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Fungal keratitis (FK) is an infectious keratopathy can cause serious damage to vision. Its severity is related to the virulence of fungus and response of inflammatory. Rosmarinic acid (RA) extracted from Rosmarinus officinalis exhibits antioxidant, anti-inflammatory and anti-viral properties. The aim of this study was to investigate the effect of RA on macrophage autophagy and its therapeutic effect on FK. In this study, we demonstrated that RA reduced expression of proinflammatory cytokine, lessened the recruitment of inflammatory cells in FK. The relative contents of autophagy markers, such as LC3 and Beclin-1, were significantly up-regulated in RAW 264.7 cells and FK. In addition, RA restored mitochondrial membrane potential (MMP) of macrophage to normal level. RA not only reduced the production of intracellular reactive oxygen species (ROS) but also mitochondria ROS (mtROS) in macrophage. At the same time, RA induced macrophage to M2 phenotype and down-regulated the mRNA expression of IL-6, IL-1β, TNF-α. All the above effects could be offset by the autophagy inhibitor 3-Methyladenine (3-MA). Besides, RA promote phagocytosis of RAW 264.7 cells and inhibits spore germination, biofilm formation and conidial adherence, suggesting a potential therapeutic role for RA in FK. • RA reduced the severity of keratitis and proinflammatory cytokine expression in vivo. • RA up-regulated the autophagy in RAW 264.7 cells and infected corneas. • 3-MA significantly counteracted the effects of RA on ameliorating FK. • RA reduced the ROS and mtROS in infected RAW 264.7 cells. • RA induced M2 phenotype of macrophage and exhibited antifungal property. [ABSTRACT FROM AUTHOR]

The purpose of this study is to evaluate the decolorization ability and detoxification effect of LAC-4 laccase on various types of single and mixed dyes, and lay a good foundation for better application of laccase in the efficient treatment of dye pollutants. The reaction system of the LAC-4 decolorizing single dyes (azo, anthraquinone, triphenylmethane, and indigo dyes, 17 dyes in total) were established. To explore the decolorization effect of the dye mixture by LAC-4, two dyes of the same type or different types were mixed at the same concentration (100 mg/L) in the reaction system containing 0.5 U laccase, and time-course decolorization were performed on the dye mixture. The combined dye mixtures consisted of azo + azo, azo + anthraquinone, azo + indigo, azo + triphenylmethane, indigo + triphenylmethane, and triphenylmethane + triphenylmethane. The results obtained in this study were as follows. Under optimal conditions of 30 °C and pH 5.0, LAC-4 (0.5 U) can efficiently decolorize four different types of dyes. The 24-hour decolorization efficiencies of LAC-4 for 800 mg/L Orange G and Acid Orange 7 (azo), Remazol Brilliant Blue R (anthraquinone), Bromophenol Blue and Methyl Green (triphenylmethane), and Indigo Carmine (indigo) were 75.94%, 93.30%, 96.56%, 99.94%, 96.37%, and 37.23%, respectively. LAC-4 could also efficiently decolorize mixed dyes with different structures. LAC-4 can achieve a decolorization efficiency of over 80% for various dye mixtures such as Orange G + Indigo Carmine (100 mg/L+100 mg/L), Reactive Orange 16 + Methyl Green (100 mg/L+100 mg/L), and Remazol Brilliant Blue R + Methyl Green (100 mg/L+100 mg/L). During the decolorization process of the mixed dyes by laccase, four different interaction relationships were observed between the dyes. Decolorization efficiencies and rates of the dyes that were difficult to be degraded by laccase could be greatly improved when mixed with other dyes. Degradable dyes could greatly enhance the ability of LAC-4 to decolorize extremely difficult-to-degrade dyes. It was also found that the decolorization efficiencies of the two dyes significantly increased after mixing. The possible mechanisms underlying the different interaction relationships were further discussed. Free, but not immobilized, LAC-4 showed a strong continuous batch decolorization ability for single dyes, two-dye mixtures, and four-dye mixtures with different structures. LAC-4 exhibited high stability, sustainable degradability, and good reusability in the continuous batch decolorization. The LAC-4-catalyzed decolorization markedly reduced or fully abolished the toxic effects of single dyes (azo, anthraquinone, and indigo dye) and mix dyes (nine dye mixtures containing four structural types of dyes) on plants. Our findings indicated that LAC-4 laccase had significant potential for use in bioremediation due to its efficient degradation and detoxification of single and mixed dyes with different structural types. • LAC-4 laccase had strong decolorization abilities for four main types of dyes • Four different interaction relationships in the decolorization of dye mixtures by laccase were found • The decolorization effects of the dyes that were very difficult to be degraded greatly improved when mixed with other dyes • Free, but not immobilized, LAC-4 laccase showed a strong continuous batch decolorization ability for single and mixed dyes • LAC-4 treatment could eliminate or reduce the phytotoxicity of single dyes and mixed dyes [ABSTRACT FROM AUTHOR]

The fungicide Mancozeb is an endocrine-disrupting chemical and the mode of action of Mancozeb on embryo implantation is largely unknown. Mancozeb (1 and 3 μg/ml) significantly reduced Jeg-3 trophoblastic spheroids attachment to endometrial epithelial Ishikawa cells. Mancozeb treatment from gestation day (GD) 1 to GD8 or from GD4 to GD8 significantly lowered the number of implantation sites with higher incidence of morphological abnormalities in the reproductive tissues. However, these were not seen in the treatment from GD1 to GD4. Mancozeb at 30 mg/kg BW/d did not alter the expression of p53, COX-2, or PGFS transcripts in the uterus, but down-regulated the PGES transcript and protein. Mancozeb treatment in human endometrial stromal cells did not alter the decidualization response, but the morphological transformation was impaired. Taken together, exposure to Mancozeb affected embryo implantation probably through the modulation of decidualization and to delineate the exact mode of action needs further investigations. • Mancozeb reduces trophoblastic spheroids attachment to endometrial epithelial cells. • Mancozeb effects on early pregnancy is main via modulating decidualization. • Mancozeb can down-regulate PGES mRNA and up regulate COX-2 protein. • Mancozeb hinders morphological transformation of stromal cell in dicidualization [ABSTRACT FROM AUTHOR]

Abstract The interaction between pure culture microorganisms has been evaluated allowing for the enhanced biodegradation of various kinds of pollutants. Arthrobacter sp. DNS10 previously enriched in an atrazine-containing soil was capable of utilizing atrazine as the sole nitrogen source for growth, and Enterobacter sp. P1 is a phosphorus-solubilizing bacterium that releases various kinds of organic acids but lacks the ability to degrade atrazine. Whether strain P1 could enhance atrazine biodegradation by the degrader strain DNS10 was investigated in this experiment. Gas chromatography and high-performance liquid chromatography results showed that co-culture of both strains degraded 99.18 ± 1.00% of the atrazine (initial concentration was 100 mg L−1), while the single strain DNS10 only degraded 38.57 ± 7.39% after a 48 h culture, and the resulting concentration of the atrazine final metabolite cyanuric acid were 63.91 ± 3.34 mg L−1 and 26.60 ± 3.87 mg L−1, respectively. In addition, the expression of the atrazine degradation-related genes trz N, atz B and atz C in co-culture treatments was 6.61, 1.81 and 3.09 times that of the single strain DNS10 culture treatment. A substrates utilization test showed that the atrazine-degrading metabolites ethylamine and isopropylamine could serve as the nitrogen source to support strain P1 growth, although strain P1 cannot degrade atrazine or utilize atrazine for growth. Furthermore, the pH of the medium was significantly decreased when strain P1 utilized ethylamine and isopropylamine as the nitrogen source for growth. The results suggest that nondegrader strain P1 could promote the atrazine biodegradation when co-cultured with strain DNS10. This phenomenon is due to metabolite exchange between the two strains. Culturing these two strains together is a new biostimulation strategy to enhance the biodegradation of atrazine by culturing these two strains together. Highlights • Growth of Enterobacter sp. P1 and Arthrobacter sp. DNS10 was promoted under co-culture condition. • Synergistic atrazine degradation was observed in co-culture of P1 and DNS10. • Strain P1 utilize atrazine metabolites as sole nitrogen source for growth. • The secretions of strain P1 promote the atrazine degrading ability of DNS10. • Expressions of atrazine-degrading genes in DNS10 were enhanced by co-cultures. [ABSTRACT FROM AUTHOR]

Most clinical stroke patients may have difficulty moving, affecting their self-care ability and quality of life, and causing serious interference with the normal life and work of other family members. At present, in clinical literature, researchers provide functional training for patients with motor disorders through repeated and effective training, which can ultimately effectively promote the recovery of limb function. Therefore, the near-infrared spectroscopy imaging technology (fNIRS) used in this study combines the diagnosis of sports injury with the mechanism of brain function. FNIRS technology has many advantages, such as fast, and non-invasive, and has shown great value in detecting brain activity. Therefore, it has become a promising method in the biomedical field, especially in the field of brain science. Based on the clinical effects of sports injury treatment, fNIRS technology is used to detect the hemodynamic changes of hemoglobin circulation in the patient's brain tissue during training, and to detect the brain activity mechanism in the exercise mechanism, providing a basis for the clinical application of this method. • Functional training for patients with motor disorders through repeated and effective training • FNIRS is used to combines the diagnosis of sports injury with the mechanism of brain function. • FNIRS is used to detect the hemodynamic changes of hemoglobin circulation in the patient's brain tissue. [ABSTRACT FROM AUTHOR]

Abstract In aircraft design, structural optimization concerning transonic aeroelastic issues is computationally impractical, due to a great number of aeroelastic analyses are required in iterative process. Reduced-Order Model (ROM) method is convenient for transonic aeroelastic analyses; however, current ROMs are not reusable during iteration, hence the time consumption is still too high. To solve the problem, this study proposes an improved ROM suitable for Arbitrary Mode Shapes (ROM-AMS), which is reusable in iterative process. By adopting Principal Component Analysis, ROM-AMS method significantly reduces the number of basis mode shapes, while improves the accuracy of flutter analysis. In an optimization case, the weight of a cropped delta wing is reduced by 28.46%, and the efficiency is 900 times higher than that of traditional ROM approaches, which demonstrates the feasibility of this method in aeroelastic optimization. Highlights • A Reduced-Order Modeling method for transonic aeroelastic optimization is proposed. • Number of basis modes can be largely reduced by Principal Component Analysis. • Efficiency of optimization is two orders of magnitudes higher than previous ROMs. [ABSTRACT FROM AUTHOR]

Natural odour compounds could be a potential alternative to synthetic herbicides. The odour compound of Periploca sepium Bunge, named 2-hydroxy-4-methoxy-benzaldehyde (HMB), is a herbicidal compound. However, its herbicidal mechanism is unclear. In this experiment, the physiological and biochemical indices, ultrastructure, and photosynthetic function of the leaves of Humulus scandens (Lour.) Merr. treated by HMB were assessed to elucidate the herbicidal mechanism. The results of physiological and biochemical indices are as follows: First, after 4 h of treatment with 2.5 and 5.0 mg/mL, the damage rates in the membrane permeation assay were 74.7% and 89.1%, respectively. Second, compared to the negative control group, multiple physiological and biochemical indices of the two treated groups were changed, including catalase content (−18.5 and −26.5 ng/mL), superoxide dismutase content (−27.4 and −56.6 ng/mL), peroxidase content (382.0 and 880.0 ng/mL), reactive oxygen species content (16.7 and 27.2 ng/mL), malondialdehyde content (8.9 and 25.2 nmol/g), and water potential values (0.2 and 0.3 MPa), except for the photosynthetic pigment contents (chlorophyll a, b, and carotene). Furthermore, the results of transmission electron microscopy showed that the organelles in the mesophyll tissue cells disappeared and severe plasmolysis led to cell atrophy after 4 h of treatment. There were fewer starch granules after 24 h of treatment, but there was no obvious abnormality in the upper and lower epidermal cells. The results of photosynthetic function showed that in the light response, the net photosynthetic rate (Pn), transpiration rate (Tr), stomatal conductance (Gs), and stomatal limitation value of the tested leaves were lower than those of the negative control group by 26.6 μmol·m−2·s−1, 7.7 mmol·m−2·s−1, 0.9 mol·m−2·s−1, and 0.2, respectively. However, the intercellular CO 2 concentration (Ci) increased and was higher than the air CO 2 concentration. In the CO 2 response, the Pn, Tr and Gs of the tested leaves first increased and then decreased, but the Ci value continuously increased and finally reached 1727.5 μmol·mol−1. It is obvious that HMB may have inhibited the effect on the photosynthetic system of the tested leaves. Overall, HMB killed the weeds by destroying the structure and multiple physiological functions of the tested leaves. [Display omitted] • The odor compound from Periploca sepium Bunge, named 2-hydroxy-4-methoxy-benzaldehyde (HMB), is an herbicidal compound. • HMB have significantly affected the leaf physiology of Humulus scandens (Lour.) Merr. • The transmission electron microscopy (TEM) results showed that the organelles in the mesophyll cells of leaves disappeared. • The results of photosynthetic function showed that HMB have inhibited net photosynthetic rate (Pn) of test leaves. [ABSTRACT FROM AUTHOR]

The workpiece is prone to self-excited vibration when turning a slender shaft and the flexibility cannot be ignored in this condition. In this paper, a new flexible tool-workpiece system is developed to investigate the nonlinear dynamics and chatter stability for in a turning process. The piecewise-nonlinear restoring function of the tool system is derived by calculating axial deformations and forces of the ball screw feed system. With the variation of time delay, the dynamic behaviors of the cutting system are analyzed by numerical method, which manifests as periodic, quasi-periodic, and chaotic motions. Through determining the critical chip width under different spindle speed, the stability lobe diagram (SLD) of nonlinear system is obtained to distinguish stable and unstable states. In addition, the dynamic characteristics and SLD of nonlinear system are compared with linear system. An experiment is carried out to observe the vibration phenomenon under stable and unstable turning conditions and verify the accuracy of stability prediction. [ABSTRACT FROM AUTHOR]

The odor compound from Periploca sepium Bunge, 2-hydroxy-4-methoxy-benzaldehyde (HMB), is an allelochemical agent and is one of the least investigated isomers of vanillin. In this study, we used label-free quantitative proteomics analysis technology to investigate the effect of HMB on the protein expression of Humulus scandens (Lour.) Merr. leaves in July 2019 on Guiyang. A total of 269 proteins of 624 identified proteins were differentially expressed, among which 21.18% of the proteins were up-regulated and 32.71% down-regulated. These proteins were classified into 11 cell components and more than 20% of differentially expressed proteins were located in cell membrane and chloroplast. Functional classification analysis showed that 12 molecular functions were altered upon HMB treatment, and the ratio of catalytic activity was the highest (19.53%). At least 12 biological functions were affected, which involved small molecule metabolic processes, organic substance metabolic processes, gene expression, and photosynthesis. Our data provide resources and insights into the biochemical mechanism by which HMB kills weeds. [Display omitted] • Two-hydroxy-4-methoxy-benzaldehyde (HMB) was isolated from Periploca sepium Bunge. • A total of 269 proteins of tested leaves were 21.18% of up-regulated and 32.71% of down-regulatedy. • Over 20% of differentially expressed proteins were located in the cell membrane and chloroplast. • The differentially proteins were altered upon HMB treatment. • Twelve biological functions were affected by HMB. [ABSTRACT FROM AUTHOR]

Mancozeb is a metal-containing ethylene bis-dithiocarbamate fungicide widely used in agriculture. Ethylene thiourea (ETU) is the primary metabolite of Mancozeb. Mancozeb has been associated with spontaneous abortions and abnormal menstruation in women. However, the effects of Mancozeb and ETU on embryo attachment remain unknown. The human blastocyst surrogate trophoblastic spheroids (JEG-3), endometrial epithelial surrogate adenocarcinoma cells (Ishikawa), or human primary endometrial epithelial cells (EECs) monolayer were used in the spheroid attachment models. Ishikawa and EECs were pretreated with different concentrations of Mancozeb or ETU for 48 h before the attachment assay. Gene expression profiles of Ishikawa cells were examined to understand how Mancozeb modulates endometrial receptivity with Microarray. The genes altered by Mancozeb were confirmed by qPCR and compared with the ETU treated groups. Mancozeb and ETU treatment inhibited cell viability at 10 μg/mL and 5000 µg/mL, respectively. At non-cytotoxic concentrations, Mancozeb at 3 μg/mL and ETU at 300 μg/mL reduced JEG-3 spheroid attachment onto Ishikawa cells. A similar result was observed with human primary endometrial epithelial cells. Mancozeb at 3 μg/mL modified the transcription of 158 genes by at least 1.5-fold in Microarray analysis. The expression of 10 differentially expressed genes were confirmed by qPCR. Furthermore, Mancozeb decreased spheroid attachment possibly through downregulating the expression of endometrial estrogen receptor β and integrin β3, but not mucin 1. These results were confirmed in both overexpression and knockdown experiments and co-culture assay. Mancozeb but not its metabolite ETU reduced spheroid attachment through modulating gene expression profile and decreasing estrogen receptor β and integrin β3 expression of endometrial epithelial cells. • The pesticide Mancozeb exerts higher cytotoxicity than its metabolite ETU. • Mancozeb suppresses trophoblastic spheroid attachment onto endometrial epithelial cells at concentration 100-fold lower than ETU. • Mancozeb modulates the gene expression profile in the endometrial cells. • Mancozeb but not ETU decreases endometrial ERβ, integrin β3 and Mucin1 expression. • Knockdown of ERβ and integrin β3 decreases spheroid attachment. • Overexpression of ERb and integrin b3 nullifies the inhibitory effect of Mancozeb on spheroid attachment. [ABSTRACT FROM AUTHOR]

Recently, accumulating studies have reported the roles of competitive endogenous RNA (ceRNA) networks in ischemia/reperfusion (I/R) injury in several organs, including the liver, kidney, heart, brain, and intestine. However, the functions and mechanisms of long noncoding RNAs (lncRNAs)—which serve as ceRNA networks in intestinal I/R injury—remain elusive. RNA expression data were retrieved from the National Center for Biotechnology Information-Gene Expression Omnibus database. Differentially expressed microRNAs (miRNAs) (miDEGs) were explored between the sham and intestinal I/R injury samples. Next, targeted lncRNAs and messenger RNAs in the database were matched based on miDEGs. Hub ceRNA networks were constructed and visualized via Cytoscape. Intersection analysis was performed to screen mDEGs between two datasets. Finally, the vital nodes of the ceRNA networks were validated by quantitative PCR. A total of 189 miDEGs were identified. Forty miRNAs were found to be associated with 240 predicted target genes from miRWalk 3.0. The ceRNA network was constructed with 10 miRNAs, including the 1700020114Rik/mmu-miR-7a-5p/Klf4 axis. Furthermore, the expression of lncRNA 1700020114Rik (P < 0.05) and messenger RNA Klf4 (P < 0.01) was markedly decreased in mouse models of intestinal I/R injury, whereas the expression level of mmu-miR-7a-5p was significantly increased (P < 0.05). The results provide novel insights into the molecular mechanism of ceRNA networks in intestinal I/R injury and highlight the potential of the 170002700020114Rik/mmu-miR-7a-5p/Klf4 axis in the prevention and treatment of intestinal I/R injury. [ABSTRACT FROM AUTHOR]

Urban green spaces play a crucial role in cities by providing near-natural environments that greatly impacts the health of residents. However, these green spaces have recently been scrutinized as potential reservoirs of antibiotic resistance genes (ARGs), posing significant ecological risks. Despite this concern, our understanding of the distribution, sources, and ecological risks associated with ARGs remains limited. In this study, we investigated the spatial distribution of soil ARGs using spatial interpolation and auto-correlation analysis. To apportion the source of soil ARGs in urban green spaces of Tianjin, Geo-detector method (GDM) was employed. Furthermore, we evaluated the ecological risk posed by ARGs employing risk quotients (RQ). The results of our study showed a significantly higher abundance of Quinolone resistance genes in the soil of urban green spaces in Tianjin. These genes were mainly found in the northwest, central, and eastern regions of the city. Our investigation identified three main factors contributing to the presence of soil ARGs: antibiotic production, precipitation, livestock breeding, and hospital. The results of ecological risk in RQ value showed a high risk associated with Quinolone resistance genes, followed by Aminoglycoside, Tetracycline, Multidrug, MLSB, Beta Lactam, Sulfonamide, and Chloramphenicol. Mantel-test and correlation analysis revealed that the ecological risk of ARGs was greatly influenced by soil properties and heavy metals. This study provides a new perspective on source apportionment and the ecological risk assessment of soil ARGs in urban green spaces. • Explore the spatial distribution of soil antibiotic resistance genes. • Identify the sources of soil antibiotic resistance genes via multiple models. • Assess the ecological risk of soil antibiotic resistance genes in urban green space. [ABSTRACT FROM AUTHOR]

Fungal keratitis (FK) is a refractory keratitis caused by excessive inflammation and fungal damage. Excessive inflammation can lead to tissue damage and corneal opacity, resulting in a poor prognosis for FK. Oxymatrine (OMT) is a natural alkaloid, which has rich pharmacological effects, such as antioxidant and anti-inflammation. However, its antifungal activity and the mechanism of action in FK have not been elucidated. This study confirmed that OMT suppressed Aspergillus fumigatus growth, biofilm formation, the integrity of fungal cell and conidial adherence. OMT not only effectively reduced corneal fungal load but also inflammation responses. OMT lessened the recruitment of neutrophils and macrophages in FK. In addition, OMT up-regulated the expression of Nrf2 and down-regulated the expression of IL-18, IL-1β, caspase-1, NLRP3 and GSDMD. Pre-treatment with Nrf2 inhibitor up-regulated the expression of IL-1β, IL-18, caspase-1, NLRP3 and GSDMD supressed by OMT. In conclusion, OMT has efficient anti-inflammatory and antifungal effects by suppressing fungal activity and restricting pyroptosis via Nrf2 pathway. OMT is considered as a potential option for the treatment of FK. • Oxymatrine alleviated the severity of mouse fungal keratitis. • Oxymatrine exerted antifungal effects to suppress A. fumigatus growth. • Oxymatrine lessened infiltration of neutrophils and macrophages in mouse fungal keratitis. • Oxymatrine suppressed the excessive inflammatory response by inhibiting pyroptosis via Nrf2 pathway during fungal infections. [ABSTRACT FROM AUTHOR]

[Display omitted] • SASH1 is identified as a novel binding partner for Eph receptors through SAM-SAM interactions, with the highest affinity for EphA8. • The high-resolution crystal structure of the EphA8/SASH1 SAM-SAM complex reveals molecular basis governing the specific inter-molecular interactions. • Cancer mutations (EphA8 R942H or G978D) impair the interaction between EphA8 and SASH1, highlighting potential implications in tumorigenesis. • SASH1 enhances EphA8 receptor kinase activation through their SAM-SAM interaction. The Eph (erythropoietin-producing human hepatocellular) receptor family, the largest subclass of receptor tyrosine kinases (RTKs), plays essential roles in embryonic development and neurogenesis. The intracellular Sterile Alpha Motif (SAM) domain presents a critical structural feature that distinguishes Eph receptors from other RTKs and participates in recruiting and binding downstream molecules. This study identified SASH1 (SAM and SH3 domain containing 1) as a novel Eph receptor-binding partner through SAM-SAM domain interactions. Our comprehensive biochemical analyses revealed that SASH1 selectively interacts with Eph receptors via its SAM1 domain, displaying the highest affinity for EphA8. The high-resolution crystal structure of the EphA8-SASH1 complex provided insights into the specific intermolecular interactions between these proteins. Cellular assays confirmed that EphA8 and SASH1 co-localize and co-precipitate in mammalian cells, with cancer mutations (EphA8 R942H or G978D) impairing this interaction. We demonstrated that SAM-SAM interaction is critical for SASH1-mediated regulation of EphA8 kinase activity, shedding new light on the Eph signaling pathway and expanding our understanding of the molecular basis of the tumor suppressor gene SASH1. [ABSTRACT FROM AUTHOR]

Pathological fractures caused by osteolytic lesions seriously threaten the health of patients. Osteoclasts play important roles in bone resorption whose hyperfunction are closely related to osteolytic lesions. Studies on osteoclast differentiation and function assist in the prevention of excessive bone loss associated diseases. We screened a variety of natural compounds with anti-inflammatory effect and found that poria cocos polysaccharide (PCP) inhibited RANKL-induced osteoclast formation and bone resorption via TRAcP staining, immunofluorescence, RT-PCR and western blot. PCP down-regulated phosphorylation of STAT3, P38, ERK and JNK, and thus repressed the expression of NFAcT1 and c-Fos during RANKL-induced osteoclastogenesis. Besides, the expression of bone resorption related genes such as TRAcP and CTSK was suppressed by PCP. The results suggest that PCP can be invoked as a candidate for the treatment of osteolytic diseases by inhibiting osteoclastogenesis. [ABSTRACT FROM AUTHOR]

Identification of rotor unbalance is critical for normal operation of rotating machinery. The single-disc and single-span rotor, as the most fundamental rotor-bearing system, has attracted research attention over a long time. In this paper, the continuous single-disc and single-span rotor is modeled as a homogeneous and elastic Euler-Bernoulli beam, and the forces applied by bearings and disc on the shaft are considered as point forces. A fourth-order non-homogeneous partial differential equation set with homogeneous boundary condition is solved for analytical solution, which expresses the unbalance response as a function of position, rotor unbalance and the stiffness and damping coefficients of bearings. Based on this analytical method, a novel Measurement Point Vector Method (MPVM) is proposed to identify rotor unbalance while operating. Only a measured unbalance response registered for four selected cross-sections of the rotor-shaft under steady-state operating conditions is needed when using the method. Numerical simulation shows that the detection error of the proposed method is very small when measurement error is negligible. The proposed method provides an efficient way for rotor balancing without test runs and external excitations. [ABSTRACT FROM AUTHOR]

[Display omitted] • M2 (PD) is the main metabolite of dammarane ginsenoside AD-1 in vivo. • Compound M3 was isolated from metabolites in vivo for the first time. • PD could significantly inhibit the proliferation and migration of MDA-MB-231 cells and induce G1-phase arrest. • PD could significantly inhibit the proliferation and migration of breast cancer in nude mice. • PD inhibited proliferation and metastasis of breast cancer cells by inducing the p38 MAPK/MMP9 pathway. Previous studies have shown that 20 (R)-25-methoxyl-dammarane-3 β , 12 β , 20 triol (AD-1) can inhibit various cancer cell lines. This study aimed to explore the effect and mechanism of AD-1 metabolite M2 (Panaxadiol; PD) on breast cancer cells of nude mice. Five AD-1 metabolites were isolated and identified using various chromatographic techniques. PD was the main component. In vitro results showed that PD could inhibit the proliferation and migration of MDA-MB-231 cells by inducing G1-phase arrest. In addition, PD down-regulated the expression of Cyclin D1, cdk2, cdk4, cdk6, P-p38, and MMP9, and up-regulated p21 and p27. In vivo results showed that PD could effectively reduce the volume, weight, and migration of breast cancer Transcriptomics analyzed 491 differentially expressed genes by GO and KEGG enrichment. RT-PCR verification confirmed that the significant down-regulation of MMP9 was consistent with transcriptomics results. In further research showed that PD regulated the protein expression of P-p38 and MMP9 in MAPK pathway. In summary, in vivo and in vitro studies showed that PD significantly inhibit the occurrence and development of breast cancer, possibly through the MAPK pathway. [ABSTRACT FROM AUTHOR]

Abstract: An integrative non-conjugative extrachromosomal genetic element, denoted as pSSVi, has been isolated from a Sulfolobus solfataricus P2 strain and was characterized. This genetic element is a double-stranded DNA of 5740 bp in size and contains eight open reading frames (ORFs). It resembles members of the pRN plasmid family in genome organization but shows only weak similarity to the latter in conserved regions. pSSVi has a copG gene similar to that of a pRN plasmid, encodes a large replication protein which, unlike a typical pRN RepA, contains no polymerase/primase domain, and lacks the plrA gene. Interestingly, pSSVi encodes an SSV-type integrase which probably catalyzes the integration of its genome into a specific site (a tRNAArg gene) in the S. solfataricus P2 genome. Like pSSVx, pSSVi can be packaged into a spindle-like viral particle and spread with the help of SSV1 or SSV2. In addition, both SSV1 and SSV2 appeared to replicate more efficiently in the presence of pSSVi. Given the versatile genetic abilities, pSSVi appears to be well suited for a role in horizontal gene transfer. [Copyright &y& Elsevier]

Note: ARC inhibits osteoclastogenesis by suppressing RANKL-induced MAPK (including JNKs and ERKs), calcium, and NFATc1 signaling pathway, as well as by promoting the expression of ROS scavenging enzymes in Nrf2/Keap1/ARE signaling pathway. Osteoporosis, characterized by disrupted bone resorption and formation, is viewed as a global health challenge. Arctiin (ARC) is a main component of Arctium lappa L, which exerts chemopreventive effects against various tumor cells. However, the role of ARC in bone remodeling is still unclear. Here, we first demonstrated that ARC inhibits osteoclast formation and bone resorption function induced by the receptor activator of nuclear factor-κB ligand (RANKL) in a dose- and time-dependent manner without exerting cytotoxic effects. Mechanistic analysis revealed that ARC not only suppresses RANKL-induced mitogen-activated protein kinase (MAPK) and calcium signaling pathways, but also enhances the expression of cytoprotective enzymes that are involved in scavenging reactive oxygen species (ROS). Further, ARC inhibits the activation of the major transcription factor nuclear factor of activated T cells 1 (NFATc1) during RANKL-induced osteoclast formation. Preclinical studies showed that ARC protects bone loss in an ovariectomy (OVX) mouse model. Conclusively, our data confirmed that ARC could potentially inhibit osteoclastogenesis by abrogating RANKL-induced MAPK, calcium, and NFATc1 signaling pathway, as well as by promoting the expression of ROS scavenging enzymes in Nrf2/Keap1/ARE signaling pathway, thereby 2 2 Atp6v0d2 preventing OVX-induced bone loss. Thus, ARC may serve as a novel therapeutic agent for the treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

• For the first time, 16 metabolites of 20(R)-25-OCH 3 -PPD were isolated and identified, of which 10 were new compounds. • We first discovered the biotransformation of dammarane-type sapogenins into oleanane-type sapogenins in rats, found a series of metabolites that changed mainly at C-29. • We studied the anticancer mechanisms of active oleanane-type sapogenin (M6). All the results suggested that M6 manifested higher efficacy on inhibiting cancer cells proliferation by inducing cell apoptosis. 20(R)-25-methoxyl-dammarane-3 β ,12 β ,20-triol (AD-1, CN Patent: 201010107476.7) is a novel derivative of dammarane-type ginsenoside. AD-1 has been shown to inhibit cancer cell proliferation without significant host toxicity in vivo , and has excellent development potential as a new anti-cancer agent. This study was designed systematically to explore the metabolic pathway of ginseng sapogenins. The metabolism of drugs in the body is a complex biotransformation process where drugs are structurally modified to different molecules (metabolites) through various metabolizing enzymes. The compounds responsible for the effects of orally administered ginseng are believed to be metabolites produced in the gastrointestinal tract, so understanding the metabolism of the drug candidate can help to optimize its pharmacokinetics. In this study, faeces samples were collected and extracted after oral administration of AD-1. The 16 metabolites of AD-1 were isolated and identified for the first time with various chromatographic techniques, including semi-preparative high performance liquid chromatography, nuclear magnetic resonance spectroscopy, and mass spectrometry; of these 16 metabolites, 10 were novel compounds. We first discovered the biotransformation of dammarane-type sapogenins into oleanane-type sapogenins in rats and found a series of metabolites that changed, mainly at C-25 and C-29. This study provides new ideas for the metabolic pathway of ginseng sapogenins. The isolated compounds were screened for their effect on the viability and proliferation against cancer cell lines (Human A549, MCF-7, HELA, HO-8901 and U87). The discovery of novel active metabolites 3 β ,12 β ,21 α ,22 β -Hydroxy-24-norolean-12-ene (M6) may lead to a new or improved drug candidate. For one, M6 could inhibit the growth of all the tested cancer cells. Among the tested cell lines, M6 exhibited the most remarkable inhibitory effect on ovarian cancer HO-8901 cells, with IC 50 value of 2.086 μM. On this basis, we studied the anticancer mechanisms of M6. The results indicated that the pro-apoptotic feature of M6 acts via a mitochondrial pathway. Our results indicated that M6 exhibited a higher inhibitory effect on cancer-cell proliferation than AD-1 by inducing cell apoptosis. Our work provides data for future investigations on the metabolic mechanism of AD-1 in vivo and the potential for future research on developing a new drug. [ABSTRACT FROM AUTHOR]