Adsorption Dynamics of Uremic Toxins to Cyclodextrin-Coated Magnetic Nano-Adsorbents.

Chronic kidney disease entails a progressive decline in kidney function, hindering the kidneys' ability to excrete fluid, electrolytes, and metabolites. This dysfunction leads to metabolite accumulation in the bloodstream, which can reach toxic concentrations. Hemodialysis is an effective means of treating patients with kidney failure, but it does not clear all toxins effectively. Engineered nano-adsorbents can potentially improve the removal of retained toxins, particularly protein-bound types. Magnetic nanoparticles coated with α-, ß-, and γ-cyclodextrin were synthesized, and physicochemical properties were characterized using thermogravimetric analysis, transmission electron microscopy, dynamic light scattering, and ζ-potential for their physiochemical properties. The effect of surface chemistry and incubation time on toxin adsorption was investigated using quantitative mass spectrometry techniques. All particle types demonstrated toxin adsorption to some level. Overall, the adsorption process was independent of metabolite concentration, suggesting a dynamic interplay between surface properties and solution composition. This insight will contribute to developing innovative adsorbent films designed to remove uremic toxins effectively.

Systematic metabolic profiling of mice with caerulein-induced acute pancreatitis.

Background: Acute pancreatitis (AP) is a complex inflammatory condition with rising incidence globally. Despite various known causes, early diagnosis remains challenging due to limitations in existing biomarkers. Metabolomics offers a promising avenue for identifying novel biomarkers and elucidating underlying pathophysiological mechanisms. Previous AP metabolomics studies primarily focused on analyzing serum, urine, and pancreatic tissues from patients or animal models. However, systematic metabolomics studies that analyze multiple tissues simultaneously are still lacking. The primary aim of our study is to obtain valuable clues to explore the pathophysiological mechanisms of AP and discover novel biomarkers to enable early detection. Methods: Using a mouse model of AP induced by cerulein, we conducted gas chromatography-mass spectrometry (GC-MS) metabolomic analysis on serum, pancreas, liver, spleen, colon, and kidney samples. Twelve male C57BL/6J mice were randomly divided into AP and control (CON) groups. Serum and tissue samples were collected, processed, and analyzed using established protocols. Multivariate statistical analysis was employed to identify differential metabolites and impacted metabolic pathways. Results: Distinct metabolic profiles were observed between AP and CON groups across multiple tissues. Elevated levels of ketone bodies, amino acids, citric acid, and lipids were noted, with significant differences in metabolite levels identified. Notably, 3-hydroxybutyric acid (3-HBA), branched-chain amino acids (BCAAs), phenylalanine, and L-lysine showed consistent alterations, suggesting their potential as early diagnostic biomarkers for AP. Pathway analysis revealed perturbations in several metabolic pathways, providing insights into the pathophysiological mechanisms underlying AP. Conclusions: Our study highlights the utility of metabolomics in identifying potential biomarkers for early diagnosis of AP and elucidating associated metabolic pathways. 3-HBA, BCAAs, phenylalanine and L-lysine emerge as promising biomarkers for further clinical validation. These findings contribute to a better understanding of AP pathophysiology and underscore the potential of metabolomics in precision medicine approaches for AP management.

Characterization and Hemocompatibility of α, ß, and γ Cyclodextrin-Modified Magnetic Nano-Adsorbents.

Kidney dysfunction leads to the retention of metabolites within the blood that are not effectively cleared with conventional hemodialysis. Magnetic nanoparticle (MNP)-based absorbents have inherent properties that make them amenable to capturing toxins in the blood, notably a large surface area that can be chemically modified to enhance toxin capture and the ability to be easily collected from the blood using an external magnetic field. Cyclodextrins (CDs) present a chemical structure that facilitates the binding of small molecules. However, the hemocompatibility of MNPs modified with films composed of different native types of CDs (α, ß, or γ) has not yet been investigated, which is information crucial to the potential clinical application of MNPs to supplement hemodialysis. To this end, films of α-, ß-, or γ-CDs were formed on MNPs and characterized. The impact of these films on the adsorbed protein structure, composition of key adsorbed proteins, and clotting kinetics were evaluated. It was found that modified MNPs did not significantly affect the secondary structure of some proteins (albumin, lysozyme, α-lactalbumin). The adsorbed proteome from platelet-poor human plasma was evaluated as a function of film properties. Compared to non-modified nanoparticles, CD-modified MNPs exhibited a significant decrease in the adsorbed protein per surface area of MNPs. The immunoblot results showed variations in the adsorption levels of C3, fibrinogen, antithrombin, Factor XI, and plasminogen across CD-modified MNPs. The hemocompatibility experiments showed that CD-modified MNPs are compatible with human whole blood, with no significant impact on platelet activation, hemolysis, or hemostasis.

Naturally selected CD7-directed CAR-T bridging allo-HSCT in refractory acute myeloid leukemia: a case report and review.

Relapsed/refractory acute myeloid leukemia (R/R-AML) has a poor prognosis. CD7 is expressed in leukemic cells in 30% of patients with AML but not in normal myeloid cells. Therefore, it can be a potential target for immunotherapy in patients with R/R-AML. Naturally selected CD7-directed chimeric antigen receptor T cells (CAR-T) have promising effects against AML based on xenotransplantation models. We report a R/R-AML case that achieved complete remission with incomplete hematologic recovery with naturally selected CD7 CAR-T therapy. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) as consolidation early after CAR T therapy, the patient experienced 12 months of disease-free survival to date. Our results confirmed that allogeneic hematopoietic stem cell transplantation after naturally selected CD7 CAR-T therapy can be a potential treatment for patients with CD7-positive R/R-AML.

Multi-residue analysis of four aminoglycoside antibiotic pesticides in plant agricultural products.

Simplified and effective pretreatment methods combined with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for the determination of four aminoglycoside antibiotic pesticides kasugamycin, validamycin, streptomycin sulfate and zhongshengmycin in high starchy content matrix (rice), high water and high acidic content matrix (citrus) and high water content matrix (melon) were established. Single-factor and central composite design (CCD) experiments were employed to optimize the pretreatment conditions, resulting in the optimal factor combinations and achieving scientifically accurate outcomes. Validation results proved satisfactory, with all four target compounds exhibiting correlation coefficients (r) exceeding 0.99 within the linear range in three matrices. The recoveries were 81.5-102.2 %, and both inter-day and intra-day relative standard deviations (RSDs) were below 10.7 %. The limits of detection (LODs) were 0.1-4.0 µg/kg, with limits of quantitation (LOQs) consistently at 50 µg/kg. Furthermore, the methods were applied to potato, grape, and cucumber matrices to further validate their applicability.

Alteration of lncRNA RHPN1-AS1 predicts clinical prognosis and regulates the progression of bladder cancer via modulating miR-485-5p.

BACKGROUND: Exploring effect biomarkers that monitor tumor progression and predict the prognosis could benefit the clinical management of bladder cancer and improve the postoperative life of patients. This study aimed to estimate the function of long non-coding (lnc)RNA RHPN1-AS1 (RHPN1-AS1) in bladder cancer and the potential molecular mechanism. METHODS: The expression of RHPN1-AS1 was evaluated in bladder cancer tissues from 115 patients and cells by polymerase chain reaction. The clinical significance of RHPN1-AS1 was assessed and its effect was also estimated in cell proliferation, migration, and invasion. The underlying molecular mechanism was explored by the dual-luciferase reporter assay. RESULTS: The expression of RHPN1-AS1 was 2.91-fold elevated in bladder cancer, which showed a close correlation with advanced tumor node metastasis stage (P = 0.013) and the presence of lymph node metastasis (P = 0.018). RHPN1-AS1 also served as a poor prognostic indicator (hazard ratio = 2.563) for bladder cancer. The knockdown of RHPN1-AS1 significantly suppressed the proliferation and metastasis ability of bladder cancer cells. Moreover, miR-485-5p was found to mediate the function of RHPN1-AS1 in bladder cancer, which was considered the underlying regulatory mechanism. CONCLUSIONS: RHPN1-AS1 serves as a prognostic biomarker and tumor promoter in bladder cancer via modulating miR-485-5p, which might be a reliable target of bladder cancer therapy.

Novel Tubeimoside I liposomal drug delivery system in combination with gemcitabine for the treatment of pancreatic cancer.

Aim: To evaluate the anti-pancreatic cancer effect of novel Tubeimoside I multifunctional liposomes combined with gemcitabine.Methods: Liposomes were prepared through the thin film hydration method, with evaluations conducted on parameters including encapsulation efficiency (EE%), particle size, polydispersity index (PDI), zeta potential (ZP), storage stability, and release over a 7-day period. The cellular uptake rate, therapeutic efficacy in vitro and in vivo and the role of immune microenvironment modulation were evaluated.Results: The novel Tubeimoside I multifunctional liposomal exhibited good stability, significant anti-cancer activity, and immune microenvironment remodeling effects. Furthermore, it showed a safety profile.Conclusion: This study underscores the potential of Novel Tubeimoside I multifunctional liposomal as a promising treatment option for pancreatic cancer.

[Box: see text].

Surface Cladding Engineering via Oxygen Sulfur Distribution for Stable Electrocatalytic Oxygen Production.

Inevitable leaching and corrosion under anodic oxidative environment greatly restrict the lifespan of most catalysts with excellent primitive activity for oxygen production. Here, based on Fick' s Law, we present a surface cladding strategy to mitigate Ni dissolution and stabilize lattice oxygen triggering by directional flow of interfacial electrons and strong electronic interactions via constructing elaborately cladding-type NiO/NiS heterostructure with controlled surface thickness. Multiple in situ characterization technologies indicated that this strategy can effectively prevent the irreversible Ni ions leaching and inhibit lattice oxygen from participating in anodic reaction. Combined with density functional theory calculations, we reveal that the stable interfacial O-Ni-S arrangement can facilitate the accumulation of electrons on surficial NiO side and weaken its Ni-O covalency. This would suppress the overoxidation of Ni and simultaneously fixing the lattice oxygen, thus enabling catalysts with boosted corrosion resistance without sacrificing its activity. Consequently, this cladding-type NiO/NiS heterostructure exhibits excellent performance with a low overpotential of 256 mV after 500 h. Based on Fick's law, this work demonstrates the positive effect of surface modification through precisely adjusting of the oxygen-sulfur exchange process, which has paved an innovative and effective way to solve the instability problem of anodic oxidation.

Realm of hepatitis E: Challenges and opportunities.

Hepatitis E virus (HEV), responsible for widespread viral hepatitis, infects approximately 2.3 billion individuals globally, with a significant mortality burden in Asia. The virus, primarily transmitted through contaminated water and undercooked meat, is often underdiagnosed, particularly in immunocompromised patients. Current HEV treatments, while effective, are limited by adverse effects, necessitating research into safer alternatives. Moreover, HEV's extrahepatic manifestations, impacting the nervous and renal systems, remain poorly understood. This study underscores the imperative for enhanced HEV research, improved diagnostic methods, and more effective treatments, coupled with increased public health awareness and preventive strategies.

Electrochemical synthesis of ß-difluoromethylamide compounds by N-benzenesulfonylacrylamide with difluorine reagents.

A mild and efficient electrochemical method for radical addition, cyclization, and migration reaction was described in this work. A difluoromethyl radical was produced by anodizing CF2HSO2Na. The resulting product was then added to olefin, underwent Smiles cyclization, and migrated to form ß-difluoromethamide compounds after the release of SO2. The process was free from metals and catalysts, gram-grade, and resistant to a variety of electron-rich substrates.

Decreased levels of PTCSC3 promote the deterioration of prostate cancer and affect the prognostic outcome of patients through sponge miR-182-5p.

BACKGROUND: Prostate cancer, characterized by its insidious onset and short overall survival, and has seen a rise in incidence over recent decades. This study aims to investigate the expression and molecular mechanism of lncRNA PTCSC3 (PTCSC3) in prostate cancer in order to develop new prognostic and therapeutic biomarkers. METHODS: The level of PTCSC3 in serum and cell samples of prostate cancer was quantitatively measured using RT-qPCR assays. The correlation between the variation in PTCSC3 levels and clinical indicators of patients was evaluated. The survival status of the prostate cancer patients included in the study was evaluated using Kaplan-Meier curve and multivariable Cox analysis. The impact of PTCSC3 overexpression on cell growth and activity was revealed by CCK-8 and Transwell assays. The targeting relationship between PTCSC3 and miR-182-5p was determined by bioinformatics prediction and luciferase activity. RESULTS: PTCSC3 was found to be downregulated in prostate cancer, and its low levels were associated with short overall survival in patients. It influenced the progression of prostate cancer by targeting miR-182-5p. Increasing PTCSC3 levels suppressed the proliferation, migration and invasion levels of cells, and miR-182-5p mimic counteracted PTCSC3's effects on cells. CONCLUSIONS: As a potential prognostic biological factor for prostate cancer, PTCSC3 may regulate the progression of prostate cancer by sponging miR-182-5p and affect the prognosis of patients.

Filter-Free UV Photodetectors Based on Unipolar Barrier Van der Waals α-In2Se3/h-BN Heterostructures.

Visible-blind ultraviolet (UV) light detection has a wide application range in scenes like space environment monitoring and medical imaging. To realize miniaturized UV detectors with high performance and high integration ability, new device structures without bulky light filters need to be developed based on advanced mechanisms. Here the unipolar barrier van der Waals heterostructure (UB-vdWH) photodetector is reported that realizes filter-free visible-blind UV detection with good stability, robustness, selectivity, and high detection performance. The UB-vdWH shows a responsivity of 2452 A W-1, a photo on-off ratio of 2.94 × 105 and a detectivity of 1.26 × 1015 Jones as a UV detector, owing to the intentionally designed barrier height that suppresses dark current and photoresponse to visible light during the transport process. The good performance remains intact during 104 test cycles or even under high temperatures, which proves the stability, and robustness of the UB-vdWH, thus shows the huge potential for a wider application range.

Machine learning methods for adult OSAHS risk prediction.

BACKGROUND: Obstructive sleep apnea hypopnea syndrome (OSAHS) is a common disease that can cause multiple organ damage in the whole body. Our aim was to use machine learning (ML) to build an independent polysomnography (PSG) model to analyze risk factors and predict OSAHS. MATERIALS AND METHODS: Clinical data of 2064 snoring patients who underwent physical examination in the Health Management Center of the First Affiliated Hospital of Shanxi Medical University from July 2018 to July 2023 were retrospectively collected, involving 24 characteristic variables. Then they were randomly divided into training group and verification group according to the ratio of 7:3. By analyzing the importance of these features, it was concluded that LDL-C, Cr, common carotid artery plaque, A1c and BMI made major contributions to OSAHS. Moreover, five kinds of machine learning algorithm models such as logistic regression, support vector machine, Boosting, Random Forest and MLP were further established, and cross validation was used to adjust the model hyperparameters to determine the final prediction model. We compared the accuracy, Precision, Recall rate, F1-score and AUC indexes of the model, and finally obtained that MLP was the optimal model with an accuracy of 85.80%, Precision of 0.89, Recall of 0.75, F1-score of 0.82, and AUC of 0.938. CONCLUSION: We established the risk prediction model of OSAHS using ML method, and proved that the MLP model performed best among the five ML models. This predictive model helps to identify patients with OSAHS and provide early, personalized diagnosis and treatment options.

Experiences of family caregivers taking care getting lost of persons with dementia: a qualitative study.

BACKGROUND: Getting lost with family members who have dementia is a significant source of stress for family caregivers. In Taiwan, family caregivers develop strategies to deal with dementia persons who may get lost. This study aimed to explore the experiences of family caregivers caring for persons with dementia who have been lost outside the home. METHODS: A descriptive phenomenological method was used. The COREQ checklist was used to ensure the explicit reporting of data. A total of 20 family caregivers caring for persons with dementia who were lost outside their homes were selected from hospital outpatient clinics and a day care center in northern Taiwan using purposive sampling. Data were analyzed using the Giorgi analysis method. RESULTS: Five main themes emerged: (i) surprised persons with dementia lost outside, (ii) using strategies to prevent persons with dementia from getting lost, (iii) using strategies to find lost persons with dementia, (iv) exhaustion in long-term care persons with dementia, and (v) coping with the care load. It was found that family caregivers were surprised, nervous, and worried about persons with dementia being lost outside. They used the first strategy to supervise persons with dementia to prevent external losses. In addition, long-term supervision of persons with dementia led to mental exhaustion in the family caregivers. Finally, the family caregivers learned about loss prevention strategies and obtained family support and care replacement workers to reduce the care burden. CONCLUSIONS: It is essential to teach family caregivers early to prevent persons with dementia from losing external strategies. Nurses also provide long-term care services to reduce the care burden on family caregivers.

Prenatal Inflammatory Exposure Predisposes Offspring to Chronic Kidney Diseases Via the Activation of the eIF2α-ATF4 Pathway.

It has recently become more recognized that renal diseases in adults can originate from adverse intrauterine (maternal) environmental exposures. Previously, we found that prenatal lipopolysaccharide (LPS) exposure can result in chronic renal inflammation, which leads to renal damage in older offspring rats. To test whether prenatal inflammatory exposure predisposes offspring to renal damage, a mouse model of oral adenine consumption-induced chronic kidney disease (CKD) was applied to offspring from prenatal LPS-treated mothers (offspring-pLPS) and age-matched control offspring of prenatal saline-treated mothers (offspring-pSaline). We found that offspring-pLPS mice presented with more severe renal collagen deposition and renal dysfunction after 4 weeks of adenine consumption than sex- and treatment-matched offspring-pSaline controls. To illustrate the underlying molecular mechanism, we subjected offspring-pLPS and offspring-pSaline kidneys to genome-wide transcriptomic analysis. Bioinformatic analysis of the sequencing data, together with further experimental confirmation, revealed a strong activation of the PERK-eIF2α-ATF4-mediated unfolded protein response (UPR) in offspring-pLPS kidneys, which likely contributed to the CKD predisposition seen in offspring-pLPS mice. More importantly, the specific eIF2α-ATF4 signaling inhibitor ISIRB was able to prevent adenine-induced CKD in the offspring-pLPS mice. Our findings suggest that the eIF2α-ATF4-mediated UPR, but not PERK, is likely the major disease-causing pathway in prenatal inflammatory exposure-induced CKD predisposition. Our study also suggests that targeting this signaling pathway is a potentially promising approach for CKD treatment.

Facile synthesis of 2-vinylindolines via a phosphine-mediated α-umpolung/Wittig olefination/cyclization cascade process.

A novel phosphine-mediated α-umpolung/Wittig olefination/cyclization cascade process between o-aminobenzaldehydes and Morita-Baylis-Hillman (MBH) carbonates has been ingeniously developed. This protocol serves as a practical tool for the facile synthesis of a broad range of 2-vinylindolines in moderate to good yields under mild reaction conditions. The applicability of this method was demonstrated with gram-scale reaction and various transformations of the corresponding product.

Increased cell-free DNA is associated with oxidative damage in patients with schizophrenia.

Cell-free DNA (cfDNA) has been found to be elevated in patients with schizophrenia (SZ), potentially derived from activated apoptosis, but the underlying mechanisms remain unknown. Moreover, whether the concentrations of cfDNA are altered with disease stage has not been investigated, which limits its clinical application as an auxiliary diagnostic marker for SZ. Using an improved fluorescence correlation spectroscopy (FCS) method that does not require DNA extraction, we measured the molar concentrations of cfDNA in plasma samples of 191 patients with SZ, 78 patients with mood disorders (MD) and 65 healthy controls (HC). We also analyzed the cfDNA composition from either the nucleus or mitochondria, oxidation markers and biochemical indexes to explore the potential mechanistic associations of the increased cfDNA levels. We found that in SZ patients, the cfDNA levels were significantly increased (P = 0.003) regardless of the different disease stages or antipsychotic medication use. Furthermore, qPCR revealed that cell-free nuclear DNA (cf-nDNA) (P = 0.041) but not cell-free mitochondrial DNA (cf-mtDNA) was elevated in SZ patients. Moreover, decreased SOD activity in SZ patients (P = 0.005) was negatively correlated with cfDNA levels (P = 0.047), and fasting blood glucose was positively correlated with cfDNA levels in SZ patients (P = 0.013). Our study provides evidence to support that the elevated cfDNA may be a convenient, effective and stable trait indicator of SZ. Further analysis showed that it mainly came from nucleus, suggesting increased apoptosis, and potentially related to oxidative stress and high blood glucose levels in patients.

A Reconfigurable Bipolar Image Sensor for High-Efficiency Dynamic Vision Recognition.

Dynamic vision perception and processing (DVPP) is in high demand by booming edge artificial intelligence. However, existing imaging systems suffer from low efficiency or low compatibility with advanced machine vision techniques. Here, we propose a reconfigurable bipolar image sensor (RBIS) for in-sensor DVPP based on a two-dimensional WSe2/GeSe heterostructure device. Owing to the gate-tunable and reversible built-in electric field, its photoresponse shows bipolarity as being positive or negative. High-efficiency DVPP incorporating front-end RBIS and back-end CNN is then demonstrated. It shows a high recognition accuracy of over 94.9% on the derived DVS128 data set and requires much fewer neural network parameters than that without RBIS. Moreover, we demonstrate an optimized device with a vertically stacked structure and a stable nonvolatile bipolarity, which enables more efficient DVPP hardware. Our work demonstrates the potential of fabricating DVPP devices with a simple structure, high efficiency, and outputs compatible with advanced algorithms.

HDAC6 inhibitor promotes reactive oxygen species-meditated clearance of Staphylococcus aureus in macrophage.

Staphylococcus aureus (S. aureus) pneumonia has become an increasingly important public health problem. Recent evidence suggests that epigenetic modifications are critical in the host immune defence against pathogen infection. In this study, we found that S. aureus infection induces the expression of histone deacetylase 6 (HDAC6) in a dose-dependent manner. Furthermore, by using a S. aureus pneumonia mouse model, we showed that the HDAC6 inhibitor, tubastatin A, demonstrates a protective effect in S. aureus pneumonia, decreasing the mortality and destruction of lung architecture, reducing the bacterial burden in the lungs and inhibiting inflammatory responses. Mechanistic studies in primary bone marrow-derived macrophages demonstrated that the HDAC6 inhibitors, tubastatin A and tubacin, reduced the intracellular bacterial load by promoting bacterial clearance rather than regulating phagocytosis. Finally, N-acetyl-L- cysteine, a widely used reactive oxygen species (ROS) scavenger, antagonized ROS production and significantly inhibited tubastatin A-induced S. aureus clearance. These findings demonstrate that HDAC6 inhibitors promote the bactericidal activity of macrophages by inducing ROS, an important host factor for S. aureus clearance and production. Our study identified HDAC6 as a suitable epigenetic modification target for preventing S. aureus infection, and tubastatin A as a useful compound in treating S. aureus pneumonia.

Biomechanical impact of different isthmus positions in mandibular first molar root canals: a finite element analysis.

OBJECTIVE: This study used image-based finite element analysis (FEA) to assess the biomechanical changes in mandibular first molars resulting from alterations in the position of the root canal isthmus. METHODS: A healthy mandibular first molar, characterized by two intact root canals and a cavity-free surface, was selected as the subject. A three-dimensional model for the molar was established using scanned images of the patient's mandibular teeth. Subsequently, four distinct finite element models were created, each representing varied root canal morphologies: non-isthmus (Group A), isthmus located at the upper 1/3 of the root (Group B), middle 1/3 of the root (Group C), and lower 1/3 of the root (Group D). A static load of 200 N was applied along the tooth's longitudinal axis on the occlusal surface to simulate regular chewing forces. The biomechanical assessment was conducted regarding the mechanical stress profile within the root dentin. The equivalent stress (Von Mises stress) was used to assess the biomechanical features of mandibular teeth under mechanical loading. RESULTS: In Group A (without an isthmus), the maximum stress was 22.2 MPa, while experimental groups with an isthmus exhibited higher stresses, reaching up to 29.4 MPa. All maximum stresses were concentrated near the apical foramen. The presence of the isthmus modified the stress distribution in the dentin wall of the tooth canal. Notably, dentin stresses at specific locations demonstrated differences: at 8 mm from the root tip, Group B: 13.6 MPa vs. Group A: 11.4 MPa; at 3 mm from the root tip, Group C: 14.2 MPa vs. Group A: 4.5 MPa; at 1 mm from the root tip, Group D: 25.1 MPa vs. Group A: 10.3 MPa. The maximum stress in the root canal dentin within the isthmus region was located either at the top or bottom of the isthmus. CONCLUSION: A root canal isthmus modifies the stress profile within the dentin. The maximum stress occurs near the apical foramen and significantly increases when the isthmus is located closer to the apical foramina.