Association of Small Airway Functional Indices With Respiratory Symptoms and Comorbidity in Asthmatics: A National Cross-Sectional Study.

Background: Small airway dysfunction (SAD) and airway inflammation are vital in asthma exacerbations. Type 2 inflammation (T2), mediated by cytokines from T helper 2 cell (Th2) such as interleukin (IL)-4, IL-5, and IL-13, is a potential mechanism underlying SAD. Research on small airway function in asthma is limited. We aimed to explore the correlation between small airway function and respiratory symptoms and comorbidity in T2 and non-T2 asthma. Methods: Derived from the National Health and Nutrition Examination Survey (NHANES), our study encompassed 2,420 asthma patients aged 6 - 79 years, including pulmonary function (PF) data such as forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75), forced expiratory volume in 1 second (FEV1), forced expiratory volume in 3 seconds (FEV3), forced expiratory volume in 6 seconds (FEV6), and forced vital capacity (FVC). To evaluate the small airway function, we calculated z-scores for FEF25-75, FEF25-75/FVC, FEV1/FEV6, and FEV3/FEV6. Logistic regression determined the adjusted odds ratios (aORs) for symptoms and comorbidity. Results: FEF25-75, FEV1/FEV6, and FEV3/FEV6 correlated with asthmatic symptoms. FEF25-75 had the strongest association with wheezing or whistling attacks. An increase of 1 standard deviations (SD) in FEF25-75 reduced recurrent wheezing (aOR: 0.70; 95% confidence intervals (95% CIs): 0.65 - 0.76) and severe attacks (aOR: 0.67; 95% CI: 0.62 - 0.94). These indices were also linked to dry cough and hay fever, particularly FEV3/FEV6 reducing hay fever risk (aOR: 0.70; 95% CI: 0.55 - 0.91) in non-T2 asthma. FEF25-75/FVC related to persistent (aOR: 0.78; 95% CI: 0.72 - 0.84) and severe attacks (aOR: 1.14; 95% CI: 1.08 - 1.22) in non-T2 groups. Lower indices combined with T2 exposure raised severe attack risk. Conclusions: In this nationwide study, small airway function correlated with symptom onset, especially in T2 asthma. Small airway injury differed between T2 and non-T2 asthma. Prospective research is needed to establish reference values.

Transcriptome data-based screening of potential host of genetic transformation for a blue-hued Bougainvillea transgene.

Bougainvillea is a popular ornamental plant. Although Bougainvillea is abundant in germplasm resources, cultivars and flower colors, there is no rare blue colour varieties, due to the absence of delphinidin-based anthocyanins. This study analyzed the Bougainvillea leaf and bract transcriptome to select hosts of genetic transformation that would be suitable for the accumulation of delphinidin. A total of 36 gigabyte (GB) of raw data was obtained by transcriptome sequencing, with 4,058 significantly differentially expressed genes, including 1,854 upregulated and 2,204 downregulated genes. Annotation of these genes was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Through annotation, two CHS genes, one F3H gene, one DFR gene, and one F3'H gene involved in the delphinidin biosynthesis pathway were identified. The expression levels of these genes and total flavonoid content in the bracts of six Bougainvillea varieties were examined through quantitative real-time PCR and spectrophotometry, respectively. Through the comprehensive evaluation based on membership function method, the suitable host order for a blue-hued Bougainvillea transgene is Singapore White>Elizabeth Angus>Ratana Yellow>China Beauty>Orange King>Brilliant Variegata. Thus, Singapore White variety was the most appropriate transgene host for blue-hued Bougainvillea. The results of this study provide a reference for the directed breeding of blue-hued Bougainvillea.

Characterization of a recombinant Aspergillus niger GZUF36 lipase immobilized by ionic liquid modification strategy.

Enzyme immobilized on magnetic nanomaterials is a promising biocatalyst with efficient recovery under applied magnets. In this study, a recombinant extracellular lipase from Aspergillus niger GZUF36 (PEXANL1) expressed in Pichia pastoris GS115 was immobilized on ionic liquid-modified magnetic nano ferric oxide (Fe3O4@SiO2@ILs) via electrostatic and hydrophobic interaction. The morphology, structure, and properties of Fe3O4@SiO2@ILs and immobilized PEXANL1 were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, x-ray diffraction, vibration sample magnetometer, and zeta potential analysis. Under optimized conditions, the immobilization efficiency and activity recovery of immobilized PEXANL1 were 52 ± 2% and 122 ± 2%, respectively. The enzymatic properties of immobilized PEXANL1 were also investigated. The results showed that immobilized PEXANL1 achieved the maximum activity at pH 5.0 and 45 °C, and the lipolytic activity of immobilized PEXANL1 was more than twice that of PEXANL1. Compared to PEXANL1, immobilized PEXANL1 exhibited enhanced tolerance to temperature, metal ions, surfactants, and organic solvents. The operation stability experiments revealed that immobilized PEXANL1 maintained 86 ± 3% of its activity after 6 reaction cycles. The enhanced catalytic performance in enzyme immobilization on Fe3O4@SiO2@ILs made nanobiocatalysts a compelling choice for bio-industrial applications. Furthermore, Fe3O4@SiO2@ILs could also benefit various industrial enzymes and their practical uses. KEY POINTS: • Immobilized PEXANL1 was confirmed by SEM, FT-IR, and XRD. • The specific activity of immobilized PEXANL1 was more than twice that of PEXANL1. • Immobilized PEXANL1 had improved properties with good operational stability.

Clinical feasibility of MRI-based synthetic CT imaging in the diagnosis of lumbar disc herniation: a comparative study.

BACKGROUND: Computed tomography (CT) and magnetic resonance imaging (MRI) are indicated for use in preoperative planning and may complicate diagnosis and place a burden on patients with lumbar disc herniation. PURPOSE: To investigate the diagnostic potential of MRI-based synthetic CT with conventional CT in the diagnosis of lumbar disc herniation. MATERIAL AND METHODS: After obtaining prior institutional review board approval, 19 patients who underwent conventional and synthetic CT imaging were enrolled in this prospective study. Synthetic CT images were generated from the MRI data using U-net. The two sets of images were compared and analyzed qualitatively by two musculoskeletal radiologists. The images were rated on a 4-point scale to determine their subjective quality. The agreement between the conventional and synthetic images for a diagnosis of lumbar disc herniation was determined independently using the kappa statistic. The diagnostic performances of conventional and synthetic CT images were evaluated for sensitivity, specificity, and accuracy, and the consensual results based on T2-weighted imaging were employed as the reference standard. RESULTS: The inter-reader and intra-reader agreement were almost moderate for all evaluated modalities (κ = 0.57-0.79 and 0.47-0.75, respectively). The sensitivity, specificity, and accuracy for detecting lumbar disc herniation were similar for synthetic and conventional CT images (synthetic vs. conventional, reader 1: sensitivity = 91% vs. 81%, specificity = 83% vs. 100%, accuracy = 87% vs. 91%; P < 0.001; reader 2: sensitivity = 84% vs. 81%, specificity = 85% vs. 98%, accuracy = 84% vs. 90%; P < 0.001). CONCLUSION: Synthetic CT images can be used in the diagnostics of lumbar disc herniation.

[Mechanism of astragaloside â £ in regulating autophagy of PC12 cells under oxygen-glucose deprivation by medicating Akt/mTOR/HIF-1α pathway].

This study explored the protective effect of astragaloside Ⅳ(AS-Ⅳ) on oxygen-glucose deprivation(OGD)-induced autophagic injury in PC12 cells and its underlying mechanism. An OGD-induced autophagic injury model in vitro was established in PC12 cells. The cells were divided into a normal group, an OGD group, low-, medium-, and high-dose AS-Ⅳ groups, and a positive drug dexmedetomidine(DEX) group. Cell viability was measured using the MTT assay. Transmission electron microscopy was used to observe autophagosomes and autolysosomes, and the MDC staining method was used to assess the fluorescence intensity of autophagosomes. Western blot was conducted to determine the relative expression levels of functional proteins LC3-Ⅱ/LC3-Ⅰ, Beclin1, p-Akt/Akt, p-mTOR/mTOR, and HIF-1α. Compared with the normal group, the OGD group exhibited a significant decrease in cell viability(P<0.01), an increase in autophagosomes(P<0.01), enhanced fluorescence intensity of autophagosomes(P<0.01), up-regulated Beclin1, LC3-Ⅱ/LC3-Ⅰ, and HIF-1α(P<0.05 or P<0.01), and down-regulated p-Akt/Akt and p-mTOR/mTOR(P<0.05 or P<0.01). Compared with the OGD group, the low-and medium-dose AS-Ⅳ groups and the DEX group showed a significant increase in cell viability(P<0.01), decreased autophagosomes(P<0.01), weakened fluorescence intensity of autophagosomes(P<0.01), down-regulated Beclin1, LC3-Ⅱ/LC3-Ⅰ, and HIF-1α(P<0.05 or P<0.01), and up-regulated p-Akt/Akt and p-mTOR/mTOR(P<0.01). AS-Ⅳ at low and medium doses exerted a protective effect against OGD-induced autophagic injury in PC12 cells by activating the Akt/mTOR pathway, subsequently influencing HIF-1α. The high-dose AS-Ⅳ group did not show a statistically significant difference compared with the OGD group. This study provides a certain target reference for the prevention and treatment of OGD-induced cellular autophagic injury by AS-Ⅳ and accumulates laboratory data for the secondary development of Astragali Radix and AS-Ⅳ.

Morphometric similarity network alterations in COVID-19 survivors correlate with behavioral features and transcriptional signatures.

OBJECTIVES: To explore the differences in the cortical morphometric similarity network (MSN) between COVID-19 survivors and healthy controls, and the correlation between these differences and behavioralfeatures and transcriptional signatures. MATERIALS & METHODS: 39 COVID-19 survivors and 39 age-, sex- and education years-matched healthy controls (HCs) were included. All participants underwent MRI and behavioral assessments (PCL-17, GAD-7, PHQ-9). MSN analysis was used to compute COVID-19 survivors vs. HCs differences across brain regions. Correlation analysis was used to determine the associations between regional MSN differences and behavioral assessments, and determine the spatial similarities between regional MSN differences and risk genes transcriptional activity. RESULTS: COVID-19 survivors exhibited decreased regional MSN in insula, precuneus, transverse temporal, entorhinal, para-hippocampal, rostral middle frontal and supramarginal cortices, and increased regional MSN in pars triangularis, lateral orbitofrontal, superior frontal, superior parietal, postcentral, and inferior temporal cortices. Regional MSN value of lateral orbitofrontal cortex was positively associated with GAD-7 and PHQ-9 scores, and rostral middle frontal was negatively related to PHQ-9 scores. The analysis of spatial similarities showed that seven risk genes (MFGE8, MOB2, NUP62, PMPCA, SDSL, TMEM178B, and ZBTB11) were related to regional MSN values. CONCLUSION: The MSN differences were associated with behavioral and transcriptional signatures, early psychological counseling or intervention may be required to COVID-19 survivors. Our study provided a new insight into understanding the altered coordination of structure in COVID-19 and may offer a new endophenotype to further investigate the brain substrate.

Design, synthesis and evaluation of novel pyrimidinylaminothiophene derivatives as FGFR1 inhibitors against human glioblastoma multiforme.

Vascular endothelial growth factor receptors (VEGFRs) have emerged as the most promising anti-angiogenic therapeutic targets for the treatment of recurrent glioblastomas (GBM). However, anti-VEGF treatments led to the high proportion of non-responder patients or non lasting clinical response and the tumor progression to the greater malignant stage. To overcome these problems, there is an utmost need to develop innovative anti-angiogenic therapies. In this study, we report the development of a series of new FGFR1 inhibitors. Among them, compound 4i was able to potently inhibit FGFR1 kinase activities both in vitro and in vivo. This compound displayed strong anti-angiogenic activity in HUVECs and anti-tumor growth and anti-invasion effects in U-87MG cell line. These results emphasize the importance of FGFR1-mediated signaling pathways in GBM and reveal that pharmacological inhibition of FGFR1 can enhance the anti-tumoral, anti-angiogenic and anti-metastatic efficiency against GBM. These data support targeting of FGFR1 as a novel anti-angiogenic strategy and highlight the potential of compound 4i as a promising anti-angiogenic and anti-metastatic candidate for GBM therapy.

The role of NLRP3 inflammasome-mediated pyroptosis in ischemic stroke and the intervention of traditional Chinese medicine.

Ischemic stroke (IS) is the second leading cause of death and disability in the world. Pyroptosis, a form of programmed cell death initiated by caspases, participates in the occurrence and development of IS. Because it can increase cell membrane permeability, mediate the release of inflammatory factors, and aggravate inflammation, inhibiting this process can significantly reduce the pathological injury of IS. The nucleotide binding oligomerization domain-like receptor family pyrin domain protein 3 (NLRP3) is a multiprotein complex whose activation is the core link of pyroptosis. In recent years, studies have reported that traditional Chinese medicine (TCM) could regulate pyroptosis mediated by NLRP3 inflammasome through multi-channel and multi-target networks and thus exert the effect against IS. This article reviews 107 papers published in recent years in PubMed, Chinese National Knowledge Infrastructure (CNKI), and WanFang Data in recent years. It has found that the activation factors of NLRP3 inflammasome include ROS, mitochondrial dysfunction, K+, Ca2+, lysosome rupture, and trans-Golgi breakdown. TLR4/NF-κB/NLRP3, ROS/TXNIP/NLRP3, AMPK/Nrf2/NLRP3, DRP1/NLRP3, TAK1/JNK/NLRP3 signaling pathways regulate the initiation and assembly of the NLRP3 inflammasome, subsequently induce pyroptosis, affecting the occurrence and development of IS. TCM can affect the above signaling pathways and regulate the pyroptosis mediated by NLRP3 inflammasome, so as to play a protective role against IS, which provides a new entry point for discussing the pathological mechanism of IS and a theoretical basis for developing TCM treasure house.

A novel and green method for recycling of waste feather for down via flash explosion with supercritical carbon dioxide.

Millions of tons of feather are produced worldwide each year and considered as a solid waste owing to technical or cost constraints to provide valuable functional characteristics. In this study, a novel and ecofriendly method to recycle waste feather and obtain a type of explosion down via flash explosion with a supercritical fluid of carbon dioxide (SCF-CO2) was developed for the first time. The effects of flash explosion parameters on the structures and properties of feather were explored by orthogonal experiments. A mechanism involving two-step procedures for the developed SCF-CO2 flash explosion is proposed. The obtained results indicate that reinforcements of flash explosion conditions, particularly the system pressure, were readily conducive to transfer the original feather to a soft down with an improved separation ratio, as well as easily weaken or break hydrogen and disulfide bonds associated in feather macromolecules. Moreover, efficient modifications of the physical characteristics, structures and surface morphologies of the waste feather were obtained by the SCF flash explosion to produce a uniform, slender and fibrous explosion down, as demonstrated by scanning electron microscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction analysis. Further tests on the SCF explosion down treated at 70.0 °C at 15.0 MPa for 30.0 min and at 90.0 °C at 20.0 MPa for 20.0 min showed remarkable enhancements in warmth retention along with comparable thermal degradation nature, as well as enhanced softness, down-proof, and other service properties in comparison to the original feather. The SCF-CO2 flash explosion is a promising approach with environment-friendly characteristics to obtain high efficiency and quality of the explosion down by recycling of waste feather.

Doctors' and Patients' Perceptions of Impacts of Doctors' Communication and Empathy Skills on Doctor-Patient Relationships During COVID-19.

BACKGROUND: During the COVID-19 pandemic, the performance of Chinese doctors may have led to improved doctor-patient relationships (DPRs). However, it is unclear how doctors and patients perceived the impact of doctors' communication and empathy skills on DPRs during the COVID-19 pandemic. OBJECTIVE: To examine the perceptions of doctors and patients on how doctors' communication skills and empathy skills influence DPRs during COVID-19. MAIN MEASURES: Doctors' and patients' perceptions of doctors' communication skills were measured using the Chinese version of the SEGUE Framework. To measure empathy skills and DPRs, the Jefferson Scale of Empathy and Difficult Doctor-Patient Relationship Questionnaire were administered to doctors, and the Consultation and Relational Empathy Measure and Patient-Doctor Relationship Questionnaire were administered to patients. RESULTS: A total of 902 doctors and 1432 patients in China were recruited during the pandemic via online or offline surveys (overall response rate of 69.8%). Both doctors and patients rated doctors' empathy skills as more impactful on DPRs than communication skills. Doctors believed that only their empathy skills influenced DPRs. But patients believed that there was a significant bi-directional relationship between doctors' communication and empathy skills and these two skills interacted to directly and indirectly influence DPRs, and doctors' empathy had a greater mediating effect than their communication. CONCLUSIONS: During COVID-19, there were both similarities and differences between Chinese doctors' and patients' views on how doctors' communication and empathy skills influenced DPRs. The greater effect of doctors' empathy skills suggests that both doctors and patients attach more importance to doctors' empathy in doctor-patient interactions. The bi-directional effect on patient outcomes suggests that both doctors' communication and empathy skills are important to patients' perceptions of DPRs.

Temperature-perturbed two-dimensional generalized correlation characteristic slice spectra combined with multivariate method to identify adulterated milk.

In order to improve the discrimination accuracy of adulterated milk, a detection method was proposed based on temperature-perturbed generalized two-dimensional (2D) correlation characteristic slice spectra. A total of 240 samples were prepared including three brands of 40 pure milk and 40 urea-tainted milk, respectively. The infrared attenuated total reflection spectra of each sample were collected at different temperatures. Synchronous 2D infrared correlation spectrum of each sample was calculated under the external perturbation of temperature. The characteristic slice spectra of each sample were extracted from synchronous 2D correlation spectrum at characteristic peaks of milk and adulterants. N-way partial least squares discriminant analysis (NPLS-DA) models of single brand and the fusion of three brands of adulterated milk were established based on 2D correlation characteristics slice spectra. For comparison, the discrimination models were established using synchronous 2D correlation spectra and one-dimensional (1D) infrared spectra at room temperature, respectively. For the three brand fusion models, the discrimination accuracies of unknown samples were 100%, 98.8% and 82.7% using 2D correlation characteristic slice spectra, 2D correlation spectra, and 1D spectra, respectively. The results showed that the proposed method not only compressed the data, but also effectively extracted the characteristic information, and improved the accuracy of discrimination.

Clinical Effect of Surgical Reconstruction of Extracranial Vertebral Artery / 中国医学科学院学报

Objective To evaluate the effect of surgical reconstruction of extracranial vertebral artery and to summarize the experience. Methods The clinical data of 15 patients undergoing surgical reconstruction of extracranial vertebral artery from September 2018 to June 2022 were collected.The operation methods,operation duration,intraoperative blood loss,operation complications,and relief of symptoms were retrospectively analyzed. Results Eleven patients underwent vertebral artery (V1 segment) to common carotid artery transposition,two patients underwent endarterectomy of V1 segment,two patients underwent V3 segment to external carotid artery bypass or transposition.The operation duration,intraoperative blood loss,and blocking time of common carotid artery varied within 120-340 min,50-300 ml,and 12-25 min,with the medians of 240 min,100 ml,and 16 min,respectively.There was no cardiac accident,cerebral hyperperfusion syndrome,cerebral hemorrhage or lymphatic leakage during the perioperative period.One patient suffered from cerebral infarction and three patients suffered from incomplete Horner's syndrome after the operation.During the follow-up (4-45 months,median of 26 months),there was no anastomotic stenosis,new cerebral infarction or cerebral ischemia. Conclusion Surgical reconstruction of extracranial vertebral artery is safe and effective,and individualized reconstruction strategy should be adopted according to different conditions.

The prevalence of mathematical difficulties among primary school children in Mainland China: a systematic review and meta-analysis.

The prevalence of mathematical difficulties (MD) among primary school children in China and its related factors remain unclear. To provide a suitable foundation for formulating appropriate screening and intervention strategies, this study aimed to estimate the prevalence of MD and its possible factors among primary school children in China. Articles were identified from seven databases and included if they reported on the prevalence of MD among primary school children in China. A total of 30,881 articles were retrieved, 975 of which were subjected to full evaluation. In total, 54 studies involving 34,815 participants (mean age 9.86 ± 3.13 years) were included. Analyses were conducted using the Meta and Metafor packages in the statistical software environment R. We used meta-regression and subgroup analyses by variable type to evaluate the potential prevalence factors. The pooled prevalence of MD among primary school children in China was 8.97%, whereas the prevalence rates of MD in lower, middle, and upper primary schools were 11.57%, 10.07%, and 4.76%, respectively. The results showed that the prevalence of MD among primary school children in China was significantly related to grade level and the cut-off points selected for screening MD and that the prevalence of MD in middle primary school was higher in girls than in boys. The prevalence of MD in primary schools in China was slightly higher than that in countries such as the United Kingdom and the United States. The prevalence of MD was higher in the lower and middle grades of primary school. The grade level and cut-off points selected during MD screening were closely related to the prevalence of MD. More attention should be paid to girls with MD in middle primary school. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023410311, identifier: CRD42023410311.

Association of angiotensin-converting enzyme insertion/deletion (ACE I/D) gene polymorphism with susceptibility to prostate cancer: an updated meta-analysis.

OBJECTIVE: This meta-analysis aims to explore the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and susceptibility to prostate cancer (PCa). METHODS: We searched studies related to ACE I/D polymorphism and susceptibility to PCa through PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases from inception to June 1, 2022. Five gene models, including allelic, dominant, recessive, homozygote, and heterozygote models, were analyzed. The pooled odds ratio (OR) was calculated using Stata 15.0 software. Publication bias was judged by the funnel plot and Egger's test, with the robustness of the findings verified by sensitivity analysis. RESULTS: Eight published articles (including ten studies) were identified. The pooled results showed that ACE I/D locus polymorphism was significantly correlated with the risk of PCa under all gene models except for the heterozygous model (D vs. I: OR= 1.58, 95% CI: 1.14-2.21; DD vs. DI+II: OR=1.68, 95% CI: 1.11-2.54; DD+DI vs. II: OR=1.76, 95% CI: 1.11-2.80; DI vs. II: OR= 1.44, 95% CI: 0.99-2.10; DD vs. II: OR= 2.12, 95% CI: 1.15-3.93). Subgroup analysis based on genotype frequencies in the control group meeting Hardy-Weinberg equilibrium showed statistically significant differences in all gene models. The funnel plot and Egger's test indicated no publication bias. The sensitivity analysis verified the robustness of the conclusions obtained in this meta-analysis. CONCLUSION: ACE I/D locus polymorphism correlates to PCa risk. Allele D, genotype DD+DI, and DD at the ACE I/D locus increase susceptibility to PCa and can therefore serve as a potential diagnostic and screening molecular marker for PCa patients.

Cytotoxic flavonoids from the leaves of Callicarpa nudiflora hook.

A new flavonoid glycoside, luteolin-3'-O-ß-D-6″-acetyl glucopyranoside (1), along with six known flavonoids, were isolated from the leaves of Callicarpa nudiflora Hook. The structures of the isolated compounds were established on the basis of extensive spectroscopic analyses. Compound 6 exhibited potent cytotoxicity and compounds 1 and 7 exhibited moderate cytotoxicity against human hepatocellular carcinoma SMMC-7721 cells.

Therapeutic drug monitoring of caffeine and its primary metabolites in plasma using LC-ESI-MS/MS for apnea of prematurity treatment: Evaluation of ultrapure water as a surrogate matrix.

The growing evidence has endorsed the view that therapeutic drug monitoring of caffeine for apnea of prematurity is helpful for dose tailoring when the therapeutic response is lacking or toxicity is suspected. However, plasma without caffeine is difficult to obtain. Therefore, a method was developed and validated to measure caffeine and its three primary metabolites (paraxanthine, theobromine and theophylline) using LC-ESI-MS/MS in human plasma and several surrogate matrices. The chromatographic separation of analytes was finally achieved on a Waters Symmetry C18 (4.6 × 75 mm, 3.5 µm) column. Several strategies were successfully applied to overcome the matrix effects: (a) appropriate dilution for sample cleanup; (b) a starting lower proportion of organic phase; and (c) multiple individual stable-labeled isotopic internal standards. The parallelism between the authentic matrix and surrogate matrices was convincing. The recovery of the analytes in both human plasma and rat plasma was acceptable over the linear range (0.500-50.0 µg/ml for caffeine and 0.0100-1.00 µg/ml for three metabolites). The method was successfully applied in 118 samples from 74 preterm infants with apnea of prematurity. The rat plasma or ultrapure water as a surrogate matrix is worthy of recommendation for routine therapeutic drug monitoring of caffeine.

Game-Based Backstepping Design for Strict-Feedback Nonlinear Multi-Agent Systems Based on Reinforcement Learning.

In this article, the game-based backstepping control method is proposed for the high-order nonlinear multi-agent system with unknown dynamic and input saturation. Reinforcement learning (RL) is employed to get the saddle point solution of the tracking game between each agent and the reference signal for achieving robust control. Specifically, the approximate optimal solution of the established Hamilton-Jacobi-Isaacs (HJI) equation is obtained by policy iteration for each subsystem, and the single network adaptive critic (SNAC) architecture is used to reduce the computational burden. In addition, based on the separation operation of the error term from the derivative of the value function, we achieve the different proportions of the two agents in the game to realize the regulation of the final equilibrium point. Different from the general use of the neural network for system identification, the unknown nonlinear dynamic term is approximated based on the state difference obtained by the command filter. Furthermore, a sufficient condition is established to guarantee that the whole system and each subsystem included are uniformly ultimately bounded. Finally, simulation results are given to show the effectiveness of the proposed method.

Novel Insights into the Roles and Mechanisms of GLP-1 Receptor Agonists against Aging-Related Diseases.

Aging and aging-related diseases have emerged as increasingly severe health and social problems. Therefore, it is imperative to discover novel and effective therapeutics to delay the aging process and to manage aging-related diseases. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), one of the classes of antihyperglycemic drugs, have been recommended to manage type 2 diabetes mellitus (T2DM). Moreover, GLP-1 RAs have been shown to protect against oxidative stress, cellular senescence and chronic inflammation, which are widely accepted as the major risk factors of aging. However, their significance in aging or aging-related diseases has not been elucidated. Herein, we explain the underlying mechanisms and protective roles of GLP-1 RAs in aging from a molecular, cellular and phenotypic perspective. We provide novel insights into the broad prospect of GLP-1 RAs in preventing and treating aging-related diseases. Additionally, we highlight the gaps for further studies in clinical applications of GLP-1 RAs in aging-related diseases. This review forms a basis for further studies on the relationship between aging-related diseases and GLP-1 RAs.