Berberine Inhibits KLF4 Promoter Methylation and Ferroptosis to Ameliorate Diabetic Nephropathy in Mice.

Inflammation, oxidative stress, fibrosis, and ferroptosis play important roles in diabetic nephropathy development. Krüppel-like factor 4 (KLF4) is a transcriptional factor, which regulates multiple cell processes and is involved in diabetic nephropathy. Berberine has various biological activities, including anti-inflammation, antioxidative stress, and antiferroptosis. Berberine has been shown to inhibit diabetic nephropathy, but whether it involves KLF4 and ferroptosis remains unknown. We established a diabetic nephropathy mice model and administered berberine to the mice. The kidney function, renal structure and fibrosis, expression of KLF4 and DNA methylation enzymes, DNA methylation of the KLF4 promoter, mitochondria structure, and expression of oxidative stress and ferroptosis markers were analyzed. Berberine rescued kidney function and renal structure and prevented renal fibrosis in diabetic nephropathy mice. Berberine suppressed the expression of DNMT1 and DNMT2 and upregulated KLF4 expression by preventing KLF4 promoter methylation. Berberine inhibited the expression of oxidative stress and ferroptosis markers, maintained mitochondria structure, and prevented ferroptosis. Berberine ameliorates diabetic nephropathy by inhibiting Klf4 promoter methylation and ferroptosis.

Spatial-temporal dynamic evolution of lewy body dementia by metabolic PET imaging.

PURPOSE: Lewy body dementia (LBD) is a neurodegenerative disease with high heterogeneity and complex pathogenesis. Our study aimed to use disease progression modeling to uncover spatial-temporal dynamic evolution of LBD in vivo, and to explore differential profiles of clinical features, glucose metabolism, and dopaminergic function among different evolution-related subtypes. METHODS: A total of 123 participants (31 healthy controls and 92 LBD patients) who underwent 18F-FDG PET scans were retrospectively enrolled. 18F-FDG PET-based Subtype and Stage Inference (SuStaIn) model was established to illustrate spatial-temporal evolutionary patterns and categorize relevant subtypes. Then subtypes and stages were further related to clinical features, glucose metabolism, and dopaminergic function of LBD patients. RESULTS: This 18F-FDG PET imaging-based approach illustrated two distinct patterns of neurodegenerative evolution originating from the neocortex and basal ganglia in LBD and defined them as subtype 1 and subtype 2, respectively. There were obvious differences between subtypes. Compared with subtype 1, subtype 2 exhibited a greater proportion of male patients (P = 0.045) and positive symptoms such as visual hallucinations (P = 0.033) and fluctuating cognitions (P = 0.033). Cognitive impairment, metabolic abnormalities, dopaminergic dysfunction and progression were all more severe in subtype 2 (all P < 0.05). In addition, a strong association was observed between SuStaIn subtypes and two clinical phenotypes (Parkinson's disease dementia and dementia with Lewy bodies) (P = 0.005). CONCLUSIONS: Our findings based on 18F-FDG PET and data-driven model illustrated spatial-temporal dynamic evolution of LBD and categorized novel subtypes with different evolutionary patterns, clinical and imaging features in vivo. The evolution-related subtypes are associated with LBD clinical phenotypes, which supports the perspective of existence of distinct entities in LBD spectrum.

PET imaging of synaptic vesicle glycoprotein 2 subtype A for neurological recovery in ischemic stroke.

PURPOSE: [18F]SynVesT-1 is a novel radiopharmaceutical for assessing synaptic density in vivo. This study aims to investigate the potential of [18F]SynVesT-1 positron emission tomography (PET) in evaluating neurological recovery in the rat model of ischemic stroke, and to compare its performance with [18F]FDG PET. METHODS: Sprague-Dawley rats were subjected to photothrombotic cerebral infarction, and safinamide was administered intraperitoneally from day 3 to day 14 post-stroke to alleviate neurological deficits. Cylinder test and forelimb placing test were performed to assess the neurological function. MRI, [18F]SynVesT-1 PET/CT and [18F]FDG PET/CT imaging were used to evaluate infarct volume, synaptic density, and cerebral glucose metabolism pre- and post-treatment. [18F]SynVesT-1 and [18F]FDG PET images were compared using Statistical Parametric Mapping (SPM) and region of interest (ROI)-based analysis. Post-mortem histological analysis was performed to validate PET images. RESULTS: Safinamide treatment improved behavioral outcomes in stroke-damaged rats. Both [18F]SynVesT-1 and [18F]FDG PET detected stroke-induced injury, with the injured region being significantly larger in [18F]FDG PET than in [18F]SynVesT-1 PET. Compared with the saline group, radiotracer uptake in the injured area significantly increased in [18F]SynVesT-1 PET after safinamide treatment, whereas no notable change was observed in [18F]FDG PET. Additionally, [18F]SynVesT-1 PET imaging showed a better correlation with neurological function recovery than [18F]FDG PET. Post-mortem analysis revealed increased neuronal numbers, synaptic density, and synaptic neuroplasticity, as well as decreased glia activation in the stroke-injured area after treatment. CONCLUSION: [18F]SynVesT-1 PET effectively quantified spatiotemporal dynamics of synaptic density in the rat model of stroke, and showed different capabilities in detecting stroke injury and neurological recovery compared with [18F]FDG PET. The utilization of [18F]SynVesT-1 PET holds promise as a potential non-invasive biomarker for evaluating ischemic stroke in conjunction with [18F]FDG PET.

Polypyrrole deposited on the core-shell structured nitrogen-doped porous carbon@Ag-MOF for signal amplification detection of chloride ions.

An electrochemical platform for signal amplification probing chloride ions (Cl-) is constructed by the composite integrating core-shell structured nitrogen-doped porous carbon@Ag-based metal-organic frameworks (NC@Ag-MOF) with polypyrrole (PPy). It is based on the signal of solid-state AgCl derived from Ag-MOF, since both NC and PPy have good electrical conductivity and promote the electron transport capacity of solid-state AgCl. NC@Ag-MOF was firstly synthesized with NC as the scaffold and then, PPy was anchored on NC@Ag-MOF by chemical polymerization. The composite NC@Ag-MOF-PPy was utilized to modify the electrode, which exhibited a higher peak current and lower peak potential during Ag oxidation compared with those of Ag-MOF and NC@Ag-MOF-modified electrodes. More importantly, in the coexistence of chloride (Cl-) ions in solution, the NC@Ag-MOF-PPy-modified electrode displayed a fairly stable and sharp peak of solid-state AgCl with the peak potentials gradually approaching zero, which might effectively overcome the background interference caused by electroactive substances. The oxidation peak currents of solid-state AgCl increased linearly with the concentration of  Cl- ions in a broad range of 0.15 µM-40 mM and 40-250 mM, with detection limits of 0.10 µM and 40 mM, respectively. The practical applicability for Cl- ions determination was demonstrated using human serum and urine samples. The results suggest that NC@Ag-MOF-PPy composite could be a promising candidate for the construction of the electrochemical sensor.

Association between chemotherapy for surgically treated rectal cancer and second primary endometrial cancer.

To examine the potential correlation between chemotherapy and the risk of individual of second primary endometrial cancer (SEC) in patients with rectal cancer (RC) and assess survival outcomes. The study employed the Surveillance, Epidemiology, and End Results database (SEER) as the primary data source, it encompasses a substantial cohort of patients diagnosed with RC between 1975 and 2018. This study involved a total of 30,847 individuals diagnosed with RC, of whom 168 individuals (5.45‰) experienced SEC. Among them, 107 patients (3.47‰) received chemotherapy treatment, while 61 patients (1.98‰) did not receive chemotherapy. The analysis of the overall occurrence of SEC revealed a significant association between SEC and chemotherapy treatment. Univariate and multivariate analyses confirmed a significant association between chemotherapy treatment and an increased risk of developing SEC in RC patients. Upon implementation of a dynamic analysis on the variables of relative risk and standardized incidence ratios, the results revealed that the likelihood of SEC escalated in tandem with advancing age. The examination of patients who developed SEC after receiving and not receiving chemotherapy revealed no substantial disparities in the 10-year overall survival (OS) and (cancer-specific survival) CSS rates. The results were the same after propensity score matching. Nevertheless, a notable discrepancy emerged when comparing the OS and CSS rates at 10 years between patients afflicted with SEC subsequent to chemotherapy and those afflicted with primary endometrial cancer, and the result was the same situation in the no-chemotherapy group. The use of chemotherapy in RC patients has been associated with an increased probability of developing specific SEC. Therefore, it is imperative to prioritize efforts aimed at reducing chemotherapy-related SEC occurrences and improving the prognosis of affected individuals.

Heparin-Modified Superparamagnetic Iron Oxide Nanoparticles Suppress Lithium Chloride/Pilocarpine-Induced Temporal Lobe Epilepsy in Rats through Attenuation of Inflammation and Oxidative Stress.

The development of antiepileptic drugs is still a long process. In this study, heparin-modified superparamagnetic iron oxide nanoparticles (UFH-SPIONs) were prepared, and their antiepileptic effect and underlying mechanism were investigated. UFH-SPIONs are stable, homogeneous nanosystems with antioxidant enzyme activity that are able to cross the blood-brain barrier (BBB) and enriched in hippocampal epileptogenic foci. The pretreatment with UFH-SPIONs effectively prolonged the onset of seizures and reduced seizure severity after lithium/pilocarpine (LP)-induced seizures in rats. The pretreatment with UFH-SPIONs significantly decreased the expression of inflammatory factors in hippocampal tissues, including IL-6, IL-1ß, and TNF-α. LP-induced oxidative stress in hippocampal tissues was in turn reduced upon pretreatment with UFH-SPIONs, as evidenced by an increase in the levels of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and a decrease in the level of lipid peroxidation (MDA). Moreover, the LP-induced upregulation of apoptotic cells was decreased upon pretreatment with UFH-SPIONs. Together, these observations suggest that the pretreatment with UFH-SPIONs ameliorates LP-induced seizures and downregulates the inflammatory response and oxidative stress, which exerts neuronal protection during epilepsy.

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.

Development of Pure Certified Reference Material of Cannabidiol.

Cannabidiol (CBD) is the major functional component in hemp and has a broad range of pharmacological applications, such as analgesic, anti-epileptic, anti-anxiety, etc. Currently, CBD is widely used in pharmaceuticals, cosmetics, and food. To ensure the quality and safety of the products containing CBD, more and more related sample testing is being conducted, and the demand for CBD-certified reference material (CRM) has also sharply increased. However, there is currently a lack of relevant reference materials. In this paper, a simple method for preparing CBD CRM was established based on preparative liquid chromatography using crude hemp extract as a raw material. A qualitative analysis of CBD was performed using techniques such as ultraviolet absorption spectroscopy (UV), infrared spectroscopy (IR), mass spectrometry (MS), nuclear magnetic resonance spectroscopy (NMR), and differential scanning calorimetry (DSC). High-performance liquid chromatography (HPLC) was used for the homogeneity and stability tests, and the data were analyzed using an F-test and a T-test, respectively. Then, eight qualified laboratories were chosen for the determination of a certified value using HPLC. The results show that the CBD CRM had excellent homogeneity and good stability for 18 months. The certified value was 99.57%, with an expanded uncertainty of 0.24% (p = 0.95, k = 2). The developed CBD CRM can be used for the detection and quality control of cannabidiol products.

Biomimetic Bone-Like Composite Hydrogel Scaffolds Composed of Collagen Fibrils and Natural Hydroxyapatite for Promoting Bone Repair.

Bone is a complex organic-inorganic composite tissue composed of ∼30% organics and ∼70% hydroxyapatite (HAp). Inspired by this, we used 30% collagen and 70% HAp extracted from natural bone using the calcination method to generate a biomimetic bone composite hydrogel scaffold (BBCHS). In one respect, BBCHS, with a fixed proportion of inorganic and organic components similar to natural bone, exhibits good physical properties. In another respect, the highly biologically active and biocompatible HAp from natural bone effectively promotes osteogenic differentiation, and type I collagen facilitates cell adhesion and spreading. Additionally, the well-structured porosity of the BBCHS provides sufficient growth space for bone marrow mesenchymal stem cells (BMSCs) while promoting substance exchange. Compared to the control group, the new bone surface of the defective location in the B-HA70+Col group is increased by 3.4-fold after 8 weeks of in vivo experiments. This strategy enables the BBCHS to closely imitate the chemical makeup and physical structure of natural bone. With its robust biocompatibility and osteogenic activity, the BBCHS can be easily adapted for a wide range of bone repair applications and offers promising potential for future research and development.

Development and Validation of a Risk Score for Mild Cognitive Impairment in Individuals with Type 2 Diabetes in China: A Practical Cognitive Prescreening Tool.

Aim: Numerous evidence suggests that diabetes increases the risk of cognitive impairment. This study aimed to develop and validate a multivariable risk score model to identify mild cognitive impairment (MCI) in patients with type 2 diabetes mellitus (T2DM). Methods: This cross-sectional study included 1256 inpatients (age: 57.5 ± 11.2 years) with T2DM in a tertiary care hospital in China. MCI was diagnosed according to the criteria recommended by the National Institute on Aging-Alzheimer's Association Workgroup, and a MoCA score of 19-25 indicated MCI. Participants were randomly allocated into the derivation and validation sets at 7:3 ratio. Logistic regression models were used to identify predictors for MCI in the derivation set. A scoring system based on the predictors' beta coefficient was developed. Predictive ability of the risk score was tested by discrimination and calibration methods. Results: Totally 880 (285 with MCI, 32.4%) and 376 (167 with MCI, 33.8%) patients were allocated in the derivation and validation set, respectively. Age, education, HbA1c, self-reported history of severe hypoglycemia, and microvascular disease were identified as predictors for MCI and constituted the risk score. The AUCs (95% CI) of the risk score were 0.751 (0.717, 0.784) in derivation set and 0.776 (0.727, 0.824) in validation set. The risk score showed good apparent calibration of observed and predicted MCI probabilities and was capable of stratifying individuals into 3 risk categories by two cut-off points (low risk: ≤ 3, medium risk: 4-13, and high risk ≥ 14). Conclusion: The risk score based on age, education, HbA1c, self-reported history of severe hypoglycemia, and microvascular disease can effectively assess MCI risk in adults with T2DM at different age. It can serve as a practical prescreening tool for early detection of MCI in daily diabetes care.

Multifunctional nanomaterials via cell cuproptosis and oxidative stress for treating osteosarcoma and OS-induced bone destruction.

Reactive Oxygen Species (ROS) refers to a highly reactive class of oxidizing species that have the potential to induce cellular apoptosis and necrosis. Cuproptosis, a type of cell death, is primarily associated with the effects of copper ions. However, the specific relationship between ROS, cuproptosis, and osteosarcoma (OS) remains relatively unexplored. Additionally, there is limited research on the use of cuproptosis in conjunction with oxidative stress for treating OS and inhibiting tumor-induced bone destruction. To address these gaps, a novel treatment approach has been developed for OS and neoplastic bone destruction. This approach involves the utilization of glutathione (GSH) and pH-responsive organic-inorganic mesoporous silica nanoparticles@Cu2S@oxidized Dextran (short for MCD). The MCD material demonstrates excellent cytocompatibility, osteogenesis, tumor suppression, and the ability to inhibit osteoclast formation. The specific mechanism of action involves the mitochondria of the MCD material inhibiting key proteins in the tricarboxylic acid (TCA) cycle. Simultaneously, the generation of ROS promotes this inhibition and leads to alterations in cellular energy metabolism. Moreover, the MCD biomaterial exhibits promising mild-temperature photothermal therapy in the second near-infrared (NIR-II) range, effectively mitigating tumor growth and OS-induced bone destruction in vivo.

The transformation of multifunctional bio-patch to hydrogel on skin wounds for efficient scarless wound healing.

Hydrogels have been widely used in various biomedical applications, including skin regeneration and tissue repair. However, the capability of certain hydrogels to absorb exudate or blood from surrounding wounds, coupled with the challenge in their long-term storage to prevent bacterial growth, can pose limitations to their efficacy in biological applications. To address these challenges, the development of a multifunctional aloin-arginine-alginate (short for 3A) bio-patch capable of transforming into a hydrogel upon absorbing exudate or blood from neighboring wounds for cutaneous regeneration is proposed. The 3A bio-patch exhibits outstanding features, including an excellent porous structure, swelling properties, and biodegradability. These characteristics allow for the rapid absorption of wound exudates and subsequent transformation into a hydrogel that is suitable for treating skin wounds. Furthermore, the 3A bio-patch exhibits remarkable antibacterial and anti-inflammatory properties, leading to accelerated wound healing and scarless repair in vivo. This study presents a novel approach to the development of cutaneous wound dressing materials.

International consensus on clinical use of presynaptic dopaminergic positron emission tomography imaging in parkinsonism.

PURPOSE: Presynaptic dopaminergic positron emission tomography (PET) imaging serves as an essential tool in diagnosing and differentiating patients with suspected parkinsonism, including idiopathic Parkinson's disease (PD) and other neurodegenerative and non-neurodegenerative diseases. The PET tracers most commonly used at the present time mainly target dopamine transporters (DAT), aromatic amino acid decarboxylase (AADC), and vesicular monoamine type 2 (VMAT2). However, established standards for the imaging procedure and interpretation of presynaptic dopaminergic PET imaging are still lacking. The goal of this international consensus is to help nuclear medicine practitioners procedurally perform presynaptic dopaminergic PET imaging. METHOD: A multidisciplinary task group formed by experts from various countries discussed and approved the consensus for presynaptic dopaminergic PET imaging in parkinsonism, focusing on standardized recommendations, procedures, interpretation, and reporting. CONCLUSION: This international consensus and practice guideline will help to promote the standardized use of presynaptic dopaminergic PET imaging in parkinsonism. It will become an international standard for this purpose in clinical practice.

In vivo cerebral metabolic and dopaminergic characteristics in multiple system atrophy with orthostatic hypotension.

PURPOSE: Multiple system atrophy (MSA) is a rare neurodegenerative disease, often presented with orthostatic hypotension (OH), which is a disabling symptom but has not been very explored. Here, we investigated MSA patients with OH by using positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) and 11C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane (11C-CFT) for in vivo evaluation of the glucose metabolism and dopaminergic function of the brain. METHODS: Totally, 51 patients with MSA and 20 healthy controls (HC) who underwent 18F-FDG PET/CT were retrospectively enrolled, among which 24 patients also underwent 11C-CFT PET/CT. All patients were divided into MSA-OH(+) and MSA-OH(-) groups. Then, statistical parametric mapping (SPM) method was used to reveal the regional metabolic and dopaminergic characteristics of MSA-OH(+) compared with MSA-OH(-). Moreover, the metabolic networks of MSA-OH(+), MSA-OH(-) and HC groups were also constructed and analyzed based on graph theory to find possible network-level changes in MSA patients with OH. RESULTS: The SPM results showed significant hypometabolism in the pons and right cerebellar tonsil, as well as hypermetabolism in the left parahippocampal gyrus and left superior temporal gyrus in MSA-OH(+) compared with MSA-OH(-). A reduced 11C-CFT uptake in the left caudate was also shown in MSA-OH(+) compared with MSA-OH(-). In the network analysis, significantly reduced local efficiency and clustering coefficient were shown in MSA-OH(+) compared with HC, and decreased nodal centrality in the frontal gyrus was found in MSA-OH(+) compared with MSA-OH(-). CONCLUSION: In this study, the changes in glucose metabolism in the pons, right cerebellar tonsil, left parahippocampal gyrus and left superior temporal gyrus were found closely related to OH in MSA patients. And the decreased presynaptic dopaminergic function in the left caudate may contribute to OH in MSA. Taken together, this study provided in vivo pathophysiologic information on MSA with OH from neuroimaging approach, which is essential for a better understanding of MSA with OH.

Associations between complexity of glucose time series and cognitive function in adults with type 2 diabetes.

AIMS: To characterize the comparative contributions of different glycaemic indicators to cognitive dysfunction, and further investigate the associations between the most significant indicator and cognitive function, along with related cerebral alterations. MATERIALS AND METHODS: We performed a cross-sectional study in 449 subjects with type 2 diabetes who completed continuous glucose monitoring and cognitive assessments. Of these, 139 underwent functional magnetic resonance imaging to evaluate cerebral structure and olfactory neural circuit alterations. Relative weight and Sobol's sensitivity analyses were employed to characterize the comparative contributions of different glycaemic indicators to cognitive dysfunction. RESULTS: Complexity of glucose time series index (CGI) was found to have a more pronounced association with mild cognitive impairment (MCI) compared to glycated haemoglobin, time in range, and standard deviation. The proportion and multivariable-adjusted odds ratios (ORs) for MCI increased with descending CGI tertile (Tertile 1: reference group [≥4.0]; Tertile 2 [3.6-4.0] OR 1.23, 95% confidence interval [CI] 0.68-2.24; Tertile 3 [<3.6] OR 2.27, 95% CI 1.29-4.00). Decreased CGI was associated with cognitive decline in executive function and attention. Furthermore, individuals with decreased CGI displayed reduced olfactory activation in the left orbitofrontal cortex (OFC) and disrupted functional connectivity between the left OFC and right posterior cingulate gyrus. Mediation analysis demonstrated that the left OFC activation partially mediated the associations between CGI and executive function. CONCLUSION: Decreased glucose complexity closely relates to cognitive dysfunction and olfactory brain activation abnormalities in diabetes.

A nano-conductive osteogenic hydrogel to locally promote calcium influx for electro-inspired bone defect regeneration.

Conductive nano-materials and electrical stimulation (ES) have been recognized as a synergetic therapy for ordinary excitable tissue repair. It is worth noting that hard tissues, such as bone tissue, possess bioelectrical properties as well. However, insufficient attention is paid to the synergetic therapy for bone defect regeneration via conductive biomaterials with ES. Here, a novel nano-conductive hydrogel comprising calcium phosphate-PEDOT:PSS-magnesium titanate-methacrylated alginate (CPM@MA) was synthesized for electro-inspired bone tissue regeneration. The nano-conductive CPM@MA hydrogel has demonstrated excellent electroactivity, biocompatibility, and osteoinductivity. Additionally, it has the potential to enhance cellular functionality by increasing endogenous transforming growth factor-beta1 (TGF-ß1) and activating TGF-ß/Smad2 signaling pathway. The synergetic therapy could facilitate intracellular calcium enrichment, resulting in a 5.8-fold increase in calcium concentration compared to the control group in the CPM@MA ES + group. The nano-conductive CPM@MA hydrogel with ES could significantly promote electro-inspired bone defect regeneration in vivo, uniquely allowing a full repair of rat femoral defect within 4 weeks histologically and mechanically. These results demonstrate that our synergistic strategy effectively promotes bone restoration, thereby offering potential advancements in the field of electro-inspired hard tissue regeneration using novel nano-materials with ES.

The Presence and Severity of NAFLD are Associated With Cognitive Impairment and Hippocampal Damage.

CONTEXT: Although cognitive impairment in nonalcoholic fatty liver disease (NAFLD) has received attention in recent years, little is known about detailed cognitive functions in histologically diagnosed individuals. OBJECTIVE: This study aimed to investigate the association of liver pathological changes with cognitive features and further explore the underlying brain manifestations. METHODS AND PATIENTS: We performed a cross-sectional study in 320 subjects who underwent liver biopsy. Among the enrolled participants, 225 underwent assessments of global cognition and cognitive subdomains. Furthermore, 70 individuals received functional magnetic resonance imaging scans for neuroimaging evaluations. The associations among liver histological features, brain alterations, and cognitive functions were evaluated using structural equation model. RESULTS: Compared with controls, patients with NAFLD had poorer immediate memory and delayed memory. Severe liver steatosis (odds ratio, 2.189; 95% CI, 1.020-4.699) and ballooning (OR, 3.655; 95% CI, 1.419-9.414) were related to a higher proportion of memory impairment. Structural magnetic resonance imaging showed that patients with nonalcoholic steatohepatitis exhibited volume loss in left hippocampus and its subregions of subiculum and presubiculum. Task-based magnetic resonance imaging showed that patients with nonalcoholic steatohepatitis had decreased left hippocampal activation. Path analysis demonstrated that higher NAFLD activity scores were associated with lower subiculum volume and reduced hippocampal activation, and such hippocampal damage contributed to lower delayed memory scores. CONCLUSIONS: We are the first to report the presence and severity of NAFLD to be associated with an increased risk of memory impairment and hippocampal structural and functional abnormalities. These findings stress the significance of early cognitive evaluation in patients with NAFLD.

Research progress of applications for nano-materials in improved QuEChERS method.

The quick, easy, cheap, effective, rugged, and safe (QuEChERS) approach is widely used in sample pretreatment in agricultural products, food, environment, etc. And nano-materials are widely used in QuEChERS method due to its small size and large specific surface area. In this review, we examine the typical applications of several commonly used nano-materials in improved QuEChERS method. These materials include multi-walled carbon nanotubes (MWCNTs) and their derivatives, magnetic nanoparticles (MNPs), metal organic frameworks (MOFs), covalent organic frameworks (COFs), graphene oxide (GO), lipid and protein adsorbent (LPAS), cucurbituril (CBs), and carbon nano-cages (CNCs), and so on. The strengths and weaknesses of each nano-material are presented, as well as the challenging aspects that need to be addressed in future research. By comparing the applications and the current technology development, this review suggests utilizing artificial intelligence (AI) to screen suitable combinations of purification agents and performing virtual simulation experiments to verify the reliability of this methodology. By doing so, we aim to accelerate the development of new products and decrease the cost of innovation. It also recommends designing smarter pretreatment instruments to enhance the convenience and automation of the sample pretreatment process and reduce the margin for human error.