Synthesis and Characterization of a Novel PET Tracer for Noninvasive Evaluation of FGL1 Status in Tumors.

Fibrinogen-like protein 1 (FGL1) is a potential novel immune checkpoint target for malignant tumor diagnosis and therapy. Accurate detection of FGL1 levels in tumors via noninvasive PET imaging might be beneficial for managing the disease. To achieve this, multiple FGL1-targeting peptides (FGLP) were designed, and a promising candidate, 68Ga-NOTA-FGLP2, was identified through a high-throughput screening approach using microPET imaging of 68Ga-labeled peptides. Subsequent in vitro cell experiments showed that uptake values of 68Ga-NOTA-FGLP2 in FGL1 positive Huh7 tumor cells were significantly higher than those in FGL1 negative U87 MG tumor cells. Further microPET imaging showed that the Huh7 xenografts were clearly visualized with a favorable contrast. ROI analysis showed that the uptake values of the tracer in Huh7 xenografts were 2.63 ± 0.07% ID/g at 30 min p.i.. After treatment with an excess of unlabeled FGLP2, the tumor uptake significantly decreased to 0.54 ± 0.05% ID/g at 30 min p.i.. Moreover, the uptake in U87 MG xenografts was 0.44 ± 0.06% ID/g at the same time point. The tracer was excreted mainly through the renal system. 18F-FDG PET imaging was also performed in mice bearing Huh7 and U87 MG xenografts, respectively. However, there was no significant difference in the uptake between the tumors with different FGL1 expressions. Preclinical data indicated that 68Ga-NOTA-FGLP2 might be a suitable radiotracer for in vivo noninvasive visualization of tumors with abundant expression of FGL1. Further investigation of 68Ga-NOTA-FGLP2 for tumor diagnosis and therapy is undergoing.

Arctigenin derivative A-1 ameliorates motor dysfunction and pathological manifestations in SOD1G93A transgenic mice via the AMPK/SIRT1/PGC-1α and AMPK/SIRT1/IL-1ß/NF-κB pathways.

AIM: Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease characterized by progressive death of upper and lower motor neurons, leading to generalized muscle atrophy, paralysis, and even death. Mitochondrial damage and neuroinflammation play key roles in the pathogenesis of ALS. In the present study, the efficacy of A-1, a derivative of arctigenin with AMP-activated protein kinase (AMPK) and silent information regulator 1 (SIRT1) activation for ALS, was investigated. METHODS: A-1 at 33.3 mg/kg was administrated in SOD1G93A transgenic mice orally from the 13th week for a 6-week treatment period. Motor ability was assessed before terminal anesthesia. Muscle atrophy and fibrosis, motor neurons, astrocytes, and microglia in the spinal cord were evaluated by H&E, Masson, Sirius Red, Nissl, and immunohistochemistry staining. Protein expression was detected with proteomics analysis, Western blotting, and ELISA. Mitochondrial adenosine triphosphate (ATP) and malondialdehyde (MDA) levels were measured using an assay kit. RESULTS: A-1 administration in SOD1G93A mice enhanced mobility, decreased skeletal muscle atrophy and fibrosis, mitigated loss of spinal motor neurons, and reduced glial activation. Additionally, A-1 treatment improved mitochondrial function, evidenced by elevated ATP levels and increased expression of key mitochondrial-related proteins. The A-1 treatment group showed decreased levels of IL-1ß, pIκBα/IκBα, and pNF-κB/NF-κB. CONCLUSIONS: A-1 treatment reduced motor neuron loss, improved gastrocnemius atrophy, and delayed ALS progression through the AMPK/SIRT1/PGC-1α pathway, which promotes mitochondrial biogenesis. Furthermore, the AMPK/SIRT1/IL-1ß/NF-κB pathway exerted neuroprotective effects by reducing neuroinflammation. These findings suggest A-1 as a promising therapeutic approach for ALS.

SIRT3: A Potential Target of Different Types of Osteoporosis.

Osteoporosis (OP) is a common age-related disease. OP is mainly a decrease in bone density and mass caused by the destruction of bone microstructure, which leads to an increase in bone fragility. SIRT3 is a mitochondrial deacetylase that plays critical roles in mitochondrial homeostasis, metabolic regulation, gene transcription, stress response, and gene stability. Studies have shown that the higher expression levels of SIRT3 are associated with decreased levels of oxidative stress in the body and may play important roles in the prevention of age-related diseases. SIRTs can enhance the osteogenic potential and osteoblastic activity of bone marrow mesenchymal stromal cells not only by enhancing PGC-1α, FOXO3, SOD2, and oxidative phosphorylation, but also by anti-aging and reducing mitochondrial autophagy. SIRT3 is able to upregulate antioxidant enzymes to exert an inhibitory effect on osteoclasts, however, it has been shown that the inflammatory cascade response can in turn increase SIRT3 and inhibit osteoclast differentiation through the AMPK-PGC-1ß pathway. SIRT3 plays an important role in different types of osteoporosis by affecting osteoblasts, osteoclasts, and bone marrow mesenchymal cells. In this review, we discuss the classification and physiological functions of SIRTs, the effects of SIRT3 on OCs osteoblasts, and BMSCs, and the roles and mechanisms of SIRT3 in different types of OP, such as diabetic OP, glucocorticoid-induced OP, postmenopausal OP, and senile OP.

Association between serum ferritin and bone turnover marker levels in type 2 diabetes mellitus patients with non-alcoholic fatty liver disease.

OBJECTIVE: To investigate the correlation between serum ferritin (SF) and bone turnover markers in type 2 diabetes mellitus (T2DM) patients with non-alcoholic fatty liver disease (NAFLD). METHODS: Seven hundred and forty-two people with T2DM were selected. Serum bone turnover markers: osteocalcin (OC), type I procollagen N-terminal peptide (PINP), ß-I type collagen carboxy-terminal peptide (ß-CTx), and 25-hydroxyvitamin D3 (25-[OH]-D) levels were detected. High SF (HF) was defined as the indicated SF levels above 400 ng/mL in males and more than 150 ng/mL in females. Patients were divided into four groups: T2DM+normal SF (non-HF); T2DM+high SF (HF); T2DM+NAFLD+non-HF; andT2DM+NAFLD+HF. Relationships between SF and bone turnover markers were analyzed. RESULTS: Compared with the T2DM+non-HF group, ß-CTx levels were higher in the T2DM+HFgroup. Compared with the T2DM+NAFLD+non-HF group, ß-CTx levels were increased and 25-(OH)-D levels decreased in the T2DM+NAFLD+HF group (all p < 0.05). SF was positively correlated with ß-CTx [ß = 0.074; 95% CI (0.003, 0.205)] and negatively correlated with 25-(OH)-D [ß=-0.108; 95%CI (-0.006, -0.001)]. Compared with the T2DM+non-HF group, an independent positive correlation was found between ß-CTx and SF in the T2DM+NAFLD+HF group [OR = 1.002; 95% CI (1.001, 1.004)]. Among males, SF was positively correlatedwith ß-CTx [ß = 0.114; 95% CI (0.031, 0.266)]. SF was negatively correlated with 25-(OH)-D levels in both male and female patients [ß=-0.124; 95% CI (0.007,0.001) and ß=-0.168; 95% CI (-0.012, -0.002)]. Among those >50 years of age and postmenopausal females, SF was negatively correlated with 25-(OH)-D levels [ß=-0.117; 95% CI (-0.007, -0.001) and ß=-0.003; 95% CI (-0.013, -0.003)]. CONCLUSION: SF level was positively correlated with ß-CTx in T2DM patients with NAFLD, which may promote bone resorption and increase the risk of bone loss.

The relationship between advanced liver fibrosis and osteoporosis in type 2 diabetes patients with MAFLD.

PURPOSE: To investigate the relationship between advanced liver fibrosis and osteoporosis in metabolic-associated fatty liver disease (MAFLD) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 1144 T2DM patients were divided into the MAFLD and non-MAFLD groups, 460 T2DM patients with MAFLD (277 males aged ≥50 years and 183 postmenopausal females) were divided into N1 (advanced liver fibrosis excluded), N2 (indeterminate advanced liver fibrosis), and N3 (advanced liver fibrosis) groups according to the non-alcoholic fatty liver fibrosis score (NFS), the differences in bone mineral density (BMD) levels and prevalence of osteoporosis were compared. Based on the tertile levels of BMD of the lumbar spine (L), T2DM patients were divided into three groups (T1, T2, and T3), and the differences in the prevalence of advanced liver fibrosis were compared. RESULTS: The BMD levels of the L4, and L1-4 in the MAFLD group were lower than those of the non-MAFLD groups in male and female T2DM patients .The BMD levels of the total hip, L4, and L1-4 in the N3 group were lower than those of the N2 and N1 groups in male and female T2DM patients with MAFLD, and the prevalence of osteoporosis in the N3 group of males was higher than that in the N1 group. The BMD levels of the total hip, L4, and L1-4 were negatively correlated with NFS in both males and females. The BMD levels of the total hip and L4 in males, and the BMD level of L4 in females were negatively associated with NFS. The prevalence of advanced liver fibrosis was higher in the T1 group than in the T2 and T3 groups in T2DM patients with MAFLD. CONCLUSION: The BMD levels in male aged ≥50 years or postmenopausal female diabetic patients with MAFLD were negatively correlated with the degree of advanced liver fibrosis, which means an increased risk of liver fibrosis with decreasing BMD.

The Effect of Tirzepatide on Weight, Lipid Metabolism and Blood Pressure in Overweight/Obese Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Aim: To explore the effects of Tirzepatide (TZP), a new hypoglycemic drug, on weight, blood lipids and blood pressure in overweight/obese patients with type 2 diabetes mellitus (T2DM). Methods: Relevant studies investigating the influence of TZP therapy on weight, lipid profiles and blood pressure in overweight/obese T2DM patients were selected from the PubMed, Embase, Web of Science and Cochrane databases from establishment until November 2022. A systematic review and meta-analysis were conducted to evaluate the effect of TZP on weight, blood lipids and blood pressure in overweight/obese patients with T2DM. Results: Eight randomized controlled trials (RCTs), comprising 7491 patients with T2DM, were included in the meta-analysis. Results showed that compared with the glucagon-like peptide-1 receptor agonist (GLP-1RA), insulin, and placebo groups, body weight, triglycerides (TG), very low-density lipoprotein cholesterol (VLDL-C), total cholesterol (TC), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), and glycosylated hemoglobin (HbA1c) levels were significantly decreased in the TZP-treated groups, while high-density lipoprotein cholesterol (HDL-C) levels increased. With the gradual increase of TZP doses, the proportions of T2DM patients with weight loss >5% gradually increased. The 10 mg and 15 mg TZP doses had a stronger effect on the levels of TG, VLDL-C, and HDL-C. Moreover, the reduction in SBP levels in the 15 mg TZP-treated group was more pronounced than those in the 10 mg and 5 mg TZP-treated groups [MD=-2.07, 95% CI (-2.52, -1.63) and MD=-3.14, 95% CI (-4.42, -1.87)]. Compared with GLP-1RA, insulin, and placebo groups, the proportions of patients with HbA1c<7% in 10mg and 15mg TZP-treated groups were significantly higher than in the 5mg TZP-treated group [OR=1.53, 95% CI (1.25, 1.8)], OR=1.7, 95% CI (1.15, 2.50)].There was no significant difference regarding the risk of adverse reactions.

Evaluation of chicken chorioallantoic membrane model for tumor imaging and drug development: Promising findings.

BACKGROUND: The chicken chorioallantoic membrane (CAM) model is a potential alternative to the mouse model based on the 3R principles. However, its value for determination of the in vivo behaviors of radiolabeled peptides through positron emission tomography (PET) imaging needed investigation. Herein, the chicken CAM tumor models were established, and their feasibility was evaluated for evaluating the imaging properties of radiolabeled peptides using a 68 Ga-labeled HER2 affibody. METHODS: Two human breast cancer cell lines were inoculated into chicken CAM and mice, respectively. The tumor-targeting potential and pharmacokinetic profile of a 68 Ga-labeled affibody, 68 Ga-MZHER, in both tumor models were also determined. RESULTS: The tumor-formation time in chicken CAM model was shorter than that of mouse model. The uptake values of human epithelial growth factor receptor-2 (HER2)-positive Bcap37 tumors in chicken CAM and mouse models were 5.36 ± 0.26% ID/g and 5.26 ± 0.43% ID/g at 30 min postinjection of 68 Ga-MZHER, respectively. At the same time points, the uptake values of HER2-negative MDA-MB-231 tumors in the chicken CAM models and mouse models were 1.57 ± 0.15% ID/g and 1.67 ± 0.25% ID/g, respectively. Ex vivo biodistribution confirmed that more radioactivity accumulated in Bcap37 tumors than in MDA-MD-231 tumors in both CAM and mouse models. CONCLUSION: In this study, the CAM tumor model was successfully prepared. The chicken CAM model is a novel tool for quickly determining the in vivo properties of radiolabeled peptides targeting biomarkers. It may be beneficial for early monitoring of the therapeutic effect of a new drug through PET imaging with specific peptides.

Repurposing iron chelators for accurate positron emission tomography imaging tracking of radiometal-labeled cell transplants.

The use of radiolabeled cells for positron emission tomography (PET) imaging tracking has been a promising approach for monitoring cell-based therapies. However, the presence of free radionuclides released from dead cells during tracking can interfere with the signal from living cells, leading to inaccurate results. In this study, the effectiveness of the iron chelators deferoxamine (DFO) and deferiprone in removing free radionuclides 89Zr and 68Ga, respectively, was demonstrated in vivo utilizing PET imaging. The use of DFO during PET imaging tracking of 89Zr-labeled mesenchymal stem cells (MSCs) significantly reduced uptake in bone while preserving uptake in major organs, resulting in more accurate and reliable tracking. Furthermore, the clearance of free 89Zr in vivo resulted in a significant reduction in radiation dose from 89Zr-labeled MSCs. Additionally, the avoidance of free radionuclide accumulation in bone allowed for more precise observation of the homing process and persistence during bone marrow transplantation. The efficacy and safety of this solution suggest this finding has potential for widespread use in imaging tracking studies involving various cells. Moreover, since this method employed iron chelator drugs in clinical use, which makes it is a good prospect for clinical translation.

Activating Tumor-Selective Liquid Metal Nanomedicine through Galvanic Replacement.

Advanced chemotherapeutic strategies including prodrug and nanocatalytic medicine have significantly advanced tumor-selective theranostics, but delicate prodrug screening, tedious synthesis, low degradability/biocompatibility of inorganic components, and unsatisfied reaction activity complicate treatment efficacies. Here, the intrinsic anticancer bioactivity of liquid metal nanodroplets (LMNDs) is explored through galvanic replacement. By utilizing a mechano-degradable ligand, the resultant size of the aqueous LMND is unexpectedly controlled as small as ≈20 nm (LMND20). It is demonstrated that LMND20 presents excellent tumor penetration and biocompatibility and activates tumor-selective carrier-to-drug conversion, synchronously depleting Cu2+ ions and producing Ga3+ ions through galvanic replacement. Together with abundant generation of reactive oxygen species, multiple anticancer pathways lead to selective apoptosis and anti-angiogenesis of breast cancer cells. Compared to the preclinical/clinical anticancer drugs of tetrathiomolybdate and Ga(NO3 )3 , LMND20 administration significantly improves the therapeutic efficacy and survival in a BCap-37 xenograft mouse model, yet without obvious side effects.

Integrative Metabolomic and Transcriptomic Landscape during Akebia trifoliata Fruit Ripening and Cracking.

Akebia trifoliata fruit is prone to crack after ripening, but little is known about the mechanism underlying the cracking process. This study integrated transcriptomic and metabolomic data, revealing significant changes in 398 metabolites and 8414 genes during ripening and cracking, mainly impacting cell-wall metabolism. Multi-omics joint analysis indicated that genes related to polygalacturonase, pectate lyase, α-amylase, and glycogen phosphorylase were up-regulated after cracking, degrading cell wall and starch. Concurrently, diminished photosynthetic metabolism and heightened phenylpropanoid metabolism suggested alterations in cuticle structure, potentially impacting cell-wall robustness. Numerous auxin and abscisic acid signaling-related genes were expressed, and we assume that they contributed to the promoting peel growth. These alterations collectively might compromise peel strength and elevate expanding pressure, potentially leading to A. trifoliata cracking. Transcription factors, predominantly ethylene response factors and helix-loop-helix family members, appeared to regulate these metabolic shifts. These findings provide valuable insights into A. trifoliata cracking mechanisms; however, direct experimental validation of these assumptions is necessary to strengthen these conclusions and expedite their commercial utilization.

Applications of multi-omics analysis in human diseases.

Multi-omics usually refers to the crossover application of multiple high-throughput screening technologies represented by genomics, transcriptomics, single-cell transcriptomics, proteomics and metabolomics, spatial transcriptomics, and so on, which play a great role in promoting the study of human diseases. Most of the current reviews focus on describing the development of multi-omics technologies, data integration, and application to a particular disease; however, few of them provide a comprehensive and systematic introduction of multi-omics. This review outlines the existing technical categories of multi-omics, cautions for experimental design, focuses on the integrated analysis methods of multi-omics, especially the approach of machine learning and deep learning in multi-omics data integration and the corresponding tools, and the application of multi-omics in medical researches (e.g., cancer, neurodegenerative diseases, aging, and drug target discovery) as well as the corresponding open-source analysis tools and databases, and finally, discusses the challenges and future directions of multi-omics integration and application in precision medicine. With the development of high-throughput technologies and data integration algorithms, as important directions of multi-omics for future disease research, single-cell multi-omics and spatial multi-omics also provided a detailed introduction. This review will provide important guidance for researchers, especially who are just entering into multi-omics medical research.

Druggability of Targets for Diagnostic Radiopharmaceuticals.

Targets play an indispensable and pivotal role in the development of radiopharmaceuticals. However, the initial stages of drug discovery projects are often plagued by frequent failures due to inadequate information on druggability and suboptimal target selection. In this context, we aim to present a comprehensive review of the factors that influence target druggability for diagnostic radiopharmaceuticals. Specifically, we explore the crucial determinants of target specificity, abundance, localization, and positivity rate and their respective implications. Through a detailed analysis of existing protein targets, we elucidate the significance of each factor. By carefully considering and balancing these factors during the selection of targets, more efficacious and targeted radiopharmaceuticals are expected to be designed for the diagnosis of a wide range of diseases in the future.

The association between triglyceride-glucose index and hyperferritinemia in patients with type 2 diabetes mellitus.

PURPOSE: To investigate the relationship between the triglyceride-glucose (TyG) index and serum ferritin (SF) levels in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 881 T2DM patients were divided into T1(TyG index < 1.66), T2 (1.66 ≤ TyG index < 2.21), and T3 (TyG index ≥ 2.21) groups according to the tertiles of the TyG index. The differences in SF levels and the prevalence of hyperferritinemia (SF ≥ 300 ng/mL for male or SF ≥ 150 ng/mL for female) were compared. The independent correlations between the TyG index and SF, and between hyperferritinemia and TyG in T2DM patients were analyzed, respectively. RESULTS: SF levels in male T2DM patients were higher in the T3 group (250.12 ng/mL) than in the T1 and T2 groups (180.45 and 196.56 ng/mL, both p < 0.01),while in female patients with T2DM,SF levels were higher in the T3 group (157.25 ng/mL) than in the T1 group (111.06 ng/mL, p < 0.05).The prevalence of hyperferritinemia in male T2DM patients was higher in the T3 group (31.3%) than those in the T1 and T2 groups (10.4% and 17.3%, both p < 0.05).The TyG index was positively correlated with SF levels in T2DM patients (R = 0.178, p < 0.001).TyG index was independently and positively correlated with SF levels after adjusting for confounders (ß = 0.097, 95%CI [2.870,38.148], p = 0.023).The TyG index was positively independently correlated with hyperferritinemia in male T2DM patients (OR = 1.651, 95%CI [1.120,2.432], p = 0.011). CONCLUSIONS: In parallel with increasing TyG index SF levels gradually increased. The TyG index was positively correlated with SF levels in patients with T2DM and was positively correlated with hyperferritinemia in male T2DM patients.

Ferroptosis: roles and molecular mechanisms in diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a serious complication of type 1 and type 2 diabetes, which leads to the aggravation of myocardial fibrosis, disorders involving systolic and diastolic functions, and increased mortality of patients with diabetes through mechanisms such as glycolipid toxicity, inflammatory response, and oxidative stress. Ferroptosis is a form of iron-dependent regulatory cell death that is attributed to the accumulation of lipid peroxides and an imbalance in redox regulation. Increased production of lipid reactive oxygen species (ROS) during ferroptosis promotes oxidative stress and damages myocardial cells, leading to myocardial systolic and diastolic dysfunction. Overproduction of ROS is an important bridge between ferroptosis and DCM, and ferroptosis inhibitors may provide new targets for the treatment of patients with DCM.

Multiomics analysis of human peripheral blood reveals marked molecular profiling changes caused by one night of sleep deprivation.

Sleep insufficiency is associated with various disorders; the molecular basis is unknown until now. Here, 14 males and 18 females were subjected to short-term (24 h) sleep deprivation, and donated fasting blood samples prior to (day 1) and following (days 2 and 3) short-term sleep deprivation. We used multiple omics techniques to examine changes in volunteers' blood samples that were subjected to integrated, biochemical, transcriptomic, proteomic, and metabolomic analyses. Sleep deprivation caused marked molecular changes (46.4% transcript genes, 59.3% proteins, and 55.6% metabolites) that incompletely reversed by day 3. The immune system in particular neutrophil-mediated processes associated with plasma superoxidase dismutase-1 and S100A8 gene expression was markedly affected. Sleep deprivation decreased melatonin levels and increased immune cells, inflammatory factors and c-reactive protein. By disease enrichment analysis, sleep deprivation induced signaling pathways for schizophrenia and neurodegenerative diseases enriched. In sum, this is the first multiomics approach to show that sleep deprivation causes prominent immune changes in humans, and clearly identified potential immune biomarkers associated with sleep deprivation. This study indicated that the blood profile following sleep disruption, such as may occur among shift workers, may induce immune and central nervous system dysfunction.

Neural Network-Based Fixed-Time Tracking and Containment Control of Second-Order Heterogeneous Nonlinear Multiagent Systems.

This study concentrates on the fixed-time tracking consensus and containment control of second-order heterogeneous nonlinear multiagent systems (MASs) with and without measurable velocity under directed topology. By defining a time-varying scaling function and approximating the unknown nonlinear dynamics with radial basis function neural networks (RBFNNs), a novel distributed protocol for solving the fixed-time tracking consensus and containment control problems of second-order heterogeneous nonlinear MASs with full states available is proposed based on a nonsingular sliding-mode control method constructed by designing a prescribed-time convergent sliding surface. For the scenario of immeasurable velocity, a fixed-time convergent states' observer is designed to reveal the velocity information when the unknown linearity is bounded. Subsequently, a distributed fixed-time consensus protocol based on observed velocity information is proposed for the extended results. Ultimately, the acquired results are verified by three simulation examples.

Constructing liquid metal/metal-organic framework nanohybrids with strong sonochemical energy storage performance for enhanced pollutants removal.

With endogenous redox systems and multiple enzymes, the storage and utilization of external energy is general in living cells, especially through photo/ultrasonic synthesis/catalysis due to in-situ generation of abundant reactive oxygen species (ROS). However, in artificial systems, because of extreme cavitation surroundings, ultrashort lifetime and increased diffusion distance, sonochemical energy is rapidly dissipated via electron-hole pairs recombination and ROS termination. Here, we integrate zeolitic imidazolate framework-90 (ZIF-90) and liquid metal (LM) with opposite charges by convenient sonosynthesis, and the resultant nanohybrid (LMND@ZIF-90) can efficiently capture sonogenerated holes and electrons, and thus suppress electron-hole pairs recombination. Unexpectedly, LMND@ZIF-90 can store the ultrasonic energy for over ten days and exhibit acid-responsive release to trigger persistent generation of various ROS including superoxide (O2•-), hydroxyl radicals (•OH), and singlet oxygen (1O2), presenting significantly faster dye degradation rate (short to seconds) than previously reported sonocatalysts. Moreover, unique properties of gallium could additionally facilitate heavy metals removal through galvanic replacement and alloying. In summary, the LM/MOF nanohybrid constructed here demonstrates strong capacity for storing sonochemical energy as long-lived ROS, enabling enhanced water decontamination without energy input.

Tradeoff Analysis Between Control Time and Energy Consumption for Delayed Neural Networks With Discontinuous Activation Functions.

This article studies finite-time stabilization of delayed neural networks (DNNs) whose activation functions are discontinuous. Several sufficient conditions for guaranteeing finite-time stabilization of considered DNNs are obtained by constructing appropriate controllers with giving upper bounds of control time. Subsequently, based on the existing definition of energy consumption, the required energy to achieve stabilization is estimated. To quantify the cost of control, an evaluation index function is constructed to analyze the tradeoff between control time and consumed energy. Ultimately, acquired results are verified by simulating two numerical examples.

Histone acetylation modifications: A potential targets for the diagnosis and treatment of papillary thyroid cancer.

Thyroid cancer is a common malignancy of the endocrine system, with papillary thyroid cancer (PTC) being the most common type of pathology. The incidence of PTC is increasing every year. Histone acetylation modification is an important part of epigenetics, regulating histone acetylation levels through histone acetylases and histone deacetylases, which alters the proliferation and differentiation of PTC cells and affects the treatment and prognosis of PTC patients. Histone deacetylase inhibitors induce histone acetylation, resulting in the relaxation of chromatin structure and activation of gene transcription, thereby promoting differentiation, apoptosis, and growth arrest of PTC cells.

Discovering new peripheral plasma biomarkers to identify cognitive decline in type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is an independent risk factor of Alzheimer's disease (AD), and thus identifying who among the increasing T2DM populations may develop into AD is important for early intervention. By using TMT-labeling coupled high-throughput mass spectrometry, we conducted a comprehensive plasma proteomic analysis in none-T2DM people (Ctrl, n = 30), and the age-/sex-matched T2DM patients with mild cognitive impairment (T2DM-MCI, n = 30) or T2DM without MCI (T2DM-nMCI, n = 25). The candidate biomarkers identified by proteomics and bioinformatics analyses were verified by ELISA, and their diagnostic capabilities were evaluated with machine learning. A total of 53 differentially expressed proteins (DEPs) were identified in T2DM-MCI compared with T2DM-nMCI patients. These DEPs were significantly enriched in multiple biological processes, such as amyloid neuropathies, CNS disorders, and metabolic acidosis. Among the DEPs, alpha-1-antitrypsin (SERPINA1), major viral protein (PRNP), and valosin-containing protein (VCP) showed strong correlation with AD high-risk genes APP, MAPT, APOE, PSEN1, and PSEN2. Also, the levels of PP2A cancer inhibitor (CIP2A), PRNP, corticotropin-releasing factor-binding protein (CRHBP) were significantly increased, while the level of VCP was decreased in T2DM-MCI patients compared with that of the T2DM-nMCI, and these changes were correlated with the Mini-Mental State Examination (MMSE) score. Further machine learning data showed that increases in PRNP, CRHBP, VCP, and rGSK-3ß(T/S9) (ratio of total to serine-9-phosphorylated glycogen synthase kinase-3ß) had the greatest power to identify mild cognitive decline in T2DM patients.