This study investigated the inhibitory effect of Siegesbeckia orientalis ethanolic extract (SOE) on growth and metastasis of hepatic tumors in C57BL/6JNarl mice, which is the model of tumor-igenesis induced by subcutaneous injection of Hepa1-6 murine hepatoma cells on the back of mice. Feeding 25 mg SOE/kg BW daily for 14 days effectively reduced the hepatoma weight in tu-mor-bearing mice by 59.7%. SOE intervention reduced the expression of anti-apoptotic Bcl-2 gene in tumor tissue by 48.5% and down-regulated the antioxidant system, by reducing the gene ex-pression of catalase (48.0%), glutathione peroxidase (46.3%), and superoxide dismutase (32.0%). In addition, SOE intervention increased the production of ROS by 21.4%, and the gene expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 by 135.3%, 179.3% and 91.7%, respectively, indicating that SOE intervention promoted the acute inflammatory response. Results of H&E staining analysis showed that SOE had the ability to inhibit angiogenesis in tumor tissue. Fur-thermore, SOE treatment inhibited the expression of migration-related genes, such as MMP-2, MMP-7, MMP-9 and β-catenin, and the inhibition rates were 24.8%, 27.4%, 10.4% and 21.9%, respectively. These results imply that SOE had the ability to suppress tumor metastasis. On the other hand, SOE intervention decreased the serum contents of inflammatory cytokines, such as TNF-α, IL-1β and IL-6 by 27.4%, 30.4%, and 30.7%, respectively, indicating that SOE intervention has an anti-inflammatory effect on normal tissues of mice. Since SOE intervention had no signif-icant effect on liver and kidney weights, and no mice died throughout the experiment, it shows that it is safe to feed SOE under this experimental condition. Based on the above results, SOE has a great potential to be used in the treatment of hepatoma.

Hepatitis E virus (HEV) is a common cause of acute hepatitis worldwide, accounting for approximately 25% of deaths among pregnant women. We previously reported that pregnancy serum facilitates HEV replication in vitro. However, the differences in host cells with HEV infection induced by pregnancy serum and fetal bovine serum (FBS) are unclear. In this study, differentially expressed proteins were identified in HEV-infected hepatoma cells (HepG2) supplemented with different sera by using isobaric tags for relative and absolute quantitation. Proteomic analysis indicated that HEV infection significantly induced 1014 differentially expressed proteins in HEV-infected HepG2 cells when supplemented with FBS compared with pregnancy serum. Further validation by Western blot confirmed that filamin A, heat-shock proteins 70 and 90, Cytochrome c, and Thioredoxin were associated with HEV infection. This comparative analysis provides an important basis to further investigate HEV pathogenesis in pregnant women and HEV replication.

The distribution of oil and gas phases around ball-raceway local regions is an important basis and foundation for determining whether a bearing is sufficiently lubricated. To obtain the oil phase distribution law in the inner raceway-ball contact local region (IBCR) and outer raceway-ball contact local region (OBCR) of the under-race lubrication ball bearing, the numerical simulation method is used. The effects of bearing rotation speed, oil flow rate, oil viscosity and oil density on these two regions are studied. The results indicate that the oil phase exhibited significant periodic changes in both time and space. Compared with that in the IBCR, the oil phase distribution in the OBCR is more uniform. Increasing the bearing rotation speed and reducing the oil flow rate made the IBCR and OBCR more uniform. Changing the oil viscosity only alters the distribution pattern of the OBCR. The oil density may not affect the fluid flow state or the oil phase distribution in the bearing.

In order to tackle the issue of severe rocking phenomenon under seismic conditions in structures equipped with steel spring isolation bearings, this paper investigates a novel type of anti-rocking bearing. Firstly, the structural configuration and working principle of the novel anti-rocking bearing are introduced, and a design method for bearing parameters is proposed. Secondly, a finite element analysis model is established using SAP2000 software to conduct nonlinear dynamic time history analysis under seismic loading. The analysis results show that the structural arrangement of the novel anti-rocking bearing reduces both the vertical displacement difference and the rocking angle of the isolation layer. The bearing exhibits a certain level of anti-rocking effect, but it may cause significant tensile forces in some bearings, necessitating the installation of anti-tensile reinforcement. The effectiveness of the anti-rocking effect improves as the stiffness of the steel tension rod in the bearing increases; however, it also leads to higher maximum tension in individual bearings as well as the total tension in all bearings. For structures equipped with the novel anti-rocking bearing, the acceleration amplifies under most cases, with amplification coefficients ranging from 0.82 to 1.55. The performance of the novel anti-rocking bearing varies significantly for different seismic waves. The stiffness of the steel tension rod should be determined considering the reference pressure of the bearing and the maximum designed tension of the bearing. Through the finite element simulation of the bearing, the mechanical properties of the bearing are basically the same as the theoretical analysis results. For the cylinder and the joint bearing, certain structural measures need to be taken to ensure its strength and stiffness.

The current study aimed to investigate the antitumor effects and potent mechanism of cytokine-induced killer (CIK) cells combined with irreversible electroporation (IRE) via an in vitro function assay in an in vivo Panc02 cell–bearing mouse model. We established an in vitro culture assay for CIK cells and determined the proportions of different peripheral lymphocytes. The antitumor effect of the combination of IRE and CIK cells in a Panc02 pancreatic-cancer (PC) subcutaneous-xenograft model was investigated; tumor size and mouse survival rates were recorded. We used flow cytometry (FCM) to analyze the proportion of intratumoral lymphocytes, the expression of chemokine receptors, and the proliferative activity of CIK cells. The proportion of cells that were positive for clusters of differentiation 3 and 8 (CD3+CD8+) and the proportion of CD3+CD56+ cells were both significantly increased after 21 days of in vitro culture. Combined IRE/CIK cell treatment significantly inhibited tumor growth and increased the survival rate of Panc02 cell–bearing mice. Furthermore, infiltration of lymphocytes into tumor tissue was significantly increased by this combination therapy compared with the untreated group or monotherapy group. In addition, IRE significantly enhanced the expression of chemokine receptors elicited by, and the proliferative activity of, CIK cells. In conclusion, IRE combined with CIK cells showed superior antitumor efficacy in a PC subcutaneous-xenograft model, which we attributed to the promotion of lymphocytic infiltration, as well as to upregulation of chemokine receptor expression and of regulators of CIK cell proliferation.

Background: Ankle fractures, comprising about 10% of musculoskeletal injuries, pose a significant healthcare burden with an increasing incidence, particularly among an aging population. This study focuses on isolated Danis-Weber type B fractures. Recent trends lean towards surgical intervention for anatomical restoration, quicker recovery, albeit with associated complications. This report aims to assess the safety and efficacy of NewClip narrow locking plate system with early weight bearing in treating isolated fibular fractures. Methods: The study includes patients with Danis-Weber type B fractures surgically treated with NewClip narrow locking plate system. Exclusions involved nondisplaced fractures, open fractures, or those requiring additional fixation.Results: Fifteen patients were enrolled in this study. Minor complications, including wound swelling, were observed in two cases. The Visual Analogue Scale (VAS) for pain exhibited a steady decline postoperatively, with almost complete resolution by the third month. At three months, the FAOS demonstrated excellent results, and final follow-up at twelve months revealed complete osseous healing without complications.Conclusions: The use of this type of plates in treating isolated fibular fractures with early weight bearing shows promising results in terms of fracture healing, pain resolution, and functional outcomes warranting further investigation with larger cohorts.

Diabetes is a major health concern that the next-generation of on-demand insulin releasing implants may overcome for personalized therapy. Therein, 3D-printed phenylboronic acid-containing subcutaneous implants with on-demand glucose-triggered drug release abilities are produced using high resolution stereolithography technology. To that end, the methacrylation of phenylboronic acid is targeted following a two-step reaction. The resulting photocurable phenylboronic acid derivative is accordingly incorporated within bioinert polyhydroxyethyl methacrylate-based hydrogels at varying loadings. The end result are sub-centimeter scaled 3D-printed bionert implants that can be remotely activated with 1,2-diols and 1,3-diols such as glucose for on-demand drug administration such as insulin. As a proof of concept, varying glucose concentration from hypoglycemia to hyperglycemia levels readily allow the release of pinacol, i.e. a model molecule with similar release properties than insulin, at respectively low and high rates. In addition, the results demonstrated that adjusting the geometry and size of the 3D-printed part is a simple and suitable method for tailoring the release behavior and dosage.

In human body, carboxylesterases (CEs) play the crucial roles in xenobiotic metabolism and lipid homeostasis. But the abnormal CEs expression is highly associated with some diseases, such as hyperlipidemia, diabetes and liver cancer. Therefore, it is of great significance to develop an efficient tool for the accurate detection of CEs in living organisms. Herein, an innovative near-infrared (NIR) fluorescent probe TTAP−AB has been designed for CEs detection based on aggregation-induced emission (AIE) mechanism. This probe exhibits rapid response (2 min), excellent sensitivity (limit of detection = 8.14×10−6 U/mL), and high selectivity towards CEs. Additionally, owing to the good biocompatibility, probe TTAP−AB enables to monitor the dynamic changes of CEs level under drug-induced modulation in living cells and zebrafish. More importantly, probe TTAP−AB is successfully employed to image the liver tumor and assist tumor resection by the real-time monitoring of CEs, indicating that TTAP−AB is promising to guide liver cancer surgery. Therefore, probe TTAP−AB can not only enrich the strategies for CEs detection in biological systems, but also has great potential for some clinical imaging applications, including medical diagnosis, preclinical research, and imaging-guided surgery.

Vibration signal analysis is regarded as a fundamental approach in diagnosing faults in rolling bearings, and recent advancements have shown notable progress in this domain. However, the presence of substantial background noise often results in the masking of these fault signals, posing a significant challenge for researchers. In response, an Adaptive Denoising Autoencoder (ADAE) approach is proposed in this paper. The data representations are learned by the encoder through convolutional layers, while the data reconstruction is performed by the decoder using deconvolutional layers. Both the encoder and decoder incorporate adaptive shrinkage units to simulate denoising functions, effectively removing interfering information while preserving sensitive fault features. Additionally, dropout regularization is applied to sparsify the network and prevent overfitting, thereby enhancing the overall expressive power of the model. To further enhance ADAE's noise resistance, shortcut connections are added. Evaluation using publicly available datasets under scenarios with known and unknown noise demonstrates that ADAE effectively enhances the signal-to-noise ratio in strongly noisy backgrounds, facilitating accurate diagnosis of faults in rolling bearings.

Weight-bearing computed tomography (WBCT) enables acquisition of three dimensional bony structure images in a physiological weight-bearing position, which is fundamental in under-standing the pathologic lesions and deformities of the ankle joint. Over the past decade, re-searchers focused on validating and developing WBCT measurements, which has significantly enhanced our knowledge of common foot and ankle disease. Consequently, understanding the application of WBCT in clinical practice is becoming more important to produce improved out-comes in the treatment of disease around the ankle joint. This review will describe an overview of what is currently being evaluated in the foot and ankle surgery using WBCT and where the course of research will be heading in the future.

A proposed low-temperature forging method aims to enhance stainless steel bearings by creating a martensitic subsurface layer, significantly boosting bearing fatigue life due to increased surface hardness. This technique induces beneficial residual stresses, particularly in axial bearings, streamlining their construction and improving machine elements. Challenges persist, especially with radial bearings, but simplicity in axial bearing forging promotes compact, resource-efficient facility construction. Future research will focus on applying this technique to axial bearing washers, potentially replicating success in other bearing components. Despite the energy ex-penditure for cooling during forging, the substantial increase in bearing fatigue life offsets this, enhancing overall longevity and reliability of critical machine components. Integration of this forging technique into bearing fabrication appears seamless, offering a promising trade-off be-tween energy use and enhanced performance.

It is imperative to conduct experimental studies on the seepage behavior of gas-bearing coal under cyclic dynamic loading conditions. This paper focuses on the evolution of coal permeability under the combined effects of dynamic loading, static loading, and gas adsorption. The principal conclusions are as follows. (1) As the frequency and amplitude of dynamic loading increase, the development of pore and fissure structures within the coal body becomes increasingly pronounced during dynamic loading cycles, resulting in a gradual rise in permeability. Notably, as the coal approaches its yielding stage, the permeability can increase by up to 47%. (2) The permeability curve is divided into four regions: the compaction reduction zone, the oscillation zone, the gradual recovery zone, and the abrupt increase zone of failure. Ultimately, in the failure phase, the permeability surges dramatically, potentially reaching 4 to 5 times the initial permeability. (3) When the static load stage is constant, the rate of change in permeability of the coal under dynamic loading decreases with increasing adsorption amount. When the adsorption amount is constant, the rate of change in permeability of the coal under dynamic loading increases with the increase in static load stress stage, with the maximum increase reaching 75.2%. It can be concluded from the rate of change in permeability and the dynamic loading sensitivity coefficient that the permeability of the coal is highly sensitive to cyclic dynamic loading, with increased sensitivity associated with larger static load stages and decreased sensitivity with greater adsorption amounts.

Glioblastoma (GBM) is an aggressive and lethal primary brain tumor with restricted treatment options and a dismal prognosis. Oncolytic virotherapy (OV) has developed as a promising approach for GBM treatment. However, reaching invasive GBM cells may be hindered by tumor-surrounding, non-neoplastic cells when the OV is applied intratumorally. In this study, using a rodent GBM model and immunofluorescence analyses, we investigated the intranasal delivery of the oncolytic adenovirus (OAV) XVir-N-31 via virus-loaded, optimized shuttle cells. Intranasal administration (INA) was selected due to its non-invasive nature and the potential to bypass the blood-brain barrier (BBB). Our findings demonstrate that INA of XVir-N-31 loaded shuttle cells successfully delivers OAVs to the core tumor and invasive GBM cells, significantly prolongs the survival of GBM bearing mice, induces immunogenic cell death and finally reduces tumor burden, all this highlighting the therapeutic potential of this innovative approach. Overall, this study provides compelling evidence for the effectiveness of INA of XVir-N-31 via shuttle cells as a promising therapeutic strategy for GBM. The non-invasive nature of INA of OV-loaded shuttle cells holds great promise for future clinical translation. However, further research is required to assess the efficacy of this approach to ultimately progress in human clinical trials.

The existing PDC(Polycrystalline Diamond Compacts) -cone hybrid bit bearing adopts a unilateral support structure, which is prone to stress concentration in the journal area, resulting in fracture and wear failure of the bearing, thus reducing the service life of the hybrid bit. In this paper, a new type of double supported bearing hybrid bit is proposed. The static strength analysis of unilateral and bilateral support bearing structures is carried out by finite element simulation, and the stress and strain distribution of the two structures under the load of 20KN-100KN is obtained. Experimental devices for unilateral and bilateral support bearing structures are designed and manufactured to complete 50KN-100KN static pressure loading experiments. The results showed that the stress and strain of unilateral and bilateral support bearing increased linearly with the increase of load. Compared with unilateral bearing, when the load was 100KN, the maximum Mises stress of bilateral bearing decreased from 358.80MPa to 211.10MPa, with a decrease of 41.16%. The maximum contact stress decreased from 415.20MPa to 378.10MPa, decreased by 8.94%, and the maximum principal strain decreased from 11.01e-4 to 9.71e-4, decreased by 11.81%. The axial strain in the danger zone was reduced by 14.68% and 17.35%, respectively. It is found that the contact stress of the simulation data is highly correlated with the bearing life, and the service life of the bilateral bearing bit is increased by 8.94%. The simulation data and experimental results provide data support for the production of hybrid bits with bilateral bearing support.

Interpore hydrates are the main occurrence forms of marine gas hydrates. Pore characteristics are a vital factor affecting the thermodynamic properties of hydrates and their distribution in sediments. Currently, the characterization of the pore system for hydrate-bearing reservoirs are little reported. Therefore this paper focus on the Krishna-Godavari Basin, via varies methods to characterize the hydrate-bearing sediments in the region. The results showed that X-ray Diffraction(XRD) combined with Scanning Electron Microscope (SEM)and Cast Thin Section (CTS) can better characterize the mineral composition in the reservoir, High Pressure Mercury Injection (HPMI) focused on the contribution of pore size to permeability, Constant Rate Mercury Injection(CRMI) had the advantage of distinguishing between pore space and pore throat, and Nuclear Magnetic Resonance Cryoporometry (NMRC) technique can not only obtain the pore size distribution of nanopores with a characterization range greater than Nitrogen Gas Adsorption (N2GA), but also quantitatively describe the trend of fluids in the pore system with temperature. As for pore system, Samples 58 and 68 all developed nanopores, the mineral distribution was relatively scattered, and they were rich in paleontological shells such as foraminifera, among which Sample 68 had more pyrite content, and abundant pyrite framboid was observed, which made the intergranular pore develop and provide more nanopores. Sample 58 has a high concentration of pore and throat, high pore connectivity, low pore curvature, and pores with a diameter of 10μm contributing to the main permeability, with an average pore radius of 2.495μm, whereas Sample 68 has poor pore connectivity, high curvature, and pores with a diameter of 1μm contributing to the main permeability, with an average pore diameter of 60 nm, which explains the obvious difference in permeability between the two samples.

Mechanical power and motion are often transmitted by the gear-rotor-bearing system. When there are fitting clearances between the housing and outer ring in bearings, complex vibration responses will be generated, which makes the operating status difficult to identify. Therefore, for analyzing dynamic responses, a dynamic model of gear-rotor-bearing systems with bearing fitting clearances is proposed. In the model, the bearing system with fitting clearances and gear pair system are combined, and the coupling relationship is determined by the gyroscopic mo-tion of the shaft. The friction force and collision force caused by fitting clearances are also con-sidered, which are simulated by the Coulomb friction model and Hertz theory. The result shows that the meshing stiffness will also be excited by the bearing displacement. When there are fit-ting clearances on the bearing, the amplitude modulation of the bearing outer raceway to the system time-domain response is intensified, and the multiple harmonic frequency of bearings and gear pairs are generated on the spectrum, as well as defect frequencies of gear pairs. As the fitting clearance is increased, the higher multiple harmonic responses will be caused. Although the response amplitude of the gearbox is increased by raising the input speed, multiple harmon-ic responses are suppressed, which makes the system mainly vibrate at the fundamental fre-quency. Then, the dynamic model and the vibration analysis are experimentally verified.

Bearing fault diagnosis is crucial for ensuring the stable operation of mechanical equipment. With the continuous development of deep learning technology, Convolutional Neural Networks (CNNs) have demonstrated significant advantages in the field of fault diagnosis. This paper proposes a new method that combines various CNN architectures to improve the accuracy of bearing fault diagnosis. We designed five different convolutional network structures, including SerConv, ResConv, One-Shot Aggregation Convolution (OSAConv), Cross-Stage Aggregation Convolution (CSAConv), and MD-DAConv. Experimental results on the Case Western Reserve University (CWRU) bearing dataset show that the proposed method exhibits high accuracy and robustness in fault diagnosis. The results indicate that strategies such as multi-directional, multi-scale, and residual connections play a crucial role in enhancing the depth and breadth of feature extraction, while simple and effective feature fusion and information transmission mechanisms are key to ensuring the robustness and generalization ability of the model.

(1) Background: In most cases, passive isolation control methods are commonly used for the seismic isolation design of bridge engineering. However, for passive seismic isolation devices, due to their non-adjustable performance parameters, it is challenging to achieve a good seismic isolation effect for structures under random and variable seismic loads in the wide frequency range of 0 Hz to 20 Hz; (2) Methods: the sensitivity of the design parameters of the seismic isolation bearing was analyzed using the optimization center gradient method, and an improved genetic algorithm was employed to quickly optimize and obtain the optimal design parameters; (3) Results: the effectiveness of the three-dimensional seismic isolation bearing was validated through experiments. (4) Conclusions: The multi-factor sensitivity analysis approach used in this study for designing novel isolation bearings is applicable not only to seismic design in bridges but also serves as a reference for parameter design in isolation bearings requiring medium to high precision in seismic performance.

In order to study the effect of explosion load on the flexural performance of RC beams, two RC beams of the same size were carried out explosion test and bearing capacity test successively. Piezoelectric intelligent aggregate was embedded in the beams in advance to monitor the damage state of the beams, which realized the whole process of damage monitoring of the concrete inside the structure from explosion damage to compression damage.Based on wavelet packet analysis and residual bearing capacity damage evaluation criteria, the beam damage was quantitatively evaluated, and the bending bearing capacity of RC beam after explosion damage was compared and analyzed.The results show that the change of concrete strain gauge signal, the phenomenon of crack development and the increase of internal crack development index indicate that the RC beam is damaged by explosion load.After explosion damage, the damage index of the beam increases and the residual bending capacity decreases, which proves that the piezoelectric intelligent aggregate sensor can effectively monitor the bending capacity change of the component after explosion damage.

Four angucycline glycosides including three new compounds landomycin N (1), galtamycin C (2) and vineomycin D (3), and a known homologue saquayamycin B (4), along with two alkaloids 1-acetyl-β-carboline (5) and indole-3-acetic acid (6), were identified from the fermentation broth of an intertidal sediments derived Streptomyces sp. Their structures were mainly established by IR, HR-ESI-MS, 1D and 2D NMR techniques. Among the isolated angucyclines, saquayamycin B displayed potent cytotoxic activity against hepatoma carcinoma cells HepG-2, SMMC-7721 and plc-prf-5, with IC50 values 0.135, 0.033 and 0.244 μM respectively, superior to positive drug doxorubicin. Saquayamycin B treatment to SMMC-7721 cells led to the typical morphological signs of apoptosis in 4',6-diamidino-2-phenylindole (DAPI) staining experiment.

Familial Alzheimer’s disease (FAD) can be caused by mutations in PSEN1 that encodes presenilin-1, a component of the gamma-secretase complex that cleaves amyloid precursor protein. Alterations in calcium (Ca2+) homeostasis and glutamate signaling are implicated in the pathogenesis of FAD, however it has been difficult to assess in humans whether or not these phenotypes are the result of amyloid or tau pathology. This study aimed to assess early calcium and glutamate phenotypes of FAD by measuring the Ca2+ response of induced pluripotent stem cell (iPSC)-derived neurons bearing PSEN1 mutations to glutamate and the ionotropic glutamate receptor agonists NMDA, AMPA and kainate compared to isogenic control and healthy lines. The data shows that in early neurons, even in the absence of amyloid and tau phenotypes, FAD neurons exhibit increased Ca2+ responses to glutamate and AMPA, but not NMDA or kainate. Together this suggests that PSEN1 mutations alter Ca2+ and glutamate signaling as an early phenotype of FAD.

The normal growth and development of skeletal muscle is essential for the health of the body. The regulation of skeletal muscle by intestinal microorganisms and their metabolites has been continuously revealed. Acetate is the predominant short-chain fatty acid synthesized by gut microbiota through the fermentation of dietary fiber, however, the underlying molecular mechanisms governing the interaction between acetate and skeletal muscle during rapid growth stage remain to be further elucidated; Here, specific pathogen-free (SPF) mice, germ-free (GF) mice, and germ-free mice supplemented with sodium acetate (GS) were used to evaluate the effects of acetate on skeletal muscle growth and development of young mice with gut microbiota deficiency; We found the concentration of serum acetate, body mass gain, succinate dehydrogenase activity and expression of myogenesis maker gene of skeletal muscle in the GS group was higher than GF group following sodium acetate supplement. Furthermore, the transcriptome analysis revealed that acetate activated biological processes regulating skeletal muscle growth and development in GF group that are inhibited due to gut microbiota deficiency. In vitro experiment, we proved that acetate up-regulated Gm16062 to promote skeletal muscle cell differentiation; Overall, our findings proved that acetate promote skeletal muscle growth and development in young mice via increase Gm16062 expression.

This study investigates the effects of xylitol, a natural sugar alcohol, on tumor progression in syngeneic mouse cancer models. Xylitol has been known for its dental health benefits, but emerging evidence suggests broader biological roles, including potential anti-cancer properties. We explored xylitol's impact on two mouse cancer models: 4T1 mammary carcinoma and B16F10 melanoma. Xylitol's efficacy in inhibiting cancer cell lines and modulating tumor progression was assessed using immunocompetent female mice. The experiments involved intratumoral and peri-tumoral administration of a 20% xylitol solution in two mouse strains: BALB/c (4T1 mammary carcinoma) and C57BL/6 (B16F10 melanoma). Tumor volume, histopathology, and metabolomic analyses were conducted to gauge xylitol's influence. The study revealed that xylitol administration initially reduced tumor growth in the B16F10 melanoma model, accompanied by alterations in tumor metabolism. However, similar effects were not observed in the 4T1 mammary carcinoma model, and melanoma tumor growth re-commenced after stroma deterioration permitted xylitol solution leakage. These findings suggest that xylitol may have potential as an adjunct therapy in cancer treatment, specifically in melanoma. The differential response between the two cancer models underscores the complexity of cancer biology and the need for further investigation into xylitol's mechanisms of action and its role in cancer therapy.

Obesity is a highly prevalent chronic disease characterized by excessive weight gain and fat accumulation. There is growing evidence that Lactiplantibacillus plantarum strains with bile salt hydrolase (BSH) activity are effective in preventing and alleviating obesity. However, few of them has confirmed the anti-obesity effect of BSH by gene deletion. In this study, 23 BSH-positive Lp. plantarum strains were screened by bile salt precipitation halo assay. Among these strains, Lp. plantarum Lp20 showed the highest BSH activity with a hydrolysis rate to glycodeoxycholic acid (GDCA) by 91.62%. Genomic sequencing and bioinformatics analysis indicated that gene bsh1 was associated with BSH activity of Lp. plantarum Lp20 and gene deletion of bsh1 confirmed the role of Bsh1 in GDCA hydrolysis. To investigate if the Bsh1 from Lp. plantarum Lp20 could alleviate obesity, the wild type and bsh1 deletion mutant strains were administered daily for 8 weeks to diet-induced obese mice, respectively. Compared with mutant strain, the wild type strain Lp20 significantly reduced body weight gain, inguinal white adipose tissue and mesenteric fat mass in obese mice. In addition, Lp20 also reduced serum total cholesterol levels and LDL-C by 20.8% and 33.3%, respectively. Furthermore, the recovered liver steatosis was only observed in Lp. plantarum Lp20 treated mice. Taken together, the bile salt hydrolase Bsh1 from Lp. plantarum Lp20 was a key functional factor on ameliorating HFD-induced obesity by reducing cholesterol levels and suppressing adipogenesis in mice.

Extremely low-frequency electromagnetic fields (ELF-EMF) are ubiquitous in industrial-11 ized environments due to the continuous use of electrical devices. Our previous studies demon-12 strated ELF-EMF affects muscle cells by modulating oxidative stress and enhancing myo-genesis. 13 This pilot study investigated these effects on skeletal muscles of sedentary adult mice, assessing 14 physiological responses to ELF-EMF exposure and potential modulation by antioxidant supplemen-15 tation. Male C57BL/6 mice were exposed to ELF-EMF (0.1 or 1.0 mT) 1 hour/day up to 5 weeks, and 16 fed a standard diet without or with N-acetyl-cysteine (NAC). Results showed transient increases in 17 muscle strength (after 2-weeks’ exposure at 1.0 mT), potentially linked to muscle fiber recruitment 18 and activation, revealed by higher PAX7 and MyH expression levels. After ELF-EMF exposure, ox-19 idative status assessment revealed transient increases in expression levels of SOD1 and catalase en-20 zymes, in total antioxidant capacity and in protein carbonyl levels, marker of oxidative damage. 21 These effects were partially reduced by NAC. In conclusion, ELF-EMF exposure affects skeletal 22 muscle physiology and NAC supplementation partially mitigates these effects, highlighting the 23 complex interactions between ELF-EMF and antioxidant pathways in vivo. Further investigations 24 on ELF-EMF as a therapeutic modality for muscle health are necessary.

Efficiency improvement is the new challenge in all fields of design. In this scenario the reduction of power losses is becoming more and more a main concern also in the design of power transmissions. Appropriate models to predict power losses are therefore from the earliest stages of the design phase. The aim of the project is to carry on lubrication simulations of several variants of a cylindrical-roller-bearing to understand the lubricant distribution and the related churning power losses. Several strategies to reduce the computational effort have been used. Among them the sectorial symmetry and three innovative meshing strategies (purely analytical with and without interfaces and analytical/subtractive) that have been implemented in the OpenFOAM® environment. The results of the different approaches were compared among them and with experimental observations showing good agreement and reasonable savings in terms of computational effort.

Small interfering RNA (siRNA) holds significant therapeutic potential by silencing target genes through RNA interference. Current clinical applications of siRNA have been primarily limited to liver diseases, while achievements in delivery methods are expanding its applications to various organs, including the lungs. Cholesterol-conjugated siRNA emerges as a promising delivery approach due to its low toxicity and high efficiency. This study focuses on developing a cholesterol-conjugated anti-Il6 siRNA and the evaluation of its potency for the potential treatment of inflammatory diseases using the example of acute lung injury (ALI). The biological activities of different Il6-targeted siRNAs containing chemical modifications were evaluated in J774 cells in vitro. The lead cholesterol-conjugated anti-Il6 siRNA after intranasal instillation demonstrated dose-dependent therapeutic effects in a mouse model of ALI induced by lipopolysaccharide (LPS). The treatment significantly reduced Il6 mRNA levels, inflammatory cell infiltration, and the severity of lung inflammation. IL6 silencing by cholesterol-conjugated siRNA proves to be a promising strategy for treating inflammatory diseases, with potential applications beyond the lungs.

Danyore Valley area is a new prospect of copper-gold mineralization in the Gilgit-Baltistan province, Kohistan terrane, northern Pakistan. The mineralization is Cu-Au vein-type, localized within quartz veins and controlled by a fracture system mainly trending NW and NE. The host units belong to the Ladakh-Kohistan arc terrane, which covers northern Pakistan and north-western India and mainly comprises Precambrian basement units, Paleozoic to Cenozoic magmatic rocks, and sedimentary strata. The mineralized wall rocks consist of Mesozoic gabbro and diorite, which have undergone an intensive hydrothermal alteration. The study area, Danyore Valley, has yet to be explored. The geological background and mineralization type in literature are scarce. Moreover, the tectonic setting, petrogenesis, age, and magmatic evolution of the gabbro-diorite hosting unit still need to be better understood. Furthermore, the sources of metals and mineralized fluids and the types of mineralization and alteration are also unexplored. This research's contribution presents the field investigation, microscopic observations, whole rock geochemistry (major, trace, and REE), mineral analysis (EPMA), in situ LA–ICP–MS zircon U–Pb age dating, and zircon trace elements data for Danyore Valley Cu-Au prospect of Kohistan Batholith. The current research work's objectives are to (a) constrain the emplacement ages of the Danyore Valley host rocks, (b) determine the petrogenesis and tectonic environment of the gabbro-diorite wall rocks, and (c) identify the mineralization style and alteration patterns of Cu-Au occurrences. The U-Pb isotopic data of studied zircons from Danyore Valley diorite specimens yielded concordia ages from 111.60 ± 0.90 Ma to 112.18 ± 0.74 Ma. Correspondingly, the gabbro rock sample displayed a concordia age of 110.21 ± 0.99 Ma, indicating the crystallization time of the host bodies is mainly the early cretaceous period (∼110 Ma). The findings of this study reveal that the calc-alkaline affinity and arc-like geochemical characteristics of the gabbro and diorite rocks have been characterized by a significant enrichment in large-ion lithophile elements and an apparent depletion in high-field strength elements. The parent magma probably originated from a partial melting process of mantle depletion, and geochemical traits are characteristic of magmas associated with subduction zones. The Danyore Valley area of Kohistan terrane is defined by the existence of several mineralized quartz veins, which are mainly sulfide assemblages. The sulfide ore is mainly comprised of chalcopyrite, pyrite, and bornite, with a smaller amount of covellite and sphalerite and significant traces of gold, which are distributed mainly in sulfides. Copper and gold mineralization of Danyore Valley is associated with phyllic, propylitic, and carbonatization alteration assemblages. Metal-rich quartz veins exhibit a spatial correlation with diorite and gabbro rocks. The discovery of several surface Cu-Au vein-type mineralized areas accompanying outcrops of copper supergene enrichment at the Danyore Valley prospect is significant evidence (predictor patterns) of porphyry-style deposits in the Gilgit district, Kohistan terrane, northern Pakistan. This work also advocates the importance of the Danyore Valley prospect and Kohistan Batholith region for further detailed geological studies.

TTF1-NP(5,2′,4′-trihydroxy-6,7,5′-trimethoxyflavone nanoparticles), derived from the traditional Changbai Mountain medicinal plant Sorbaria sorbifolia (SS), has been showedits anti-cancer effect in various liver cancer cell types and tissues. The present study was designed to evaluate the antitumor mechanism of the TTF1-NP against HepG2 hepatoma cells and HepG2 cells-induced hepatocarcinoma (HCC) in nude mouse model. Here we demonstrated that TTF1-NP inhibits tube formation of HUVECs and HepG2 cell migration and invasion, and inhibits tumor growth in nude mice implanted with HepG2 cells through the downregulation of STAT3 protein and activation, along with VEGF, KDR, bFGF, MMP2 and MMP9 levels. We further revealed that TTF1-NP decreased the DNA-binding capacity of STAT3. Together our results provide a mechanism by which TTF1-NP suppresses cancer cell migration, invasion and angiogenesis through the action of STAT3 and suggests TTF1-NP as a potential therapy for hepatocellular cancer treatment.

Amphiphilic block copolymers of N-vinyl pyrrolidone (NVP) and various vinyl esters (VEs), PNVP-b-PVEs, namely vinyl butyrate (VBu), vinyl decanoate (VDc) and vinyl stearate (VSt) were synthesized by RAFT polymerization techniques. The sequential addition of monomers methodology was employed starting from the polymerization of NVP followed by the polymerization of the VEs monomer. The reaction was conducted at 80oC in dioxane solutions using AIBN as initiator and O-ethyl S-(phthalimidylmethyl) xanthate as the CTA. The block copolymers were characterized by Size Exclusion Chromatography (SEC) and NMR spectroscopy. The thermal transitions of the copolymers were studied by Differential Scanning Calorimetry (DSC), whereas their thermal stability via Thermogravimetric Analysis (TGA) and Differential Thermogravimetry (DTG).

To further explore the bearing capacity and sustainable construction of vacuum drainage pipe (VDP) piles, field tests were carried out to compare and analyze the ultimate single pile bearing capacity, pile side friction and pile end resistance of ordinary piles and vacuum drainage pipe piles. The effect of the VDP pile on energy conservation and emission reduction in practical projects is discussed. The results shows that the VDP pile basically eliminated the soil squeeze and did not cause excessive relative displacement of pile and soil after vacuum consolidation. The VDP pile enhances pile side friction resistance, resulting in a 17.6% increase in ultimate bearing capacity compared to traditional piles. The VDP pile method can reduce carbon emissions by 31.4% compared to traditional methods. This study provides guidance for the production and design of VDP piles in the future and demonstrates their potential for energy conservation and emission reduction benefits compared to traditional methods.

Mandible is a bony structure of neuroectodermal origin with unique characteristics that support dentition and jaw movements. In the present study we investigated the effects of gestational exposure to a mixture of endocrine disrupting chemicals (EDCs) on mandibular growth in mice. The mixture under study (Mixture N1) has been associated with neurodevelopmental effects in both a human cohort and animal studies. Pregnant mice were exposed throughout gestation to 0.5x (times of pregnant women exposure levels), 10x, 100x and 500x of Mixture N1, or the vehicle, and the mandibles of the male offspring were studied in adulthood. Micro-CT analysis showed non-monotonic effects of Mixture N1 in the distances between specific mandibular landmarks and in the crown width of M1 molar, as well as changes in the mandibular bone characteristics. The alveolar bone volume was reduced, and the trabecular separation was increased in the 500X exposed mice. Bone volume in the condyle head was increased in all treated groups. The Alcian blue stained area of pre-hypertrophic chondrocytes in condyle’s head was increased in 0.5x, 10x and 100x groups, while the Safranin-O-stained area of mature hypertrophic chondrocytes was respectively reduced. This is the first indication that prenatal exposure to an epidemiologically defined EDC mixture, associated with neurodevelopmental impacts, can also affect mandibular growth in mammals.

In this work, studies were carried out on the extraction of silver and gold from cakes of pressure oxidation leaching of sulfide concentrate containing pyrite and arsenopyrite. The addition of gypsum at a consumption of 0.1 g/g of concentrate helps to increase silver extraction from 13.4 to 95–98% at the cyanidation stage, with no conditioning operation. Gold recovery was 99%. An increase in gypsum consumption contributes to the formation of BFAS with an increased content of sulfate sulfur, and a decrease in the As/S(sulfate) molar ratio in the cake from 3.7 down to 0.88 contributes to an increase in silver extraction at the cyanidation stage up to 98%, and its further decrease from 0.88 down to 0.58 leads to a gradual reducing silver transfer into solution from 98 down to 75.1% at the cyanidation stage. Basic ferric sulfate (BFS) is not formed in this case, since according to EDS mapping the distribution of arsenic and sulfur over iron-containing particles is uniform. According to TCLP analysis, the cake obtained after pressure oxidation leaching with the addition of gypsum and cyanidation is stable and suitable for disposal, since the final concentration of arsenic in the solution was 0.45 mg/dm3.

Methylmercury (MeHg) intoxication is a global health concern. Although MeHg neurotoxicity is well-recognized, less is known about MeHg's effects on metabolism. In this study, we evaluated MeHg intoxication (20mg/L in drinking water for 20 days) effects on liver and epididymal white fat (EWF) in young ApoE knockout (ko) and wild-type mice. The former is well-known to show spontaneous dyslipidemia. Hg levels in hair, liver, and EWF were measured to assess the degree of MeHg exposure. We also evaluated body weight gain, plasma triglycerides, total cholesterol levels, and liver injury by assessing steatosis score, AST, ALT, SOD, and TBAR levels. To evaluate EWF, we analyzed mean wet weight and adipocyte diameter, plasma leptin levels and metabolomics. Hg levels were markedly higher among intoxicated mice. ApoE ko mice showed higher Hg in the hair but lower levels in the liver and EWF than wild-type controls. Among wild-type mice, MeHg compromised weight gain and increased liver TBAR levels compared to non-challenged controls. Among non-intoxicated mice, ApoE deficiency significantly increased triglyceride, total cholesterol, and liver transaminases with reduced EWF wet weight, hepatic SOD, and plasma leptin levels. MeHg accumulation together with ApoE deficiency elevated total cholesterol, triglycerides, hepatic transaminases, and TBARS. We found distinct EWF metabolite activity in different scenarios of ApoE deficiency and MeHg intoxication, highlighting increased cardiovascular risk especially when both challenges occur. Further studies are required to elucidate the underlying mechanisms involved in these effects and the target nutritional interventions in most need to ameliorate them.

Dipeptidyl peptidase 9 (DPP9) is a multifunctional intracellular protease with roles in tumour growth, inflammation and mitochondrial function. We developed a hepatocyte-specific DPP9 knockout mouse (DPP9-KO) to explore DPP9 in a mouse model of hepatocellular carcinoma (HCC). DPP9-KO mice were generated by crossing Albumin-Cre mice (Wt/Wt Cre+/+) with DPP9 floxed mice (Fl/Fl Cre-/-). Mice were treated with Diethylnitrosamine and Thioacetamide then an atherogenic High Fat Diet until 28 weeks of age. DPP9-KO mice had reduced liver and subcuta-neous adipose tissue mass and lower fasting plasma glucose, fewer small macroscopic liver nod-ules compared to DPP9-WT mice. However, there were no differences in the total number of mac-roscopic liver nodules, tumour burden, inflammation score and steatosis score. Consistent with the known ability of DPP9 to suppress NLRP1 activation, activated caspase-1 protein was ele-vated in DPP9-KO mouse liver. Additionally, Nfkbib, Cxcl10 and Ccl5 mRNA and protein levels of autophagy marker beclin1 and tumour suppressor p53 were increased. In conclusion, DPP9 de-pletion in hepatocytes may reduce liver cancer initiation, via mechanisms that may include in-creased autophagy and innate tumour suppression in this experimental model. Finally, the data supports DPP9 having a role in glucose regulation by the liver.

Abstract: Non-alcoholic fatty liver disease (NAFLD) begins with lipid accumulation within hepatocytes, but the relative contributions of different macronutrients is still unclear. We inves-tigated the impact of fatty acids, glucose and fructose on lipid accumulation in primary human hepatocytes (PHH) and three different hepatoma cell lines: HepG2, Huh7 and McA-RH7777 (McA). Cells were treated for 48 hours with fatty acids (0 or 200μM), glucose (5mM or 11mM) and fructose (0mM, 2mM or 8mM). Lipid accumulation was measured via Nile Red staining. All cell types accumulated lipid in response to fatty acids (P<0.001). PHH and McA, but not HepG2 or Huh7 cells, accumulated more lipid with 11mM glucose plus fatty acids (P=0.004, fatty acid x glucose interaction, for both), but only PHH increased lipid accumulation in response to fructose (P<0.001). Considerable variation was observed between PHH cells from different individuals. Lipid accumulation in PHH was increased by insulin (P=0.003) with inter-individual variability. Similarly, insulin increased lipid accumulation in both HepG2 and McA cells, with a bigger response in McA in the presence of fatty acids (P<0.001 for fatty acid x insulin). McA were more insulin sensitive than either HepG2 or Huh7 cells in terms of AKT phosphorylation (P<0.001 insulin x cell type interaction). Hence glucose and fructose can contribute to the accumulation of lipid in PHH with considerable inter-individual variation, but hepatoma cell lines are not good models of PHH.

Matrix metalloproteinases have been implicated in muscular dystrophy progression and recent studies described the role of MMP-10 in skeletal muscle pathology of young dystrophic mice. Nevertheless, its implication in dystrophin deficient hearts is still missing. Here, we aimed at investigating MMP-10 implication in severe muscular dystrophic progression and characterize MMP-10 loss in skeletal and cardiac muscles of aged dystrophic mice. We examined the histopathological effect of MMP-10 ablation in aged mdx mice, both in the hind limb muscles and heart tissues. We have found that MMP-10 loss compromises survival rates of aged mdx mice, with skeletal and cardiac muscles developing a chronic inflammatory response. Our findings indicate that MMP-10 is implicated in severe muscular dystrophy progression, identifying a new area of investigation that could lead to future therapies for dystrophic muscles.

The epidemic of obesity has increased worldwide and is associated with comorbidities as diabetes as cardiovascular disease. Strategies that modulate body weight and improves glycemic metabolism has increased, and the bariatric surgeries as Sleeve Gastrectomy (SG) has been highlighted in obesity treatment. However, the mechanism by which SG reduces body weight and improves glycemic control are unknow. C57BL mice were submitted to a 10 weeks high fat-diet protocol and submitted to SG. Food intake, fed/fasted glycemia and hypothalamic anorexigenic and orexigenic gene expression were evaluated. SG reduces body weight, fasting glycemia, insulinemia and leptinemia in obese mice. Moreover, SG reduces food and total calorie intake with no alterations in the expression of anorexigenic and orexigenic gene expression. These data indicates that SG improves obesity associated alterations, at least in part, by reduction on food intake. This effect is not associated with the classic food intake pathway in hypothalamus, indicating the involvement of supplementary pathways in this process.

Epigenetic mechanisms, including histone post-translational modifications (PTMs), play a critical role in regulating pain perception and the pathophysiology of burn injury. However, the epigenetic regulation and molecular mechanisms underlying burn injury-induced pain remain insufficiently explored. Spinal dynorphinergic (Pdyn) neurons contribute to heat hyperalgesia induced by severe scalding-type burn injury through p-S10H3-dependent signaling. Beyond p-S10H3, burn injury may impact various other histone H3 PTMs. Double immunofluorescent staining and histone H3 protein analyses demonstrated significant hypermethylation at H3K4me1 and H3K4me3 sites and hyperphosphorylation at S10H3 within the spinal cord. By analyzing Pdyn neurons in the spinal dorsal horn, we found evidence of chromatin activation with a significant elevation in p-S10H3 immunoreactivity. We used RNA-seq analysis to compare the effects of burn injury and forma-lin-induced inflammatory pain on spinal cord transcriptomic profiles. We identified 98 DEGs for burn injury and 86 DEGs for formalin-induced inflammatory pain. A limited number of shared differentially expressed genes (DEGs) suggest distinct central pain processing mechanisms between burn injury and formalin models. KEGG pathway analysis supported this divergence, with burn injury activating Wnt signaling. This study enhances our understanding of burn injury mechanisms and uncovers converging and diverging pathways in pain models with different origins.

Succinate is proposed to be a mediator of muscle exercise-induced adaptations. We studied metabolic health and changes of muscle mass in 6-month-old male mice after 12 weeks of feeding regular diet (RD, 13.4 kcal% fat, 66.8 kcal% carbohydrate, 29.8 kcal% protein), high fat diet (HFD, 60 kcal% fat, 20 kcal% carbohydrates, 20 kcal% protein) and ketogenic diet (KD, 80 kcal% fat, &lt;1 kcal% carbohydrates, 20 kcal% protein) with or without 2% succinate supplements (SUS) in drinking water (n=8-12 per group). Functional overloading of the plantaris muscle (PL) was induced in a group of mice by denervation of the gastrocnemius and soleus muscles at week 6 of feeding different diets. HFD induced the greatest (p &lt; 0.001) increase in body and fat mass. HFD and KD lead to significant (p &lt; 0.01) impairment in glucose tolerance compared to RD. SUS blunted (p &lt; 0.01) initial surge in energy intake when mice were switched from RD to HFD, but did not influence any measures of metabolic health after 12 weeks of the study. Functional overloading lead to ~25% increase in PL mass which was not affected by diet or SUS. In conclusion, SUS does not have a long-term effect on metabolic health or muscle mass.

Objective: Lower extremity ischemia-reperfusion injury (IRI) may occur with trauma-related vascular injury and various vascular diseases, during the use of a tourniquet, temporary clamping of the aorta in aortic surgery, and acute or bilateral acute femoral artery occlusion. Mitochondrial dysfunction and increased basal oxidative stress in diabetes may cause an increase in the effects of increased reactive oxygen species (ROS) and mitochondrial dysfunction due to IRI. It is of great importance to examine therapeutic approaches that can minimize the effects of IRI, especially for patient groups under chronic oxidative stress. Cerium oxide (CeO2) nanoparticles mimic the antioxidant enzymes and act as a catalyst that scavenges ROS. In this study, it was aimed to investigate whether CeO2 has protective effects on skeletal muscles in lower extremity IRI in mice with streptozocin-induced diabetes. Methods: A total of 38 Swiss albino mice were divided into six groups as follows: control group (group C, n=6), diabetes group (group D, n=8), diabetes-CeO2 (group DCO, n=8), diabetes-ischemia/reperfusion (group DIR, n=8), and diabetes-ischemia/reperfusion-CeO2 (group DIRCO, n=8). DCO and DIRCO groups were given doses of CeO2 0.5mg/kg intraperitoneally 30 minutes before the IR procedure. A 120-minute ischemia-120-minute reperfusion period with 100% O2 was performed. At the end of the reperfusion period, muscle tissues were removed for histopathological and biochemical examinations. Results: Total antioxidant status (TAS) levels were found to be significantly lower in group DIR compared with group D (p=0.047 and p=0.022, respectively). In group DIRCO and total oxidant status (TOS) levels were found to be significantly higher than in group DIR (p

Background: Leishmaniasis is a significant global public health issue that is caused by parasites from Leishmania genus. With limited treatment options and rising drug resistance, there is a pressing need for new therapeutic approaches. Molecular chaperones, particularly Hsp90, play a crucial role in parasite biology and are emerging as promising targets for drug development. Objective: This study evaluates the efficacy of 17-DMAG in treating BALB/c mice from cutane-ous leishmaniasis through in vitro and in vivo approaches. Materials and Methods: We assessed 17-DMAG cytotoxic effect on bone marrow-derived mac-rophages (BMMΦ) and its effects against L. braziliensis promastigotes and intracellular amastigotes. Additionally, we tested the compound's efficacy in BALB/c mice infected with L. braziliensis via intraperitoneal administration to evaluate the reduction of lesion size and de-crease of parasite load in the ears and lymph nodes of infected animals. Results: 17-DMAG showed selective toxicity [selective index=432) towards Leishmania amastigotes, causing minimal damage to host cells. The treatment significantly reduced lesion sizes in mice and results in parasite clearance from ears and lymph nodes. It also diminished in-flammatory responses and reduced the release of pro-inflammatory cytokines (IL-6, IFN-g, TNF) and the regulatory cytokine, IL-10, underscoring its dual leishmanicidal and anti-inflammatory properties. Conclusion: Our findings confirm the potential of 17-DMAG as a viable treatment for cutaneous leishmaniasis and support further research into its mechanisms and potential applications against other infectious diseases.

According to previous studies the median raphe region (MRR) is known to contribute significantly to social behavior. Beside serotonin, there are reports of a small population of dopaminergic neu-rons in this region. Dopamine is linked to reward and locomotion, but very little has been known about its role in the MRR. To address that, we first confirmed the presence of dopaminergic cells in the MRR of mice (immunohistochemistry, RT-PCR) and humans (RT-PCR). Next, we used chemogenetic technology in mice containing Cre enzyme under the promoter of the dopamine transporter (DAT). With the help of an adeno-associated virus, artificial receptors were expressed in the dopaminergic cells of the MRR (DAT-MRR). Four weeks later, extensive behavioral charac-terization started 30 minutes after the injection of the artificial ligand (Clozapine-N-Oxide). Stimu-lation of DAT-MRR decreased social interest without influencing aggression and with an increase in social discrimination. Additionally, inhibition of the same cells increased the friendly social be-havior during social interaction test. No behavioral changes were detected in anxiety, memory and locomotion. All in all, dopaminergic cells were present both in the mice and human MRR, and manipulation of dopaminergic neurons of the MRR elicited a specific social response.

The service conditions of underground coal mine equipment are poor, and it is difficult to accurately extract the fault characteristics of rolling bearings. In order to better improve the accuracy of fault identification of rolling bearings, a fault detection method based on multiscale permutation entropy and SOA-SVM is proposed. First, the whale optimization algorithm is used to select the modal analysis number K and the penalty factor α of the variational mode decomposition algorithm. Then, the vibration signal of rolling bearings is dissolved according to the optimized variational mode decomposition algorithm, and the multi-scale permutation entropy of the main intrinsic mode function is calculated. Finally, the feature values of the matrix are entered into the SVM algorithm optimized by the seagull optimization algorithm to obtain the classification result. The experimental results based on the published rolling bearing datasets of Western Reserve University show that the identification success rate of the proposed method can reach 98.75%. The fault detection of the rolling bearings can be completed accurately and efficiently.

Condition monitoring of bearings is an open issue. The use of the stator current to monitor induction motors has been validated as a very advantageous and practical way to detect several types of faults. Nevertheless, for bearing faults the use of vibrations or sound generally offers better results in the accuracy of the detection although with some disadvantages related to the sensors used for monitoring. To improve the performance of bearing monitoring, it is proposed to take advantage of more information available in the current spectra, beyond the usually employed, incorporating the amplitude of a significant number of sidebands around the first eleven harmonics, growing exponentially the number of fault signatures. This is especially interesting for inverter-fed motors. But, in turn, this leads to the problem of overfitting when applying a classifier to perform the fault diagnosis. To overcome this problem, and still exploit all the useful information available in the spectra, it is proposed to use shrinkage methods, which have been lately proposed in machine learning to solve the overfitting issue when the problem has much more variables than examples to classify. A case study with a motor is shown to prove the validity of the proposal

Keywords: domain adversarial; channel reconstruction; transfer learning; fault diagnosis

The dissolution of Al2O3 non-metallic inclusions from slag containing FexO was investigated in this study. The slag system used in the experiments was a quaternary system of CaO-SiO2-Al2O3-FexO. The composition of the slag was studied by fixing the basicity (CaO/SiO2 ratio) to 1 and varying the FexO content to 10 and 20wt%. In addition, the experimental temperature was varied as 1550℃, 1575℃, and 1600℃ to study the effect of temperature on the Al2O3 dissolution behavior. The experimental equipment is a single hot thermocouple apparatus. The dissolution rate of Al2O3 particles increased linearly with increasing temperature and FexO content. In addition, the mass transfer activation energy of Al2O3 dissolution in FexO 10wt% and FexO 20wt% was calculated by an Arrhenius type analysis. The obtained mass transfer activation energies were 159 and 189 kJ/mole, respectively.

Nitride and carbide are the second phases which play an important role in the performance of bearing steel, and their precipitation behavior is complicated. In this study, TiN-MC_x precipitations in GCr15 bearing steels were obtained by non-aqueous electrolysis, and their precipitation mechanisms were studied. TiN is the effective heterogeneous nucleation site for Fe₇C₃ and Fe₃C, therefore, MC_x can precipitate on the surface of TiN easily, its chemistry component consists of M₃C and M₇C₃ (M = Fe, Cr, Mn) and Cr₃C₂. TiN-MC_x with high TiN volume fraction, TiN forms in early stage of solidification, and MC_x precipitates on TiN surface after TiN engulfed by the solidification advancing front. TiN-MC_x with low TiN volume fraction, TiN and MC_x form in late stage of solidification, TiN can not grow sufficiently and is covered by a large number of precipitated MC_x particles.

In recent years, polyureas with dynamic hindered urea bonds (HUBs), as a class of promising biomedical polymers, have attracted attention as a benefit of their controlled hydrolytic property. The effect of the chemical structures on the properties of polyureas and their assemblies was rarely reported. In this study, four kinds of polyureas with different chemical groups have been synthesized, and the polyurea from cyclohexyl diisocyanate and tert-butyl diamine showed the fastest hydrolytic rate. The amphiphilic polyurea composed of hydrophobic cyclohexyl-tert-butyl polyurea and hydrophilic poly(ethylene glycol) was synthesized for controlled delivery of antitumor drug paclitaxel (PTX). The PTX-loaded PEGylated polyurea micelle more effectively entered into the murine breast cancer 4T1 cells and inhibited the corresponding tumor growth in vitro and in vivo. Therefore, the PEGylated polyurea with adjustable degradation might be a promising polymer matrix for drug delivery.

Advanced glycation end-products (AGEs) form through non-enzymatic glycation of various proteins. Optic nerve degeneration is a frequent complication of diabetes, and retinal AGEs accumulation is strongly linked to diabetic retinopathy development. Type 2 diabetes mellitus (T2DM) is a major risk factor for Alzheimer's disease (AD), with patients often exhibiting optic axon degeneration in the nerve fiber layer. Notably, a gap exists in our understanding of how AGEs contribute to neuronal degeneration in the optic nerve within the context of both diabetes and AD. Our previous work demonstrated that glyceraldehyde (GA)-derived toxic advanced glycation end-products (TAGE) disrupt neurite outgrowth through TAGE-β-tubulin aggregation and tau phosphorylation in neural cultures. In this study, we further illustrated GA-induced suppression of optic nerve axonal elongation via abnormal β-tubulin aggregation in mouse retinas. Elucidating this optic nerve degeneration mechanism holds promise for bridging the knowledge gap regarding vision loss associated with DM and AD.

Much research has been conducted to determine how hair regeneration is regulated, as this could provide therapeutic, cosmetic, and even psychological interventions for hair loss. The current study focused on the hair growth effect and effective utilization of fatty oil obtained from Bryde's whales through high-throughput DNA microarray approach in conjunction with immunohistochemical observations. The research also examined the mechanisms and factors involved in hair growth. In an experiment using female C57BL/6J mice, the vehicle control group (VC: propylene glycol: ethanol: water), the positive control group (MXD: 3% minoxidil), and the experimental group (WO: 20% Whale Oil) were topically applied to the back of the mouse. The results showed that 3% MXD and 20% WO were more effective than VC in promoting hair growth, especially 20% WO. Furthermore, in hematoxylin and eosin-stained skin tissue, an increase in the number of hair follicles and subcutaneous tissue thickness was observed with 20% WO. Whole-genome transcriptomic analysis also showed that 20% WO may have lower stress- and inflammation-related responses than 3% MXD. Therefore, whale oil can be expected to be used as a safe hair growth agent.

A series of polynuclear, dinuclear, and mononuclear Mo(VI) complexes were synthesized with the hydrazonato ligands derived from 5-methoxysalicylaldehyde and the corresponding hydrazides (isonicotinic hydrazide (H2L1), nicotinic hydrazide (H2L2), 2-aminobenzhydrazide (H2L3) or 4-aminobenzhydrazide (H2L4)). The metallosupramolecular compounds obtained from non-coordinating solvents, [MoO2(L1,2)]n (1 and 2) and [MoO2(L3,4)]2 (3 and 4), formed infinite structures and metallacycles, respectively. By blocking two coordination sites with cis-dioxo ligands, the molybdenum centers have three coordination sites occupied by the ONO donor atoms from the rigid hydrazone ligands and one by N atom of pyridyl or amine-functionalized ligand subcomponents from the neighbouring Mo building units. The reaction in methanol afforded the mononuclear analogues [MoO2(L1-4)(MeOH)] (1a-4a) with additional monodentate MeOH ligand. All isolated complexes were tested as catalysts for cyclooctene epoxidation using tBuOOH (TBHP) as an oxidant in water. The impact of the structure and ligand lability on the catalytic efficiency in homogeneous cyclooctene epoxidation was elucidated through theoretical considerations. Thus, dinuclear assemblies exhibited better catalytic activity than mononuclear or polynuclear complexes.

In this study, methyl/tbutyl salicylate bearing zirconium complexes (C1-C8) were prepared by reaction of zirconium (IV) propoxide/butoxide with salicylic acid, 3-methylsalicylic acid, 4-methylsalicylic acid, and 3,5-di-tert-butylsalicylic acid in alcohols, respectively. All these complexes (C1-C8) were characterized by 1H-NMR, 13C-NMR, FTIR, mass spectroscopy (MS), elemental, and thermogravimetric analyses (TGA). These complexes were utilized as catalysts in ring opening polymerization (ROP) of ε-caprolactone and were very effective. Polycaprolactone (PCL) was characterized by 1H-NMR, 13C-NMR, and gel permeation chromatography (GPC). In this study, perhaps for the first time, the effects of electron donating substituents (Me and tBu) on ε-caprolactone polymerization reactions on salicylate ligands linked to zirconium atoms were investigated.

The study’s objective was to evaluate the influence of thinning on the quality and regularity of yield of 'Regina' cherries grown on a dwarf Gisela 5 rootstock. The experiments were conducted in the years 2009-2012 in Western Poland. Trees were thinned using a chemical agent, ammonium thiosulphate (ATS) at doses of 20g ATS × L-1, 30g ATS × L-1 and 40g ATS × L-1, and by hand, and the results of chemical and hand thinning were compared with those obtained for unthinned trees. The course of weather conditions in winter and during flowering had a significant impact on yield. Chemical thinning is known to be an effective method to regulate fruiting of pome trees, but it can also be successful if applied to cherry trees, as reflected by the alternate bearing index, which was the lowest after applying ATS at a dose of 40g. ATS treatment improved fruit quality in full crop years. Thinning resulted in, among other things, larger and darker fruit and higher content of total soluble solids and titratable acidity. Treatment with 40g ATS × L-1 significantly stimulated the vegetative growth of trees.

This study investigated the effects of fish oil (FO) treatment, particularly enriched with eicosapentaenoic acid (EPA), on obesity induced by a high-fat diet (HFD) in mice. The investigation focused on elucidating the impact of FO on epigenetic modifications in white adipose tissue (WAT) and the involvement of adipose-derived stem cells (ASCs). C57BL/6j mice were submitted to a control diet or a HFD for 16 weeks, treated (or not) with FO for the last 8 weeks. WAT was removed for RNA and protein extraction, while ASCs were isolated, cultured, and treated with Leptin. All samples were analyzed using functional genomics tools, including PCR-array, RT-PCR and Western Blot assays. Mice receiving HFD displayed increased body mass, fat accumulation, and altered gene expression associated with WAT inflammation and dysfunction. FO supplementation attenuated these effects, a potential protective role against HFD-induced obesity. Analysis of H3K27 revealed HFD-induced changes in histone, which were partially reversed by FO treatment. The study further explored leptin signaling in ASCs, suggesting a potential mechanism for ASC dysfunction in the leptin-rich environment of obese WAT. Overall, FO supplementation demonstrated efficacy in mitigating HFD-induced obesity, influencing epigenetic and molecular pathways, and shedding light on the role of ASCs and leptin signaling in WAT dysfunction associated with obesity.

This study addresses the critical issue of dowel-bearing strength in Bambusa blumeana, a key sus-tainable construction material crucial for climate change mitigation. Given the lack of bamboo connection standards, the research focuses on determining the dowel-bearing strength of Bambusa blumeana, emphasizing factors such as dowel diameter, node placements, and the physical prop-erties of bamboo. A predictive equation is derived, enhancing the practicality of bamboo in struc-tural design. The results underscore a notable correlation between dowel diameter and character-istic strength, with implications for engineering practices. Node placements significantly affect dowel-bearing capacity, while bamboo's physical attributes, including thickness, culm diameter, and moisture content, exhibit modest correlations with strength. The derived equation aims to assist in structural design, mitigating splitting and bearing failures in bamboo structures. This research establishes a foundation for optimizing the use of Bambusa blumeana in sustainable construction, advancing the understanding of its dowel-bearing strength for improved sustainability and resili-ence in the construction industry. Future research suggestions include exploring bamboo-mortar composites, additional node placements, and employing more comprehensive empirical equations and curve-fitting techniques. The study advocates for further investigations with more diverse and larger bamboo samples to bolster robustness. Additionally, delving into bamboo ductility may offer valuable insights.

A flexible structure is applied to improve the lubrication performance of a misaligned journal bearing. The journal bearing is representative sliding bearing and there are damages due to metal-to-metal contact by misalignment. Since misalignment is an unavoidable phenomenon, a journal bearing with a flexible structure was proposed as a way to improve it. The lubrication characteristics of the bearing are evaluated numerically under steady-state condition. EHL (elastohydrodynamic lubrication) analysis considering elastic deformation was performed. The lubrication performance is compared in accordance with variation of the geometry of the flexible structure and evaluated based on the minimum film thickness. Moreover, the results of the journal bearing with flexible structure are compared with those of the journal bearing without the flexible structure. The flexible structure is then applied in the form of a groove to the area supporting high load on the journal bearing; it is elastically deformed by the generated oil-film pressure, which helps to obscure a larger oil film. Through numerical analysis, it is found that the journal bearing with flexible structure can improve the lubrication performance in the misaligned condition.

This study aims to improve the shaft with hexagon joints to be a type not requiring welding or bolts in the static load test . In order to evaluate the bearing capacity of helical piles, two sites were selected to conduct pile installation for the field test and the pile load test. For the pile load test, the static pile load test and the dynamic pile load test were carried out, and torque was measured during pile installation for the field test to compare and analyze expected bearing capacity and thus assess the feasibility of the method for estimating the bearing capacity. The field pile load test revealed the bearing capacity of the gravity grout pile was the same or greater than 600kN in the static pile load test in accordance with AC 358 Code. The non-grout pile showed the bearing capacity the same or smaller than 600kN, suggesting gravity grouting is required. Moreover, the field pile load test was used to establish the bearing capacity equation considering the torque in pile installation, and a small number of samples were used to establish the equation which can be used as a basic data.

Background: Smad4, a critical tumor suppressor gene, plays a significant role in pancreatic biology and tumorigenesis. Genetic background and sex are known to influence phenotypic outcomes, but their impact on pancreatic weight in Smad4-deficient mice remains unclear. This study investigates the impact of Smad4 deficiency on pancreatic weight in F1 mice from diverse Collaborative Cross (CC) lines, focusing on the influence of genetic background and sex. Methods: F1 mice were generated by crossbreeding female CC mice with C57BL/6J-Smad4tm1Mak males. Genotyping confirmed the presence of Smad4 knockout alleles. Mice were housed under standard conditions, euthanized at 80 weeks, and their pancreatic weights were measured, adjusted for body weight, and analyzed for effects of Smad4 deficiency, sex, and genetic background. Results: The overall population of F1 mice showed a slight but non-significant increase in adjusted pancreatic weights in heterozygous knockout mice compared to wild-type mice. Sex-specific analysis revealed no significant difference in males but a significant increase in adjusted pancreatic weights in heterozygous knockout females. Genetic background analysis showed that lines CC018 and CC025 substantially increased adjusted pancreatic weights in heterozygous knockout mice. In contrast, other lines showed no significant difference or varied non-significant changes. The interplay between genetic background and sex further influenced these outcomes. Conclusion: Smad4 deficiency affects pancreatic weight in a manner significantly modulated by genetic background and sex. This study highlights the necessity of considering these factors in genetic research and therapeutic development, demonstrating the value of the Collaborative cross-mouse population in dissecting complex genetic interactions.

Determining the estrous cycle stages in mice is essential for optimizing breeding strategies, synchronizing experimental time lines, and facilitating studies in behavior, drug testing, and genetics. It is critical for reducing the production of genetically unmodified offspring in the generation and investigation of genetically modified animal models. An accurate detection of the estrus cycle is particularly relevant in the context of the 3Rs—Replacement, Reduction and Refinement. The estrous cycle, encompassing the reproductive phases of mice, is key to refining experimental designs and addressing ethical issues related to the use of animals in research. This study presents results from two independent laboratories on the efficacy of the Mouse Estrus Detector (MED) from Elmi Ltd. (Latvia) for the accurate determination of the estrus phase. The female mice of five strains/stocks (CD1, FVB/N, C57Bl6/J, B6D2F1, and Swiss) were used. The results showed that the MEDProTM is a low -traumatic, simple, rapid and painless method of estrus detection that supports the principles of the 3Rs. The use of the MEDProTM for estrus detection in mice caused minimal stress, enhanced mating efficiency, facilitated an increase in the number of embryos for the in vitro fertilization and allowed the production of the desired number of foster animals.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder, with a highly variable expression of phenotypes (restricted interest or activity and repetitive behavior in communication and social interactions), genes (mutation), markers (alteration of transcription) and pathways. Loss of function of the CC2D1A gene appears to primarily affect the brain, leading to a range of behavioral problems in humans. In our study published in 2020; we found that the expressions of miR-19a-3p, miR-361-5p, miR-150-5p, miR-3613-3p, miR-126-3p and miR-499a-5p were downregulated in the serum samples of autistic patients and their families. Here, acquired non-Mendelian hereditary character in a genetically defined mouse model of autism (Cc2d1a +/-) correlates with the transcriptional alteration of five miRNAs. We seek to test the hypothesis that miRNA levels are varying by changes in RNA/DNA structure during development, thereby creating transcription alteration. Behavioral tests were conducted on the offspring of Cc2d1a +/- mutant and control mice, such as novel object, social interaction, marble burying and tail suspension behavior. Two RNA fractions were isolated from mouse hippocampal tissues and sperm cells by standard TRIzol extraction: total RNA and fraction of RNA bound to DNA in the form of a DNA/RNA hybrid (R-loop). The expression levels of miR-19a-3p, miR-361-5p, miR-150-5p, miR-126-3p and miR-499a-5p were investigated by quantitative real-time RT-PCR. We report differences in the distribution of five miRNAs in the hippocampus between male and female mice in RNA fractions, particularly in colonies of Cc2d1a +/- mice. Furthermore, the number of miRNAs engaged in the DNA/RNA hybrid fraction is generally higher in the mutant pedigree than in the control group. On the other hand, in sperm both fractions are at lower levels than in controls. R-loops contribute to the physiology and pathology of organisms including human disease. Here we report a variation in five miRNA levels between gender and tissue. Our results suggest that the transcription levels of these five miRNAs are directly regulated by their RNA.

Blind deconvolution (BD) is one of the effective methods that help pre-process vibration signals and assist in bearing fault diagnosis. Currently, most BD methods design an optimization criterion and use frequency or time domain information independently to optimize a deconvolution filter. It recovers weak periodic impulses related to incipient faults. However, the random noise interference may cause the optimizer to overfit. The time-domain-based BD methods tend to extract fault-unrelated single peak impulse, and the frequency-domain-based BD methods tend to retain the maximum energy frequency component, which will lose the fault-related harmonics frequency components. To solve the above issue, we propose a hybrid criterion that combines the kurtosis for time domain optimization and the $G-l_1/l_2$ norm for the frequency domain. These two criteria are monotonically increasing and decreasing, so they mutually constrain to avoid overfitting. After that, we design a multi-task one-dimensional convolutional neural network with time and frequency branches to achieve an optimal solution for this hybrid criterion. The multi-task neural network realizes the simultaneous optimization of two domains. Experimental results show that our proposed method outperforms other state-of-the-art methods.

The purpose of feature selection is to find important features from the original high-dimensional space. As atypical feature selection algorithm, Locally linear embedding(LLE)-based feature selection algorithm, which applies the idea of LLE to the graph-preserving feature selection framework, has been received wide attention. However, LLE-based feature selection framework is sensitive to noise and K-nearest neighbors. To address these problems, an improved LLE-based feature selection algorithm, robust LLE (RLLE) vote, is proposed. In this algorithm, $l_1$ and $l_2$ regularization are introduced into the high-dimensional reconstruction model of LLE. Furthermore, RLLE vote also proposes a criterion to measure the difference between the reconstruction features and the original features, and then the importance features can be selected by this criteria. Extensive experiments are carried out on a benchmark fault data set and the bearing data set collected from our own laboratory, and the experimental results demonstrate that RLLE vote achieves the most significant performance compared existing state-of-art methods.

In a recent article, Smoom et al. identified an important amino acid variation in the helicase RTEL1 of the Algerian mouse (Mus spretus). Since the latter has telomeres five times shorter than the laboratory mouse (belonging to the Mus musculus species), they introduced this variation in laboratory mice, in order to obtain an engineered strain with human-length telomeres. Succeeding in doing this, they established the “Telomouse” strain. Here I demonstrate that, in reality, Mus spretus does not show this variation: the key amino acid is conserved in all rodent species, which all have human-length telomeres (including wild Mus musculus species). This finding in no way compromises the value of the research of Smoom et al. and the utility of the Telomouse strain. Rather, it raises the question of how the telomere length of Mus musculus (as a species) should be considered and the important consequences it has on studies on inter-species comparison.

Gastrointestinal tumors including pancreatic and colorectal cancers represent one of the greatest public health issues worldwide, leading to million global deaths. Recent research demonstrated that the human heavy chain ferritin (HFt) can encapsulate different type of drugs in its cavity and can bind to its receptor, CD71, in several solid and hematological tumors, thus highlighting the potential use of ferritin for tumor-targeting therapies. Here, we describe the development and characterization of a novel nanomedicine based on the HFt that is named The-0504. In particular, this novel system is a nano-assembly comprising an engineered version of HFt that entraps about 80 molecules of a potent, wide-spectrum, non-camptothecin topoisomerase I inhibitor (Genz-644282). The-0504 can be produced by a standardized pre-industrial process as a pure and homogeneously formulated product with favourable lyophilization properties. The preliminary anticancer activity was evaluated in cultured cancer cells and in a mouse model of pancreatic cancer. Overall results reported here make The-0504 a candidate for further preclinical development against CD-71 expressing deadly tumors

In this study one of the most innovative sintering techniques up to date was evaluated: Electro-Sinter-Forging (ESF). Despite it has been proved to be effective in densifying several different metallic materials and composites, bearing steels such as 100Cr6 have never been processed so far. Pre-alloyed Astaloy CrM powders have been ad-mixed with either graphite or graphene and then processed by ESF to produce a 100Cr6 equivalent composition. Porosity has been evaluated by optical microscopy and compared to that one of 100Cr6 commercial samples. Mechanical properties such as hardness and transverse rupture strength were tested on samples produced by employing different process parameters and then submitted to different treatments (machining, heat treatment). The experimental characterization highlighted that porosity is the factor mostly affecting mechanical resistance of the samples, correlating linearly to the transverse rupture strength. Hardness on the other side does not correlate to the mechanical resistance because process related cracking has a higher effect on the final properties. Promising results were obtained that give room to the sinterability by ESF of materials difficult to sinter by conventional press and sinter techniques.

Gender and biological sex have distinct impacts on the pathogenesis of type 2 diabetes (T2D). Estrogen deficiency is known to predispose female mice to T2D. In our previous study, we found that high-fat, high-sucrose diet (HFHSD) induces T2D in male mice through the miR-10b-5p/KLF11/KIT pathway, but not in females, highlighting hormonal disparities in T2D susceptibility. However, the underlying molecular mechanisms of this hormonal protection in females remain elusive. To address this knowledge gap, we utilized ovariectomized, estrogen-deficient female mice, fed them a HFHSD to induce T2D, and investigated the molecular mechanisms pathway in estrogen-deficient diabetic female mice, cell lines, and patients with T2D in female. Initially, female mice fed a HFHSD exhibited delayed onset of T2D, but ovariectomy-induced estrogen deficiency promptly precipitated T2D without delay. Intriguingly, insulin (INS) was upregulated, while insulin receptor (INSR) and protein kinase B (AKT) were downregulated in these estrogen-deficient diabetic female mice, indicating insulin-resistant T2D. These dysregulations of INS, INSR, and AKT were mediated by a miR-10a/b-5p-NCOR2 axis. Treatment of miR-10a/b-5p effectively alleviated hyperglycemia in estrogen-deficient T2D female mice, while β-estradiol temporarily reduced hyperglycemia. Consistent with the murine findings, plasma samples from female T2D patients exhibited significant reductions in miR-10a/b-5p, estrogen, and INSR, but increased insulin levels. Our findings suggest that estrogen protect against insulin-resistant T2D in females through miR-10a/b-5p/NCOR2 pathway, indicating the potential therapeutic benefits of miR-10a/b-5p restoration in female T2D management.

Excessive oxidative stress and exercise-induced fatigue reduce physical performance and can lead to dysfunction in antioxidant systems within muscular and hepatic tissues. Integrating natural substances with exercise may mitigate fatigue via anti-oxidant effects. This study aims to compare and evaluate the effects of exercise and supplementation with Sundarbans honey vs energy drinks on the strength, anxiety physiological profiles, and hepatic antioxidant capacity in mice undergoing extraneous exercise and fatigue. Forty-eight four-week-old Swiss albino mice were randomly assigned to one of eight groups: (1) Control, (2) Speed™ (Sp), (3) Royal Tiger™ (RT), (4) Sundarbans Honey (SH), (5) Exercise (Ex), (6) Exercise + Sundarbans Honey (Ex+SH), (7) Exercise + Speed™ (Ex+Sp), and (8) Exercise + Royal Tiger™ (Ex+RT). Supplements were administered via oral gavage: Sp (2.5 ml/kg BW), RT (2.5 ml/kg BW), and SH (1 g/kg BW), four times a week for 60 days. Mice in the Ex, Ex+SH, Ex+Sp, and Ex+RT groups underwent daily swimming and running. The strength, fatigue, anxiety levels, lipid profiles, and antioxidant biomarkers were evaluated post-treatment. The SH, Ex, and Ex+SH groups exhibited significantly enhanced physical performance (p<0.05). Plasma lipid profiles, including LDL, triglycerides, total cholesterol, and fatigue-related biomarkers (ALP, AST, ALT, LDH, CK, LA, BUN, and glucose) were markedly increased in the Sp and RT groups but decreased in the SH, Ex, and Ex+SH groups compared to control (p<0.05). Exercise-induced fatigue elevated the Nrf2/HO-1 antioxidant defense system in liver tissue. IL-6 levels were reduced in the SH, Ex, and Ex+SH groups (p<0.05). These findings indicate that regular exercise combined with SH supplementation increases strength and improves lipid profiles, reducing exercise-induced oxidative stress and fatigue via modulation of the Nrf2/HO-1 pathway in liver tissue. These results highlight SH supplementation’s potential as a complementary strategy to enhance exercise outcomes and mitigate exercise-induced stress.

Background and Purpose: Oxidative stress is an important factor in the pathogenesis of neurological problems. One of the compounds causing oxidative stress is diazinon. In the present project, the protective role of gallic acid compound in reducing oxidative stress in brain tissue of mice exposed to diazinon was investigated. Method: In this study, eight groups of six series of mice including the first group (control) of normal saline, the second group of diazinon (40 kg/mg) as IP, three groups of diazinon with gallic acid (50, 100, 200 kg/mg), was prescribed as a single dose and for 24 hours. The atropine + pralidoxime group was also evaluated as a standard treatment group. At 24 hours after the last dose, the animals were sacrificed and brain tissue was examined to assess oxidative stress parameters, including glutathione content, protein carbonyl content, lipid peroxidation, reactive oxygen species (ROS) and mitochondrial function in mitochondria isolated from brain tissue. Results: The results of this research showed that oxidative stress biomarkers increased significantly (P<0.001) in the diazinon group compared to the control group. Oxidative stress was significantly reduced in the groups receiving gallic acid at a dose of 200 and 100 kg/mg of diazinon compared to the diazinon group. Conclusion: The results of the present study show that diazinon causes damage to brain tissue by inducing oxidative stress. Therefore, according to the reduction of oxidative stress by gallic acid compound, it can be concluded that this compound can protect against brain toxicity caused by diazinon in animal model by stimulating antioxidant and radical scavenging pathways.

We have previously reported that 60% sucrose diet-fed ChREBP knockout mice (KO) showed body weight loss resulting in lethality. We aimed to elucidate whether sucrose and fructose metabolism are impaired in KO. Wild type mice (WT) and KO were fed a diet containing 30% sucrose with/without 0.08% miglitol, an α-glucosidase inhibitor, and these effects on phenotypes were tested. Furthermore, we compared metabolic changes of oral and peritoneal fructose injection. Thirty percent sucrose diet feeding did not affect phenotypes in KO. However, miglitol induced lethality in 30% sucrose-fed KO. Thirty percent sucrose plus miglitol diet-fed KO showed increased cecal contents, increased fecal lactate contents, increased growth of lactobacillales and Bifidobacterium and decreased growth of clostridium cluster XIVa. ChREBP gene deletion suppressed the mRNA levels of sucrose and fructose related genes. Next, oral fructose injection did not affect plasma glucose levels and liver fructose contents; however, intestinal sucrose and fructose related mRNA levels were increased only in WT. In contrast, peritoneal fructose injection increased plasma glucose levels in both mice; however, the hepatic fructose content in KO was much higher owing to decreased hepatic Khk mRNA expression. Taken together, KO showed sucrose intolerance and fructose malabsorption owing to decreased gene expression.

Congenital Disorders of Glycosylation (CDG) are a heterogenous group of primarily autosomal recessive mendelian diseases caused by disruptions in the synthesis of lipid linked oligosaccha-rides and their transfer to proteins. CDGs affect multiple organ systems and vary in presentation, even within families. Here we describe a chemically induced mouse mutant, tvrm76, with early onset photoreceptor degeneration. The recessive mutation was mapped to Chromosome 9 and as-sociated with a missense mutation in the Dpagt1 gene encoding UDP-N-acetyl-D-glucosamine:dolichyl-phosphate N-acetyl-D-glucosaminephosphotransferase (EC 2.7.8.15). The mutation is predicted to cause a substitution of aspartic acid with glycine at residue 166 of DPAGT1. Increased expression of Ddit3, and elevated levels of HSPA5 (BiP) sug-gest the presence of early-onset endoplasmic reticulum (ER) stress. These changes were associated with induction of photoreceptor apoptosis in tvrm76 retinas. Mutations in human DPAGT1 cause Myasthenic Syndrome 13 and severe forms of Congenital Disorder of Glycosylation Type Ij. In contrast, Dpagt1tvrm76 homozygous mice present with congenital photoreceptor degeneration without overt muscle or muscular junction involvement. Our results suggest the possibility of DPAGT1 mutations in human patients that present primarily with retinitis pigmentosa with little or no muscle disease. Variants in DPAGT1 should be considered when evaluating cases of non-syndromic retinal degeneration.

The Sanaga River Valley is a deep-seated structure of about 220 km in width, bounded on its northern and southern sides by 025-0550 fault zones. Its internal structure has been very little described before this study. It is characterized by the presence of surface features where a thick stratum of shale and argillaceous sandstones have been documented. The use of electrical resistivity tomography for near-surface imaging and hydrogeological prospecting within shale succession is widespread. However, several methods of spatial modeling of resistivity contours are generally proposed for the interpretation of inverse resistivity model sections. To determine the most appropriate method for interpreting resistivity tomographies in the context of subsoil marked by significant heterogeneity, logarithmic contour intervals, and linear contour interval processing were implemented on data collected over five areas. The data consists of outcrops data, cuttings samples from groundwater boreholes, and resistivity sections ranging in length from 240 to 1000 m. Well-control of the inverse resistivity model sections derived from both processes shows that the linear contour intervals modeling gives a more realistic picture of the reservoir size of the wa-ter-bearing sand in both shale and argillaceous sandstone succession. The sedimentary architecture over Sanaga fault breccia is marked by vertical intrusion anomalies up to 80 m high. The shape of these anomalies, as well as the very low resistivity values that characterize them, suggests that they could be related to mud intrusion.

This review covers the last 25 years literature on analogs of suberoylanilide hydroxamic acid (SAHA, known also as Vorinostat) acting as HDAC inhibitor. In particular, the topic has been focused on the synthesis and biological activity of compounds where the phenyl group (the surface recognition moiety, CAP) of SAHA has been replaced by an azaheterocycle through a direct bond with amide nitrogen atom, and the methylene chain in the linker region is of variable length. Most of the compounds reported displayed good to excellent inhibitory activity against HDACs and in many cases showed anti-proliferative activity against human cancer cell lines.

The vibration signal of the engine contains strong background noise and many kinds of modulating components, which is difficult to diagnose. Variational mode decomposition (VMD) is a recently introduced adaptive signal decomposition algorithm with a solid theoretical foundation and good noise robustness compared with empirical mode decomposition (EMD). VMD can effectively avoid endpoint effect and modal aliasing. However, VMD cannot effectively eliminate the random noise in the signal, so the random decrement technique is introduced to solve the problem. Based on the crankshaft bearing fault simulation experiment, the four kinds of wear state vibration signals are decomposed by VMD, and the modal components with smaller permutation entropy are selected as fault components. Then the fault component is processed by the random decrement technique, and the Hilbert envelope spectrum of the fault component is obtained. Compared with the fault feature extraction method based on EMD and EEMD, the feature extraction results of the proposed method are better than those of the above two methods. The simulation analysis and the simulation test of the crankshaft bearing fault verify the effectiveness of the proposed method.

Background and Objective: In an experiment designed to explore the mechanisms of fludrocortisone-induced high blood pressure, we serendipitously observed aortic aneurysms in mice infused with fludrocortisone. The purpose of this study was to investigate whether fludrocortisone induces aortic pathologies in both normocholesterolemic and hypercholesterolemic mice. Methods and Results: Male adult C57BL/6J mice were infused with either vehicle (85% polyethylene glycol 400 (PEG-400) and 15% dimethyl sulfoxide (DMSO); N=5) or fludrocortisone (12 mg/kg/day dissolved in 85% PEG-400 and 15% DMSO; N=15) for 28 days. Fludrocortisone-infused mice had higher systolic blood pressure, compared to mice infused with vehicle. Fludrocortisone induced aortic pathologies in 4 of 15 mice with 3 having pathologies in the ascending and aortic arch regions and 1 having pathology in both the ascending and descending thoracic aorta. No pathologies were noted in abdominal aortas. Subsequently, we infused either vehicle (N=5/group) or fludrocortisone (N=15/group) into male ApoE -/- mice fed a normal laboratory diet or LDL receptor -/- mice fed either normal or Western diet. Fludrocortisone increased systolic blood pressure, irrespective of mouse strain or diet. In ApoE -/- mice infused with fludrocortisone, 2 of 15 mice had ascending aortic pathologies, but no mice had abdominal aortic pathologies. In LDL receptor -/- mice fed normal diet, 5 had ascending/arch pathologies, 1 had pathologies in the ascending, arch, and suprarenal aortic regions. In LDL receptor -/- mice fed Western diet, 2 died of aortic rupture in either the descending thoracic or abdominal region, and 2 of the 13 survived mice had ascending/arch aortic pathologies. Aortic pathologies included hemorrhage, wall thickening or thinning, or dilation. Given the low incidence, only ascending aortic diameter in LDLR -/- mice fed Western diet reached statistical significance, compared to their vehicle. Conclusion: Fludrocortisone induces aortic pathologies independent of hypercholesterolemia. The findings in mouse studies have the potential to provide caution to people who are taking or have taken fludrocortisone that could have an increased risk of aortic pathologies.

Cholesterol homeostasis is pivotal for cellular function. Acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1), also abbreviated as SOAT1, is an enzyme catalyzing the storage of excess cholesterol to cholesteryl esters. ACAT1 is an emerging target to treat diverse diseases including atherosclerosis, cancer, and neurodegenerative diseases. F12511 is a high affinity ACAT1 inhibitor. Previously, we developed a stealth liposome-based nanoparticle to encapsulate F12511 to enhance its delivery to the brain and showed its efficacy in treating a mouse model for Alzheimer’s disease (AD). In this study, we introduce F26, a close derivative of F12511 metabolite in rats. F26 was encapsulated in the same DSPE-PEG2000/phosphatidylcholine (PC) liposome-based nanoparticle system. We employed various in vitro and in vivo methodologies to assess F26's efficacy and toxicity compared to F12511. Results demonstrate that F26 is more effective and durable than F12511 in inhibiting ACAT1, in both mouse embryonic fibroblasts (MEFs) and in multiple mouse tissues including the brain tissues, without exhibiting any overt systemic or neurotoxic effects. This study demonstrates the superior pharmacokinetic and safety profile of F26 in wild-type mice, and suggests its therapeutic potential against various neurodegenerative diseases including AD.

This paper presents the results of an experimental and analytical study on the behavior of cold-formed thick-walled steel plates connected by a single bolt under double shear. Experimental studies were conducted on a total of 54 bolted connections fabricated from two thickness of cold-formed thick-walled steel plates with the nominal thickness of 6 mm and 10 mm. The effects of end distance, edge distance and steel plate thickness were investigated on the bolt bearing behavior. Codes of (modified) ANSI/AISC 360-16 and EN1993-1-8 were applied to predict failure modes and bearing resistance of connections and the predictions were compared with that of measurements. A method was proposed to calculate the elongation of bolt hole at ultimate load. The studies show that fractures occurred on shear planes of specimens failed by shear out due to reduced ductility caused by cold forming process. The modified ANSI/AISC gives the most accurate predictions of failure modes and bearing resistance. However, the bearing resistance will be overestimated if the reduction in area of shear planes caused by occurrence of fracture is ignored for specimens with end distance being higher than 2.0d0 and a reduction factor is needed for calculating bearing resistance of connections. The method proposed in our paper can predict the elongation of bolt hole very well.

This paper realizes early bearing fault warning through bearing fault time series prediction, and proposes a bearing fault time series prediction model based on optimized maximum correlation kurtosis deconvolution (MCKD) and long short-term memory (LSTM) recurrent neural network to ensure bearings operation reliability. The model is based on lifecycle vibration signal of the bearing, to begin, the cuckoo search (CS) is utilized to optimize the parameter filter length L and deconvolution period T of MCKD, taking into account the influence and periodicity of the bearing time series, the fault impact component of the optimized MCKD deconvolution time series is improved. Then select the LSTM learning rate α depending on deconvolution time series. Finally, the dataset obtained through various preprocessing approaches are used to train and predict the LSTM model. The average prediction accuracy of the optimized MCKD-LSTM model is 26 percent higher than that of the original time series, proving the efficiency of this method, and the prediction results track the real fault data well, according to the XI'AN JIAOTONG University XJTU-SY bearing dataset.

In this paper, we introduce the Prognostics and Health Management of gear bearing system using autoencoder neural networks. Bearings and gears are the most common mechanical components in rotating machines, and their health conditions are of great concern in practice. This study presents an outlier modeling method for forecasting the gear bearing system failure using the health indicators constructed from mechanical signal processing and modeling. Outlier modeling aims to find patterns in data that are significantly different from what is defined as normal. In the unsupervised outlier modeling setting, prior labels about the anomalousness of data points are not available. In such cases, the most common techniques for scoring data points for outlyingness include distance-based methods density-based methods, and linear methods. The conventional outlier modeling methods have been used for a long time to detect anomalous observations in data. However, this paper shows that autoencoders are a very competitive technique compared to other existing methods. The developed method is demonstrated using the IMS bearing data from NASA Acoustics and Vibration Database.

(1) Background: Impaired colonic motility is common in patients with ulcerative colitis. The patients often complain the symptoms related to colonic motility dysfunction such as loose stools or diarrhea and these symptoms make therapy more challenging; (2) Methods: This study aimed to examine the movement of the colon in mice with ulcerative colitis and determine if the glial-derived neurotrophic factor (GDNF) may enhance aberrant colonic motility through Connexin 43 (Cx43).A model of ulcerative colitis was created using 32 male C57BL/6 mice. Colonic transit time was measured in all mice, and colon tissues were examined using hematoxylin-eosin staining (HE) and transmission electron microscopy (TEM). The levels of GDNF and Cx43 were determined via immunohistochemistry, immunofluorescence, and RT-PCR techniques. The levels of C-reactive protein (CRP),TNF-α, IL-1β, and IL-6 were quantified using the enzyme-linked immunosorbent assay (ELISA); (3) Results: 1) The UC models were effectively established by administering dextran sodium sulfate (DSS) water. Mice with ulcerative colitis exhibited a delay in colonic transit time. 2) GDNF can improve the delayed movement of the colon in mice with UC by activating the Cx43 protein; (4) Conclusions: GDNF can ameliorate impaired colonic motility in mice with ulcerative colitis, and its mechanism is related to the activity of Cx43. GDNF could potentially be utilized as a therapeutic option for addressing aberrant colonic motility in patients.

The pervasive presence of atmospheric pollution, particularly polycyclic aromatic hydrocarbons such as 7,12-dimethylbenz(a)anthracene, instigates aberrant cellular and tissue conditions, precipitating oxidative damage and inflammatory cascades conducive to the onset of cancer, notably mammary cancer. Given the hepatic metabolism of 7,12-dimethylbenz(a)anthracene, liver damage can be found and the imperative of employing natural antioxidants becomes apparent. In this study, we first showed that 7,12-dimethylbenz(a)anthracene-intoxication escalates body weight, disrupts lipid profiles, and incites serum oxidative damage. Concurrently, hepatic and renal oxidative stress ensue, accompanied by heightened antioxidant enzyme activity in the 7,12-dimethylbenz(a)anthracene-exposed group compared to controls (p&lt;0.05). Interestingly, P.lentiscus co-administration rectifies biochemical imbalances, significantly attenuates oxidative stress aberrations, and augments antioxidant enzyme responses (p&lt;0.05). Importantly, histological analysis evinces P.lentiscus's shielding effect against 7,12-dimethylbenz(a)anthracene induced hepatocyte injury and steatosis. Furthermore, our investigations unveil P.lentiscus’s anti-proliferative efficacy against different human breast cancer cell lines. Thus, our findings underscore P.lentiscus‘s robust anti-proliferative, antioxidant, and hepato-protective capacities, mitigating metabolic disturbances, oxidative stress propagation in liver and kidney functions, and potential histological alterations, thereby impeding 7,12-dimethylbenz(a)anthracene induced mammary cancer initiation. We posit that P.lentiscus may serve as a prophylactic agent against breast cancer and liver oxidative damage instigated by this carcinogen.

Tracked vehicles play a vital role in accessing challenging terrains, offering stability, traction, and versatility for various applications, including deep-sea exploration. However, the seafloor and sediment contain valuable but poorly understood resources, making it a significant challenge for tracked vehicles during exploration. Consequently, it is imperative to conduct comprehensive studies before considering these terrains for off-road purposes. In this study, we developed a rigid, flexible track vehicle equipped with various sensors, focusing on monitoring pressure sinkage. Cohesive soils like Bentonite and Diatom soil, particularly when combined with sand and gravel mixtures, were used for the investigation and assessed for ground pressure, bearing capacity, and sinkage in rigid-flexible tracked vehicles on these characterized terrains under varying moisture conditions. Our findings indicated that increased moisture content in bentonite soil resulted in significantly higher track slippage and sinkage compared to diatomaceous earth soil. Regarding soil behavior, diatom soil exhibited notable compaction and sinkage characteristics compared to bentonite soil. These significant variations between these two soil types under changing moisture conditions highlight the complexity of such terrains. Therefore, understanding the soil and its physical properties is crucial before applying them to natural terrains. Furthermore, this study emphasizes the importance of precision in assessing the physical properties of natural terrains for the development of tracked vehicles for off-road exploration. This knowledge contributes to better vehicle design and a deeper comprehension of terrain mechanics.

The fault diagnosis of the gearbox is primarily based on the analysis of the harmonic response. However, the generation mechanism of the harmonic response of the gear pair is still not distinctly explained in a healthy gearbox. Therefore, this paper is dedicated to establishing a dynamic model of the gearbox for this issue. In this model, the contact force of the bearing and the meshing stiffness of the gear pair are determined by the Hertz theory and the potential energy method, then the shaft motion is used as the connection to establish the coupling relationship between the gear pair and the bearing. After this dynamic model is confirmed by experiments and existing models, the coupling relationship inside the gearbox and the harmonic response of the gear pair are studied using this model. The result demonstrates that a closed control loop is formed due to the vibration transmission between the gear pair, the bearing and the shaft, and there is a strong coupled vibration between the gear pair and the bearing in the gearbox. Due to the generation of the center distance error, misalignment angle and disorganized meshing process of the gear pair, the meshing stiffness is altered, which excites the harmonic response of the gear pair. When the speed of the gearbox is increased, although the vibration amplitude of the gearbox is increased, the system predominantly vibrates at the fundamental frequency, and the harmonic of the gear pair is also shifted to the low frequency band.

Past exploration for U deposit in the Philippines discovered the mineralization of radioactive allanite in Palawan. The allanite occurs as sand component in the heavily populated beach of Erawan, San Vicente, Palawan. This work assessed the risks associated with the radionuclides in Erawan beach by in situ ground radiometric survey of K, U, and Th in 694 sampling points. Principal component analysis (PCA) and Pearson correlation coefficient were used to determine the similarity between the radionuclides and to identify other probable anthropogenic sources of radionuclides. Our results show that the mean activity concentrations of K (597.8 Bq kg^-1) and Th (93.15 Bq kg^-1) are equivalent to 1.5 and 3.1 times of the world average natural radioactivity levels in soil, respectively, while the mean U (34.7 Bq kg^-1) is similar to the world average. The mean radiological risk assessments like radium equivalent, gamma specific activity index, external hazard index, internal hazard index, absorbed gamma dose rate, annual effective dose equivalent, annual gonadal equivalent dose, and excess lifetime cancer risk are 213.96 Bq kg^-1, 0.78, 0.58, 0.67, 97.24 nGy h^-1, 119.25 µSv y^-1, 684.39 µSv y^-1, and 0.42 (10^-3), respectively. Th consistently correlated most to the risks. We attribute the occurrence of Th to the presence of allanite, K to fertilizer use for farming, and U to both the allanite and farming. The results of our study can provide important baseline data for future detailed studies or monitoring of the long-term effects of elevated radiation levels to the local population of Erawan.

: The interaction of the Activating Transcription Factor 6 (ATF6), a key effector of the unfolded protein response (UPR) in the endoplasmic reticulum, with the neuronal calcium sensor Downstream Regulatory Element Antagonist Modulator (DREAM) is a potential therapeutic target in neurodegeneration. Modulation of the interaction ATF6-DREAM with repaglinide (RP) induced neuroprotection in a model of Huntington´s disease. Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder with no cure, characterized by the progressive loss of motoneurons resulting in muscle denervation, atrophy, paralysis and death. The aim of this work was to investigate the potential therapeutic significance of DREAM as a target for intervention in ALS. We found that the expression of the DREAM protein was reduced in the spinal cord of SOD1G93A mice compared to wild type littermates. RP treatment improved motor strength and reduced the expression of the ALS progression marker collagen type XIX1 (Col191 mRNA) in the quadriceps muscle in SOD1G93A mice. Moreover, treated SOD1G93A mice showed reduced motoneuron loss and glial activation and increased ATF6 processing in the spinal cord. These results indicate that the modulation of the DREAM-ATF6 interaction ameliorates ALS symptoms in SOD1G93A mice.

Background/Objectives Gastroparesis, a chronic digestive disorder characterized by delayed gastric emptying, often results from diabetes, post-surgical complications, autoimmune diseases, and neurological disorders. In approximately 50% of cases, the cause is idiopathic gastroparesis (IGD). Recent studies suggest a link between chronic enteroviral infections and persistent gas-trointestinal symptoms, including delayed gastric emptying. This study investigates the effects of a silydianin-rich extract from Silybum marianum seeds on enteroviral infections in vitro and the mitigation of delayed gastric emptying in mice. Silydianin, a key bioactive compound known for its liver-protective and antioxidant properties, has not been extensively studied for its impact on enteroviral infections and gastroparesis; Methods NMR spectroscopy (¹H, ¹³C, and DEPT) identi-fied silydianin as the primary compound, with minor flavonolignans and trace amounts of an oxidation product. The study assessed the cytotoxicity and antiviral activity of the extract at various stages of the viral life cycle, including virucidal activity, cell protection, and post-infection effects, using neutral red assays in RD cells, with results confirmed by real-time PCR. The viruses studied included Coxsackievirus B2, Coxsackievirus A10, Poliovirus SL-1, and Enterovirus EV71. The impact on delayed gastric emptying was evaluated in a mouse model of gastroparesis using doses of 100 and 200 mg/kg compared to a control; Results: The silydianin-rich extract exhibited con-sistent antiviral activity, with the highest selectivity index (SI) for EV71 (4.08) during virucidal activity. It provided moderate cell protection, with EC50 values ranging from 120.88 to 186.10 µg/mL and SI values from 2.20 to 3.39. Post-infection treatment showed varying efficacy, with Coxsackie A10 demonstrating the highest SI (3.90). In vivo, the extract at 200 mg/kg significantly improved gastric emptying to 96.47% and slightly increased gastrointestinal transit from 50.33% to 61.46%; Conclusions These results suggest that silydianin may be effective in treating enteroviral infections and enhancing intestinal function, making it a promising candidate for gastroparesis treatment and warranting further research.

Fucoidans, known for their diverse biological properties such as anti-inflammatory, antiviral, antitumor, and immune-stimulatory effects, have recently gained attention for their potential benefits in exercise endurance, muscle mass, and anti-fatigue. However, the mechanisms by which fucoidans enhance exercise performance are still unclear. To investigate these effects, we administered 400 mg/kg/day of fucoidan extract derived from Undaria pinnatifida to sixty-four C57BL/6J mice over ten weeks. We evaluated changes in running activity, mitochondrial-related gene expression in skeletal muscle, and alterations in the intestinal microbiome. Our results showed that fucoidan supplementation significantly increased daily running distance and muscle mass by 25.5% and 10.4%, respectively, in mice on a standard chow diet, and with more modest effects observed in those on a high-fat diet (HFD). Additionally, fucoidan supplementation led to a significant increase in beneficial gut bacteria, including Bacteroides/Prevotella, Akkermansia muciniphila, and Lactobacillus, along with a notable reduction in the Firmicutes/Bacteroidetes ratio, indicating improved gut microbiome health. Mechanistically, fucoidan supplementation upregulated the mRNA expression of key genes related to mitochondrial biogenesis and oxidative capacity, such as COX4, MYH1, PGC-1α, PPAR-γ, and IGF1, in both standard chow and HFD-fed mice. Our findings suggest that fucoidan supplementation enhances exercise performance, improves muscle function, and positively modulates the gut microbiome in mice, regardless of diet. These effects may be attributed to fucoidans' potential prebiotic role, promoting the abundance of beneficial gut bacteria and contributing to enhanced exercise performance, increased muscle strength, and improved recovery.

Corticosterone, an end product of the hypothalamic-pituitary-adrenal (HPA) axis, is a crucial stress hormone. Dysregulated HPA axis and corticosterone release play pivotal roles in the onset and persistence of symptoms of stress-related psychiatric disorders such as anxiety. The intake of nutrients, probiotics, and prebiotic supplements decreases blood corticosterone levels. The dipeptide L-carnosine is composed of beta-alanine and L-histidine and is commercially available as a nutritional supplement for recovery from fatigue. L-carnosine is involved in stress-induced corticosterone responses and anxiety behaviors in rodents. Here, we assessed the effect of L-carnosine in CD157 knockout (KO) mice, a murine model of autism spectrum disorder (ASD). The uptake of L-carnosine suppressed the increase in plasma corticosterone levels in response to acute stress and attenuated anxiety-like behaviors in CD157 KO mice. These results suggest that L-carnosine supplementation may relieve anxiety by suppressing excessive stress responses in individuals with ASD.

Natural gas hydrate has gained significant attention in recent years. To safely and sustainably exploit the natural gas from gas hydrate-bearing sediments, it is crucial to understand the long-term mechanical characteristics of the hydrate reservoir. In this study, the influence of hydrate and fine particles on the strain rate dependence of hydrate-bearing sediments under plane strain conditions has been studied. The experimental results show that the strain rate dependency of the mechanical properties of hydrate-bearing sediments is positively correlated with hydrate saturation instead of the morphology of hydrate in sediments. The residual strength of hydrate-bearing sediments is primarily controlled by the hydrate saturation and is independent of the strain rate. Changes in hydrate saturation, and fines content, can affect the relationship between the strain rate and shear band angle. Finally, the local volumetric expansion effect of hydrate-bearing sediments without fines content is more significant and shows a strong strain rate dependence characteristic. Overall, this study provides valuable insights into the long-term mechanical characteristics of hydrate reservoirs. These insights can contribute to the development of a constitutive model of hydrate-bearing sediments with time-dependence in the future, and which is meaningful to the exploitation of natural gas hydrate.

Grinding processes’ stochastic nature poses a challenge in predicting the quality of the resulting surfaces. Post-production measurements for form, surface roughness, and circumferential waviness are commonly performed due to infeasibility in measuring all quality parameters during the grinding operation. Therefore, it is challenging to diagnose the root cause of quality deviations in real-time resulting from variations in the machine’s operating condition. This paper introduces a novel approach to predicting the overall quality of the individual parts. The grinder is equipped with sensors to implement condition-based maintenance and is induced with five frequently occurring failure conditions for the experimental test runs. The crucial quality parameters are measured for the produced parts. Fuzzy c-means (FCM) and Hotelling’s T-squared (T2) have been evaluated to generate quality labels from the multi-variate quality data. Benchmarked random forest regression models are trained using fault diagnosis feature set and quality labels. Quality labels from the T2 statistic of quality parameters are preferred over FCM approach for their repeatability. The model, trained from T2 labels achieves more than 94% accuracy when compared to the measured ring disposition. The predicted overall quality using the sensors’ feature set is compared against the threshold to reach a trustworthy maintenance decision.

In recent years, intelligent fault diagnosis algorithms using deep learning method have achieved much success. However, the signals collected by sensors contain a lot of noise, which will have a great impact on the accuracy of the diagnostic model. To address this problem, we propose a one-dimensional convolutional neural network with multi-scale kernels (MSK-1DCNN) and apply this method to bearing fault diagnosis. We use a multi-scale convolution structure to extract different fault features in the original signal, and use the ELU activation function instead of the ReLU function in the multi-scale convolution structure to improve the anti-noise ability of MSK-1DCNN; then we use the training set with pepper noise to train the network to suppress overfitting. We use the Western Reserve University bearing data to verify the effectiveness of the algorithm and compare it with other fault diagnosis algorithms. Experimental results show that the improvements we proposed have effectively improved the diagnosis performers of MSK-1DCNN under strong noise and the diagnosis accuracy is higher than other comparison algorithms.

Cysteine-glutathione mixed disulfide (CySSG), a prodrug of glutathione (GSH) --the “Master Antioxidant”, was found to be orally bioavailable in mice, and protected against a toxic dose of acetaminophen. If oral bioavailability can also be demonstrated in humans, this suggests a wide range of applicability for CySSG.

The high reliable correlations between CBR and DCP in general proposed are presented in this paper. We analyzed the test data and correlations from many researchers to find the best equation for prediction the CBR from DCP test. The findings show that all correlations from existing paper are based on local material and cannot apply to soil in a different location in general purpose. New correlations between CBR and DCP were proposed and validated in this paper for general uses. The validation confirmed that these new correlations can predict well with higher R2.

In this study, two donor-acceptor (D-A) type conjugated polymers namely PQSeCz and PQSeFl were designed and synthesized. Selenophene was incorporated as a π -bridge, quinoxaline as an acceptor unit while carbazole and fluorene were used as the donor units. Polymers were synthesized via palladium catalyzed Suzuki polymerization reaction. All molecules were characterized by 1H and 13C NMR Spectroscopy. The weight and number average molecular weights of the two polymers were determined by gel permeation chromatography (GPC). Electrochemical and spectroelectrochemical characterizations of the polymers were performed to investigate their optoelectronic properties. Oxidation potentials were 1.15 V/ 0.82 V and 1.11 V/ 0.82 V for PQSeCz and PQSeFl respectively, while reduction potentials were -1.26 V /-1.14 V and -1.48 V/ -1.23 V, respectively. In the visible region, maximum absorption wavelengths for the two polymers were 551 nm and 560 nm, respectively. Optical band gaps (Egop) were found from the lowest energy π – π∗ transition onsets as 1.71 eV and 1.58 eV, respectively. Both polymers showed good solubility in common solvents.

Rats, including those of the Sprague Dawley strain, may kill mice. Because of this muridical behavior, it is standard practice in many research animal housing facilities to separate mice from rats (i.e., the predators) to minimize stress for the mice. We therefore tested the effect of cohousing on the stress levels of mice from either the C57BL/6J (BL6) or the CD1 strain and Sprague Dawley (SD rat) by determining their fecal corticosterone or cortisol metabolites (FCM) concentration and investigated how cohousing impacts a behavioral assay, i.e., conditioned place preference for intragenus (i.e., mouse-mouse or rat-rat) dyadic social interaction (DSI CPP) that had been shown be sensitive to social factors, especially to handling by humans. We found that the two delivery batches of BL6 mice or SD rats, respectively, had different stress levels at delivery that were statistically significant for the BL6 mice. Even so, the BL6 mice cohoused with rats had significantly increased FCM concentrations, indicative of higher stress levels, as compared to (1) BL6 mice housed alone or (2) BL6 mice at delivery. In contrast to their elevated stress levels, the attractiveness for contextual cues associated with mouse-mouse social interaction (DSI CPP) even increased in rat-cohoused BL6 mice, albeit nonsignificantly. Thus, cohousing BL6 mice and rats did not impair a behavioral assay in BL6 mice that had proved to be sensitive to handling stress by humans in our laboratory. SD rats cohoused with BL6- or CD1 mice and CD1 mice cohoused with SD rats showed DSI CPP that was not different from our previously published data on SD rats and BL6 mice of the Jackson- or NIH substrain obtained in the absence of cohousing. Our findings suggest that the effect of cohousing rats and mice under the conditions described above on their stress levels as opposed to their behavior might be less clearcut than generally assumed and might be overriden by conditions that cannot be controlled, i.e., different deliveries. Our findings can help to use research animal housing resources, which usually are limited, more efficiently.

Introduction: The environmentally acquired aerobic spore-forming (EAS-Fs) bacteria that are ubiquitous in nature (e.g. soil) are transient colonisers of the mammalian gastro-intestinal tract. Without regular exposure, their numbers quickly diminish. These species of bacteria have been suggested to be essential to the normal functioning of metabolic and immunogenic health. The modern Western lifestyle restricts exposure to these EAS-Fs, possibly explaining part of the pathogenesis of many Western diseases. To date, the only animal studies that address specific microbiome modelling are based around germ-free animals. We have designed a new animal model that specifically restricts exposure to environmental sources of bacteria. Methodology: A new protocol, termed Super Clean, that involves housing mice in autoclaved individually ventilated cages (IVCs), with autoclaved food / water, and strict ascetic handling practice was first experimentally validated. The quantification of EAS-Fs was assessed by heat-treating faecal samples and measuring colony forming units (CFUs). This was then compared to mice in standard-conditions. Mice were housed in their respective groups from birth until 18 months. Stool samples were taken throughout the experiment to assess for abundance in transiently acquired environmental bacteria. Clinical, biochemical, histological, and gene expression markers were analysed for diabetes, hypercholesterolaemia, obesity, inflammatory bowel disease, and non-alcoholic fatty liver disease (the “diseases of the West”). Results: Our results show that stringent adherence to the Super Clean protocol produces a significantly decreased abundance of aerobic spore-forming Bacillota after 21 days. This microbiomic shift was correlated with significantly increased levels of obesity and impaired glucose metabolism. There was no evidence of colitis, liver disease or hypercholesterolaemia. Conclusion: This new murine model successfully isolates EAS-Fs, and has the potential utility for future research allowing for the investigation into the clinical impact living in relative hygienic conditions.

5-Pentadecylresorcinol (C15) is a natural alkylresorcinol that has been shown to protect against complications caused by imbalanced nutrition. Although the exact mechanisms of beneficial activity of C15 are not known, we assume that the protective effects of C15 on metabolic health are mediated by their modulatory influence on the composition of the intestinal microbiota and functional activity. Cobamides and vitamin B12 are believed to be crucial modulators of mammalian gut ecosystems. We proposed that C15 may influence the representation of enzymes and pathways for vitamin B12 synthesis in the gut microbiome, providing compositional and functional changes in the microbial community. High-throughput metagenome sequencing of the contents of the small and large intestines of C57Bl6 mice fed a regular or high-fat diet with or without C15 supplementation was performed followed by reconstruction of the metabolic activity of the microbiota to clarify the role of C15 in vitamin B12 synthesis by the gut microbiota. It has been established that C15 significantly increases the representation of the cobalamin salvage pathway and enzymes in the microbiome of the large intestine of mice fed a high-fat diet. The genera Clostridium, AF12, and [Ruminococcus] had shown the highest number of correlations with enzymes for B12 synthesis and were negatively associated with the representation of probiotic bacteria. Therefore, the beneficial effect of C15 on the gut microbiota community can be achieved by modulating B12 synthesis that, in turn, serves as one of the key regulators of gut microbiota ecology.

The pervasive presence of atmospheric pollution, particularly polycyclic aromatic hydrocarbons such as 7,12-dimethylbenz(a)anthracene, instigates aberrant cellular and tissue conditions, precipitating oxidative damage and inflammatory cascades conducive to the onset of cancer, notably mammary cancer. Given the hepatic metabolism of 7,12-dimethylbenz(a)anthracene, the imperative of employing natural antioxidants becomes apparent. In this study, we delve into the antioxidant and hepato-protective properties of Pistacia lentiscus against 7,12-dimethylbenz(a)anthracene-induced toxicity, alongside exploring its potential anticancer attributes. Our investigations unveil Pistacia lentiscus's anti-proliferative efficacy against human breast cancer cell lines. Notably, 7,12-dimethylbenz(a)anthracene-intoxication escalates body weight, disrupts lipid profiles, and incites serum oxidative damage. Concurrently, hepatic and renal oxidative stress ensue, accompanied by heightened antioxidant enzyme activity in the 7,12-dimethylbenz(a)anthracene-exposed-group compared to controls (p&lt;0.05). Nonetheless, Pistacia lentiscus co-administration rectifies biochemical imbalances, significantly attenuates oxidative stress aberrations, and augments antioxidant enzyme responses (p&lt;0.05). Importantly, histological analysis evinces Pistacia lentiscus's shielding effect against 7,12-dimethylbenz(a)anthracene induced hepatocyte injury and steatosis. Our findings underscore Pistacia lentiscus's robust anti-proliferative, antioxidant, and hepato-protective capacities, mitigating metabolic disturbances, oxidative stress propagation in liver and kidney functions, and potential histological alterations, thereby impeding 7,12-dimethylbenz(a)anthracene-induced mammary cancer initiation. We posit that Pistacia lentiscus may serve as a prophylactic agent against breast cancer instigated by this carcinogen.

JIS SUJ2 is most widely used in bearing steels. The advantages are good hardenability, excellent fatigue, wear resistance and comprehensive mechanical properties. For wear resistance and fatigue resistance of the steel are getting more and more attention, the residual stress state and its distribution on the surface of the heat affect zone are critical factors affecting the fatigue life and wear resistance of the parts. In this study, using the SUJ2 as the material to talk about the surface residual stress and retained austenite distribution. Doing the quenching and tempering treatment to obtain different microstructures, using the induction method to re-quench the case region. After the heat treatment, measuring the residual stress and retained austenite volume on the surface by X-ray diffraction, observing the microstructure and comparing the hardness. The results show that the microstructure after heat treatment contains unsolidified carbides, tempered martensite and retained austenite. The residual stress on the surface is the tensile state. In the re-hardened area after induction quenching, the residual stress is all compressive, and the values are more than -800 MPa. In conclusion, in the same output power condition can be observed that the microstructure of the specimens before induction hardening has a significant impact on the effective case depth. The surface residual stress has changed from a tensile to a compressive state. In the re-hardened area, the maximum of the residual compressive stress increased with the austenitized temperature increase.

Platinum group metals (PGMs) high-grade ore tonnage from Merensky reef keeps on depreciating forcing the metallurgical industry to explore beneficiating PGMs from upper group 2 (UG2) ore which has up to 60% content of chromite and from secondary sources. The PGMs are naturally associated with base metal sulphides and the efficacy of the PGMs extraction processes is dependent on the processing of PGMs-bearing base metal sulphides. These processes include concentrating PGMs-bearing base metal sulphides through flotation, oxidation, etc. prior the metal extraction processes. The evolving mineralogy of PGMs ores has necessitated the use of multiple reagents to enhance the efficiency of the concentration process. This has led to an increased amount of inor-ganic chemicals disposal to the environment and the processing of PGMs to be less economic. Bio-technology has been investigated as a potential low cost, ecologically safe substitute for many current minerals processing methods. The metabolites produced by microorganisms have been used for many years with great success in the leaching and flotation of metals from medium and low-grade sulphide minerals. The possible application of microorganism mainly Acidithiobacillus ferrooxidans (A. ferrooxidans) in the metallurgical processing of PGMs-bearing base metal sulphides is systematically reviewed in this paper. The main emphasis is on the use of A. ferrooxidans in bio-oxidation and bioleaching, as well as their potential to substitute inorganic reagents in the flo-tation of PGMs-bearing base metal sulphides from primary and secondary sources