TCGA) data. Results: The study focused on rectal cancer, as it exhibited the most promising results. The patients were split into two subgroups, each comprising 50% of the total, based on the TSC gene expression levels. This division was made to assess the clinical characteristics associated with the expression of TSC1 and TSC2 genes. In the study, lower TSC1 expression was linked to venous invasion in rectal cancer patients, and there was also a related trend with lymphatic invasion, although it didn't reach statistical significance. Lower TSC2 expression was observed in younger patients and had some associations with sex and M stage, but these correlations were not statistically significant. When it came to survival analysis, TSC1 expression did not significantly impact overall survival, while higher TSC2 expression was associated with a poorer prognosis in rectal cancer. To enhance our comprehension, additional research, especially in larger case studies, is needed to explore the molecular mechanisms and clinical characteristics of TSC genes in colorectal cancer.

The state detection of power cable is very important to ensure the reliability of power supply. Traditional sensors are mostly based on electric field detection, the operation is complex, and its efficiency needs to be improved. This paper optimizes the design and development of the magnetic field detection sensor for AC power cables. Firstly, through the establishment of the magnetic field sensor model, it is determined that permalloy is the material of the magnetic core, the optimal aspect ratio of the magnetic core is 20, and the ratio of coil length to core length is 0.3. Secondly, the coil simulation model is established, and it is determined that the optimal number of turns of the coil is 11000 turns, the diameter of the enamelled copper wire is 0.08mm, and the equivalent magnetic field noise of the sensor is 0.06pT. Finally, the amplifying circuit based on negative magnetic flux feedback is designed and the sensor is assembled, and the experimental circuit is built for sensitivity test. the results show that the sensitivity of the magnetic field sensor is 327.6mV/μT. The sensor designed in this paper has the advantages of small size, high sensitivity, easy to carry and high reliability.

Metabolomic analysis of biological fluids and tissues has become an increasingly routine tool in the biological toolbox. However, challenges remain to be overcome, including developing strategies to maximise coverage of the metabolome without requiring large sample volumes. Here we describe a multimodal strategy that combines data using both LC-MS and GC-MS from a unique vial with a sample of plasma (20µl) or a sample of brain tissue (3mg). Using a split phase extraction the non-aqueous phase was analyzed by reversed phase (RP) LC-MS, whilst the aqueous phase was analyzed using hydrophilic liquid interaction chromatography (HILIC)LC-MS, with both phases also analysed using GC-MS after derivatization of the extract. Analytical performance was assessed in 7 rat cerebellum samples and a pilot study of 40 plasma samples (20 vs. 20: AD vs. healthy controls). The method, which uses four hours of instrument time, measured 20,707 metabolite features in brain samples and 17,266 in plasma samples, from those 44.1% features displayed CV’s below 15% and 75.2% below 30%. The method has potential to resolve subtle biological differences and to correlate metabolite composition directly to clinical outcomes including MMSE, age and ADCS-ADL. This method can acquire in the order of 20K metabolic features when low volumes are available.

23-Hydroxy ursolic acid (23-OH UA) is a potent atheroprotective and anti-obesogenic phytochemical, with anti-inflammatory and inflammation resolving properties. In this study, we examined whether dietary 23-OH UA protects mice against the acute onset and progression of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). Female C57BL/6 mice were fed either a defined low-calorie maintenance diet (MD) or an MD supplemented with 0.2 % wgt/wgt 23-OH UA for 5 weeks prior to actively inducing EAE and during the 30 days post-immunization. We observed no difference in the onset of EAE between both groups of mice, but ataxia and EAE disease severity were suppressed by 52% and 48%, respectively, and disease incidence was reduced by over 49% in mice that received 23-OH UA in their diet. Furthermore, disease-associated weight loss was strikingly ameliorated in 23-OH UA-fed mice. ELISPOT analysis showed no significant differences in frequencies of T cells producing IL-17 or IFN- between 23-OH UA fed mice and control mice, suggesting that 23-OH UA does not appear to regulate peripheral T-cell responses. In summary, our findings demonstrate that dietary 23-OH UA may represent an effective oral adjunct therapy for the prevention and treatment of relapsing-remitting MS.

L-Theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effect, regulation of immune response, relaxing neural tension, reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPRmt) in UVC-exposed nematodes. In addition, L-theanine treatment also up-regulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provided a theoretical basis for the possibility that tea drinking may prevent mitochondrial related diseases.

Abstract: (1) Background: No consensus has been reached on indicators and protocols for monitoring drug concentrations in organ transplant recipients for the immunosuppressant mycophenolic acid (MPA) in clinical therapy.In this study, we propose to establish a Ultra Performance Liquid Chromatography–Tandem Mass Spectrometry (UPLC-MS/MS) for quantitative determination of MPA and its metabolites ( mycophenolic acid carboxybutoxyether, MPAG and mycophenolic acid carboxyglucuronide, AcMPAG) concentrations in peripheral blood mononuclear cells (PBMCs) and to assess the clinical application of PBMCs concentration detection of MPA and its metabolites in infection prediction in Chinese kidney transplant recipients(KTRs); (2) Methods: PBMCs were isolated with Ficoll-Paque solution, and cells were counted. Acetonitrile precipitated proteins to extract the target compounds.Waters ACQUITY UPLC BEH C18 column of 1.7μm (2.1 mm*50 mm) and an ACQUITY-Xevo TQ-S UPLC-MS/MS system were used for the detection with mobile phases: water and methanol (containing 2 mmol/L NH4Ac + 0.1% formic acid); flow rate: 0.3 mL/min. After gradient elution, the samples were positively ionized by an electrospray positive ion source (ESI) and then quantitatively analyzed by a triple quadrupole tandem mass spectrometer in multiple reaction monitoring (MRM) mode. The performance of the established method was evaluated through a series of validation experiments according to the requirements of the relevant guidelines. We enrolled 7 KTRs with stable conditions and 8 KTRs with infection from August to November 2022, who were treated at the West China Hospital of Sichuan University.Their peripheral blood samples were collected and detected MPA, MPAG, and AcMPAG concentrations in PBMCs using the methods mentioned above and evaluated for their clinical application in the prediction and monitoring of infections in KTRs; (3) Results: After validation of the methodology, the UPLC-MS/MS method established in this study for the determination of MPA, MPAG, and AcMPAG concentrations in PBMCs showed good linearity in the quantitative ranges of 0.0625-50 ng/ml, 0.5-50 ng/ml and 0.1-20 ng/ml, and the selectivity, specificity, matrix effect, carry-over contamination, reproducibility, precision and accuracy all satisfied the requirements.AcMPAG in PBMCs was poorly stabilized and showed significant degradation after -80°C storage for 24 h or 3 cycles of freeze-thaw.There was a large variability in MPA and MPAG concentrations in PBMCs of KTRs and it correlated poorly with plasma MPA concentrations (rs=0.206,p=0.117).Subgroup analysis showed that the correlation between MPA in plasma and PBMCs was still poor in the infected group(rs=0.201,p=0.116), but significant correlation in the stable group (rs=0.643,p=0.001). A significantly higher level of MPA in PBMCs was observed in the infected group than those in the stable group at 2h and 4h after drug dosing (p&lt;0.05).AcMPAG concentrations in PBMCs of KTRs were extremely low and virtually undetectable.ROC curve analysis (area under the curve, AUC) was performed for infection after renal transplantation with indicators of significant difference showed that the area AUC for PBMCs-MPA-C4 was 0.928 ,for PBMCs-MPA-C2 was 0.875,and for Plasma-MPA-C4 was 0.803; (4) Conclusions: In this study, a method based on UPLC-MS/MS was developed and validated for the simultaneous determination of MPA, MPAG, and AcMPAG concentrations in PBMCs.With easy operability and good stability, this method provides a reliable analytical method for the clinical implementation of the detection of MPA, MPAG, and AcMPAG concentrations in PBMCs.The concentrations of MPA and MPAG in PBMCs from KTRs were highly variable and were closely associated with the development of infections after renal transplantation.Monitoring MPA and MPAG in PBMCs may be useful indicators for mycophenolic acid therapeutic drug concentration monitoring (TDM) in KTRs.

Epilepsy is a chronic neuronal disorder characterized by periodic, unpredictable, and recurrent seizures due to either a genetically determined or an acquired brain disorder. Although many anti-epileptics drugs (AEDs) are developed to control epilepsy, 30% of patients still need additional drugs or experience recurrent seizures and psychiatric and behavioral side effects. Thus, the need for medical care for patients with uncontrolled epilepsy remains unmet. The Genus Artemisia L. is one of the largest genera in the Asteraceae family with more than 500 species widely distributed in Europe, Asia, and North America. Many Artemisia species have been used in various treatments since ancient times as folk remedies. They demonstrated strong antioxidant, anti-inflammatory, antimicrobial, antimalarial, and antitumor activity. Recent studies reveal that some species of Artemisia demonstrated a therapeutic benefit for epilepsy by its anti-oxidant, anti-inflammatory, neuroprotective, and anticonvulsant properties. In this review, we investigate the current state of the literature regarding the neuroprotective and antiepileptic potentials of the genus Artemisia and its possible underlying mechanisms.

By using geodesic equations to obtain a gravitational potential generated from a point-like source, we end up in the concept of a nearly Newtonian gravity to analyse effective potentials of quasi-circular orbits. By means of an approximate solution from an axially static and symmetric Weyl metric, we study an effective gravitational potential to obtain its related rotation curves, orbital planes and orbits. Moreover, using as initial condition a Plummer sphere, some prospects on star cluster disruption are also discussed in this framework.

The pH-related metabolic paradigm has rapidly grown in cancer research and treatment. In this contribution, this recent oncological perspective has been laterally for the first time in order to integrate neurodegeneration within the energetics of the cancer acid-base conceptual frame. At all levels of study, molecular, biochemical, metabolic and clinical, the intimate nature of both processes appears to be opposite mechanisms occurring at the far ends of a physiopathological intracellular pH/extracellular pH (pHi/pHe) spectrum. This wide-ranged original approach now permits an increase in our understanding of these opposite processes, cancer and neurodegeneration, and, as a consequence, allows to propose new avenues of treatment based upon the intracellular and microenvironmental hydrogen ion dynamics regulating and deregulating the biochemistry and metabolism of both cancer and neural cells. Under the same perspective, the etiopathogenesis and special characteristics of multiple sclerosis (MS) becomes an excellent model for the study of neurodegenerative diseases and, utilizing this pioneering approach, we find that MS appears to be a metabolic disease even before an autoimmune one. Also within this paradigm, several important aspects of MS, from mitochondrial failure to microbiota functional abnormalities, are analyzed in depth.

An increased risk of multiple sclerosis (MS) had been found when individuals had consumed large amounts of processed meat and sausages at young age (Lauer, 2014). Furthermore it was found in many studies that MS patients had acquired a number of common childhood infections at higher ages than controls. Therefore, MS patients from an epidemiological long-term investigation in Germany and different hospital controls, were evaluated for a statistical interaction of these two factors. 324 MS patients and 242 hospital controls were inquired. The study focussed on age 0 - 16. Subjects were tested for additive interaction by multiple linear regression analysis (Knol et al., 2007). There was an additive interaction of the age at any common childhood infection with the consumption of scalded sausages (regression estimate = 0.1370; standard error = 0.0603; p = 0.0239). In contrast, no such interaction could be shown for: animal fats; smoked meat (e.g. ham and bacon); and cold - smoked German salami. Thus there was a synergy of the intake of scalded sausages (e.g. frankfurters, bolognas, etc.) and age at common childhood infections, for the later risk of MS.

Plain lakes play a crucial role in the hydrological cycle of a watershed, but their interactions with adjacent rivers and downstream water bodies can create complex river-lake relationships, often leading to frequent flooding disasters. Taking Poyang Lake as an example, this paper delves into its interaction with the Yangtze River, revealing the spatiotemporal patterns of flood propagation within the lake and its impact on surrounding flood control measures. The aim is to provide insights for flood management in similar environments worldwide. This study employs a comprehensive approach combining hydrological statistical analysis and two-dimensional hydrodynamic modeling, based on extensive hydrological, topographic, and socio-economic data. The results indicate that the annual maximum outflow from Poyang Lake is primarily controlled by floods within the watershed, while the highest annual lake water level is predominantly influenced by floods from the Yangtze River. The peak discharge typically reaches the lake outlet within 48 hours, with the peak water level taking slightly longer at 54 hours. However, water storage in the lake can shorten the time for the peak discharge to arrive. When converging with floods from the Yangtze River, the peak water level may be delayed by up to 10 days due to the top-supporting interaction. Furthermore, floods from the "Five Rivers" propagate differently within the lake, affecting various lake regions to differing degrees. Notably, floods from the Fu River cause the most significant rise in lake water level under the same flow rate. The top-supporting effect from the Yangtze River also significantly impacts the water surface slope of Poyang Lake. When the Yangtze River flood discharge far exceeds that of the "Five Rivers" (i.e., when the top-supporting intensity f value exceeds 4), the lake surface becomes as flat as a reservoir. During major floods in the watershed, the water level difference in the lake can increase dramatically, potentially creating a "dynamic storage capacity" of up to 840 million cubic meters.

Actinidia arguta (Sieb. et Zucc.) Planch. ex Miq. is abundant of vitamin C and bioactive compounds with high antioxidant activities. In this study, eight wild A. arguta accessions from different areas in Northeast China were collected. Some bioactive compounds were examined on the different tissues of different germplasms including four kinds of leaves, petioles and fruits. The method of UPLC-MS was used to detect the flavonoid compounds. The results showed that some bioactive compounds including vitamin C, soluble sugar, free amino acid, total phenolics and flavonoids content showed significant differences between six tissues of A. arguta accessions and showed significant variability with maturity. In eight accessions, the highest vitamin C content was found in young apical leaves of ‘CBS-6’ (7.47 mg/g fresh weight), and the highest soluble sugar content was in fruits of ‘CJ-1’ (196.52 mg/g fresh weight) and the highest total phenolic content and total flavonoids content were in young apical leaves of ‘CBS-11’ (3.48 mg/g fresh weight) and of ‘CBS-3’ (2.00 mg/g fresh weight), respectively. Ten flavonoid compounds including kaempferol, isorhamnetin and quercetin were detected in leaves, petioles and fruits. The total content of flavonoids were highest in young apical leaves (10219.84 µg·g-1) and the lowest in fruits (78.75 µg·g-1). Based on the comparison of the contents of several bioactive compounds, the two accessions ‘CJ-1’ and ‘CBS-8’ had relatively outstanding performance, and in the comprehensive evaluation of the antioxidant activity among different tissues, the young leaves had the strongest antioxidant activity. These results highlighted the antioxidant potentialities of A. arguta leaves as a major source of phenolics and vitamin C as well as flavonoids. It provided a theoretical basis for the utilization of leaves of A. arguta.

(1) Background: The aim of the research was to present and emphasize the importance of magnetic resonance imaging (MRI) in diagnosing Achilles tendon (AT) ruptures by presenting case reports. (2) Materials and Methods: The sample of respondents included 7 patients (4 males and 3 females, 2 athletes and 5 non-athletes), aged 25 to 58 years, with AT injuries, who were examined and treated at the Institute for Treatment and Rehabilitation "Niška Banja", Niš, Serbia. Ankle examinations with MRI were conducted using the Esaote O-scan 0.3 T machine. The examinations were performed without the application of a paramagnetic contrast agent and without the use of anesthesia. Results: The MRI method's sensitivity and overall diagnostic accuracy were excellent, with 100% true positives. In our study, the method accurately detected the presence, location, and severity of AT injuries in all cases. MRI is an important and reliable method for detecting AT injuries, classifying them, monitoring the course of recovery, and assessing the effects of therapy. Conclusions: An unrecognized or delayed diagnosis of an AT injury can lead to chronic changes. Timely diagnosis (clinical examination, ultrasonography, magnetic resonance imaging) and appropriate treatment (conservative or operative) enable patients to return to normal activities, including sports. Unfortunately, the use of MRI is limited by restricted access and the cost of the examination.

Background: Upper extremities’ function impairments (UEFI) and gait impairment are frequently reported even in the early stages of Multiple Sclerosis (MS) disease. These motor deficits can negatively affect the quality of life (QOL) in MS patient. Exercise has been repeatedly introduced as a beneficial adjuvant therapy for MS, attenuating a wide range of physical and psychological symptoms without any side effects or increased risks of relapse or exacerbation in disease symptoms.Aim: This paper investigates the effect of multi-function swing suspension training (MFSST) program on upper and lower extremities’ function (ULEF), and QOL in MS women according to expanded disability status scale (EDSS) score.Design: Experimental method with a pre-test and post-test design with control group. Setting: The department of Sports Injuries and Corrective Exercise at the Shahid Bahonar University of Kerman.Population: Forty-seven MS women.Methods: Eligible subjects who matched the selection criteria were randomly assigned into three groups as follow: i. Intervention group A (EDSS of 2 – 4), ii. Intervention group B (EDSS of 4.5 – 6.5), and iii. Control group (EDSS of 2 – 6.5). The intervention groups have been trained by the SET program for a duration of 8 weeks. At baseline and after the intervention, the upper extremities’ function (UEF) and the lower extremities’ function (LEF) were assessed by 9-hole peg test (9HPT) and the timed 25-foot walk (T25FW) test, respectively. Moreover, participants’ QOL was measured using the Short Form questionnaire (SF-36).Results: A significant difference was found between the pre-test and post-test variables of walking speed and upper extremity endurance in intervention groups, and between the intervention groups and control group (P < 0.05). Compared to control group, both intervention groups showed improvements in all subscales of QOL, except emotional role limitation score.Conclusions: In summary, these results show that the present protocol of MFSST could be effective in improving ULEF and QOL in MS patients, showing the improvements after 4^th week. Moreover, this protocol was more useful for patients with an EDSS score of more than 4.5. Therefore, it seems that exercise therapy should be considered as a beneficial clinical intervention approach to improve ULEF and QOL in MS patients.

This study presents an innovative analytical method for the detection and quantification of 14 β-agonists in pork using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method involves the use of a solid phase microextraction (SPME) probe, consisting of a wooden tip coated with polyacrylonitrile (PAN) and molecularly imprinted polymer (MIP). This probe has been integrated into an automated extraction device, designed in our laboratory to extract the target analytes prior to LC-MS/MS analysis. Compared to the traditional solid-phase extraction (SPE) procedure, the proposed approach significantly reduces the costs related to adsorbent ma-terial and solvent consumption, and shortens purification time, thereby reducing both the tech-nical workload and associated expenses. The methodology has been carefully validated in ac-cordance with the National Standard of the People's Republic of China (GB/T 22286-2008), evalu-ating key parameters including the limit of detection (LOD), limit of quantification (LOQ), matrix effects, linearity, and both intra-day and inter-day precision. The average recovery rates for all β-agonists were observed to lie between 71.6% and 82.2%, with relative standard deviations (RSDs) consistently below 15% for both types of precision. The LOD and LOQ values were found to range from 0.09 to 0.39 μg/kg and 0.27 to 0.99 μg/kg, respectively. In terms of accurate detection of positive samples, the developed method demonstrated a closer approximation to the true value of the sample compared to the National Standard method GB/T 31658.22-2022. Overall, the proposed method exhibits substantial promise for the routine assessment of β-agonists in pork and presents a practical alternative for compliance monitoring in regulatory settings.

An observational cohort study of patients diagnosed with endometrial cancer (EC) stage IA G1, or atypical endometrial hyperplasia (AHE), undergoing organ-preserving treatment, was conducted. Objective of the study: to determine CDO1, PITX2, and CDH13 gene methylation levels in early endometrial cancer and atypical hyperplasia specimens obtained before organ-preserving treatment in the patients with adequate response and with insufficient response to hormonal treatment. Materials and methods: 41 endometrial specimens obtained during diagnostic uterine curettage in women with EC (n=28) and AEH (n=13), willing to preserve reproductive function, were studied; 18 specimens of endometrial cancer IA stage G1 from peri- and early postmenopausal women (comparison group) were included in the study. The control group included 18 endometrial specimens from healthy women obtained by diagnostic curettage for missed abortion and/or intrauterine adhesions. Methylation levels were analyzed using the modified MS-HRM method. Results: All 13 women with AEH had complete response (CR) to medical treatment. In the group undergoing organ-preserving treatment for uterine cancer IA stage G1 (n=28), 14 patients had complete response (EC CR group) and 14 had not (non-CR). It was found that all groups had statistically significant differences in CDO1 gene methylation levels with the control group (p&lt;0.001) except for the EC CR group (p=0.21). The p-value of difference between EC CR and EC non-CR groups was &lt;0.001. The differences in PITX2 gene methylation levels between the control and study groups were also significantly different (p&lt;0.001), except for AEH group (p=0.21). For the difference between EC CR and EC non-CR groups, the p-value was 0.43. For CDH13 gene methylation levels, statistically significant differences were found between the control and EC non-CR groups (p&lt;0.001), and the control and EC comparison groups (p=0.005). When comparing the EC CR group with EC non-CR group, the p-value for this gene was &lt;0.001. Simultaneous assessment of CDO1 and CDH13 genes methylation allowed to accurately distinguish between EC CR and EC non-CR groups (AUC=0.96). Conclusion: Assessment of CDO1 and CDH13 gene methylation in endometrial specimens from patients with endometrial cancer (IA stage G1), planned for medical treatment, can predict the treatment outcome.

We previously reported a novel secondary progressive multiple sclerosis (SPMS) model, progressive experimental autoimmune encephalomyelitis (pEAE), in oligodendroglia-specific Cx47-inducible conditional knockout (Cx47 icKO) mice. Based on our prior study showing the efficacy of iguratimod (IGU), an anti-rheumatic drug, for acute EAE treatment, we aimed to elucidate the effect of IGU on the SPMS animal model. We induced pEAE by immunizing Cx47 icKO mice with myelin oligodendrocyte glycoprotein peptide 35–55. IGU was orally administered from 17 to 50 days postimmunization. We also prepared primary mixed glial cell culture and measured cytokine levels in the culture supernatant after stimulation with designated cytokines (IL-1α, C1q, TNF-α) and lipopolysaccharide. A migration assay was performed to evaluate the effect of IGU on the migration ability of T cells toward mixed glial cell cultures. IGU treatment ameliorated the clinical signs of pEAE, decreased the demyelinated area, and attenuated glial inflammation on immunohistochemical analysis. Additionally, IGU decreased the intrathecal IL-6 level and infiltrating Th17 cells. The migration assay revealed reduced Th17 cell migration and IL-6 levels in the culture supernatant after IGU treatment. Collectively, IGU successfully mitigated the clinical signs of pEAE by suppressing Th17 migration through inhibition of IL-6 production by proinflammatory-activated glial cells.

The carbonyl iron particles were dispersed in a polychloroprene rubber (CR) matrix under an external magnetic field for practical application as microwave absorption composites film. The film prepared under external magnetic field with a thickness of only 0.54 mm showed least reflection loss of -15.98 dB and the reflection loss value less than -10.0 dB over the frequency range of 11.4~14.8 GHz. In comparison with the microwave absorption properties of calculation by transmission line theory based on the tested relative complex permittivity and permeability and film prepared by general route without external magnetic field, the film made with external magnetic field exhibited more excellent microwave absorption properties, strongly depending on the increment of anisotropy and rearrangement of magnetic particles. The results indicated the composite film made under external magnetic field have excellent microwave absorption properties, which suggest that the composites thin film could be used as a thinner and lighter microwave absorber.

This study is aimed to point out the possible application of the Enzyme-Linked ImmunoSorbent Assay (ELISA) test on table olives. Because olives, like many other foods, are not free from mycotoxin contamination, the main focus of this work was assessing the presence or absence of aflatoxins and ochratoxin A. The work was carried out in two phases. In the first phase, tests were carried out on commercial olives to assess the efficacy of the method and the kit (Veratox® 'Neogen' and AgraQuant® 'Romer Labs') by comparing them with the Liquid Chromatography coupled to a mass-mass spectrometer (LC-MS/MS); in order to understand if there were any interferences in antigen-antibody recognition; subsequently, mycotoxins were inoculated on the same samples with a known quantity, in order to assess the concentrations obtained and compare them to the expected ones. The second step involved modifying the method, so to improve the recovery of inoculated mycotoxins in the samples under study. Afterwards we evaluated the presence of mycotoxins in table olives supplied in the project. The results showed the effectiveness of the ELISA test, especially in the mycotoxin recovery phase. Indeed, after the modification of the mycotoxin extraction method, recoveries increased from 55% to over 70% for aflatoxins, and from 40% to over 55% for ochratoxin A. When analysing the samples provided by the above-mentioned company, the results showed some false positives, in particular in relation to ochratoxin A ’s analysis, mainly related to the first sample submission. Taking this into account, the ELISA test can be considered as an initial screening method applicable as a control programme for the evaluation of mycotoxins in olives which helps by saving time and costs. It should always be kept in mind that, if positive values should emerge, the LC-MS/MS analysis should be carried out.

Seeds from several Ribes taxa were surveyed for phenolic compounds and in vitro antiproliferative activity against HT-29 colorectal cancer cells. Total phenolic compounds were analysed through the Folin-Ciocalteu procedure, while phenolic profiles were analysed by LC coupled to a single mass spectrometer Orbitrap using an electrospray interface (ESI). Antitumor effects were established using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Total phenolics ranged from 11.4 in R. alpinum to 94.8 mg of caffeic acid equivalents (CAE)/g in R. nigrum 'Koksa'. Concerning phenolic compounds, four were hydroxylated benzoic acids, four cinnamic acid derivatives, eight flavonoids, and nine flavonoid glycosides. The growth inhibition against HT-29 cancer cells was exercised much better by R. nigrum 'Koksa' and Ribes 'Erkeeni' (GI50 37 and 42 µg/ml). All Ribes extracts, except R. nigrum 'Hara katarlik', showed higher activity than that of R. rubrum (GI50 at 72 h: 99 µg/ml). Interestingly, the highly bioactive extract from Ribes 'Erkeeni' contains all detected phenolics, while R. nigrum 'Koksa' lacks only populnin. Therefore, the high bioactivity found for such extracts could be due to a synergy due to all detected compounds. This work constitutes a comprehensive action for expanding knowledge on the phenolic profiles and antitumor activity of GLA-rich Ribes seeds.

This is a report on a dynamic autonomous magnetic interaction which does not depend on polarities resulting in short ranged repulsion involving one or more inertial bodies and a new class of bound state based on this interaction. Both effects are new to the literature, found so far. Experimental results are generalized and reported qualitatively. Working principles of these effects are provided within classical mechanics and found consistent with observations and simulations. The effects are based on the interaction of a rigid and finite inertial body (an object having mass and moment of inertia) endowed with a magnetic moment with a cyclic inhomogeneous magnetic field which does not require to have a local minimum. Such a body having some DoF involved in driven harmonic motion by this interaction can experience a net force in the direction of the weak field regardless of its position and orientation or can find stable equilibrium with the field itself autonomously. The former is called polarity free magnetic repulsion and the latter magnetic bound state. Experiments show that a bound state can be obtained between two free bodies having magnetic dipole moment. Various schemes of trapping bodies having magnetic moments by rotating fields are realized as well as rotating bodies trapped by a static dipole field in presence of gravity. Also, a special case of bound state called bipolar bound state between free dipole bodies is investigated.

Cohesion in the refractory metals Cr, Mo, and W is phenomenologically described in this work via a n-body energy functional with a set of physically motivated parameters that were optimized to reproduce selected experimental properties characteristic of perfect and defective crystals. The functional contains four terms accounting for the hard-core repulsion, the Thomas-Fermi kinetic energy repulsion and for contributions to the binding energy of s and d valence electrons. Lattice dynamics, molecular statics, and molecular dynamics calculations show that this model describes satisfactorily thermodynamic properties of the studied metals whereas, unlike other empirical approaches from the literature, predictions of phonon dispersion relations and of surface and point defect energetics reveal in fair good agreement with experiments. These results suggest that the present model is well adapted to large-scale simulations and whenever total energy calculations of thermodynamic properties are unfeasible

Precipitation is a crucial driver for many environmental processes and weather radars are capable of providing precipitation information with high spatial and temporal resolution. However, radar-based quantitative precipitation estimates (QPE) are also subject to various potential uncertainties. This study explores the development, uncertainties and potentials of the hourly operational German radar-based and gauge-adjusted QPE called RADOLAN and its reanalysed radar climatology dataset named RADKLIM in comparison to ground-truth rain gauge data. The precipitation datasets are statistically analysed across various time scales ranging from annual and seasonal aggregations to hourly rainfall intensities in regard to their capability to map long-term precipitation distribution, to detect low intensity rainfall and to capture heavy rainfall. Moreover, the impacts of season, orography and distance from the radar on long-term precipitation sums are examined in order to evaluate dataset performance and to describe inherent biases. Results revealed that both radar products tend to underestimate total precipitation sums and particularly high intensity rainfall. But our analyses also showed significant improvements throughout the RADOLAN time series as well as major advances through the climatologic reanalysis regarding the correction of typical radar artefacts, orographic and winter precipitation as well as range-dependent attenuation.

The following study reports on the first thraustochytrid isolates identified from Iceland. They were collected from three different locations off the northern coast of the country (Location A, Skagaströnd; Location B, Hveravík; and Location C, Eyjafjörður). Using 18S rDNA sequence analysis, isolates from Locations A and B were identified within the Thraustochytrium kinnei species while other isolates within the Sicyoidochytrium minutum species when compared to other known strains. Cells isolated from Locations A (2.10 ± 0.70 g/L) and B (1.54 ± 0.17 g/L) produced more biomass than the ones isolated from Location C (0.43 ± 0.02 g/L). This study offers the first-time examination of the utility of byproducts from fisheries as a nitrogen source in media formulation for thraustochytrids. Experiments showed that isolates produced more biomass (per unit of substrate) when cultured on nitrogen of marine (2.55 ± 0.74 g/L) as compared to of commercial origin (1.06 ± 0.57 g/L). Glycerol (2.43 ± 0.56 g/L) was a better carbon source than glucose (1.84 ± 0.57 g/L) in growth studies. Fatty acid (FA) profiles showed that the isolates from Location C (S. minutum) had low ratios of monounsaturated (4.21 ± 2.96%) and omega-6 (0.68 ± 0.59%) FAs. However, the isolates also had high ratios of docosahexaenoic acid (DHA; 35.65 ± 1.73%) and total omega-3 FAs (40.39 ± 2.39%), indicating that they could serve as a source of marine oils for human consumption and in aquaculture feeds. The T. kinnei isolates from Location A could be used in biodiesel production due to their high ratios of monounsaturated (18.38 ± 6.27%) long chain (57.43 ± 8.27%) FAs.

MicroRNAs (miRNAs), particularly miR-16 and miR-21, play a crucial role in mul-tiple myeloma (MM) pathogenesis by regulating gene expression. This study evalu-ated the prognostic significance of circulating miR-16 and miR-21 expression levels in 48 patients with MM at diagnosis treated with lenalidomide/dexamethasone (LD) compared with 15 healthy individuals (HI). All patients were treated with LD, 13 at first line and 35 at relapse, of whom 21 were tested twice at diagnosis and before LD initiation. The results revealed significantly lower levels of miR-16 and miR-21 in patients than in HIs, both at diagnosis and relapse, with decreased miR-16 levels at diagnosis, indicating improved overall survival (OS) (p value 0.024). Furthermore, miR-16 and miR-21 levels were associated with disease markers, while both corre-lated with the depth of response and mir-16 with sustained response to LD treatment. The ratios of both miR-16 and miR-21 expression levels (prior to LD treat-ment/diagnosis) below 2 predicted a shorter time to response (P = 0.027) and a longer time to next treatment (P = 0.042), respectively. These findings suggested a prognostic value for serum miR-16 and miR-21 levels in MM, as their expression levels corre-lated with disease variables and treatment outcomes.

Introduction: The gastrointestinal tract (GI) is the second most affected organ system in systemic sclerosis or systemic/localized scleroderma (SSc) and is an important topic for research. Approximately 90% of patients with scleroderma exhibit pathology of the GI tract. The systemic scleroderma has the potential to impact any part of the gastrointestinal tract, between the oral cavity and anorectum. The pathological complications of scleroderma adversely impact the health-related quality of life of the affected patients and increase the treatment burden of patients and medical professionals. Study Aim: We summarized the epidemiology, commonly reported clinical manifestations, complications, and available therapies for treating the GI pathology in systemic scleroderma patients. Methodology: We performed a literature review using the keywords "systemic sclerosis," "scleroderma," "GI manifestations in scleroderma," and "GI complications of scleroderma" across databases, including Google Scholar, Medline, Embase, and PubMed. We also analyzed a range of case reports concerning scleroderma manifestations and treatment modalities. Results: Our research revealed the annual incidence of SSc attributing to19.3 cases per million adults in the United States. We found the highest incidence of systemic scleroderma in patients within the age range of 44-55 years. Our results affirmed 5:1 incidence of systemic scleroderma that confirmed the higher impact of this disease condition in females than male populations. We found that the gastrointestinal manifestations of systemic scleroderma predominantly elevate the morbidity and mortality incidence among the affected patients. Esophageal and intestinal manifestations impact 90% and 40-70% of patients with systemic scleroderma. The small bowel hypomotility and small intestinal bacterial overgrowth (SIBO) in systemic scleroderma cases trigger the episodes of malabsorption and malnutrition that eventually add to 50% of the mortality rate. Systemic sclerosis is associated with the high incidence of fecal incontinence that triggers depression and its deleterious mental health manifestations in many clinical scenarios. Conclusion: The gastrointestinal complications in systemic sclerosis potentially deteriorate the daily living activities of the affected patients. The systematic management of the gastrointestinal complications of systemic scleroderma warrants multidisciplinary approaches. Prospective studies should focus on developing targeted therapies for improving the recovery patterns and prognostic outcomes in systemic scleroderma cases.

Soybean, maize and bean are crops of great economic importance, but in the last years suffered with infestations of the caterpillar Helicoverpa armigera, being the main problem the resistance of this pest to most pesticides. Avermectin emamectin benzoate was recently released to control this pest. Other avermectins, like abamectin, doramectin, eprinomectin and ivermectin are used in large scale because they potent acaricidal, anthelmintic, and insecticidal activities. Thus, a simple and fast method for the determination of avermectins in these crops based on a quick, easy, cheap, effective, rugged and safe (QuEChERS) extraction procedure and ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) analysis was developed and validated. For extraction, water followed by acetonitrile:isopropanol and a partition step with salts was stablished. With the clean-up step using activated EMR-Lipid, limits of detection of 1.2 μg kg-1 for abamectin, doramectin, emamectin benzoate and ivermectin, and of 2.4 μg kg-1 for eprinomectin were achieved. Accuracy and precision evaluated at low levels presented satisfactory results. The method was successfully applied in commercial samples and is a good alternative for routine analysis.

Background: Multifunctional nanoparticles are known for their wide range of biomedical applications. Controlling the magnetic properties of these nanoparticles is imperative for various applications, including therapeutic angiogenesis. The study was performed to evaluate the magnetic properties and their control mechanisms by the external magnetic field. Methods: A 100nm magnetic nanoparticle was placed in the magnetic field, and parametrically the magnet field strength and distance was evaluated. Various models of magnetic strength and disposition were evaluated. Magnetic flux density, force/weight, and magnetic gradient strength were the parameters evaluated in electromagnetic computational software. Results: The seven-coil method with three centrally placed coils as Halbach array, and each coil with a flux density of 7 Tesla, and with a coil dimension of 20cmx20cm (square model) of each coil showed a good magnetic strength and force/weight parameters in a distance of 15cm from the centrally placed coil. The particles were then evaluated for their motion characteristics in saline. It showed good displacement and acceleration properties. After that, the particles were theoretically assessed in a similar mathematical model after parametrically correcting the drag force. After application of high drag forces, the particles showed adequate motion characteristics. When the particle size was reduced further, the motion characteristics were preserved even with high drag forces. Conclusion: There is potential for a novel method of controlling multifunctional magnetic nanoparticles using high magnetic fields. Further studies are required to evaluate the motion characteristics of these particles in-vivo and invitro.

When dealing with limited sample sizes or missing values in time series data, achieving high accuracy in forecasting becomes challenging. This challenge is particularly common in wind energy forecasting, where many wind farms lack complete data. In this paper, we employ the widely-used ARIMA (Autoregressive Integrated Moving Average) model for time series forecasting. To address the difficulties posed by limited sample sizes and missing values, we adopt a unique approach by utilizing multiple ARIMA models for different datasets. A key distinction from other multiple models methods for time series forecasting lies in each model within our approach using its own dataset, making the fusion process more intricate. To overcome this, we incorporate neural networks and two techniques for model fusion: direct fusion with a learning mechanism and compensation for missing data through training. For each ARIMA model, we introduce a noise estimation method to circumvent the white noise assumptions inherent in ARIMA models. Finally, we apply these methods to wind energy prediction, and our experimental results showcase a significant enhancement in forecasting accuracy.

Histone demethylases, enzymes responsible for removing methyl groups from histone proteins, have emerged as critical players in regulating gene expression and chromatin dynamics, thereby influencing various cellular processes. LSD2 and LSD1 have attracted considerable interest among these demethylases because of their associations with cancer. However, while LSD1 has received significant attention, LSD2 has not been recognized to the same extent. In this study, we conduct a comprehensive comparison between LSD2 and LSD1, with a focus on exploring LSD2's implications. While both share structural similarities, LSD2 possesses unique features. Functionally, LSD2 shows diverse roles, particularly in cancer, with tissue-dependent roles. Additionally, LSD2 extends beyond histone demethylation, impacting DNA methylation and DNA damage repair pathways. This study underscores the distinct roles of LSD2, providing insights into their contributions to cancer and other cellular processes.

Accurately estimating shrub biomass in arid and semi-arid regions is critical for understanding ecosystem productivity and carbon stocks at both local and global scales. However, capturing the shrub biomass accurately by satellite observations is challenging due to the short and sparse features of shrubs. In this study, we presented a framework to estimate shrub biomass at a 10m spatial resolution by integrating ground in-situ data, unmanned aerial vehicle (UAV), Sentinel-2, and Sentinel-1 observations. The pilot study was conducted in the Helan mountains of Ningxia province, China. First, the spatial distribution map of shrubland and other land cover types was generated in 2023. Then, a prediction model of shrub biomass was developed in a Random Forest Regression (RFR) approach driven by different predicted variable datasets based on in-situ measurements, UAV, and satellite images. Finally, the developed model was used to produce the biomass map of shrubland in 2023. The uncertainty was characterized by creating a standard deviation (SD) map using the Leave-One-Out Cross-Validation (LOOCV) method in the shrub biomass estimates. The resultant shrubland distribution map in 2023 has an F1 score of 0.92. The shrub biomass model driven by spectral bands and vegetation indices (R2= 0.62) demonstrated superior performance than that only driven by spectral bands (R2=0.33) or vegetation indices (R2=0.55). The uncertainty of the estimated biomass was lower than 4%, with the lowest values (<2%) happening in the high shrub coverage (>30%) and biomass production (>30kg/m2) regions. Furthermore, the findings show that the magnitude of shrub biomass was affected by the aridity and precipitation significantly in the study region. This study provides a workflow to accurately monitor the biomass of shrublands in a complicated environment based on remote sensing images from multi-platform observations.

Turmeric, Curcuma longa L., is a type of medicinal plant characterized by its perennial nature and rhizomatous growth. It is a member of the Zingiberaceae family and is distributed across the world’s tropical and subtropical climates, especially in South Asia. Its rhizomes are highly valued for food supplements, spices, flavoring agents, and yellow dye in South Asia since ancient times. It exhibits a diverse array of therapeutic qualities that encompass its ability to combat diabetes, reduce inflammation, act as an antioxidant, exhibit anticancer properties, and promote anti-aging effects. In this study, organic extracts of C. longa rhizomes were subjected to HPLC separation followed by mass spectrometry analysis. The Global Natural Product Social Molecular Networking (GNPS) approach was utilized for the first time in this ethnobotanically important species to conduct an in-depth analysis of its metabolomes based on their fragments. A total of 30 metabolites including 16 diarylheptanoids, 1 diarylpentanoid, 3 bisabolocurcumin ethers, 4 sesquiterpenoids, 4 cinnamic acid derivatives, and 2 fatty acid derivatives were identified. Among 16 diarylheptanoids identified in this study, five of them are reported for the first time in this species.

Tamarix nilotica (Ehrenb.) Bunge (Tamaricaceae), an indigenous plant to the Middle East region, is well-known as a medicinal plant for treating many human ailments. The current study aimed at exploring the polyphenols profile of T.nilotica alcohol soluble fraction of aqueous extract, assessing its in-vivo antifibrotic activity and the possible underlying mechanism, to unravel the impact of quantitative difference of sulphated polyphenols content on the antifibrotic activity of T.nilotca grown in two different habitats. Polyphenols profiling of T. nilotica extracts was performed using HPLC-HRESI-QTOF-MS-MS. The major polyphenol components included sulphated flavonoids, phenolic acids and free aglycones. The antifibrotic activity was evaluated through carbon tetrachloride-induced liver fibrosis in rats. Biochemical evaluations revealed that both fractions ameliorated the increased levels of hepatic aminotransferases, lipid peroxidation, hydroxyproline, α-smooth muscle actin (α-SMA), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB). Moreover, both fractions reduced catalase activity (CAT) and enhanced hepatic glutathione (GSH) content. Histopathological imaging undoubtedly confirmed such results. In conclusion, T. nilotica polyphenols rich fraction exhibited potential antifibrotic activity in rats. Significant alterations in GSH levels were recorded based on sulphated polyphenol metabolites content.

A single mode waveguide grating coupler based on multiple Si-SiO₂ pairs onto Si substrate has been designed. Numerical analysis has been carried out to calculate optimum thickness of the layers of Si-SiO₂ that ensures the constructive interference between reflected waves and actual guided wave for high coupling efficiency. Based on the results, an optimal design is developed and modeled by using a 2-D finite difference time domain (2-D FDTD) simulator that dictates a coupling efficiency of as much as 78% (-1.07 dB) at the wavelength of 1550 nm, and a 1-dB bandwidth of 77 nm. The numerical method will be useful to calculate the optimum thicknesses of the layers for any reflector based grating coupler of different materials.

In the former mining district of La Carolina (southern Spain), waste materials were accumulated without first waterproofing the substrate. Additionally, these mining dams were abandoned without any type of restoration, conditions that present a significant risk of contaminating the surrounding soils and waters. Prior to carry out the necessary works for isolating these residues, morphological characterization of the contact with the base substrate is needed. For that purpose, in recent years, different indirect study techniques have been used, among which electrical to-mography stands out. In this work, a less common geophysical technique, magnetometry, both in its magnetic and gra-diometric modalities, is used as an alternative method to analyse the geometry and structure of a mining dam. The results obtained with this methodology are compared with the results provided by electrical techniques, as well as with direct data from mechanical surveys and aerial photo-graphs prior to waste deposition. The magnetic anomaly curves obtained with geometric models generated with the Mag2dc program were also analysed. This comparative study shows the use-fulness of magnetic prospecting in characterizing the base geometry of these mining structures and therefore the interest in its application to environmental characterization studies.

Solanum nigrum fruits have been conventionally available as a material of beverage due to its nutritional substances such as minerals, vitamins, amino acids, proteins, sugars, polyphenols and anthocyanins. Here has rarely reported on the characterizaton of the components and the regulatory mechanism of Anthocyanins in S. nigrum. In this study, we determined that the peel and flesh of S. nigrum fruits shared the similar HPLC profiles, but the different contents and total antioxidant activities for Anthocyanins. After an efficient purification method mainly including extraction with pH 1.0 distilled water and then desorption with pH 1.0 95% ethanol after a DM-130 resin adsorption step to obtain more pure anthocyanins extracts, the purity of anthocyanins extract from S. nigrum fruits reached to 56.1%. Moreover, eight anthocyanins from S. nigrum fruit were identified with HPLC-MS/MS for the first time. A typical R2R3-MYB transcription factor gene, SnMYB, was also cloned for the first time by RACE-PCR from S. nigrum. Moreover, the contents of anthocyanins was shown a good correlation (r = 0.93) with the expression levels of SnMYB during the fruits developmental stages. Most significantly, SnMYB successfully produced high anthocyanins contents (1.03 mg/g) when SnMYB was transiently expressed in tobacco leaves. Taken together, S. nigrum fruits are a promising resource for anthocyanins extraction and SnMYB is an activator that positively regulates anthocyanins biosynthesis in S. nigrum.

In spite of prevalence gaps in several micronutrients supporting immune function, significance of their deficits/supplementation for efficacy of vaccines is underinvestigated. Thus, influence of supplementation combining vitamins C and D, zinc, selenium and manganese, and N-acetyl-cysteine on mouse IgG responses and underlying mechanisms to seasonal quadrivalent influenza vaccine (QIV) was investigated. QIV was given in two doses (28 days apart). The supplementation starting 5 days before the first injection increased the total serum IgG titre, through stimulation of germinal centre (GC) reaction in secondary lymphoid organs (SLOs), as indicated by increase in the frequency of GC B cells and follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells. Additionally, the supplementation “optimized” IgG response following the second QIV injection by supporting more favorable (in respect to virus clearance) IgG2a response through favoring Th1 differentiation as indicating by Th1 (INF-γ) /Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely reflected partly their antioxidant action (as indicated by redox status analyses) on Th cell differentiation. Thus, the study forms solid base for further research aimed at repurposing use this safe and inexpensive micronutrient combination as an adjuvant for virus influenza vaccine.

Sphingolipids are ubiquitous in eukaryotes and certain prokaryotes, where they serve as vital components of biological membranes and as bioactive molecules. Chloroplasts have complex membrane structures that play crucial roles in photosynthesis, but their specific sphingolipidome remains unreported. In this study, we used high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) to analyze the sphingolipidome of purified Arabidopsis thaliana chloroplasts. We detected 92 chloroplast sphingolipids. The chloroplast sphingolipidome differed from total leaf (TL) samples, having a higher content of free long-chain bases and hydroxyceramides, and a greater proportion of complex sphingolipids with 16C fatty acid (FA) forms. Notably, chloroplast glucosylceramides were predominantly the d18:1 h16:0 and t18:1 h16:0 forms, rather than the 24C FA form found in TL and other cellular structures. Comparing the sphingolipidomes of different cellular structures underscores the inhomogeneity of intracellular distribution of sphingolipids. This provides a robust reference for further elucidating the function of sphingolipids in plant cells.

Plaque psoriasis is a common, long-lasting illness that affects the immune system and causes significant negative impacts on a patient's physical health, well-being, and ability to work effectively. Deucravacitinib (DEU) is the first oral medication used in the treatment of plaque psoriasis, a chronic skin condition that causes red, scaly patches on the skin. DEU is a type of medication called an oral Janus kinase (JAK) inhibitor, which works by blocking specific enzymes that play a role in the inflammation and immune response associated with psoriasis. Therefore, a quick, easy, novel, reliable, sensitive, and straightforward Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) approach was used to analyse DEU in plasma samples. The LC-MS/MS method for the determination of DEU in human plasma was based on using trimethoprim as an internal standard (IS). The separation of DEU and IS was carried out via liquid-liquid extraction (LLE). The isolated substances were then subjected to the chromatographic system using the ACE-C18 column (4.6x100 mm, 5 µm). The mobile phase employed consisted of methanol and a solution of 2 mM ammonium formate (80:20 v/v, respectively). The flow rate used was set at 0.9 mL min-1. The creative strategy was performed by running an ABSCIEX API 4000 mass spectrometer with an electron spray ionization source in Multiple Reaction Monitoring (MRM) modes. The ion transitions m/z 426.3  358.2 was used for DEU quantitation, while the ion transitions m/z 291.1  261.1 was used for trimethoprim quantitation. The accuracy, precision, linearity, recovery, and selectivity of DEU were deemed acceptable when validated for a concentration range between 0.500 to 601.050 ng/mL, utilizing a weighting factor of 1/x2.

NH4Cl is one of the nitrogen sources for microalgal cultivation. However, excessive amounts of NH4Cl affects microalgal physiology and biomass contents. In this study, the effects of ammonium on microalgal growth and TAG content in the green microalga (Chlamydomonas reinhardtii) was investigated. Microalgal growth and TAG content under photoautotrophic conditions were found to be unchanged with 17 mM of ammonium, while this compound interfered with microalgal growth and induced TAG content under mixotrophic conditions with acetate supplementation. This suggested that ammonium could induce TAG production when acetate occurred in microalgal cultivation. Further, the effects of two different concentrations of NH4Cl (17 mM and 60 mM) on the cells under mixotrophic conditions were investigated. The results showed that both concentrations reduced microalgal growth, but induced total lipid and TAG content, especially after a 4-day cultivation. The oxygen evolution and Fv/Fm ratio showed that both concentrations completely inhibited the oxygen evolution on Day 4. The 60 mM NH4Cl reduced the Fv/Fm ratio from 0.7 to 0.48 indicating that ammonium supplementation directly affects the microalgae photosynthesis performance. A total of 1782 proteins were successfully identified using proteomics analysis. Among them, there were nine overexpressed proteins and four proteins were underexpressed. Using the protein–ligand interaction analysis, nitrogen metabolism is involved under NH4Cl conditions. This information can provide biochemical knowledge for microalgae development for sustainable energy usage.

In the last decade, the tremendous improvement in the sensitivity and also affordability of Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) have revolutionized its application in pharmaceutical analysis, resulting in wide-spread of employing LC-MS/MS for determining pharmaceutical compounds including anticancer drugs in pharmaceutical research and also industries. Currently, LC-MS/MS has been widely used to quantify small molecule oncology drugs in various biological matrices to support preclinical and clinical Pharmacokinetic studies in R & D of oncology drugs. This mini-review article will describe the state-of-the art LC-MS/MS and its application in rapid quantification of small molecule anticancer drugs. In addition, efforts have also been made in this review to address several key aspects in the development of rapid LC-MS/MS methods, including sample preparation, chromatographic separation and matrix effect evaluation.

A sensitive and robust liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of nimbolide in mouse serum. Exemestane was used as the internal standard (IS). Here, we employed acetonitrile-based protein precipitation (PPT) for serum sample preparation, and performed chromatographic separation using an ODS Hypersil C18 column (100×2.1 mm, 5µm) with gradient elution (0.1% formic acid in water vs 100% acetonitrile). The run time was 6 min. Instrumental analysis was performed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) in the multiple-reaction monitoring (MRM) under positive mode. A good linear calibration was achieved in the 5–1000 ng/ml range. The intra- and inter-day precisions for nimbolide were ≤ 12.6% and ≤ 13.9 % respectively. Intra-day accuracy ranged from 96.9% – 109.3% while inter-day accuracy ranged from 94.3% – 110.2%. The matrix effect of nimbolide, detected but consistent at low and high concentrations, do not affect linearity of standard curve. In conclusion, we have developed and validated a sensitive analytical method for determination of a novel natural compound nimbolide in mouse serum and it has been successfully applied to our preclinical study in investigating the pharmacokinetic properties of nimbolide, which could greatly facilitate the preclinical development of the promising lead compound for anticancer therapy.

To assess if SARS-CoV-2 infection induces changes in the urinary volatilomic fingerprint able to be used in the non-invasive COVID-19 diagnosis and management, urine samples of SARS-CoV-2 infected patients (62), recovered COVID-19 patients (30), and non-infected individuals (41) were analysed using solid-phase microextraction technique in headspace mode, combined with gas chromatography hyphenated with mass spectrometry (HS-SPME/GC-MS). In total, 101 volatile organic metabolites (VOMs) from 13 chemical families were identified, being terpenes, phenolic compounds, norisoprenoids, and ketones the most represented groups. Overall, a decrease in the levels of terpenes and phenolic compounds was observed in the control group, whereas norisoprenoids and ketones showed a significant increase. In turn, a remarkable increase was noticed in norisoprenoids and ketones and a milder increase in alcohols, furanic, and sulfur compounds in the recovery group than in the COVID-19 group. Multivariate statistical analysis identified sets of VOMs with the potential to constitute volatile signatures for COVID-19 development and progression. These signatures are composed of D-carvone, 3-methoxy-5-(trifluoromethyl)aniline (MTA), 1,1,6-trimethyl-dihydronaphthalene (TDN), 2-heptanone, and 2,5,5,8a-tetramethyl-1,2,3,5,6,7,8,8-octahydro-1-naphthalenyl ester acetate (TONEA) for COVID-19 infection and nonanoic acid, α-terpinene, β-damascenone, α-isophorone, and trans-furan linalool for patients recovering from the disease. This study provides evidence that changes in the urinary volatilomic profile triggered by SARS-CoV-2 infection constitute a promising and valuable screening and/or diagnostic and management tool for COVID-19 in clinical environment.

Melanocortins play crucial roles in regulating the stress response, inflammation, and skin pigmentation. In this review, we focus on the melanocortin 1 receptor (MC1R), a G protein-coupled receptor primarily known for regulating skin pigmentation and exhibiting anti-inflammatory effects. First, we provide an overview of the structure, signaling pathways, and related diseases of MC1R. Next, we discuss the potential therapeutic use of synthetic peptides and small molecule modulators of MC1R, highlighting the development of various drugs that enhance stability through amino acid sequence modifications and small molecule drugs to overcome limitations associated with peptide characteristics. Notably, MC1R-targeted drugs have applications beyond skin pigmentation-related diseases, which predominantly affect MC1R in melanocytes. These drugs can also be useful in treating inflammatory diseases with MC1R expression present in various cells. Our review underscores the potential of MC1R-targeted drugs to treat a wide range of diseases and encourages further research in this area.

An ability of different molecular potentials to reproduce the properties of 2D molybdenum disulphide polymorphs is examined. Structural and mechanical properties, as well as phonon dispersion of the 2H, 1T and 1T’ single-layer MoS2 (SL MoS2) phases, were obtained using density functional theory (DFT) and molecular statics calculations (MS) with Stillinger-Weber, REBO, SNAP, and ReaxFF interatomic potentials. Quantitative systematic comparison and discussion of the results obtained are reported.

This paper is aimed at studying the temporal evolution of the surface displacements occurred over the past few years in the ocean-reclaimed platforms of the Shanghai megacity (China), which are mainly ascribable to consolidation processes of large dredger fills and alluvial deposits. With respect to previous analyses carried out over the same area, this work provides a joint multi-platform differential interferometry synthetic aperture radar (DInSAR) analysis, based on the application of the advanced Small BAseline Subset (SBAS) algorithm. This led us to retrieve long-term deformation time-series that are helpful for a better understanding of the on-going deformation phenomena. To this aim, we have exploited two sequences of SAR data collected by the ASAR/ENVISAT and by the COSMO-SkyMed (CSK) sensors, respectively, spanning the whole time period from 2007 to 2016. Unfortunately, the large time gap (of about three years) existing between the available ASAR/ENVISAT and CSK datasets gave rise to additional difficulties for their combination. Nevertheless, this problem has been faced by benefiting from the knowledge of a time-dependent model describing the temporal evolution of the expected deformations affecting the Shanghai ocean-reclaimed platforms.

Bat feces were reported in ancient Chinese medicine books to have the effect of reducing heat and improving eyesight, but the mechanism of vision improvement still needs further research. To this end, we used 2,2-diphenyl-1-picrylhydrazyl (DPPH) and liquid chromatography/tandem mass spectrometry (LC/MS/MS) to analyze the antioxidant capacity of and the types of vitamins in bat feces. We hoped to screen the pharmacological components of bat feces, and to explain the role that these components may play in the treatment of visual deterioration. Our results found that bat feces had a good antioxidant capacity and mainly contain vitamins B1 (thiamine), B2 (riboflavin), B3 (nicotinamide), B3 (nicotinic acid), and B5 (pantothenic acid). Although these vitamins may help maintain the health of the optic nerve and cornea, the vitamin content of bat feces is low, but the heavy metal content is high, as shown using inductively coupled plasma mass spectrometry (ICP-MS) analysis. Therefore, we suggest that the use of bat feces as traditional Chinese medicine to improve vision should be strictly restricted.

Background. Amyotrophic Lateral Sclerosis (ALS) is a devastating disease involving motor neuron degeneration. The few drugs approved for treatment have at most a marginal benefit, and death usually occurs 2-5 years after diagnosis. Methods. A thorough manual examination of the relevant literature, covering over 35,000 papers. Results. Two major phenomena that are generally not known to clinicians were found. First, insulin signaling is impaired in ALS even in patients not diagnosed with diabetes (DB). Almost all studies that have explicitly tested insulin function in non-DB ALS patients using glucose tolerance tests (18 out of 20, 1964-2022, different groups) have found it to be impaired. Second, there is strong evidence for excessive insulin-independent glucose uptake (IIGU) in ALS. In addition, (i) early/late diabetes are associated with increased/decreased risk, respectively; (ii) insulin-based diabetes drugs are protective in ALS in large retrospective human studies; and (iii) strong animal and human evidence shows that insulin opposes all of the major pathological processes in ALS. Conclusion. Most ALS patients have insulin impairment, yet this is commonly not diagnosed, likely because excessive IIGU normalizes glucose levels. The impairment promotes disease progression. Late diabetes is associated with decreased risk because high glucose levels indicate non-excessive IIGU, and because diabetes drugs are protective. Insulin-based treatment (e.g., GLP1 agonists, insulin) is beneficial and can be disease-modifying in ALS and in frontotemporal dementia variants comorbid with ALS. ALS patients should be routinely tested for insulin function and treated if test results are positive.

Wheat is one of the global strategic crops and ranks third in terms of cereals production. Wheat crop is exposed to many fungal infections during the cultivation stages, some of which have the ability to secrete numbers of toxic secondary metabolites that threaten the quality of grains, consumer health, producer economics and global trade exchange. Fifty-four random samples were collected from wheat which originated from different countries. The samples included 14 of soft wheat to study the extent of their contamination with Deoxynivalenol (DON) and T-2 toxin by auto-ELISA technology and r-biopharm Microtiter plate. All samples were contaminated with DON toxin except one sample, and the contamination average ranged between 40.7 and 1018.8 µg kg-1. The highest contamination rates were in Lithuanian and the lowest in Indian wheat. Meanwhile the highest average level of T-2 toxin contamination was in Lithuanian wheat grains with a rate of 377.4µg kg-1 and the lowest in Polish wheat with an average of 115.3µg kg-1. GC-MS/MS and multiple reaction monitoring mode (MRM), was used to detect 15 triazole derivatives in collected samples, which may be used to combat fungal diseases on wheat during the growing season. Only 9 derivatives were found; Simeconazole, Penconazole, Hexaconazole, Cyproconazole, Diniconazole, Tebuconazole, Metconazole, Fenbuconazole and Difenoconazole. These derivatives varied according to the origin of wheat samples as well as their its concentration whereas, another 6 derivatives were not detected in all samples. A direct inverse relationship was found between the DON concentration in the samples and the residues of Simeconazole, Penconazole, Diniconazole, Tebuconazole, Metconazole, Fenbuconazole and Difenoconazole and the T-2 toxin showed the same relationship except for Tebuconazole. The safe and rational use of some triazole derivatives may be a new approach and a promising strategy not only to reduce plant diseases and their problems, but also to get rid of some mycotoxins as contaminates.

Andean blueberries are wild berries grown and consumed in Ecuador which contain high values of bioactive compounds, mainly anthocyanins, with powerful antioxidant activity. The aim of this study was to evaluate the profile and contents of (poly)phenols and carotenoids in Andean blueberry by HPLC-DAD-MSn and determine a wide range of its biological activities. The antioxidant capacity of this fruit was evaluated in vitro by three different methods and in vivo using the zebrafish animal model, also the toxicity effect was determined by the zebrafish embryogenesis test. Besides, the antimicrobial activity and the capacity of Andean blueberry to produce hemagglutination in blood cells were evaluated. Finally, the bioaccessibility of (poly)phenols and related antioxidant capacity were determined in the different phases of an in vitro digestion. The global results indicated no toxicity of Andean blueberry, weakly bacteriostatic activity, and high contents of anthocyanins and antioxidant capacity, which were partially bioaccesible in vitro (~ 50 % at the final intestinal step), contributing to the knowledge of its health benefits for consumers and its potential use in the food and pharmaceutical industry as functional ingredient.

Shoulder tendinopathies produce pain and reduce functionality. The aim of this randomized clinical trial was to analyze the effects of Percutaneous electrolysis (PE), Percutaneous peripheral Nerve Stimulation (PNS) and eccentric exercise (EE), on pain (NPRS), strength, electromyographic activity, ultrasound characteristics of the tendon (echogenicity, thickness and hypervascularization) and functionality (DASH and SPADI) on individuals with supraspinatus tendinopathy. Participants (n=50) were divided into two groups, they received 4 treatment sessions, one per week, of PE and PNS (n=25) or 10 treatment sessions of TENS and US (n=25). Both groups performed EE program consisted of 3 sets of 10 repetitions of each of the 3 exercises, twice a day, during the 4 weeks. Follow-up was carried out at 4, 12 and 24 weeks after the start of the intervention. There are statistically significant differences in the analysis between groups (p&lt;0.001) in the post-treatment and follow-up measurements favorable to the PE+PNS+EE treatment on pain (NPRS), strength, supraspinatus electromyographic amplitude, ultrasound characteristics of the tendon (echogenicity, thickness and hypervascularization) and DASH and SPADI questionnaires. The combined treatment PE, PNS and EE is an effective option in the clinical management of tendinopathies, with positive results in the short and long term on the variables studied.

Due to similarities in genetics, cellular response, and behavior, Drosophila is used as a model organism in addiction research. A well described behavioral response examined in flies is the induced increase in locomotor activity after a single dose of volatilized cocaine (vCOC) and volatilized methamphetamine (vMETH) known as sensitivity, and the escalation of the locomotor response after the repeated dose, known as the locomotor sensitization. However, knowledge about how vCOC and vMETH affect different neurotransmitter systems over time is scarce. We used LC-MS/MS to systematically examine changes in the concentration of neurotransmitters, metabolites and non-metabolized COC and METH in the whole head homogenates of male flies one to seven hours after single and double vCOC or vMETH administrations. vMETH leads to complex changes in the levels of examined substances over time, while vCOC strongly and briefly increases concentrations of dopamine, tyramine and octopamine followed by a delayed degradation into N-acetyl dopamine and N-acetyl tyramine. The first exposure to psychostimulants leads to significant and dynamic changes in the concentrations relative to the second administration when they are more stable over several hours. Further investigations are needed to understand neurochemical and molecular changes post-psychostimulant administration.

In this study, the microbial strain was isolated from the humus soil to ferment Sophora flavescens and Eleutherococcus sessiliflorus extracts. The isolated microbial was identified as Bacillus genus by 16S rRNA sequence analysis. The fermented plant extracts exhibited the antifungal effects against four types of the plant pathogens such as P. carotorum, B. cinerea, C. fructicola Sau-3, and C. gloeosporioides according to incubation time. Especially, the fermented plant extracts showed the most active activities for Colletotrichum genus to inhibit mycelium growth. Metabolite changes in fermented S. flavescens and E. sessiliflorus extracts were confirmed through LC-Q-TOF/MS. Flavonoid and peptide derivatives were improved in fermented S. flavescens and E. sessiliflorus extracts compared to their unfermented one, respectively. This study suggested that the isolated Bacillus microbial fermentation could be a valuable tool in improving the bioactivity of S. flavescens and E. sessiliflorus extracts to have potential with more environmentally-friendly antifungal agents.

This article summarizes studies using the AIQS-DB method to analyze various types of samples for different purposes. This is a method developed to simultaneously analyze nearly 1500 compounds and is widely used worldwide. The method is highly effective for environmental samples such as water, soil, sediment, and air. Recognizing its potential, this article aims to promote the further application and development of AIQS-DB in research related to food analysis and source tracing. Furthermore, if a suitable dataset can be constructed, it could help research quickly and cost-effectively discover the new bioactive compounds from plant medicine.

A convenient and fast multiresidue method for the efficient identification and quantification of 72 pesticides belonging to different chemical classes in red and white grape wines have been developed. The analysis was based on gas chromatography tandem quadrupole mass spectrometric determination (GC–MS/MS). An optimization strategy involved the selection of MWCNTs amount and cleanup procedure cycle times for m-PFC was performed to achieve ideal recoveries and reduce sample matrix compounds in the final extracts. The optimized procedure obtained consistent recoveries between 70.2 and 108.8% (70.2% and 108.8% for white wine, 72.3% and 106.0% for red wine) , with relative standard deviations (RSDs) generally lower than 8.3% at three spiking levels of 0.01, 0.05 and 0.2 mg/kg. Linearity was studied in the range between 0.005 and 0.2 mg/kg using pesticide standards prepared both in pure solvent and in the presence of matrix, showing coefficients of determination (R²) higher than 0.985 for all the pesticides. To improve accuracy, matrix matched calibration curves were used for calculating the quantification results. Finally, the method was used successfully in detecting pesticide residues in commercial gape wines.

Erlotinib inhibits epithelial growth factor receptor (EGFR) kinase activity and is used to treat non-small cell lung cancer (NSCLC). Despite its high efficacy, recurrence can occur in patients who become resistant to the drug. To address the underlying mechanism of Erlotinib resistance, we investigated additional mechanisms related to mode-of-drug-action, by multiple protein-binding interactions, besides EGFR by using drug affinity responsive target stability (DARTS) and liquid chromatography-mass spectrometry (LC-MS/MS) methods with non-labeled Erlotinib. DNA polymerase alpha subunit B (POLA2) was identified as a new Erlotinib binding protein that was validated by the DARTS platform, complemented with cellular thermal shift assays. Genetic knock-down of POLA2 promoted the anti-proliferative effect of the drug in the Erlotinib-resistant cell line H1299 with high POLA2 expression, whereas overexpression of POLA2 restored anti-proliferative effects in the Erlotinib-sensitive cell line HCC827 with low POLA2 expression. Importantly, POLA2 expression levels in four NSCLC cell lines were positively correlated with anti-proliferative Erlotinib efficacy, verified by bio-statistical analysis (Pearson correlation coefficient, R=0.9886). These results suggest that POLA2 is a novel complementary target protein of Erlotinib, and could clinically provide validity as a surrogate marker for drug resistance in patients with NSCLC.

This article proposes an interferometer which should in principle split further an initially split beam to yield new sets of beams, effectively multiplying the number of beams that can be subjected to detectable interference. It can be considered a modification to the Michelson interferometer that introduces additional arrays of beam splitters, mirrors and detectors. It is expected of the interferometer to provide us with a set or sets of data holding details of phase changes in multiple interference patterns detectable by multiple detectors, enabling comparative analysis of data for multiple interference patterns recorded from a single measurement or activity. The number of multiplied beams possible is not limited, as it only depends on the specific amount of beam splitters required for certain experiments and practicals. The interference of multiple beams may improve sensitivity and detection for instrumentation purposes. The use of multiplied beam interferometry may also extend to quantum computation, particularly in linear optical quantum computation scheme as it enable production of multiple coherent beams which may exhibit properties of entanglement, making it suitable for developing optical multi-qubit systems.

In this study, a new approach to pesticide permeation through the apple peel into the pulp is discussed. The tested compounds can be classified, based on mode of action, as systemic (boscalid, cyprodinil, pirimicarb, propiconazole and tebuconazole) or contact (captan, cypermethrin and fludioxonil) pesticides. The barrier effect was assessed using a Franz flow-type vertical diffusion cell system. Residue analysis was performed using a modified quick, easy, cheap, efficient, rugged and safe (QuEChERS) extraction method coupled to gas chromatography with tandem mass spectrometry (GC-MS/MS). The limits of detection (LODs) ranged between 2.6 µg kg-1 (pirimicarb) and 17 µg kg-1 (captan), with the coefficient of variability (CV) lower than 6%, while recoveries ranged from 85% (boscalid) to 112% (captan) at 0.1 and 1 mg kg-1 spiked levels. The highest peel penetration was observed for pirimicarb, captan and cyprodinil, with cumulative permeation of 90, 19 and 17 µg cm-2, respectively. The total absorption was in the range from 0.32% (tebuconazole) to 32% (pirimicarb). Only cypermethrin was not quantitatively detected in the pulp and its use can be recommended in crop protection techniques. The obtained results indicate that molecular weight, octanol-water partition coefficient and water solubility are important parameters determining the process of pesticide absorption.

Exposure to bisphenol analogues can occur in several ways throughout the food production chain with their presence at higher concentrations representing a risk to human health. This study aimed to develop effective analytical methods to simultaneously quantify BPA and fifteen bisphenol analogues (i.e., bisphenol AF, bisphenol AP, bisphenol B, bisphenol BP, bisphenol C, bisphenol E, bisphenol F, bisphenol G, bisphenol M, bisphenol P, bisphenol PH, bisphenol S, bisphenol Z, bisphenol TMC and tetramethyl bisphenol F) present in canned foods and beverages. Samples of foods and beverages available in the Swiss and EU markets (n = 22) including canned pineapples, ravioli and beer were prepared and analyzed using QuEChERS GC-MS. The quantification method was compared to a QuEChERS LC-MS/MS analysis. This allowed for the selective and efficient quantitative simultaneous analysis of bisphenol analogues. Quantities of these analogues were present in 20 of the 22 samples tested with the most frequent analytes at higher concentrations; BPA and BPS being discovered in 78% and 48% of cases respectively. The study demonstrates the robustness of QuEChERS GC-MS for determining low quantities of bisphenol analogues in canned foods. However, further studies are necessary to achieve full knowledge of the extent of bisphenol contamination in the food production chain and its associated toxicity.

We establish a new Gagliardo-Nirenberg inequality characterized by radial symmetry and involving potentials exhibiting pure power polynomial behaviour. As an application of our result, we investigate the existence of extremals for this inequality, which also correspond to stationary solutions for the nonlinear Schrödinger equation with inhomogeneous nonlinearity, competing with Hs-subcritical nonlinearities, either of local or non-local nature.

The endogenous miRNAs of breast milk are the products of more than 1,000 nonprotein-coding genes, giving rise to mature small regulatory molecules of 19–25 nucleotides. They are incorporated in macromolecular complexes, loaded on Argonaut proteins, sequestrated in exosomes, lipid complexes, or present in exfoliated cells of epithelial, endothelial, or immune origins. Their expression is dependent on the stage of lactation, however their detection depends on progress in RNA sequencing and the reappraisal of small RNAs definition. Some miRNAs from plants are detected in breast milk, opening the possibility of stimulation of immune cells of the allergic repertoire. Each miRNA harbors a seeding sequence, which targets mRNAs, gene promoters, or long noncoding RNAs. Their activities depend on their bioavailability. Efficient doses of miRNAs are estimated at roughly 100 molecules in the cytoplasm of target cells from in vitro and in vivo experiments. Each miRNA is included in networks of stimulation/inhibition/sequestration driving the expression of cellular phenotypes. Three types of stress applied during lactation to manipulate miRNA supply, have been explored on the rodent offspring: foster mother, cafeteria diet, early weaning. The review present the main mature miRNAs described across current mothers’ cohorts, their bioavailability in experimental models, and the studies assessing the potentials of miR-26 or miR-320 miRNA families to alter offspring phenotype.

This study investigates how digital alchemy can enhance literature and language teaching through a combination of online and face-to-face learning. It uses constructivist learning theory and the SAMR model to examine how digital tools and resources can transform learner engagement, critical thinking, and creativity. The study gathered data from interviews, focus groups, and document analysis with 30 participants from private HEI schools. The results show that digital alchemy through blended learning allows learners to personalize and collaborate in their exploration of various literary texts. However, the study also identifies some challenges related to resource availability and educator training. The study emphasizes the importance of using digital alchemy in literature and language teaching and suggests some ways for educators, administrators, and policymakers to effectively use digital tools and resources for student-centered teaching methods in the digital era.

The paper examines common elements between Lévai’s and Milson’s potentials obtained by Liouville transformations of two rational canonical Sturm-Liouville equations (RCSLEs) with even density functions which are exactly solvable via Jacobi polynomials in a real or accordingly imaginary argument. We refer to the polynomial numerators of the given rational density function as ‘tangent polynomial’ (TP) and thereby term the aforementioned potentials as ‘e-TP’ A special attention is given to the overlap between the two potentials along symmetric curves which represent two different forms of the Ginocchio potential exactly quantized via Gegenbauer and Masjed-Jamei polynomials respectively. Our analysis reveals that the actual interconnection between Lévai’s parameters for these two rational realizations of the Ginocchio potential is much more complicated than one could expect based on the striking resemblance between two quartic equations derived by Lévai for ‘averaged’ Jacobi indexes.

In this work, the conceptions of the electrodynamics of action-at-a-distance and of electromagnetic fields are reviewed and confronted, with the aim of clarifying whether it is possible to propose a Weberian theory of action-at-a-distance, which together with a renewed mechanics (both re-specting the existence of a limiting velocity c) could constitute a framework capable of yielding predictions equivalent to those of the conventional Maxwell-Lorentz and SRT framework. In this work, it is shown that, considering basic assumptions about the interaction process, understanding it as an action exchange process, it is possible to derive the expression of the electrodynamic Phipps’ potential energy between two interacting charges. It is also shown that, with the same assumptions and the additional hypothesis that the interaction is supported by a mediating agent (aether or field) which is perturbed by the transmission of action, this perturbation obeys the wave equation (one of the main drawbacks of Weberian electrodynamics). Another aim of the work is to confront the relational electrodynamic formulations (supported by Galilean transformations that assume a universal time) with the Maxwell-Lorentz formulation of electromagnetism (linked to Lorentz transformations that entail local times), in order to elucidate whether the space-time to which the SRT leads us is a mere mathematical artifice or an inescapable reality.

There is currently no unified explanation for the origin of Earth's magnetic field, planetary magnetic fields, stellar magnetic fields, and neutron star magnetic fields, and most importantly, none of these theories have been experimentally verified. This paper is based on a new unified theory of mechanics and its derived applications, which may provide a better explanation for the origin of magnetic fields in celestial bodies and can be experimentally tested to better answer the observed phenomena: (1) the greater the mass of the celestial body, the stronger the magnetic field; (2) the faster the rotation speed of the celestial body, the stronger the magnetic field; (3) the higher the density of the celestial body, the stronger the magnetic field produced.

A comprehensive lipid profile was analyzed in patients with non-small cell lung cancer (NSCLC) using nanoflow ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. The study investigated 297, 202, and 166 lipids in saliva, plasma, and fecal samples, respectively, comparing NSCLC patients to healthy controls. Lipids with significant changes (&gt;2-fold, p&lt;0.05) were further analyzed in each sample type. Both saliva and plasma exhibited similar lipid alteration patterns in NSCLC, but saliva showed more pronounced changes and fecal lipids had weak correlation with those of saliva and plasma. Total triglycerides (TGs) increased (&gt;2–3 folds) in plasma and saliva but decreased in fecal samples. Three specific TGs (50:2, 52:5, and 54:6) were significantly increased in NSCLC across all sample types. A common ceramide species (d18:1/24:0) decreased in both plasma and saliva but increased in fecal samples. Additionally, phosphatidylinositol 38:4 decreased by approximately 2-fold in plasma and saliva. Phosphatidylserine 36:1 was selectively detected in saliva and showed a subsequent decrease, making it a potential biomarker for predicting lung cancer. The study identifies 27 salivary, 10 plasma, and 16 fecal lipids as candidate markers for NSCLC by statistical evaluations. Moreover, it highlights the potential of saliva in understanding changes in lipid metabolism associated with NSCLC.

Volatile organic compounds (VOCs) released from plants have been correlated with disease-status. Analysis of VOCs using GC-MS is time-consuming, laboratory-based, and requires specialist training. Electronic nose devices (E-nose) provide a portable alternative. Three different E-nose devices were compared to assess how accurately they could detect Mango Twig Tip Dieback and Panama disease in banana. The devices were initially trained on known volatiles, then pure cultures of Pantoea sp., Staphylococcus sp., and Fusarium odoratissimum, and finally, on infected and healthy mango leaves and field-collected, infected banana pseudo-stems. The experiments were repeated three times with six replicates for each host-pathogen pair. The variation between healthy and infected host materials was evaluated by principal component and linear discriminant analysis, cross-validation and chemometric data analysis. GC-MS analysis was conducted contemporaneously and identified an 80% similarity between healthy and infected plant material. The portable C 320 was 100% successful in discriminating known volatiles but had a low capability in differentiating healthy and infected plant substrates. The advanced devices (PEN 3 / MSEM 160) successfully detected healthy and diseased samples with a high variance. The results suggest that E-nose devices are more sensitive and accurate in detecting changes of VOCs between healthy and infected plants compared to headspace GC-MS.

Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by pathological processes involving autoimmunity, vasculopathy, and resultant extensive skin and organ fibrosis. Recent studies have demonstrated activation and aberrant wound healing responses in the epithelial layer of the skin in this disease, implicating the epithelial keratinocytes as a source of pro-fibrotic and inflammatory mediators. In this paper we investigated the role of Immunoglobulin G (IgG) autoantibodies directed against epithelial cells, as potential initiators and propagators of pathological keratocyte activation and the ensuing SSc fibrotic cascade. A keratinocyte cell-based ELISA is used to evaluation binding of SSc IgG. SSc skin biopsies were stained by immunofluorescence for the presence of IgG in the keratinocyte layer. Moreover, IgG purified from SSc sera is evaluated for the potential to activate keratinocytes in tissue culture and to induce signaling in TLR2 &amp; 3 reporter cell lines. We demonstrate enhanced binding of SSc IgG to keratinocytes, and activation of these cells leading to release of IL-1α, representing a potential initiating pathway in this disease.

Anti-microbial drugs and coccidiostat compounds are commonly used in poultry farming. These compounds are subsequently excreted and released into the environment via broiler litter (BL) and can re-enter the food chain as fertilizer and/or animal feed. Residues of such drugs can encourage the appearance of antibiotic-resistant bacteria (ARB), as well as toxicity, when found in animal feed. The aim of this study was to develop a multi-residue analytic method for assessing 30 an-ti-microbial drugs and coccidiostats associated with BL and investigate the effects of stacking treatment on anti-microbial and coccidiostat residue degradation in BL used for ruminant feed at the lab-scale. Today, most analytical methods used to identify and quantitate these drug residues are traditional, and may be specific to some antimicrobials. All call for lengthy sample preparation and may present limitations in assessing broiler litter. Such conventional mul-ti-anti-microbial/coccidiostat residue detection assays employ liquid-liquid extraction (LLE) and solid phase extraction (SPE) for sample purification. In our research, LLE and SPE were replaced by Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) clean-up steps for 30 an-ti-microbials and coccidiostats used in broiler farming and detection by liquid chromatography mass spectrometry (LC/MS/ MS). Using this method, recoveries were 70-120%, with the exception of norfloxacin and narasin, which showed recoveries of 67 and 68%, respectively. This analytical meth-od results show that eight samples were not detected in 42 samples, while in 34 samples, one or more drugs were present. Eighteen anti-microbial and coccidiostat residues were detected dur-ing one year sample collaction. The most frequently detected residues were narasin, nicarbazin, monensin, robenidine, oxytetracycline, chlortetracycline, norfloxacin and sulfachloropyridazine, seen at levels from 0.4 to 8.9 mg•kg-1 (ppm). Nineteen anti-microbials and one coccidiostat were degraded to 95% by the stacking treatment. However, tilmicosin and eight coccidiostats persisted in litter (26-100%). The use of antimicrobials and coccidiostats in animal farming is of paramount concern with respect to human, animal and environmental contamination issues and as a source of resistant pathogenic bacteria. Still, most farmers use BL as ruminant feed and fertilizer without processing. Even though the effects of the stacking treatments on degradation of antimicrobials were significantly high, the degradation of coccidiostats and tilmicosin was limited. Clearly, BL should be treated and supervised before use as feed supplement or for land application. Hence, the present method, designed to support these goals, was optimized in terms of sensitivity and se-lectivity for the analytes addressed.

Cathinone is a natural stimulant found in Catha edulis and commonly used in new psychoactive substances. The objective of this study was to examine the disposition kinetics and metabolic profile of cathinone and its metabolite cathine through a single oral dose of cathinone administration in rats. Cathine and cathinone concentrations were identified and quantified using ion trap liquid chromatography (LC-IT/MS), while the metabolic profile was determined using the quadrupole time of flight UPLC-QTOF/MS method in the serum, brain, lung, liver, kidney, and heart over a period of 0, 0.5, 2.5, 6, 12, 24, 48, and 72 hours. The findings revealed a dynamic interplay between the pharmacokinetics of cathinone and its impact on organ-specific biomarkers. The distribution of cathinone and cathine was determined in serum, brain, heart, lung, kidney, and liver. The highest concentration of cathinone was found in the kidney at 1438.6 ug/L. It gradually decreased to 1.97 within 48 hours and disappeared after 72 hours. Within half an hour, cathinone levels in the lungs, liver, and heart were found to be 859, 798.9, and 385.8 ug/L, respectively. However, within 2.5 hours, these levels decreased to 608.1, 429.3, and 309.1 ug/L and kept decreasing until they became undetectable after 24 hours. The concentration of cathinone in the rat brain reduces quickly, dropping to undetectable levels within six hours, with levels decreasing from 712.7 ug/L after just 30 minutes. In the brain and serum, cathine reached its highest levels at 2.5 hours, while in other organs, it peaked at 0.5 hours. This indicates that the conversion of cathinone to cathine is slower in the brain and serum. The study found that cathinone's pharmacokinetics have a significant impact on organ-specific biomarkers. After administering the cathinone, there was a sharp change in biomarker levels, particularly in the liver and brain, during the initial hours. It is essential to investigate the correlation between the changes in biomarkers found in the brain and the levels of cathinone and cathine. The results have significant implications for drug development, pharmacovigilance, and clinical practices involving cathinone. In conclusion, this comprehensive analysis of cathinone's impact on organ-specific biomarkers provides a basis for informed decision-making in medical practices and further research into the cathinone's pharmacological properties.

A novel, rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the evaluation of OTS167 pharmacokinetics in mouse serum. SN-38 was optimized to be selected as the internal standard. Chromatographic separation was performed on a BDS Hypersil C18 column (100 x 2.1 mm, 5 µm) using gradient elution with mobile phase solvent A as water containing 0.1% formic acid and solvent B as acetonitrile containing 0.1% formic acid. The analysis was carried out using multiple reaction monitoring (MRM) with a triple-quadrupole mass spectrometer operated in the positive electrospray ionization mode. Mass transitions of 487.2 > 348.0 and 393.2 > 349.2 were monitored for OTS167 and SN-38 respectively. The standard calibration curve demonstrated high linearity at a range of 5-1000 ng/mL, with a coefficient of determination (r2) ≥ 0.996. The accuracy for OTS167 ranged from 92.3% to 102.2% and the precision was ≤ 12.7%. Recovery was consistent at about 83% to 89%. No significant matrix effect was observed. This method was successfully applied to monitor the pharmacokinetic profiles in mice over 24 h after ingestion of 5 mg/kg of OTS167. Maximum serum concentrations (3197 ng/mL) of OTS167 was observed at 1.67 hour after OTS167 ingestion via garage at 5 mg/kg and area under the curve (AUC) was 28579 h*ng/mL, suggesting that OTS167 can be quickly absorbed after oral administration.

Beyond their significant contribution to the dietary and industrial supplies, marine algae are considered to be a potential source of some unique metabolites with diverse health benefits. The pharmacological properties, such as antioxidant, anti-inflammatory, cholesterol homeostasis, protein clearance and anti-amyloidogenic potentials of algal metabolites endorse their protective efficacy against oxidative stress, neuroinflammation, mitochondrial dysfunction, and impaired proteostasis which are known to be implicated in the pathophysiology of neurodegenerative disorders and the associated complications after cerebral ischemia and brain injuries. As was evident in various preclinical studies, algal compounds conferred neuroprotection against a wide range of neurotoxic stressors, such as oxygen/glucose deprivation, hydrogen peroxide, glutamate, amyloid β, or 1-methyl-4-phenylpyridinium (MPP+) and, therefore, hold therapeutic promise for brain disorders. While a significant number of algal compounds with promising neuroprotective capacity have been identified over the last decades, a few of them have had access to clinical trials. However, the recent approval of an algal oligosaccharide, sodium oligomannate, for the treatment of Alzheimer's disease enlightened the future of marine algae-based drug discovery. In this review, we briefly outline the pathophysiology of neurodegenerative diseases and brain injuries for identifying the targets of pharmacological intervention, and then review the literature on the neuroprotective potentials of algal compounds along with the underlying pharmacological mechanism, and present an appraisal on the recent therapeutic advances. We also propose a rational strategy to facilitate algal metabolites-based drug development.

A single water pollution by dyes is a huge environmental problem; there is a necessity to produce new decolorization methods that are effective, cost-attractive, and suitable in industrial use. Magnetic chitosan polymers offer the advantage of easy separation from the dye solution. In this work, a Chitosan-Fe polymer was synthesized, characterized, and tested for removal of the azo dye Direct Red 83:1 from water. The polymer was characterized in terms of surface morphology (SEM), elemental analysis (EA), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), infrared spectrophotometry (IR), X-ray powder diffraction (XRD) and density functional theory (DFT). The reported results hint that 1 g and pH 7.0 were the best conditions to carry out both kinetic and isotherm models. To understand the adsorption behavior of Direct Red 83:1 onto the polymers, adsorption rate and maximum adsorption capacity were calculated using kinetic tests and isotherm curves respectively. The kinetic data and mechanism of the adsorption process were analyzed by three models and the equilibrium data by three adsorption isotherms. The results indicated that the adsorption process follows a pseudo-second-order kinetics (R2= 0.999) and fits the Temkin isotherm (R2= 0.946), indicating that the adsorption occurred on heterogeneous surfaces. The newly synthesized Chitosan-Fe polymer exhibited good adsorption properties and easy separation of cleaned water.

The bipartite entanglement is comprehensively investigated in the mononuclear molecular complex (Et3NH)[Ni(hfac)2L], where HL denotes 2-(2-hydroxy-3-methoxy-5-nitrophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-3-oxide-1-oxyl and hfacH stands for hexafluoroacetylacetone. From the magnetic point of view, the molecular compound (Et3NH)[Ni(hfac)2L] consists of an exchange-coupled spin-1 Ni2+ magnetic ion and a spin-12 nitronyl-nitroxide radical substituted nitrophenol. The nickel-radical molecular complex affords an experimental realization of a mixed spin-(12, 1) Heisenberg dimer with a strong antiferromagnetic exchange coupling J/kB= 505 K and two distinct g-factors gRad=2.005 and gNi=2.275. By adopting this set of magnetic parameters we demonstrate that the Zeeman splitting of a quantum ferrimagnetic ground-state doublet due to a weak magnetic field may substantially reinforce the strength of bipartite entanglement at low temperatures. The molecular compound (Et3NH)[Ni(hfac)2L] maintains sufficiently strong thermal entanglement even at room temperature, vanishing only above 546 K. Specifically, the thermal entanglement in the nickel-radical molecular complex retains approximately 40% of the maximum value corresponding to perfectly entangled Bell states at room temperature, which implies that this magnetic compound provides suitable platform of a molecular qubit with potential implications for room-temperature quantum computation and quantum information processing.

MicroRNAs (miRNAs) are small endogenous RNAs that regulate gene expression post-transcriptionally by targeting either the 3′ untranslated or coding regions of genes. They have been reported to play key roles in a wide range of biological processes. The recent remarkable developments of transcriptomics technologies, especially next-generation sequencing technologies and advanced bioinformatics tools, allow more in-depth exploration of messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs) including miRNAs. These technologies have offered great opportunities for a deeper exploration of miRNA involvement in farm animal diseases, as well as livestock productivity and welfare. In this review, we provide an overview of the current knowledge of miRNA roles in farm animal diseases with a particular focus on diseases of economic importance. In addition, we discuss the steps and future perspectives of using miRNAs as biomarkers and molecular therapy for livestock disease management as well as the challenges and opportunities for understanding the regulatory mechanisms of miRNAs related to disease pathogenesis.

The aim of this study was to investigate the parameters affecting the extraction of positive molecules such as chlorogenic acids and antioxidants, as well as potentially carcinogenic substances such as acrylamide, in different coffee brewing methods. Three coffee varieties, each assigned to different roasting degree, were used to prepare coffee brews following eight diverse preparation methods. Acrylamide was quantified by HPLC-MS/MS instrument while chlorogenic acids and caffeine by HPLC-DAD system. Three spectrophotometric analyses were also performed (DPPH, TFC and TPC) to evaluate antioxidant activity as well. The results showed that the main brewing parameters, that have the greatest influence on the final content of these compounds were the volume of water used, more specifically the brewing ratio (coffee to water ratio), the extraction time and the particle size of the coffee powder.

Brazil chicken production is around 13 million tons and about a third is exported to over 150 countries, placing Brazil as the world largest chicken meat producer, and therefore it is crucial to follow the legislation of all importer markets. This study conducted a survey by chance in 45 meat industries able to export. Therefore, 2580 chicken meat samples were collected and submitted to 11 analyte extraction and chromatographic verification of compliance in an accredited laboratory. Ten chemical residues (amoxicillin, bacitracin, colistin, dinitolmide + zoalene, spectinomycin, roxarsone, tiamulin, tylosin, trenbolone acetate and virginiamycin) were investigated in chicken meat and one (halofuginone hydrobromide) in chicken liver. The results showed that no compound exceeded the maximum residue limits established by seven legislations. All residue concentrations found were below the method quantification limit, thereby confirming the capability of Brazilian chicken meat industries in complying to foreign markets.

In electric circuits, energy is delivered by electromagnetic fields through the space, as suggested by Kraus and Carver. They provide insights by showing electric/magnetic fields and Poynting vector directions around a DC circuit. In this work, the energy flow mechanism by Kraus and Carver is further studied theoretically for arbitrary terminal potentials of a DC power source.

This review reports the available technologies for the flexible utilization of biomass towards negative CO₂ emissions and addresses the possibility to couple biogas production plants with the electrical grid converting excess electrical energy into storable chemical molecules. This changed mind-set towards biomass utilization can lead readily to the implementation of negative CO₂ emission along the entire bioenergy supply chain without limiting the potential for Power-to-X applications. First, the technologies for direct conversion of waste and wood into gaseous energy carriers are screened, to highlight the potential for the production of renewable fuels. Second, the processes for the removal of CO₂ from biogenic gas streams are analysed in terms of technological performance, cost and further potential for the CO₂ recovered. These technologies are the key to pre-combustion CO₂ capture and negative emissions. Third, the possibility of coupling biomass conversion and synthetic fuels production is explored, providing an overview on the technical maturity of the various energy storage processes. The flexible use of biomass can be an essential part of the future CO₂-free energy systems, as it can directly provide energy carriers all around the year and also large quantities of climate-neutral carbon for the production of synthetic fuels with renewable energy. In turn, when no additional renewable electricity is available, the CO₂ by-product from biofuel synthesis can be used for the negative emissions. This opens the way to an efficient strategy for the seasonal storage of electrical energy, realizing a carbon-neutral energy system coupled with the development of carbon-negative energy strategy.

Plant growth promoting rhizobacteria (PGPR) are a diverse group of microorganisms including genera such as Pseudomonas, Bacillus, Serratia, Enterobacter and Klebsiella. These bacteria have the ability to colonize roots externally and internally, and to directly enhance plant growth employing various mechanisms like phytohormone production and nutrient mineralization. These microbes can also promote plant growth indirectly by secreting antimicrobial compounds (e.g., siderophores, hydrogen cyanide) to antagonize root pathogens or by inducing defensive responses in the plant. Interestingly, there are also cases where production of antibiotic compounds such as 2,4-Diacetylphloroglucinol have the direct effect of enhancing plant growth and yield, irrespective of their biocontrol effects. The objective of this paper is to review publications showcasing PGPRs that have the capacity to both control root pathogens and stimulate plant growth, and to discuss what mechanisms might be involved.

Cholesterol-derived bile acids (BAs) affect numerous physiological functions such as glucose homeostasis, lipid metabolism and absorption, intestinal inflammation and immunity, as well as intestinal microbiota diversity. Diet influences the composition of the BA pool. The present study analyzes the impact of a dietary supplementation with a freeze-dried blueberry powder (BBP) on the fecal BA pool composition. The diet of 11 men and 13 women at risk for metabolic syndrome was supplemented with 50g/day of BBP for 8 weeks, and feces were harvested before (pre) and after (post) BBP consumption. BAs were profiled using liquid chromatography coupled to tandem mass spectrometry. No significant changes in total BAs were detected when comparing pre- vs post-BBP consumption samples. However, post-BBP consumption samples exhibited significant accumulations of glycine-conjugated BAs (p=0.04), glycochenodeoxycholic (p=0.01) and glycoursodeoxycholic (p=0.01) acids, as well as a significant reduction (p=0.03) of the secondary BA levels, when compared to pre-BBP feces (p=0.03). In conclusion, the fecal bileacidome is significantly altered after the consumption of BBP for 8 weeks. While additional studies are needed to fully understand the underlying mechanisms and physiological implications of these changes, our data suggest that the consumption of blueberries can modulate toxic BAs elimination.

Synthetic cannabinoids are a series of synthetic substances that mimic the effects of natural cannabinoids and produce a much stronger toxicity than natural cannabinoids, which have become the most abused family of new psychoactive substances. A solid-phase extractive-liquid chromatography-triple quadrupole/linear ion trap mass spectrometry method was developed to determine 11 synthetic cannabinoids in rat urine. The factors affecting recovery were optimized, and Oasis HLB was selected to extract synthetic cannabinoids simultaneously. The results showed that the linear correlation coefficients of the synthetic cannabinoids ranged from 0.993 to 0.999, and the limit of quantitation ranged from 0.01 to 0.1 ng/mL, and the spiked recoveries ranged from 69.90% to 118.39%. This method has the advantages of good purification ability, simple operation, and good reproducibility, and can be used for the high sensitivity analysis of various synthetic cannabinoids in urine.

Gold clusters protected by 3-MBA ligands (MBA = mercaptobenzoic acid, -SPhCO2H) have attracted recent interest for their unusual structures and advantageous ligand-exchange and bioconjugation properties. Azubel et al. first determined the core structure of an Au68-complex, which was estimated to have 32 ligands (3-MBA groups). To explain the exceptional structure-composition and reaction properties of this complex, and its larger homologs, Tero et al. proposed a “dynamic stabilization” via carboxyl O-H--Au interactions. Herein, we report the first results of an integrated LC/MS analysis of unfractionated samples of gold / 3-MBA clusters, spanning the narrow size range 13.4 to 18.1 kDa. Using high-throughput procedures adapted from bio-macromolecule analyses, we show that integrated capillary HPLC-ESI-MS, based upon aqueous-methanol mobile phases and ion-pairing reverse-phase chromatography, can separate several major components from the nanoclusters mixture that may be difficult to resolve by standard native gel electrophoresis due to their similar size and charge. For each component, one obtains a well-resolved mass spectrum, nearly free of adducts or signs of fragmentation. A consistent set of molecular mass determinations is calculated from detected charge-states tunable from 3- (or lower), to 2+ (or higher). One thus arrives at a series of new compositions (n, p) specific to the Au/3-MBA system. The smallest major component is assigned to the previously unknown (48, 26); the largest one is evidently (67, 30), vs. the anticipated (68, 32). Various explanations for this discrepancy are considered. A prospective is given for the several members of this novel series, along with a summary of the advantages and present limitations of the micro-scale integrated LC/MS approach to characterize such metallic-core macro-molecules, and their derivatives.

Re-investigation of the chemical composition of the annual plant Mitracarpus scaber Zucc. led to the identification of clarinoside, a new pentalogin derivative containing a rare quinovose moiety, and the known compound harounoside. While the planar structure was fully determined using tandem MS and quantum mechanics calculations (QM), the tridimensional structure was unravelled after isolation and NMR analysis. The absolute configuration was assigned by comparison of experimental and theoretical SRCD spectra. Both compounds were tested for anti-inflammatory activity and compound 1 showed the ability to inhibit the production of interleukin-8 (Il-8) with an IC₅₀ of 9.17 µM.

In the study of relativistic jets one of the key open questions is their interaction with the environment on the microscopic level. Here, we study the initial evolution of both electron–proton (e^- - p⁺) and electron–positron (e^±) relativistic jets containing helical magnetic fields, focusing on their interaction with an ambient plasma. We have performed simulations of "global" jets containing helical magnetic fields in order to examine how helical magnetic fields affect kinetic instabilities such as the Weibel instability, the kinetic Kelvin-Helmholtz instability (kKHI) and the Mushroom instability (MI). In our initial simulation study these kinetic instabilities are suppressed and new types of instabilities can grow. In the e^- - p⁺ jet simulation recollimation-like instability occurs and jet electrons are strongly perturbed. In the e^± jet simulation a recollimation-like instability occurs at early times followed by a kinetic instability and the general structure is similar to a simulation without helical magnetic field. Simulations using much larger systems are required in order to thoroughly follow the evolution of global jets containing helical magnetic fields.

Tree peony flowers are traditional ornamental and medicinal materials in China. In this study, 23 tree peony flowers at a broad color spectrum were analyzed. Gas chromatography-mass spectrometer (GC-MS) revealed that tree peony flowers are rich in sugars and organic acids. Up to 18 amino acids were identified by liquid chromatography-mass spectrometer (LC-MS), including all essential amino acids, except for methionine. The majority of amino acids were significant positively correlated with each other and were significant negatively correlated with glucose, fructose and galactose. A total of 11 polyphenols were identified in these tree fresh peony flowers by LC-MS. There was a high consistency in grouping peony flowers by using sugars and organic acids and amino acids, which differed from that based on color components and polyphenols. Tree peony flowers are also rich in K, Ca, Mg and Fe. In together, peony flowers can be a good resource of health-promoting compounds.

Technological advances in DBS hardware and software represent a significant growth area in functional neurosurgery. These advancements have the potential to significantly enhance treatment outcomes and expand the scope of neurological disorders that can be effectively addressed through DBS interventions. The introduction of directional DBS marks a new phase in neuromodulation, offering extended benefits for patients with Parkinson's disease, more efficient optimization of clinical outcomes, and targeted treatment of refractory symptoms through data-driven approaches. Implementing a multimodal programming strategy, incorporating novel current fractionation technology and image-guided tools for lead localization and brain sensing, further reduces reliance on traditional trial-and-error programming methods, paving the way for a more predictive application of this therapy. These advancements are expected to drive the development of sophisticated closed-loop stimulation systems capable of integrating continuous data streams for improved patient care.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects both the upper and lower motor neurons in the nervous system, causing muscle weakness and severe disability. The progressive course of the disease reduces the functional capacity in the affected patients, limits daily activities and leads to complete dependence on caregivers, ultimately resulting in a fatal outcome. Respiratory dysfunction mostly occurs later in the disease and is associated with a worse prognosis. 46 participans were included in our study, with 23 patients in ALS group and 23 individuals in the control group. The ultrasound examination of the phrenic nerve (PN) was performed by two authors using a high-resolution "Philips EPIQ 7" ultrasound machine with a linear 4-18 MHz transducer. Our study revealed that the phrenic nerve is significantly smaller on both sides in ALS patients compared to the control group arba controls (p < 0.001). Only one significant study on PN ultrasound in ALS, conducted in Japan, also showed significant results (p < 0.00001). These small studies are particularly promising, as they suggest that ultrasound findings could serve as a additinioal diagnostic tool for ALS

Transcranial photobiomodulation (tPBM) has been suggested as a non-invasive neuromodulation tool. Repetitive administration of light-emitting diode (LED)-based tPBM for several weeks significantly improved human cognition. To understand the electrophysiological effects of LED-tPBM on the human brain, we investigated alterations by repeated tPBM in vigilance performance and brain networks using electroencephalography (EEG) in healthy participants. Active and sham LED-based tPBM were administered to the right forehead of young participants twice a week for four weeks. The participants performed a psychomotor vigilance task (PVT) during each tPBM/sham experiment. A 64-electrode EEG system recorded electrophysiological signals from each participant during the first and last visits in the 4-week study. Topographical maps of EEG power enhanced by tPBM were statistically compared for the repeated tPBM effect. A new data-processing framework combining the group singular value decompensation (gSVD) with eLORETA was implemented to identify EEG brain networks. The reaction time of PVT in the tPBM-treated group was significantly improved over four weeks compared to that in the sham group. We observed acute increases in EEG delta and alpha powers during 10-min LED-tPBM while the participants performed the PVT task. We also found that theta, beta, and gamma EEG powers significantly increased globally after four weeks of LED-tPBM. Combining gSVD with eLORETA enabled us to identify EEG brain networks and the corresponding network power changes by repeated 4-week tPBM. This study clearly demonstrated that 4-week prefrontal LED-tPBM can neuromodulate several key EEG networks, implying a possible causal effect between modulated brain networks and improved psychomotor vigilance outcomes.

In view of the problem that the output thrust of solenoid actuator is affected by various factors and is difficult to calculate in actual working conditions, this paper proposes a semi-analytical model constructed by magnetic field subdomain method with internal and external boundary conditions in cylindrical coordinate system for calculation, and the general solution equations of magnetic vector potential for each subdomain are derived and solved by MATLAB. Taking a push-pull electromagnet as an example, the finite element simulation and experimental comparative analysis are carried out. The correctness and applicable conditions of the subdomain method are illustrated by comparing the gradient plot of magnetic vector potential, inductance curve and electromagnetic force. By calculating the output thrust after considering the core gravity, spring force and electromagnetic force, it is shown that this method has the advantage of computational flexibility compared with the finite element method, and it is easier to write special algorithms according to various working conditions to calculate the important parameters in engineering applications.

Background: Disparity in adult mortality (AM) with reference to social dynamics and health care has not been sufficiently examined. This study aimed to identify the gap in the understanding of AM in relation to religion, political stability, economic level, and universal health coverage (UHC). Methods: A cross-national study was performed with different sources of data, using the administrative record linkage theory. We created a new data set using data from the 2013 World Bank data catalogue by region, The Economist (Political instability index 2013), Stuckler David et al. (Universal health coverage, 2010), and religious categories of all UN country members. Descriptive statistics, a t-test, an ANOVA followed by a post hoc test, and a linear regression were used where applicable. Result: The average AM rate for males and females was 0.20 ± 0.10 and 0.14 ± 0.10, respectively. AM was significantly higher in economically weak countries, countries with political instability, countries with traditional religion, without achievement of UHC, and Sub-Saharan Africa (p<0.01). There was high disparity of AM between countries with and without UHC (F = male: 61.89, female: 51.85, p<0.001) and between groups with low and high income (F = male: 36.33, female: 42.39, p<0.001). UHC and political stability would significantly reduce AMR by > 0.41 in both sexes and high economic status would reduce male AMR by 0.44, and female AMR by 0.70, in relation to countries without UHC, with political instability, and low economic status. Conclusions: Disparities in AM can be reduced after the achievement of UHC and economically productive activities for those adults affected by conflict and political unrest.

Vitamin D is crucial for athletes' health and performance. Although the exact vitamin D requirements for athletes have not been established, maintaining 25(OH)D levels of at least 40 ng/ml is considered beneficial. This study aimed to determine whether an individual loading dose formula for vitamin D supplementation is suitable to meet a target value of 40 ng/ml and is more effective than standardized supplementation. In a 10-week supplementation study during the winter months in Germany, 90 athletes with insufficient vitamin D levels (25(OH)D<30ng/ml) were randomly assigned to receive either a universal dose of 2000 IU/day of vitamin D or a loading dose of 4000 IU/day, followed by a maintenance dose of 1000 IU/day. Total 25(OH)D concentration was measured from dried blood spots at three time points: at baseline, at the computed date of 40ng/ml, and after the 10-week period. Additionally, a vitamin D-specific questionnaire was issued. On the day when 25(OH)D blood concentrations of 40 ng/ml were calculated to prevail, the individualized group had a significantly higher 25(OH)D level than the standardized group (41.1+-10.9 ng/ml vs. 32.5+-6.4 ng/ml, p<0.001). This study demonstrated that the examined formula is suitable for athletes to achieve a 25(OH)D concentration of 40 ng/ml. This indicates that a personalized approach is more effective than a one-size-fits-all approach in restoring adequate vitamin D levels in athletes.