Osmundacetone ameliorates Alzheimer's-like pathologies by inhibiting ß-amyloid fibrillation, oxidative damage and neuroinflammation in APP/PS1 transgenic mice.

BACKGROUND: ß-Amyloid (Aß) fibrillation is critical for Aß deposition and cytotoxicity during the progression of Alzheimer's disease (AD). Consequently, anti-Aß monoclonal antibody drugs targeting Aß oligomers and aggregation are considered potential therapeutic strategies for AD treatment. Similar to the working mechanisms of anti-Aß monoclonal antibody drugs, our study identified osmundacetone (OAC), a small-molecule compound isolated from the traditional Chinese medicine Rhizoma Osmundae, as exerting anti-AD effects by targeting Aß. PURPOSE: This study sought to determine whether OAC influences the Aß burden in APP/PS1 mice and to identify potential regulatory mechanisms. METHODS: Five-month-old APP/PS1 mice were injected intraperitoneally with OAC at a dose of 1 mg/kg for 12 weeks. The cognitive functions of the mice were assessed via the Morris water maze test and the open field test. Osmundacetone was analyzed via molecular docking, an isothermal dose‒response fingerprint-cellular context thermal shift assay, a thioflavine T fluorescence assay, and an atomic force microscopy assay to analyze the effects of OAC on Aß fibrillation. Immunofluorescence, immunoblotting, and immunohistochemistry were used to assess Aß clearance, AD pathology, oxidative stress, and inflammatory responses. RESULTS: The innovative biochemical and physical data illustrated that the ability of OAC to inhibit Aß fibrillation was accomplished by binding directly to Aß, which differed from the majority of previously reported natural polyphenols that modulate the Aß content and structure in an indirect manner. The inhibition of Aß fibrosis by OAC subsequently promoted Aß lysosomal degradation, resulting in a decreased Aß burden in APP/PS1 mice. Furthermore, OAC treatment inhibited oxidative damage by upregulating glutathione peroxidase expression and attenuated the production of inflammatory factors by downregulating nuclear factor-kB phosphorylation in APP/PS1 mice. CONCLUSION: These findings demonstrate, for the first time, that OAC could reduce the brain Aß burden in APP/PS1 mice by inhibiting Aß fibrillation through direct binding to Aß and improve cognitive dysfunction by attenuating oxidative damage and neuroinflammation. These findings indicate that OAC may be a promising candidate for the treatment of AD.

Molecularly imprinted polymer gel with superior recognition and adsorption capacity for amphenicol antibiotics in food matrices.

A molecular-imprinted polymer (MIP) gel with high effective recognition of amphenicol antibiotics was synthesized for the first time based on layered double hydroxide (LDH) as the support and initiator, and functionalized ß-cyclodextrin (ß-CD) as the functional monomer. The synergistic effect of molecular imprinting recognition and ß-CD host-guest affinity enabled MIP gel to exhibit excellent selectivity (imprinted factors: 3.9-9.4) and high adsorption capacity (28.9-75.4 mg g-1) for amphenicol antibiotics. Different adsorption isotherms and kinetics models were followed, suggesting heterogeneous single-layer recognition and chemical adsorption. After 5 cycles of adsorption and desorption, the adsorption capacity of MIP gel retained above 83.6 %, demonstrating favorable reproducibility and stability. Under optimal conditions, the method validation showed a satisfactory limit of detection (5-10 µg L-1), good correlation (r2 > 0.9967), and respectable recovery (82.6-105.3 %). The MIP gel was applied to extract amphenicol antibiotics from food matrices, achieving recoveries in the range of 78.3-104.5 %. Importantly, the recognition mechanism was studied in detail using density functional theory. Therefore, the established method demonstrates high sensitivity and can be applied as a new tactic for detecting amphenicol antibiotics in food matrices.

Magnetic resonance imaging combined with serum endolipin and galactagoglobin-3 to diagnose cerebral infarction in the elderly with diabetes mellitus.

BACKGROUND: Magnetic resonance imaging (MRI) combined with serum endothelin and galactagoglobin-3 (Gal-3) can improve the clinical diagnosis of diabetes mellitus complicated with cerebral infarction. AIM: To analyze the clinical value of MRI combined with serum endolipin and Gal-3 for the diagnosis of cerebral infarction in the elderly with diabetes mellitus. METHODS: One hundred and fifty patients with acute cerebral infarction hospitalized between January 2021 and December 2023 were divided into two groups according to comorbid diabetes mellitus, including 62 and 88 cases in the diabetic and nondiabetic cerebral infarction groups. Serum samples were collected to detect the expression of serum endolipoxins, and Gal-3, and cranial MRI was performed at admission. Differences between the two groups were compared to analyze the diagnostic value of these parameters. RESULTS: Serum endolipin and Gal-3 expression were higher in the diabetic cerebral infarction group (P < 0.05). The arterial wall area, vessel area, normalized wall index, and lumen stenosis rate were higher in the diabetic cerebral infarction group, while the rate of arterial lumen moderate and severe stenosis was 48.39% higher (36.36%, P < 0.05). The percentage of large (29.03%) and multiple infarcts (33.87%) in the diabetic cerebral infarction group was higher (13.64% and 20.45%), and the incidence rate of lacunar infarcts was lower (37.10% vs 65.91%) (P < 0.05). The total incidence of arterial plaque in patients in the diabetic cerebral infarction group was 96.77% higher (69.32%), while the incidence of necrotic lipid core plaque was 58.06% higher (26.14%) (P < 0.05). Receiver operating characteristic curve analysis was performed to assess the diagnosis utility of these techniques. MRI in combination with serum endoglin and Gal-3 had the highest area under the curve, the Yoden index, sensitivity and specificity (P < 0.05). CONCLUSION: The expression of serum endolipin and Gal-3 in elderly patients with diabetes mellitus with cerebral infarction showed an elevated trend, and the degree of luminal stenosis was severe. MRI predominantly revealed large and multiple infarct foci. This combined index examination can improve the clinical diagnosis of diabetes mellitus combined with cerebral infarction.

Rhamnolipids-based bio-supramolecular solvents as green and sustainable media for extraction of pyrethroid insecticides in water and food matrices.

A novel bio-supramolecular solvent (bio-SUPRAS) based on rhamnolipids (RLs) was designed for efficient extraction of pyrethroid insecticides in water and food matrices. Benefiting from RLs as amphiphiles equipped with the attractive properties of bio-degradable, low toxicity and high stability, bio-SUPRAS was spontaneously generated through salt induced coagulation. The bio-SUPRAS was characterized by cryo-scanning electron microscope and main factors influencing the extraction performance were investigated in detail. Under the optimized conditions, the method was found to have desirable limits of detection (5∼10 µg l-1), good precision (RSDs<16.9 %) and satisfactory recovery (75.2 %∼94.3 %). More importantly, the extraction mechanism was studied by density functional theory systematically. Following greenness assessment, the technique was successfully used for enrichment of pyrethroid pesticides in real samples before HPLC-UV analysis. Thus, the method showed the outstanding merits of eco-efficient, green, time-saving, and had favorable application prospect to remove trace analytes from intricate sample matrices.

Biomechanical evaluation of ortho-bridge system and proximal femoral nail antirotation in intertrochanteric fractures with lateral wall fracture based on finite element analysis.

Background: The integrity of the lateral wall in femoral intertrochanteric fractures significantly impacts fracture stability and internal fixation. In this study, we compared the outcomes of treating intertrochanteric fractures with lateral wall involvement using the ortho-bridge system (OBS) combined with proximal femoral nail antirotation (PFNA) versus simple PFNA from a biomechanical perspective. Methods: Finite-element models of femoral intertrochanteric fractures with lateral wall involvement were subjected to fixation with OBS combined with PFNA and simple PFNA. Von Mises stress measurements and corresponding displacement assessments for each component of the model, including the proximal femur and lateral wall, were used to evaluate the biomechanical effects of OBS fixation on bone and intramedullary nail stability. Results: Using PFNA alone to fix intertrochanteric fractures with lateral wall involvement resulted in von Mises stress levels on the lateral wall exceeding safe stress tolerances for bone growth. OBS fixation significantly reduced stress on the lateral wall of the femur and minimized the stress on each part of the intramedullary nail, reducing the overall displacement. Conclusion: In cases of intertrochanteric fractures with lateral wall involvement, PFNA fixation alone may compromise the biomechanical integrity of the lateral femoral wall, increasing the risk of postoperative complications. The addition of OBS to PFNA significantly reduces stress on the lateral femoral wall. Consequently, OBS should be considered for lateral wall fixation when managing intertrochanteric fractures combined with lateral wall fractures.

Forward programming of human induced pluripotent stem cells via the ETS variant transcription factor 2: rapid, reproducible, and cost-effective generation of highly enriched, functional endothelial cells.

AIMS: Endothelial cell (EC) dysfunction plays a key role in the initiation and progression of cardiovascular disease. However, studying these disorders in ECs from patients is challenging; hence, the use of human induced pluripotent stem cells (hiPSCs) and their in vitro differentiation into ECs represents a very promising approach. Still, the generation of hiPSC-derived ECs (hECs) remains demanding as a cocktail of growth factors and an intermediate purification step are required for hEC enrichment. Therefore, we probed the utility of a forward programming approach using transgenic hiPSC lines. METHODS AND RESULTS: We have used the transgenic hiPSC line PGP1 ETV2 isoform 2 to explore the in vitro differentiation of hECs via doxycycline-dependent induction of the ETS variant transcription factor 2 (ETV2) and compared these with a standard differentiation protocol for hECs using non-transgenic control hiPSCs. The transgenic hECs were highly enriched without an intermediate purification step and expressed-as non-transgenic hECs and human umbilical vein endothelial cells-characteristic EC markers. The viability and yield of transgenic hECs were strongly improved by applying EC growth medium during differentiation. This protocol was successfully applied in two more transgenic hiPSC lines yielding reproducible results with low line-to-line variability. Transgenic hECs displayed typical functional properties, such as tube formation and LDL uptake, and a more mature phenotype than non-transgenic hECs. Transgenic hiPSCs preferentially differentiated into the arterial lineage; this was further enhanced by adding a high concentration of vascular endothelial growth factor to the medium. We also demonstrate that complexing lentivirus with magnetic nanoparticles and application of a magnetic field enables efficient transduction of transgenic hECs. CONCLUSION: We have established a highly efficient, cost-effective, and reproducible differentiation protocol for the generation of functional hECs via forward programming. The transgenic hECs can be genetically modified and are a powerful tool for disease modelling, tissue engineering, and translational purposes.

Merging Quinoxalin-2(1H)-ones Excitation with Cobaloxime Catalysis: C3 Alkylation of Quinoxalin-2(1H)-ones with Unactivated Alkyl Iodides and Carboxylic Acids under Light.

Reported herein is a practical, economical, and efficient construction of 3-alkylated quinoxalin-2(1H)-ones with alkyl carboxylic acids and alkyl iodides by quinoxalin-2(1H)-one excitation and cobaloxime catalysis. Primary, secondary, and tertiary alkyl iodides and carboxylic acids all could be efficiently transferred into target products with excellent functional group tolerance. Mechanism studies reveal that the quinoxalin-2(1H)-one derivatives could be directly excited and yield alkyl carbon radicals from alkyl carboxylic acids and alkyl iodides with the aid of the cobaloxime complex.

Designing green and recyclable switchable supramolecular deep eutectic solvents for efficient extraction of flavonoids from Scutellariae Radix and mechanism exploration.

A green and recyclable switchable supramolecular deep eutectic solvent (SS-DES) was designed and prepared for effective extraction of flavonoids from Scutellariae Radix. The novel SS-DES has both excellent extraction performance of DES and the host guest inclusion of cyclodextrin, thereby showing superior extraction efficiency and selectivity. The characteristic of polarity switching can endow the SS-DES with achieving homogeneous extraction and rapid two-phase separation, shorting per-treatment time largely. Parameters affecting the extraction performance were investigated by the response surface methodology. The results indicated that the SS-DES showed better extraction yield of total flavonoids (157.95 mg/g) compared with pure DES (135 mg/g) and traditional organic solvent (60 % ethanol, 104.87 mg/g). Moreover, the switching mechanism of SS-DES was characterized by FT-IR and 1H NMR, and the extraction mechanism was studied by density functional theory and molecular docking analysis. After evaluating the ecological impact of the method, the cytotoxicity of SS-DES was investigated and the result displayed that its toxicity was very low or even negligible with the EC50>2000 mg/L. After being adsorbed by macroporous AB-8 resin, the regenerated SS-DES was recycled 5 times and the extraction efficiency still remained above 90 %, indicating the desirable reusability. Therefore, the proposed method was efficient and sustainable, and revealed favorable application prospect for the extraction of bio-active compounds from plant materials.

A 23-year bibliometric analysis of the development of global research on hereditary renal carcinoma.

Objectives: Medical research continues to be extensively devoted to investigating the pathogenesis and treatment approaches of hereditary renal cancer. By aspect including researchers, institutions, countries, journals, and keywords, we conduct a bibliometric analysis of the literature pertaining to hereditary renal cancer over the last 23 years. Methods: From the Web of Science Core Collection, we conducted a search for publications published between January 1, 2000 and November 28, 2023. Reviews and original articles were included. Results: A cumulative count of 2,194 publications met the specified criteria for inclusion. The studies of the included articles involved a collective of 2,402 institutions representing 80 countries. Notably, the United States exhibited the highest number of published documents, constituting approximately 45.49% of the total. The preeminent institution in this discipline is the National Cancer Institute (NCI), which maintains a publication volume of 8.98%. In addition to being the most prolific author (125 publications), Linehan WM's works received the highest number of citations (11,985). In a comprehensive count, 803 journals have published related articles. In the top 10 most recent occurrences were the terms "hereditary leiomyomatosis" and "fumarate hydratase." Conclusion: This is the first bibliometric analysis of the literature on hereditary renal cancer. This article offers a thorough examination of the present status of investigations concerning hereditary renal cancer during the previous 23 years.

Electrochemiluminescence resonance energy transfer detection of HBsAg based on Co doped 3D porous luminol-based conjugates and quencher UiO-66-NH2@Au.

An electrochemiluminescence (ECL) biosensor based on ECL resonance energy transfer (ECL-RET) was designed to sensitively detect hepatitis B virus surface antigen (HBsAg). In this ECL-RET system, luminol was employed as ECL donor, and gold nanoparticles functionalized zirconium organoskeleton (UiO-66-NH2@Au) was prepared and served as ECL acceptor. The UiO-66-NH2@Au possessed an ultraviolet-visible (UV-vis) absorption between 400 nm and 500 nm, and the absorption spectra overlapped with the ECL spectrum of luminol. Furthermore, Graphene oxide-poly(aniline-luminol)-cobalt nanoparticles conjugates (GO-PALu-Co) was prepared to optimize the ECL behavior through the catalysis of Cobalt nanoparticles and served as a stable 3D porous film to load capture probe primary antibody (Ab1). Based on the ECL-RET biosensing method, the UiO-66-NH2@Au-labeled Ab2 and target HBsAg could pair with primary antibody Ab1 to form sandwich-type structure, and the ECL signal of GO-PALu-Co was quenched. Under optimized experimental conditions, the ECL-RET analytical method represented eminent analytical performance for HBsAg detection with a wide linear relationship from 2.2 × 10-13 to 2.2 × 10-5 mg/mL, and a detection limit of 9 × 10-14 mg/mL (S/N = 3), with spiked sample recoveries ranging from 97.27 % to 102.73 %. The constructed sensor has good stability, reproducibility, and specificity. It can be used to detect HBsAg in human serum and has the potential to be used for the sensitive detection of other disease biomarkers.

[Effects of Different Proportions of Ammonium Sulfate Replacing Urea on Soil Nutrients and Rhizosphere Microbial Communities].

In order to investigate the effects of ammonium sulfate, an industrial by-product, on soil nutrients and microbial community when applied in different proportions instead of using urea as nitrogen fertilizer, a pot corn experiment was conducted. A completely randomized block experimental design was used, with a total of five treatments:CK (no fertilization), U10S0 (100 % urea), U8S2 (80 % urea + 20 % ammonium sulfate), U6S4(60 % urea + 40 % ammonium sulfate), and U0S10 (100 % ammonium sulfate). The basic physical and chemical properties of soil and the dry weight of maize plants were determined by conventional methods, and microbial sequencing was performed using the Illumina NovaSeq platform. The experiment results showed that:① In each growth stage of maize, the pH of soil treated with fertilization (7.85-8.15) was decreased compared with that of CK (8.1-8.21), and the pH showed a decreasing trend with the increase in ammonium sulfate content. ② The soil available nitrogen content increased gradually with the increase in the ammonium sulfate ratio at each growth stage of maize. Compared with that in the CK and U10S0 treatments, the ratio in the U0S10 treatment increased 30.56 % to 63.68 % and 13.22 % to 38.43 %, respectively. The variation trend of organic carbon content was opposite to that of available nitrogen (U8S2 > U6S4 > U0S10), and the addition of ammonium sulfate was still higher than that of U10S0 at other growth stages except for the seedling stage. ③ The protease activity of all fertilization treatments was higher than that of the control, and the protease activity was gradually enhanced with the continuous growth of corn and the increase in the ammonium sulfate ratio. The protease activity of the U0S10 treatment was higher than that of the U10S0 treatment at each growth stage of corn, which increased by 10.54 %-100 %. Soil sucrase activity ranged from 0.04 to 0.24 mg·(g·24 h)-1, and those in the U0S10 treatments were significantly higher than those in the U10S0 and CK treatments at all growth stages, increasing by 20.32 % to 99.16 % and 24.31 % to 79.33 %, respectively. ④ The species abundance of bacteria and fungi in maize rhizosphere under all fertilization treatments were lower than those under the CK treatment, followed by those under the U10S0 treatment. The species diversity trend of the bacterial community in the three treatments with ammonium sulfate replacing urea were U8S2 > U0S10 > U6S4, and that of fungi were U6S4 > U8S2 > U0S10. ⑤ The maize dry weight of the U10S0 treatment and U0S10 treatment was the highest, which was 39.47 % and 36.16 % higher than that of the CK treatment, respectively, but the difference was not significant. The Pearson model showed that the species abundance and diversity of soil rhizosphere fungi and bacteria were affected by relevant environmental variables, among which pH value and soil available nitrogen content were the most important factors affecting microbial diversity. In conclusion, when corn planting in calcareous brown soil, replacing urea with a certain proportion of ammonium sulfate can improve soil nutrients more than urea alone, which affects the growth and rhizosphere microbial community of corn to a certain extent and has a greater yield.

Different interfaces for stabilizing liquid-liquid, liquid-gel and gel-gel emulsions: Design, comparison, and challenges.

Interfaces play essential roles in the stability and functions of emulsion systems. The quick development of novel emulsion systems (e.g., water-water emulsions, water-oleogel emulsions, hydrogel-oleogel emulsions) has brought great progress in interfacial engineering. These new interfaces, which are different from the traditional water-oil interfaces, and are also different from each other, have widened the applications of food emulsions, and also brought in challenges to stabilize the emulsions. We presented a comprehensive summary of various structured interfaces (stabilized by mixed-layers, multilayers, particles, nanodroplets, microgels etc.), and their characteristics, and designing strategies. We also discussed the applicability of these interfaces in stabilizing liquid-liquid (water-oil, water-water, oil-oil, alcohol-oil, etc.), liquid-gel, and gel-gel emulsion systems. Challenges and future research aspects were also proposed regarding interfacial engineering for different emulsions. Emulsions are interface-dominated materials, and the interfaces have dynamic natures, as the compositions and structures are not constant. Biopolymers, particles, nanodroplets, and microgels differed in their capacity to get absorbed onto the interface, to adjust their structures at the interface, to lower interfacial tension, and to stabilize different emulsions. The interactions between the interface and the bulk phases not only affected the properties of the interface, but also the two phases, leading to different functions of the emulsions. These structured interfaces have been used individually or cooperatively to achieve effective stabilization or better applications of different emulsion systems. However, dynamic changes of the interface during digestion are only poorly understood, and it is still challenging to fully characterize the interfaces.

Lead Isotope Signatures and Source Identification of Heavy Metals in Vegetable Soils Irrigated with Swine Wastewater of Jiangxi Province, China.

The rapid development of livestock and poultry industry in China has caused serious environment pollution problems. To understand the heavy metals accumulation and identify their sources, 7 heavy metals contents and lead isotope ratios were determined in 24 soil samples from vegetable fields irrigated with swine wastewater in Dongxiang County, Jiangxi Province, China. The results showed that the concentration of Cr, Ni, Cu, Zn, As, Cd and Pb in the swine wastewater irrigated vegetable soils varied from 38.5 to 86.4, 7.57 to 30.6, 20.0 to 57.1, 37.5 to 174, 9.18 to 53.1, 0.043 to 0.274 and 12.8 to 37.1 mg/kg, respectively. The soils were moderately to heavily polluted by As, moderately polluted by Cr, Ni, Cu, Zn and Cd, and unpolluted to moderately polluted by Pb. Sampling soils were classified as moderately polluted according to the Nemerow comprehensive pollution index. Lead isotope and Principal Component Analysis (PCA) analysis indicated that swine wastewater irrigation and atmospheric deposition were the primary sources of the heavy metals.

Advanced lithography materials: From fundamentals to applications.

The semiconductor industry has long been driven by advances in a nanofabrication technology known as lithography, and the fabrication of nanostructures on chips relies on an important coating, the photoresist layer. Photoresists are typically spin-coated to form a film and have a photolysis solubility transition and etch resistance that allow for rapid fabrication of nanostructures. As a result, photoresists have attracted great interest in both fundamental research and industrial applications. Currently, the semiconductor industry has entered the era of extreme ultraviolet lithography (EUVL) and expects photoresists to be able to fabricate sub-10 nm structures. In order to realize sub-10 nm nanofabrication, the development of photoresists faces several challenges in terms of sensitivity, etch resistance, and molecular size. In this paper, three types of lithographic mechanisms are reviewed to provide strategies for designing photoresists that can enable high-resolution nanofabrication. The discussion of the current state of the art in optical lithography is presented in depth. Practical applications of photoresists and related recent advances are summarized. Finally, the current achievements and remaining issues of photoresists are discussed and future research directions are envisioned.

Preparation of PLCL/ECM nerve conduits by electrostatic spinning technique and evaluationin vitroandin vivo.

Objective. Artificial nerve scaffolds composed of polymers have attracted great attention as an alternative for autologous nerve grafts recently. Due to their poor bioactivity, satisfactory nerve repair could not be achieved. To solve this problem, we introduced extracellular matrix (ECM) to optimize the materials.Approach.In this study, the ECM extracted from porcine nerves was mixed with Poly(L-Lactide-co-ϵ-caprolactone) (PLCL), and the innovative PLCL/ECM nerve repair conduits were prepared by electrostatic spinning technology. The novel conduits were characterized by scanning electron microscopy (SEM), tensile properties, and suture retention strength test for micromorphology and mechanical strength. The biosafety and biocompatibility of PLCL/ECM nerve conduits were evaluated by cytotoxicity assay with Mouse fibroblast cells and cell adhesion assay with RSC 96 cells, and the effects of PLCL/ECM nerve conduits on the gene expression in Schwann cells was analyzed by real-time polymerase chain reaction (RT-PCR). Moreover, a 10 mm rat (Male Wistar rat) sciatic defect was bridged with a PLCL/ECM nerve conduit, and nerve regeneration was evaluated by walking track, mid-shank circumference, electrophysiology, and histomorphology analyses.Main results.The results showed that PLCL/ECM conduits have similar microstructure and mechanical strength compared with PLCL conduits. The cytotoxicity assay demonstrates better biosafety and biocompatibility of PLCL/ECM nerve conduits. And the cell adhesion assay further verifies that the addition of ECM is more beneficial to cell adhesion and proliferation. RT-PCR showed that the PLCL/ECM nerve conduit was more favorable to the gene expression of functional proteins of Schwann cells. Thein vivoresults indicated that PLCL/ECM nerve conduits possess excellent biocompatibility and exhibit a superior capacity to promote peripheral nerve repair.Significance.The addition of ECM significantly improved the biocompatibility and bioactivity of PLCL, while the PLCL/ECM nerve conduit gained the appropriate mechanical strength from PLCL, which has great potential for clinical repair of peripheral nerve injuries.

Analysis of Inclisiran in the US FDA Adverse Event Reporting System (FAERS): a focus on overall patient population and sex-specific subgroups.

BACKGROUND: Our study aimed to identify inclisiran-related adverse events(AEs) for primary hypercholesterolemia and arteriosclerotic cardiovascular disease(ASCVD) from the US FDA Adverse Event Reporting System (FAERS) database, analyzing its links to AEs in the overall patient population and sex-specific subgroups to improve medication safety. METHODS: We analyzed inclisiran-related AEs signals by using statistical methods like Reporting Odds Ratio (ROR), Proportional Reporting Ratios (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma-Poisson Shrinker (MGPS). RESULTS: Analyzing 2,400 AE reports with inclisiran as the primary suspected drug in the FAERS database, we identified 70 AE signals over 13 organ systems using the above four methods. Notable findings were strong signals for systemic diseases and various reactions at the site of administration (ROR 1.49, 95% CI 1.41-1.57), and various musculoskeletal and connective tissue diseases (ROR 4.07, 95% CI 3.83-4.03) in overall and gender-specific populations. Myalgia, a new ADE signal not in the drug insert, was a top signal by intensity and frequency (ROR 14.76, 95% CI 12.84-16.98). CONCLUSION: Our study revealed the strongest AE signals associated with inclisiran in both the overall population and gender subgroups, highlighting potential risks in clinical medication use and guiding balanced clinical decision-making.

Tetraspanin CD82 Correlates with and May Regulate S100A7 Expression in Oral Cancer.

Many metastatic cancers with poor prognoses correlate to downregulated CD82, but exceptions exist. Understanding the context of this correlation is essential to CD82 as a prognostic biomarker and therapeutic target. Oral squamous cell carcinoma (OSCC) constitutes over 90% of oral cancer. We aimed to uncover the function and mechanism of CD82 in OSCC. We investigated CD82 in human OSCC cell lines, tissues, and healthy controls using the CRISPR-Cas9 gene knockout, transcriptomics, proteomics, etc. CD82 expression is elevated in CAL 27 cells. Knockout CD82 altered over 300 genes and proteins and inhibited cell migration. Furthermore, CD82 expression correlates with S100 proteins in CAL 27, CD82KO, SCC-25, and S-G cells and some OSCC tissues. The 37-50 kDa CD82 protein in CAL 27 cells is upregulated, glycosylated, and truncated. CD82 correlates with S100 proteins and may regulate their expression and cell migration. The truncated CD82 explains the invasive metastasis and poor outcome of the CAL 27 donor. OSCC with upregulated truncated CD82 and S100A7 may represent a distinct subtype with a poor prognosis. Differing alternatives from wild-type CD82 may elucidate the contradictory functions and pave the way for CD82 as a prognostic biomarker and therapeutic target.

Extending Unique 1D Double-Chains to 2D Layers with Birefringent Gain by Introducing a Hydroxyl Group.

It remains a significant hurdle for discovering birefringent materials in the deep ultraviolet (DUV, λ < 200 nm). It is well-known that the OH anions are recognized for their capability to eliminate the dangling bonds from terminal oxygen atoms, promoting the ultraviolet (UV) cutoff edge blueshift and regulating the crystal structure. Here, two new barium hydroxyborates, Ba3B11O18(OH)3(H2O) (BaBOH) and Na2BaB10O16(OH)2(H2O)2 (NaBaBOH), were designed and synthesized while displaying different dimensions. Remarkably, BaBOH presents novel one-dimensional (1D) [B22O37(OH)6]∞ double-chains formed by a new fundamental building block (FBB)[B11O21(OH)3]. NaBaBOH possesses a 2D [B10O16(OH)2]∞ layer with a less common FBB [B10O19(OH)2]. They enrich the structural diversity of hydroxyborates. Moreover, NaBaBOH exhibits a broad transparent window within the DUV spectral range (<190 nm) and possesses a favorable birefringence of 0.064. Furthermore, detailed summaries and structural comparisons have been implemented for all hydroxyborates containing alkali and alkaline-earth metals. This reveals that the OH group modulation strategy can be appropriately employed for the structural design.

The association of leader-member exchange and team-member exchange with nurses' innovative behaviours: A cross-sectional study.

AIM: To measure the association of leader-member exchange and team-member exchange with nurses' innovative behaviours through social exchange theory. BACKGROUND: The field of nursing is actively advocating innovation. Other fields have proven that leader-member exchange and team-member exchange can promote innovative behaviour, but such an association is not clear in nursing. DESIGN: A cross-sectional study. METHODS: A total of 560 nurses were selected from five tertiary hospitals in Henan Province (China) by multistage sampling. Data were collected from a self-report questionnaire. Thirty nurses in the pre-survey were used to verify the validity of the questionnaire. SPSS PROCESS macro was used to verify the association of leader-member exchange and team-member exchange with nurses' innovative behaviours. RESULTS: Leader-member exchange and team-member exchange were significantly associated with nurses' innovative behaviours, and team-member exchange had a mediating effect on the relationship between leader-member exchange and innovative behaviour. CONCLUSIONS: Leader-member exchange and team-member exchange positively affect nurses' innovative behaviours. Leader-member exchange can promote nurses' innovative behaviours through the mediating role of team-member exchange. IMPACT: This study indicated that leader-member exchange and team-member exchange should be given more attention in promoting nurses' innovative behaviours. This finding has implications for the promotion of innovative behaviours in nurses. Leaders need to focus on the innovative needs of nurses and offer support. Meanwhile, leadership training programs are necessary for managers to create positive team relationships. PATIENT OR PUBLIC CONTRIBUTION: No patient or public involvement.

pH-responsive CuS/DSF/EL/PVP nanoplatform alleviates inflammatory bowel disease in mice via regulating gut immunity and microbiota.

The clinical treatment of inflammatory bowel disease (IBD) is challenging. We developed copper sulfate (CuS)/disulfiram (DSF)/methacrylic acid-ethyl acrylate copolymer (EL)/polyvinylpyrrolidone (PVP) nanoplatform (CuS/DSF/EL/PVP) and evaluated its efficiency for treating IBD. After oral administration, the pH-sensitive EL protected the CuS/DSF/EL/PVP against degradation by acidic gastric juices. Once the colon was reached, EL was dissolved, releasing DSF and Cu2+. Further, the main in vivo metabolite of DSF can bind to Cu2+ and form copper (II) N, N-diethyldithiocarbamate (CuET), which significantly alleviated acute colitis in mice. Notably, CuS/DSF/EL/PVP outperformed CuS/EL/PVP and DSF/EL/PVP nanoplatforms in reducing colonic pathology and improving the secretion of inflammation-related cytokines (such as IL-4 and IL-10) in the colonic mucosa. RNA-seq analysis revealed that the nanoplatform reduced colonic inflammation and promoted intestinal mucosal repair by upregulating C-type lectin receptor (CLR)-related genes and signaling pathways. Furthermore, CuS/DSF/EL/PVP showed potential for improving colitis Th1/Th17 cells through innate immunity stimulation, down-regulation of inflammatory cytokines, and upregulation of anti-inflammatory cytokines. Additionally, the intervention with CuS/DSF/EL/PVP led to increased intestinal flora diversity, decreased Escherichia-Shigella abundance, and elevated levels of short-chain fatty acid (SCFA)-producing bacteria Prevotella, Lactobacillus, and Bifidobacterium, indicating their potential to modulate the dysregulated intestinal flora and suppress inflammation. STATEMENT OF SIGNIFICANCE: Our study introduces the CuS/DSF/EL/PVP nanoplatform as a therapeutic strategy for treating inflammatory bowel disease (IBD). This approach demonstrates significant efficacy in targeting the colon and alleviating acute colitis in mice. It uniquely modulates gut immunity and microbiota, exhibiting a notable impact on inflammation-related cytokines and promoting intestinal mucosal repair. The nanoplatform's ability to regulate gut flora diversity, combined with its cost-effective and scalable production, positions it as a potentially transformative treatment for IBD, offering new avenues for personalized medical interventions.