Prognostic value of metabolic syndrome in patients with heart failure and malnutrition.

BACKGROUND: Malnutrition is severely associated with worst prognosis of patients with heart failure (HF). Malnourished patients with the metabolic syndrome (MS) can result in a double burden of malnutrition. We aimed to investigate the impact of the MS on clinical outcomes in malnourished HF patients. METHODS: We examined 529 HF patients at risk of malnutrition with a mean age of (66 ± 10) years and 78% (415) were male. Nutritional status defined primarily by the prognostic nutritional index (PNI), with PNI < 40 being defined as malnutrition. The follow-up endpoint was cardiovascular death or all-cause death. RESULTS: During the 36-month follow-up, survival rates for cardiovascular and all-cause death were significantly lower in the MS group than in the non-MS group (log-rank P < 0.01). Multivariate Cox proportional hazards regression models showed that MS was independently associated with cardiovascular death (HR:1.759, 95%CI:1.351-2.291, p < 0.001) and all-cause death (HR:1.326, 95%CI:1.041-1.689, p = 0.022) in malnourished patients with HF. MS significantly increased the predictive value of cardiovascular death (AUC:0.669, 95%CI:0.623-0.715, p < 0.001) and all-cause death (AUC:0.636, 95%CI:0.585-0.687, p < 0.001) on the basis of established risk factors. The predictive effect of MS on cardiovascular death was independent of sex, age, functional class and left ventricular ejection fraction. CONCLUSIONS: In malnourished patients with HF, MS is an independent risk factor for cardiovascular and all-cause mortality. MS significantly enhance the predictive value for clinical events in patients.

Optimization study of a closed-cycle low-temperature evaporation system based on mathematical model and CFD.

Treating high salt and high organic matter wastewater (HHW) generated during rapid socio-economic development is a significant challenge. This study aims to optimize a closed-cycle low-temperature evaporation (CCLE) system using mathematical modelling to be adapted to industrial applications. By using mathematical modelling and computational fluid dynamics (CFD), this study investigated the operating mechanism of the system under different operating conditions. Parametric analysis shows that increasing the compressor evaporation temperature and decreasing the condensation temperature is conducive to improving the performance of the heat pump unit, thereby increasing the wastewater treatment efficiency of the system and that a smaller heat transfer coil windward area is conducive to heat and mass transfer within the humidifier. The unique characteristics of the CCLE system are identified, and the wastewater treatment process under various operating conditions is explained. These findings may provide supporting information for the treatment of HHW by the CCLE system.

Molecular Dynamics Simulation of Lipid Nanoparticles Encapsulating mRNA.

mRNA vaccines have shown great potential in responding to emerging infectious diseases, with their efficacy and stability largely dependent on the delivery vehicles-lipid nanoparticles (LNPs). This study aims to explore the mechanisms by which LNPs encapsulate mRNA, as well as the effects of different N/P ratios and acid types in nucleic acid solutions on the structure and properties of LNPs, using the ethanol solvent injection method as the encapsulation technique. Six systems were designed, based on the composition and proportions of the existing mRNA vaccine mRNA-1273, and molecular dynamics (MD) simulations were employed to investigate the self-assembly process of LNPs. Ethanol was used as a solvent instead of pure water to better mimic experimental conditions. The results indicate that lipid components self-assemble into nanoparticles under neutral conditions, with the ionizable lipid SM-102 predominantly concentrating in the core of the particles. Upon mixing with nucleic acids in acidic conditions, LNPs undergo disassembly, during which protonated SM-102 encapsulates mRNA through electrostatic interactions, forming stable hydrogen bonds. Cluster structure analysis revealed that the four lipid components of LNPs are distributed sequentially from the outside inwards as DMG-PEG 2000, DSPC, cholesterol, and protonated SM-102. Moreover, LNPs constructed under low pH or low N/P ratios using citric acid exhibited larger volumes and more uniform distribution. These findings provide a scientific basis for further designing and optimizing LNP components to enhance the efficacy of mRNA vaccine encapsulation.

Transmembrane serine protease TMPRSS2 implicated in SARS-CoV-2 infection is autoactivated intracellularly and requires N-glycosylation for regulation.

Transmembrane protease serine 2 (TMPRSS2) is a membrane-bound protease expressed in many human epithelial tissues, including the airway and lung. TMPRSS2-mediated cleavage of viral spike protein is a key mechanism in severe acute respiratory syndrome coronavirus 2 activation and host cell entry. To date, the cellular mechanisms that regulate TMPRSS2 activity and cell surface expression are not fully characterized. In this study, we examined two major post-translational events, zymogen activation and N-glycosylation, in human TMPRSS2. In experiments with human embryonic kidney 293, bronchial epithelial 16HBE, and lung alveolar epithelial A549 cells, we found that TMPRSS2 was activated via intracellular autocatalysis and that this process was blocked in the presence of hepatocyte growth factor activator inhibitors 1 and 2. By glycosidase digestion and site-directed mutagenesis, we showed that human TMPRSS2 was N-glycosylated. N-glycosylation at an evolutionarily conserved site in the scavenger receptor cysteine-rich domain was required for calnexin-assisted protein folding in the endoplasmic reticulum and subsequent intracellular trafficking, zymogen activation, and cell surface expression. Moreover, we showed that TMPRSS2 cleaved severe acute respiratory syndrome coronavirus 2 spike protein intracellularly in human embryonic kidney 293 cells. These results provide new insights into the cellular mechanism in regulating TMPRSS2 biosynthesis and function. Our findings should help to understand the role of TMPRSS2 in major respiratory viral diseases.

Spatial position is a key determinant of N-glycan functionality of the scavenger receptor cysteine-rich domain of human hepsin.

The scavenger receptor cysteine-rich (SRCR) domain is a key constituent in diverse proteins. N-glycosylation is important in protein expression and function. In the SRCR domain of different proteins, N-glycosylation sites and functionality vary substantially. In this study, we examined the importance of N-glycosylation site positions in the SRCR domain of hepsin, a type II transmembrane serine protease involved in many pathophysiological processes. We analysed hepsin mutants with alternative N-glycosylation sites in the SRCR and protease domains using three-dimensional modelling, site-directed mutagenesis, HepG2 cell expression, immunostaining, and western blotting. We found that the N-glycan function in the SRCR domain in promoting hepsin expression and activation on the cell surface cannot be replaced by alternatively created N-glycans in the protease domain. Within the SRCR domain, the presence of an N-glycan in a confined surface area was essential for calnexin-assisted protein folding, endoplasmic reticulum (ER) exiting, and zymogen activation of hepsin on the cell surface. Hepsin mutants with alternative N-glycosylation sites on the opposite side of the SRCR domain were trapped by ER chaperones, resulting in the activation of the unfolded protein response in HepG2 cells. These results indicate that the spatial N-glycan positioning in the SRCR domain is a key determinant in the interaction with calnexin and subsequent cell surface expression of hepsin. These findings may help to understand the conservation and functionality of N-glycosylation sites in the SRCR domains of different proteins.

A NEW DOSE DETERMINATION METHOD FOR HP(3) AND DP LENS FOR BETA REFERENCE RADIATION QUALITIES.

For the purpose of obtaining the smaller uncertainties for Hp(3) and Dp lens in 90Sr/90Y beta reference fields, a new dose determination method based on the Monte-Carlo simulation was proposed. The conversion coefficients from the absorbed dose in air, at the reference point of the extrapolation ionisation chamber, Dair, det to Hp(3; α) and the conversion factors from Dair, det to Dp lens(α) were calculated with EGSnrc, respectively, for the irradiation angles from 0° to 60°. Compared with the dose determination method in International Organization for Standardization (ISO) 6980 standard, the uncertainty reductions of 7.7-52.8% for Hp(3; α) and 7.9-55.0% for Dp lens(α) were achieved, respectively. In addition, for the conversion coefficients from the reference absorbed dose DR to Hp(3; α), the calculations were performed for more irradiation conditions, which are not included in the current ISO 6980 standard. For the calculations of the conversion factors from DR to Dp lens(α), the eye and head phantoms with Chinese characteristics were utilised, which makes the conversion factors more suitable for use in China.

Recognition and release of uridine and hCNT3: From multivariate interactions to molecular design.

As a vital target for the development of novel anti-cancer drugs, human concentrative nucleoside transporter 3 (hCNT3) has been widely concerned. Nevertheless, the lack of a comprehensive understanding of molecular interactions and motion mechanism has greatly hindered the development of novel inhibitors against hCNT3. In this paper, molecular recognition of hCNT3 with uridine was investigated with molecular docking, conventional molecular dynamics (CMD) simulations and adaptive steered molecular dynamics (ASMD) simulations; and then, the uridine derivatives with possibly highly inhibitory activity were designed. The result of CMD showed that more water-mediated H-bonds and lower binding free energy both explained higher recognition ability and transported efficiency of hCNT3. While during the ASMD simulation, nucleoside transport process involved the significant side-chain flip of residues F321 and Q142, a typical substrate-induced conformational change. By considering electronegativity, atomic radius, functional group and key H-bonds factors, 25 novel uridine derivatives were constructed. Subsequently, the receptor-ligand binding free energy was predicted by solvated interaction energy (SIE) method to determine the inhibitor c8 with the best potential performance. This work not only revealed molecular recognition and release mechanism of uridine with hCNT3, but also designed a series of uridine derivatives to obtain lead compounds with potential high activity.

Analysis and Study on the Quality of Life of Patients Undergoing Transcatheter Aortic Valve Replacement.

OBJECTIVE: Explore the factors affecting the QO of life after transcatheter aortic valve replacement (TAVR) and analyze and evaluate their surgical efficacy and postoperative survival status. METHODS: Through correlation analysis and multiple regression analysis, we predict various clinical characteristics and postoperative quality and predict clinical changes in L postoperative quality. RESULTS: The quality of life of patients with the disease has gradually improved and improved from 6 months after surgery. The differences in the three aspects of its physiological mechanism function, physiological function function, overall health, and vitality are statistically significant (p < 0.05). CONCLUSION: Compared with traditional open-thoracic aortic valve (AV) surgery, TAVR has the significant advantages of smaller surgical incision and less trauma to the patient, which has become one of the reasons why patients are willing to accept it.

Antibacterial mechanism of Biochanin A and its efficacy for the control of Xanthomonas axonopodis pv. glycines in soybean.

BACKGROUND: Xanthomonas axonopodis pv. glycines (Xag) is a hazardous pathogen able to cause bacterial pustule disease in soybean, reducing crop yield and quality. Although flavonoids rutin and genistein are known to play an important role in soybean defence, soybean is only able to produce Biochanin A in low concentration. RESULTS: In this work, Biochanin A was found to produce higher antibacterial activity against Xag in comparison with genistein (minimum inhibitory concentration < 100 µg/mL). Biochanin A was able to inhibit DNA synthesis and flagella formation in Xag, and altered the composition of the bacterial membrane. These effects reduced swimming motility, extracellular protease activity and biofilm formation. Further, Biochanin A was tested for the control of Xag in soybean leaves, showing similar, or even higher, inhibitory ability in comparison with some products commonly used for the control of this pathogen. CONCLUSIONS: The antibacterial properties of Biochanin A against Xag have been studied for the first time, revealing new insights on the potential applications of this isoflavonoid for the management of bacterial pustule disease. © 2020 Society of Chemical Industry.

Design, implementation, and control of a six-axis compliant stage.

This paper presents the development of a new compact six-axis compliant stage employing piezoelectric actuators to achieve six-axis actuation with nanometer resolution. The integration of direct metrology in the object space, based on real-time visual feedback, enables high-precision motion control. In order to achieve greater motion range, the simple and compact decoupled mechanical structure utilizes two-tap displacement amplifiers for in-plane motion and semibridge amplifiers for out-of-plane motion. The kinematic analysis of the stage is presented. Laterally sampled white light interferometry was implemented to measure the out-of-plane motion of the stage, and a measurement model associated with the designed target patterns is developed to estimate the in-plane motion in real time. Together, they form a visual tracking system and are integrated with the six-axis compliant stage to realize precision six-axis real-time visual servo-control. Experimental results demonstrate that the six-axis compliant stage has the motion range of 77.42 microm, 67.45 microm, 24.56 microm, 0.93 mrad, 0.95 mrad, and 3.10 mrad, and the resolution of +/-5 nm, +/-8 nm, +/-10 nm, +/-10 murad, +/-10 murad, and +/-20 murad for x-axis, y-axis, and z-axis translation and rotation, respectively.

[A comparative study of the clinical effects between two kinds of negative-pressure wound therapy].

OBJECTIVE: To compare the differences of the clinical effects, side effects and treatment-related cost between two kinds of negative-pressure wound therapy (NPWT). METHODS: Forty-four inpatients with acute, subacute, and chronic wounds were divided into simplified NPWT group (A group) and conventional NPWT group (B group) according to the random number table. Wounds of patients in A group were treated with gauze + continuous suction with hospital central negative pressure (-10.64 kPa) for 24 hs; wounds of patients in B group were treated with sponge + interrupted suction with a purpose-designed suction appliance (-16.63 kPa) for 24 hs. Gross wound condition, treatment time, survival rates of skin graft and flap, changes of bacterial species on wound, treatment cost, and ratio of side effects between two groups were compared. RESULTS: There was no significant difference between A and B groups in respect of gross wound condition, treatment time [A group (29 +/- 12) d, B group (26 +/- 13) d, P > 0.05], changes of bacterial species, survival rates of skin graft [A group (98 +/- 4)%, B group (98 +/- 4)%, P > 0.05] and flap (A group 98%, B group 100%, P > 0.05). Treatment cost of A group yen(374 +/- 134) was obviously lower than that of B group yen(9825 +/- 4956) (P < 0. 01), while more side effects were observed in A group (33.3%) than that in B group (5.0%) (P < 0.05). CONCLUSIONS: Both simplified NPWT and NPWT with purpose-designed appliance can effectively improve wound healing. The simplified method may cause many side effects and has a potential risk of inciting nosocomial infection, but it can be conveniently employed with a low cost. In contrast, the cost of using purpose-designed appliance should be cut down to meet the aim of generalization.

[Observation on the therapeutic effects of negative-pressure wound therapy on the treatment of complicated and refractory wounds].

OBJECTIVE: To study the effects of negative-pressure wound therapy (NPWT) on the treatment of complicated and refractory wounds. METHODS: Sixty-seven patients with complicated or refractory wounds admitted to our hospital from September 2005 to November 2008 were randomly divided into NPWT group (n = 35) and conventional treatment (CT) group (n = 32). Wounds of patients in NPWT group were treated with interrupted suction under a pressure of -16.63 kPa for 24 hs, or continuous suction under a pressure of -10.64 kPa for 24 hs. Wounds of patients in CT group were covered with petrolatum gauze overlaid with isotonic saline gauze and dry gauze. Duration of treatment, times of operation, treatment cost, and the process of healing were compared between two groups. RESULTS: The duration of treatment, treatment cost and times of operation of patients in NPWT group were obviously less or fewer than those of CT group (P < 0.05). Wounds of patients in NPWT group were mainly healed by themselves (40.0%) or healed after free skin grafting (40.0%). While wounds in patients in CT group healed mainly after tissue flap transplantation (66.7%) or free skin grafting (23.3%). CONCLUSIONS: Compared with CT, NPWT can shorten the length of hospital stay, reduce operation frequency and treatment cost, and it is easier to carry out in the surgery of treating complicated and refractory wounds, which is worth generalization.