Cancer researchers are fascinated by the chemistry of diverse natural products which show exciting potential as anticancer agents. In this study, we aimed to investigate the anticancer properties of watermelon rind extract (WRE) by examining its effects on cell proliferation, apoptosis, senescence, and global gene expression in human renal cell adenocarcinoma cells (HRAC-769-P) in vitro. Our metabolome data analysis of WRE exhibited untargeted phyto-constituents and targeted citrulline (22.29 µg/mg). HRAC-769-P cells were cultured in RPMI-1640 media and treated with 22.4, 44.8, 67.2, 88.6, 112, 134.4, and 156.8 mg mL-1 for 24, 48, and 72 hrs. At 24 hrs after treatment, (88.6 mg ml-1 of WRE) cell proliferation significantly reduced, more than 34% compared to the control. Cell viability decreased 48 and 72 hours after treatment to 45% and 37%, respectively. We also examined poly caspase, SA-beta-galactosidase (SA-beta-gal), and wound healing activities using WRE. All treatments induced an early poly caspase response and a significant reduction in cell migration. Further, we analyzed the transcript profile of the cells grown at 44.8 mg ml-1 of WRE after 6 hours using RNA sequencing (RNAseq) analysis. We identified 186 differentially expressed genes (DEGs), including 149 upregulated genes and 37 downregulated genes, in cells treated with WRE compared to the control. The differentially expressed genes were associated with NF-Kappa B signaling and TNF pathways. Crucial apoptosis-related genes such as BMF, NPTX1, NFKBIA, NFKBIE, and NFKBID might induce intrinsic and extrinsic apoptosis. Another possible mechanism is a high quantity of citrulline may lead to induction of apoptosis by the production of increased nitric oxide. Hence, our study suggests the potential anticancer properties of WRE and provides insights into its effects on cellular processes and gene expression in HRAC-769-P cells.

Motivation: It is essential for the diagnosis and treatment of renal cancers to segment kidney tumours precisely and effectively. In medical image segmentation tasks, deep learning models have demonstrated promising results, and the UNet model is widely employed in this field. However, optimising the UNet model for kidney tumour segmentation further can improve its efficacy and deployment feasibility. Related Works: Previous works have explored various techniques to improve the efficiency of deep learning models in medical image segmentation. Image partitioning methods divides the input image into smaller regions, enabling parallel processing and reducing memory requirements. Pruning techniques eliminates redundant or insignificant weights, neurons and connections, resulting in a more compact and efficient model architecture. However, the UNet model architecture and its complexity in the context of kidney tumor segmentation using UNet remains unexplored. Methodology: The proposed methodology consists of adaptive partitioning and weight pruning. Adaptive partitioning divides the UNet model into smaller sub-models, facilitating parallel processing and accelerating inference without compromising segmentation accuracy. Weight pruning techniques remove redundant or less significant weights from the UNet-P model, reducing complexity and improving inference time by eliminating unnecessary computations. The adaptive partitioning and weight pruning processes are seamlessly integrated within the UNet-P architecture, resulting in an optimized model for kidney tumor segmentation. Results: We performed experiments utilising a dataset of KiT 23 CT scan images containing images of kidney malignancies. Compared to the standard UNet model, the optimised UNet-PWP model with adaptive partitioning and weight pruning obtained significant efficiency gains. The adaptive partitioning permitted parallel computation of sub-models, which accelerated inference times. Weight pruning decreased the UNet-PWP model’s complexity without compromising segmentation accuracy, thereby enhancing efficiency. The results of our experiments demonstrated the efficacy of the proposed method with 98% accuracy, demonstrating its potential for deployment in health sector.

The leaves of Ligustrum robustum have been applied as Ku-Ding-Cha, a functional tea to clear heat and remove toxins; and served as a folk medicine to deal with diabetes, obesity, and hypertension. Trans-p-hydroxycinnamic acid and its esters, which were isolated from the leaves of L. robustum, might be a new resource to prevent diabetes and its complications because of their strong -glucosidase and fatty acid synthase (FAS) inhibitory activities and antioxidant effect. However, the quantitative analytical method for trans-p-hydroxycinnamic acid and its esters in the leaves of L. robustum hasn’t been reported so far. In addition, it was difficult and troublesome to analyze no less than 34 trans-p-hydroxycinnamic acid esters by usual HPLC. Therefore, a new HPLC-UV method using hydrolyzation with sodium hydroxide for quantitation of trans-p-hydroxycinnamic acid and its esters in the leaves of L. robustum was developed in the present study. The optimal hydrolyzation conditions were as follows: 1 mL sodium hydroxide aqueous solution (1 M) was added into 1 mL the extract of L. robustum and incubated at 80 °C for 2 h , and then 1 mL hydrochloride (1 M) solution was added. HPLC analysis was performed in reverse phase mode using a C-18 column, eluting with methanol-0.1% acetic acid aqueous solution (40:60, v/v) in isocratic mode at a flow rate of 1.0 mL/min, and detecting at 310 nm. The analytical method was simple and rapid, which simplified greatly the analytical process. The method was validated in terms of linearity, limit of detection (LOD), limit of quantification (LOQ), precision, and accuracy. High linearity was demonstrated with correlation coefficient of 1.000 for trans-p-hydroxycinnamic acid. The LOD and LOQ values were 1.55 and 4.69 μg/mL, respectively. The relative standard deviations (RSD) of intra-day and inter-day variabilities for trans-p-hydroxycinnamic acid were less than 2%. The percentage recovery of trans-p-hydroxycinnamic acid was 101.2% ± 0.8%. Finally, the proposed method was applied successfully to the determination and comparison of the contents of trans-p-hydroxycinnamic acid and its esters in various extracts of the leaves of L. robustum. The 60%-70% ethanol extracts of L. robustum showed the highest contents of free trans-p-hydroxycinnamic acid (3.96-3.99 mg/g), and the 50%-80% ethanol extracts of L. robustum displayed the highest contents of trans-p-hydroxycinnamic acid esters (202.6-210.6 mg/g). The method can be applied also to the quality control of the products of L. robustum.

Neurokinin-1 receptor (NK-1R) antagonists exert an antitumor action, are safe and do not cause serious side-effects. These antagonists (via the NK-1R) exerted multiple actions against cancer: antiproliferative and anti-Warburg effects, apoptosis, anti-angiogenic and antimetastatic. These multiple effects have been shown in a broad-spectrum of cancers. The drug aprepitant (an NK-1R antagonist) is currently used in clinical practice as antiemetic. In in vivo and in vitro studies, aprepitant also showed the aforementioned multiple antitumor actions against many types of cancer. A successful combination therapy (aprepitant and radiotherapy) has recently been reported in a patient suffering from lung carcinoma: the tumor mass disappeared and side-effects were not observed. Aprepitant could be considered as an intelligent bullet against cancer. The administration of aprepitant in cancer patients to prevent recurrence and metastasis after surgical procedures, thrombosis and thromboembolism is discussed as well as the possible link, through the SP/NK-1R system, between cancer and depression. Our main aim is to review the multiple antitumor actions exerted by aprepitant and the use of this drug is suggested in cancer patients. Altogether, the data support the reprofiling of aprepitant for a new therapeutic use as an antitumor agent.

This study aimed to assess the ecotoxicological effects of the interaction of fullerene (C₆₀) and benzo[a]pyrene (B[a]P) on the marine mussel, Mytilus galloprovincialis. The uptake of nC₆₀, B[a]P and mixtures of nC₆₀ and B[a]P into tissues was confirmed by GC-MS, LC-HRMS and ICP-MS. Biomarkers of DNA damage as well as proteomics analysis were applied to unravel the toxic effect of B[a]P and C₆₀. Antagonistic responses were observed at the genotoxic and proteomic level. Differentially expressed proteins (DEPs) were only identified in the B[a]P single exposure and the B[a]P mixture exposure groups containing 1 mg/L of C₆₀, the majority of which were down-regulated (~52%). No DEPs were identified at any of the concentrations of nC₆₀ (p < 0.05, 1% FDR). Using DEPs identified at a threshold of (p < 0.05; B[a]P and B[a]P mixture with nC₆₀), gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis indicated that these proteins were enriched with a broad spectrum of biological processes and pathways, including those broadly associated with protein processing, cellular processes and environmental information processing. Among those significantly enriched pathways, the ribosome was consistently the top enriched term irrespective of treatment or concentration and plays an important role as the site of biological protein synthesis and translation. Our results demonstrate the complex multi-modal response to environmental stressors in M. galloprovincialis.

A Pogorelov polytope is a combinatorial simple 3-polytope realizable in the Lobachevsky (hyperbolic) space as a bounded right-angled polytope. It has no 3- and 4-gons and may have any prescribed numbers of k-gons, k ≥ 7. Any polytope with only 5-, 6- and at most one 7-gon is Pogorelov. For any other prescribed numbers of k-gons, k ≥ 7, we give an explicit construction of a Pogorelov and a non-Pogorelov polytopes. Any Pogorelov polytope different from Löbel polytopes can be constructed from the 5- or the 6-barrel by cuttings off pairs of adjacent edges and connected sums with the 5-barrel along a 5-gon with the intermediate polytopes being Pogorelov. For fullerenes there is a stronger result. Any fullerene different from the 5-barrel and the (5, 0)-nanotubes can be constructed by only cuttings off adjacent edges from the 6-barrel with all the intermediate polytopes having 5-, 6- and at most one additional 7-gon adjacent to a 5-gon. This result can not be literally extended to the latter class of polytopes. We prove that it becomes valid if we additionally allow connected sums with the 5-barrel and 3 new operations, which are compositions of cuttings off adjacent edges. We generalize this result to the case when the 7-gon may be isolated from 5-gons.

Some studies have demonstrated that in vivo degradation processes are influenced by the material’s physico-chemical properties. The present study compares two hydroxyapatites manufactured on an industrial scale, deproteinized at low and high temperatures, and how physico-chemical properties can influence the mineral degradation process of material performance in bone biopsies retrieved 6 months after maxillary sinus augmentation. Residual biomaterial particles were examined by field scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) to determine the composition and degree of degradation of the bone graft substitute material. According to the EDX analysis, the Ca/P ratio significantly lowered in the residual biomaterial (1.08±0.32) compared to the initial composition (2.22±0.08) for the low-temperature sintered group, which also presented high porosity, low crystallinity, low density, a large surface area, and poor stability and a high resorption rate compared to the high-temperature sintered material. This demonstrates that variations in the physico-chemical properties of bone substitute material clearly influence the degradation process. Further studies are needed to determine whether the resorption of deproteinized bone particles proceeds slowly enough to allow sufficient time for bone maturation to occur.

The emergence of the Internet of Things (loT) has led to remarkable advancements in various sectors such as urbanization, manufacturing, and healthcare, intending to enhance the quality of life and contribute to the world economy. However, by the conclusion of 2024, ti is projected that the global network of the Internet of Things (IoT) will encompass over 207billion interconnected devices. The immense data collected and exchanged are often stored in centralized servers, leading to vulnerabilities such as data breaches. Blockchain technology, originally developed for cryptocurrency transactions, provides a possible solution for these challenges with its decentralized, immutable, and encrypted features. This survey provides a comprehensive discussion regarding the fusion of Blockchain technology and the loT, covering architectural alignment, application, security, and limitations. The contributions of this survey include an overview of Blockchain technology and its secure applications, the integration of Blockchain into IoT , an examination of suitable methods for Blockchain integration,and a taxonomy or security and limitations of loT and blockchain integration.

Abstract. The remarks by the Supreme Leader of the Islamic Revolution on the toll of the famines that afflicted occupied Iran in World War I and World War II indicate a desire to incorporate these calamities in Iran’s national narrative and collective memory. His criticism of famine historiography and stated toll numbers, and the unfolding catastrophic famine in Gaza, justify and necessitate a fresh look at each famine’s historiography and toll. This article re-estimates the toll of each famine by including many overlooked and neglected primary sources and in ways not previously done. It builds a trajectory of Iran’s demographic development from 1810 to 1944, and derives the toll of each famine. The World War II famine and typhus epidemics had claimed 5.5 million. World War I famine was also more deadly, though the 1869-73 famine was not far behind. At least 15.5 million Iranians died in the two world wars, a fact nowhere reflected in the history of the conflicts. Iran’s 1944 population of 12 million was unchanged from that of 1850 and a century of population growth obliterated

Introduction: maxillary hypoplasia and mandibular asymmetry may be corrected with orthognathic surgery at the completion of growth. Many patients require segmental Le Fort I osteotomies to obtain the most stable results. Unfortunately, if Invisalign is chosen for pre-surgical preparation, ClinCheck © software does not allow for prediction when these complex surgeries are planned. The objective of this paper was to show the potential of aligners beyond its software in most complex cases like multiple-piece maxillary osteotomies in cleft and non-cleft patients. Method: Thirteen patients who underwent pre-surgical treatment with clear aligners-Invisalign (study group) were matched in terms of diagnosis, surgical procedure, and orthodontic complexity with thirteen patients treated using fixed appliances (control group). A technique based on simple superimposition was devised to enhance the software for creating a suitable occlusion for segmental pre-surgical treatments. Virtual curves following the lower arch were employed to guide the correct pre-surgical positions of the upper teeth. The amount of impressions required in both groups to achieve satisfactory pre-surgical alignment of the segmented arches was compared. Results: one or no refinement phase were needed in the Invisalign group to reach an acceptable pre-surgical occlusion while the amount of pre-surgical impressions taken in order to reach adequate coordination with fixed appliance treatment was slightly higher. The average overall treatment duration did not show a statistically significant variation between the groups. Conclusions: it appears that clear aligner could serve as an effective treatment for individuals with skeletal discrepancies, including cleft and craniofacial anomalies, necessitating segmental Le Fort I osteotomies when aided by the suggested superimposition approach during digital pre-surgical movement simulations. More sophisticated softwares will certainly be implemented in the future.

High incidence of epithelial malignancies in HIV-1 infection is associated with co-infection with oncogenic viruses, such as high-risk human papillomaviruses (HR HPVs), most often HPV16. A collaboration between HIV-1 and HR HPVs in the malignant transformation of epithelial cells exposed to both viruses have long been anticipated. Here, we delineated the effects on in vitro and in vivo properties of HPV16-infected cervical cancer cells of HIV-1 reverse transcriptase. Epidermoid carcinoma Ca Ski cells were made to express RT of HIV-1 clade A (RT_A) or Green Fluorescence Protein (GFP) by lentiviral transduction, subclones with one or six copies of RT_A and six copies of GFP DNA were generated. Expression by subclones of GFP was assessed by flow cytometry, and of RT_A, by Western blotting. Cells were assessed for the levels of mRNA of the RT_A, E6 and its isoforms, and cellular factors characterizing oxidative stress, and EMT by the real-time PCR. Parameters of glycolysis and mitochondrial respiration were assessed by Seahorse technology. Subclones were surveyed for the changes in cell cycle, doubling time, migration capacity, clonogenic activity and for the capacity to form tumors in nude mice. Ca Ski RT_A produced 20-55 fg of RT_A per cell. Expression of RT_A caused a proportional increase in the expression of E6*I isoform. In Ca Ski, RT_A suppressed mitochondrial respiration and oxygen consumption, and increased glycolysis. Compared to parental cells and GFP control, transcription in Ca Ski RT_A of epithelial (E-CADHERIN) state marker was increased, and of mesenchymal (VIMENTIN) decreased, indicating acquisition by cells of the hybrid epithelial/mesenchymal (E/M) phenotype. While Ca Ski GFP and Ca Ski RT_A with one gene insert had reduced migration rate, decreased clonogenic activity in vitro, and diminished capacity to form tumors in nude mice, increase in RT_A copicity/expression mitigated these effects. Altogether, expression of HIV-1 RT_A gave Ca Ski cells the plasticity required to overcome negative effects of lentiviral transduction and potentially increased their tumorigenicity.

This study aimed to detect picobirnavirus (PBV) in the fecal samples of wild and domestic animals from 2014 to 2016 in the Amazon biome. Fecal samples from different animals, including birds (n=41) and mammals (n=217) were used. The PAGE test showed negativity for PBV. However, 32 samples (12.4%, 32/258) showed positive results in RT-PCR analyses. Among the positive sam-ples, pigs and cats, both with 28.12% (9/32), registered the highest frequencies. In phylogenetic analysis, eight sequences from positive samples grouped in the Genogroup 1 of PBV (PBV GI). PBV occurrence was significantly related to cats and pigs, but not other mammals or birds, in-dependently of their geographical origin. Nucleotide analysis demonstrated similarity among the feline group, but the absence of a defined structure between the clades. PBVs are highly wide-spread viruses that can affect the most diverse types of hosts in the Amazon biome, including humans.

The selectin of a demand forecasting method is critical for companies aiming to avoid manufacturing overproduction or shortages in pursuit of sustainable development. Various qualitative and quantitative criteria with different weights must be considered during the evaluation of a forecasting method. The qualitative criteria and criteria weights are usually assessed in linguistic terms. Aggregating these various criteria and linguistic weights for evaluating and selecting demand forecasting methods in sustainable manufacturing is a major challenge. This paper proposes an extension of fuzzy Elimination and Choice Translating Reality (ELECTRE) I to resolve this problem. In the proposed method, fuzzy weighted ratings are defuzzified with the signed distance to develop a crisp ELECTRE I model. Moreover, an extension to ELECTRE I is developed by suggesting an extended modified discordance matrix and a closeness coefficient for ranking alternatives. The proposed extension can overcome the problem of information loss which can lead to incorrect ranking result when using the Hadamard product to combine concordance and modified discordance matrices. A comparison is conducted to show the advantage of the proposed extension. Finally, a numerical example is used to demonstrate the feasibility of the proposed method; furthermore, a numerical comparison is made to display the advantage of the proposed method.

To evaluate the relative importance of IGF-I expression in various cell types for endochon-dral ossification, we quantified the trabecular bone at the secondary spongiosa and epiphysis of the distal femur in 8-12-week-old male mice with a global knockout of the Igf-I gene as well as conditional deletion of the Igf-I gene in osteoblasts, chondrocytes, osteo-blasts/chondrocytes, and their corresponding control wild type littermates. The osteoblast-, chondrocyte- and osteoblast/chondrocyte-specific Igf-I conditional knockout mice were generated by crossing Igf-I floxed mice with Cre transgenic mice in which Cre expression is under the control of Col1α2 or Col2α1 promoter. We found that global disruption of Igf-I resulted in 80% and 70% reduction in bone size, which is defined as total volume, at the secondary spongiosa and epiphysis of the distal femur, respectively. Abrogation of Igf-I in Col1α2-producing osteoblasts, but not Col2α1-producing chondrocytes, decreased bone size by 25% at both the secondary spongiosa and epiphysis while deletion of the Igf-I globally or specifically in osteoblasts or chondrocytes reduced trabecular bone mass by 25%. By contrast, global Igf-I knockout but not conditional knockout of Igf-I in osteoblasts and/or chondrocytes reduced trabecular bone mass in the epiphysis. The reduced trabecu-lar bone mass at the secondary spongiosa in osteoblast- and/or chondrocyte-specific Igf-I conditional knockout mice is caused by reduced trabecular number and increased trabec-ular separation. Immunohistochemistry studies revealed that expression levels of chon-drocyte (COL10, MMP13) and osteoblast (BSP) markers were reduced in the secondary spongiosa and the epiphyses in the global Igf-I knockout mice. Our data indicate that local and endocrine IGF-I actions in bone are pleiotropic and dependent on cell type as well as the bone compartment where IGF-I acts.

Myocardial infarction (MI) is a serious cardiovascular disease that can lead to death. Cardiac troponin I (cTnI) is a biomarker of MI in the circulation system. For detection cTnI protein, many method suffer the same problem, time-consuming. Main drawbacks are time consuming, have tedious operation, require an expensive reader for translating signals, and require non-accessible reagents. Our goal is to create a kit for cTnI protein testing, that the result can easily be read by color difference. The main breakthrough is, the resolution between different concentration can be told by eyes. The result will be future used to create a commercial, potable, convenient, daily-used rapid-test kit. In this study, a cTnI biosensor is proposed that can be read by the naked eye, performs diagnosis based on the pattern color, does not require a reader machine, is easy to operate, and is portable. Our work proposed a device that shortens the diagnosis time, has a quantitative analysis range of 0.32 –200 ng/mL in the human serum matrix, has a 0.32 ng/mL limit of detection (LOD), and shows many advantages comparing to traditional cTnI ELISA plate.

A locally-rotationally-symmetric Bianchi-I model filled with strange quark matter (SQM) is explored in f(R, T) gravity. We take f(R, T) = R + 2 f(T) = R + 2λT, where R is the Ricci scalar, T is the trace of energy-momentum tensor and λ is an arbitrary constant. Exact solutions are obtained by assuming that the expansion scalar is proportional to the shear scalar. This yields a constant value for the deceleration parameter, q = 2, which corresponds to the decelerated phase of the universe. The model is found to be physically viable for λ < −1. SQM during early evolution mimics ultra-relativistic radiation whereas at late times, it behaves as dust, quintessence or even the cosmological constant depending on the value of λ. The effective matter acts as a stiff fluid irrespective of the matter content and of the f(R, T) terms. The model is shear free at late times but remains anisotropic throughout the evolution. In the absence of the f(R, T) terms, SQM accelerates the universe. In the specific case when SQM vanishes at late times, the effect of f(R, T) is to accelerate the universe. The model admits the possibility that SQM could be an alternative to dark energy.

Chorioamnionitis (CA) at term of pregnancy can have infectious and/or inflammatory origin and is associated with adverse outcomes. Triple I (Intrauterine Inflammation, Infection or both, TI) has been proposed to reduce the overdiagnosis of infection and the neonatal overtreatment. The aim of the study is to identify clinical and histological variables predicting adverse outcomes when TI has been suspected and/or confirmed. This retrospective cohort study included 404 pregnancies ≥37 g.a. that were divided into 5 all-inclusive and mutually exclusive groups. TI was defined according to NICHD definition of 2015 and it could be confirmed (TI+) or not (TI-) by histological examination. Signs of infection/inflammation not respecting the definition of TI were classified as “Clinical suspicion”, supported (CS+) or not (CS-) by histology. Histological chorioamnionitis (HCA) without clinical manifestation represented fifth group. Whole Placental Involvement (WPLI), was defined as a histological inflammation involving maternal and fetal side. There were 113 TI+, 30 TI-, 186 CS+, 35 CS- and 40 isolated HCA. WPLI was diagnosed in 133 cases (39.2%). Composite neonatal outcome (CNO) occurred in 114 cases (28.2%) while composite maternal outcome (CMO) occurred in 192 cases (47.5%). TI+ compared to CS+ was more predictive of CNO (p=0.001), CMO (p<0.001) and WPLI (p=0.005). WPLI was related both to CNO (p<0.001) and CMO (p=0.046). TI+ and WPLI showed similar sensitivity but different specificity in predicting CNO. At logistic regression, CNO was independently predicted by TI+ (OR 2.21; p=0.001) and by WPLI (OR 2.23; p=0.001). TI, compared to CS, is a better predictor of CNO and can be useful for the identification of newborns at risk.

Bacterial nitroreductase enzymes that convert prodrugs to cytotoxins are valuable tools for creating transgenic targeted ablation models to study cellular function and cell-specific regeneration paradigms. We recently engineered a nitroreductase (“NTR 2.0”) for substantially enhanced reduction of the prodrug metronidazole, which permits faster cell ablation kinetics, cleaner interrogations of cell function, ablation of previously recalcitrant cell types, and extended ablation paradigms useful for modelling chronic diseases. To provide insight into the enhanced enzymatic mechanism of NTR 2.0, we have solved the X-ray crystal structure at 1.85 Angstroms resolution and compared it to the parental enzyme, NfsB from Vibrio vulnificus. We additionally present a survey of reductive activity with eight alternative nitroaromatic substrates, to provide access to alternative ablation prodrugs, and explore applications such as remediation of dinitrotoluene pollutants. The predicted binding modes of four key substrates were investigated using molecular modelling.

Glutamate excitotoxicity is implicated in the pathogenesis of many disorders, including stroke, traumatic brain injury, and Alzheimer’s disease, for which central insulin resistance is a comorbid condition. Massive glutamate release primarily through ionotropic N-methyl-D-aspartate receptors (NMDARs) causes a sustained rise in [Ca2+]i, followed by mitochondrial depolarization and an increase in intracellular O2• (superoxide) production. Recently, we found that insulin protected neurons against excitotoxicity by diminishing the delayed calcium deregulation (DCD), However, a role of insulin in superoxide production in excitotoxicity still needs to be clarified. The present study is aimed to investigate the effects of insulin on glutamate-evoked superoxide generation and DCD using the fluorescent indicators dihydroethidium, MitoSOX Red, and Fura-FF in rats cultured cortical neurons. We found that insulin significantly diminished both the intracellular and mitochondrial superoxide production in neurons exposed to glutamate and there was a strong linear correlation between [Ca2+]i and intracellular superoxide. MK 801, an inhibitor of NMDAR-gated Ca2+ influx, completely abrogated the glutamate effects in both the presence and absence of insulin. In experiments on sister cultures, insulin diminishes neuronal death. Thus, collectively, data obtained suggest that insulin diminishes glutamate-induced superoxide production in neurons via fall of [Ca2+]i increased and thereby improves viability of neurons

There is high confidence that climate change has increased the probability of concurrent temperature-precipitation extremes, changed their spatial-temporal variations, and affected the relationships between drivers of such natural hazards. However, the extent of such changes has been less investigated in Australia. Daily weather data (131 years, 1889-2019) at 700 grid cells (1◦ × 1◦) across Australia was obtained to calculate annual and seasonal mean daily maximum temperature (MMT) and total precipitation (TPR). A nonparametric multivariate copula framework was adopted to estimate the return period of compound hot-dry (CHD) events based on an ‘And’ hazard scenario (hotter than a threshold ‘And’ drier than a threshold). CHD extremes were defined as years with joint return periods of larger than 25 years. Mann-Kendall nonparametric tests was used to analyse trends in MMT and TPR as well as in the frequency of univariate and CHD extremes. A general cooling-wetting trend was observed over 1889-1989. Significant increasing trends were detected over 1990-2019 in the frequency and severity of hot extremes across the country while trends in dry extremes were mostly insignificant (and decreasing). Results showed a significant increase in the association between temperature and precipitation at various temporal scales. The frequency of CHD extremes was mostly stable over 1889-1989, but significantly increased between 1990 and 2019 at 44% of studied grid cells, mostly located in the north, south-east and south-west. Spatial homogeneity (i.e. connectedness) and propagation of extreme events from one grid cell to its neighbouring cells was investigated across Australia. It can be concluded that this connectedness has not significantly changed since 1889.

Geopolymer cement has been popularly studied nowadays compared to ordinary Portland cement because it demonstrated superior environmental advantages due to its lower carbon emissions and waste material utilization. This paper focuses on the formulation of geopolymer cement from nickel-laterite mine waste (NMW) and coal fly ash (CFA) as geopolymer precursors, and sodium hydroxide (SH) and sodium silicate (SS) as alkali activators. Different mix formulations of raw materials are synthesized to produce a geopolymer based from an I-optimal design and obtained different compressive strengths. A mixed formulation of 50% NMW and 50% CFA, SH-to-SS ratio of 0.5, and an activator-to-precursor ratio of 0.429 yielded the highest 28-day unconfined compressive strength (UCS) of 22.10 ± 5.40 MPa. Furthermore, using an optimized formulation of 50.12% NMW, SH-to-SS ratio of 0.516, and an activator-to-precursor ratio of 0.428, a UCS value of 36.30 ± 3.60 MPa was obtained. The result implies that the synthesized geopolymer material can be potentially used for concrete structures and pavers, pedestrian pavers, light traffic pavers, and plain concrete.

FER zeolites has a unique framework structure and acid distribution, and is widely studied as a catalyst for reactions such as n-butene skeletal isomerization and dimethyl ether carbonylation. The BAS located in the 10-MR of FER zeolites serves as the active site for the isomerization reaction of n-butene skeletal to produce isobutene. In contrast, the acid site found in the 8-MR is prone to side reactions, such as polymerization and cracking, which can adversely affect the selectivity of isobutene. This study prepared five types of FER zeolites using different method, inducing Na-form or H-form crystal seeds without organic structure directing agents (OSDAS), using pyridine alone as a template, and combining the seeds with pyridine. The differences in the structure and acid distribution of the five zeolites were investigated, as well as their catalytic performance for the the skeletal isomerization of n-Butene. Experiments and characterization results showed that under hydrothermal synthesis conditions, the FER-PY+SH zeolites synthesized by using both H-form zeolites seeds and pyridine exhibited the highest aluminum concentrations at T1 and T3 positions, along with the greatest BAS of 10-MR. This unique composition contributed to the highest selectivity of isobutene. The FER-PY+SH catalyst was continuously used for 720 hours at 350 ℃, 0.1 MPa, and n-butene mass space velocity of 2.0 h^-1 for three recycles on 2160 h. During this period, the conversion of n-butene over 39%, while the selectivity of isobutene exceeded 95%.The catalyst exhibited excellent stability and activity.

Drug resistance in melanoma is a major hindrance in cancer therapy. Growth hormone (GH) plays a pivotal role in contributing to resistance to chemotherapy. Knocking down or blocking the GH receptor has been shown to sensitize the tumor cells to chemotherapy. Extensive studies have demonstrated that exosomes, a subset of extracellular vesicles, play an important role in drug resistance by transferring key factors to sensitize cancer cells to chemotherapy. In this study, we explore how GH modulates exosomal cargoes from melanoma cells and their role in drug resistance. We treated the melanoma cells with GH, doxorubicin, and GHR antagonist, pegvisomant, and analyzed the exosomes released. Additionally, we administered these exosomes to recipient cells. The GH-treated melanoma cells released exosomes with elevated levels of ABC transporters (ABCC1 and ABCB1), N-cadherin and MMP2, enhancing drug resistance and migration in recipient cells. GHR antagonism reduced these exosomal levels, restoring drug sensitivity and attenuating migration. Overall, our findings highlight a novel role of GH in modulating exosomal cargoes that drive chemoresistance and metastasis in melanoma. This understanding provides insights to the mechanisms of GH in melanoma chemoresistance and suggests GHR antagonism as a potential therapy to overcome chemoresistance in melanoma treatment.

The present study describes the preparation of a composite material consisting of thermoplastic polyurethane-poly (n-isopropylacrylamide) (TPU-PNIPAM), which was employed for the se-lective adsorption separation of alcohol/water mixed solutions for the first time. The findings revealed that TPU and PNIPAM were interconnected through interchain hydrogen bonding, resulting in exposed hydrophobic isopropyl groups while covering the hydrophilic hydrogen bond sites. Selective separation of alcohols from alcohol/water mixed solutions occurred via London dispersion forces between alkyl groups. Increasing the PNIPAM load on the TPU surface led to a decrease in available hydrogen bond sites capable of bonding with water molecules, an increase in dispersible isopropyl groups interacting with alcohol alkyl groups, and enhanced selective adsorption capacity of TPU-PNIPAM towards alcohol/water mixed solutions. Moreover, TPU-PNIPAM exhibited a characteristic fast-slow-fast-equilibrium ad-sorption curve for different initial concentrations of alcohol/water mixtures, and its selective adsorption capacity increased when temperature reached 55℃. In addition to these general trends, under identical conditions, the selective adsorption capacity of TPU-PNIPAM gradually increased by methanol < ethanol < isopropyl alcohol < propyl alcohol, thus indicating a positive correlation between selectivity performance and hydrophobicity level.

The field of fluorescence sensing, leveraging various supramolecular self-assembled architectures constructed from macrocyclic pillar[n]arenes, has seen significant advancement in recent decades. This review comprehensively discusses, for the first time, the recent innovations in the synthesis and self-assembly of pillar[n]arene-based supramolecular architectures (PSAs) containing metal coordination sites, along with their practical applications and prospects in fluorescence sensing. Integrating hydrophobic and electron-rich cavities of pillar[n]arenes into these supramolecular structures endow the entire system with self-assembly behavior and stimulus responsiveness. Employing the host–guest interaction strategy coupled with complementary coordination forces, PSAs exhibiting both intelligent and controllable properties are successfully constructed. This provides a broad horizon for advancing fluorescence sensors capable of detecting environmental pollutants. This review aims to establish a solid foundation for the future development of fluorescence sensing applications utilizing PSAs. Additionally, current challenges and future perspectives in this field are discussed.

In this paper the thermodynamic and reactivity study of light alcohol fuels was prepared, based on experimental and numerical results. We also tested the influence of water addition on fundamental properties of the combustion reactivity dynamics in closed vessels, like the maximum explosion pressure, maximum rate of pressure rise and the explosion delay time of alcohol-air mixtures. Substances that we investigated were: methanol, ethanol, n-propanol and iso-propanol. All experiments were conducted at initial conditions of 323.15 K and 1 bar in a 20 dm3 closed testing vessel. We investigated the reactivity and thermodynamic properties during the combustion of liquid fuel-air mixtures with equivalence ratios between 0.3-0.7 as well as some admixtures with water, to observe water mitigation effects. All light alcohols samples were prepared at the same initial conditions on a volumetric basis by mixing the pure components. The volumetric water content of the admixtures was varied from 10 to 60 vol%. The aim of water addition was to investigate the influence of thermodynamic properties of light alcohols and to find out to which extent a water addition may accomplish mitigation of combustion dynamics and thermodynamic reactivity.

A enantioselective tandem transformation concerning asymmetric allylic decarboxylative addition and cyclization of N-nosylimines with vinylethylene carbonates (VECs) in the presence of [Rh(C2H4)2Cl]2, chiral sulfoxide-N-olefin tridentate ligand has been developed. The reaction of VECs with various substituted N-nosylimines proceeded smoothly under mild conditions, giving highly functionalized oxazolidine frameworks in good to high yields with good to excellent enantioselectivity.

Abstract: Objective: The aim of this study is to evaluate the effectiveness of an affective-sexual education programme among 14-15 year-old adolescents and its impact on their perception of their health. Design: This is a quantitative, descriptive and prospective quasi-experimental study, employing various cross-sections throughout the school year. It constitutes an educational promotion intervention where a health blog serves as a supplementary component to the "Health and School" programme. This phase is assessed using specific tools designed to evaluate scales. The study aims to assess the programme's effectiveness in the areas of knowledge and attitudes related to sexuality, sexually transmitted diseases, and affectivity. Additionally, it aims to evaluate the intervention's impact on 292 secondary school students, divided into a control group (N=144) and an intervention group (N=148). Both groups belong to the same population and have undergone affective-sexual education interventions focusing on gender and sexual diversity perspectives. The assessment considers perceptions and behaviours related to knowledge about HIV and other STDs/STIs, attitudes towards HIV, health anxiety, and AIDS phobia. Cross-sectional comparisons between the control and intervention groups are conducted at three points during the school year: longitudinal study, baseline, at month 4, and at month 9 post-intervention. Methods: Median and interquartile range, Wilcoxon test for numerical variables and Fisher's test for categorical variables were calculated according to intervention group. Results: 53% of the students reported a very good perception of health, compared to 45% with a good perception. Boys reported a good perception of health (85%) and had perceptions of their physical appearance and health (p=0.023) and (p<0.001) in the intervention group. Differences were found between perceptions of physical appearance in the control group, which was close to normal (p=0.429). In terms of level of knowledge about HIV and other STDs/STIs, the most significant difference was found in knowledge about HIV transmission, which varied between groups. Conclusions: Early affective-sex education sessions have an impact on health perception and behaviours related to knowledge about HIV and other STDs/STIs, leading to reduced anxiety in adolescents. School nurses should focus on health promotion, prevention of sex-related diseases, healthy attitudes from a gender perspective and integrated affective relationships in all their dimensions.

Inflammation is a conserved process that involve the activation of immune and non-immune cells aiming at protecting the host from bacteria, viruses, toxins and injury. However, unresolved inflammation and permanent release of pro-inflammatory mediators are responsible for the promotion of a condition called “low-grade systemic chronic inflammation”, characterized by tissue and organ damages, metabolic changes and increased susceptibility to non-communicable diseases. Several studies have demonstrated that different dietary components may influence modifiable risk factors for diverse chronic human pathologies. Marine n-3 polyunsaturated fatty acids (n-3 PUFAs), mainly eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), are well recognized anti-inflammatory and immunomodulatory agents able to influence many aspects of the inflammatory process. The aim of this article is to review the recent literature that relates to the modulation of human disease, such as rheumatoid arthritis, by n-3 PUFAs.

Ransomware attacks have risen alarmingly, with encryption techniques becoming more complex. This paper introduces a novel detection model tailored for ransomware's distinctive characteristics. The Intel PIN tool extracts Windows API invocation sequences related to file operations. These sequences are used to construct n-grams, forming feature vectors enhanced by a new Class Feature Weighting (CFW) metric to improve malware detection. Preliminary results demonstrate elevated accuracy and precision versus existing methods. The major contributions are: (1) Introducing an innovative deep learning model for few-shot ransomware classification using entropy features and transfer learning. (2) Achieving high weighted F1-score in classifying ransomware variants into families with limited training data. (3) Demonstrating the potential of entropy-based features to capture intricacies lost in image-based approaches, improving detection of new strains.

Rapid analysis and characterization of compounds by mass spectrometry may overlook trace compounds, although targeted analysis methods can significantly improve detection sensitivity, it is difficult to discover novel scaffold compounds. This study developed a strategy for discovering trace compounds in the aging process of traditional Chinese medicine based on MS fragmentation and known metabolic pathway. Specifically, we found that the characteristic component of C. reticulata 'Chachi', methyl N-methylanthranilate (MMA), fragmented in ESI-CID to produce rearrangement ion 3-hydroxyindole, which has been proven to exist in trace amounts in C. reticulata 'Chachi' comparing with the reference substance by LC-MS/MS. By combining the known metabolic pathways of 3-hydroxyindole and the possible methylation reactions that may occur during aging, 10 possible indole derivatives were untargeted predicted. These compounds were confirmed to originate from MMA by purchasing or synthesizing reference substances and all of them were detected in C. reticulata 'Chachi' through LC-MS/MS analysis, achieving trace compound analysis from untargeted to targeted. It may contribute to explain the aging mechanism of C. reticulata 'Chachi' and the strategy of CID-induced special rearrangement ion binding metabolic pathway has potential application value in discovering trace compounds.

Audio recording in classrooms is a common practice in educational research, with applications ranging from detecting classroom activities to analysing student behaviour. Previous research has employed neural networks for classroom activity detection and speaker role identification. However, these recordings are often affected by background noise that can hinder further analysis, and the literature has only sought to identify noise with general filters and not specifically designed for classrooms. Although the use of high-end microphones and environmental monitoring can mitigate this problem, these solutions can be costly and potentially disruptive to the natural classroom environment. In this context, we propose the development of a neural network model that can specifically detect and filter out background noise in classroom recordings. This model would allow the use of lower quality recordings without compromising analysis capability, thus facilitating data collection in natural educational environments and reducing the costs associated with high-end recording equipment.

Microwave absorbers with lightweight, good stability and high efficiency have attracted much attention for their applications in many contemporary fields. In this work, the 3D porous (Ni@NO-C)n/NO-C composite absorber was prepared by a wet chemistry method with Ni chains and melamine as precursors, in which NO-C (N,O-doped carbon) encapsulated Ni particles are homogenously dispersed in the 3D porous networks of NO-C in the form of (Ni@NO-C)n chains. The special microstructure of the as-prepared material is proved to be benefit for the improvement of its microwave adsorption performance. The as-synthesized (Ni@NO-C)n/NO-C composite ab-sorber exhibited an effective absorption bandwidth of 4.1 GHz and an extremely large reflection loss of -72.3 dB. The excellent microwave absorbing performances can be ascribed to the coopera-tive consequence of dielectric loss and magnetic loss along with the balance between attenuation capability and impedance match.

Bimetallic (or multimetallic) catalysis has emerged as a powerful tool in modern chemical synthesis, offering improved reaction control and versatility. This review focuses on the recent de-velopments in bimetallic sequential catalysis for the synthesis of nitrogen heterocycles, essential building blocks in pharmaceuticals and fine chemicals. The cooperative action of two (and sometimes more) different metal catalysts enables intricate control over reaction pathways, enhancing selectivity and efficiency of N-heterocyclic compounds synthesis. By activating less reactive substrates, this multimetal catalytic strategy opens new synthetic possibilities for challenging compounds. The use of catalytic materials in bimetallic systems reduces waste and improves atom efficiency, aligning with green chemistry principles. With a diverse range of metal combinations and reaction conditions, bimetallic catalysis provides access to a broad array of N-heterocyclic compounds with various functionalities. This paper highlights the significant progress made in the past decade in this topic, emphasizing the promising potential of bimetallic catalysis in drug discovery and the fine chemical industries.

Seafood products are the main dietary source of n-3 polyunsaturated fatty acids (n-3 PUFA), which are essential for human health. However, due to the widespread use of processed fish products, the presence of these n-3 PUFAs may be subject to changes related to different processing methods. The aim of this study was to determine the fatty acid composition, with a focus on n-3 polyunsaturated fatty acids (n-3 PUFAs), in different processed fish and shellfish food of EU and non-EU origin purchased in supermarkets and ethnic food shops in Messina (Italy), using gas chromatography with flame-ionization detector (GC-FID). From the fatty acid profile, the atherogenic index (AI), thrombogenicity index (TI) and flesh-lipid quality index (FLQ) were determined: 0.13-1.04 (AI), 0.31-9.84 (TI) and 0.41-29.90 (FLQ). The percentages of saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids had the following ranges: 13.55-50.48%, 18.91-65.58%, 13.84-52.73%, respectively. All samples showed a good presence of PUFAs and, in particular, eicosapentaenoic (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) were the main n-3 polyunsaturated fatty acids (n-3 PUFA).

Soil nitrogen (N) is a common limiting factor where soil N cycling is a key component of agro-ecosystems. Soil N transformation processes are largely mediated by microbes and understanding bacteria involvement in soil N cycling in agricultural systems has both agronomic and environmental importance. This 2-yr field scale study examined the abundances and spatial distributions of total bacterial community (16s RNA), bacterial involved in nitrification (amoA), and de-nitrification (narG, nirK, and nosZ) and soil physicochemical properties of winter wheat (Triticum aestivum L.) – soybean (Glycene max L.) double cropping with 2-3 weeks of spring grazing (WGS) and without grazing (WS) and of tall fescue (Festuca arundinacea (L.) Schreb.) pasture (TF) managed to near natural conditions with similar grazing. The TF had a significantly higher abundance of 16S rRNA, amoA, narG, nirK, and nosZ genes than the WS and WGS, which had similar levels between themselves. Soil organic matter (OM) and soil pH had a stronger effect on the N-cycling bacteria gene abundance. All bacterial gene concentrations and soil pH showed non-random distribution patterns with 141-186 m range autocorrelation. These results indicate that biological N transformation processes are more important in natural agricultural systems and the abundance of N-cycling bacteria can be manipulated by field scale management strategies.

Differences in the physical and chemical properties of reclaimed water (RW) and natural surface water (SW) lead to the differences in terms of nitrogen and phosphorus release when pipeline sediments enter these water bodies. The nitrogen and phosphorus release kinetics from pipe sediments with different particle sizes have been investigated. The results demonstrated that both SW and RW had a pH buffering effect after sediment addition, and the final pH (approximately 8.1) of RW was lower. The release of total phosphorus (TP) and ammonia nitrogen ( NH₄⁺-N) fitted the first-order kinetic model where the release of TP reached equilibrium; TP release was inhibited in both SW and RW, where RW exhibited the lowest (by a factor of 1.23~2.44) release (0.002 mg/g). The release of NH4+-N was promoted in both SW and RW; the maximum release in RW was 0.0188 mg/g. The amounts of NH₄⁺-N released in SW and RW were 1.02-1.40 and 1.30-1.80 times that of the control group (CG), respectively. The percentage of TP and NH₄⁺-N release in the three groups was highest in 75-154 μm pipe sediment, reaching 34.53% and 43.51% in SW and RW, respectively. These results can assist in the development of water quality evolution models for specific urban scenarios, and provide important guidance for the precise regulation of recharge water quality during and after rainfall.

The development of antimicrobial resistance to conventional antibiotics is a major global health challenge. Infections caused by multidrug-resistant gram-negative bacteria have been named one of the most urgent global health threats. Considerable efforts are devoted to developing new antibiotic drugs and investigating the mechanism of antibiotic resistance. Recently, Anti-Microbial Peptides (AMPs) have emerged as a new platform for the target and design of novel drug resistant anti-microbial agents promising a new therapeutic strategy. AMPs are rapid, potent, possess an unusually broad spectrum of activity, and have shown efficacy as topical agents. Unlike traditional therapeutics that interfere with essential bacterial enzymes, AMPs interact with microbial membranes through electrostatic interactions and physically damage cell integrity. However, naturally occurring AMPs have limited selectivity and modest efficacy. Therefore, recent efforts have focused on the development of synthetic AMP analogs as suitable drug targets. This work explores the development of novel antimicrobial agents which mimic the structure of graft-copolymers and mirror the mode of action of an AMP. Chitosan-graft-polypeptide side chains are synthesized by the ring-opening polymerization of N-carboxyanhydrides of L-lysine and L-leucine initiated from the functional groups of chitosan. The derivatives with random- and block-copolymer side chains are explored as drug targets. These graft copolymer systems exhibit activity against clinically significant pathogens and disrupt biofilm formation. This work highlights the potential of chitosan-graft-polypeptide structures in biomedical applications.

The cytosolic PNGase (peptide:N-glycanase; Png1 in yeast; NGLY1/Ngly1 in human/mice), also known as peptide-N4-(N-acetyl-beta-glucosaminyl)-asparagine ami-dase, is a well-conserved deglycosylation enzyme (EC 3.5.1.52) which catalyzes the non-lysosomal hydrolysis of an N(4)-(acetyl-β-D-glucosaminyl) asparagine residue into N-acetyl-β-D-glucosaminylamine and a peptide containing an aspartate residue. This enzyme (NGLY1) plays essential roles in clearance of misfolded or unassembled gly-coproteins through a process named ER-associated degradation (ERAD). Accumulating evidence also points out that NGLY1 deficiency can cause an autosomal recessive hu-man genetic disorder associated with abnormal development and congenital disorder of deglycosylation. In addition, the loss of NGLY1 can affect multiple cellular pathways, including but not limited to NFE2L1 pathway, Creb1/Atf1-AQP pathway, BMP path-way, AMPK pathway, and SLC12A2 ion transporter, which might be the underlying reasons for a constellation of clinical phenotypes of NGLY1 deficiency. The current comprehensive review indeed uncovers the detailed NGLY1’s structure and its im-portant roles for participation in ERAD, involvement in CDDG and potential treatment for NGLY1 deficiency.

Surface modification of polypropylene (PP) films is achieved using gamma-irradiation-induced grafting to proffer with antimicrobial activity. The copolymer was obtained through a versatile two-step route; pristine PP is exposed to gamma rays and grafted using methyl methacrylate (MMA), then N-vinylimidazole (NVI) is grafted onto the copolymer PP-g-MMA by simultaneous irradiation. The characterization included Fourier-Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscope (SEM), Thermogravimetric Analysis (TGA), X-ray Photoelectron Spectroscopy (XPS), and physicochemical analysis of swelling and contact angle. The copolymer (PP-g-MMA)-g-NVI was loaded with vancomycin, and the drug released was quantified by UV-vis spectrophotometry at different pH. The surface of (PP-g-MMA)-g-NVI exhibited pH-responsiveness and moderate hydrophilicity, suitable properties for controlled drug release.

In our tactic to construct bio-active molecules, a series of novel pyrimido[2,1-c][1,2,4]triazine-3,4-diones based heterocycles, were synthesized and evaluated for their in vitro antimicrobial impacts. The exploratory bioassay results declared that, the majority of the evaluated compounds exhibited considerable anti-microbial activity comparable to the reference drugs. Conjugates 15j, 15f, 15i, 15h, 15g and 15a were found to be the most potent antibacterial, indicating that conjugates bearing electron-attracting substituents exhibited higher potency than these with electron-releasing substituents.

This study investigated the removal characteristics of N-nitrosamines and their precursors at three pilot-scale water reclamation plants. These plants applies different integrated membrane systems: (1) microfiltration (MF) / nanofiltration (NF) / RO; (2) sand filtration/three-step RO; and (3) ultrafiltration (UF) / NF and UF / RO. Variable removal of N-nitrosodimethylamine (NDMA) by the RO membrane processes could be attributable to membrane fouling and feed water temperature. The effect of membrane fouling on N-nitrosamines removal was extensively evaluated at one of the plants by conducting one month of operation and chemical cleaning of the RO membrane element. Membrane fouling enhanced N-nitrosamines removal by the pilot-scale RO membrane process. This finding contributes to better understanding of variable removal of NDMA by RO membrane processes. This study also investigated the removal characteristics of N-nitrosamines precursors. The NF and RO membrane processes greatly reduced NDMA formation potential (FP), but the UF process had little effect. The contributions of MF, NF, and RO membrane processes for reducing FPs of NDMA, N-nitrosopyrrolidine (NPYR) and N-nitrosodiethylamine (NDEA) were different, suggesting different size distributions of their precursors.

Helicobacter pylori cytotoxin-associated gene A protein (CagA) has been associated with the increase in virulence and risk of cancer. It has been demonstrated that CagA's translocation is dependent on its interaction with phosphatidylserine. We evaluated the variability of the N-terminal CagA in 127 sequences reported in NCBI, by referring to molecular interaction forces with the Phosphatidylserine and the docking of 3 mutations chosen from variations in specific positions. The major sites of conservation of the residues involved in CagA-Phosphatidylserine interaction were 617, 621 and 626 which had no amino acid variation. Position 636 had the lowest conservation score, so mutations in this position were evaluated to observe the differences in intermolecular forces of the CagA-Phosphatidylserine complex. We evaluated the docking of 3 mutations: K636A, K636R and K636N. The models of the crystal and mutations presented a ΔG of −8.919907, −8.665261, −8.701923, −8.515097 Kcal/mol, respectively, while mutations K636A, K636R, K636N and the crystal structure presented 0, 3, 4 and 1 H-bonds, respectively. Likewise, the bulk effect of the ΔG and amount of H-bonds was estimated in all of the docking models. The type of mutation affected both the ΔG (χ²(1) = 93.82, p-value < 2.2 × 10⁻¹⁶) and the H-bonds (χ²(1) = 91.93, p-value < 2.2 × 10⁻¹⁶). In all the data, 76.9% of the strains that exhibit the K636N mutation produced a severe pathology. The average H-bond count diminished when comparing the mutations with the crystal structure of all the docking models, which means that other molecular forces are involved in the CagA-Phosphatidylserine complex interaction.

We demonstrate for the first time efficient mechanical to electrical energy conversion using InGaN/GaN nanowires (NWs). Using an atomic force microscope equipped with a modified Resiscope module, we analyse the piezoelectric energy generation of GaN NWs and demonstrate an important enhancement when integrating in their volume a thick In-rich InGaN insertion. The piezoelectric response of InGaN/GaN NWs can be tuned as a function of the InGaN insertion thickness and position in the NW volume. The energy harvesting is favoured by the presence of a PtSi/GaN Schottky diode which allows to efficiently collect the piezo-charges generated by InGaN/GaN NWs. Average output voltages up to 330 ± 70 mV and a maximum value of 470 mV per NW has been measured for nanostructures integrating 70 nm-thick InGaN insertion capped with a thin GaN top layer. This latter value establishes an increase of about 35% of the piezo-conversion capacity in comparison with binary p-doped GaN NWs. By considering these output signals, we estimate a maximum power density generated by one layer of dense InGaN/GaN-based NW of about 3.3 W/cm². These results settle the new state-of-the-art for piezo-generation from GaN-based NWs and offer a promising perspective for extending the performances of the piezoelectric sources.

Sparkling wines elaborated by means Ancestral method, also called Pét-Nats, are nowadays gaining an increasing share of the market. However, the scientific information about these wines is very scarce. For that reason, the aim of this research was to compare the physicochemical composition and sensory attributes of a representative sampling of commercial sparkling wines elaborated by Ancestral and Traditional methods. Ancestral sparkling wines were more heterogenous than Traditional sparkling wines because some of them showed lower internal pressure, higher turbidity, higher colour intensity and less foamability. These differences would be probably because the ancestral elaboration protocol is not so well defined as in the case of Traditional sparkling wines. However, Ancestral method has the advantage of being able to work with riper grapes and with lower doses of sulphur dioxide.

. The Tau protein is associated with microtubule function in the neuron and is crucial for normal axonal transport. In several different neurodegenerative disorders, Tau misfolding leads to hyper-phosphorylation (p-Tau) and intracellular p-Tau aggregates known as neurofibrillary tangles (NFTs). This is particularly evident in individuals with Down syndrome (DS), who develop Alzheimer’s disease-like (AD) neuropathology early in life with almost complete penetrance, associated with the development of dementia symptoms in their 40s or 50s. Our previous findings have shown that certain forms of p-Tau are present already in childhood in individuals with DS in neuron-derived exosomes, suggesting an early phosphorylation profile in this population that could influence the development of AD pathology. Misfolded p-Tau isoforms are known to be seeding competent and may be responsible for spreading AD pathology in different regions of the brain. This review is focused on the accumulation of p-Tau in the brain of individuals with DS and potential consequences for brain function.

Plasmonic nanomaterials have garnered considerable attention in the scientific community due to their applicability in light-mediated technologies, owing to tunability, large light absorption cross-sections, transparency, and potential scalability. While single morphology plasmonic nanoparticles exhibit substantial absorption cross-sections, their effectiveness is limited to a narrow energy window, especially under polychromatic illumination like sunlight. Integrating plasmonics with a Fabry-Pérot nanocavity is a promising approach to broaden the absorption energy range of the photosystem. Traditionally, the fabrication of these nanocavities involves clean room processes, posing scalability challenges. This study presents a novel approach, demonstrating the successful enhancement of light absorption in a plasmonic photoelectrode system through a Fabry-Pérot nanocavity created using bottom-up solution methods. This innovative technique not only overcomes the scalability issues associated with clean room processes but also enables the production of scalable photosystems that can be rendered entirely opaque or semitransparent. Such versatility opens up a multitude of application possibilities for these photosystems.

Pancreatic neuroendocrine tumor (P-NET) is a rare neoplasm originating in the neuroendocrine system. Carcinoid syndrome occurs in approximately 19% of patients with functional P-NETs, typically when liver metastases occur. NETs diagnosis is frequently late, along with symptoms related to hormone hypersecretion. We described the case of a patient with a low-grade non-functional P-NET, but with a typical clinical presentation of a carcinoid syndrome; moreover, we reviewed the literature regarding this topic. An 81-year-old male was admitted to our Department of Internal Medicine at Cannizzaro Hospital (Catania, Italy) because of the onset of abdominal pain with nausea, loose stools and episodic flushing. Firstly, an abdominal contrast-enhanced CT scan showed a small pancreatic hypervascular mass; then a gallium-68 DOTATOC integrated PET/CT revealed an elevated expression of SSTR receptors. Serum Chromogranin A and urinary 5-HIAA measurements resulted negative. Given the small size of the lesion (8 mm), we preferred to perform an endoscopic ultrasonography (EUS) with fine-needle biopsy (EUS-FNB), allowing the diagnosis of low-grade (G1) non-functional P-NET (NF-P-NET). Surgery was waived, while a follow-up strategy was chosen. Early recognition of P-NETs, although rare, is necessary to improve patient’s survival. EUS-FNB should be the protocol of choice for an early characterization of these tumors.

Since the first description of SARS-CoV-2 in China in 2019, thousands of variants have emerged worldwide. For some of them, the constellation of mutations caused changes in virus biology, pathogenicity, infectivityity and transmissibility resulting in dissemination throughout the world. Gamma variant (P.1) differs from SARS-CoV-2 Wuhan strain (B.1) by 12 amino acids in the Spike (S) protein, and presented mutations related to greater affinity for the receptor angioten-sin-converting enzyme 2 (ACE-2) and/or immune escape. The Gamma variant and subvariants were responsible for the second wave of COVID-19 in the Brazilian city of Manaus, characterized by high mortality and rapid transmission. The ability of variants to induce cytokine production may be closely related to their pathogenicity. Herein we observed that there was no significant difference in the quantity of cytokines among macrophages or neutrophils infected with P.1 and B.1 strains. Also, no significant difference was observed in the absolute number of macrophages and neutrophils infected with these variants. Furthermore, no evidence of SARS-CoV-2 replication was observed in macrophages when infected by the two analyzed variants. Our findings suggest that the difference in the epidemiological outcome observed during the P.1 variant spread when compared to B.1, it is not explained by differences in the quantity of cytokines and absolute number of macrophages or neutrophils. Through bioinformatics analysis of the S protein, we observed that the physicochemical differences between the variants and subvariants of P.1, probably refer to the degree of infectivity, due to the impact caused in the recognition of antibodies and receptor af-finity

By employing a variation of the polyamidation method using in situ silylated diamines and acid chlorides, it has been possible to obtain a rod-type polyamide: poly(p-phenylene terephthalamide) (PPTA, a polymer used in the high value-added material Kevlar), with a molecular weight much higher than that obtained with the classical, and industrial, polyamidation method. The optimization of the method has consisted in using, together with the silylating agent, a mixture of pyridine and a high pKa tertiary amine. The research has been complemented by a combination of nuclear magnetic resonance and molecular simulation studies, which have determined that the improvements in molecular weight derive mainly from the formation of silylamide groups in the growing polymer.

Manipulation of radiation pattern control is challenging, especially at low frequencies. In this paper, we demonstrate that acoustic metamaterials as an effective array of quadrupoles can remarkably improve the directionality of acoustic radiation at low frequencies, compared with previous metamaterials as monopole and dipole structures. The directivity of the acoustic radiation can be adjusted by changing the characteristic parameter and the symmetry of the structure, which provide a flexible method of adjustable radiation di-rections. The directionality can be further improved by constructing linear array of structure. Our work opens an approach of acoustic radiation control via quadrupolar metamaterials.

We investigate the effect of geopolitical risk on the returns of the Information Technology, Communication Services, and Consumer Staples sector firms within the S&P 500 index. We use the event study methodology and perform more than 17,000 regressions to provide empirical evidence at the sector level that geopolitical risk leads to different responses across these 3 sectors. The response of the Information Technology sector is negative for all event windows under study, except the one spanning 10 days prior to the geopolitical event and 10 days after. The Communication Services sector has positive returns as a result of geopolitical events for all event windows, except the one from the geopolitical event date and 5 days after. The Consumer Staples sector shows a negative impact on geopolitical risk for all event windows except the one from the geopolitical event date and 5 days after, demonstrating a negative correlation to the Communication Services sector.

The Industrial Internet of things (IIoT) enabled smart system has entered into a golden era of rapid technology growth. IIoT is a concept to make every system interrelated such that they are able to collect and transfer data over a wireless network without human intervention. In this paper, we discuss the development of an IoT enabled system to monitor the vibration signature of equipment as part of prognosis and availability management system (P&AM) that serves to prevent unplanned operation downtime and catastrophic failure of a whole system. In order to simply the complexity of processing video content and performing inference, the Intel OpenVINO platform was selected because of it’s simplicity, portability across Intel AI processors, performance and comprehensiveness of it’s analytical and diagnostics capabilities that can be tested in Intel’s DevCloud. The IIoT system consists of a High Performance Computing (HPC) platform based on Intel’s Xeon processors and Movidius AI accelerator, Intel’s OpenVINO toolkit for AI, a Regul high performance programmable controller capturing vibration data through sensors and a low-latency network connection. Notifications of anomalies are sent to a smartphone. This paper reveals an approach for the features extraction and selection, known as feature engineering, of the equipment component we want to protect. Feature engineering is the first step for the P&AM of these components and extends to the whole system. The broader aim of this paper is to help technical leaders at the exploring or experimenting stages of their AI framework to learn the concepts of implementing algorithms using datasets that have real value to their companies. Datasets generated and referred to in this paper were generated by simulation under various material failure scenarios.

Wound infections evidently appeared in times of World War I that accounted a significant mortality and morbidity rate among injured soldiers. Currently, around 11 million people worldwide require medical treatment for wound infections and 300,000 die every year due to untreated wound infection. The extensive use of antibiotics to treat wound infection leads to emerging new microbial strains that are resistant to many antibiotics. There is a growing concern on the emergence and re-emergence of drug-resistant pathogens such as multi-resistant bacterial strains. Hence, the development of new antimicrobial compounds or the modification of those that already exist to improve antibacterial activity is a high priority area of research. During the past few decades, nanotechnology has arisen with new promising technology for synthesis of nanobiomaterials. Metallic nanoparticles (NPs) are considered as new alternative treatment with superior antibacterial activity. In this study, new formulation of titanium oxide (TiO2) NPs with different sizes were synthesized and characterized. Genotoxicity, mutagenicity and antibacterial activities of TiO2 NPs against the causative agents of wound infection were investigated. Antibacterial activity of TiO2 NPs was conducted against three ATCC ® bacterial strains: methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Pseudomonas aeruginosa. The results clearly illustrate a superior antibacterial activity of all newly formulated TiO2 NPs against the most causative agents of wound infection. Most of our TiO2 NPs showed non-genotoxic and non-mutagenic results at the maximum concentrations. Findings of this study will enhance the future of the therapeutic strategies against the resistant pathogenic strains that cause wound infections.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), coronavirus disease 2019 (COVID-19)-induced infection is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or hypercoagulation and thrombosis. Thrombotic and bleeding or thrombotic pathologies are significant accompaniments to acute respiratory syndrome and lung complications in COVID-19. Thrombotic events and bleeding, often occurs in subjects with weak multiple risk factors and co-morbidities. Of particular interest are the various circulating inflammatory coagulation biomarkers involved directly in clotting, with specific focus on fibrin(ogen), D-dimer, P-selectin and von Willebrand Factor (vWF). Central to activity of these biomarkers are their receptors and signaling pathways on endothelial cells, platelets and erythrocytes. In this review, we discuss vascular implications of COVID-19, and relate this to circulating biomarker, endothelial, erythrocyte and platelet dysfunction. During the progression of the disease, these markers may either be within healthy levels, upregulated or eventually depleted. Most significant is that patients need to be treated early in the disease progression, when high levels of vWF, P-selectin and fibrinogen are present with still low levels of D-dimer. Progression to vWF and fibrinogen depletion with high D-dimer levels and even higher P-selectin levels, followed by the cytokine storm, will be indicative of a poor prognosis. We conclude by looking at point-of-care devises and methodologies in COVID-19 management and suggest that a personalized medicine approach should be considered in the treatment of patients.

Phosphorus (P) is an important element in a complete and balanced fertility program that can improve crop P use efficiency and ultimately productivity and profitability. Phosphatic fertilizers use without organic fertilizers leads to gradual decline in soil organic matter, native nutrient status and ultimately reduction in agricultural productivity and economic growth. The objectives of this was to evaluate P efficiencies with incorporation of peach sources, beneficial microbes and P application. From sustainability points of view, alternative use of different sources and forms of organic sources alone or in combination with inorganic P and beneficial microbes possess potential for improving productive capacity of the soil. Separate field experiments (one each on maize and soybean as a test crop) were conducted at Agriculture Research Institute Mingora Swat (ARI) for two consecutive years in summer season of 2016 (year one) and 2017 (year two). For the first time such a study were conducted to utilize peach leftovers and biomass (leaves, twigs, fruits, stones and barks partially decomposed, its compost and biochar) along with three phosphorus (P) levels (50, 75, 100 kg P ha-1) and two beneficial microbes (PSB and Trichoderma) on such a way to enhance soil sustainability and P use efficiency of soybean and maize. The results revealed that organic sources had significant effect on soybean and maize P use efficiency (PUE), P agronomic efficiency (PAE), partial factor productivity (PFPp) and soil P concentration. In experiment 1 among the organic sources, peach residues increased soil P (12.0 mg kg-1) as compared to peach compost and biochar (8.6 & 11.7 mg kg-1). Soil P concentration was maximum (12.1 mg kg-1) with PSB than Trichoderma (9.5 mg kg-1). Application of P at 100 kg ha-1increased soil P contents (16.9 mg kg-1) as compared to 50 and 75 kg P ha 1 (5.9 & 9.6 mg kg-1) respectively. P concentration was increased drastically in year 2 (12.4 mg kg-1) than year one (9.1 mg kg-1). PUE in both crops (soybean and maize) was maximum (25.6 & 28.4%) with peach biochar than compost and residues along with Trichoderma (21.7 & 27.8%). Highest PUE in soybean was recorded with 75 kg P ha-1(22.2%) however in maize maximum PUE was noted with 50 kg P ha-1(33.5%). PAE and PFPp in both crops was maximum with biochar and soil application of Trichoderma than other organic sources and PSB. Among the P levels highest PAE in soybean and maize was recorded with 75 kg ha-1whereas PFPp in soybean was maximum with 75 kg P ha-1 and interestingly in maize it was noted with 50 kg ha-1. Conclusively soybean and maize PAE, PFPp and PUE was higher with biochar, soil incorporation of Trichoderma and P at the rate of 75 kg ha-1 and can improve soybean and maize yield and soil productivity on sustainable basis.

Endocannbinoids system (ECS) engrossed a considerable interest as potential therapeutic targets in various carcinomas and cancer related conditions alongside with neurodegenerative diseases. Cannabinoids are implemented in several physiological processes such as appetite stimulation, energy balance, pain modulation and the control of chemotherapy induced nausea and vomiting (CINV). However, pharmacokinetics and pharmacodynamics interactions could be perceived in drug combinations, so in this short review we tried to shed the light over the potential drug interactions of medicinal cannabis. Hitherto, few data have been provided to the healthcare practitioners about the drug-drug interactions of cannabinoids with other prescription medications. In general, cannabinoids are usually well tolerated, but the bidirectional effects may be expected with concomitant administered agents via affected membrane transporters (glycoprotein p, breast cancer resistance proteins) and metabolizing enzymes (Cytochrome P450 and UDP- glucuronosyltransferases). The caveats should be undertaken to closely monitor the responses of cannabis users with certain drugs to guard their safety, especially for the elderly and people with chronic diseases or kidney and liver conditions.

Hypothesis: Anti-diabetic drugs modulate p-21 activated kinase (PAK) signaling Introduction: Type 2 diabetes mellitus (T2DM) is a chronic inflammatory disease associated with increased cancer risk. PAK signaling is implicated in cellular homeostasis when regulated, and cancer when unrestrained. Recent reports provided a role for PAK signaling in glucose homeostasis, but the role of PAKs in the pathogenesis of T2DM is unknown. Here we performed a mini-meta analysis to explore if anti-diabetic drugs modify PAK signaling pathways, and provide insight regarding modulation of these pathways to potentially reduce diabetes-associated cancer risk. Methods: PAK interacting partners in T2DM were identified using online STRING database. Correlation studies were performed via systematic literature review to understand the effect of anti-diabetic drugs on PAK signaling. Mini meta analysis correlated multiple clinical studies and revealed the overall clinical response rate and percentage of adverse events in piogliazone (n=53) and metformin (n=91) treated patients with PAK-associated diseases. Results: A total of 30 PAK interacting partners were identified (10: reduced beta-cell mass; 10: beta-cell dysfunction; 10: obesity-insulin resistance) which were highly associated with Wnt, and G-protein signaling. Anti-diabetic drug metformin activated signaling pathways upstream; whereas pioglitazone inhibited pathways downstream of PAK. Overall clinical response upon pioglitazone treatment was 53%. 79% of pioglitazone and 75% of metformin treated patients had adverse events. Pioglitazone reduced molecular-PAK biomarkers of proliferation (Ki67 and CyclinD1), and metformin had the opposite effect. Conclusions: PAK signaling in T2DM likely involves Wnt and G-protein signaling which may be altered by anti-diabetic drugs metformin and pioglitazone. Apart from the therapeutic limitations of adverse events, pioglitazone may be promising in chemoprevention, however long-term multi-centered studies, which initiate pioglitazone treatment early will be required to fully assess the full potential of these drugs.

Hypothesis: Anti-diabetic drugs modulate p-21 activated kinase (PAK) signaling Introduction: Type 2 diabetes mellitus (T2DM) is a chronic inflammatory disease associated with increased cancer risk. PAK signaling is implicated in cellular homeostasis when regulated, and cancer when unrestrained. Recent reports provided a role for PAK signaling in glucose homeostasis, but the role of PAKs in the pathogenesis of T2DM is unknown. Here we explored whether PAK signaling should be targeted via chemoprevention to reduce diabetes-associated cancer risk. Methods: PAK interacting partners in T2DM were identified using online STRING database. Systematic literature review provided the effect of anti-diabetic drugs on PAK signaling. Review of clinical studies revealed the overall clinical response rate and percentage of adverse events in piogliazone (n=53) and metformin (n=91) treated patients with PAK-dependent diseases. Results: A total of 30 PAK interacting partners were identified (10: reduced beta-cell mass; 10: beta-cell dysfunction; 10: obesity-insulin resistance) which were highly associated with Wnt, and G-protein signaling. Anti-diabetic drug metformin activated signaling pathways upstream; whereas pioglitazone inhibited pathways downstream of PAK. Overall clinical response upon pioglitazone treatment was 53%. 79% of pioglitazone and 75% of metformin treated patients had adverse events. Pioglitazone reduced molecular-PAK biomarkers of proliferation (Ki67 and CyclinD1), and metformin had the opposite effect. Conclusions: PAK signaling in T2DM involves Wnt and G-protein signaling which is altered by anti-diabetic drugs metformin and pioglitazone. Apart from the therapeutic limitations of adverse events, pioglitazone is promising in chemoprevention, however long-term multi-centered studies, which initiate pioglitazone treatment early will be required to fully assess the full potential of these drugs.

The productivity of forests is often considered to be limited by the availability of phosphorus (P). Knowledge of the role of organic and inorganic P in humid subtropical forest soils is lacking. In this study, we used chemical fractionation and 31P nuclear magnetic resonance (NMR) spectroscopy to characterize the form of P and its distribution in undisturbed perhumid Chamaecyparis forest soils. The toposequence of transects was investigated for the humic layer from summit to footslope and lakeshore. The clay layer combined with a placic-like horizon in the subsoil may affect the distribution of soil P because both total P and organic P (Po) contents in all studied soils decreased with soil depth. In addition, Po content was negatively correlated with soil crystalline Fe oxide content, whereas inorganic P (Pi) content was positively correlated with soil crystalline Fe oxide content and slightly increased with soil depth. Thus, Pi may be mostly adsorbed by soil crystalline Fe oxides in the soils. Among all extractable P fractions, the NaOH-Po fraction appeared to be the major component, followed by NaHCO3-Po; the resin-P and HCl-Pi fractions were lowest. In addition, we found no typical trend for Pi and Po contents in soils with topographical change among the three sites. From the 31P-NMR spectra, the dominant Po form in soils from all study sites was monoesters with similar spectra. The 31P-NMR findings were basically consistent with those from chemical extraction. Soil formation processes may be the critical factor affecting the distribution of soil P. High precipitation and year-round high humidity may be important in the differentiation of the P species in this landscape.

P-band radar remote sensing applied during the Airborne Microwave Observatory of Subcanopy and Subsurface (AirMOSS) mission has shown great potential for estimation of root zone soil moisture. When retrieving the soil moisture profile (SMP) from P-band radar, a mathematical function describing the vertical moisture distribution is required. Because only a limited number of observations are available, the number of free parameters of the mathematical model must not exceed the number of observed data. For example, a second order polynomial that contains 3 free parameters was presumed based on in-situ SMP data. The polynomial is currently parameterized based on 3 backscatter observations provided by AirMOSS (i.e. one frequency at three polarizations of HH, VV and HV). In this paper, a more realistic, physically-based SMP model containing 3 free parameters is derived based on a solution to Richards’ equation for unsaturated flow in soils. Evaluation of the new SMP model based on both numerical simulations and measured data revealed that it exhibits greater flexibility for fitting measured and simulated SMPs than the currently applied polynomial. It is also demonstrated that the new SMP model can be reduced to a second order polynomial at the expense of fitting accuracy.

Various strategies have been employed to improve the reliability of 2D, 3D, and co-culture in vitro models of nonalcoholic fatty liver disease, including using extracellular matrix proteins, such as collagen I, to promote cell adhesion. While studies have demonstrated the significant benefits of culturing cells on collagen I, its effects on HepG2 and HepaRG cell lines after exposure to palmitate (PA) have not been investigated. Therefore, this study aimed to assess the effects of PA-induced lipotoxicity in HepG2 and HepaRG cultured in the absence or presence of collagen I. HepG2 and HepaRG cultured in the absence or presence of collagen I were exposed to PA, followed by analyses that assessed cell proliferation, viability, adhesion, cell death, mitochondrial respiration, reactive oxygen species production, gene and protein expressions, and triacylglycerol accumulation. Culturing HepG2 on collagen I was associated with increased cell proliferation, adhesion, expression of integrin receptors, and improved cellular spreading compared to culturing them in the absence of collagen I. PA-induced lipotoxicity was greater in collagen I-cultured HepG2 than those cultured in the absence of collagen I. In summary, the present study demonstrated for the first time that collagen I-cultured HepG2 exhibited exacerbated cell death following exposure to PA through integrin-mediated death. The findings from this study may serve as a caution to those using 2D models or 3D scaffold-based models of HepG2 in the presence of collagen I.

Background: IL-15 is a homeostatic cytokine for human T and NK cells. However, whether other cytokines influence the effect of IL-15 is not known. We have studied the impact that IL-10, TGF-, IL-17A and IFN- have on the IL-15-induced proliferation of human T cells and the expression of HLA class I (HLA-I) molecules. Methods: Peripheral blood lymphocytes (PBL) were labeled with CFSE, and stimulated for 12 days with IL-15 in the absence or presence of the other cytokines. The proportion of proliferating T cells and the expression of cell surface HLA-I molecules were analyzed by flow cytometry. Results: The IL-15-induced proliferation and expansion of T cells was paralleled by an increase in the expression of HC-10-reactive HLA-I molecules, namely on T cells that underwent ≥5-6 cycles of cell division. Noteworthy, the IL-15-induced proliferation of T cells was potentiated by IL-10 and TGF-β, but not by IL-17 or IFN-, and was associated with a decrease in the expression of HC-10-reactive molecules. Conclusions: The cytokines IL-10 and TGF-β potentiate the proliferative capacity that IL-15 has on human T cells in vitro, an effect that is associated with a reduction in the amount of HC-10 reactive HLA class I molecules induced by IL-15.

The gold(I) N-heterocyclic carbene (NHC) complexes, containing a combination of 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (iPr) and the corresponding 7-azaindole derivative (HL1-4), were prepared and structurally characterized. The complexes of the composition of [Au(iPr)(HLn)], where n = 1–4 for 5-fluoro-7-azaindole (1), 5-bromo-7-azaindole (2), 3-chloro-7-azaindole (3) and 3-iodo-7-azaindole (4), were further evaluated for their in vitro anti-cancer and anti-inflammatory activities. The results showed that complexes (1–4) behave as considerably cytotoxic against human ovarian cancer cell line A2780 (with IC50 = 4–9 mircoM) and cisplatin-resistant cell line A2780R (with IC50 = 5–8 microM, except for 2 with IC50 > 25 microM), providing significantly higher cytotoxicity than anticancer drug cisplatin. Moreover, they also revealed a relatively good selectivity over normal cells (MRC-5), with the values of selectivity index, SI > 2.5. The complex 4 was further studied for its cellular effects in A2780 cells by cell cycle analysis, induction of apoptosis, intracellular ROS production, activation of caspases 3/7 and disruption of mitochondrial membrane potential. The ability of complexes (1–4) to influence the activity of pro-inflammatory transcription factor NF-κB and secretion of TNF-α were evaluated, showing that complex 4 reveals comparable effects as the inflammatory drug Auranofin.

Chinese divination of I Ching has a history of thousands of years. The six lines changes in 64 hexagrams have exceeded one billion scenarios, and the inherent laws among them have not been well revealed to this day. By using big data's technology and coin toss method, this paper simulates the change of 64 hexagrams, and explores the probability and proportion of each hexagram during the change from the perspective of quantification, as well as the maximum and minimum conversion rate of hexagram change. This paper summarizes the basic characteristics and the basic law of hexagram change, and accordingly constructs the spatial form of hexagram change, and reveals the hidden secrets of the ancient Book of changes (I Ching). To achieve this goal, we randomly toss three coins 600 million times to generate 100 million hexagrams. According to the basic rules of hexagram divination, we calculate the hexagram changes. The results showed that: (1) Changes of things are mostly simple changes. The probability of 1 billion randomly generated hexagrams from one to three dynamic lines is close to 80%. (2) About 17% of the 64 hexagrams have no dynamic lines, which means that a significant proportion of the 64 hexagrams are invariant. (3) Small probability changing hexagram certainty and large probability changing hexagram uncertainty. (4) After generating one billion hexagrams at random, the topographic map with the probability of changing hexagrams has axial symmetry and fractal geometric characteristics, and the fractal characteristics are mainly manifested in that the changes on both sides of the symmetry are presented based on the triangle background. These results reflect the obvious characteristics and internal regularity of the changes in the 64 hexagrams of the I Ching. This article provides new ideas for scientific exploration of the internal laws of the 64 hexagrams in the I Ching.

Although many policosanols from different sources, such as sugar cane, rice bran, and insects, have been marketed worldwide, there has been no comparative study of the in vivo efficacy using a hyperlipidemic animal model. This study compared the efficacy of treating dyslipidemia with four different policosanols, including one sugar cane wax alcohol from Cuba (Raydel®) and three policosanols from China (Xi’an Natural sugar cane, Xi’an Realin sugar cane, and Shaanxi rice bran) in hyperlipidemic zebrafish. After 12 weeks of consumption of each policosanol (final 0.1% in diet, wt/wt) and high cholesterol diet (HCD, final 4%, wt/wt) in a tetrabit, the Raydel policosanol group and Xi’an Natural policosanol group showed the highest survivability of approximately 81%, whereas the Xi’an Realin policosanol group and Shaanxi policosanol group showed 57% and 67% survivability, respectively. Among five HCD groups, the Raydel policosanol group showed the lowest serum total cholesterol (TC, p<0.001 versus HCD control) and triglyceride (TG, p<0.001 versus HCD control) with the highest percentage of high-density lipoproteins (HDL)-C in TC. The Raydel policosanol group also showed the lowest serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels with the least infiltration of inflammatory cells and interleukin-6 production in hepatocytes. In the ovary, the Raydel policosanol group also showed the highest contents of mature vitellogenic oocytes with the lowest production of reactive oxygen species and cellular apoptosis in ovarian cells. In the testis, the Raydel policosanol group also showed the healthiest morphology for spermatogenesis with the least interstitial area and reactive oxygen species (ROS) production in testicular cells. In conclusion, 12 weeks of Raydel policosanol consumption resulted in remarkable improvement of the blood lipid profile, amelioration of inflammation in the liver, and enhancement of the cell morphology in the ovary and testis with the highest survivability under the HCD.

The inositol triphosphate associated proteins IRAG1 and IRAG2 are cGMP kinase substrate proteins, which regulate intracellular Ca2+. Previously, IRAG1 was discovered as a 125 kDa membrane protein at the endoplasmic reticulum, that is associated with the intracellular Ca2+ channel IP3R-I and the PKGIβ and inhibits IP3R-I upon PKGIβ-mediated phosphorylation. IRAG2 is a 75 kDa membrane protein homologue of IRAG1 and was recently also determined as a PKGI substrate protein. Several (patho-)physiological functions of IRAG1 and IRAG2 were meanwhile and recently elucidated in a variety of human and murine tissues, e.g. of IRAG1 in various smooth muscles, heart, platelets and other blood cells, of IRAG2 in pancreas, heart, platelets and taste cells. Hence, lack of IRAG1 or IRAG2 leads to diverse phenotypes in these organs, e.g. smooth muscle and platelet disorders or secretory deficiency, respectively. This review aims to highlight the recent research regarding these both regulatory proteins to envision its molecular and (patho-)physiological tasks and to unravel its functional interplay as possible (patho-)physiological counterparts.

Should our planet be visited by an extraterrestrial civilization, the prevailing assumption would undoubtedly be that the extraterrestrial civilization is Type I i.e. its capacity for interstellar travel results from its technological development. This assumption is dangerous for it unnecessarily leads to the Extraterrestrial Tandem Hypothesis (ETH): the belief than an extraterrestrial civilization technologically capable of interstellar travel must also be technologically compatible with the inexorably rapid annihilation of life on Earth. Such a state of things would compromise the planet’s capacity to stage a confident defense should the extraterrestrials prove belligerent. The presumption of Type I extraterrestrials (on the premise of the capacity for interstellar travel alone) is unfounded as extraterrestrials may be Type II i.e. capable of interstellar travel by virtue of natural intrinsic or extrinsic factors. This paper advances, most importantly, that the fundamental policy of first contact should be the employment of various strategies toward the evaluation of the technological capacity of visiting extraterrestrials. This evaluation must be particularly devoted to the detection of Type II extraterrestrials masquerading as Type I (using concealment and Wizard of Oz strategies). Integral to this detection are the concepts of the precedence relation and The Extraterrestrial Exclusion Principle (EEP). A precedence relation is a qualitative relation expressing the relative difficulty of producing a technological action. The Extraterrestrial Exclusion Principle states that a Type I extraterrestrial life form is excluded from certain actions. Such actions are lower in precedence than interstellar travel and may be described as in violation of the EEP or EEP forbidden. EEP actions reveal extraterrestrials to be Type II. As an example, the value of the Hawking Warning is subjected to EEP analysis. Furthermore, a hypothetical conundrum in linguistics termed the Kryptonian Linguistic Paradox (KLP) is discussed as a case of an EEP forbidden act. Finally, the paper explores the limitations of the stated fundamental policy of first contact.

A gold(I) complex with a triphenylphosphine and a monodentate N,N-dimethyldithiocarbamate ligand was synthesized and characterized by Raman spectroscopy and single crystal X-ray diffraction. DFT calculations (Gaussian 09, PBE1PBE/Lanl2dz) were undertaken for a single complex in the gas-phase. The DFT-optimized structure is in good agreement with the crystal structure and the DFT-calculated Raman spectrum also is in excellent agreement with the experimental spectrum. Assignments of the Raman peaks are based on these DFT calculations. Frontier molecular orbitals were calculated and their nature is discussed.

Exposure to even low levels of the environmental pollutant cadmium (Cd), increases the risk of kidney damage. The body burden of Cd at which kidney damage occurs is not, however, reliably defined. Here, multiple-regression and mediation analyses were applied to data from 737 non-diabetic Thai nationals, of which 32.2% had hypertension and 9.1% had an estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2 (low eGFR). The excretion rates of Cd (ECd) and N-acetyl-β-D-glucosaminidase (ENAG), a marker of tubular injury, were normalized to creatinine clearance (Ccr) as ECd/Ccr and ENAG/Ccr. Doubling ECd/Ccr increased the risks of having a low eGFR [POR = 2.71 (95% CI:1.97, 3.74), p &lt; 0.001] and severe tubular injury [POR = 4.80 (95% CI: 1.35, 17.1), p = 0.015]. ENAG/Ccr was strongly associated with ECd/Ccr in both men (β = 0.447, p &lt;0.001) and women (β = 0.394, p &lt;0.001), while showing a moderate inverse association with eGFR only in women (β = −0.178, p = 0.002). A moderate association of ENAG/Ccr and ECd/Ccr was found in the low- (β = 0.287, p = 0.001), and the high-Cd body burden groups (β = 0.145, p = 0.004), but ENAG/Ccr was inversely associated with eGFR only in the high-Cd body burden group (β = −0.223, p &lt;0.001). These findings together with an insignificant mediated effect suggested that Cd-induced injury that causes release of NAG plays little or no role in the nephron destruction that reduces GFR.

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Early detection and the modification of risk factors, such as diet, can reduce its incidence. Among food components the polyamines are important for maintaining gastrointestinal health and are metabolites of gut microbiota. Their disruption is linked to CRC, making polyamines a potential marker of the disease. This study analyzed the relationship between dietary components, including polyamines, and the presence of polyamines in feces to determine whether their presence could contribute to predicting the occurrence of colorectal lesions in patients. Fifty-nine participants of both sexes (aged 50 to 70 years) who had undergone colonoscopy screening for CRC (18 without and 41 with colorectal lesions) participate in the study. A nutritional survey and determination of fecal polyamine content were performed. Specific dietary components and putrescine levels were higher in patients with colorectal lesions. The diet ratio of putrescine/spermidine and the fecal content of N-acetyl putrescine and cadaverine were elevated in patients with precancerous lesions and adenocarcinomas, showing a potential predictive value for the presence of colorectal lesions. These findings suggest that N-acetyl putrescine and cadaverine could be complementary markers for the diagnosis of suspected colorectal lesions.

The existences of the N→C dative bonds in the complexes between N-containing molecules and fullerenes have been verified both theoretically and experimentally. However, finding stable N→C dative bonds is still a highly challenging task. In this work, we investigated computationally the N→C dative bonds in the complexes formed by fullerene C60 with 1,2,5-chalcogenadiazoles, 2,1,3-benzochalcogenadiazoles and 1,2,4,5-chalcogenatriazoles, respectively. It was found that the N→C dative bonds are formed along with the formation of the N–Ch···C (Ch = S, Se, Te) chalcogen bonds. In the gas phase, from S-containing complexes through Se-containing complexes to Te-containing complexes, the intrinsic interaction energies become more and more negative, which indicates that the N–Ch···C chalcogen bonds can facilitate the formation of the N→C dative bonds. The intrinsic interaction energies are compensated by the large deformation energy of fullerene C60. The total interaction energies of Te-containing complexes are negative, while both of the total interaction energies of S-containing complexes and Se-containing complexes are positive. This means that the N→C dative bonds in the Te-containing complexes are more easily observed in experiments in comparison with those in the S-containing complexes and Se-containing complexes. This study provides a new theoretical perspective on the experimental observation of the N→C dative bonds in the complexes involving fullerenes. Further, the formation of stable N→C dative bonds in the complexes involving fullerenes can significantly change the properties of fullerenes, which will greatly simulate and expand the application range of fullerenes.

The early elongation events in transcription or translational control in the N-terminal of genes are assuming critical roles in their heterologous expression. The secretory expression of the alkaline pectin lyase APL in B. subtilis were studied to explore the effects of the N-terminal 5-7 amino acids sequences of different signal peptides on gene transcription and protein secretion in this study. The first 5 amino acid sequences of the N-terminal of the signal peptide LipA were identified to play an important role in promoting the expression of APL for the first time. Meanwhile, it also revealed that the signal peptide LipA could lead to higher secretory expression than other signal peptides not because of its sequence structure associated with secretion is stronger but because the N-terminal sequences showed greater advantages in gene transcription. At this basis, the recombinant strain structed in this work showed a new record for the highest extracellular yields (12 295 U/ml) of APL in B. subtilis which was 1.9 times higher than that expressed in the recombinant Escherichia coli strain we had reported before. The novel theories revealed in this study would assuming significance roles for improving expression of foreign proteins in or out of the cells.

N-methyl-D-aspartate receptors (NMDARs) are the main class of ionotropic receptor for the ex-citatory neurotransmitter glutamate. It plays a crucial role in the permeability of Ca2+ ions and excitatory neurotransmission in the brain. Being heteromeric receptors, they are composed of sev-eral subunits, including two obligatory GluN1 subunits (eight splice variants) and regulatory GluN2 (GluN2A~D) and/or GluN3 (GluN3A~B) subunits. Widely distributed in the brain, they regulate other neurotransmission systems and are therefore involved in essential functions such as synaptic transmission, learning and memory, plasticity, excitotoxicity. The present review will discuss the physiopathological impacts of NMDAR and particularly GluN2A and GluN2B subu-nits in cognitive processes and neurodegenerative diseases (Alzheimer's disease, Huntington's disease, Parkinson's disease). The pharmacology of different NMDAR antagonists and their po-tentialities will be presented. In particular, a focus will be given on fluoroethylnormemantine (FENM), an investigational drug with very promising developments as a tomography radiotracer for NMDARs, an anxiolytic in post-traumatic stress disorder and a neuroprotective agent in Alzheimer's disease.

The objective of this study was to analyze the mental workload using EEG and eye tracking data and classify it using machine learning algorithms. The machine learning model was developed based on the simultaneous recording of eye tracking and EEG measurements during the experimental process. The experiments involved 15 university students, consisting of 7 women and 8 men. Throughout the experiments, the researchers utilized the n-back memory task and the NASA-Task Load Index (TLX) subjective rating scale to assess various levels of mental workload. The findings revealed that as the task difficulty increased, there was an increase in the diameter of both the right and left pupils, the number of fixations, the number and duration of saccades, and the number and duration of blinks. Conversely, variables related to fixation duration decreased. The EEG results indicated that theta power in the prefrontal, frontal, and front central regions increased with task difficulty. Additionally, alpha power increased in the frontal regions but decreased in the temporal, parietal, and occipital regions as the task became more challenging. Furthermore, low beta power significantly decreased in almost all brain regions as the task difficulty increased. In terms of the four-class classification problem, the mental workload level can be predicted with an accuracy rate of 76.59% using 34 selected features. This study has made a significant contribution to the literature by presenting a four-class mental workload estimation model that utilizes different machine learning algorithms.

In archaea, the interaction of HerA helicase and NurA nuclease is required for 3' end resection during DNA double-stranded break repair, and its disruption results in unfaithful DNA repair. Interactions transpire by the four conserved domains, including the N-terminal HAS domain (HerA-ATP synthase), which serves as a binding site for the exonuclease NurA. As a HerA hexamer between its two subunits, the conserved C-terminal brace extension functions as an adjacent brace. DBD serves as a location for DNA binding, which causes the DNA strands to be propelled into the HerA pocket to begin unwinding. The putative pore entrance is made up of four helix coils, which provide a suitable charged surface for guiding DNA into the pore. The crystal structure of the complex HerA-NurA allows for the identification of key residues for protein-protein interaction. This allows us to predict that most archaeal HerA orthologs will be able to interact with one another. Archaeal HerA is a homo-hexameric assembly featuring a DNA-binding domain that is conserved. It also features distinctive ATP and NurA binding domains. Following the structure and sequence conservation criteria, we find one HerA ortholog in Pyrobaculum calidifontis and multiple HerA paralogs, but the role of none is established yet.Interestingly, orthologous HerA is part of an Mre11-Rad50 gene neighborhood while paralogous HerA is not, which could be misleading. As a result, it sought to describe the criteria that may be used as a possible fingerprint for identifying orthologous genes, as well as the cloning procedures and tactics that would aid in the confirmation of the HerA helicase in P. calidifontis. Their confirmation is based on PCR cloning and characterization following HerA construct creation.

The efficiency and performance of Proton Exchange Membrane Fuel Cells (PEMFCs) are primarily influenced by ORR electrocatalysts. In recent years, atomically dispersed met-al-nitrogen-carbon (M-N-C) catalysts have gained significant attention due to their high active center density, high atomic utilization, and high activity. These catalysts are now considered the preferred alternative to traditional noble metal electrocatalysts. The unique properties of M-N-C catalysts are anticipated to enhance the energy conversion efficiency and lower the manufac-turing cost of the entire system, thereby facilitating the commercialization and widespread ap-plication of fuel cell technology. This article initially delves into the origin of performance and degradation mechanisms of Fe-N-C catalysts from both experimental and theoretical perspectives. Building on this foundation, the focus shifts to strategies aimed at enhancing the activity and durability of atomically dispersed Fe-N-C catalysts. These strategies encompass the use of bi-metallic atoms, atomic clusters, heteroatoms (B, S, and P), and morphology regulation to optimize catalytic active sites. The article concludes by detailing the current challenges and future pro-spects of atomically dispersed Fe-N-C catalysts.

The utilization of titanium dioxide (TiO2) as a photocatalyst for the treatment of wastewater has attracted significant attention in the environmental field. Herein, we have prepared a NH2-MIL-125-derived TiO2@N-doped C Visible Light Catalyst through an in-situ calcination method. The nitrogen element in the organic connector is released through calcination, simul-taneously doping into the sample, thereby enhancing its spectral response to cover the visible region. The as-prepared TiO2@N-doped C catalyst exhibited preserved cage structure even after calcination, thereby alleviating the optical shielding effect and further augmenting its photo-catalytic performance by increasing the reaction sites between the catalyst and pollutants. The calcination time of the TiO2@N-doped C-450 °C catalyst was optimized to achieve a balance be-tween the TiO2 content and nitrogen doping level, ensuring efficient degradation rates for basic fuchsin (99.7%), Rhodamine B (89.9%), and tetracycline hydrochloride (93%) within 90 minutes.

We report on recent experimental results on β decay into self-conjugate (N=Z) nuclei with mass number 58≤A≤70. Super-allowed β decays from the Jπ=0+ ground state of a Z=N+2 parent nucleus are to the isobaric analogue state, through so-called Fermi transitions, and to Jπ=1+ states, by way of Gamow–Teller (GT) transitions. The operator of the latter decay is a generator of Wigner’s SU(4) algebra and as a consequence GT transitions obey selection rules associated with this symmetry. Since SU(4) is progressively broken with increasing A, mainly as a consequence of the spin–orbit interaction, this symmetry is not relevant for the nuclei considered here. We argue, however, that the pseudo-spin–orbit splitting can be small in nuclei with 58≤A≤70, in which case nuclear states exhibit an approximate pseudo-SU(4) symmetry. To test this conjecture, GT decay strength is calculated with use of a schematic Hamiltonian with pseudo-SU(4) symmetry. Some generic features of the GT β decay due to pseudo-SU(4) symmetry are pointed out. The experimentally observed GT strength indicates a restoration of pseudo-SU(4) symmetry for A=70.

Based on the elasticity theory, this paper deals with the static analysis of a cracked double beam system in presence of a Winkler medium. The double-beam system is also supposed to be constrained at both ends by elastically flexible springs, with transverse and rotational stiffness. Using a variational formulation, the static governing equations are derived and solved by using analytical and numerical approaches. In the first approach, the closed-form solutions for the displacements functions are obtained based on the Euler-Bernoulli beam theory. In the second approach, the Cell-Discretization Method (CDM) is performed, according to which the two beams are reduced to a set of rigid bars linked together by means of elastic constraints, where the bending stiffness of the bars is concentrated. The resulting stiffness matrix is easily deduced, and the governing equations of the static problem can be immediately solved. A comparative analysis is performed in order to verify the accuracy and validity of the proposed method. This study focuses on the effect of various parameters including the crack depth and position, boundary conditions, elastic medium and slenderness. The validity of the proposed analysis is confirmed by comparing the present results with those obtained from the other approach. In particular, the results obtained by closed-form solution and Cell-discretization method (CDM) are compared by Finite element method (FEM). Accuracy of the results has been evaluated by making comparisons with the results in literature and reported in bibliography. It is demonstrated that the proposed algorithm provides a simple and powerful tool in dealing with the static analysis of a double-beam system. Finally, some concluding remarks are made.

Japanese pepper (sansho, Zanthoxylum piperitum) contains several types of sanshools belonging to N-alkylamides. Because of long-chain unsaturated fatty acids present in their structure, sanshools are prone to oxidative deterioration, which poses problems in processing. Here, we evaluated the effects of antioxidants from the genus Zanthoxylum in preventing sanshool degradation using accelerated tests. An ethanolic extract of segment membranes of the sansho fruit pericarp was incubated at 70 °C for 7 days with different antioxidants to determine the residual amount of hydroxy-α-sanshool (HαS) in the extract. α-Tocopherol (α-Toc) showed excellent HαS-stabilizing activity at low concentrations. Among phenolic acids, we noted that the HαS-stabilizing activity increased with the number of hydroxy groups per molecule. For example, gallic acid and its derivatives exhibited excellent sanshool-stabilizing activity. Quercetin was found to be a superior HαS stabilizer compared with hesperetin and naringenin. However, the effective concentration was much higher for phenolic compounds than for α-Toc. These substances are believed to play a role in preventing the decomposition of sanshools in the pericarp of sansho. These sanshool stabilizers should be useful in the development of new beverages, foods, cosmetics, and pharmaceuticals that take advantage of the taste and flavor of sansho.

N-Acetyl-L-glutamate kinase (NAGK) catalyzes the rate-limiting step in the ornithine/arginine biosynthesis pathway in eukaryotic and bacterial oxygenic phototrophs. NAGK is the most highly conserved target of the PII signal transduction protein in Cyanobacteria and Archaeplastida (red algae and Chlorophyta). However, yet there is still much to be learnt on how NAGK is regulated in vivo. The use of unicellular green Chlamydomonas reinhardtii as a model system has already been instrumental in identifying several key regulation mechanisms that control nitrogen (N) metabolism. With a combination of molecular-genetic and biochemical approaches, we show the existence of the complex CrNAGK control at transcriptional level, which is dependent on N source and N availability. In growing cells, CrNAGK requires CrPII to properly sense the feedback inhibitor arginine. Moreover, we provided primary evidence that CrPII is only partly responsible for regulating CrNAGK activity to adapt to changing nutritional conditions. Collectively, our results suggest that in vivo CrNAGK is tuned at transcriptional and post-translational levels, and CrPII and additional as yet unknown factor(s) are integral parts of this regulation.

3,4-Dihydroquinolin-2(1H)-ones represent a class of valuable bioactive compounds with six-membered nitrogen-containing heterocyclic structures. The development of simple, mild and efficient synthetic methods has been widely concerned by synthetic chemists. In this review, we have summarized a series of different synthetic strategies for the synthesis of dihydroquinoline-2(1H)-ones via catalytic annulation of α,β-unsaturated N-arylamides in the past decade, including covering electrophilic cyclization, radical initiated cyclization and photochemical cyclization reactions. Besides, the substrate scope and mechanistic details are also discussed. This paper will provide a useful reference for the development of diverse synthesis methodologies of 3,4-dihydroquinolin-2(1H)-ones.

N-acetyl-L-cysteine (NAC), a sulfhydryl-containing compound, is mainly used as a mucolytic and as an antidote for acetaminophen overdose. Flow injection and sequential injection systems were designed and optimized with the aim of providing precise, accurate and reliable flow methods for NAC determination in pharmaceuticals with very low sample and reagent consumption. Proposed methods are based on a redox reaction wherein NAC reduces a complex of Cu(II) and bathocuproine disulfonate (BCS) to orange [Cu(BCS)2]3– complex, which absorption was measured at λmax = 483 nm. The optimized FIA and SIA configuration yielded a linear calibration curve with correlation coefficients (R2 = 0.9999 and R2 = 0.9996) in the concentration range of 3.0 × 10–7 – 3.0 × 10–5 mol L–1 and analytical frequency of 120 h–1 for the FIA method and 4.0 × 10–7 – 4.0 × 10–5 mol L–1, at sampling rate 60 h–1 for the SIA method. The proposed flow methods were successfully applied for the determination of NAC in pharmaceutical products, as the results showed good agreement with the standard method prescribed by Pharmacopoeia. Recoveries were in the range from 98.4% to 101.9% for the FIA method and from 97.2% to 101.8% for the SIA method.

The chelating aluminum complex [2-(Me2NCH2)C2B10H10]AlX2 (X = Br 3, CH3 4) was synthesized using 2-dimethylaminomethyl-o-carboranyl lithium (2) with aluminum tribromide or dimethylaluminum bromide, resulting in a modest yield. Compound 4 was obtained by reacting compound 3 with CH3Li in toluene. All compounds were characterized by infrared (IR) spectroscopy, 1H, 11B, 13C nuclear magnetic resonance (NMR) spectroscopy, and X-ray crystallography. X-ray structural studies of CabNAlBr2 (3) and CabNAlMe2 (4) indicated that the Al atom was located at the center of a distorted tetrahedron. Crystal structures of the CabNAlBr2 (3) [a = 8.9360(3) Å, b = 12.0358(9) Å, c = 14.7730(4) Å, α = β = γ = 90°] and the CabNAlMe2 (4) [a = 8.9551(3) Å, b = 11.9126(9) Å, c = 14.7711(4) Å, α = β = γ = 90°] were obtained. The reactivity of aluminum complexes 3 and 4 with Lewis bases, such as H2O, pyridine, alkylamines, and arylamines, confirmed their rapid decomposition.

This study aimed to investigate the possibility of using one-shot hyperspectral airborne images to recognize crops for an area with many small plots. The results showed that unsupervised clustering methods could classify crops with an accuracy of 80%, which improved to 90% when restricted to only grain crops, using a single airborne hyperspectral recording. However, additional layers such as NDVI, DTM, slope, and aspect did not improve classification accuracy. For comparison, the accuracy of clustering time series Sentinel-2 images with NDVI layers and DTM-derived data yielded an accuracy of: 74% ,Sentinel-2 time series 68% and single one registration before harvest - 39%. The results of the random forest classification were slightly less accurate due to a lack of sufficient reference data. However, it is challenging to verify the reported accuracy of crop recognition in the literature above 90% due to differences in analysis methodologies, reference data selection, pixel/object approaches, metric choice, and calculation formulas used.

We recently proposed that topological quantum computing might be based on $SL(2,\mathbb{C})$ representations of the fundamental group $\pi_1(S^3\setminus K)$ for the complement of a link $K$ in the $3$-sphere. The restriction to links whose associated $SL(2,\mathbb{C})$ character variety $\mathcal{V}$ contains a Fricke surface $\kappa_d=xyz -x^2-y^2-z^2+d$ is desirable due to the connection of Fricke spaces to elementary topology. Taking $K$ as the Hopf link $L2a1$, one of the three arithmetic two-bridge links [the Whitehead link $5_1^2$, the Berge link $6_2^2$, the double-eight link $6_3^2$] or the link $7_3^2$, the $\mathcal{V}$ for those links contains the reducible component $\kappa_4$, the so-called Cayley cubic. In addition, the $\mathcal{V}$ for the later two links contains the irreducible component $\kappa_3$, or $\kappa_2$, respectively. Taking $\rho$ to be a representation with character $\kappa_d$ ($d<4$), with $|x|,|y|,|z| \le 2$, then $\rho(\pi_1)$ fixes a unique point in the hyperbolic space $\mathcal{H}_3$ and is conjugate to a $SU(2)$ representation (a qubit). Even though details on the physical implementation remain open, more generally, we show that topological quantum computing may be developed from the point of view of three-bridge links, the topology of the $4$-punctured sphere and Painlev\'e VI equation. The $0$-surgery on the $3$ circles of the Borromean rings L6a4 is taken as an example.

The C/N ratio is an extremely important parameter in the composting process, which is directly responsible for the growth of microorganisms. A low C/N ratio contributes to higher emissions of greenhouse gases and odorous substances, such as ammonia (NH3), which is formed by nitrogen mineralization. Due to the highly toxic effects of ammonia, it is a particularly unwanted by-product that can disrupt the composting process because it poisons microorganisms and cause environmental issues. The activity of anammox bacteria, so far analyzed only in wastewater treatment processes, is a particularly efficient method of nitrogen removal, having an advantage over the conventional methods used previously. Our study proofs the presence of anammox bacteria during composting, what gives an opportunity to improve the process and reduce its impact on atmospheric pollution. Despite the aerobic nature of this process, the composted mass of waste presents conditions conducive to the development of these ammonia oxidizing bacteria, as well as other strains of microorganisms cooperating with them. This makes it possible to compost at a low C/N ratio; in addition, there is no need for additional energy supply through aeration, as the processes carried out by anammox bacteria do not require oxygen.

Among the first discovered and most prominent cellular oncogenes is MYC, which encodes a bHLH-ZIP transcription factor (Myc) that both activates and suppresses numerous genes involved in proliferation, energy production, metabolism and translation. Myc belongs to a small group of bHLH-ZIP transcriptional regulators (the Myc Network) that includes its obligate heterodimerization partner Max and six “Mxd proteins” (Mxd1-4, Mnt and Mga) each of which heterodimerizes with Max and largely oppose Myc’s functions. More recently, a second group of bHLH-ZIP proteins (the Mlx Network) has emerged. It is comprised of the Myc-like factors ChREBP and MondoA, which, in association with the Max-like member Mlx, regulate smaller and more functionally restricted sets of target genes, some of which are shared with Myc. Opposing ChREBP and MondoA are heterodimers comprised of Mlx and Mxd1, Mxd4 and Mnt, which also structurally and operationally link the two Networks. We discuss here the functions of these “Extended Myc Network” members with particular emphasis on the roles played by Max, Mlx and Mxd proteins in suppressing normal and neoplastic growth. These roles are complex due to the temporally- and tissue-restricted expression of Extended Myc Network proteins in normal cells, their regulation of both common and unique target genes and, in some cases, their functional redundancy.

This paper provides a methodology for the production of synthetic images for training neural networks to recognise shapes and objects. There are many scenarios in which it is difficult, expensive and even dangerous to produce a set of images that is satisfactory for the training of a neural network. The development of 3D modelling software has nowadays reached such a level of realism and ease of use that it seemed natural to explore this innovative path and to give an answer regarding the reliability of this method that bases the training of the neural network on synthetic images. The results obtained in the two proposed use cases, that of the recognition of a pictorial style and that of the recognition of migrants at sea, leads us to support the validity of the approach, provided that the work is conducted in a very scrupulous and rigorous manner, exploiting the full potential of the modelling software. The code produced, which automatically generates the transformations necessary for the data augmentation of each image, and the generation of random environmental conditions in the case of Blender and Unity3D software, is available under the GPL licence on GitHub. The results obtained lead us to affirm that through the good practices presented in the article, we have defined a simple, reliable, economic and safe method to feed the training phase of a neural network dedicated to the recognition of objects and features, to be applied to various contexts.

Although sources of seston are much more complicated in lakes compared to marines, the influences of different source on the spatiotemporal variations in seston stoichiometry are still underexplored, especially in large eutrophic floodplain lakes. Here, we investigated the seston stoichiometry across a typical large eutrophic floodplain lake (Lake Taihu) over one year. In addition, we used the n-alkanes proxies for source estimation which are more robust than other elemental indicators (e.g. C: N ratios). Throughout the study, the average value of C: N: P ratio of 143: 19: 1 across Lake Taihu was higher than the classical Redfield ratio, but closed to the synthesized data from other lakes. Generally, seston C: N ratios varied the least across all environments, but C: P and N: P ratios varied widely and shown a significant seasonal pattern with lower ratios of N: P and C: P during senescence seasons and higher ratios in the growing seasons. This seasonal change was mainly associated with the shift from terrestrial-derived seston to algal-derived seston as, the significant lower ratios of terrestrial-derived seston from surrounding agricultural watershed. Spatially, the mean ratios of each site were similar, except relative high values of C: P and N: P ratios in the algal dominated area. Statistically, the predictive power of environmental variables was strongly improved by adding n-alkanes proxies. However, apart from sources indicators, particulate phosphorus (PP) contents also partly explained the spatiotemporal variations in stoichiometric ratios. Nevertheless, the mechanisms behind the dynamics of PP could be totally different and source-specific. This study highlights the priority of using n-alkanes proxies as tools to identify the source of seston which is essential to interpret the spatiotemporal variations in seston stoichiometric ratios among eutrophic floodplain lakes.

Transition-metal-catalyzed amide bond formation from alcohols and amines is an atom-economic and eco-friendly route. Herein, we identified a highly active in situ N-heterocyclic carbene (NHC)/ruthenium (Ru) catalytic system for this amide synthesis. Various substrates, including sterically hindered ones, could be directly transformed into the corresponding amides with the catalyst loading as low as 0.25 mol%. In this system, we replaced the p-cymene ligand of the Ru source with a relatively labile cyclooctadiene (cod) ligand so as to more efficiently obtain the corresponding poly-carbene Ru species. Expectedly, the weaker cod ligand could be more easily substituted with multiple mono-NHC ligands. Further HR-MS analyses revealed that two tetra-carbene complexes were probably generated from the in situ catalytic system.

In the present study, the performance of a 70 L photobioreactor, operating outdoors, was investigated using a purple bacterial strain as Rhodopseudomonas sp. S16-VOGS3 for producing poly-3-hydroxybutyrate (PHB). The novel photobioreactor was equipped with 5L-shaped rows; the bottom of every row was placed in a stainless-steel tank containing water with controlled temperature. The photofermentation trials were carried out under fed-batch mode and under a semi-continuous regimen using lactic acid as carbon source. The effect of the irradiance and the C/N ratio on the PHB accumulation was investigated, in order to evaluate the optimal bacterial growth. The results showed the feasibility of the prototype photobioreactor for the production of PHB by Rhodopseudomonas sp. S16-VOGS3 under the natural light/dark cycle. During the fed-batch growth (144 h long), the cumulative PHB increased quickly reaching the maximum value of 377 mg/L and decreased to 255 mg/L during the semi-continuous regimen (336 h long).

Several studies suggests that ghrelin (GHRL) has neurobiological effects that extend beyond control of food intake. Our previous results confirmed that GHRL modulates the secretory activity of the pineal gland (PG) through nocturnal melatonin (MEL) secretion in sheep, the seasonally reproductive animals. Here we investigated the effects of GHRL (10 ng/ml) on the expression of enzymes limiting synthesis of MEL, including tryptophan 5-hydroxylase 1 (TPH1), serotonin N-acetyltransferase (AA-NAT) and its phosphorylated form p31T-AA-NAT in sheep PG explants (n = 72) during the 4-hour incubation in a gas-liquid interface, at a short (SD) and long (LD) photoperiods. After each hour of incubation selected explants were frozen in liquid nitrogen and stored at -80°C for subsequent analysis (real-time PCR, western-blotting, ELISA). Results show that GHRL regulates nightly MEL secretion in a TPH1-independent manner. The factor modulating GHRL activity was photoperiod. During SD photoperiod GHRL significantly reduced the expression of p31T-AA-NAT, AA-NAT and inhibited MEL secretion from PG explants. Whereas, during LD photoperiod no effect of GHRL on MEL secretion and expression of examined enzymes was noted. Studies indicate that GHRL directly affects PG under in vitro conditions and causes MEL secretion in animals which exhibit seasonality in reproductive and metabolic processes.

Minimizing optical losses in resonant cavities is crucial for improving photonic device performance. This study focuses on the development of a simulation tool to analyze scattering losses in Fabry-Pérot interferometers (FPI), offering precise modeling of waveguide dynamics and contributing to accurate loss predictions across various platforms. Optical cavities often suffer from scattering losses due to surface roughness and material defects. Our approach integrates theoretical models and simulations to quantify these losses, utilizing the FPI as a model system. We identified upper and lower reflectivity thresholds, beyond which accurate measurement of losses becomes unreliable. For reflectivity below a certain threshold, measurement errors arise, while excessively high reflectivity can reduce fringe visibility and introduce detector sensitivity issues. Simulations were used to validate the model's ability to predict reflectivity and attenuation in waveguides with varying loss levels. The software’s flexibility to adjust transmission parameters for different cavity configurations enhances its utility for a broad range of photonic systems. Our study offers a novel methodology for optical loss analysis, with practical applications in optimizing photonic devices. By providing a reliable tool for precise loss measurement, this work supports advancements in optical technologies, enabling the design of more efficient, high-performance devices across various applications.

Poor therapeutic outcomes have been attributed to inter-individual and interethnic variability in cytochrome P450 (CYP450)-dependent metabolism and altered drug retention associated with P-glycoprotein (P-gp). An individualized pharmacotherapeutic approach would benefit the genetically diverse South African population. The study aim was to develop a validated, targeted, analytical method to quantify seven probe drugs and their metabolites in dried blood spots (DBS) using the Mitra™ volumetric absorptive micro-sampling device for blood collection. An Agilent liquid chromatography (LC) system coupled to a Sciex 4000 QTRAP tandem mass spectrometer (MS) was used for method optimization and validation. Targeted LC-MS/MS methods were validated according to ICH guidelines. The validated LC-MS/MS method met the required bioanalytical standards for specificity, sensitivity, linearity, accuracy, precision, carry-over, and stability. This study successfully validated the use of DBS, collected with the Mitra™ microsampling device, to measure expected probe drug and metabolite concentrations using the “Geneva phenotyping cocktail” for the purpose of simultaneous phenotyping of in vivo CYP450 metabolic activity of the CYP1A2, -2B6, -2C9, -2C19, -2D6, and -3A4 enzymes, and P-gp transport activity. However, statistical analysis using Bland-Altman plots showed that not all analytes exhibited linear distribution pharmacokinetics between DBS and plasma, which influenced the predicted vs real plasma concentrations based on measurements in a DBS matrix. These findings were attributed to the blood-to-plasma concentration ratio, the physicochemical properties and stability of the analytes, and the extraction efficiency of the Mitra™ sampler. More research is required before DBS sampling can be substituted for conventional plasma sampling

Starvation of photoreceptors induced by reduced dysregulated ocular blood flow is proposed as a common pathway for the pathogenesis of retinitis pigmentosa (RP). The current study evaluated the safety and efficacy of ophthalmic nerve stimulation (ONS) as an ocular blood flow neuromodulator, combined with ascorbic acid (AA) as a potent anti-oxidant in the treatment of RP. Additionally, the initial characteristics of rod responders were identified. Forty participants with simple, non-syndromic RP presented with a characteristic triad of RP (the bone spicule pigmentation, attenuation of retinal blood vessels, and waxy optic disc pallor), were en-rolled in a prospective open-label single-armed interventional study. The severity of the disease was clinically graded into six stages. Patients with an established diagnosis of RP; aged ≥ 4 years, with best corrected visual acuity (BCVA) ≥ 20/400 were included. All participants were daily treated with bilateral ONS sessions combined with intravenous administration of AA for two weeks. The primary efficiency endpoint was 6 months’ changes in scotopic vision as measured by a 10-item, 100-point, Low Luminance Questionnaire-10 (LLQ-10). The secondary efficiency points included best corrected visual acuity (BCVA) and contrast sensitivity. Rod responders were defined by ≥ 25 points increment of LLQ-10 score at 6 months after treatment. The results showed that ONS combined with AA treatment significantly improved low luminance vision, BCVA, and contrast sensitivity in patients with RP (p≤ 0.05). At 6-month visit, twenty-four (60%) patients were identified as rod responders and 16 (40%) patients were rod-non-responders. The mean change in LLQ-10 score was (46.35 ±16.81) in rod responders versus (4.9 ± 7.6) in non-responders (p < 0.0001). A clinically significant improvement of BCVA (≥0.2 logMAR) and contrast sensitivity (≥0.3 log unit) were demonstrated in 50% of the right eyes of rod responders. No serious adverse effects were reported and headache in 5 patients (12.5%) was the only en-countered side effect in this study. In conclusion, ocular neuromodulation is a safe therapeutic strategy for RP. It significantly improved night vision, BCVA, and contrast sensitivity. Determinants of rod responders include a shorter duration of night blindness, an earlier stage of the disease, and a relatively thicker ganglion cell layer at baseline. Additionally, two therapeutic scenarios were recognized; an early disease-modifying intervention that restores night vision and reverses the disease process and a late cone rescue intervention that improves/maintains central vision.

Abstract: Pasteurella spp. is a gram-negative bacterium that is part of the oral and upper respira-tory tract microbiota of many animals such as canids and felines. In humans it can produce pa-thology primarily associated with animal bites or scratches. In addition, members of this genus, and especially Pasteurella multocida, may also be involved in systemic infections, mainly in im-munocompromised patients in close contact with pets. The aim of this study is to analyse the prevalence and clinical characteristics of infections caused by Pasteurella spp. as well as the sensitivity profile of these isolates obtained in the Microbiology laboratory of the Hospital Can Misses (Ibiza, Ibiza and Formentera Health Area, ASEF) in the period from January 2013 to December 2018. The group of islands of Ibiza and Formentera is known as the Pitiusas Islands. Retrospective descriptive study in which all Pasteurella spp. isolates were analysed in the Microbiology Laboratory of Hospital Can Misses from 1 January 2013 to 31 De-cember 2018. Bacterial identification was performed by Vitek 2 automated biochemical test panel (bioMérieux, Spain) and antimicrobial susceptibility by E-test or antibiotic discs in Mueller-Hinton blood agar, interpreted based on European Committee on An-timicrobial Susceptibility Testing (EUCAST) standards, 2022 version. Medical records were systematically reviewed by collecting demographic data of infected patients, comorbidities, epidemiological data and clinical features of the infection. A total of 22 isolates of Pasterurella spp. were obtained from 22 different patients, 62.8% female, from three different species: 18 P. multocida, 2 P. canis and 2 P. pneumo-tropica. Most isolates came from soft tissue infection samples: 7 wound exudates and 5 abscess material. The antibiotics tested with the highest sensitivity profile were gen-tamicin and cefepime (100% sensitivity). The species most commonly isolated in our environment is P. multocida. Close contact with companion animals, especially cats and dogs, is the main risk factor for Pasteurella spp. infections, although in many cases such contact cannot be established. So Pasteurella spp. infection should be considered a zoonosis in possible emergency, especially in rural areas such as Pitiusas Islands.

We introduce the notion of p-adic magic contraction on p-adic Hilbert space. We derive p-adic Halmos dilation, p-adic Egervary N-dilation, p-adic von Neumann inequality and p-adic Sz.-Nagy dilation for p-adic magic contraction.

Stabilized un-doped Zinc Telluride (ZnTe) thin films were grown on glass substrates under vacuum using closed space sublimation (CSS) technique. A dilute copper nitrate solution (0.1/100 ml) was prepared for copper doping known as ion exchange process in the matrix of ZnTe thin film. The reproducible polycrystalline cubic structure of undoped and Cu doped ZnTe thin films with preferred orientation (111) was confirmed by X-rays diffraction (XRD) technique. Lattice parameter analyses verified the expansion of unit cell volume after incorporation of Cu species into ZnTe thin films samples. The micrographs of scanning electron microscopy (SEM) were used to measure the variation in crystal sizes of samples. The energy dispersive X-rays was used to validate the elemental composition of undoped and Cu-doped ZnTe thin films. The bandgap energy 2.24 eV of ZnTe thin film decreased after doping Cu to 2.20 eV may be due to the introduction of acceptors states near to valance band. Optical studies showed that refractive index was measured from 2.18 to 3.24 whereas thicknesses varied between 220 nm to 320 nm for un-doped and Cu doped ZnTe thin film respectively using Swanepoel model. The oxidation states of Zn⁺², Te⁺² and Cu⁺¹ through high resolution X-ray photoelectron spectroscopy (XPS) analyses was observed. The resistivity of thin films changed from ~10⁷ Ω-cm for undoped ZnTe to ~1 Ω-cm for Cu-doped ZnTe thin film, whereas p-type carrier concentration increased from to respectively. These results predicted that Cu-doped ZnTe thin film can be used as an ideal, efficient and stable intermediate layer between metallic and absorber back contact for the heterojunction thin film solar cell technology.