Switching and non-switching dead-beat sliding mode control with monotonic convergence.

Performance requirements necessitate control designs that assure not only transient response specifications but also steady-state accuracy. Monotonic convergence of the tracking error is crucial for an efficient control design to prevent the performance degradation caused by overshooting. This needs a balanced consideration of both reaching conditions and the monotonic convergence, in the context of sliding mode control. In this paper, the dynamic behaviour of the dead-beat sliding mode control is characterized and the signum function is replaced by employing a non-switching one, in order to reduce chattering. The paper conducts a thorough analysis of monotonic convergence of both the switching and the non-switching error dynamics. By deriving the conditions for monotonic convergence, the control parameters can be strategically chosen to ensure monotonic convergence of the tracking error. Numerical and experimental results are presented to validate effectiveness of the proposed control scheme, which evaluate the tracking performance achieved by both the switching and the non-switching control methods.

Quantitative and Qualitative Parameters of DCE-MRI Predict CDKN2A/B Homozygous Deletion in Gliomas.

RATIONALE AND OBJECTIVES: Homozygous deletion (HD) of CDKN2A/B holds important prognostic value in gliomas. This study aimed to explore the predictive potential of conventional MRI characteristics combined with dynamic contrast-enhanced MRI parameters in predicting CDKN2A/B HD status in gliomas. MATERIALS AND METHODS: Preoperative MRI data of 105 patients (69 without CDKN2A/B HD, and 36 with CDKN2A/B homozygous deletion) with gliomas were retrospectively collected. Conventional MRI features and dynamic contrast-enhanced-MRI qualitative parameter time-intensity curve type, quantitative parameters Ktrans, Kep, Ve, Vp, and iAUC were obtained. Logistic regression models for prediction of CDKN2A/B HD status were constructed in all types of gliomas and both subtypes of IDH-mutant and IDH-wild gliomas. RESULTS: Multivariate analysis for all patients demonstrated that age (OR=1.103, p = 0.002) and Ktrans (OR=1.051, p < 0.001) independently predicted CDKN2A/B HD. In IDH-mutant subgroup, multivariate analysis results indicated that Ktrans (OR=1.098, p = 0.031) emerged as autonomous predictors of CDKN2A/B HD. In IDH-wild subgroup, age (OR=1.111, p = 0.002) and Ktrans (OR=1.032, p = 0.001) were independent predictors of CDKN2A/B HD according to the multivariate analysis. The areas under the receiver operating characteristic curve of the corresponding models were 0.90, 0.95 and 0.84, respectively. CONCLUSION: Ktrans can serve as valuable predictive parameters for identifying CDKN2A/B HD status in all types of gliomas and both subtypes of IDH-mutant and IDH-wild gliomas. These findings provide a foundation for precise preoperative non-invasive diagnosis and personalized treatment approaches for glioma patients.

Olfactory deficit: a potential functional marker across the Alzheimer's disease continuum.

Alzheimer's disease (AD) is a prevalent form of dementia that affects an estimated 32 million individuals globally. Identifying early indicators is vital for screening at-risk populations and implementing timely interventions. At present, there is an urgent need for early and sensitive biomarkers to screen individuals at risk of AD. Among all sensory biomarkers, olfaction is currently one of the most promising indicators for AD. Olfactory dysfunction signifies a decline in the ability to detect, identify, or remember odors. Within the spectrum of AD, impairment in olfactory identification precedes detectable cognitive impairments, including mild cognitive impairment (MCI) and even the stage of subjective cognitive decline (SCD), by several years. Olfactory impairment is closely linked to the clinical symptoms and neuropathological biomarkers of AD, accompanied by significant structural and functional abnormalities in the brain. Olfactory behavior examination can subjectively evaluate the abilities of olfactory identification, threshold, and discrimination. Olfactory functional magnetic resonance imaging (fMRI) can provide a relatively objective assessment of olfactory capabilities, with the potential to become a promising tool for exploring the neural mechanisms of olfactory damage in AD. Here, we provide a timely review of recent literature on the characteristics, neuropathology, and examination of olfactory dysfunction in the AD continuum. We focus on the early changes in olfactory indicators detected by behavioral and fMRI assessments and discuss the potential of these techniques in MCI and preclinical AD. Despite the challenges and limitations of existing research, olfactory dysfunction has demonstrated its value in assessing neurodegenerative diseases and may serve as an early indicator of AD in the future.

Altered Dynamics of Brain Spontaneous Activity and Functional Networks Associated With Cognitive Impairment in Patients With Type 2 Diabetes.

BACKGROUND: Cognitive impairment is increasingly recognized as an important comorbidity and complication of type 2 diabetes (T2D), affecting patients' quality of life and diabetes management. Dynamic brain activity indicators can reflect changes in key neural activity patterns of cognition and behavior. PURPOSE: To investigate dynamic functional connectivity (DFC) changes and spontaneous brain activity based on resting-state functional magnetic resonance imaging (rs-fMRI) in patients with T2D, exploring their correlations with clinical features. STUDY TYPE: Retrospective. SUBJECTS: Forty-five healthy controls (HCs) (22 males and 23 females) and 102 patients with T2D (57 males and 45 females). FIELD STRENGTH/SEQUENCE: 3.0 T/T1-weighted imaging and rs-fMRI with gradient-echo planar imaging sequence. ASSESSMENT: Functional networks were created using independent component analysis. DFC states were determined using sliding window approach and k-means clustering. Spontaneous brain activity was assessed using dynamic regional homogeneity (dReHo) variability. STATISTICAL TESTS: One-way analysis of variance and post hoc analysis were used to compare the essential information including demographics, clinical data, and features of DFC and dReHo among groups. Diagnostic performance was assessed using receiver operating characteristic (ROC) curve. P-values <0.05 were taken to indicate statistical significance. RESULTS: T2D group had significantly decreased mean dwell time and fractional windows in state 4 compared to HC. T2D with mild cognitive impairment showed significantly increased dReHo variability in left superior occipital gyrus compared to T2D with normal cognition. Mean dwell time and number of fractional windows of state 4 both showed significant positive correlations with the Montreal cognitive assessment scores (r = 0.309; r = 0.308, respectively) and the coefficient of variation of dReHo was significantly positively correlated with high-density lipoprotein cholesterol (r = 0.266). The integrated index had an area under the curve of 0.693 (95% confidence interval = 0.592-0.794). DATA CONCLUSION: Differences in DFC and dynamic characteristic of spontaneous brain activity associated with T2D-related functional impairment may serve as indicators for predicting symptom progression and assessing cognitive dysfunction. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Construction and validation of molecular subtype and signature of immune cell-related telomeric genes and prediction of prognosis and immunotherapy efficacy in ovarian cancer patients.

BACKGROUND: Ovarian cancer (OVC) has emerged as a fatal gynecological malignancy as a result of a lack of reliable methods for early detection, limited biomarkers and few treatment options. Immune cell-related telomeric genes (ICRTGs) show promise as potential biomarkers. METHODS: ICRTGs were discovered using weighted gene co-expression network analysis (WGCNA). ICRTGs were screened for significant prognosis using one-way Cox regression analysis. Subsequently, molecular subtypes of prognosis-relevant ICRTGs were constructed and validated for OVC, and the immune microenvironment's landscape across subtypes was compared. OVC prognostic models were built and validated using prognosis-relevant ICRTGs. Additionally, chemotherapy susceptibility drugs for OVC patients in the low- and high-risk groups of ICRTGs were screened using genomics of drug susceptibility to cancer (GDSC). Finally, the immunotherapy response in the low- and high-risk groups was detected using the data from GSE78220. We conducted an immune index correlation analysis of ICRTGs with significant prognoses. The MAP3K4 gene, for which the prognostic correlation coefficient is the highest, was validated using tissue microarrays for a prognostic-immune index correlation. RESULTS: WGCNA analysis constructed a gene set of ICRTGs and screened 22 genes with prognostic significance. Unsupervised clustering analysis revealed the best molecular typing for two subtypes. The Gene Set Variation Analysis algorithm was used to calculate telomere scores and validate the molecular subtyping. A prognostic model was constructed using 17 ICRTGs. In the The Cancer Genome Atlas-OVC training set and the Gene Expression Omnibus validation set (GSE30161), the risk score model's predicted risk groups and the actual prognosis were shown to be significantly correlated. GDSC screened Axitinib, Bexarotene, Embelin and the GSE78220 datasets and demonstrated that ICRTGs effectively distinguished the group that responds to immunotherapy from the non-responsive group. Additionally, tissue microarray validation results revealed that MAP3K4 significantly predicted patient prognosis. Furthermore, MAP3K4 exhibited a positive association with PD-L1 and a negative relationship with the M1 macrophage markers CD86 and INOS. CONCLUSIONS: ICRTGs may be reliable biomarkers for the molecular typing of patients with OVC, enabling the prediction of prognosis and immunotherapy efficacy.

Non-alcoholic fatty liver disease is associated with brain function disruption in type 2 diabetes patients without cognitive impairment.

AIMS: To investigate the neural static and dynamic intrinsic activity of intra-/inter-network topology among patients with type 2 diabetes (T2D) with non-alcoholic fatty liver disease (NAFLD) and those without NAFLD (T2NAFLD group and T2noNAFLD group, respectively) and to assess the relationship with metabolism. METHODS: Fifty-six patients with T2NAFLD, 78 with T2noNAFLD, and 55 healthy controls (HCs) were recruited to the study. Participants had normal cognition and underwent functional magnetic resonance imaging scans, clinical measurements, and global cognition evaluation. Independent component analysis was used to identify frequency spectrum parameters, static functional network connectivity, and temporal properties of dynamic functional network connectivity (P < 0.05, false discovery rate-corrected). Statistical analysis involved one-way analysis of covariance with post hoc, partial correlation and canonical correlation analyses. RESULTS: Our findings showed that: (i) T2NAFLD patients had more disordered glucose and lipid metabolism, had more severe insulin resistance, and were more obese than T2noNAFLD patients; (ii) T2D patients exhibited disrupted brain function, as evidenced by alterations in intra-/inter-network topology, even without clinically measurable cognitive impairment; (iii) T2NAFLD patients had more significant reductions in the frequency spectrum parameters of cognitive executive and visual networks than those with T2noNAFLD; and (iv) altered brain function in T2D patients was correlated with postprandial glucose, high-density lipoprotein cholesterol, and waist-hip ratio. CONCLUSION: This study may provide novel insights into neuroimaging correlates for underlying pathophysiological processes inducing brain damage in T2NAFLD. Thus, controlling blood glucose levels, lipid levels and abdominal obesity may reduce brain damage risk in such patients.

Effects of repetitive transcranial magnetic stimulation and their underlying neural mechanisms evaluated with magnetic resonance imaging-based brain connectivity network analyses.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain modulation and rehabilitation technique used in patients with neuropsychiatric diseases. rTMS can structurally remodel or functionally induce activities of specific cortical regions and has developed to an important therapeutic method in such patients. Magnetic resonance imaging (MRI) provides brain data that can be used as an explanation tool for the neural mechanisms underlying rTMS effects; brain alterations related to different functions or structures may be reflected in changes in the interaction and influence of brain connections within intrinsic specific networks. In this review, we discuss the technical details of rTMS and the biological interpretation of brain networks identified with MRI analyses, comprehensively summarize the neurobiological effects in rTMS-modulated individuals, and elaborate on changes in the brain network in patients with various neuropsychiatric diseases receiving rehabilitation treatment with rTMS. We conclude that brain connectivity network analysis based on MRI can reflect alterations in functional and structural connectivity networks comprising adjacent and separated brain regions related to stimulation sites, thus reflecting the occurrence of intrinsic functional integration and neuroplasticity. Therefore, MRI is a valuable tool for understanding the neural mechanisms of rTMS and practically tailoring treatment plans for patients with neuropsychiatric diseases.

Jieduquyuziyin prescription enhances CD11a and CD70 DNA methylation of CD4+ T cells via miR-29b-sp1/DNMT1 pathway in MRL/lpr mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Jieduquyuziyin prescription (JP) is a traditional Chinese medicine utilized to treat systemic lupus erythematosus (SLE). Its efficacy has been confirmed through clinical trials and empirical evidence, leading to its authorized use in Chinese hospitals. The development of JP exemplifies the integration of traditional wisdom and scientific approaches, demonstrating the interdisciplinary essence of ethnopharmacology. These results emphasize the potential value of traditional medicine in addressing autoimmune disorders. AIM OF THE STUDY: This study aims to address the effect of JP in MRL/lpr mice and elucidate the pharmacological mechanism by which JP targets CD11a and CD70 DNA methylation via the miR-29b-sp1/DNMT1 pathway. MATERIALS AND METHODS: MRL/lpr mice were divided into three groups: the model group (received distilled water), the positive group (administered AAV/miR-29b-3p inhibitor), and the JP group (treated with JP decoction). C57BL/6 mice were constituted as a control group. Through ELISA assay, serum and urine samples were assessed for anti-dsDNA, TNF-α, TGF-ß, IL-2, and UP. HE and Masson staining were conducted to reveal renal pathology. Genome DNA was extracted from CD4+ T cells of mice spleens to evaluate methylation level. The methylation of CD11a, CD70, and CD40L promoter regions was analyzed by targeted bisulfate sequencing. Their expression at the mRNA and protein levels was examined using quantitative real-time PCR, western blot analysis, immunohistochemistry, and immunofluorescence staining of kidney tissues. Furthermore, the molecular mechanisms underlying the regulation of the miR-29b-sp1/DNMT1 pathway by JP were explored with Jurkat cells transfected with miR-inhibitors or miR-mimics. RESULTS: Mice treated with JP exhibited a significant decrease in anti-dsDNA, TNF-α, TGF-ß, and UP, accompanied by a significant increase in IL-2. HE staining revealed JP effectively mitigated renal inflammatory response, while Masson staining indicated a reduction in collagen fiber content. In addition, JP exhibited a significant impact on the global hypomethylation of SLE, as evidenced by the induction of high methylation levels of CD11a and CD70 promoter regions, mediated through the miR-29b-sp1/DNMT1 pathway. CONCLUSION: Our findings demonstrate JP exerts a protective effect against spontaneous SLE development, attenuates renal pathological changes, and functions as a miRNA inhibitor to enhance CD11a and CD70 DNA methylation through the modulation of the miR-29b-sp1/DNMT1 pathway.

Biological traits of the zoophytophagous predatory mirid Nesidiocoris poppiusi (Heteroptera: Miridae), a candidate biocontrol agent in China.

Mirid predators are increasingly used in biological control of multiple greenhouse crops pests. However, due to great morphological similarity and tiny body size, some mirid predators have been largely confused with their allied species. Nesidiocoris tenuis Reuter as a commercial mirid predator was confused largely with Nesidiocoris poppiusi Carvalho in China. To evaluate the biocontrol potential of N. poppiusi, its biological traits and the functional response to Bemisia tabaci Gennadius were studied compared with N. tenuis under laboratory conditions. The results showed that no significant differences of the developmental times from the first instar to adult stages between the 2 mirids fed on Corcyra cephalonica Stainton eggs were observed, while N. poppiusi had better population growth parameters than N. tenuis. Under the condition with prey, both female and male of N. poppiusi lived significantly longer than those of N. tenuis. It could lay 74.0 eggs, which was significantly higher than that of N. tenuis (30.2 eggs). Under the condition without prey, both N. poppiusi and N. tenuis couldn't complete development to adulthood on tomato, tobacco, muskmelon, and cabbage leaves, however, tobacco and tomato were more suitable than the other 2 plants. A type II functional response was observed for both males and females of the 2 predators. Nesidiocoris poppiusi females consumed significantly more B. tabaci pupae than N. tenuis when prey densities were large than 30. Our results indicated that N. poppiusi could be a promising candidate for biological control of B. tabaci.

URB2 as an important marker for glioma prognosis and immunotherapy.

Introduction: Glioma is the most common primary brain tumor and primary malignant tumor of the brain in clinical practice. Conventional treatment has not significantly altered the prognosis of patients with glioma. As research into immunotherapy continues, glioma immunotherapy has shown great potential. Methods: The clinical data were acquired from the Chinese Glioma Genome Atlas (CGGA) database and validated by the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) dataset, Clinical Proteomic Tumor Analysis Consortium (CPTAP) database, and Western blot (WB) analysis. By Cox regression analyses, we examined the association between different variables and overall survival (OS) and its potential as an independent prognostic factor. By constructing a nomogram that incorporates both clinicopathological variables and the expression of URB2, we provide a model for the prediction of prognosis. Moreover, we explored the relationship between immunity and URB2 and elucidated its underlying mechanism of action. Results: Our study shows that URB2 likely plays an oncogenic role in glioma and confirms that URB2 is a prognostic independent risk factor for glioma. Furthermore, we revealed a close relationship between immunity and URB2, which suggests a new approach for the immunotherapy of glioma. Conclusion: URB2 can be used for prognosis prediction and immunotherapy of glioma.

Spatial navigation is associated with subcortical alterations and progression risk in subjective cognitive decline.

BACKGROUND: Subjective cognitive decline (SCD) may serve as a symptomatic indicator for preclinical Alzheimer's disease; however, SCD is a heterogeneous entity regarding clinical progression. We aimed to investigate whether spatial navigation could reveal subcortical structural alterations and the risk of progression to objective cognitive impairment in SCD individuals. METHODS: One hundred and eighty participants were enrolled: those with SCD (n = 80), normal controls (NCs, n = 77), and mild cognitive impairment (MCI, n = 23). SCD participants were further divided into the SCD-good (G-SCD, n = 40) group and the SCD-bad (B-SCD, n = 40) group according to their spatial navigation performance. Volumes of subcortical structures were calculated and compared among the four groups, including basal forebrain, thalamus, caudate, putamen, pallidum, hippocampus, amygdala, and accumbens. Topological properties of the subcortical structural covariance network were also calculated. With an interval of 1.5 years ± 12 months of follow-up, the progression rate to MCI was compared between the G-SCD and B-SCD groups. RESULTS: Volumes of the basal forebrain, the right hippocampus, and their respective subfields differed significantly among the four groups (p < 0.05, false discovery rate corrected). The B-SCD group showed lower volumes in the basal forebrain than the G-SCD group, especially in the Ch4p and Ch4a-i subfields. Furthermore, the structural covariance network of the basal forebrain and right hippocampal subfields showed that the B-SCD group had a larger Lambda than the G-SCD group, which suggested weakened network integration in the B-SCD group. At follow-up, the B-SCD group had a significantly higher conversion rate to MCI than the G-SCD group. CONCLUSION: Compared to SCD participants with good spatial navigation performance, SCD participants with bad performance showed lower volumes in the basal forebrain, a reorganized structural covariance network of subcortical nuclei, and an increased risk of progression to MCI. Our findings indicated that spatial navigation may have great potential to identify SCD subjects at higher risk of clinical progression, which may contribute to making more precise clinical decisions for SCD individuals who seek medical help.

Cadmium contamination triggers negative bottom-up effects on the growth and reproduction of Frankliniella occidentalis (Thysanoptera: Thripidae) without disrupting the foraging behavior of its predator, Orius sauteri (Heteroptera: Anthocoridae).

Heavy metal contaminants may influence tri-trophic interactions among plants, herbivores, and their natural enemies and affect the results of pest management practices. We examined how the widely distributed heavy metal cadmium (Cd) could modify interactions between kidney bean, Phaseolus vulgaris L., western flower thrips, Frankliniella occidentalis Pergande, and a predator, Orius sauteri (Poppius) by examining Cd effects on the feeding damage on leaves, the growth and reproduction of the thrips, and the feeding and plant location selection behaviors of predators. Leaf feeding damage was significantly reduced only at the highest Cd treatment (625 mg L-1). Survival, reproduction, and population growth of thrips decreased with the increase of Cd treatment concentration (0, 25, and 625 mg L-1). The reproduction rate of thrips from the highest Cd treatment group was reduced to less than 30% of the controls. Predator choice of plants was not impacted at the lowest level of Cd treatment (25 mg L-1) when prey were excluded, but the predators were deterred from plants treated at the high level of Cd (625 mg L-1). However, the predators responded strongly to the presence of prey, and the Cd-based deterrence was effectively eliminated when prey were added. Thus, the presence of Cd can cause a bottom-up effect on the fitness of pests without disrupting the foraging behavior of its predator. Our results provide baseline data on the toxic impacts on the pest and predator, and indicate that the ecology of the system and the biological control efficiency would be potentially impacted by high levels of Cd (625 mg L-1).

Critical roles of linker length in determining the chemical and self-assembly stability of SN38 homodimeric nanoprodrugs.

Homodimeric prodrug nanoassemblies (HDPNs) have been widely studied for efficient cancer therapy by virtue of their ultra-high drug loading and distinct nanostructure. However, the development of SN38 HDPNs is still a great challenge due to the rigid planar aromatic ring structure. Improving the structural flexibility of homodimeric prodrugs by increasing the linker length may be a potential strategy for constructing SN38 HDPNs. Herein, three SN38 homodimeric prodrugs with different linker lengths were synthesized. The number of carbon atoms from the disulfide bond to the adjacent ester bond is 1 (denoted as α-SN38-SS-SN38), 2 (ß-SN38-SS-SN38), and 3 (γ-SN38-SS-SN38), respectively. Interestingly, we found that α-SN38-SS-SN38 exhibited extremely low yield and poor chemical stability. Additionally, ß-SN38-SS-SN38 demonstrated suitable chemical stability but poor self-assembly stability. In comparison, γ-SN38-SS-SN38 possessed good chemical and self-assembly stability, thereby improving the tumor accumulation and antitumor efficacy of SN38. We developed the SN38 HDPNs for the first time and illustrated the underlying molecular mechanism of increasing the linker length to enhance the chemical and self-assembly stability of homodimeric prodrugs. These findings would provide new insights for the rational design of HDPNs with superior performance.

A new type of bladeless turbine for compressed gas energy storage system.

Nowadays, energy storage engineering is an important means to relieve the problem of energy shortage. In this investigation, we design a kind of vaneless turbine originating from a Tesla turbine with a diameter and an air gap of 250 mm and 0.5 mm, respectively. Importantly, such a vaneless turbine removes the feature of an air outlet in the middle and adopts other ways of entering and leaving on both sides, so as to strengthen the rotor, because there is no need for a large hole in the middle of the rotor. Furthermore, the rotor dynamics characteristics of the vaneless turbine are calculated by six different modes. We also obtain the critical speed in different modes. Moreover, the flow field performances, such as the velocity and pressure of fluid (air), are investigated using the finite element simulation method. In addition, the bench test is built to obtain the output characteristics of a vaneless turbine. The maximum output torque is about 5.56 Nm at 992 rpm, and the maximal rotational speed of the vaneless turbine can reach 3200 rpm. Our work provides new ideas and guidance for the design and research of the new generation of the vaneless turbine.

Natural Compounds for SIRT1-Mediated Oxidative Stress and Neuroinflammation in Stroke: A Potential Therapeutic Target in the Future.

Stroke is a fatal cerebral vascular disease with a high mortality rate and substantial economic and social costs. ROS production and neuroinflammation have been implicated in both hemorrhagic and ischemic stroke and have the most critical effects on subsequent brain injury. SIRT1, a member of the sirtuin family, plays a crucial role in modulating a wide range of physiological processes, including apoptosis, DNA repair, inflammatory response, and oxidative stress. Targeting SIRT1 to reduce ROS and neuroinflammation might represent an emerging therapeutic target for stroke. Therefore, we conducted the present review to summarize the mechanisms of SIRT1-mediated oxidative stress and neuroinflammation in stroke. In addition, we provide a comprehensive introduction to the effect of compounds and natural drugs on SIRT1 signaling related to oxidative stress and neuroinflammation in stroke. We believe that our work will be helpful to further understand the critical role of the SIRT1 signaling pathway and will provide novel therapeutic potential for stroke treatment.

Anoikis resistance in diffuse glioma: The potential therapeutic targets in the future.

Glioma is the most common malignant intracranial tumor and exhibits diffuse metastasis and a high recurrence rate. The invasive property of glioma results from cell detachment. Anoikis is a special form of apoptosis that is activated upon cell detachment. Resistance to anoikis has proven to be a protumor factor. Therefore, it is suggested that anoikis resistance commonly occurs in glioma and promotes diffuse invasion. Several factors, such as integrin, E-cadherin, EGFR, IGFR, Trk, TGF-ß, the Hippo pathway, NF-κB, eEF-2 kinase, MOB2, hypoxia, acidosis, ROS, Hsp and protective autophagy, have been shown to induce anoikis resistance in glioma. In our present review, we aim to summarize the underlying mechanism of resistance and the therapeutic potential of these molecules.

Predicting MGMT Promoter Methylation in Diffuse Gliomas Using Deep Learning with Radiomics.

This study aimed to investigate the feasibility of predicting oxygen 6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in diffuse gliomas by developing a deep learning approach using MRI radiomics. A total of 111 patients with diffuse gliomas participated in the retrospective study (56 patients with MGMT promoter methylation and 55 patients with MGMT promoter unmethylation). The radiomics features of the two regions of interest (ROI) (the whole tumor area and the tumor core area) for four sequences, including T1 weighted image (T1WI), T2 weighted image (T2WI), apparent diffusion coefficient (ADC) maps, and T1 contrast-enhanced (T1CE) MR images were extracted and jointly fed into the residual network. Then the deep learning method was developed and evaluated with a five-fold cross-validation, where in each fold, the dataset was randomly divided into training (80%) and validation (20%) cohorts. We compared the performance of all models using area under the curve (AUC) and average accuracy of validation cohorts and calculated the 10 most important features of the best model via a class activation map. Based on the ROI of the whole tumor, the predictive capacity of the T1CE and ADC model achieved the highest AUC value of 0.85. Based on the ROI of the tumor core, the T1CE and ADC model achieved the highest AUC value of 0.90. After comparison, the T1CE combined with the ADC model based on the ROI of the tumor core exhibited the best performance, with the highest average accuracy (0.91) and AUC (0.90) among all models. The deep learning method using MRI radiomics has excellent diagnostic performance with a high accuracy in predicting MGMT promoter methylation in diffuse gliomas.

Natural Products for the Treatment of Post-stroke Depression.

Post-stroke depression (PSD) is the most frequent and important neuropsychiatric consequence of stroke. It is strongly associated with exacerbated deterioration of functional recovery, physical and cognitive recoveries, and quality of life. However, its mechanism is remarkably complicated, including the neurotransmitters hypothesis (which consists of a monoaminergic hypothesis and glutamate-mediated excitotoxicity hypothesis), inflammation hypothesis, dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, and neurotrophic hypothesis and neuroplasticity. So far, the underlying pathogenesis of PSD has not been clearly defined yet. At present, selective serotonin reuptake inhibitors (SSRIs) have been used as the first-line drugs to treat patients with PSD. Additionally, more than SSRIs, a majority of the current antidepressants complied with multiple side effects, which limits their clinical application. Currently, a wide variety of studies revealed the therapeutic potential of natural products in the management of several diseases, especially PSD, with minor side effects. Accordingly, in our present review, we aim to summarize the therapeutic targets of these compounds and their potential role in-clinic therapy for patients with PSD.

Gut microbiota mediated the therapeutic efficacies and the side effects of prednisone in the treatment of MRL/lpr mice.

BACKGROUND: Growing evidences indicate that the alterations in gut microbiota are associated with the efficacy of glucocorticoids (GCs) in the treatment of systemic lupus erythematosus (SLE). However, there is no evidence to prove whether gut microbiota directly mediates the effects of GCs. METHODS: Using the MRL/lpr mice, this study firstly addressed the effects of three doses of prednisone on gut microbiota. Then, this study used fecal microbiota transplantation (FMT) to transfer the gut microbiota of prednisone-treated MRL/lpr mice into the blank MRL/lpr mice to reveal whether the gut microbiota regulated by prednisone had similar therapeutic efficiency and side effects as prednisone. RESULTS: The effects of prednisone on gut microbiota were dose-dependent in the treatment of MRL/lpr mice. After transplantation into MRL/lpr mice, prednisone-regulated gut microbiota could alleviate lupus, which might be due to decreasing Ruminococcus and Alistipes and retaining the abundance of Lactobacillus. However, prednisone-regulated gut microbiota did not exhibit side effects as prednisone. The reason might be that the pathogens upregulated by prednisone could not survive in the MRL/lpr mice as exogenous microbiota, such as Parasutterella, Parabacteroides, and Escherichia-Shigella. CONCLUSIONS: These data demonstrated that the transplantation of gut microbiota may be an effective method to obtain the therapeutic effects of GCs and avoid the side effects of GCs.

Genetically Predicted Serum Iron Status Is Associated with Altered Risk of Systemic Lupus Erythematosus among European Populations.

BACKGROUND: Observational epidemiological studies have reported an inconsistent relation between iron status and risk of systemic lupus erythematosus (SLE). Moreover, it remains uncertain whether the observed association is causal or due to confounding or reverse causality. OBJECTIVES: We aimed to investigate the association between serum iron status and risk of SLE using a 2-sample Mendelian randomization (MR) approach. METHODS: Genetic instruments for iron status including serum iron, log-transformed ferritin, transferrin saturation, and transferrin were identified from a large-scale genome-wide association study (GWAS) performed by the Genetics of Iron Status Consortium among 48,972 individuals of European ancestry (55% female). Three independent single nucleotide polymorphisms (rs1800562, rs1799945, and rs855791) concordantly related with 4 iron status biomarkers were selected as instrumental variables. Summary statistics of SLE were obtained from a publicly available GWAS of 4036 patients with SLE and 6959 controls of European descent. The MR study was conducted using the inverse-variance weighted (IVW) method, supplemented with MR-Egger regression and simple- and weighted-median methods. Leave-one-out analysis was further performed to test the robustness of our findings. ORs with 95% CIs were calculated. RESULTS: Genetically predicted iron status was associated with altered risk of SLE, with ORs of 0.79 (95% CI: 0.66, 0.94), 0.54 (95% CI: 0.34, 0.85), 0.82 (95% CI: 0.71, 0.94), and 1.36 (95% CI: 1.06, 1.76) per 1-SD increase in iron, log-transformed ferritin, transferrin saturation, and transferrin using the IVW method, respectively. MR-Egger regression did not indicate potential pleiotropic bias. Sensitivity analyses produced similar findings, suggesting the robustness of the association. CONCLUSIONS: Our study suggested that high iron status may be associated with a reduced risk of SLE among European populations. Further studies are warranted to elucidate the mechanism underlying the protective role of iron against susceptibility to SLE.