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Cancer immunotherapy, with an aim to enhance host immune responses, has been recognized as a promising therapeutic treatment for cancer. A diversity of immunomodulatory agents, including tumor-associated antigens, adjuvants, cytokines and immunomodulators, has been explored for their ability to induce a cascading adaptive immune response. Nanoscale metal-organic frameworks (nMOFs), a class of crystalline-shaped nanomaterials formed by the self-assembly of organic ligands and metal nodes, are attractive for cancer immunotherapy because they feature tunable pore size, high surface area and loading capacity, and intrinsic biodegradability. In this review we summarize recent progress in the development of nMOFs for cancer immunotherapy, including cancer vaccine delivery and combination of in situ vaccination with immunomodulators to reverse immune suppression. Current challenges and future perspectives for rational design of nMOF-based cancer immunotherapy are also discussed.

Background Conventional approach to myocardial strain analysis relies on a software designed for the left ventricle (LV) which is complex and time-consuming and is not specific for right ventricular (RV) and left atrial (LA) assessment. This study compared this conventional manual approach to strain evaluation with a novel semi-automatic analysis of myocardial strain, which is also chamber-specific. Methods Two experienced observers used the AutoStrain software and manual QLab analysis to measure the LV, RV and LA strains in 152 healthy volunteers. Fifty cases were randomly selected for timing evaluation. Results No significant differences in LV global longitudinal strain (LVGLS) were observed between the two methods (-21.0% ± 2.5% vs. -20.8% ± 2.4%, p  = 0.230). Conversely, RV longitudinal free wall strain (RVFWS) and LA longitudinal strain during the reservoir phase (LASr) measured by the semi-automatic software differed from the manual analysis (RVFWS: -26.4% ± 4.8% vs. -31.3% ± 5.8%, p <  0.001; LAS: 48.0% ± 10.0% vs. 37.6% ± 9.9%, p <  0.001). Bland–Altman analysis showed a mean error of 0.1%, 4.9%, and 10.5% for LVGLS, RVFWS, and LASr, respectively, with limits of agreement of -2.9,2.6%, -8.1,17.9%, and -12.3,33.3%, respectively. The semi-automatic method had a significantly shorter strain analysis time compared with the manual method. Conclusions The novel semi-automatic strain analysis has the potential to improve efficiency in measurement of longitudinal myocardial strain. It shows good agreement with manual analysis for LV strain measurement. Graphical Abstract

Compared with individuals with hearing loss, tinnitus patients without hearing loss have more psychological or emotional problems. Tinnitus is closely associated to abnormal metabolism and function of the limbic system, a key brain region for emotion experience, but the underlying molecular mechanism remains unknown. Using whole‐brain microvasculature dynamics imaging, the anterior cingulate cortex (ACC) is identified as a key brain region of limbic system involve in the onset of salicylate‐induced tinnitus in mice. In the tinnitus group, there is enhanced purine metabolism, oxidative phosphorylation, and a distinct pattern of phosphorylation in glutamatergic synaptic pathway according to the metabolome profiles, quantitative proteomic, and phosphoproteomic data of mice ACC tissue. Electroencephalogram in tinnitus patients with normal hearing thresholds show that the functional connectivity between pregenual anterior cingulate cortex and the primary auditory cortex is significantly increased for high‐gamma frequency band, which is positively correlated with the serum glutamate level. These findings indicate that ACC plays an important role in the pathophysiology of tinnitus by interacting with the primary auditory cortex and provide potential molecular targets in the ACC for tinnitus treatment. Anterior cingulate cortex (ACC) is a brain region of limbic system. There is enhanced metabolism and a distinct pattern of phosphorylation in glutamatergic synaptic pathway in ACC tissue of tinnitus mice. Electroencephalogram in tinnitus patients show increased functional connectivity between ACC and the primary auditory cortex. These findings indicate that ACC involves in the pathophysiology of tinnitus by interacting with the primary auditory cortex.

Basic fibroblast growth factor (bFGF) is a multifunctional factor in acceleration of cell proliferation, differentiation and transference, and therefore widely used in clinical applications. In this study, expression vector pWX-Nt03 harboring a codon-optimized bFGF gene was constructed and introduced into the tobacco chloroplasts by particle bombardment. After four rounds of selection, bFGF was proved to integrate into the chloroplast genome of regenerated plants and two of four transgenic plants were confirmed to be homoplastomic by PCR and Southern hybridization. ELISA assay indicated that bFGF represented approximately 0.1% of total soluble protein in the leaves of transplastomic tobacco plants. This is the first report of bFGF expression via chloroplast transformation in model plant, providing an additional option for the production of chloroplast-produced therapeutic proteins.

The irregular wave disturbance attenuation problem for jacket-type offshore platforms involving the nonlinear characteristics is studied. The main contribution is that a digital-control-based approximation of optimal wave disturbances attenuation controller (AOWDAC) is proposed based on iteration control theory, which consists of a feedback item of offshore state, a feedforward item of wave force and a nonlinear compensated component with iterative sequences. More specifically, by discussing the discrete model of nonlinear offshore platform subject to wave forces generated from the Joint North Sea Wave Project (JONSWAP) wave spectrum and linearized wave theory, the original wave disturbances attenuation problem is formulated as the nonlinear two-point-boundary-value (TPBV) problem. By introducing two vector sequences of system states and nonlinear compensated item, the solution of introduced nonlinear TPBV problem is obtained. Then, a numerical algorithm is designed to realize the feasibility of AOWDAC based on the deviation of performance index between the adjacent iteration processes. Finally, applied the proposed AOWDAC to a jacket-type offshore platform in Bohai Bay, the vibration amplitudes of the displacement and the velocity, and the required energy consumption can be reduced significantly.

The road disturbance rejection problem for vehicle active suspension involving the nonlinear characteristics is researched in this paper. A continuous-time state space of nonlinear vehicle active suspension is established first, in which the road disturbance is generated from the output of an introduced exosystem based on the ground displacement power spectral density. After that, based on the dynamics of road roughness and the internal model principle, a disturbance compensator with zero steady-state error is designed, which is related to the dynamic characteristics of road disturbance and independent of the control system model. By combining the vehicle active suspension system and the designed road disturbance compensator, an augmented system is obtained without explicit indication of road disturbance. Then by solving a series of decoupled nonlinear two-point-boundary-value problem and employing an iterative computing algorithm, an approximation optimal road disturbance rejection controller is obtained. Finally, the simulation results illustrate that the proposed approximation optimal road disturbance rejection controller can reduce the values of sprung mass acceleration, tire deflection, suspension deflection, and energy consumption and compensate the nonlinear behaviors of vehicle active suspension effectively.

Chymosin (also known as rennin) plays an essential role in the coagulation of milk in the cheese industry. Chymosin is traditionally extracted from the rumen of calves and is of high cost. Here, we present an alternative method to producing bovine chymosin from transgenic tobacco plants. The CYM gene, which encodes a preprochymosin from bovine, was introduced into the tobacco nuclear genome under control of the viral 35S cauliflower mosaic promoter. The integration and transcription of the foreign gene were confirmed with Southern blotting and reverse transcription PCR (RT-PCR) analyses, respectively. Immunoblotting analyses were performed to demonstrate expression of chymosin, and the expression level was quantified by enzyme-linked immunosorbent assay (ELISA). The results indicated recombinant bovine chymosin was successfully expressed at an average level of 83.5 ng/g fresh weight, which is 0.52% of the total soluble protein. The tobacco-derived chymosin exhibited similar native milk coagulation bioactivity as the commercial product extracted from bovine rumen.

In this paper, a disturbance attenuation controller is presented for networked vehicle active suspension with measurement noise and random control delay. By defining the appearing probabilities of control delay as the membership function, the Takagi–Sugeno ( T – S ) fuzzy model of networked vehicle active suspension is established with the consideration of the persistent irregular road disturbance, the random actuator delay, and the measurement noise. By designing a transformation vector, the disturbance attenuation control problem is reformulated as an equivalence two-point-boundary-value problem under the constrains of a delay-free system with respect to an equivalence performance index. After that, an optimal disturbance attenuation controller is proposed by solving a Riccati equation and a Stein equation, in which a Kalman filter is employed to estimate the road disturbance state with Gaussian white noise. Finally, by employing a simple vehicle active suspension, simulation results show that the designed controller can attenuate the vibration and compensate the control delay for the networked T – S fuzzy vehicle active suspension, in which the values of the sprung mass acceleration, the suspension deflection and the tyre deflection can be reduced effectively.

This paper focuses on the fuzzy guaranteed cost H ∞ control problem for uncertain nonlinear vehicle active suspension system with random actuator time delay. Its main contribution to the literature is that a fuzzy guaranteed cost H ∞ controller (FGCHC) is proposed to ensure the resulting closed-loop vehicle active suspension system to be asymptotically stable and guarantee the performance index to be less than a preset upper bound. More specifically, taking the varying masses and the uncertainties caused by random actuator delay into consideration, a discrete-time Takagi-Sugeno fuzzy model for vehicle active suspension is obtained based on an augmented vector, which is without explicit of random actuator delay. By employing the Lyapunov stability theory and the linear matrix inequality (LMI) approach, the existence condition and the design approach for proposed FGCHC are presented. Meanwhile, the computability for proposed FGCHC is guaranteed by solving a corresponding convex optimization problem. By analyzing performance requirements for vehicle active suspension under different simulation scenarios, simulation results demonstrate that the proposed FGCHC can offset the vibration and compensate the varying masses and uncertainties for vehicle active suspension effectively.

Rice blast is a major destructive fungal disease that poses a serious threat to rice production and the improvement of blast resistance is critical to rice breeding. The antimicrobial peptide MSI-99 has been suggested as an antimicrobial peptide conferring resistance to bacterial and fungal diseases. Here, a vector harboring the MSI-99 gene was constructed and introduced into the tobacco chloroplast genome via particle bombardment. Transformed plants were obtained and verified to be homoplastomic by PCR and Southern hybridization. In planta assays demonstrated that the transgenic tobacco plants displayed an enhanced resistance to the fungal disease. The evaluation of the antimicrobial activity revealed that the crude protein extracts from the transgenic plants manifested an antimicrobial activity against E. coli, even after incubation at 120 °C for 20 min, indicating significant heat stability of MSI-99. More importantly, the MSI-99-containing protein extracts were firstly proved in vitro and in vivo to display significant suppressive effects on two rice blast isolates. These findings provide a strong basis for the development of new biopesticides to combat rice blast.