Incremental prognostic value of 18F-FDG myocardial ischemic memory imaging for major adverse cardiovascular events in patients with suspected unstable angina.

BACKGROUND: The additional prognostic value of 18F-FDG PET myocardial ischemic memory imaging for patients with suspected unstable angina (UA) is not well established. This study aimed to determine whether 18F-FDG PET imaging provides incremental prognostic information for predicting major adverse cardiac events (MACE) compared to clinical risk factors, GRACE score, and coronary artery calcium score (CACS) in suspected UA patients. METHODS: In this post-hoc analysis of a prospective study, 265 suspected UA patients (62.3% male, mean age 65.0±9.4 years) were enrolled. 18F-FDG positive was defined as focal or focal on diffuse uptake patterns. MACE included cardiovascular death, acute myocardial infarction, heart failure, rehospitalization for UA, and stroke. Multivariable Cox regression was used to identify predictors of MACE, and the incremental prognostic value of 18F-FDG PET imaging was assessed using C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: Over a median follow-up of 25 months, 51 patients (19.2%) experienced MACE. 18F-FDG positive (HR=3.220, 95% CI: 1.630-6.360, P<0.001) , as well as 18F-FDG standardized uptake ratio (SUR) (HR=1.330, 95%CI: 1.131-1.564, P=0.0006) and Extent (HR=1.045, 95%CI: 1.028-1.062, P<0.0001), were independent predictors of MACE. The addition of 18F-FDG PET imaging significantly improved risk stratification beyond clinical factors, the GRACE score, and CACS, with improved C-index (0.769 vs 0.688, P=0.045), NRI (0.324, P=0.020), and IDI (0.055, P=0.027). CONCLUSION: 18F-FDG PET myocardial ischemic memory imaging significantly improves prognostic assessment for suspected UA patients, providing valuable additional risk stratification beyond clinical risk factors, GRACE score, and CACS.

In vitro and in vivo activities of scutellarein, a novel polyphosphate kinase 1 inhibitor against Acinetobacter baumannii infection.

BACKGROUND: Inorganic polyphosphate (polyP)-targeted polyphosphate kinase 1 (PPK1) has attracted much attention by virtue of its importance in bacterial pathogenicity and persistence, as well as its exclusive presence in microorganisms. However, only very few drugs have been found to be efficacious in inhibiting the Acinetobacter baumannii (A. baumannii) PPK1 protein. RESULTS: In this study, we identified Scutellarein (Scu), a potent PPK1 inhibitor that could significantly influence PPK1-regulated motility, biofilm formation, and bacterial persistence, which was further validated by the results of transcriptome analysis. Mechanistic explorations revealed that Scu achieved its enzyme inhibitory activity predominantly through direct engagement with the active center of PPK1. Moreover, the survival rate of Galleria mellonella larvae was increased by about 35% with 20 mg/kg of Scu treatment. The remarkable therapeutic benefits of Scu were also observed in the mouse pneumonia model, shown mainly by reduced bacterial colonization, pathological lesions, and inflammatory factors. CONCLUSION: Our results revealed that Scu could attenuate the pathogenicity and persistence of A. baumannii by interfering with its important kinase PPK1.

Ginkgolic Acid as a carbapenem synergist against KPC-2 positive Klebsiella pneumoniae.

The successful evolution of KPC-2 in bacteria has limited the clinical practice of carbapenems. This dilemma deteriorated the prognosis of associated infections and hence attracted increasing attention from researchers to explore alternative therapeutic options. Here, the enzyme inhibition assay was first performed to screen for a potent KPC-2 inhibitor. The synergistic effect of the candidate with carbapenems was further confirmed by checkboard minimum inhibitory concentration (MIC) assay, time-killing assay, disk diffusion method, and live/dead bacteria staining analysis. The mechanisms by which the candidate acts were subsequently explored through molecular dynamics (MD) simulations, etc. Our study found that Ginkgolic Acid (C13:0) (GA) exhibited effective KPC-2 inhibitory activity in both laboratory strain and clinical strain containing KPC-2. It could potentiate the killing effect of carbapenems on KPC-2-positive Klebsiella pnenmoniae (K. pnenmoniae). Further explorations revealed that GA could competitively bind to the active pocket of KPC-2 with meropenem (MEM) via residues Trp104, Gly235, and Leu166. The secondary structure and functional groups of KPC-2 were subsequently altered, which may be the main mechanism by which GA exerted its KPC-2 inhibitory effect. In addition, GA was also found to synergize with MEM to disrupt membrane integrity and increase membrane permeability, which may be another mechanism by which GA reinforced the bactericidal ability of carbapenems. Our study indicated that GA was a significant KPC-2 inhibitor that could prolong the lifespan of carbapenems and improve the prognosis of patients.

Transcriptome and metabolite profiles reveal the role of benzothiadiazole in controlling isoprenoid synthesis and berry ripening in chardonnay grapes.

Benzothiadiazole (BTH) regulates grape development, ripening, volatiles, and phenolics. This study used metabolomics and transcriptomics to understand how exogenous BTH affects Chardonnay grapes' maturation and synthesis of isoprenoids. A 0.37 mM BTH solution was sprayed during the swelling and veraison stages, and then the ripe grapes were analyzed. Our results show that BTH application significantly increased levels of important isoprenoids such as free terpinen-4-ol, bound linalool, and 8'-apo-ß-carotenal. Additionally, BTH was found to modulate several signaling pathways, including those involved in ethylene biosynthesis, salicylic acid synthesis, the abscisic acid pathway, and sugar metabolism, by regulating the expression of genes like VvACO4, VvTAR, VvPLD, VvTIP1-1, VvSTKs, VvPK, VvSUC2, VvGST4, and VvSTS. BTH also promoted grapevine resistance by up-regulating the expression of VvHSP20, VvGOLS4, VvOLP, and VvPR-10. Furthermore, BTH affected isoprenoids biosynthesis by regulating the expression of VvTPS35 and VvMYB24. Moreover, 13 hub genes in the MEgreen module were identified as crucial for the biosynthesis of isoprenoids. BTH application during the swelling stage remarkably promoted isoprenoid biosynthesis more effectively than veraison. Our study provides insights into the molecular mechanisms underlying BTH-induced regulation of grape development and offers a promising approach for enhancing the quality and resistance of grapes.

Impact of awareness of sports policies, school, family, and community environmental on physical activity and fitness among children and adolescents: a structural equation modeling study.

BACKGROUND: Understanding the impact of environmental factors on physical activity (PA) and physical fitness (PF) is crucial for promoting a healthy lifestyle among children and adolescents. This study examines how awareness of sports policies, school, family, and community environments influence PA and PF in Chinese youth. METHODS: A cross-sectional study was conducted with 2747 children and adolescents (mean age 12.90 ± 2.49; 48.2% male) from 17 schools across five Chinese cities. Environmental factors were assessed via questionnaires, and PA levels were measured using the International Physical Activity Questionnaire-Short Form (IPAQ-SF). PF metrics, including BMI, waist-to-height ratio, grip strength, vertical jump, and 20-m shuttle run test (20-mSRT), were measured onsite. Structural Equation Modeling (SEM) was used to explore relationships between environmental factors and PA/PF outcomes. RESULTS: The school environment scored highest (78.0 ± 9.5), while the community environment scored lowest (38.7 ± 18.0). Family environment positively influenced low-intensity PA (LPA) (ß = 0.102, P < 0.001) but negatively affected moderate-to-vigorous PA (MVPA) (ß = -0.055, P = 0.035). Community environment and awareness of sports policies positively impacted MVPA (ß = 0.216, P < 0.001; ß = 0.072, P = 0.009, respectively). Family environment positively influenced BMI reduction (ß = -0.103, P < 0.001) but negatively affected grip strength (ß = -0.063, P = 0.018). Community environment improved grip strength and 20-mSRT performance (ß = 0.088, P = 0.002; ß = 0.065, P = 0.027). CONCLUSIONS: School environments, despite high scores, do not significantly impact PA and PF. Community environments, though scoring lower, positively affect MVPA, grip strength, and 20-mSRT. Awareness of sports policies boosts MVPA, while family environments support LPA and BMI but are inversely related to MVPA and grip strength. Integrated strategies involving community infrastructure, family support, and policy awareness are essential for promoting active lifestyles among children and adolescents.

A FRET/TICT based multifunctional fluorescent probe for the monitoring of SO2 derivatives and viscosity in living cells and real samples.

SO2 derivatives and viscosity are important intracellular indicators, which are closely associated with various physiological metabolisms in organisms. The unregulated contents of SO2 derivatives and viscosity in vivo commonly related to some disorders. In this work, probe JFT was developed relying on FRET and TICT mechanisms for the simultaneous detection of SO2 derivatives and viscosity. JFT can rapidly detect viscosity levels with continuously enhanced fluorescence signals at 582 nm basing on the increasing of viscosity. Moreover, JFT was also sensitive to the changes of SO2 derivatives level with a low detection limit (61.5 nM), rapid responding time (with 16 min), excellent selectivity and anti-interference capacity. JFT could detect bisulfite in real water, wine and food samples with high accuracy and recovery rate. Cell imaging indicated that JFT could monitor the endogenous SO2 derivatives and viscosity in mitochondria. Importantly, JFT could recognize the cancer cells basing on the cell imaging difference of JFT in AGS and GES-1 cells.

Control nucleation for strong and tough crystalline hydrogels with high water content.

Hydrogels, provided that they integrate strength and toughness at desired high content of water, promise in load-bearing tissues such as articular cartilage, ligaments, tendons. Many developed strategies impart hydrogels with some mechanical properties akin to natural tissues, but compromise water content. Herein, a strategy deprotonation-complexation-reprotonation is proposed to prepare polyvinyl alcohol hydrogels with water content as high as ~80% and favorable mechanical properties, including tensile strength of 7.4 MPa, elongation of around 1350%, and fracture toughness of 12.4 kJ m-2. The key to water holding yet improved mechanical properties lies in controllable nucleation for refinement of crystalline morphology. With nearly constant water content, mechanical properties of as-prepared hydrogels are successfully tailored by tuning crystal nuclei density via deprotonation degree and their distribution uniformity via complexation temperature. This work provides a nucleation concept to design robust hydrogels with desired water content, holding implications for practical application in tissue engineering.

Ipilimumab and nivolumab plus radioembolization as salvage therapy for atezolizumab and bevacizumab refractory hepatocellular carcinoma resulting in complete pathologic response.

Unresectable hepatocellular carcinoma unresponsive to first-line immunotherapy has a poor prognosis with modest response to tyrosine kinase inhibitors in the second line. In these patients, the benefit of local therapy with immunotherapy rechallenge is unknown. Radioembolization is a guideline-supported locoregional therapy for HCC that has shown the potential for synergy in combination with immunotherapy. This report describes a patient with veno-invasive HCC and extrahepatic invasion of the right kidney which progressed on atezolizumab and bevacizumab and was subsequently downstaged to resection with ipilimumab and nivolumab plus radioembolization yielding a complete pathologic response. The patient is currently more than 2 years since diagnosis without evidence of disease recurrence.

Efficient generation of singlet oxygen (1O2) by CoP/Ni2P@NF for degradation of sulfamerazine through a heterogeneous electro-Fenton process at circumneutral pH.

In electro-Fenton (EF), the development of a catalytic material with wide pH application range and high interference resistance is more suitable for practical wastewater treatment. In this study, the nanoneedle-shaped CoP/Ni2P heterostructure loaded onto a nickel foam substrate (CoP/Ni2P@NF) was successfully fabricated, which was used as a cathode material for heterogeneous electro-Fenton (Hetero-EF) to degrade sulfamerazine (SMR) at circumneutral pH. The SMR degradation efficiency within 90 min went to 100% and 87% at initial pH of 6.8 and 11, respectively. Experiments and theoretical calculations demonstrated that the heterostructure of CoP/Ni2P redistributed the interfacial charge and accelerated the electron transfer, resulting in different two-electron oxygen reduction (2e-ORR) selectivity and activity than CoP and Ni2P. The ion interference and complex water quality experiment exhibited that the degradation performance remained almost unchanged, showing better anti-interference ability and complex water quality applications. Through quenching experiments and EPR tests, it is confirmed that singlet oxygen (1O2) was the major reactive oxygen species (ROS) and 1O2 was converted from hydroxyl radical (·OH) adsorbed on the catalyst surface. This study provides an efficient catalyst for the application of Hetero-EF to remove organic compounds in complex water at circumneutral pH.

Natural medicine can substitute antibiotics in animal husbandry: protective effects and mechanisms of rosewood essential oil against Salmonella infection.

Aniba rosaeodora essential oil (RO) has been traditionally used in natural medicine as a substitute for antibiotics due to its notable antidepressant and antibacterial properties. Salmonella, a prevalent pathogen in foodborne illnesses, presents a major challenge to current antibiotic treatments. However, the antibacterial efficacy and mechanisms of action of RO against Salmonella spp. remain underexplored. This study aims to elucidate the chemical composition of RO, evaluate its antibacterial activity and mechanisms against Salmonella in vitro, and further delineate its anti-inflammatory mechanisms in vivo during Salmonella infection. Gas chromatography-mass spectrometry (GC-MS) was utilized to characterize the chemical constituents of RO. The antibacterial activity of RO was assessed using minimal inhibitory concentration (MIC) and time-kill assays. Various biochemical assays were employed to uncover the potential bactericidal mechanisms. Additionally, mouse and chick models of Salmonella infection were established to investigate the prophylactic effects of RO treatment. RO exhibited significant antibacterial activity against both Gram-positive and Gram-negative bacteria, with an MIC of 4 mg·mL-1 for Salmonella spp. RO treatment resulted in bacterial damage through the disruption of lipid and purine metabolism. Moreover, RO reduced injury and microbial colonization in infected mice and chicks. RO treatment also modulated the host inflammatory response by inhibiting proinflammatory pathways. In conclusion, our findings demonstrate that RO is effective against Salmonella infection, highlighting its potential as an alternative to antibiotics for antibacterial therapy.

Supported Cu3 cluster on N-doped graphene: An efficient triatom catalyst for CO electroreduction to propanol at low potential.

Electroreduction of carbon monoxide into high-energy fuel is an excellent energy strategy for sustainable development, but the high yield of multi-carbon products remains a difficult challenge. Inspired by the successful synthesis of various trimer metal clusters and studies on electrocatalysis of CO to C3 products by Cu-based catalysts, Cu3 supported on N-doped graphene structures (Cu3@NG) are investigated as electrocatalysts for CORR toward propanol in this paper. Due to the appropriate Cu-Cu bond length, the moderate charge of the Cu site, mild CO adsorption energy, and 100 % CO coverage, the absorbed 3*CO substance can form the critical *CO-CO-CO intermediate with a rather low kinetic barrier of 0.25 eV. The limiting potential of the whole process for the formation of propanol is just -0.15 V. Our work not only showed that Cu3@NG is an excellent catalyst for the formation of propanol with high selectivity at low potential but also indicated that the *CO coverage can greatly reduce the CO hydrogenation potential and bonding of some intermediates such as *CH2O. This research will provide a new idea for the material design of products tending to multi-carbon.

Polymeric PD1/PDL1 bispecific antibody enhances immune checkpoint blockade therapy.

Immune checkpoint blockade (ICB) therapy, particularly PD1/PDL1 inhibition, has demonstrated success in bolstering durable responses in patients. However, the response rate remains below 30 %. In this study, we developed a polymeric bispecific antibody (BsAb) targeting PD1/PDL1 to enhance ICB therapy. Specifically, poly(L-glutamic acid) (PGLU) was conjugated with a double cyclic Fc binding peptide, Fc-III-4C, through condensation reactions between the -COOH group of PGLU and the -NH2 group of Fc-III-4C. This conjugate was then mixed with αPD1 and αPDL1 monoclonal antibodies (mAbs) in an aqueous solution. Mechanistically, the PD1/PDL1 BsAb (BsAbαPD1+αPDL1) acts as a bridge between tumor cells and CD8+ T cells, continuously activating CD8+ T cells to a greater extent. This leads to significantly suppressed tumor growth and prolonged survival in a mouse model of colon cancer compared to treatment with either a single mAb or a mixture of free mAbs. The tumor suppression rate achieved by the BsAbαPD1+αPDL1 was 90.1 %, with a corresponding survival rate of 83.3 % after 48 days. Thus, this study underscores the effectiveness of the BsAbαPD1+αPDL1 as a synchronizing T cell engager and dual ICBs, offering theoretical guidance for clinical ICB therapy.

Development and validation of a nomogram for predicting advanced liver fibrosis in patients with chronic hepatitis B.

Background: The progression of chronic hepatitis B (CHB) to liver fibrosis and even cirrhosis is often unknown to patients, but noninvasive markers capable of effectively identifying advanced liver fibrosis remains absent. Objective: Based on the results of liver biopsy, we aimed to construct a new nomogram to validate the stage of liver fibrosis in CHB patients by the basic information of CHB patients and routine laboratory tests. Methods: Patients with CHB diagnosed for the first time in the First Affiliated Hospital of Anhui Medical University from 2010 to 2018 were selected, and their basic information, laboratory tests and liver biopsy information were collected. Eventually, 974 patients were enrolled in the study, while all patients were randomized into a training cohort (n = 732) and an internal validation cohort (n = 242) according to a 3:1 ratio. In the training cohort, least absolute shrinkage and selection operator (Lasso) regression were used for predictor variable screening, and binary logistic regression analysis was used to build the diagnostic model, which was ultimately presented as a nomogram. The predictive accuracy of the nomograms was analyzed by running operating characteristic curve (ROC) to calculate area under curve (AUC), and the calibration was evaluated. Decision curve analysis (DCA) was used to determine patient benefit. In addition, we validated the built models with internal as well as external cohort (n = 771), respectively. Results: Ultimately, the training cohort, the internal validation cohort, and the external validation cohort contained sample sizes of 188, 53, and 149, respectively, for advanced liver fibrosis. Gender, albumin (Alb), globulin (Glb), platelets (PLT), alkaline phosphatase (AKP), glutamyl transpeptidase (GGT), and prothrombin time (PT) were screened as independent predictors. Compared with the aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), and King's score, the model in the training cohort (AUC = 0.834, 95% CI 0.800-0.868, p < 0.05) and internal validation cohort (AUC = 0.804, 95% CI 0.742-0.866, p < 0.05) showed the best discrimination and the best predictive performance. In addition, DCA showed that the clinical benefit of the nomogram was superior to the APRI, FIB-4 and King's scores in all cohorts. Conclusion: This study constructed a validated nomogram model with predictors screened from clinical variables which could be easily used for the diagnosis of advanced liver fibrosis in CHB patients.

Effect of nicotine mouth spray on urges to vape: A randomized, placebo-controlled, pharmacodynamic clinical trial in exclusive e-cigarette users.

AIMS: To determine whether nicotine mouth spray provides rapid and prolonged relief of urges to vape and measure the steady-state plasma nicotine levels during vaping and ad libitum mouth spray usage in e-cigarette users. DESIGN: Randomized, parallel group, double-blind trial. SETTING: Single site at Hammersmith Medicines Research Ltd (HMR), London, UK. PARTICIPANTS: 216 (25.9% females, average age 27.6 ± 7.63 [standard deviation, SD]) exclusive vapers who used their e-cigarette within 30 minutes of waking up and had vaped about 2 years on average. INTERVENTIONS: Two sprays of 1 mg nicotine mouth spray (Nicorette QuickMist Freshmint, n = 109), or placebo (identical in appearance and presentation, n = 107). MEASUREMENTS: Urge to vape was rated on a 100 mm visual analogue scale before and repeatedly for 2 hours after administration. The primary outcome measured average change from baseline in urges to vape ratings during the first hour. FINDINGS: Nicotine mouth spray achieved statistically significantly greater reductions in urges to vape than placebo from the first assessment point at 30 seconds to 1 hour, when the estimated mean treatment difference was 11.90 mm (95% confidence interval [CI] = 6.86-16.95, P < 0.001). The integrated urge to vape over 11 hours ad libitum usage showed a statistically significant benefit compared with placebo (2.00 [0.88 SD] vs 2.51 [0.84 SD], P < 0.001). Mean steady-state plasma nicotine concentrations were lower after nicotine mouth spray usage compared with vaping (6.22 [4.70 SD] ng/ml vs 9.91 [7.59 SD] ng/ml, respectively). Adverse events were more commonly reported in the nicotine mouth spray group and were mostly mild. CONCLUSIONS: Among regular e-cigarette users, nicotine mouth spray provided statistically significant and fast relief of urges to vape one hour after dosing. Nicotine mouth spray showed statistically significant reductions in urges to vape as soon as 30 seconds and up to 2 hours after dosing compared with placebo, and nicotine mouth spray was well-tolerated and safe.

Comparative study of machine-and deep-learning based classification algorithms for biomedical Raman spectroscopy (RS): case study of RS based pathogenic microbe identification.

One key aspect pushing the frontiers of biomedical RS is dedicated machine- or deep- learning (ML or DL) algorithms. Yet, systematic comparative study between ML and DL algorithms has not been conducted for biomedical RS, largely due to the limited availability of open-source and large Raman spectra dataset. Therefore we compared typical ML partial least square-discriminant analysis (PLS-DA) and DL one dimensional convolution neural network (1D-CNN) based pathogenic microbe identification on 12,000 Raman spectra from six species of microbe (i.e., K. aerogenes (Klebsiella aerogenes), C. albicans (Candida albicans), C. glabrata (Candida glabrata), Group A Strep. (Group A Streptococcus), E. coli1 (Escherichia coli1), E. coli2 (Escherichia coli2)) when 100%, 75%, 50% and 25% of the 12,000 Raman spectra were retained. The total Raman dataset was analyzed with 80% split for training and 20% for testing. The 100% retained testing dataset accuracy, area under curve (AUC) of the receiver operating characteristic (ROC) curve were 95.25% and 0.997 for 1D-CNN, which are higher than those (89.42% and 0.979) of PLS-DA. Yet, PLS-DA outperforms 1D-CNN for 75%, 50% and 25% retained testing dataset. The resultant accuracies and AUCs demonstrated the performance reliance of PLS-DA and 1D-CNN on Raman spectra number. Besides, both loadings on the latent variables of PLS-DA and the saliency maps of 1D-CNN largely captured Raman peaks arising from DNA and proteins with comparable interpretability. The results of the current work indicated that both ML and DL algorithms should be explored for application-wise Raman spectra identification to select whichever with higher accuracies and AUCs.

Anoectochilus roxburghii Extract Extends the Lifespan of Caenorhabditis elegans through Activating the daf-16/FoxO Pathway.

As a significant global issue, aging is prompting people's interest in the potential anti-aging properties of Anoectochilus roxburghii (A. roxburghii), a plant traditionally utilized in various Asian countries for its purported benefits in treating diabetes and combating aging. However, the specific anti-aging components and mechanisms of A. roxburghii remain unclear. This study aims to investigate the anti-aging effects and mechanisms of A. roxburghii extract E (ARE). Caenorhabditis elegans (C. elegans) were exposed to media containing different concentrations of ARE whose superior in vitro radical scavenging capacity was thus identified. Lifespan assays, stress resistance tests, and RT-qPCR analyses were conducted to evaluate anti-aging efficacy, reactive oxygen species (ROS) levels, antioxidant enzyme activity, and daf-16, sod-3, and gst-4 levels. Additionally, transcriptomic and metabolomic analyses were performed to elucidate the potential anti-aging mechanisms of ARE. Fluorescence protein assays and gene knockout experiments were employed to validate the impacts of ARE on anti-aging mechanisms. Our results revealed that ARE not only prolonged the lifespan of C. elegans but also mitigated ROS and lipofuscin accumulation, and boosted resistance to UV and heat stress. Furthermore, ARE modulated the expression of pivotal anti-aging genes including daf-16, sod-3, and gst-4, facilitating the nuclear translocation of DAF-16. Significantly, ARE failed to extend the lifespan of daf-16-deficient C. elegans (CF1038), indicating its dependency on the daf-16/FoxO signaling pathway. These results underscored the effectiveness of ARE as a natural agent for enhancing longevity and stress resilience to C. elegans, potentially to human.

Better efficacy of sequential combination with balloon pulmonary angioplasty after long-term riociguat for patients with inoperable chronic thromboembolic pulmonary hypertension.

The present study aimed to evaluate the efficacy of long-term riociguat sequentially combined with balloon pulmonary angioplasty (BPA) for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Eight inoperable CTEPH patients were enrolled in this study, who have been administrated riociguat 2.5 mg three times daily for about 8 years, then underwent several sessions of BPA procedures. Data are prospectively collected to evaluate clinical outcomes, hemodynamics, exercise capacity, and right heart size and function by echocardiography at baseline, 8 years after riociguat, and 3 months after the final BPA. Eight patients (mean age 54.9 ± 11.4 years) were treated with riociguat 2.5 mg three times daily for 95.0 ± 10.7 months. Cardiac index (CI) (1.5 ± 0.5 L/min/m2 to 2.4 ± 0.6 L/min/m2, p = 0.005), 6 min walking distance (6MWD) (329.6 ± 87.5 m to 418.1 ± 75.8 m, p = 0.016), and pulmonary vascular resistance (PVR) (1336.9 ± 320.2 dyn·s·cm-5 to 815.4 ± 195.6 dyn·s·cm-5, p = 0.008) were significant improvement after riociguat treatment. Mean 4.1 ± 1.6 additional combinational BPA sessions and mean 18.8 ± 8.1 balloon dilations were performed. Mean pulmonary artery pressure (54.1 ± 11.1 mmHg to 33.6 ± 7.7 mmHg, p = 0.002) and PVR (815.4 ± 195.6 dyn·s·cm-5 to 428.3 ± 151.2 dyn·s·cm-5, p＜0.001) were further decreased. CI (2.4 ± 0.6 L/min/m2 to 2.7 ± 0.7 L/min/m2, p = 0.028) and 6MWD (418.1 ± 75.8 m to 455.7 ± 100.0 m, p = 0.038) were increased significantly. After long-term riociguat treatment, sequential combination with BPA delivered considerably incremental benefits on exercise capacity and pulmonary hemodynamics, as well as right heart size and function of technically inoperable CTEPH patients.

Inhibitive Mechanism of Loquat Flower Isolate on Tyrosinase Activity and Melanin Synthesis in Mouse Melanoma B16 Cells.

Melanin naturally exists in organisms and is synthetized by tyrosinase (TYR); however, its over-production may lead to aberrant pigmentation and skin conditions. Loquat (Eriobotrya japonica (Thunb.) Lindl.) flowers contain a variety of bioactive compounds, while studies on their suppressive capabilities against melanin synthesis are limited. Loquat flower isolate product (LFP) was obtained by ethanol extraction and resin purification, and its inhibitory efficiency against TYR activity was investigated by enzyme kinetics and multiple spectroscopy analyses. In addition, the impact of LFP on melanin synthesis-related proteins' expression in mouse melanoma B16 cells was analyzed using Western blotting. HPLC-MS/MS analysis indicated that LFP was composed of 137 compounds, of which 12 compounds, including flavonoids (quercetin, isorhamnoin, p-coumaric acid, etc.) and cinnamic acid and its derivatives, as well as benzene and its derivatives, might have TYR inhibitory activities. LFP inhibited TYR activity in a concentration-dependent manner with its IC50 value being 2.8 mg/mL. The inhibition was an anti-competitive one through altering the enzyme's conformation rather than chelating copper ions at the active center. LFP reduced the expression of TYR, tyrosinase-related protein (TRP) 1, and TRP2 in melanoma B16 cells, hence inhibiting the synthesis of melanin. The research suggested that LFP had the potential to reduce the risks of hyperpigmentation caused by tyrosinase and provided a foundation for the utilization of loquat flower as a natural resource in the development of beauty and aging-related functional products.

The Value of Drawing Practice in Plastic Surgery Training.

ABSTRACT: No specialty has such close relationship with art as plastic surgery among medicine. Both are intensely creative processes that combine technology with utmost dexterity and now are undervalued in the medical education. Art is a reservoir that provides a surgeon with creativity and improved dexterity. It is beneficial for the surgeons to practice drawing, for it can bring passion and inspiration, enhance observation and imagination, improve dexterity and accuracy, and help keep a good relation with patients. In some way, plastic surgery is art and plastic surgeon is artist.