The current work reveals the fine tuning between stability zones and randomness of GI/M/1 Pointwise Stationary Fluid Flow Approximation (PSFFA) model of the non-stationary D/M/1 queueing system. More specifically, this clearly provides more insights into developing a contemporary PSFFA theory that unifies non-stationary queueing theory with chaos theory and fields in both theoretical physics and chaotic systems. This opens new grounds for stability analysis of non-stationary queueing systems. A notable application of GI/M/1 queueing model to achieve ultra-low latency of autonomous driving service is highlighted. Concluding remarks associated with future avenues of research are given.

An exposition is undertaken to reveal the significant impact of the time-dependent root parameter, on the stability of Pointwise Stationary Fluid Flow Approximation (PSFFA) model of the non-stationary queueing system. This opens new grounds to stability analysis of non-stationary queueing systems. Potential PSFFA applications of IoT are highlighted.

Positive recurrence for a single-server queueing system is established under generalised intensity conditions of service which does not assume existence of the density distribution function of service but a certain integral type lower bound as a sufficient condition. Positive recurrence implies existence of the invariant distribution and a guaranteed slow convergence to it in the total variation metric.

The preparation of transition metal salt ammine complexes having oxidizing anions is a great challenge due to the reaction between the ammonia and oxidizing anions during the synthesis of these materials. However, they have an important role in the development of new oxidants in organic chemistry and especially as precursors in the preparation of mixed metal oxides and alloys in controlled temperature thermal decomposition reactions. Therefore, the synthetic procedures to prepare the complexes of transition metal permanganate, pertechnetate, and perrhenate (VIIB group tetraoxometallates) salts with ammonia as ligand or co-ligand have been comprehensively reviewed. The available data about the structure and spectroscopic properties of these compounds, including the hydrogen bonds that act as redox reaction centers under their thermal decomposition are given and evaluated. Their thermal decomposition processes and products have been summarized. The available pieces of information about their role in organic oxidation reactions like the oxidation of benzyl alcohols, and regeneration of oxo-compounds from oximes and phenylhydrazones including the kinetics of these processes have also been collected.

The current work reports the upper bound of the state variable of the of the Pointwise Steady Fluid Flow Approximation (PSFFA) model of non-stationary M/Ek/1 queueing system.

Acid proteins capable of nucleating Ca2+ and displaying aggregation capacity play key roles in the formation of calcium carbonate biominerals. EF-hands are among the largest Ca2+-binding motif in proteins. Gad m 1, an Atlantic cod β-parvalbumin isoform, is a monomeric EF-hand protein that acts as a Ca2+ buffer in fish muscle and is able to form amyloids under acidic conditions. Since nucleating Ca2+ protein have a propensity to form extended β-strand structures, we wondered whether amyloid assemblies of a protein containing refolded EF-hand motifs were able to influence the in vitro calcium carbonate crystallization. Here we have used the Gad m 1 chain as model to generate monomeric and amyloid assemblies and analyze their effect on in vitro calcite formation. We found that only amyloid assemblies alter calcite morphology.

This research introduces a pioneering solution to the challenges posed by gastrointestinal tract (GI) cancer in radiation therapy, focusing on the imperative task of precise organ segmentation for minimizing radiation-induced damage. GI imaging has historically used manual demarcation, which is laborious and uncomfortable for patients. We address this by introducing the ResECA-U-Net deep learning model, a novel combination of the UNet and ResNet34 architectures. Furthermore, we further augment its functionality by incorporating the Efficient Channel Attention (ECA-Net) methodology. By utilizing data from the UW-Madison Carbone Cancer Centre, we carefully investigate several image processing techniques designed to capture critical local characteristics. With its foundation in computer vision concepts, the ResECA-U-Net model is excellent at extracting fine details from GI images. Sophisticated metrics such as intersection over union (IoU) and the dice coefficient are used to evaluate performance. Our study's outcomes demonstrate the effectiveness of the suggested method, yielding an impressive 96.27% Dice coefficient and 91.48% IoU. These results highlight the significant contribution that our strategy has made to the advancement of cancer therapy. Beyond its scientific merits, this work has the potential to significantly enhance cancer patients' quality of life and provide better long-term outcomes. Our work is a significant step towards automating and optimizing the segmentation process, which can potentially change how GI cancer is treated completely.

The current study characterizes the transient M/M/1 queue manifold info-geometrically, through devising Fisher Information matrix(FIM) and its inverse(IFIM). Additionally, the impact of stability on the existence of IFIM and explore the geodesic equations of motion has been revealed. More potentially, the paper discusses some info-geometric applications to Machine Learning are highlighted. Closing remarks with some challenging open problems combined with the next phase of research are given.

This paper provides a new discovery that adds to the contemporary theory of modelling of non-stationary queues, by capturing analytically the behavior of the root parameter, for the G1/M/1 PSFFA model of non-stationary Ek/M/1 queue. Additionally, it has been also revealed that the resulting root parameter reduces to the PSFFA model of non-stationary queue. Potential applications of PSFFA to Computer engineering are provided. Some challenging open problems are addressed combined with closing remarks and future research directions.

Titania is one of the most comprehensively studied nanostructures due to its widespread applications in production of catalytic, gas- sensing and corrosion- resistance materials [1]. M-polynomial of nanotubes has been vastly investigated as it produces many degree-based topological indices which are numerical parameters capturing structural and chemical properties. These indices are used in the development of quantitative structure-activity relationships (QSARs) in which the biological activity and other properties of molecules are correlated with their structure like boiling point, stability, strain energy etc of chemical compounds. In this paper, we determine M-polynomials of single-walled titanium (SW TiO2) nanotubes and recover important topological degree based indices of them to theoretically judge these nanotubes. We also use Maple to plot surfaces associated to different types of single-walled titanium (SW TiO2) nanotubes.

It has been discovered that representing odd integers as modified binary expressions of the form $\sum \limits_{n > m}2^n + 2^m - 1$ for $m \geq 1$ helps in understanding the dynamics of Collatz-type sequences. Starting with the original Collatz sequence $3x + 1$, it is found that when the odd step is applied to an odd integer $\sum \limits_{n > m}2^n + 2^m - 1$, an even integer $3\left(\sum \limits_{n > m}2^{n}\right) + 2^{m + 1} + 2^m - 2$ is obtained, which is exactly once divisible by 2, unless the lowest index reduces to zero. This implies that the sequence alternates between odd and even steps $m$ times. This governs the dynamics of the Collatz-type sequences because the value of $m$ determines the number of times the integer can be divided by 2 in each even step. A shortcut method is developed based on this dynamics that states that the even integer after $m$ odd-even steps are completed is $\left(\left(\frac{3}{2}\right)^m \sum \limits_{n > m}2^n\right) + 3^m - 1$. A shortcut method of this magnitude has never been utilized anywhere. The shortcut method for the modified Collatz sequence $5x + 1$ is also presented.

In this paper, we extend the KdVSKR equations in (1+1)-dimension and (2+1)-dimension to fractional KdVSKR equations with modified Riemann-Liouville derivative. The (2+1)-dimensional KdVSKR equation, which is a recent extension of (1+1)-dimensional KdVSKR equation, can model the resonances of solitons in shallow water. By means of the Hirota bilinear method, finite symmetry group method and consistent Riccati expansion method, many new interaction solutions have been derived. Soliton-cnoidal interaction solution of the (1+1)-dimensional fractional KdVSKR equation has been derived for the first time. For the (2+1)-dimensional frac-tional KdVSKR equation, two-wave interaction solutions and three-wave interaction solutions, including dark-soliton-sine interaction solution, bright-soliton-elliptic interaction solution, and lump-hyperbolic-sine interaction solution, have been derived. Impact of the fractional order on the shapes of these solutions has been illustrated by figures. Three-wave interaction solutions of fractional systems have not been reported in the existing references. The research idea in this paper can be applied to other fractional differential equations.

This paper investigates the search for an exact analytic solution to a temporal first-order differential equation that represents the number of customers in a non-stationary or time-varying

Abstract: As a low-input crop, Miscanthus offers numerous advantages that, in addition to agricultural applications, permits its exploitation for energy, fuel, and material production. Depending on the Miscanthus genotype, season, and harvest time as well as plant component (leaf versus stem), correlations between structure and properties of the corresponding isolated lignins differ. Here, a comparative study is presented between lignins isolated from M. x giganteus, M. sinensis, M. robustus and M. nagara using a catalyst-free organosolv pulping process. The lignins from different plant constituents are also compared regarding their similarities and differences regarding monolignol ratio and important linkages. Results showed that the plant genotype has the weakest influence on monolignol content and interunit linkages. In contrast, structural differences are more significant among lignins of different harvest time and/or season. Analyses were performed using fast and simple methods such as nuclear magnetic resonance (NMR) spectroscopy. Data was assigned to four different linkages (A: b-O-4 linkage, B: phenylcoumaran, C: resinol, D: b-unsaturated ester). In conclusion, A content is particularly high in leaf-derived lignins at just under 70 % and significantly lower in stem and mixture lignins at around 60 % and almost 65 %. The second most common linkage pattern is D in all isolated lignins, the proportion of which is also strongly dependent on the crop portion. Both stem and mixture lignins, have a relatively high share of approximately 20 % or more (maximum is M. sinensis Sin2 with over 30 %). In the leaf-derived lignins, the proportions are significantly lower on average. Stem samples should be chosen if the highest possible lignin content is desired, specifically from the M. x giganteus genotype, which revealed lignin contents up to 27 %. Due to the better frost resistance and higher stem stability, M. nagara offers some advantages compared to M. x giganteus. Miscanthus crops are shown to be very attractive lignocellulose feedstock (LCF) for second generation biorefineries and lignin generation in Europe.

In this work, an algorithm was developed to measure the respiration rate for an embedded device that can be used by a field robot for relief operation. With this algorithm, the rate measurement was calculated based on direct influences of respiratory-induced intensity variation (RIIV) on blood flow in cardiovascular pathways. For that, a photoplethysmogram (PPG) sensor was used to determine changes in heartbeat frequencies. The PPG sensor readings were filtered using an Information Filter and a Fast Fourier transform (FFT) to determine the state of RIIV. With a relatively light initialization, the information filter can estimate unknown variables based on a series of measurements containing noise and other inaccuraties. Therefore, this filter is suitable for application on an embedded device. For faster calculation time in the implementation, the FFT analysis was calculated only for a major peak in the frequency domain. Test and measurement of respiration rate was conducted based on the device algorithm and spirometer. Heartbeat measurement was also evaluated by comparing the heartbeat data of the PPG sensor and the medical tool kit. Based on the test, the implemented algorithm can measure respiration rate with about 80% accuracy compared with the spirometer.

Background/Objectives: Meconopsis has long been used in traditional Tibetan medicine to treat various diseases. However, blue-flowered Meconopsis (M. betonicifolia) is becoming increasingly scarce due to overharvesting. As a potential alternative, yellow-flowered Meconopsis (M. integrifolia) shows promise but requires comprehensive characterization. This study aimed to evaluate and compare the anti-inflammatory potential of yellow- and blue-flowered Meconopsis species. Methods: LC-MS was used to analyze the chemical profiles of yellow- and blue-flowered Meconopsis. Putative targets of shared constituents were subjected to GO and disease enrichment analysis. The LPS-induced RAW264.7 macrophage model was employed to assess anti-inflammatory effects. Metabolomics was applied to gain mechanistic insights. Results: LC-MS revealed over 70% chemical similarity between species. Enrichment analysis associated targets with inflammation-related pathways. In macrophage assays, both species demonstrated dose-dependent anti-oxidative and anti-inflammatory activities, with yellow Meconopsis exhibiting superior efficacy. Metabolomics showed modulation of key inflammatory metabolic pathways. Conclusions: This integrative study validated yellow-flowered Meconopsis as a credible alternative to its blue-flowered counterpart for anti-inflammatory applications. Metabolic profiling provided initial clues regarding their multi-targeted modes of action, highlighting clinical relevance and potential for sustainable utilization and biodiversity conservation.

Recently, various applications of indoor location-based services using Wi-Fi fingerprint data have been studied. However, since fingerprint data collected at a specific location does not have continuous information between signals and correlation information between signals, path data cannot exist in principle. Therefore, most indoor positioning technologies are based on predicting the position of a stationary positioner at a specific location based on signal data collected at a specific location in the indoor space. Due to the discontinuous nature of these signals, they are unable to account for user movement. Therefore, there is a need for techniques to improve the accuracy of indoor positioning in moving situations. This paper proposes a method for enriching all data points with relevant information to obtain improved indoor positioning results and an improved technique for generating movement path data. The proposed technique generates relevant information with continuity by expressing data points as Bounding Boxes (BB) and subsequently clustering them using grid cells. Through the proposed method, we represented and expanded the indoor location data, which consists of data points, as BB. However, data points represented by BB do not have any adjacency information with each other, and as a result, it is not possible to create a movement path between neighboring BB. To solve the problem, we used clustering, a machine learning technique that categorizes data points into groups, to group BBs. This was done by constructing a YOLO (You Only Look Once) grid cell that included all BBs and clustered them into grid cells that were divided into specific regions through the suggestion phase. The clustering results align with the indoor structure of the building, indicating that the data points have been appropriately clustered. BBs inside a grid cell are contained within a moveable area and have related information. We also generated association information between neighboring grid cells through the proposal technique, and then generated path information that can be traveled between grid cells. In this paper, we use the movement path information generated from a dataset as training data for machine learning, and through this, we propose an enhanced indoor positioning technology.

From a differential geometric perspective, information geometry (IG) aims to characterise the structure of statistical geodesic models. The research done for this paper offers a novel method for modelling the information geometry of a queuing system. From the perspective of IG, the manifold of the transient M/M/infinity queue is described in this context. The Fisher Information matrix (FIM) as well as the inverse of (FIM), (IFIM) of transient M/M/infinity QM are devised. In addition to that, new results that uncovered the significant impact of stability of QM on the existence of (IFIM) are obtained. Moreover, the Geodesic equations of motion of the coordinates of the underlying transient are obtained. Also, it is revealed that stable QM is developable (i.e., has a zero Gaussian curvature) and has a non-zero Ricci Curvature Tensor (RCT). Novel stability dynamics of transient M/M/iInfinity queue manifold is revealed by discovering the mutual dual impact between the behaviour of (RCT) and the stability(instability) phases of M/M/Infinity QM. Furthermore, a new discovery that presents the significant impact of stability of queue manifold and the continuity of the unique representation between M/G/1 queue manifold and Ricci Curvature Tensor (RCT). The information matrix exponential (IME) is devised. Also, it is shown that stability of the devised (IME) enforces the instability of M/M/ Infinity QM. More interestingly, novel relativistic info-geometric queueing theoretic links are revealed .

Seven patients in our clinical program who were diagnosed with high burden (>10%) premature ventricular contractions (PVCs) and concomitant significant upper GI disease with no other significant cardiac history demonstrated a significant reduction in the burden of PVCs following surgical or procedural interventions of the upper GI tract [68.34% reduction, p=0.024). Furthermore, in all cases, the origin of the PVCs was from the base of the right ventricular outflow tract (RVOT). This is the first report in the literature that we are aware of to report this unique association for which we propose a dual mechanism of action of vagally mediated upper GI driven PVCs and a direct anatomical effect of these upper GI anatomies on the right ventricular outflow tract (RVOT) of the heart. These are very prelimary findings that warrant larger clinical and mechanistic studies that may ultimately define a new subset of PVCs for which we propose a term, “E-PVCs”.

A new set of basis functions is presented. The foundation in mathematics is established. To reconstruct a signal, it is compared to the Fourier basis functions. The M-basis functions' potential applications are also presented.

In South Korea, demolition waste (DW) management has become increasingly significant owing to the rising number of old buildings. Effective DW management requires an efficient approach that accurately quantifies and predicts the generation of DW (DWG) of various types, which necessitates access to the required information or technology capable of achieving this. Hence, we developed an artificial intelligence-based model that predicts the generation of ten DW types, specifically from buildings in redevelopment areas. We used an artificial neural network algorithm with < 10 neurons in the hidden layer to derive individual input variables and optimal hyperparameters for each DW type. All DWG prediction models achieved an average validation and test prediction performance (R²) of 0.970 and 0.952, respectively, with their ratios of percent deviation ≥ 2.5, ver-ifying them as excellent models. Moreover, a Shapley additive explanations analysis revealed that DWG was most impacted by the floor area for all the DW types, with a positive correlation with DWG. Conversely, other factors showed either a positive or negative correlation with DWG de-pending on the DW type. The study findings will enable demolition companies and local gov-ernments in making informed decisions for efficient DW management and resource allocation by accurately predicting the generation of various types of DW.

A surgical microscope is large in size, which makes it impossible to be portable. The distance between the surgical microscope and the observation tissue is 15–30 cm, and the adjustment range of the right and left of the camera is a maximum of 30°. Therefore, the surgical microscope is generated attenuation (above 58%) of irradiation optical source owing to the long working distance. Moreover, the observation of tissue is affected because of dazzling by ambient light as the optical source power is strong (55 to 160 mW/cm2). Further, observation blind spot phenomena will occur due to the limitations in adjusting the right and left of the camera. Therefore, it is difficult to clearly observe the tumor. In this study, a compact pen-type probe with a portable surgical microscope is presented. The proposed surgical microscope comprises a small and portable pen-type probe that can adjust the working distance between the probe and the observed tissue. In addition, it allows the adjustment of the viewing angle and fluorescence brightness. The proposed probe has no blind spots or optical density loss.

A surgical microscope is large in size, making portability impossible. The distance between the surgical microscope and the observation tissue is 15 to 30 cm, while the maximum adjustment range of the camera to the right and left is 30°. Therefore, surgical microscopes cause attenuation (above 58%) of the irradiation optical source owing to the long working distance. Moreover, the observation of tissue was dazzled with ambient light because the optical power source was strong (50 to 160 mW/cm2). Owing to the limited ability to adjust the camera to the right and left, a blind spot occurs with a surgical microscope. Therefore, it is difficult to clearly observe a tumor. In this study, a compact pen-type probe with a portable surgical microscope is proposed. The pen-type probe is small with a portable shape, and is capable of adjusting the working distance between itself and the observed tissue. It is also possible to adjust the viewing angle and fluorescence brightness. The proposed pen-type probe has no blind spots or optical density loss.

Present-day lifestyle associated with high calorie-fat intake and accumulation, as well as energy imbalance, has led to the development of obesity and its comorbidities, which have emerged as some of the major health issues globally. To combat the disease, many studies have reported the anti-obesity effects of natural compounds in foods, with some advantages over chemical treatments. Carotenoids, particularly xanthophyll derived from seaweeds, have attracted the attention of researchers due to their notable biological activities, which are associated mainly with their antioxidant properties. Their involvement in oxidative stress modulation, regulation of major transcription factors and enzymes as well as their antagonistic effects on various obesity parameters have been examined in both in-vitro and in-vivo studies. The present review is a collation of published research over the last decade on the anti-oxidant properties of seaweed xanthophyll carotenoids, with a focus on fucoxanthin and astaxanthin and their mechanisms of action in obesity prevention and treatment.

Obesity is a condition associated with the accumulation of excess fat in the body, energy imbalance, lipogenesis etc. which increases adipose tissue mass through adipogenesis and probes a health risk. Its prevalence has become a large burden on the world at large. One of the solutions to tackling obesity is with the use of bioactive compounds. We critically examined the effectiveness of hibiscus sabdariffa (HS) on various parameters associated with development of obesity such as; effect of HSE on body weight and energy expenditure, effect of HSE on fat accumulation, effect of HSE on lipase inhibition, effect of HSE on adipocyte differentiation/adipogenesis. This review has gathered reports on the various anti-obesity effects of HS bioactives in cell and animal models, as well as in humans. Reports have shown that hibiscus sabdariffa derived bioactives are potent in the treatment of obesity with evident reduction in body weight, inhibition of lipid accumulation and suppression of adipogenesis through PPARγ pathway and other transcriptional factors.

This study aimed to investigate the effects of lupin flake supplementation on the growth, plasma parameters, carcass characteristics, and meat composition of late-fattening Hanwoo steers. The steers (n = 40) were randomly divided into the four groups with 10 steers each: LP0 (Lupin flake 0%), LP3 (lupin flake 3%), LP6 (Lupin flake 6%), and LP9 (lupin flake 9%). The total digestible nutriant intake increased as the concentration of lupin increased (linear and quadratic effects; P &lt; 0.05). The thiobarbituric acid-reactive substance content in the strip loins decreased as lupin flake supplementation levels increased (linear and quadratic effects; P &lt; 0.05), while carnosine levels increased linearly (P &lt; 0.05). As the lupin flake supplementation level increased, anserine and creatinine contents increased linearly and quadratically (P &lt; 0.05). Similarly, adenosine triphosphate (ATP) and adenosine monophosphate (AMP) contents increased with increasing lupin flake supplementation levels in linear and quadratic effects (P &lt; 0.001). Palmitoleic acid content increased significantly with increasing lupin flake supplementation level (linear and quadratic effects; P &lt; 0.05). The content of oleic acid in the strip loin was not significant, but the unsaturated fatty acid (UFA) (P &lt; 0.05) and n-6/n-3 ratio (P &lt; 0.05) increased. The results of this study indicated that although lupin flake supplementation did not markedly affect the growth, carcass characteristics, or meat composition of late-fattening Hanwoo steers, it exerted a positive effect on the flavor, taste profiles (anserine, creatinine, ATP, and AMP), hypotonicity(TBARS), and healthy meat production (UFA and n-6/n-3 ratio) related to beef.

Background. Transferrin receptor 1 (TfR1), glucose transporter 1 (GLUT1), and CD98hc are candidates for targeted therapy at the blood-brain barrier (BBB). Our objective was to challenge the expression of TfR1, GLUT1, and CD98hc in brain capillaries by the histone deacetylase inhibitor (HDACi) valproic acid (VPA). Methods. Primary mouse brain capillary endothelial cells (BCECs) and brain capillaries isolated from mice injected intraperitoneally with VPA were examined using RT-qPCR and ELISA. Targeting to the BBB was performed by injecting monoclonal anti-TfR1 (Ri7217)-conjugated gold nanoparticles measured using ICP-MS. Results. In BCECs co-cultured with glial cells, Tfrc mRNA expression was significantly higher after 6 h VPA returning to baseline after 24 h. In vivo Glut1 mRNA expression was significantly higher in males, but not females', receiving VPA, whereas Cd98hc mRNA expression was unaffected by VPA. TfR1 increased significantly in vivo after VPA, whereas GLUT1 and CD98hc were unchanged. Uptake of anti-TfR1-conjugated nanoparticles was unaltered by VPA in spite upregulated TfR expression. Conclusions. VPA upregulates TfR1 in brain endothelium in vivo and in vitro. VPA does not increase GLUT1 and CD98hc proteins. The increase in TfR1 does not result in higher anti-TfR1 antibody targetability, suggesting targeting sufficiently occurs with available transferrin receptors without further contribution from accessory VPA-induced TfR1.

We report on the occurrence of natural Magnesium Alumina Silicate Hydrate (M-(A)-S-H) cement at Feragen and Leka in eastern and western Trøndelag Norway, respectively. Both occurrences are located in the sub-arctic climate zone and form in glacial till and moraine material deposited on ultramafic rock during the Weichselian glaciation. Weathering of serpentinized peridotite dissolve brucite and result in a relative high pH alkaline fluid that subsequently reacts with the felsic minerals of the till (quartz, plagioclase, K-feldspar) to form a cement consisting of an amorphous material or a mixture of nanocrystalline Mg-rich phyllosilicates, including illite. The presence of plagioclase in the till results in the enrichment of alumina in the cement, i.e., forms M-A-S-H instead of the M-S-H cement. Dissolution of quartz results in numerous etch-pits and negative quartz crystals filled with M-A-S-H cement. Where the quartz dissolution is faster that the cement precipitation, a honeycomb-like texture is formed. Compositionally the cemented till (tillite) contains more MgO and has a higher loss of ignition than the till, suggesting that the cement is formed by a MgO fluid that previously reacted with the peridotite. The M-(A)-S-H cemented till represent a new type of duricrust, coined magsilcrete. The study of natural Mg-cement provides information on peridotites as a Mg-source for Mg-cement and as a feedstock for CO2 sequestration.

The misuse of antibiotics during the last decades led to the emergence of multidrug resistant pathogenic bacteria. This phenomenon constitutes a major public health issue. Consequently, the discovery of new antibacterials in the short term is crucial. Colicins, due to their antibacterial properties, thus constitute good candidates. These toxin proteins, produced by E. coli to kill enteric relative competitors, exhibit cytotoxicity through ionophoric activity or essential macromolecule degradation. Among the 25-colicin types known to date, colicin M (ColM) is the only one colicin interfering with peptidoglycan biosynthesis. Accordingly, ColM develops its lethal activity in E. coli periplasm by hydrolyzing the last peptidoglycan precursor, lipid II, into two dead-end products, thereby leading to cell lysis. Since the discovery of its unusual mode of action, several ColM orthologs have also been identified based on sequence alignments; all of the characterized ColM-like proteins display the same enzymatic activity of lipid II degradation and narrow antibacterial spectra. This publication aims at being an exhaustive review about what is currently known on this new family of antibacterial enzymes as well as on their potential use of food preservatives or therapeutic agents.

Background: This study aimed to examine the obesity¬ stress, weight control behavior, and self-control in overweight and obese female university students, and identify the mediating effect of self-control in the relationship between obesity stress and weight control behavior. Methods: This study employed a descriptive correlational design. A total of 109 female university students who were overweight and obese participated in the study. Data were analyzed using descriptive statistics, Pearson's correlation coefficient analysis, and Bootstrapping using Hayes' PROCESS macro for mediation. Results: Significant relationships between obesity stress and weight control behavior (r=0.25, p<0.001), obesity stress and self-control (r=-0.36, p<0.001), and weight control behavior and self-control (r=.26, p<.001) were observed. Self-control showed indirect mediating effect on the relationship between obesity stress and weight control behavior. Conclusion: Therefore, development of programs and strategies for improving self-control is necessary in order to decrease obesity among female university students.

Lifestyle interventions can prevent type 2 diabetes (T2DM). However, some in-dividuals do not experience anticipated improvements despite weight loss. Bi-omarkers to identify such individuals at early stages are lacking. IGF-1 and IGFBP-1 were shown to predict T2DM onset in prediabetes. We assessed if these markers also predict the success of lifestyle interventions, thereby possibly guid-ing personalized strategies. We analyzed fasting serum levels of IGF-1, IGFBP-1 and IGFBP-2 in relation to changes in metabolic and anthropometric parameters, including intrahepatic li-pids (IHL) and visceral adipose tissue (VAT) volume measured by MRI, in 345 high-risk prediabetic participants (54% female; aged 36-80 years). Participants were enrolled in three randomized dietary intervention trials and assessed both at baseline and one year post-intervention. Statistical analyses were performed using IBM SPSS Statistics (version 28), significance set at p

Heavy metals have adverse effects on microalgae growth and metabolism. Photosynthesis and lipid profile are quite sensitive to heavy metal toxicity. The impact of chromium (Cr) on growth and photosynthetic activity of Dictyosphaerium pulchellum and Micractinium pusillum exposed to different concentrations (0 – 500 μg L-1) was investigated for 11 days. The influence of Cr on cell density and cell number followed similar trends, indicating a possible correlation among these growth responses. A significant (p &lt; 0.05) increase in lipid content was observed with the increasing concentration of Cr however, growth was suppressed at higher concentrations exceeding 100 μg L-1. Addition of Cr in the cell culture medium showed a negative effect on quantum yield (Fv/Fm) and a photosynthetic inhibition of &gt; 65% was noted in both species at 500 μg L-1. However, the lipid gravimetric analysis presented inner cell lipid content up to 36% and 30% of dry weight biomass for D. pulchellum and M. pusillum, respectively. The effects of chromium on growth and lipid accumulation in both microalgae species was concentration and exposure time dependent. This shows that an appropriate concentration of chromium in culture medium could be beneficial for higher lipid accumulation in freshwater eukaryotic microalgae species.

Hepatitis B surface antigen (HBsAg) is not only the biomarker of hepatitis B virus (HBV) infection and expression activity in hepatocytes, but also contributes to viral specific T cell exhaustion and HBV persistent infection. Therefore, anti-HBV therapies targeting HBsAg to achieve HBsAg loss are key approaches for HBV functional cure. In this study, we found that YZH-106, a rupestonic acid derivative, inhibited HBsAg secretion and viral replication. Further investigation demonstrated that YZH-106 promoted the lysosomal degradation of viral L- and M-HBs proteins. Mechanistic study by Biacore and docking analysis revealed that YZH-106 bound directly to PreS2 domain of L- and M-HBsAg, thereby blocking their entry to the endoplasmic reticulum (ER) and promoting their degradation in cytoplasm. Our work thereby provide basis for design of novel compound therapy to target HBsAg against HBV infection.

This article presents a novel analysis of Indus Seal M-282 [1] excavated from Mohenjo-Daro, a key Indus Valley Civilization site. Utilizing the proposed Sindhu Prakrit alphabet, the study investigates the relationship between the seal's iconography and the inscribed text. By examining the potential for a close correlation between these elements, the analysis aims to decipher the meaning embedded within the seal's motifs, potentially offering new insights into Indus Valley communication and symbolism.

Astroviruses (AstVs) have been detected in a wide range of animal species, including mammals and birds. Recently, a novel AstVs associated with neurological symptoms has been detected in the brain of some mammals. Raccoon dog AstV has been reported recently in China. However, there have been no reports in South Korea. Therefore, the present study aimed to detect and genetically characterize AstVs in intestine and brain tissues of 133 wild raccoon dogs collected in Korea between 2017 and 2019. Seven wild raccoon dogs were positive for AstV, four of which were also detected in brain tissue. Analysis of the capsid protein amino acid sequences of raccoon dog AstVs detected in Korea revealed a high similarity to canine AstVs, suggesting possible interspecies transmission between raccoon dogs and dogs. Phylogenetic and capsid protein amino acid sequence analysis of raccoon dog AstVs detected in brain 17-148B strain belonged to the HMO clade and exhibited conserved sequences found in neurotropic AstVs (NT-AstVs), indicating their potential as NT-AstVs. However, the pathogenicity and transmission routes of the raccoon dog AstV detected in Korea have not yet been elucidated, so further research and continued surveillance for AstV in wild raccoon dogs are needed.

Hepatocellular carcinoma (HCC), one of the leading causes of death worldwide, has a causal nexus with liver injury, inflammation, and regeneration that accumulate over decades. Observations from recent studies have accounted for the involvement of the gut-liver axis in the pathophysiological mechanism responsible for HCC. The human intestine nurtures a diversified colony of microorganisms residing in the host ecosystem. The intestinal barrier is critical for conserving the normal physiology of the gut microbiome. Therefore, a rupture of this barrier or dysbiosis cause the intestinal microbiome to serve as the main source of portal-vein endotoxins such as lipopolysaccharide, in the progression of hepatic diseases. Indeed, increased bacterial translocation is a key sign of HCC. Considering the limited number of clinical studies on HCC with respect to the microbiome, we focus on the clinical as well as animal studies involving the gut microbiota with the current understandings of the mechanism by which the intestinal dysbiosis promotes hepatocarcinogenesis. Future research might offer mechanistic insights into the specific phyla targeting the leaky gut, as well as microbial dysbiosis, and their metabolites, as key pathways that drive HCC-promoting microbiome-mediated liver inflammation and fibrosis, thereby restoring the gut barrier function.

Ras homolog enriched in brain (Rheb1 and Rheb2), a small GTPase, regulates neuronal activity and has drawn attention for its implications in cancer development, especially breast cancer. This study explores the multifaceted role of Rheb1 in cancer, elucidating its involvement in crucial cel-lular processes such as proliferation, apoptosis resistance, migration, invasion, metastasis, and inflammatory responses. Despite these acknowledged connections, a comprehensive understanding of the intricate interplay between Rheb1 and cancer remains elusive. This review consolidates cur-rent knowledge on the impact of Rheb1 on cancer hallmarks and examines the potential of Rheb1 as a therapeutic target in cancer treatment. The review underscores the need for a more profound comprehension of the molecular mechanisms underlying Rheb1-mediated oncogenic processes. Furthermore, the review emphasizes the exploration of Rheb1 inhibitors as a promising avenue for cancer therapy. This study, by bringing to light the complex associations between Rheb1/Rheb2 and cancer, delivers valuable insights to the scientific community. These insights are instrumental in guiding the identification of novel targets and advancing the development of effective therapeu-tic strategies for treating cancer.

Wildfires present a significant risk to societies globally due to population growth, con- centrated activities, climate change, and extreme environmental conditions. To establish effective fire suppression and management policies, it is crucial to determine whether the distance between ignition points and urban areas is increasing or decreasing. This study analyses 101,597 fires in Spain and California between 2007 and 2015, using the Mann-Kendall test to determine trends. The study analyses the location and cause of fires to determine their distance from human constructions over time at two spatial scales. The findings suggest that wildfires are not moving away from buildings and, in some areas, are moving significantly closer.

Background: Amyloid beta peptides (Aβ) have been identified as the main pathogenic agents in Alzheimer’s disease (AD). Soluble Aβ oligomers, rather than monomer or insoluble amyloid fibrils, show membrane-binding capacity to red blood cells (RBCs) and trigger several morphological and functional alterations in RBCs that can result in impaired oxygen transport and delivery. Since bioactive lipids have been recently proposed as potent protective agents against Aβ toxicity, we investigated the role of sphingosine-1-phosphate (S1P) in signaling pathways involved in the mechanism underlying ATP release in Aβ-treated RBCs. Methods: In RBCs following different treatments, ATP, 2,3 DPG, cAMP levels, and caspase 3 activity were determined by spectrophotometric and immunoassay. Results: S1P rescued the inhibition of ATP release from RBCs triggered by Aβ through a mechanism involving caspase-3 and restoring 2,3 DPG and cAMP levels within the cell. Conclusions: These findings reveal the molecular basis of S1P protection against Aβ in RBCs and suggest new therapeutic avenues in AD.

Cathepsin D (CatD; EC 3.4.23.5) family peptidases of parasitic organisms are regarded as potential drug targets as they play critical roles in the physiology and pathobiology of parasites. Previously, we characterized the biochemical features of cathepsin D isozyme 2 (CatD2) in the carcinogenic liver fluke Clonorchis sinensis (CsCatD2). In this study, we performed all-atomic molecular dynamics simulations by applying different systems for the ligand-free/bound forms under neutral and acidic conditions to investigate the pH-dependent structural alterations and associated functional changes in CsCatD2. CsCatD2 showed several distinctive characteristics as follows: 1) CsCatD2-inhibitor complex formed more hydrogen bonds; 2) acidic pH caused major conformational transitions from open to closed state in this enzyme; 3) neutral pH induced displacement of the N-terminal part to hinder the accessibility of the active site and open allosteric site of this enzyme; and 4) the flap dynamics metrics, including distance (d1), TriCα angles (θ1 and θ2), and dihedral angle (ϕ), account for the asymmetrical twisting motion of the active site of this enzyme. These findings provide an in-depth understanding of the pH-dependent structural dynamics of CsCatD2 and basic information for the rational design of an inhibitor as a drug targeting CsCatD2.

The effectiveness of a hybrid technique for identifying seismic damage in planar, multistory, steel X or V-braced frames is demonstrated here through an example of a six-story frame. This proposed technique, referred to as “M and P”, combines the instrumental Monitoring (M) with Pushover analysis (P). According to the methodology, the diagram of stepping eigenfrequencies of the frame in the inelastic region is initially plotted against seismic roof displacement. The fundamental natural frequency detected via the monitoring process is then utilized in this key diagram to reveal the inelastic roof displacement that corresponds to the damage state of the steel braced frame. This displacement is subsequently used as the target in the pushover analysis, facilitating the identification of seismic damage in the existing steel braced frame. Finally, the damage image is correlated with the damage stiffness matrix of the frame at the same inelastic roof displacement. The investigation results indicate that combining instrumental monitoring with pushover analysis enables accurate identification of seismic damage potential in existing steel braced frames.

A new heterocyclic compound, 2-(2,6-diisopropylphenyl)-1-methylimidazo[1,5-a]quinolin-2-ium tetrafluoroborate 1 was obtained from its precursor, N-(2,6-diisopropylphenyl)-N-(quinolin-2-ylmethyl)acetamide 2, by POCl3-mediated cyclization. For the first time – the tertiary acetamide 2, precursor of 1, was synthesized by using commercially available starting materials. The structure of 1 was unquestionably confirmed by 1H-, 13C-, 2D-NMR-, IR- spectroscopy and mass-spectrometry. Its optical properties were also studied.

The World Health Organization(WHO) in 2016 considered mHealth as: “the use of mobile wireless technologies including smart devices such as smartphones and smartwatches for public health” as an important resource for health services delivery and public health given their ease of use, broad reach and acceptance. WHO emphasizes the potential of this technology to increase access to health information, services and skills as well as promoting positive changes in health behaviors and management of diseases. In this regard, the capability of smartphones and smartwatches for m-health monitoring as well as verification of the patient the signal has become an important component of mHealth system. Most of the smartwatches could extract more than one bioelectrical signal therefore, therefore they provide suitable platform for extracting health data for e-monitoring. The existing approaches have not considered the integrity of data obtained from these smart devices. Therefore, it is important that the integrity of the collected data be verified continuously through user authentication. This could be done using any of the bioelectrical signals extracted and transmitted for e-monitoring. In this article, a smartwatch is used for extracting bioelectrical signal before decomposing the signal into sub-bands of Detail and Approximation Coefficient for user authentication. To select suitable features using biorthogonal wavelet decomposition of signal from a non-intrusive extraction, a detailed experiment is conducted extracting suitable statistical features from the bioelectrical signal from 30 subjects using different biorthogonal wavelet family. Ten features are extracted using Biorthogonal wavelet to decompose the signal into three levels of sub-band Detail and Approximation Coefficient and features extracted from each level the decomposed Detail and Approximation Coefficients. Comparison analysis is done after the classification of the extracted features based on the Equal Error Rate (EER). Using Neural Network (NN) classifier, Biorthogonal Wavelet Detail Coefficient Sub-band level 3 of bior1.1 achieved the best result of EER 13.80% with the fusion of the best sub-band three levels of bior1.1 achieving a better result of 12.42% EER.

Let R be a commutative ring with identity and m, n be positive integers. In this paper, we introduce the class of (m,n)-prime ideals which lies properly between the classes of prime and (m,n)-closed ideals. A proper ideal I of R is called (m,n)-prime if for a,b∈R, a^{m}b∈I implies either aⁿ∈I or b∈I. Several characterizations of this new class with many examples are given. Analougus to primary decomposition, we define the (m,n)-decomposition of ideals and show that every ideal in an n-Noetherian ring has an (m,n)-decomposition. Furthermore, the (m,n)-prime avoidance theorem is proved.

We report on metastable defects introduced in n-type 4H-SiC material by epithermal and fast neutron irradiation. The epithermal and fast neutron irradiation defects in 4H-SiC are much less explored compared to electron or proton irradiation induced defects. In addition to silicon vacancy (Vsi) and carbon antisite-carbon vacancy (CAV) complex, the neutron irradiation has introduced four deep level defects, all arising from the metastable defect, the M-center. The metastable deep level defects were investigated by deep level transient spectroscopy (DLTS), high-resolution Laplace DLTS (L-DLTS) and isothermal DLTS. The existence of the fourth deep level M4, recently observed in ion implanted 4H-SiC, has been additionally confirmed in neutron irradiated samples. The isothermal DLTS technique has been proven as a useful tool for studying the metastable defects.

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.

Despite the effectiveness of insulin injections in managing hyperglycemia in Type 1 Diabetes, they fall short in addressing autoimmunity and regenerating damaged islets. This review aims to explore the potential of various treatment modalities for T1DM, including mesenchymal stem cells (MSCs), MSC-derived exosomes, gene therapy, islet allotransplantation, and pancreatic islet cell transplantation. Results: MSCs demonstrate efficacy in T1DM treatment through immunomodulation and tissue regeneration, although further research is warranted to optimize their therapeutic potential. Gene therapy presents a promising approach despite challenges such as donor shortage and immune rejection. Pancreatic islet cell transplantation emerges as a viable option, albeit with associated risks including graft rejection and the need for immunosuppression. Teplizumab, an FDA-approved humanized monoclonal antibody, revolutionizes the treatment landscape of Type 1 Diabetes by significantly delaying its onset, offering a paradigm shift since the discovery of insulin Conclusion: Ongoing studies and technological advancements in T1DM management offer a promising outlook for improved treatments and possibly even eradication on a global scale. MSCs, MSC-derived exosomes, gene therapy, and pancreatic islet transplantation hold considerable potential.

Pulmonary infections with Mycobacterium avium occur in susceptible individuals following exposure to the bacterium in the environment, where it often persists in biofilms. Many methods have been used to generate biofilms of M. avium, and it is unknown whether different approaches generate similar structures and cell phenotypes. To make a parallel comparison of in vitro biofilm ultrastructure, extracellular matrix (ECM) composition, and drug susceptibility of biofilm resident bacteria, we used two published methods to generate M. avium biofilms: four week incubation in M63 medium or 24 hour exposure to dithiothreitol (DTT). Scanning electron microscopy revealed differences in biofilm ultrastructure between the two methods, including variation in appearance of ECM materials and morphology of resident cells, while light microscopy and staining with calcofluor white indicated that both biofilms contained polysaccharides characteristic of cellulose. Measuring susceptibility of biofilms to degradation by enzymes suggested differences in structurally important ECM molecules, with DTT biofilms having important protein and, to a lesser extent, cellulose components, and M63 biofilms having moderate protein, cellulose, and DNA components. Both biofilms conferred resistance to the bactericidal effects of amikacin and clarithromycin, with resident cells being killed at &gt;10-fold lower rates than planktonic cells at almost all concentrations. Though these comparisons indicate differences in biofilm responses by M. avium under differing conditions, they also suggest common features of biofilm formation including cellulose production and antimicrobial resistance.

The topological index is a numerical quantity based on the characteristics of various invariants or molecular graph. For ease of discussion, these indices are classified according to their logical derivation from topological invariants rather than their temporal development. Degree based topological indices depends upon the degree of vertices. This paper computes degree based topological indices of Bismuth Tri-Iodide chains and sheets with the help of M-polynomial.

The objectives of the study were to determine the spatial rate of CO₂ flux (Net Ecosystem Exchange) and soil moisture in a wetland ecosystem applying Sentinel-1 IW (Interferometric Wide) data of VH (Vertical Transmit/Horizontal Receive—cross polarization) and VV (Vertical Transmit/Vertical Receive—like polarization) polarization. In-situ measurements of carbon flux, soil moisture, and LAI (Leaf Area Index) were carried out over the Biebrza Wetland in north-eastern Poland. The impact of soil moisture and LAI on backscattering coefficient (σ°) calculated from Sentinel-1 data showed that LAI dominates the influence on σ° when soil moisture is low. The models for soil moisture have been derived for wetland vegetation habitat types applying VH polarization (R² = 0.70 to 0.76). The vegetation habitats: reeds, sedge-moss, sedges, grass-herbs, and grass were classified using combined one Landsat 8 OLI (Operational Land Imager) and three TerraSAR-X (TSX) ScanSAR VV data. The model for the assessment of Net Ecosystem Exchange (NEE) has been developed based on the assumption that soil moisture and biomass represented by LAI have an influence on it. The σ° VH and σ° VV describe soil moisture and LAI, and have been the input to the NEE model. The model, created for classified habitats, is as follows: NEE = f (σ° Sentinel-1 VH, σ° Sentinel-1 VV). Reasonably good predictions of NEE have been achieved for classified habitats (R² = 0.51 to 0.58). The developed model has been used for mapping spatial and temporal distribution of NEE over Biebrza wetland habitat types. Eventually, emissions of CO₂ to the atmosphere (NEE positive) has been noted when soil moisture (SM) and biomass were low. This study demonstrates the importance of the capability of Sentinel-1 microwave data to calculate soil moisture and estimate NEE with all-weather acquisition conditions, offering an important advantage for frequent wetlands monitoring.

A suitable waste management strategy is crucial for a sustainable and efficient circular economy in the construction sector, and requires precise data on the volume of demolition waste (DW) gen-erated. Therefore, we developed an optimal machine learning (ML) model to forecast the quantity of recycling and landfill waste based on the characteristics of DW. A dataset comprising infor-mation on the characteristics of 150 buildings, demolition equipment utilized, and volume of five waste types generated (i.e., recyclable mineral, recyclable combustible, landfill specified, and landfill mix waste, and recyclable minerals) was constructed. ML models were developed to predict the quantities of such waste. Artificial neural network, decision tree, gradient boosting machine, k-nearest neighbors, linear regression, random forest (RF), and support vector regression were applied, and optimal models were derived via hyperparameter tuning. The RF model demonstrated superior performance. In both validation and test phases, the “recyclable mineral waste” and “recyclable combustible waste” models achieved accuracies of of 0.987 and 0.972, re-spectively. The “recyclable metals” and “landfill specified waste” models achieved accuracies of 0.953 and 0.858 or higher, respectively. Moreover, the “landfill mix waste” model exhibited an accuracy of 0.984 or higher. SHapley Additive exPlanations analysis highlighted floor area as the primary input variable influencing model performance. The type of equipment employed in demolition emerged as another crucial input variable impacting the volume of recycling and landfill wastes generated. The developed model can provide precise data on waste management, thereby facilitating the decision-making process for industry professionals.

This paper presents a system for identification of wind features, such as gusts and wind shear. These are of particular interest in the context of energy-efficient navigation of Small Unmanned Aerial Systems (UAS). The proposed system generates real-time wind vector estimates and a novel algorithm to generate wind field predictions. Estimations are based on the integration of an off-the-shelf navigation system and airspeed readings in a so-called direct approach. Wind predictions use atmospheric models to characterize the wind field with different statistical analyses. During the prediction stage, the system is able to incorporate, in a big-data approach, wind measurements from previous flights in order to enhance the approximations. Wind estimates are classified and fitted into a Weibull probability density function. A Genetic Algorithm (GA) is utilized to determine the shaping and scale parameters of the distribution, which are employed to determine the most probable wind speed at a certain position. The system uses this information to characterize a wind shear or a discrete gust and also utilizes a Gaussian Process regression to characterize continuous gusts. The knowledge of the wind features is crucial for computing energy-efficient trajectories with low cost and payload. Therefore, the system provides a solution that does not require any additional sensors. The system architecture presents a modular decentralized approach, in which the main parts of the system are separated in modules and the exchange of information is managed by a communication handler to enhance upgradeability and maintainability. Validation is done providing preliminary results of both simulations and Software-In-The-Loop testing. Telemetry data collected from real flights, performed in the Seville Metropolitan Area in Andalusia (Spain), was used for testing. Results show that wind estimation and predictions can be calculated at 1 Hz and a wind map can be updated at 0.4 Hz. Predictions show a convergence time with a 95% confidence interval of approximately 30 s.

Background This study aimed to identify the prominent risk factors that may trigger danger signals of early onset of vascular deregulation in T1D. The risk factors we have identified may serve as dual-purpose biomarkers of rapid diagnosis that offer prospective tailor-made resolution therapeutics. Methods The healthy control (HC) was compared with individuals diagnosed with T1D for the risk factors of vascular deregulation in published research studies from year 2013 to 2023. The PubMed, Web of Science and Google Scholar databases were searched from 1/1/2013 to 1/9/2023. The risk of bias was assessed with the Cochrane (ROBINS-I ) tool, which is relevant to clinical subjects. A random effect model for continuous data was followed and analysed by RevMan 5.4 and GraphPad Prism software. Results 80 relevant case-control studies having 5293 HC and 7492 T1D patients were included. The age and sex-matched HC consisted of persons free of disease and not under any medication while clinical subjects of all age groups were included. 28 risk factors were grouped into six primary outcome models, all of which favoured the T1D synonymous with a high risk of CVD. Conclusions Our findings have strong implications for improving the quality of life and health economics related to vascular disease in T1D. HbA1c% is the most effective biomarker, followed by FBG, LDL-C, and AI% which the clinicians could evaluate using a simple blood test or non-invasive techniques. (Protocol registered at https://www.crd.york.ac.uk/prospero/ CRD42022384636).

A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development. In this study, miR-1 potential role in early cardiac chamber differentiation is analyzed through specific signaling pathways. For this, we performed in chick embryos functional experiments by means of miR-1 microinjections into the posterior cardiac precursors -of both primitive endocardial tubes- committed to sinoatrial region fates. Subsequently, embryos were subjected to whole mount in situ hybridization, immunohistochemistry and RT-qPCR analysis. As a relevant nov-elty, our results revealed that miR-1 increases Tbx5, Gata4 and AMHC1, while this microRNA diminishes Mef2c expression, during early differentiation of cardiac sinoatrial region. Further-more, we observed in this developmental context that miR-1 upregulates CRABPII and RARß, and downregulates CRABPI, which are three crucial factors in retinoic acid signaling pathway. Interestingly, we also noticed that miR-1 directly interacts with HDAC4 and Calmodulin, as well as with Erk2/MAPK1, which are three key factors actively involved in Mef2c regulation. Our study shows, for the first time, a key role of miR-1 as an epigenetic regulator in early differenti-ation of cardiac sinoatrial region through orchestrating opposite actions between retinoic acid and Mef2c, fundamental to properly assign cardiac cells to their respective heart chambers. A better understanding of those molecular mechanisms modulated by miR-1 will definitely help in fields applied to therapy and cardiac regeneration and repair.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, and despite advances in treatment, survival rates are still low; therefore, the development of novel drugs is imperative. Acetylcorynoline (ACN) is derived from Corydalis ambigua. The effect of ACN on colon cancer is still unknown. Therefore, we investigated its potential effects. Our data showed that ACN inhibited cell viability and proliferation. Moreover, ACN induced apoptosis and cell cycle arrest by inhibiting cell growth. In the present study, we hypothesized that ACN regulates c-Myc through CNOT2 or MID1IP1. ACN reduced the protein expression of oncogenic genes, decreased c-Myc half-life, and rapidly inhibited the serum stimulation response. Moreover, knockdown of CNOT2 and MID1IP1 with ACN increased apoptosis and further reduced the expression of oncogenes. In addition, ACN exhibited a synergistic effect with low-dose of 5-fluorouracil (5-FU) and doxorubicin (Dox). Collectively, our data demonstrates that ACN inhibited c-Myc expression through CNOT2 and MID1IP1 and induced apoptosis. These findings indicate the potential of ACN as a therapeutic agent against colon cancer.

During HIV-1 virus assembly the genomic RNA (vRNA) is selected for packaging by the viral protein Gag because it contains a specific packaging signal, Psi. While there have been numerous studies of Gag-Psi interactions, there is almost no information on kinetic aspects of this interaction. We have investigated the kinetics of Gag binding to different RNAs using switchSENSE DRX2 technology. We measured the association rate of Gag binding to monomeric Psi, to a “Multiple Binding Site Mutant” Psi that is inactive for genome packaging in vivo, and to a scrambled Psi. We discovered that Gag binds more rapidly to Psi RNA than to the mutant or scrambled RNAs. Furthermore, rapid Gag association kinetics are retained within sub-regions of Psi: Gag associates more rapidly with RNA containing only the 3’ two of the three Psi stem-loops than with monomeric RNA containing the 5’ two stem-loops or a scrambled RNA. No differences were detectable with individual Psi stem-loops. Interestingly, the rate of binding of Gag molecules to Psi increases with increasing Gag concentration, suggesting cooperativity in binding. The results are consistent with the hypothesis that selectivity in packaging derives from kinetic differences in initiation of particle assembly.

REV-ERBα and its paralog, REV-ERBβ encoded by NR1D1 and NR1D2 genes, are key nuclear receptors that link the circadian timing system and metabolic homeostasis. Since heme is an endogenous ligand, REV-ERBs have been considered key components of the circadian molecular clock that can be pharmacologically targeted to treat various circadian rhythm-related diseases, such as cardiometabolic, inflammatory, and neuropsychiatric diseases, as well as cancer. REV-ERBs are believed to be functionally redundant and compensatory, although they often affect the expression of gene subsets in an isoform-specific manner. Therefore, this study aimed to identify the redundant and distinct roles of each isoform in controlling its target genes by comparing the transcriptome profiles of a panel of mutant U2OS human osteosarcoma cells in which either NR1D1 or NR1D2 was ablated. Indeed, our transcriptomic analyses revealed that most REV-ERB-regulated genes were controlled by redundant or even additive actions. However, the RNA expression profiles of each single mutant cell line also provided strong evidence for isoform-dependent actions. For example, REV-ERBα were more responsible for regulating the NF-κΒ signaling pathway, whereas a group of extracellular matrix components required REV-ERBβ to maintain their expression. We found that REV-ERBs have isoform-selective functions in the regulation of certain circadian output pathways, despite their overlapping roles in the circadian molecular clock. Thus, the development of isoform-selective REV-ERB modulators may help treat metabolic disturbances and certain types of cancer.

Soil naturally contains fluorine, but concerns arise when its levels or bioavailability are increased by human activities or specific compounds. South Korea faces challenges in regulating soil fluorine pollution despite implementing stricter total fluorine standards than many developed countries. Moreover, these regulations can be economically unfeasible because of the naturally high background levels of fluorine in the soil in Korea. This review explores the global landscape of soil fluorine management strategies and examines potential solutions that reconcile environmental protection with economic concerns. We recommend a shift towards regulating specific and hazardous fluorine compounds rather than total content, and prioritizing remediation efforts based on assessments of bioavailable fluorine. This approach may help Korea establish a more effective and sustainable strategy for managing soil fluorine pollution.

Recently, astroviruses (AstVs) have been associated with neurological symptoms in pigs, cattle, sheep, minks, muskoxes, alpacas, and humans. To investigate genotypes of porcine astrovirus (PAstV) and neuroinvasive (Ni) PAstV in South Korea, five domestic pigs with neurological symptoms from three farms were tested using reverse transcriptase PCR, histopathology, and in situ hybridization (ISH). All five genotypes of PAstV were detected in brain tissues and coinfection of PAstV with multiple genotypes was observed. To the best of our knowledge, this is the first study to report pig infection by Ni-PAstV with multiple genotypes in South Korea.

The seismic damage in reinforced concrete bridges is identified in this study using the "M and P" hybrid technique initially developed for planar frames. The proposed methodology involves a series of pushover and instantaneous modal analyses with a progressively increasing target deck displacement along the longitudinal direction of the bridge. From the results of these analyses, the diagram of the instantaneous eigenfrequency of the bridge, ranging from the health state to near collapse, is plotted against the inelastic seismic deck displacement. By pre-determining the eigen-frequency of an existing bridge along its longitudinal direction through "monitoring and frequency identification", the target deck displacement corresponding to the damage state can directly be found from this diagram. Subsequently, the damage can be identified by examining the results of the pushover analysis at the step where the target deck displacement is indicated. The effectiveness of this proposed technique is evaluated in the context of multiple span bridges with unequal pier heights, illustrated through an example of a four-span bridge. The findings demonstrate that the damage potential in bridge piers can be successfully identified by combining the results of a monitoring process and pushover analysis.

It has been more than a century since Erlang published his paper in 1909. The classical queueing system for the M/D/c queue has been investigated by many authors. The key is to find the roots of an equation using explicit or numerical methods. We present an alternate form of explicit solution(s) of this/these root(s) using the Lambert-W function in this paper. In addition, the unsaturated probabilities of the number of customers in the system is derived explicitly in terms of this/these root(s). Finally, the mean number of customers in the system and the mean queueing delay are obtained from these probabilities. The exact queueing delay formula for the M/D/c queue is expressed in closed-form in terms of the root(s). Numerical results show that they are in excellent agreement with the numerical results published by Seelen, Tijms and Van Hoorn.

Let R be a commutative ring and m, n be positive integers. We define a proper submodule N of an R-module M to be (m,n)-closed if for r∈R and b∈M, r^{m}b∈N implies rⁿ∈(N:_{R}M) or b∈N. This class of submodules lies properly between the classes of prime and primary submodules. Many characterizations, properties and supporting examples concerning this class of submodules are provided. The notion of (m,n)-modules is introduced and characterized. Furhermore, the (m,n)-closed avoidance theorem is proved. Finally, the (m,n)-closed submodules in amalgamated modules are studied.

Cardiovascular disease is the leading cause of death worldwide. A key factor in assessing the risk of cardiovascular disease is left ventricular functional evaluation. Left ventricular (LV) systolic function is evaluated by measuring the left ventricular ejection fraction (LVEF) using echocardiography data. Therefore, quick and accurate left ventricle segmentation is important for estimating the LVEF. However, it is difficult to accurately segment the left ventricle due to changes in the shape and area of the left ventricle during cardiac cycles. In this study, we proposed a framework that considers changes in the shape and area of the left ventricle during the cardiac cycle by applying the convolutional long short-term memory (CLSTM) approach. In addition, we evaluated the left ventricular segmentation and multidimensional quantification of the proposed system in comparison to manual and automated segmentation methods. In addition, to assess the validity of CLSTM, the values of multi-dimensional quantification metrics were compared and analyzed using graphs and Bland–Altman plots on a frame-by-frame basis. We demonstrated that the CLSTM method effectively segments the left ventricle by considering the LV activity. In conclusion, we demonstrated that LV segmentation based on our framework may be utilized to accurately estimate LVEF values.

This paper explores the application of the generalized double reduction method to the (1+1)-dimensional Kaup-Boussinesq (K-B) system, which models nonlinear wave propagation. Double reduction method is a structured and systematic approach in the analysis of partial differential equations (PDEs). We first identify the Lie point symmetries of the K-B system and construct four non-trivial conservation laws using the multiplier method. The association between the Lie point symmetries and the conservation laws is established, and the generalized double reduction method is then applied to transform the B-K system into second-order differential equations or algebraic equations. The reduction process allowed us to derive two exact solutions for the K-B system, illustrating the method’s effectiveness in handling nonlinear systems. This work highlights the effectiveness of the generalized double reduction method in simplifying and solving nonlinear nonlinear systems of PDEs, contributing to a deeper understanding of the systems.

We summarize structural instabilities exhibited by the one dimensional (1D) (arene)2X family of organic conductors in relation with their electronic and magnetic properties. With a charge transfer of one electron to each anion X these salts exhibit a quarter-filled (hole) conduction band located on the donor stacks. Compounds built with donors such as fluorenthene and perylene derivatives and anions X such PF6 or AsF6 exhibit a high temperature (TP~170K) conventional Peierls transition which is announced by a sizeable regime of 1D 2kF charge density wave fluctuations (kF is the Fermi wave vector of the 1D electron gas located on Per stacks). Surprisingly, and probably because of the presence of a multi-sheet warped Fermi surface, the Peierls transition is considerably reduced in the perylene series α-(Per)2[M(mnt)2] where X is the dithiolate molecule with M=Au, Cu, Co and Fe. A special attention is devoted in this paper to physical properties of α-(Per)2[M(mnt)2] salts which with M=Pt, Pd and Ni incorporate segregated S=1/2 1D antiferromagnetic (AF) dithiolate stacks with 1D metallic Per stacks. We analyse conjointly the structural and magnetic properties of these salts in relation with the 1D spin-Peierls (SP) instability located on the dithiolate stacks. We show that the SP instability of the Pd and Ni derivatives occurs in the classical (adiabatic limit) while the SP instability of the Pt derivative occurs in the quantum (anti-adiabatic limit). Furthermore we show that in the Pd and Ni derivatives frustrated 1st neighbour direct and 2nd neighbour indirect (through a fine tuning with the mediated 2kF RKKY coupling interaction on Per stacks) AF interactions add their contribution to the SP instability to open a singlet-triplet gap. Our analysis of the data show unambiguously that magnetic α-(Per)2[M(mnt)2] salts are a typical realization of the physics predicted for two chain 1D Kondo lattices.

Extensive genome structure variation, such as copy number variations (CNVs) and presence/absence variations, is the basis for the remarkable maize genetic diversity; however, the effect of CNVs on maize herbivory defense remains largely underexplored. Here, we report that the naturally occurring duplication of the maize 9-lipoxygenase gene, ZmLOX5, leads to increased resistance of maize to herbivory by fall armyworms (FAW). Previously, we showed that ZmLOX5-derived oxylipins are required for defense against chewing insect herbivores and identified several inbred lines, including Yu796, that contained duplicated CNVs of ZmLOX5, referred to as Yu796-2×LOX5. To test whether introgression of the Yu796-2×LOX5 locus into the herbivore-susceptible B73 background that contains a single ZmLOX5 gene is a feasible approach to increase resistance, we generated a series of near-isogenic lines that contained either 2, 1 or 0 copies of the Yu796-2×LOX5 locus in the B73 background by six back crosses (BC6). Droplet digital PCR (ddPCR) confirmed the successful introgression of the Yu796-2×LOX5 locus in B73. The resulting B73-2×LOX5 inbred line displayed increased resistance against FAW associated with increased expression of ZmLOX5, increased wound-induced production of its primary oxylipin product, the α-ketol, 9-hydroxy-10-oxo-12(Z),15(Z)-octadecadienoic acid (9,10-KODA), and the downstream defense hormones regulated by this molecule, 12-oxo-phytodienoic acid (12-OPDA) and abscisic acid (ABA). Surprisingly, wound-induced JA-Ile production was not increased in B73-2×LOX5, resulting from the increased JA catabolism. Furthermore, B73-2×LOX5 displayed enhanced drought tolerance likely due to increased ABA and 12-OPDA content. Taken together, this study revealed that the duplicated CNV of ZmLOX5 quantitively contributes to maize antiherbivore defense and presents proof-of-concept evidence that the introgression of naturally occurring duplicated CNVs of a defensive gene into the productive, but susceptible, crop varieties is a feasible breeding approach for enhancing plant resistance to herbivory and tolerance to abiotic stress.

For very first time, we report the synthesis of 8-(2-methoxyphenyl)-6-methyl-2-(1-methyl-1H-benzo[d]imidazol-2-yl)quinoline 1. This was achieved in several steps, including usage of Suzuki reaction for functionalization of 2-(1H-benzo[d]imidazol-2-yl)quinoline moiety. The new compound exhibits blue fluorescence. Its structure was confirmed with 1D- and 2D-NMR spectroscopy, IR-spectroscopy, high-resolution mass spectrometry and X-ray analysis.

In this paper, we study the dynamics of following system of nonlinear difference equations x_n+1 = x_n-1y_n - 1, y_n+1 = y_n-1z_n - 1, z_n+1 = z_n-1x_n - 1. Especially we investigate the periodicity, boundedness and stability of related system of difference equations.

Carbon nanotubes (CNTs) can be considered as semi-rigid all-carbon polymers. However, unlike conventional polymers that can form 3D networks such as hydrogels or elastomers through crosslinking with each other in solution, the cylindrical carbon lattice of CNTs was not believed to be directly crosslinkable in solution until our recent discovery of UV-defluorination driven direct CNT crosslinking. In this study, we further reveal that the UV-defluorination-driven crosslinked CNTs are metastable and can decompose more readily than fluorinated or pristine CNTs upon exposure to Raman laser irradiation. Specifically, we investigate the stability of UV-defluorinated single-walled and multi-walled fluoro-nanotubes using Raman spectroscopy under controlled varying laser power. The results indicate that both the defluorinated single-walled and multi-walled CNTs are thermally less stable than pristine CNTs or untreated fluorinated CNTs, which can be attributed to the strains on the crosslinking bonds created from the curved carbon lattice of linked CNTs. This instability, particularly evident under high-power laser irradiation, leads to combustion processes ignited at relatively lower temperatures that cause an extended burned area centered on the laser spot, offering potential future applications as mechanically robust, lightweight materials with feasible post-use degradation options.

The lymphocyte function–associated antigen-1 (LFA-1) (also CD11a/CD18 and αLβ2), is just one of many integrins in the human body, but its significance derives from its exclusive presence in leukocytes. In this review, we summarize the studies relating LFA-1 and its major ligand ICAM-1 (CD54) with cancer, through the function of lymphocytes and myeloid cells on tumor cells. We consider how LFA-1 mediates the interaction of leukocytes with tumors and the role of ICAM-1 in tumor dynamics, which can be independent of its interaction with LFA-1. A more detailed examination of LFA’s role within B-cell chronic lymphocytic leukemia is made. Finally, we discuss the role of LFA-1-harboring exosomes in tumor growth and metastasis.

In this article, we investigate two types of double dispersion equations in two dierent dimensions. Double dispersion equation were derived to describe long nonlinear wave evolution in a thin hyperelastic rod. Conservation laws are obtained for these equations by the application of the multiplier method. Finally, travelling waves and line travelling waves are respectively considered for these two equations.

While significant efforts have been made to recycle metals like lithium or cobalt for sustainable development in the battery industry, other high-value materials in the renewable energy sector, such as fluorinated carbon nanotubes (FCNTs), have not been adequately explored for re-utilization after their quality has been downgraded. FCNTs are expensive and energy-intensive to produce, making their sustainable use crucial. This study explores the potential of reusing quality-downgraded fluorinated carbon nanotubes (QD-FCNTs) as eco-friendly nano-additives in microgel composites for water retention applications. By employing a surface treatment process that avoids additional energy costs and environmentally harmful chemicals, we successfully enhanced the interaction between QD-FCNTs and microgels. This treatment significantly improved water retention time by reducing rapid evaporation, enabling sustained water release. Our findings demonstrate a promising avenue for the sustainable application of quality-downgraded fluorinated carbon nanotubes in agricultural and environmental technologies.

Clarifying the impact mechanism of digital transformation of enterprises on the M&A efficiency of listed companies can provide a factual basis for improving capital market regulatory policies. Taking the mergers and acquisitions of listed companies from 2007 to 2021 as a research sample, the influence mechanism of the digital transformation degree of companies on their M&A efficiency was studied. The research results show that the digital transformation of listed companies will improve their M&A efficiency. Digital transformation will reduce the degree of mispricing of stocks of M&A companies, curb conflicts between managers and agents of M&A companies, and improve their M&A efficiency. Further research finds that the promotion effect of digital transformation on M&A efficiency is more significant in non-state-owned companies, with a higher degree of financing constraint and high analyst attention. In the future, regulatory authorities should actively promote the digital transformation of listed companies, curb mispricing and management agency problems in the capital market with digital governance, and improve the efficiency of mergers and acquisitions in the capital market.

Purpose. Moraxella is an ocular bacterial pathogen isolated in cases of keratitis, conjunctivitis, and endophthalmitis. Gram-negative brick-shaped diplobacilli from ocular specimens, and slow growth in culture, are early indications of Moraxella ocular infection; however, identifying Moraxella to species can be complex and inconsistent. Methods. In this study, bacteria consistent with Moraxella were identified to species using: 1) DNA sequencing coupled with vancomycin susceptibility, 2) MALDI-TOF Mass Spectrometry, and 3) Biolog ID System. Study samples consisted of 9 ATCC Moraxella controls, 82 isolates from keratitis, 21 isolates from conjunctivitis, and 4 isolates from endophthalmitis. Results. The ATCC controls were correctly identified. For keratitis, 66 (80.5%) were identified as M. nonliquefaciens, 7 (9.0%) as M. lacunata, 5 (6%) as M. osloensis, 2 (2.5%) as Acinetobacter lwoffi, 1 (1.0%) as M. bovis/nonliquefaciens, and 1 (1.0%) as M. osloensis/nonliquefaciens. For conjunctivitis, 9 (43.0%) were identified as M. osloensis, 6 (29.0%) as M. nonliquefaciens, 3 (14.3%) as Roseomonas, 2 (9.5%) as Acinetobacter (parvus, junii), and 1 (4.5%) as M. catarrhalis/M. nonliquefaciens. From endophthalmitis, 3 of 4 of the isolates were M. nonliquefaciens. Overall, M. nonliquefaciens and M. osloensis were identified in 70% (75 of 107) and 13% (14 of 107) of cases, respectively, totaling 83% (89 of 107). Conclusions. M. nonliquefaciens and M. osloensis are important bacterial pathogens of the eye as determined by DNA sequencing, MALDI-TOF MS, and Biolog. Although Moraxella catarrhalis is a clinical pathogen, other species of Moraxella appear to have a prominent role in eye infections.

Graph theory plays a crucial role in modeling and designing of chemical structure or chemical network. Chemical Graph theory helps to understand the molecular structure of molecular graph. The molecular graph consists of atoms as vertices and bonds as edges. Topological indices capture symmetry of molecular structures and give it a mathematical language to predict properties such as boiling points, viscosity, the radius of gyrations etc. In this article, we study the chemical graph of carbon Crystal structure of graphite and cubic carbon and compute several degree-based topological indices. Firstly we compute M-Polynomials of these structures and then from these M-polynomials we recover nine degree-based topological indices.

The paper deals with the problem of choosing the best O&M strategy for wind power plants. Current maintenance theory considers just production opportunities and minimizes the maintenance costs, but with the liberalization of the electricity market also the electricity price has become an important variable to take into account in the O&M scheduling. Another important variables that is often neglected by the existing maintenance theory is the weather condition. This paper proposes a new strategy that takes into account the electricity price and weather conditions, improves the expected profit of the systems, and reduce the overall maintenance and logistic costs. The maintenance schedule is formalized as an optimization problem where the discounted cumulative profit of a wind generation portfolio in a fixed-time horizon (e.g. two years ahead), subject to the technologically-derived maintenance time constraints is optimized. Both the theoretical and computational aspects of the proposed O&M strategy are discussed. Results show that taking into account market and weather opportunities in the design of the maintenance strategy, it is possible to achieve a more complete scheduling for a given set of wind power plants.

Rising antimicrobial resistance (AMR) in Salmonella serotypes host-adapted to cattle is of increasing concern to the beef and dairy industry. The bulk of the existing literature focuses on AMR post-slaughter. In comparison, the understanding of AMR in Salmonella among pre-harvest cattle is still limited, particularly in Texas, which ranks top five in beef and dairy exports in the United States; inherently, the health of Texas cattle has nationwide implications for the health of the United States beef and dairy industry. In this study, long-read whole genome sequencing and bioinformatic methods were utilized to analyze antimicrobial resistance genes (ARGs) in 98 isolates from beef and dairy cattle in the Texas Panhandle. Fisher exact tests and elastic net models accounting for population structure were used to infer associations between ARGs and antimicrobial phenotypic profiles and metadata. Gene mapping was also performed to assess the role of mobile genetic elements in harboring ARGs. ARG were found to be statistically different between the type of cattle operation and Salmonella serotypes. Beef operations were statistically significantly associated with more resistance genes compared to dairy operations. Salmonella Heidelberg, followed by Salmonella Dublin isolates, were associated with the most ARGs. Additionally, specific classes of ARGs were only present within mobile genetic elements.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive neurological disorder and shares many radiological and clinical features with other more prevalent myelopathies. Here, we quantified spinal cord and brain volumes in adults with HAM/TSP in comparison with healthy volunteers (HVs) and participants diagnosed with multiple sclerosis (MS). Clinical disability and MRI were assessed in 24 HVs, 43 HAM/TSP, and 46 MS participants. Spinal cord cross-sectional area (SCCSA) and brain tissue volumes were measured and compared. HAM/TSP participants had significantly lower SCCSA at C2-3 (54.0±8 mm2), C4-5 (57.8±8 mm2), and T4-9 (22.7±4 mm2) and significantly elevated brain white matter hyperintensity (WMH) fraction (0.004±0.008) was compared to HVs (C2-3: 69.4±8 mm2, C4-5: 75.1±9 mm2, T4-9: 34.1±4 mm2; all p &lt; 0.0001; and WMH: 0.0004±0.0007; p &lt; 0.001). In HAM/TSP, SCCSA at all levels but not WMH showed the significant correlation with clinical disability scores. Brain white matter hyperintensities in HAM/TSP, therefore, may not be related to clinical disability. SCCSA and WMH in our limited MS cohort were higher than the HAM/TSP cohort (67.6±8 mm2, 72.7±9 mm2, 33.4±5 mm2; p &lt; 0.0001). Principal component analysis suggested that SCCSA and WMH may be used to differentiated HAM/TSP from MS. Understanding these differences may help establish early diagnostic criteria for HAM/TSP patients.

Background and Objectives Neurofibromatosis 1 (NF1 MIM # 162200), also known as von Recklinghausen disease, is among the most common autosomal dominantly transmitted disorders characterized mainly by neurocutaneous manifestations such as café au lait spots, intertriginous freckling, various types of neurofibromas (cutaneous neurofibromas or plexiform tumors), neurological manifestations, and bone abnormalities. It occurs with an incidence of 1:3000–1:4000 cases. Cone-rod dystrophies belong to the large group of retinal dystrophies, a highly heterogeneous group of disorders clinically manifested mainly by damage to cone and rod cells and have a broad spectrum of clinical manifestations. Many genes are involved in their etiology, with more than 100 currently identified, including the CRX gene responsible for the autosomal dominant form of cone-rod dystrophy (ad CORD). Materials and Methods: The authors present an intriguing case of a patient diagnosed with Neurofibromatosis type 1 (NF1) as an infant and ocular involvement (myopia and astigmatism onset at age 15), which yielded a surprising molecular testing result. Results: Molecular DNA analysis identified a rare occurrence of two mutational variants, including a pathogenic variant in the NF1 gene, c.3871-2A, and a likely pathogenic variant in the CRX gene c.119G>A. Conclusions: The authors present this case to highlight the surprises offered by molecular testing in a condition where the diagnosis is usually based on clinical criteria, thus providing patients with competent genetic advice.

The bark of Rhus verniciflua Stokes (RVS) is used as a food additive and herbal medicine for various inflammatory disorders and cancer in Eastern Asia. RVS exerted anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, but whether this effect occurs in macrophages after oral administration has not been determined. We used a thioglycollate-induced peritonitis model to obtain macrophages from mice given RVS. We examined the systemic inflammatory response to intraperitoneal LPS. RVS-treated mice had an increased population of peritoneal exudate cells expressing CD11b and SRA. Increased uptake of Alexa Fluor 488-labeled acetylated lipoprotein was observed in monocyte-derived macrophages from RVS-treated mice. When these cells from the RVS group were stimulated with LPS, the levels of tumor necrosis factor (TNF)- and interleukin (IL)-6 in the supernatant decreased, but the level of IL-12 increased. The surface expression of CD86 was reduced, but surface expression of class II MHC molecules was increased. RVS suppressed the serum levels of LPS-induced TNF- and IL-6. RVS enhanced monocyte differentiation in thioglycollate-induced peritonitis by increasing scavenger receptor expression and activity. Macrophages isolated from mice given RVS responded differently to LPS. These findings demonstrate that RVS confers selective anti-inflammatory activity without causing the overall inhibitory effects on immune cells.

Introduction: Although aging is a natural phenomenon, in recent years it has accelerated. One key factor implicated in the aging process is oxidative stress. Oxidative stress play also role in frailty (frail) and metabolic syndrome (MetS). Methods: 66 elderly persons (65 years old and older) with no acute or severe chronic disorders were assessed: waist circumference (WC), arterial blood pressure, glycemia, glycated hemoglobin (HbA1c), plasma lipids and activity of erythrocyte superoxide dismutase (SOD-1). Patients were classified as NonMetS-Nonfrail (n=19), NonMetS-frail (n=20), MetS-Nonfrail (n=17), and MetS-frail (n=10). Results: There were no significant differences in superoxide dismutase activity among investigated elderly groups. However, the data suggests that MetS individuals, both frail and nonfrail, have higher risk factors for cardiovascular disease compared to NonMetS individuals. The correlations analyses of SOD-1 and other metabolic indices suggest that SOD-1 levels may be influenced by age, total cholesterol, HDL cholesterol, and fasting glucose levels in certain groups of seniors. Conclusions: Aging is associated with decreased antioxidant enzyme SOD-1 activity with glucose alteration in frailty syndrome as well as with lipids disturbances in metabolic syndrome.

With the widespread use of the Internet of Things, underwater control and monitoring systems for purposes such as ocean data sampling, natural disaster prevention, underwater surveillance, submarine exploration, and the like have become a popular and challenging topic in computers. So far, various topology control and routing solutions have been proposed for these networks. However, as technology expands and applications grow, so does the need for a stable underwater communication platform. On the other hand, underwater communication is associated with challenges such as node mobility, long propagation delays, low bandwidth, limited resources, and high error rates. In this research, for the first time, a topology control platform based on the RPL tree is modelled by applying its structural changes underwater. The proposed RPLUW methods in the case of RPLUWM fixed nodes are introduced to support the mobility of nodes underwater. Flexible objective functions, utilisation of decision-making systems, and application of control schedules in these methods have increased network life, reduced overhead, and increased node efficiency. The simulation results of the proposed method, in comparison with recent methods in this field, show an increase in network efficiency.

The Drosophila spermatogenesis has the renewal of germline stem cells, meiosis of spermatocytes, and morphological transformation of spermatids into mature sperm. We previously demonstrated that Ocnus (ocn) plays an essential role in spermatogenesis. ValRS-m (Valyl-tRNA synthetase, mito-chondrial) gene was downregulated in ocn RNAi testes. By hatchability testing, we found that ValRS-m-knockdown induced complete sterility of male flies. We also concluded that ValRS-m-knockdown inhibited the transition from spermatogonia to spermatocytes and caused accumulated spermatogonia in testes. To understand the intrinsic reason for this destruction, we further conducted transcriptome sequencing analysis in ValRS-m RNAi testes. A total of 7710 dif-ferentially expressed genes (DEGs) were identified to have at least a 2-fold change with a p-value of

In order to investigate the coordination chemistry of O-alkyl N-aryl thiocarbamate ligands, BiI3 has been reacted with two equivalents of MeOC(=S)N(H)Ph in MeCN solution to afford the dinuclear title compound complexes [{I2Bi(μ2-I)2BiI2}{1-MeOC(=S)N(H)Ph}4] 1. Compound 1 has been characterized by IR, UV and NMR spectroscopy, the dinuclear framework has be ascertained by a single-crystal X-ray diffraction study performed at 100 K.

Cyclin dependent kinase 1 (CDK1) has been primarily identified as a key cell cycle regulator in both mitosis and meiosis. Recently, an extramitotic function of CDK1 emerged when evidence was found that CDK1 is involved in many cellular events that are essential for cell proliferation and survival. In this review we summarize the involvement of active CDK1 in the initiation and elongation steps of protein synthesis in eukaryotes. During its activation CDK1 influences the initiation of protein synthesis, promotes the activity of specific translational initiation factors and affects the functioning of a subset of elongation factors. Our review provides insights into gene expression regulation during the transcriptionally silent cell cycle/M-phase and describes quantitative and qualitative translational changes based on the extramitotic role of the cell cycle master regulator CDK1, to optimize temporal synthesis of proteins to sustain division-related processes: mitosis and cytokinesis.

The Bax inhibitor-1 (BI-1) gene family, which is required for plant growth, development, and stress tolerance, remains largely unexplored in cauliflower. In this study, we identified and characterized cauliflower BI-1 family genes. On the basis of aligned homologous sequences and collinearity with Arabidopsis genes, we identified nine cauliflower BI-1 genes, which encoded proteins that varied regarding length, molecular weight, isoelectric point, and subcellular localization (i.e., Golgi apparatus, plasma membrane, cell membrane, and chloroplast). Phylogenetic analyses detected evolutionary conservation and divergence among these genes. Ten structural motifs were identified, with Motif 5 crucial for inhibiting apoptosis. According to the cis-regulatory elements in their promoters, these genes likely influence hormone signaling and stress responses. Expression profiles among tissues highlighted the diversity in the functions of these genes, which were significantly expressed in the silique and root. Focusing on BobBIL4, we investigated its role in brassinosteroid (BR)-mediated root development and salt stress tolerance. BobBIL4 expression levels increased in response to BR and salt treatments. The functional characterization of this gene in Arabidopsis revealed it enhances root growth and salinity tolerance. These findings provide insights into BI-1 gene functions in cauliflower, while also highlighting the potential utility of BobBIL4 for improving crop stress resistance.

Soil-borne Trichoderma spp. have been extensively studied for their biocontrol activities against pathogens and growth promotion ability with plants. However, the beneficial effect of Trichoderma on inducing resistance against insect herbivores has been considered only recently. Among diverse Trichoderma species, consistent with previous reports, we showed that root colonization by T. virens triggered induced systemic resistance (ISR) to leaf-infecting fungal pathogens. Whether T. virens induces ISR to insect pests has not been tested before. In this study, we investigated whether T. virens affects jasmonic acid (JA) biosynthesis and defense against fall armyworm (FAW) and western corn rootworm (WCR). Unexpectedly, the results showed that T. virens colonization of maize seedlings grown in autoclaved soil suppressed wound-induced production of JA, resulting in reduced resistance to FAW. Similarly, the bacterial endophyte Pseudomonas chlororaphis 30-84 suppressed systemic resistance to FAW due to reduced JA. Further comparative analyses of the systemic effects of these endophytes when applied into sterile or non-sterile field soil showed that both T. virens and P. chlororaphis 30-84 triggered ISR against hemibiotrophic fungal pathogen Colletotrichum graminicola in both soil conditions, but only suppressed resistance to FAW in sterile soil. In contrast to the effect on FAW defense, T. virens colonization of maize roots suppressed WCR larvae survival and weight gain. This is the first report suggesting the potential role of T. virens as a biocontrol agent against WCR.

Accumulating reports have suggested that an inability to clear dead cells is a cause of inflammation and cancer and that the fascia is associated with cancer metastasis. Novel corpuscle-connected filiform structures (CCFSs) entangled on the fascia of the internal organs of rats were selectively visualized with high repeatability (93%) under vital staining with Janus Green B (JGB). Serial sections of CCFSs stained with haematoxylin and eosin and with Mattson Trichrome were microscopically examined. In parallel, the immunohistochemistry with CD31, Lyve 1, scanning electron microscopy, and transmission electron microscopy (TEM) were also used to investigate the novel properties of the CCFSs. All of the CCFSs enclosed JGB-stained granules, which was verified by the impromptu coupling of stereo and light microscopes and fluorescence-activated cell sorting. The functions of the CCFSs were discovered under fluorescence microscopy and confocal laser scanning microscopy to be implicated in cell death: fragmented DNAs and f-actins with extracellular DNAs. The dead cells in the CCFSs were verified by using terminal deoxynucleotidyl transferase dUTP nick end labelling and TEM. Moreover, the CCFS had a relatively-high concentration of calcium, a main element for cell death in tissue, which was measured in 2-dimensionally images using time-of-flight secondary ion mass spectrometry. Taken these results, we report for the first time that novel reticular CCFSs are widely entangled on the fascia of the internal organs of rats with the implication for cell death.

Euler’s product formula over the primes and Euler’s zeta function equate to enshrine the Fundamental Theorem of Arithmetic that every integer > 1 is the product of a unique set of primes. The product formula has no zero, and with a domain ≤1 Euler’s zeta diverges. Dirichlet’s eta function η(s), negates alternate terms of zeta, permitting convergence when s∈C and Re(s) < 1, and its non-trivial zeros {ρ}, have a deep relationship with the distribution of the primes. The Riemann Hypothesis is that all the non-trivial zeros have Re(ρ) = 1/2. This work examines the symmetries in a partial Euler’s zeta series with a complex domain equating it to the difference between two finite vector series whose matched terms have mirror-image arguments, but whose magnitudes differ when Re(s) ≠ 1/2. Analytical continuation generates a modified eta series η_l(s), in which every l^th term is multiplied by (1-l). If the integer l is appropriately determined by the Im(s), similar paired finite vector series have a difference that closely follows η_l (s) and their terminal vectors intersect in a unique way permitting zeros only when Re(s) = 1/2. Furthermore, those vectors tracking the derivatives of the series, have a special relationship permitting zeros of the differential only when Re(s) > 1/2.

The process of developing therapies to treat rare diseases is fraught with financial, regulatory, and logistical challenges that have limited our ability to build effective treatments. Recently, a novel type of therapy called antisense therapy has shown immense potential for the treatment of rare diseases, particularly through single-patient N-of-1 trials. Several N-of-1 antisense therapies have been developed recently for rare diseases, including the landmark study of milasen. In response to the success of N-of-1 antisense therapy, the Food and Drug Administration (FDA) has developed unique guidelines specifically for the development of antisense therapy to treat N-of-1 rare diseases. This policy change establishes a strong foundation for future therapy development, and addresses some of the major limitations that previously hindered the development of therapies for rare diseases.

Severe inherited alpha-1 antitrypsin deficiency (AATD) is an autosomal genetic condition linked to chronic obstructive pulmonary disease (COPD). The significance of heterozygous, milder deficiency variants (Pi*M, Pi*S, Pi*Z) is less clear. We studied AATD genotypes in 145 children (up to 72 months old) with assessed wheezing severity using the Pediatric Respiratory Assessment Measure (BCCH PRAM score). A control group of 74 children without airway obstruction was included. AAT concentration and Pi phenotype were determined from dry blood spot samples using nephelometry and real-time PCR; PiS and PiZ alleles were identified by isoelectrofocusing. Among the wheezers, the Pi*S allele incidence was 2.07% (3 cases) and Pi*Z allele was 6.9% (10 cases). The Pi*Z allele frequency was higher in wheezers compared to controls (44.8% vs. 20.27%) and the general Lithuanian population (44.8% vs. 13.6%) and was similar to adult COPD patients in Lithuania: Pi*S 10.3% vs. 15.8% and Pi*Z 44.8% vs. 46.1%. No association was found between AAT genotypes and wheezing severity. Finding that wheezer children exhibit a frequency of Z* and S* alleles like that found in adults with COPD suggests a potential genetic predisposition that links early wheezing in children to the development of COPD in adulthood. Larger cohort studies are needed to confirm this finding.

Soil and Water Assessment Tool (SWAT) was used to simulate five glacierized river basins that are global in coverage and vary in climate. The river basins included the Narayani (Nepal), Vakhsh (Central Asia), Rhone (Switzerland), Mendoza (Central Andes, Argentina), and Central Dry Andes (Chile) with a total area of 85,000 km2. A modified SWAT snow algorithm was applied in order to consider spatial variation of associated snow melt /accumulation by elevation band across each subbasin. In the previous studies, melt rates varied as a function of elevation resulting from an air temperature gradient while the snow parameters were constant throughout the entire basin. A major improvement of the new snow algorithm is separating the glaciers from seasonal snow based on their characteristics. Two SWAT snow algorithms were evaluated in simulation of monthly runoff from glaciered watershed: 1) the snow parameters are lumped (i.e. constant throughout the entire basin) and 2) the snow parameters are spatially variable based on elevation band-subbasin (i.e. modified snow algorithm). Applying the distributed SWAT snow algorithm improved the model performance in simulation of monthly runoff with snow-glacial regime, so that mean RSR decreased to 0.49 from 0.55 and NSE increased to 0.75 from 0.69. Improvement of model performance was negligible in simulation of monthly runoff from the basins with monsoon runoff regime.

Cells respond to DNA double-strand breaks by initiating DSB repair and ensuing a cell cycle checkpoint. The primary responder to DSB repair is non-homologous end joining, an error prone repair pathway. However, when DSBs are generated after DNA replication in the G2 phase of the cell cycle, a second DSB repair pathway, homologous recombination, can come into action. Both ATM and ATR are important for DSB-induced DSB repair and checkpoint responses. One method of ATM and ATR working together is through the DNA end-resection of DSBs. As a readout and marker of DNA end-resection, RPA is phosphorylated at Ser4/Ser8 of the N-terminus of RPA32 in response to DSBs. Here, the significance of RPA32 Ser4/Ser8 phosphorylation in response to DNA damage, specifically in S phase to G2 phase of the cell cycle is examined. RPA32 Ser4/Ser8 phosphorylation in G2 synchronized cells is necessary for increases in TopBP1 and Rad9 accumulation on chromatin and full activation of the ATR-dependent G2 checkpoint. In addition, our data suggest RPA Ser4/Ser8 phosphorylation modulates ATM-dependent KAP-1 phosphorylation and Rad51 chromatin loading in G2 cells.

In present paper, spatial Minkowski Pythagorean Hodograph (MPH) curves are characterized with Rational Rotation Minimizing Frames (RRMFs). We define Euler-Rodrigues Frame (ERF) for MPH curves and by means of this concept, we reach the definition of MPH curves of type (n, m). Expressing the conditions provided by these curves in the form of Minkowski-Hopf map that we define, it is aimed to establish a connection with the Lorentz force which occurs during the process of Computer Numerical Control (CNC) type sinker Electronic Discharge Machines (EDMs). This approach is reinforced by split quaternion polynomials. Finally, we give conditons satisfied by MPH curves of low degree to be type (n, m) and construct illustrative examples.

In this work, we derive the spectral efficiency, secrecy outage probability, and bit error rate of a communication system assisted by a large intelligent surface (LIS). We consider a single-antenna user and an array of antennas at the transmitter side and the possibility of a direct link between transmitter and receiver. Additionally, there is a single-antenna eavesdropper with a direct link to the transmitter, which is modeled as a Nakagami-m distributed fading coefficient. The channels from transmitter to the LIS and from the LIS to the user may or may not have the line-of-sight (LoS) and are modeled by the Nakagami- m distribution. Moreover, we assume that the LIS elements perform non-ideal phase cancellation leading to a residual phase error that assumes a Von Mises distribution. We show that the resulting channel can be accurately approximated by a Gamma distribution whose parameters are analytically estimated using the moments of the equivalent signal-to-noise ratio. We also provide an upper bound for the error probability for M-QAM modulations. With the derived formulas, we analyze the effect of the strength of the LoS link by varying the Nakagami parameter, m.

Coxsackievirus B3 (CVB3) is one of the most common pathogens that cause myocarditis in humans. However, a sufficient therapeutic drug was not developed yet. Caboxamycin, a benzoxazole antibiotic, isolated from the culture broth of the marine strain Streptomyces sp., SC0774, displayed an antiviral effect in the CVB3-infected HeLa cells and CVB3-induced myocarditis mouse model. Caboxamycin significantly inhibited CVB3 VP1 production and cleavage of translation factor eIF4G1 from CVB3-infected HeLa cells at a 100 μg/ml concentration. Moreover, virus RNA amplification was dramatically reduced by caboxamycin treatment in HeLa cells. The caboxamycin cardiac protective effect was observed on the CVB3-mediated myocarditis mice model. The caboxamycin-treated mice survival was significantly increased compared to untreated mice (treated vs untreated, 100 vs 45 %). Heart histologic findings showed that myocardium damage and inflammation were significantly decreased by caboxamycin treatment. Caboxamycin directly inhibited caspase3 activity and cardiac myocytes apoptosis. These results suggested that caboxamycin strongly suppressed cardiac myocyte apoptosis and effectively inhibited the proliferation of CVB3 from in vitro and in vivo conditions. Furthermore, this study proposed that caboxamycin could potentially be applied in developing a new antiviral drug for CVB3-induced myocarditis.

Placenta-derived mesenchymal stem cells (PD-MSCs) have been highlighted as therapeutic sources in several degenerative diseases. Recently, microRNAs (miRNAs) were mediated one of the therapeutic mechanisms of PD-MSCs in regenerative medicine. To enhance the therapeutic effects of PD-MSCs, we established functionally enhanced PD-MSCs with phosphatase of regenerating liver-1 overexpression (PRL-1(+)). However, the profile and functions of miRNAs induced by PRL-1(+) PD-MSCs in a rat model with hepatic failure prepared by bile duct ligation (BDL) remained unclear. Hence, the objectives of the present study were to analyze the expression of miRNAs and investigate their therapeutic mechanisms for hepatic regeneration via PRL-1(+) in a rat model with BDL. We selected candidate miRNAs based on microarray analysis. Under hypoxic conditions, compared with invaded naïve PD-MSCs, invaded PRL-1(+) PD-MSCs showed improved integrin-dependent migration ability through RHO family-targeted miRNA expression (e.g., hsa-miR-30a-5p, 340-5p, and 146a-3p). Moreover, rno-miR-30a-5p and 340-5p regulated engraftment into injured rat liver by transplanted PRL-1(+) PD-MSCs through the integrin family. Additionally, an increase in PDGFRA by suppressing rno-miR-27a-3p improved vascular structure in rat liver tissues after PRL-1(+) PD-MSCs transplantation. Furthermore, decreased rno-miR-122-5p was significantly correlated with increased proliferation of hepatocytes in liver tissues by PRL-1(+) PD-MSCs by activating IL-6 signaling pathway through the repression of rno-miR-21-5p. Taken together, these findings improve the understanding of therapeutic mechanisms based on miRNA-mediated stem cell therapy in liver diseases.

Background: Ventilator-associated pneumonia (VAP) is among the most common healthcare-associated infections in Pediatric Intensive Care Units (PICUs). Because of the lack of a gold-standard diagnostic test, early diagnosis of VAP is challenging. We investigated whether bronchial biomarkers interleukin-4 (IL-4), plasminogen activator inhibitor-1 (PAI-1) and soluble receptor for advanced glycation end products (RAGE) could contribute in early VAP diagnosis through their fluctuation in time in critically ill pediatric patients. Methods: Bronchial secretions were collected from PICU patients with VAP on days 1 and 6. PAI-1, RAGE and IL-4 levels were measured by ELISA. Protein concentrations between high and low VAP suspicion patients were compared using unpaired Student’s t or Mann–Whitney U tests. Results: Twenty PICU patients, with median age 7.75yrs (range 0.5-15.3), mechanically ventilated for ≥48hrs with increased oxygenation requirements and VAP clinical/laboratory signs were enrolled. They were divided in VAP high-suspicion (n=12) or low-suspicion (n=8) groups based on Clinical Pulmonary Infection Score (cutoff:6). ΡΑΙ-1 και RAGE levels did not differ between high- or low-VAP suspicion groups the 1st or 6th days (p-value&gt;0.05). IL-4 was not detected in bronchial secretions. Conclusion: Bronchial concentrations of IL-4, PAI-1 and RAGE in critically ill children are not correlated with high- or low-VAP suspicion.

Non-alcoholic steatohepatitis (NASH) is diagnosed by the occurrence of fat buildup, inflammation, and fibrotic changes within the liver. NASH has the capacity to proceed to the advancement of decompensated cirrhosis and carcinoma by inflammation and oxidative stress. Although Agrimonia pilosa has traditionally been used medicinal purposes, its effects on the liver remains incompletely elucidated. In this research, we assessed the therapeutic outcomes of Agrimonia pilosa extract (APE) on free fatty acid (FFA)-treated HepG2 cellular hepatic steatosis and in a choline-deficient, L-amino acid-defined, high-fat diet with 0.1% methionine (CDAHFD)-induced NASH mouse model. In FFA-treated cells, APE inhibited intracellular lipid accumulation, and regulated the mRNA and protein expressions of modulators of fatty acid (FA) synthesis as well as FA oxidation proteins, through down-regulation of the AMP-activated protein kinase/sirtuin 1 signaling pathway. In the CDAHFD-induced NASH mouse model, APE significantly enhanced liver histology and serum levels of liver damage. APE also significantly attenuated hepatic expression of mRNA and proteins related to FA synthesis, inflammation, and fibrosis. Furthermore, APE mitigated the expression levels of oxidative stress and endoplasmic reticulum stress. Overall, these discoveries indicate that Agrimonia pilosa has the potential to treat NASH by regulating hepatic lipid metabolism, alleviating inflammation, and mitigating oxidative stress.

Background In this study we investigated in detail the role of cannabidiol (CBD), Beta-caryophyllene (BC), or their combinations in diabetic peripheral neuropathy (DN). The key factors that contribute to DN include mitochondrial dysfunction, inflammation, and oxidative stress. Methods Briefly, Streptozotocin (STZ) (55 mg/kg) was injected intraperitoneally to induce DN in Sprague Dawley rats and performed procedures including Randall Sellito Calipers, Von Frey Aesthesiometer, hot plate, and cold plate methods to determine mechanical and thermal hyperalgesia in vivo. The blood flow to the nerves was assessed by using the Laser Doppler device. Schwann cells were exposed to high glucose (HG) at a dose of 30 mM to induce hyperglycemia and DCFDA, JC1 & Mitosox staining were done to determine mitochondrial membrane potential, reactive oxygen species and mitochondrial superoxides in-vitro. The rats were administered i.p with BC (30mg/kg), CBD (15mg/kg), or combination while Schwann cells were treated with 3.65 µM CBD, 75 µM BC, or combination to assess their role in DN amelioration. Results Our results revealed that exposure to BC and CBD diminished HG-induced hyperglycemia in Schwann cells, in part, through reducing mitochondrial membrane potential, reactive oxygen species and mitochondrial superoxides. Further, BC and CBD combination treatment in-vivo could prevent the deterioration of mitochondrial quality control system by promoting autophagy and mitochondrial biogenesis while improving blood flow. CBD and BC treatments also reduced pain hypersensitivity to hyperalgesia and allodynia with increased antioxidant and anti-inflammatory action in diabetic rats. These in vivo effects were attributed to significant upregulation of AMPK, SIRT3, Nrf2, PINK1, PARKIN, LC3B, Beclin1 and TFAM functions while downregulation of NLRP3 inflammasome, NFκB, COX2 and p62 activity was noted as determined by western blotting. Conclusion the present studies demonstrated that STZ & HG induced oxidative and nitrosative stress play a crucial role in the pathogenesis of diabetic neuropathy. We find, for the first time, that CBD and BC combination ameliorate DN via modulating the mitochondrial quality control system.