The hybrid nanosystem for the identification and magnetic hyperthermia immunotherapy of metastatic sentinel lymph nodes as a multifunctional theranostic agent.

Lymphatic metastasis is the main cause of early-stage tumor spread, making the identification and therapy of metastatic sentinel lymph nodes (SLNs) are highly desirable in clinic. Currently, suspected malignant SLNs typically undergo a series of independent operations in clinical practice, including imaging, staining, sentinel lymph node biopsy (SLNB) and lymph node dissection (LND), which brings inconvenience to diagnosis and treatment, and may cause postoperative complications for patients. Moreover, the ordinary removal of tumor-draining lymph nodes (TDLNs) may do harm to systemic immunity required for tumor eradication. Hence, we utilized the hybrid nanosystem (SPIOs + RPPs) we constructed before for the integrated staining, ultrasound imaging, and therapy of metastatic SLNs. In this study, SPIOs + RPPs could migrate into SLNs successfully to stain them black for easy visual identification. Beyond staining, the hybrid nanosystem could realize contrast enhanced ultrasound (CEUS) imaging in SLNs. Meanwhile, it could inhibit cancer cells to lower the tumor burden and reverse immune-suppressive microenvironment of metastatic SLNs effectively via magnetic hyperthermia immunotherapy in VX2 tumor-bearing rabbits with popliteal fossa lymph node metastasis. These findings indicate that SPIOs + RPPs is a potential multifunctional theranostic agent for detection and therapy of lymphatic metastasis.

Infertility risk assessment with ultrasound in congenital adrenal hyperplasia male patients.

Testicular adrenal rest tumor (TART) is a prevalent complication associated with congenital adrenal hyperplasia (CAH), culminating in gonadal dysfunction and infertility. Early hormonal intervention is preventive, but excessive glucocorticoid poses risks. Developing reliable methods for early TART diagnosis and monitoring is crucial. The present study aims to formulate a scoring system to identify high-risk infertility through analysis of TART ultrasound features. Grayscale and power Doppler ultrasound were employed in this retrospective study to evaluate testicular lesions in male CAH patients. Lesion assessment encompassed parameters such as range, echogenicity, and blood flow, and these were subsequently correlated with semen parameters. Results of 49 semen analyzes from 35 patients demonstrated a notable inverse correlation between lesion scores and both sperm concentration (rs = - 0.83, P < 0.001) and progressive motility (rs = - 0.56, P < 0.001). The ROC curve areas for evaluating oligospermia and asthenozoospermia were calculated as 0.94 and 0.72, respectively. Establishing a lesion score threshold of 6 revealed a sensitivity of 75.00% and specificity of 93.94% for oligospermia and a sensitivity of 53.85% and specificity of 100.00% for asthenozoospermia. These findings underscore the potential utility of incorporating ultrasound into routine CAH patient management, facilitating timely interventions to preserve male fertility.

Smartphone app-based interventions on physical activity behaviors and psychological correlates in healthy young adults: A systematic review.

BACKGROUND: The issue of low physical activity (PA) levels among the youth is a longstanding concern. Smartphone applications offer a promising avenue for delivering interventions that are both accessible and engaging. Up to now, there appears to be a gap in the literature, with no systematic reviews assessing the efficacy of smartphone apps in encouraging increased physical activity among healthy young adults. OBJECTIVE: To synthesize the effects of a smartphone app-based intervention on PA and PA-related psychological correlates in healthy young adults (18-35 years old). METHODS: A search was conducted on eighteen databases: PubMed, Medline, Web of Science, SPORTDiscus, Scopus, Academic Search Premier, Communication and Mass Media Complete, Article First, Biomed Central, BioOne, EBSCOHost, JSTOR, ProQuest, SAGE Reference Online, ScienceDirect, SpringerLink, Taylor&Francis, and Wiley Online. The search covered the period up until December 2023. This research included all randomized controlled trials (RCTs) that evaluated the effectiveness of smartphone app-based interventions on PA and PA related psychological outcomes in healthy young adults. The overall impact was determined by vote counting based on the direction of effect and aggregating p values. The quality of the evidence was evaluated using an 8-item scale. This study has been registered in the PROSPERO database with the identification number CRD42023390033. RESULTS: A total of 8403 articles were retrieved, and based on the predefined inclusion and exclusion criteria, seven articles were selected for inclusion. Among these articles, four high-quality RCTs were identified, and the results of vote counting and combining p values methods suggested that smartphone-based app interventions did not demonstrate significant effectiveness in improving PA and PA-related psychological outcomes. However, some improvements were observed. The analysis results, which were categorized into fitness apps and health apps based on the characteristics of the interventions, also failed to demonstrate significant intervention effects. CONCLUSION: The findings indicate that, currently, there are no significant effects of smartphone app interventions on improving PA and PA-related psychological outcomes in healthy young adults aged 18-35 years. It is important to note that these findings should be interpreted with caution due to the limited number of included studies. Future research should focus on employing high-quality study designs to determine the true effects of interventions and analyze various smartphone app interventions. These analyses should encompass different app characteristics (e.g., fitness app and health app), various combinations (e.g., fitness app alone and fitness app in combination with other interventions), diverse intervention goals (e.g., PA and PA along with other outcomes), and multiple intervention characteristics (e.g., frequency and duration).

[Screening for Characteristic Genes of Different Traditional Chinese Medicine Syndromes of Psoriasis Vulgaris: A Study Based on Bioinformatics and Machine Learning]. / ç”Ÿç‰©ä¿¡æ¯å­¦å’Œæœºå™¨å­¦ä¹ ç­›é€‰é“¶å±‘ç— ä¸­åŒ»è¯åž‹ç‰¹å¾åŸºå› .

Objective: To screen for the key characteristic genes of the psoriasis vulgaris (PV) patients with different Traditional Chinese Medicine (TCM) syndromes, including blood-heat syndrome (BHS), blood stasis syndrome (BSS), and blood-dryness syndrome (BDS), through bioinformatics and machine learning and to provide a scientific basis for the clinical diagnosis and treatment of PV of different TCM syndrome types. Methods: The GSE192867 dataset was downloaded from Gene Expression Omnibus (GEO). The limma package was used to screen for the differentially expressed genes (DEGs) of PV, BHS, BSS, and BDS in PV patients and healthy populations. In addition, KEGG (Kyoto Encyclopedia of Genes and Genes) pathway enrichment analysis was performed. The DEGs associated with PV, BHS, BSS, and BDS were identified in the screening and were intersected separately to obtain differentially characterized genes. Out of two algorithms, the support vector machine (SVM) and random forest (RF), the one that produced the optimal performance was used to analyze the characteristic genes and the top 5 genes were identified as the key characteristic genes. The receiver operating characteristic (ROC) curves of the key characteristic genes were plotted by using the pROC package, the area under curve (AUC) was calculated, and the diagnostic performance was evaluated, accordingly. Results: The numbers of DEGs associated with PV, BHS, BSS, and BDS were 7699, 7291, 7654, and 6578, respectively. KEGG enrichment analysis was focused on Janus kinase (JAK)/signal transducer and activator of transcription (STAT), cyclic adenosine monophosphate (cAMP), mitogen-activated protein kinase (MAPK), apoptosis, and other pathways. A total of 13 key characteristic genes were identified in the screening by machine learning. Among the 13 key characteristic genes, malectin (MLEC), TUB like protein 3 (TULP3), SET domain containing 9 (SETD9), nuclear envelope integral membrane protein 2 (NEMP2), and BTG anti-proliferation factor 3 (BTG3) were the key characteristic genes of BHS; phosphatase 15 (DUSP15), C1q and tumor necrosis factor related protein 7 (C1QTNF7), solute carrier family 12 member 5 (SLC12A5), tripartite motif containing 63 (TRIM63), and ubiquitin associated protein 1 like (UBAP1L) were the key characteristic genes of BSS; recombinant mouse protein (RRNAD1), GTPase-activating protein ASAP3 Protein (ASAP3), and human myomesin 2 (MYOM2) were the key characteristic genes of BDS. Moreover, all of them showed high diagnostic efficacy. Conclusion: There are significant differences in the characteristic genes of different PV syndromes and they may be potential biomarkers for diagnosing TCM syndromes of PV.

Impacts of landscape patterns on plant species diversity at a global scale.

Landscape patterns are important drivers of biodiversity. Owing to differences in vegetation types, sampling methods, diversity measures, spatial scales, and landscape levels, the impact of landscape patterns on biodiversity remains widely debated. Using a global standardized plant community database and land use and land cover maps at 30-m resolution, for the period 1990-2017, we calculated plant species α- and ß-diversity, and landscape metrics at patch- and landscape-levels, and discerned the direct and indirect impacts of landscape patterns on plant species diversity based on environmental factors, namely climate, spatial features, and human disturbance. We found that landscape patterns exhibited the main indirect effects, whereas climate factors exhibited dominant direct effects on plant α-diversity via the direct effects of patch patterns and functional traits. With respect to ß-diversity, landscape-level patterns exerted more direct than indirect effects. These effects are strongly dependent on scale. Landscape- and patch-level patterns had opposite effects on plant diversity, depending on their composition and spatial structure, demonstrating that their effects could be mediated by one another. The adaptation of plants to landscape patterns is mainly through variations in leaf area, plant height, specific leaf area, stem density, seed biomass, and other seed-dispersal traits, which vary across vegetation types. Our findings highlight the importance of functional traits and diversity in understanding the mechanism by which landscape patterns influence plant species diversity; accordingly, we recommend balancing the spatial structure of patch- and landscape-level patterns to enhance variation in functional traits, and, ultimately, to maintain global plant diversity.

[Meta-analysis of case-control studies on obesity risk factors in children aged 3-6 years in China].

OBJECTIVE: To explore the risk factors of obesity in children aged 3-6 years in China. METHODS: Using search terms, preschooler, obesity, risk factors/influence factors, case-control studies, and language limited to Chinese and English, search databases(CNKI, Wanfang, VIP, CBM, PubMed, Web of science, Embase, The Cochrane library). To collect domestic and foreign literature on the case-control study design of obesity risk factors in preschool children in China published from January 1, 2000 to June 30, 2021. Stata 14.0 software was used for Meta-analysis of the included literature, and publication bias test and sensitivity analysis were performed. RESULTS: A total of 11 770 people were included in 12 papers, including 4092 in the case group and 7678 in the control group. Meta analysis shows: birth weight ≥4000 g OR=2.176, 95% CI 1.507-3.143; strong appetite OR=3.860, 95%CI 2.991-4.980; fast eating OR=2.836, 95%CI 2.552-3.152; mother overweight and obesity OR=1.903, 95%CI 1.213-2.986; mother's low level of education OR=1.744, 95%CI 1.100-2.766; Physical inactivity OR=1.488, 95%CI 1.267-1.748. CONCLUSION: Birth weight ≥ 4000 g, fast eating speed, strong appetite, mother overweight and obesity, mother's low level of education, and physical inactivity are risk factors for obesity in children aged 3-6 years.

Geniposide inhibits SphK1 membrane targeting to restore macrophage polarization balance in collagen-induced arthritis mice.

Imbalance of macrophage polarization plays a critical role in the progression of rheumatoid arthritis (RA). Geniposide (GE) has been shown to exert anti-inflammatory effects. However, the effect of GE on macrophage polarization remains unclear. Here, we investigated the regulation of GE on the imbalance of macrophage polarization in RA and how it functions. We established a mouse model of collagen-induced arthritis (CIA) and isolated bone marrow-derived macrophages (BMDMs). The results confirmed that pro-inflammatory M1 macrophages were dominant in CIA mice, but the polarization imbalance of macrophages was restored to a certain extent after GE treatment. Furthermore, the membrane targeting of sphingosine kinase 1 (SphK1) was increased in BMDMs of CIA mice, as manifested by increased membrane and cytoplasmic expression of p-SphK1 and high secretion level of sphingosine-1-phosphate (S1P). RAW264.7 cells were stimulated with lipopolysaccharide (LPS)-interferon (IFN)-γ or interleukin (IL)-4 to induce M1 or M2 phenotype, respectively, to revalidate the results obtained in BMDMs. The results again observed SphK1 membrane targeting in LPS-IFN-γ-stimulated RAW264.7 cells. Selective inhibition of SphK1 by PF543 or inhibition of the S1P receptors by FTY720 both restored the proportion of M1 and M2 macrophages in LPS-IFN-γ-stimulated RAW264.7 cells, confirming that SphK1 membrane targeting mediated a proportional imbalance in M1 and M2 macrophage polarization. In addition, GE inhibited SphK1 membrane targeting and kinase activity. Taken together, results confirmed that the inhibition of SphK1 membrane targeting by GE was responsible for restoring the polarization balance of macrophages in CIA mice.

Phosphorus status and adsorption characteristics of perennial vegetable-cultivated soils in South China.

Phosphorus (P) is an essential element for crop production and a key source of nonpoint pollution in agroecosystems. In this study, we sought to analyze P levels and the factors affecting soil P availability, via P adsorption, in a typical field system that is characterized by the year-round cultivation of vegetables. A total of 190 sites were sampled from vegetable fields in Guangdong Province, South China. Within the research area, average concentrations of 124.49 mg P kg-1 and 1.55 g P kg-1 were recorded for available P (AP) and total P (TP), respectively, which are 8.53- and 1.78-fold higher, respectively, than the corresponding values recorded in 1980. The determined P adsorption maximum (Qm) averaged at 488.38 mg kg-1, which represents a reduction of 16% compared to the values obtained four decades ago. Accumulations of both TP and AP were found to be negatively correlated with the soil's maximum adsorption buffering capacity (MBC), although no significant correlations with the soil binding energies (k) and Qm, were seen. However, soil pH was found to be significantly correlated with k and Qm. Furthermore, both free Mn oxides (Mnd) and silt concentrations in the soil were found to contribute to explaining the variations in Qm. Collectively, the findings of this study provide evidence to indicate that there has been an excessive accumulation of P in the perennial vegetable fields of Guangdong Province over the past four decades, which may have had negative effects on the P supply potential of the soil by reducing the maximum adsorption buffering capacity.

Hirudin, a thrombin inhibitor, attenuates TGF-ß-induced fibrosis in renal proximal tubular epithelial cells by inhibition of protease-activated receptor 1 expression via S1P/S1PR2/S1PR3 signaling.

Renal interstitial fibrosis (RIF) is the final common outcome of numerous chronic kidney diseases, contributing to end-stage renal disease. Hirudin, a thrombin inhibitor, has attracted increased attention as a potential treatment approach for renal fibrosis. The present study aimed to investigate the molecular mechanism underlying the effect of hirudin on fibrosis in renal proximal tubular epithelial cells. An in vivo mouse RIF model established using unilateral ureteral obstruction (UUO) and an in vitro of RIF using the renal tubular epithelial cell line HK-2 treated with TGF-ß were used. Expressions of sphingosine-1-phosphate (S1P) receptors (S1PR)1-4 and protease-activated receptor 1 (PAR1) were measured by reverse transcription-quantitative PCR and western blotting in mice with UUO and TGF-ß induced HK-2 cells. Western blotting was used to detect the expression of N-cadherin, Slug, E-cadherin, Collagen IV, fibronectin, MMP9 and monocyte chemoattractant protein-1. Immunofluorescence staining was conducted to measure α-SMA level expression. The results demonstrated that the expression levels of S1PR1, S1PR2, S1PR3, S1PR4 and PAR1 were upregulated in both TGF-ß-induced HK-2 cells and renal tissues from mice with unilateral ureteral ligation. Notably, hirudin inhibited TGF-ß-induced PAR1, S1PR2 and S1PR3 upregulation in both HK-2 cells and renal tissues. Additionally, the inhibition of S1PR2 and S1PR3 resulted in PAR1 downregulation. Furthermore, treatment with S1P and PAR1 agonists abolished the effect of hirudin on the expression of EMT, fibrosis-related proteins and monocyte chemoattractant protein 1. In conclusion, hirudin attenuated TGF-ß-induced fibrosis in proximal renal tubular epithelial HK-2 cells by inhibiting PAR1 expression via the S1P/S1PR2/S1PR3 signaling pathway. Therefore, hirudin may be considered as a promising therapeutic agent for RIF.

Geniposide downregulates the VEGF/SphK1/S1P pathway and alleviates angiogenesis in rheumatoid arthritis in vivo and in vitro.

The VEGF/SphK1/S1P pathway is closely related to angiogenesis in rheumatoid arthritis (RA), but the precise underlying mechanisms are unclear at present. Here, we explored the involvement of the VEGF/SphK1/S1P cascade in RA models and determined the effects of GE intervention. Our results showed abnormal expression of proteins related to this pathway in RA synovial tissue. Treatment with GE effectively regulated the signal axis, inhibited angiogenesis, and alleviated RA symptoms. In vitro, TNF-ɑ enhanced the VEGF/SphK1/S1P pathway in a co-culture model of fibroblast-like synoviocytes (FLS) and vascular endothelial cells (VEC). GE induced downregulation of VEGF in FLS, restored the dynamic balance of pro-/antiangiogenic factors, and suppressed SphK1/S1P signaling in VEC, resulting in lower proliferation activity, migration ability, tube formation ability, and S1P secretion ability of VEC cells. Additionally, SphK1-specific small interfering RNA (siRNA) blocked the VEGF/SphK1/S1P cascade, which can effectively alleviate the stimulatory effect of FLS on VEC and further enhanced the therapeutic effect of GE. Taken together, our results demonstrate that GE suppresses the VEGF/SphK1/S1P pathway and alleviates the stimulation of VEC by FLS, thereby preventing angiogenesis and promoting therapeutic effects against RA.

Ultrasound lymphatic imaging for the diagnosis of metastatic central lymph nodes in papillary thyroid cancer.

OBJECTIVES: Up to 40% of papillary thyroid cancer (PTC) patients have lymph node metastasis, a condition that implies persistent, recurrent, or progressive disease. However, the American Joint Committee on Cancer Manual states that there is no reliable examination for adequate lymph node staging. Therefore, our aim is to develop a lymphatic imaging technique using ultrasonography to address this challenge. METHODS: We consecutively enrolled PTC patients who underwent ultrasound (US) lymphatic imaging via the peritumoral injection of contrast media. Identification of the sentinel lymph nodes and the targeted sentinel lymph nodes was separately based on the lymphatic drainage pathway and the enhancement patterns. Every identified targeted node was assigned a score, according to the features on conventional US and enhancement patterns, and was referred for ultrasound-guided fine-needle aspiration. Cytological and histopathologic results represented the statuses of the targeted lymph nodes and overall central lymph nodes, respectively, which were applied to evaluate the diagnostic performance of US lymphatic imaging. RESULTS: In total, 100 PTC patients were included. On the basis of the cytological results, the sensitivity (97.1%, 95% confidence interval [CI]: 84.7-99.9%) of detecting positive targeted nodes by US lymphatic imaging significantly increased by 45.5% at a threshold of 4 or higher (p = 0.0001), without loss of specificity (p = 1.0000). The surgical results showed that the metastatic degree was positively correlated with an increase in the score (τ: 0.671, p < 0.001). CONCLUSION: Ultrasound lymphatic imaging has a high diagnostic performance, and its corresponding scoring system facilitates grading of the nodal burden in the central compartment. KEY POINTS: • Ultrasound neck lymphatic imaging is an effective contrast-enhanced ultrasound (CEUS) technique (applied after the peritumoral injection of contrast media) for identifying sentinel lymph nodes in the central compartment by tracing the imaged afferent lymphatic vessel. • Lack of enhancement or perfusion defects is the typical enhancement pattern for recognizing the involved central lymph nodes. • Ultrasound lymphatic imaging for identification of positive central lymph nodes before surgery may effectively avoid complications associated with the surgical sentinel node procedure.

Inhibition of sphingosine 1-phosphate (S1P) receptor 1/2/3 ameliorates biological dysfunction in rheumatoid arthritis fibroblast-like synoviocyte MH7A cells through Gαi/Gαs rebalancing.

Sphingosine 1-phosphate (S1P) exerts its various physiological and pathological effects by interacting with G protein-coupled receptors. In addition, S1P can induce biological dysfunction in fibroblast-like synoviocytes (FLSs) in the development of rheumatoid arthritis (RA). However, the mechanism underlying this S1P-induced dysfunction remains unclear. An imbalance between Gαi and Gαs can affect the level of cAMP, an important regulator of numerous cell functions. Therefore, we studied the effects of S1P receptor (S1PR) 1-, 2-, and 3-associated Gαi/Gαs imbalance on the biological function of rheumatoid arthritis fibroblast-like synoviocyte (MH7A cells). The results showed that blocking S1PR1/3 and Gαi, and activating Gαs, inhibited the proliferation, migration, invasion, and proinflammatory cytokine release of MH7A cells in a S1P-induced inflammation model, whereas suppressing S1PR2 only affected the invasion and the release of proinflammatory cytokines of these cells. Analysis of the expression of S1PR1/2/3 and Gαi/Gαs further showed that S1PR1/2/3 could regulate the Gαi/Gαs balance. Furthermore, our data suggested that the level of cAMP was also affected. Combined, our results showed that impaired S1PR1/2/3 signalling can affect MH7A cells biological function via Gαi/Gαs-cAMP signalling, which can provide a new idea for the treatment of RA.

Catalytic Asymmetric Addition of Diorganozinc Reagents to Pyrazole-4,5-Diones and Indoline-2,3-Diones.

The catalytic enantioselective diorganozinc additions to cyclic diketones including pyrazolin-4,5-diones and isatins have been developed. In the presence of morpholine-containing chiral amino alcohol ligand, the corresponding chiral cyclic tertiary alcohols were produced in good to excellent yields (up to 97 %) and enantioselectivities (up to 95 % ee). The notable feature of this protocol includes its mild reaction conditions, Lewis acid additives free and broad functional group tolerance.

Anti-Inflammatory Effect of Geniposide on Regulating the Functions of Rheumatoid Arthritis Synovial Fibroblasts via Inhibiting Sphingosine-1-Phosphate Receptors1/3 Coupling Gαi/Gαs Conversion.

The activated Gα protein subunit (Gαs) and the inhibitory Gα protein subunit (Gαi) are involved in the signal transduction of G protein coupled receptors (GPCRs). Moreover, the conversion of Gαi/Gαs can couple with sphingosine-1-phosphate receptors (S1PRs) and have a critical role in rheumatoid arthritis (RA). Through binding to S1PRs, sphingosine-1-phosphate (S1P) leads to activation of the pro-inflammatory signaling in rheumatoid arthritis synovial fibroblasts (RASFs). Geniposide (GE) can alleviate RASFs dysfunctions to against RA. However, its underlying mechanism of action in RA has not been elucidated so far. This study aimed to investigate whether GE could regulate the biological functions of MH7A cells by inhibiting S1PR1/3 coupling Gαi/Gαs conversion. We use RASFs cell line, namely MH7A cells, which were obtained from the patient with RA and considered to be the main effector cells in RA. The cells were stimulated with S1P (5 µmol/L) and then were treated with or without different inhibitors: Gαi inhibitor pertussis toxin (0.1 µg/mL), S1PR1/3 inhibitor VPC 23019 (5 µmol/L), Gαs activator cholera toxin (1 µg/mL) and GE (25, 50, and 100 µmol/L) for 24 h. The results showed that GE may inhibit the abnormal proliferation, migration and invasion by inhibiting the S1P-S1PR1/3 signaling pathway and activating Gαs or inhibiting Gαi protein in MH7A cells. Additionally, GE could inhibit the release of inflammatory factors and suppress the expression of cAMP, which is the key factor of the conversion of Gαi and Gαs. GE could also restore the dynamic balance of Gαi and Gαs by suppressing S1PR1/3 and inhibiting Gαi/Gαs conversion, in a manner, we demonstrated that GE inhibited the activation of Gα downstream ERK protein as well. Taken together, our results indicated that down-regulation of S1PR1/3-Gαi/Gαs conversion may play a critical role in the effects of GE on RA and GE could be an effective therapeutic agent for RA.

Metabolic Interaction between Ammonia and Baicalein.

Ammonia is treated as a primary waste product of cellular metabolism in vivo and can contribute to the alteration of neurotransmission, oxidative stress, and cerebral edema and astrocyte swelling when its concentration in the brain is high. The objective of this study was to determine whether bioactive polyphenol baicalein had the capacity to trap ammonia in vitro and in vivo. Under in vitro conditions, baicalein rapidly reacted with ammonia to generate two monoaminated products and one diaminated product under different reaction times. These three major aminated products were purified from the reaction mixture, and their structures were characterized as 5-NH2-baicalein, 6-NH2-baicalein, and 5,6-di-NH2-baicalein based on the analysis of their HR-MS and 1D- and 2D-NMR data. In mice, both 5-NH2-baicalein and 6-NH2-baicalein were detected in 24 h fecal and urine samples collected from mice treated with baicalein (200 mg/kg) through oral gavage, and 6-NH2-baicalein was also detected in mouse plasma and brain samples collected at 0.5 h after baicalein treatment. Significant amounts of 6-NH2-baicalein were detected in all mouse samples including feces, urine, plasma, and brain. The levels of 6-NH2-baicalein in feces and urine were significantly higher than those of 5-NH2-baicalein. Furthermore, the average level of 6-NH2-baicalein was very close to that of baicalein (3.62 vs 3.77 ng/g) in mouse brain, suggesting it is possible that baicalein has the capacity to be absorbed rapidly into the circulation system and then cross the blood-brain barrier into the brain to detoxify ammonia in the blood and brain. In conclusion, this study confirmed that baicalein, a flavonoid with a vic-trihydroxyl structure on the A-ring, has the potential to detoxify ammonia and treat ammonia-associated chronic diseases.

Synchronous Sampling-Based Direct Current Estimation Method for Self-Sensing Active Magnetic Bearings.

Active magnetic bearings (AMBs) commonly use pulse-width modulation to reduce analogous hardware and manufacturing costs, but they experience sensing process, sensing accuracy and stability problems. To address these issues, a synchronous sampling-based direct current estimation (SS-DCE) method is proposed herein with a bistate switching power amplifier. First-considering the reluctance evolution mechanism of AMBs-a coupling relation mathematical model between rotor displacement and voltage/current is presented to acquire the rotor position from the working coil current alone. Then-assuming that the switching current was an approximately triangular signal-a DCE for the rotor position was established based on the estimation inductance of the charging/discharging phase. Finally-to decrease the phase shift caused by the self-sensing filters and position estimation algorithms-the SS-DCE method was introduced to conduct precise position detection for rotors with high velocities. The simulation and experimental results indicated that the proposed method could improve the sensing accuracy and stability. Compared to other AMB position estimation methods, the simple linearity of the SS-DCE method was greatly improved and could be controlled below 4%. Evaluation using frequency response analysis showed that the SS-DCE method had excellent dynamic accuracy and could perform at a higher phase margin, especially for the uprising/landing transient state. Moreover, there was a phase margin of 158° at the natural frequency of 19.26 HZ, and the peak sensitivity in the 50-250 µm range reached 10.7 dB.

The Effects of Dexmedetomidine in a Rat Model of Sepsis-Induced Lung Injury are Mediated Through the Adenosine Monophosphate-Activated Protein Kinase (AMPK)/Silent Information Regulator 1 (SIRT1) Pathway.

BACKGROUND This study aimed to investigate the effects of dexmedetomidine in a rat model of sepsis-induced lung injury and the role of the adenosine monophosphate-activated protein kinase (AMPK) gene and silent information regulator 1 (SIRT1) gene signaling pathway. MATERIAL AND METHODS Sixty 28-week-old healthy male Sprague-Dawley rats were randomly divided into three groups, the sham group, the model group, and the dexmedetomidine-treated group. The rat model of sepsis-induced lung injury was developed by surgical cecal ligation and puncture. Lung tissues examined histologically in the three study groups. Cell apoptosis was measured using the TUNEL assay, and the expression of inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-1ß (IL-1ß), and IL-10 were measured in rat lung tissue by enzyme-linked immunosorbent assay (ELISA). Apoptosis-associated proteins and AMPK/SIRT1 pathway-associated protein expression levels were detected using Western blot. RESULTS Dexmedetomidine significantly increased the survival rate and reduced the body temperature of rats in the model group with sepsis-induced lung injury, reduced lung injury, significantly reduced apoptosis in lung tissues, and reduced the expression levels of TNF-alpha, and IL-1ß, and increased the levels of IL-10. Dexmedetomidine significantly reduced the expression of caspase-3 in the rat lung tissue (P<0.01), and significantly increased the expression of Bcl-2/Bax and the phosphorylation levels of AMPK, SIRT1, nuclear factor-kappaB (NF-kappaB), and forkhead box class O 3a (FOXO3a). CONCLUSIONS In a rat model of sepsis-induced lung injury, dexmedetomidine reduced lung damage by activating the AMPK/SIRT1 signaling pathway and reduced the expression of inflammatory cytokines and cell apoptosis.

New pectin-induced green fabrication of Ag@AgCl/ZnO nanocomposites for visible-light triggered antibacterial activity.

The pectin (CEP) was used as matrix material to prepare Ag@AgCl/ZnO nanocomposites with a green method for photocatalytic antibacterial activity in visible-light. Briefly, Ag@AgCl plasmonic hybrids were prepared in the CEP macromolecule matrix with size control, which was attributed to the stability of carboxyl and hydroxyl groups on the CEP. Subsequently, an effective and green two-steps approach was explored for the fabrication of CEP-Ag@AgCl/ZnO nanocomposites with resource saving and environment friendly. Interestingly, more Ag+ was converted into metallic Ag in the CEP-Ag@AgCl/ZnO than that in the CEP-Ag@AgCl. This phenomenon was attributed that the reducibility of free hemiacetal hydroxyl groups on CEP was realized with the help of NaOH in the preparation of CEP-ZnO. In addition, the CEP chains were not obviously destroyed except for the change in the crystallinity after the preparation of the CEP-Ag@AgCl/ZnO nanocomposites, indicating that the method was non-destructive. Moreover, the pH triggered release of Zn2+ and low release of Ag+ in CEP-Ag@AgCl/ZnO nanocomposites with excellent photocatalytic antibacterial activity were confirmed in this work. The proposed green process provides a new idea for the large-scale production of antibacterial pectin-based nanocomposites in industry with a low-cost.

Biotransformation of Myricetin: A Novel Metabolic Pathway to Produce Aminated Products in Mice.

SCOPE: In this study, whether amination is a novel metabolic pathway of myricetin, one of the major dietary flavonoids found in fruits, vegetables, and tea, and whether the aminated metabolite of myricetin remains bioactive, are investigated. METHODS AND RESULTS: It is found that myricetin with a vic-trihydroxyl group on the B ring can chemically react with ammonia via the formation of myricetin quinone to generate the aminated product in vitro. As expected, the amination occurs on position 4´ of the B-ring of myricetin. The structure of this new product is confirmed by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry and is named 4´-NH2 -myricetin. Using the synthetic 4´-NH2 -myricetin as a standard, the presence of this compound is searched for in fecal samples collected from myricetin-treated mice using LC-MS, and 4´-NH2 -myricetin is confirmed as the metabolite of myricetin in mice for the first time. Furthermore, two metabolites of myricetin, the mono-methylated myricetin and the microbial-derived metabolite 3,4,5-trihydroxyphenylacetic acid, are confirmed to be aminated in vivo based on LC-MS data analysis. After administration of different doses of myricetin through oral gavage, the amination of myricetin shows a dose-dependent response in feces. A similar trend is observed for the amination of the mono-methylated myricetin, but not for the microbial-derived metabolite 3,4,5-trihydroxyphenylacetic acid. In plasma, the trend of a dose-dependent response for the amination of myricetin and its mono methylated metabolite is observed, and the plasma concentration of the aminated 3,4,5-trihydroxyphenylacetic acid at 200 mg kg-1 dose is significantly higher than those at the 100 and 400 mg kg-1 doses. Interestingly, it is observed that the aminated myricetin retains the anti-inflammatory activity of myricetin. CONCLUSION: This result demonstrates that amination is a novel biotransformation mechanism of myricetin to produce aminated metabolites.

Identifying macrophage enrichment in atherosclerotic plaques by targeting dual-modal US imaging/MRI based on biodegradable Fe-doped hollow silica nanospheres conjugated with anti-CD68 antibody.

Macrophage recruitment has emerged as the crucial force driving the initiation and progression of atherosclerotic lesions. Therefore, the identification of macrophages in plaques is of vital importance for identifying vulnerable plaques, and noninvasive imaging methods are particularly desirable. Some studies have reported that MRI can detect plaque macrophages through targeted nanoparticles, but it is still hard for an US to detect macrophages in atherosclerotic plaque. In this study, anti-CD68 receptor-targeted Fe-doped hollow silica nanoparticles (CD68-Fe-HSNs) were fabricated as a dual-modal US/MRI contrast agent for identifying macrophages of aorta ventralis atherosclerotic plaques in ApoE-/- mice, confirmed by immunofluorescence and bio-TEM. This system possesses biodegradable characteristics even though it is an inorganic mesoporous nanosystem, indicating its potential high biocompatibility for further in vivo research. We expect that these dual-modal US/MRI nanoparticles will play a role in assessing vulnerable plaque in future research studies.