Model-free fast integral terminal sliding-mode control method based on improved fast terminal sliding-mode observer for PMSM with unknown disturbances.

This paper presents a novel model-free fast integral terminal sliding-mode control (MFFITSMC) method based on an improved fast terminal sliding-mode observer (IFTSMO) for permanent magnet synchronous motor (PMSM) drive system, which can effectively eliminate the impact caused by unknown disturbances, such as parameter perturbations and external disturbances. The PMSM mathematical model with unknown disturbances is first established, and the ultra-local model (ULM) of the PMSM speed loop is constructed. Next, the model-free fast integral terminal sliding-mode controller is designed in the speed loop based on the ULM. Then, the IFTSMO is designed to precisely estimate the unknown term of the ULM, and the estimated unknown term is fed back to the MFFITSMC controller to perform compensation for unknown disturbances in real time. Finally, compared with the proportional-integral (PI) control method and the conventional model-free sliding-mode control (MFSMC) method, the results of simulations and experiments demonstrate that the presented MFFITSMC method reduces the dependence on the precise model and achieves the purpose of anti-disturbance control of the PMSM drive system.

Sonocatalytic Optimization of Titanium-Based Therapeutic Nanomedicine.

Recent considerable technological advances in ultrasound-based treatment modality provides a magnificent prospect for scientific communities to conquer the related diseases, which is featured with remarkable tissue penetration, non-invasive and non-thermal characteristics. As one of the critical elements that influences treatment outcomes, titanium (Ti)-based sonosensitizers with distinct physicochemical properties and exceptional sonodynamic efficiency have been applied extensively in the field of nanomedical applications. To date, a myriad of methodologies has been designed to manipulate the sonodynamic performance of titanium-involved nanomedicine and further enhance the productivity of reactive oxygen species for disease treatments. In this comprehensive review, the sonocatalytic optimization of diversified Ti-based nanoplatforms, including defect engineering, plasmon resonance modulation, heterojunction, modulating tumor microenvironment, as well as the development of synergistic therapeutic modalities is mainly focused. The state-of-the-art Ti-based nanoplatforms ranging from preparation process to the extensive medical applications are summarized and highlighted, with the goal of elaborating on future research prospects and providing a perspective on the bench-to-beside translation of these sonocatalytic optimization tactics. Furthermore, to spur further technological advancements in nanomedicine, the difficulties currently faced and the direction of sonocatalytic optimization of Ti-based therapeutic nanomedicine are proposed and outlooked.

Ultrasound-Amplified Enzyodynamic Tumor Therapy by Perovskite Nanoenzyme-Enabled Cell Pyroptosis and Cascade Catalysis.

Overcoming apoptosis resistance to achieve efficient breast cancer treatment remains a challenge. The precise induction of another form of programmed cell death, pyroptosis, is an excellent alternative for treating cancer. Ultrasound (US)-enhanced enzyme dynamic (enzyodynamic) therapy is developed by employing LaFeO3 (LFO) perovskite nanocrystals as a substrate to increase the rate of deleterious reactive oxygen species (ROS) generation for intensive cell pyroptosis. LFO nanocrystals possess quadruple enzyme-mimicking activities, including oxidase-, peroxidase-, glutathione peroxidase-, and catalase-mimicking activities, which undertake the dominant therapeutic task through cascade catalytic reactions, including the reversal of hypoxic microenvironment, depletion of endogenous glutathione, and continuous output of ROS. US exogenous stimulation increases the transition rate of the intermediate complex to Fe (II) and favors incremental ROS production, by which the ROS burst-induced pyroptosis process is accomplished through the ROS-TXNIP-NLRP3-GSDMD pathway. Both in vitro and in vivo antineoplastic outcomes affirm the ascendancy of LFO nanozyme-induced pyroptosis. This work highlights the critical role of US coupled with nanocatalytic reactors in pyroptosis-dominant breast cancer treatment with the apoptosis resistance circumvention feature.

A Randomized, Double-Blind, Parallel Controlled, Single-Dose Phase I Study Comparing the Pharmacokinetics, Safety, and Immunogenicity of the Infliximab Biosimilar CMAB008 and the Reference Product in Healthy Chinese Male Subjects.

This study aimed to evaluate the pharmacokinetics (PK), safety, and immunogenicity of the infliximab biosimilar CMAB008 compared to the reference product (Remicade) in healthy Chinese male subjects to provide the basis for the similarity evaluation of the 2 drugs. In this phase I randomized, double-blind, parallel-controlled, single-dose study, a total of 90 subjects were randomized 1:1 to receive CMAB008 or infliximab reference product with single intravenous injections (5 mg/kg). Blood samples were collected at designed time points for PK and immunogenicity assessment. If the 90%CI of the geometric mean ratio of area under the plasma concentration-time curve from 0 to the time of the last observation, maximum observed plasma concentration, area under the plasma concentration-time curve from 0 to infinity was completely within the range of 80% to 125%, the PK bioequivalence was established. Other PK parameters including time to maximum plasma concentration, half-life time, clearance, apparent volume of distribution, and last measurable concentration time point were also assessed. Adverse events (AEs) were recorded. Serum concentration-time profiles were similar across the 2 groups, and PK parameters were comparable in the 2 groups. The 90%CI of the geometric mean ratio of test to reference was within the predefined bioequivalence range of 80% to 125%. The AEs occurred similarly in 2 groups. One serious AE (rhabdomyolysis, grade 3) occurred in the test group. The total positive rates of antidrug antibody and neutralizing antibodies in the test group (85.7% and 5.6%, respectively) were numerically lower than infliximab reference product group (90.9% and 15%, respectively). The PK profile of the 2 groups is statistically equivalent. The preliminary safety and immunogenicity evaluation of the 2 drugs are comparable.

A phase I study comparing the pharmacokinetics of the biosimilar (RD12014) with liraglutide (Victoza) in healthy Chinese male subjects.

This study aimed to evaluate the pharmacokinetics (PKs), safety, and immunogenicity of the biosimilar (RD12014) compared to reference liraglutide (Victoza) in healthy Chinese male subjects, so as to provide the basis for the similarity evaluation of the two drugs. Eligible subjects were randomized 1:1 to two sequences (RD12014-Victoza or Victoza-RD12014). Subjects received a single 0.6 mg dose of Victoza or RD12014 by abdominal subcutaneous injection during the first period. After a 7-day washout period, subjects received the alternative drug during the second period. Blood samples were collected at predefined timepoints for PKs and immunogenicity assessment. The primary PK end points were maximum plasma concentration (Cmax ) and area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last ). PK bioequivalence was achieved, if the 90% confidence intervals (CIs) of the geometric mean ratio (GMR) of Cmax and AUC0-last were within the range of 80.00-125.00%. Safety was assessed throughout the study. The 90% CIs of the GMR of RD12014 to Victoza for Cmax and AUC0-last were completely within the range of 80.00-125.00%. Thirteen treatment-related adverse events (TRAEs) were reported in 11 subjects (22.4%) in the RD12014 group, compared to 12 TRAEs reported in 12 subjects (24.5%) in the Victoza group. The blood samples of 49 subjects were negative for anti-drug antibody and the neutralizing antibody was not further detected. This study demonstrated PK similarity of RD12014 to Victoza in healthy Chinese male subjects. Safety and immunogenicity profiles were comparable between the two groups.

Diblock Copolymers Containing Titanium-Hybridized Polyhedral Oligomeric Silsesquioxane Used as a Macromolecular Flame Retardant for Epoxy Resin.

In this paper, the 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO)-containing diblock copolymer poly[(p-hydroxybenzaldehyde methacrylate)m-b-(2-((6-oxidodibenzo[c,e][1,2]oxaphosphinin-6-yl)oxy)ethyl methacrylate)n] (abbrev. poly(HAMAm-b-HEPOMAn)) was synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization. When it was continued to react with titanium-hybridized aminopropyl-polyhedral oligomeric silsesquioxane (Ti-POSS) through a Schiff-base reaction, new grafted copolymers poly[(Ti-POSS-HAMA)m-b-HEPOMAn] (abbrev. PolyTi) were obtained. Then, they were used as macromolecular flame retardant to modify epoxy resin materials. The thermal, flame retardant and mechanical properties of the prepared EP/PolyTi composites were tested by TGA, DSC, LOI, UL-94, SEM, Raman, DMA, etc. The migration of phosphorus moiety from epoxy resin composites was analyzed by immersing the composites into ethanol/H2O solution and recording the extraction solution by UV-Vis spectroscopy. The results showed that the added PolyTi enhanced the glass transition temperature, the carbon residue, the graphitization of char, LOI, and mechanical properties of the EP/PolyTi composites when compared to pure cured EP. Furthermore, the phosphorus moieties were more likely to migrate from EP/DOPO composites than that from EP/PolyTi composites. Obviously, compared with small molecular flame retardant modified EP, the macromolecular flame retardant modified EP/PolyTi composites exhibited better thermal stability, flame retardancy, and resistance to migration.

US Contrast Agent Arrival Time Difference Ratio for Benign versus Malignant Subpleural Pulmonary Lesions.

Background US has proven valuable in the diagnosis of subpleural pulmonary lesions (SPLs); however, existing US indicators have limitations. Purpose To propose and validate a revised contrast-enhanced (CE) US indicator for differential diagnosis of benign and malignant SPLs and to compare its performance with existing CE US diagnostic criteria. Materials and Methods This prospective study (Chinese clinical trial registry, ChiCTR1800019828) enrolled patients with SPLs between May 2019 and August 2020. They were divided into a developmental cohort (DC) and a validation cohort (VC). In the DC, the optimal indicator was selected from five CE US indicators. In the VC, the selected indicator was compared with existing CE US diagnostic criteria using the area under the receiver operating characteristic curve (AUC). Pathologic analysis, microbial evidence, and clinical follow-up were used as reference standards for all SPLs. Results A total of 902 participants (DC, 424 participants; VC, 478 participants) with SPLs (mean age, 56 years ± 17; 593 men) were evaluated. The arrival time (AT) difference ratio proved to be the optimal indicator to distinguish benign from malignant SPLs. In the overall (regardless of lesion size), large (vertical diameter >3 cm), and small (vertical diameter ≤3 cm) lesion groups, the cutoff values of the AT difference ratio were 43%, 42%, and 50% and the AUCs obtained from the VC were 0.91 (95% CI: 0.88, 0.93), 0.97 (95% CI: 0.94, 0.98), and 0.77 (95% CI: 0.71, 0.83) respectively, which were higher than those of lesion-lung AT difference greater than 2.5 seconds (0.81 [P < .001], 0.85 [P < .001], and 0.7 [P = .005], respectively), lesion AT greater than 7.5 seconds (0.65 [P < .001], 0.64 [P < .001], and 0.63 [P < .001], respectively), and lesion AT greater than 10 seconds (0.67 [P < .001], 0.68 [P < .001], and 0.64 [P < .001] respectively). Conclusion The US contrast agent arrival time difference ratio enables better differentiation of benign and malignant subpleural lesions when compared with existing diagnostic criteria. Online supplemental material is available for this article. Published under a CC BY 4.0 license.

Tiotropium added to low- to medium-dose inhaled corticosteroids (ICS) versus low- to medium-dose ICS alone for adults with mild to moderate uncontrolled persistent asthma: A systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety profile of tiotropium when added to low- to medium-dose inhaled corticosteroid (ICS) regimen versus low- to medium-dose ICS alone for adults with mild to moderate uncontrolled persistent asthma. DATA SOURCES: The online databases Pubmed, Embase and the Cochrane Library were searched for relevant data published up to November 14, 2017; we also conducted a supplementary search using clinicaltrials.gov. STUDY SELECTIONS: Only randomized control trials were included in this review. RESULTS: Four studies met our inclusion criteria for this review. In our review, two crossover studies were rated as "high risk" in the domain of "other bias" because a washout was not performed between each intervention. Lung function was significantly improved in the patient group receiving low- to medium-dose ICS with tiotropium. Results were consistent between each of three subgroups (tiotropium dry powder inhaler 18 µg or Respimat Soft Mist inhaler 5 µg, Respimat Soft Mist inhaler 2.5 µg, and Respimat Soft Mist inhaler 1.25 µg). Although no significant difference in Asthma Control Questionnaire (ACQ) score was found between the two treatment groups, substantial heterogeneity was observed. The incidence of serious adverse events between the two treatment groups was not statistically significant. CONCLUSIONS: Tiotropium as a once daily add-on to low- to medium-dose ICS may be efficacious and well-tolerated treatment in adults with moderate uncontrolled asthma. However, as only a few studies were identified, more studies of better design and long-term trial duration are required in the future.

N-Bromosuccinimide (NBS)-Catalyzed C-H Bond Functionalization: An Annulation of Alkynes with Electron Withdrawing Group (EWG)-Substituted Acetyl Indoles for the Synthesis of Carbazoles.

An N-bromosuccinimide-catalyzed intermolecular annulation of acetyl indoles with alkynes was developed, allowing for regioselective formation of valuable carbazoles through direct C-H bond functionalization. The readily available catalyst, wide substrate scope, gram scale synthesis, and mild conditions make this method practical. Mechanistic investigations indicate that the bromination of acetyl indole takes place to generate a bromide intermediate, followed by coupling with an alkyne and intramolecular cycloaromatization to furnish carbazole products.

Modeling the water-satisfied degree for production of the main food crops in China.

Water resources are one of the important factors that influence regional crop production and the food security of humans. Most traditional models of crop water demand analysis are built on the basis of a certain crop or macroscopic analysis, which neglect regional crop allocation and the difference of water demand in different crop growing periods. In this paper, a new assessing model, the satisfied degree of crop water requirement, is developed to assess the impacts of water resources on production of six main food crops in China. The six main food crops are spring wheat, winter wheat, corn, early season rice, middle-season rice and late rice. The results show that: (1) there are serious risks of water shortage in China, even in south China with its abundant precipitation; (2) the satisfied degree of crop water demand represents great temporal-spatial changes. On spatial distribution the risks are high in major bases of food production due to influences of cropping system and crop-combinations. Northwest China is a special interesting case. In seasonal fluctuation water shortage is severe in March and September. These risks seriously restrict food production in China. The results also show that the strategic measures of water resources management must be chosen carefully to deal with food security and regional sustainable development in China.

From hypertension to stroke: mechanisms and potential prevention strategies.

Stroke is a major cause of disability and death worldwide. Prevention aimed at risk factors of stroke is the most effective strategy to curb the stroke pandemic. Hypertension is one of the most important risk factors for stroke. Despite the substantial evidence of the benefits of lowering blood pressure, conventional treatment does not normalize the burden of major cardiovascular events in patients with hypertension. Fully understanding the factors involved in the hypertension-induced stroke helps to develop new strategies for stroke prevention. Antihypertensive therapies selected should have positive blood pressure-independent effects on stroke risk. This review summarizes the factors involved in the hypertension-induced stroke, such as oxidative stress, inflammation, and arterial baroreflex dysfunction, and potential strategies for its prevention, therefore, provides clues for clinicians.