GTSE1 promotes nasopharyngeal carcinoma proliferation and angiogenesis by upregulating STMN1.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant tumor with poor survival rate. G2 and S phase-expressed-1 (GTSE1) takes part in the progression of diverse tumors as an oncogene, but its role and potential mechanism in NPC remain unknown. METHODS: The GTSE1 expression was analyzed by western blot in NPC tissues and cells. Knock-down experiments were conducted to determine the function of GTSE1 in NPC by cell counting kit-8, the 5-ethynyl-2'-deoxyuridine (EdU) incorporation experiment, cell scratch wound-healing experiment, transwell assays, tube forming experiment and western blot. In addition, the in vivo role of GTSE1 was addressed in tumor-bearing mice. RESULTS: The expression of was increased in NPC. Silencing of GTSE1 suppressed cell viability, the percent of EdU positive cells, and the number of invasion cells and tubes, but enhanced the scratch ratio in NPC cells. Mechanically, downregulation of GTSE1 decreased the expressions of FOXM1 and STMN1, which were restored with the upregulation of FOXM1. Increased expression of STMN1 reversed the effects of the GTSE1 silencing on proliferation, migration, invasion and angiogenesis of NPC cells. Furthermore, knockdown of GTSE1 repressed the tumor volume and tumor weight of xenografted mice. CONCLUSION: GTSE1 was highly expressed in NPC, and silencing of GTSE1 ameliorated the malignant processes of NPC cells by upregulating STMN1, suggesting a possible therapeutical target for NPC.

A novel BODIPY-based theranostic agent for in vivo fluorescence imaging of cerebral Aß and ameliorating Aß-associated disorders in Alzheimer's disease transgenic mice.

ß-Amyloid (Aß) aggregation is increasingly recognized as both a biomarker and an inducer of the progression of Alzheimer's disease (AD). Here, we describe a novel fluorescent probe P14, developed based on the BODIPY structure, capable of simultaneous visualization and inhibition of Aß aggregation in vivo. P14 shows high binding affinity to Aß aggregates and selectively labels Aß plaques in the brain slices of APP/PS1 mice. Moreover, P14 is able to visualize overloaded Aß in both APP/PS1 and 5 × FAD transgenic mice in vivo. From the aspect of potential therapeutic effects, P14 administration inhibits Aß aggregation and alleviates Aß-induced neuronal damage in vitro, as well as reduces central Aß deposition and ameliorates cognitive impairment in APP/PS1 transgenic mice in vivo. Finally, P14 is applied to monitor the progression of Aß aggregation in the brain of 5 × FAD transgenic mice and the intervention effect itself by fluorescence imaging. In summary, the discovery of this fluorescent agent might provide important clues for the future development of theranostic drug candidates targeting Aß aggregation in AD.

Establishment and verification of a prediction model based on clinical characteristics and computed tomography radiomics parameters for distinguishing benign and malignant pulmonary nodules.

Background: The radiographic classification of pulmonary nodules into benign versus malignant categories is a pivotal component of early lung cancer diagnosis. The present study aimed to investigate clinical and computed tomography (CT) clinical-radiomics nomogram for preoperative differentiation of benign and malignant pulmonary nodules. Methods: This retrospective study included 342 patients with pulmonary nodules who underwent high-resolution CT (HRCT) examination. We assigned them to a training dataset (n=239) and a validation dataset (n=103). There are 1781 tumor characteristics quantified by extracted features from the lesion segmented from patients' CT images. The features with poor reproducibility and high redundancy were removed. Then a least absolute shrinkage and selection operator (LASSO) logistic regression model with 10-fold cross-validation was used to further select features and build radiomics signatures. The independent predictive factors were identified by multivariate logistic regression. A radiomics nomogram was developed to predict the malignant probability. The performance and clinical utility of the clinical-radiomics nomogram was evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: After dimension reduction by the LASSO algorithm and multivariate logistic regression, four radiomic features were selected, including original_shape_Sphericity, exponential_glcm_Maximum Probability, log_sigma_2_0_mm_3D_glcm_Maximum Probability, and ogarithm_firstorder_90Percentile. Multivariate logistic regression showed that carcinoembryonic antigen (CEA) [odds ratio (OR) 95% confidence interval (CI): 1.40 (1.09-1.88)], CT rad score [OR (95% CI): 2.74 (2.03-3.85)], and cytokeratin-19-fragment (CYFRA21-1) [OR (95% CI): 1.80 (1.14-2.94)] were independent influencing factors of malignant pulmonary nodule (all P<0.05). The clinical-radiomics nomogram combining CEA, CYFRA21-1 and radiomics features achieved an area of curve (AUC) of 0.85 and 0.76 in the training group and verification group for the prediction of malignant pulmonary nodules. The clinical-radiomics nomogram demonstrated excellent agreement and practicality, as evidenced by the calibration curve and DCA. Conclusions: The clinical-radiomics nomogram combined of CT-based radiomics signature, along with CYFRA21-1 and CEA, demonstrated strong predictive ability, calibration, and clinical usefulness in distinguishing between benign and malignant pulmonary nodules. The use of CT-based radiomics has the potential to assist clinicians in making informed decisions prior to biopsy or surgery while avoiding unnecessary treatment for non-cancerous lesions.

Miniature mass spectrometer-based point-of-care assay for quantification of metformin and sitagliptin in human blood and urine.

Metformin (MET) and sitagliptin (STG) are widely used as the first-line and long-term oral hypoglycemic agents for managing type 2 diabetes mellitus (T2DM). However, the current lack of convenient and rapid measurement methods poses a challenge for individualized management. This study developed a point-of-care (POC) assay method utilizing a miniature mass spectrometer, enabling rapid and accurate quantification of MET and STG concentrations in human blood and urine. By combining the miniature mass spectrometer with paper spray ionization, this method simplifies the process into three to four steps, requires minimal amounts of bodily fluids (50 µL of blood and 2 µL of urine), and is able to obtain quantification results within approximately 2 min. Stable isotope-labeled internal standards were employed to enhance the accuracy and stability of measurement. The MS/MS responses exhibited good linear relationship with concentration, with relative standard deviations (RSDs) below 25%. It has the potential to provide immediate treatment feedback and decision support for patients and healthcare professionals in clinical practice.

Left bundle branch pacing vs ventricular septal pacing for cardiac resynchronization therapy.

Background: The outcomes of left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP) in patients with heart failure remain to be learned. Objective: The objective of this study was to assess the echocardiographic and clinical outcomes of LBBP, LVSP, and deep septal pacing (DSP). Methods: This retrospective study included patients who met the criteria for cardiac resynchronization therapy (CRT) and underwent attempted LBBP in 5 Mayo centers. Clinical, electrocardiographic, and echocardiographic data were collected at baseline and follow-up. Results: A total of 91 consecutive patients were included in the study. A total of 52 patients had LBBP, 25 had LVSP, and 14 had DSP. The median follow-up duration was 307 (interquartile range 208, 508) days. There was significant left ventricular ejection fraction (LVEF) improvement in the LBBP and LVSP groups (from 35.9 ± 8.5% to 46.9 ± 10.0%, P < .001 in the LBBP group; from 33.1 ± 7.5% to 41.8 ± 10.8%, P < .001 in the LVSP group) but not in the DSP group. A unipolar paced right bundle branch block morphology during the procedure in lead V1 was associated with higher odds of CRT response. There was no significant difference in heart failure hospitalization and all-cause deaths between the LBBP and LVSP groups. The rate of heart failure hospitalization and all-cause deaths were increased in the DSP group compared with the LBBP group (hazard ratio 5.10, 95% confidence interval 1.14-22.78, P = .033; and hazard ratio 7.83, 95% confidence interval 1.38-44.32, P = .020, respectively). Conclusion: In patients undergoing CRT, LVSP had comparable CRT outcomes compared with LBBP.

Prognostic significance of ß2-microglobulin decline index in multiple myeloma.

Purpose: To assess the prognostic significance of ß2-microglobulin decline index (ß2M DI) in multiple myeloma (MM). Methods: 150 MM patients diagnosed with MM were enrolled in this study. Cox proportional hazards model was used to analyze the uni- and multivariate prognosis in training cohort (n=105). A new combined prognostic model containing ß2M DI was built up based on the data in training cohort. The validation group was used to verify the model. Results: ß2M DI showed significant correlation with prognosis in both uni- and multivariate analyses and had a good correlation with complete response (CR) rate and deep remission rate. The ROC and calibration curves in validation cohort (n=45) indicated a good predictive performance of the new model. Based on the median risk score of the training group, we classified patients into high- and low- risk groups. In both training and validation groups, patients in the low-risk group had longer overall survival (OS) time than that in the high-risk group (p<0.05). Conclusion: ß2M DI is a good predictive index for predicting treatment response and survival time in MM patients. The prognostic model added with ß2M DI showed a better correlation with OS.

Antitumor effects of a novel photosensitizer-mediated photodynamic therapy and its influence on the cell transcriptome.

Photodynamic therapy (PDT) is a promising cancer treatment. This study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[ρ-diethylene triamine pentaacetic acid-aminophenyl]-10,15,20-triphenyl-porphyrin (DTP) mediated PDT (DTP-PDT). Cell viability, reactive oxygen species (ROS), and apoptosis were measured with a Cell Counting Kit-8 assay, DCFH-DA fluorescent probe, and Hoechst staining, respectively. Cell apoptosis- and autophagy-related proteins were examined using western blotting. RNA sequencing was used to screen differentially expressed mRNAs (DERs), and bioinformatic analysis was performed to identify the major biological events after DTP-PDT. Our results show that DTP-PDT inhibited cell growth and induced ROS generation in MCF-7 and SGC7901 cells. The ROS scavenger N-acetyl-L-cysteine (NAC) and the P38 MAPK inhibitor SB203580 alleviated DTP-PDT-induced cytotoxicity. DTP-PDT induced cell apoptosis together with upregulated Bax and downregulated Bcl-2, which could also be inhibited by NAC or SB203580. The level of LC3B-II, a marker of autophagy, was increased by DTP-PDT. A total of 3496 DERs were obtained after DTP-PDT. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that DERs included those involved in cytosolic ribosomes, the nuclear lumen, protein binding, cell cycle, protein targeting to the endoplasmic reticulum, and ribosomal DNA replication. Disease Ontology and Reactome enrichment analyses indicated that DERs were associated with a variety of cancers and cell cycle checkpoints. Protein-protein interaction results demonstrated that cdk1 and rps27a ranked in the top 10 interacting genes. Therefore, DTP-PDT could inhibit cell growth and induce cell apoptosis and autophagy, partly through ROS and the P38 MAPK signaling pathway. Genes associated with the cell cycle, ribosomes, DNA replication, and protein binding may be the key changes in DTP-PDT-mediated cytotoxicity.

Application and effect of tension-reducing suture in surgical treatment of hypertrophic scar.

PURPOSE: To investigate the application and effectiveness of tension-reducing suture in the repair of hypertrophic scars. METHODS: A retrospective analysis of clinical data was conducted on 82 patients with hypertrophic scars treated at the Department of Burns and Plastic Surgery of Nanjing Drum Tower Hospital from September 2021 to December 2022. Patients were operated with combination of heart-shaped tension-reducing suturing technique and looped, broad, and deep buried (LBD) suturing technique or conventional suture method. Outcomes of surgical treatment were assessed before and 6 months after surgery using the Patient and Observer Scar Assessment Scale (POSAS) and the Vancouver Scar Scale (VSS). RESULTS: Improvements were achieved on scar quality compared to that preoperatively, with a reduction in scar width (1.7 ± 0.6 cm vs. 0.7 ± 0.2 cm, P < 0.001). Assessment using the POSAS and VSS scales showed significant improvements in each single parameter and total score compared to preoperative values (P < 0.05). The Combination method group achieved better score in total score of VSS scale, in color, stiffness, thickness and overall opinion of PSAS scale, and in vascularity, thickness, pliability and overall opinion of OSAS scale. CONCLUSION: The amalgamation of the heart-shaped tension-reducing suturing technique and the LBD suturing technique has shown promising outcomes, garnering notably high levels of patient satisfaction in the context of hypertrophic scar repair. Patients have exhibited favorable postoperative recoveries, underscoring the clinical merit and the prospective broader applicability of this approach in the realm of hypertrophic scar management.

Endovascular thrombectomy with versus without intravenous thrombolysis in patients with acute basilar artery occlusion: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: The benefit and safety of intravenous thrombolysis before endovascular thrombectomy in patients with acute ischemic stroke caused by basilar artery occlusion (BAO) remains unclear. This article aims to investigate the clinical outcomes and safety of endovascular thrombectomy with versus without intravenous thrombolysis in acute BAO stroke patients. METHODS: We conducted a comprehensive search of PubMed, Embase, Cochrane, and Web of Science databases to identify relevant literature pertaining to patients with acute BAO who underwent endovascular thrombectomy alone or intravenous thrombolysis bridging with endovascular thrombectomy (bridging therapy), until January 10, 2024. The primary outcome was functional independence, defined as a score of 0-2 on the modified Rankin Scale at 90 days. The safety outcome was mortality at 90 days and symptomatic intracranial hemorrhage within 48 h. Effect sizes were computed as risk ratio (RR) with random-effect models. This study was registered in PROSPERO (CRD42023462293). RESULTS: A total of 528 articles were obtained through the search and articles that did not meet the inclusion criteria were excluded. Finally, 2 RCTs and 10 cohort studies met the inclusion criteria. The findings revealed that the endovascular thrombectomy alone group had a lower rate of functional independence compared to the bridging therapy group (29% vs 38%; RR 0.78, 95% CI 0.68-0.88, p < 0.001), lower independent ambulation (39% vs 45%; RR 0.89, 95% CI 0.82-0.98, p = 0.01), and higher mortality (36% vs 28%, RR 1.22, 95% CI 1.08-1.37, p = 0.001). However, no differences were detected in symptomatic intracranial hemorrhage between the two groups (6% vs 4%; RR 1.12, 95% CI 0.74-1.71, p = 0.58). CONCLUSION: Intravenous thrombolysis plus endovascular thrombectomy seemed to led to better functional independence, independent ambulation, and lower risk of mortality without increasing the incidence of intracranial hemorrhage compared to endovascular thrombectomy alone. However, given the non-randomized nature of this study, further studies are needed to confirm these findings.

Built-in Electric Fields in Heterostructured Lamellar Membranes Enable Highly Efficient Rejection of Charged Mass.

Separation membranes with homogeneous charge channels are the mainstream to reject charged mass by forming electrical double layer (EDL). However, the EDL often compresses effective solvent transport space and weakens channel-ion interaction. Here, built-in electric fields (BIEFs) are constructed in lamellar membranes by assembling the heterostructured nanosheets, which contain alternate positively-charged nanodomains and negatively-charged nanodomains. We demonstrate that the BIEFs are perpendicular to horizontal channel and the direction switches alternately, significantly weakening the EDL effect and forces ions to repeatedly collide with channel walls. Thus, highly efficient rejection for charged mass (salts, dyes, and organic acids/bases) and ultrafast water transport are achieved. Moreover, for desalination on four-stage filtration option, salt rejection reaches 99.9% and water permeance reaches 19.2 L m-2 h-1 bar-1. Such mass transport behavior is quite different from that in homogeneous charge channels. Furthermore, the ion transport behavior in nanochannels is elucidated by validating horizontal projectile motion model.

The polysaccharides from Balanophora polyandra enhanced neuronal autophagy to ameliorate brain function decline in natural aging mice through the PI3K/AKT/mTOR signaling pathway.

The decline of aging brain neurons is the main cause of various neurodegenerative disease. This study aimed to examine the impact of Balanophora polyandra polysaccharides (BPP) against aging related neuronal deterioration. C57BL/6 mice were fed with regular feed for 27 months to establish a natural aging mouse model. From 3 months of age, mice in the drug-treated group were respectively fed with feed containing 0.05 or 0.18% BPP until 27 months of age. The effects of BPP treatment on the pathological changes of neurons in mice brain were evaluated, as well as autophagy-related and signaling pathway proteins. BPP treatment had a notable positive impact on the pathological injury of cortical and hippocampal neurons, alleviated neuronal degeneration, and enhanced the staining of Nissl bodies in natural aging mice. Furthermore, BPP upregulated autophagy-related proteins LC3 II/I, Parkin, and PINK1 in the cortex and hippocampus of aging mice, and significantly decreased the expression of p62, PI3K, p-protein Kinase B (AKT), and p-mTOR. Immunofluorescence results showed a reduction in the brightness of LC3, which mainly coexpressed with NeuN in natural aging mice brain, and increased LC3-positive neurons were observed after BPP treatment. Collectively, BPP treatment enhanced neuronal autophagy to improve brain functional degradation through the PI3K/AKT/mTOR signaling in natural aging mice. These finding suggested that BPP has potential to mitigate or delay the neurodegeneration associated with aging and further investigation was needed to validate its efficacy in elderly populations.

Hyperforin ameliorates neuroinflammation and white matter lesions by regulating microglial VEGFR2 /SRC pathway in vascular cognitive impairment mice.

AIM: To explore the neuroprotective potential of hyperforin and elucidate its underlying molecular mechanisms involved in its therapeutic effects against vascular cognitive impairment (VCI). METHODS: The active compounds and possible targets of Hypericum perforatum L. that may be effective against VCI were found by network pharmacology in this research. We utilized bilateral common carotid artery occlusion (BCCAO) surgery to induce a VCI mouse model. Morris water maze (MWM) and Y-maze tests were used to assess VCI mice's cognitive abilities following treatment with hyperforin. To evaluate white matter lesions (WMLs), we utilized Luxol fast blue (LFB) stain and immunofluorescence (IF). Neuroinflammation was assessed using IF, western blot (WB), and enzyme-linked immunosorbent assay (ELISA). The effects of hyperforin on microglia were investigated by subjecting the BV2 microglial cell line to oxygen-glucose deprivation/reperfusion (OGD/R) stimulation. The expressions of VEGFR2 , p-SRC, SRC, VEGFA, and inflammatory markers including IL-10, IL-1ß, TNF-α, and IL-6 were subsequently assessed. RESULTS: The VEGFR2 /SRC signaling pathway is essential for mediating the protective properties of hyperforin against VCI according to network pharmacology analysis. In vivo findings demonstrated that hyperforin effectively improved BCCAO-induced cognitive impairment. Furthermore, staining results showed that hyperforin attenuated WMLs and reduced microglial activation in VCI mice. The hyperforin treatment group's ELISA results revealed a substantial decrease in IL-1ß, IL-6, and TNF-α levels. According to the results of in vitro experiments, hyperforin decreased the release of pro-inflammatory mediators (TNF-α, IL-6, and IL-1ß) and blocked microglial M1-polarization by modulating the VEGFR2 /SRC signaling pathway. CONCLUSION: Hyperforin effectively modulated microglial M1 polarization and neuroinflammation by inhibiting the VEGFR2 /SRC signaling pathways, thereby ameliorating WMLs and cognitive impairment in VCI mice.

Differential diagnosis of rare adrenal cellular schwannomas: A case report.

BACKGROUND: Adrenal cellular schwannomas are exceptionally rare stromal tumors that are often misdiagnosed due to the lack of specific radiological, serological, or clinical features. In this report, we describe the differential diagnosis of a rare adrenal cellular schwannoma. METHODS: A 69-year-old man with a history of persistent hypertension, chronic kidney disease, hypertensive heart disease, and cardiac insufficiency was hospitalized due to bilateral lower extremity edema lasting for 3 months. Plain computed tomography at that time revealed a space-occupying lesion in the right adrenal gland. As serum levels of catecholamines, cortisol, and adrenocorticotropic hormone were within normal ranges, the edema was attributed to the chronic kidney disease and cardiac insufficiency, and the patient was referred to our hospital for surgical treatment. Contrast-enhanced computed tomography revealed heterogeneous enhancement in the adrenal mass indicating pheochromocytoma. An irregularly shaped 5 cm mass with a complete capsule in the right adrenal gland was laparoscopically resected. The postoperative histopathological diagnosis was adrenal cellular schwannoma. RESULTS: The postoperative course was unremarkable and the tumor did not recur during 5 years of follow-up. CONCLUSION: Adrenal cellular schwannoma is a very rare tumor that is extremely difficult to preoperatively diagnose. Histological and immunohistochemical analyses are required for differential diagnosis and confirmation. Cellular schwannomas can transform into malignant peripheral nerve sheath tumors, but not often. Consequently, regular postoperative follow-up is required for such patients, especially imaging.

Exploring the Application of Graphene Oxide-Based Nanomaterials in the Repair of Osteoporotic Fractures.

Osteoporotic fractures are induced by osteoporosis, which may lead to the degradation of bone tissues and microstructures and impair their healing ability. Conventional internal fixation therapies are ineffective in the treatment of osteoporotic fractures. Hence, developing tissue engineering materials is crucial for repairing osteoporotic fractures. It has been demonstrated that nanomaterials, particularly graphene oxide (GO), possess unique advantages in tissue engineering due to their excellent biocompatibility, mechanical properties, and osteoinductive abilities. Based on that, GO-nanocomposites have garnered significant attention and hold promising prospects for bone repair applications. This paper provides a comprehensive insight into the properties of GO, preparation methods for nanocomposites, advantages of these materials, and relevant mechanisms for osteoporotic fracture applications.

Kaempferol ameliorated alcoholic hepatitis through improving intestinal barrier function by targeting miRNA-155 signaling.

INTRODUCTION: To investigate the effect and mechanism of Kaempferol on alcoholic steatohepatitis. METHODS: C57BL/6 N mice were utilized to establish Binge-on-Chronic alcohol exposure mice model. Kaempferol was given as the interventional drug to chronic alcohol-fed mice for six weeks to assess its effects. In vitro, intestinal epithelial Caco-2 cells were stimulated by alcohol, and miRNA-155 mimics were used to further study the effect of kaempferol to miRNA-155 signaling in intestinal epithelial cells. HE staining and oil red O staining were used to observe the liver and intestinal tissue damage in each group of mice, and ALT, AST, IL-1B and TNF-a were detected by kits; LPS expression was detected by ELISA kit, and the expression of IL-1B and TNF-a was assessed by qRT-PCR; activated inflammatory response of liver and colon tissue and the related signalling pathway activation. RESULTS: Kaempferol treatment significantly improved pathological changes such as steatosis and vacuolated lesions in liver tissue of the alcohol diet model group, and reduced serum ALT and AST enzyme activities and liver tissue interleukin-1ß and tumour necrosis factor-α mRNA expression levels. Kaempferol significantly reduced the expression of miRNA-155 in the intestinal tissue of alcohol-fed mice, significantly increased their SOCS1 protein expression, inhibited the activation of nuclear factor kappa-B and significantly increased the production of the intestinal tight junction proteins occludin and ZO-1. What's more, kaempferol significantly reduced serum LPS levels in ASH mice. In vitro experiments showed that compared with the control group, kaempferol significantly inhibited the expression level of miRNA-155 in Caco-2 cells under ethanol exposure, decreased the activation of nuclear factor kappa-B, led to an increase in the expression of SOCS1 protein, and increased the production level of occludin protein in Caco-2 cells under the effect of alcohol. In contrast, overexpression of miRNA-155 significantly decreased occludin and SOCS1 protein production and increased nuclear factor kappa-B activation levels in Caco-2 cells, and the administration of kaempferol significantly inhibited this effect. CONCLUSION: Kaempferol improved the stability of gut barrier function to ameliorate hepatic injury induced by alcohol intake through enhancing occludin protein expression, by targeting miR-155 to inhibit the excessive inflammatory response in the intestine.

Enhancing enzyme immobilization: Fabrication of biosilica-based organic-inorganic composite carriers for efficient covalent binding of D-allulose 3-epimerase.

D-allulose, an ideal low-calorie sweetener, is primarily produced through the isomerization of d-fructose using D-allulose 3-epimerase (DAE; EC 5.1.3.30). Addressing the gap in available immobilized DAE enzymes for scalable commercial D-allulose production, three core-shell structured organic-inorganic composite silica-based carriers were designed for efficient covalent immobilization of DAE. Natural inorganic diatomite was used as the core, while 3-aminopropyltriethoxysilane (APTES), polyethyleneimine (PEI), and chitosan organic layers were coated as the shells, respectively. These tailored carriers successfully formed robust covalent bonds with DAE enzyme conjugates, cross-linked via glutaraldehyde, and demonstrated enzyme activities of 372 U/g, 1198 U/g, and 381 U/g, respectively. These immobilized enzymes exhibited an expanded pH tolerance and improved thermal stability compared to free DAE. Particularly, the modified diatomite with PEI exhibited a higher density of binding sites than the other carriers and the PEI-coated immobilized DAE enzyme retained 70.4 % of its relative enzyme activity after ten cycles of reuse. This study provides a promising method for DAE immobilization, underscoring the potential of using biosilica-based organic-inorganic composite carriers for the development of robust enzyme systems, thereby advancing the production of value-added food ingredients like D-allulose.

Ca-Mg modified attapulgite for phosphate removal and its potential as phosphate-based fertilizer.

The urgent concerns of controlling water body eutrophication and the alleviating phosphorus shortage have led to an urgent need for action. The removal of phosphate from polluted waters and its reuse are essential for the prevention of eutrophication and for the sustainable utilization of phosphate resources. In this study, modified attapulgite with different Ca:Mg molar ratios was synthesized to facilitate the recovery of phosphate, with subsequent use of soil fertilizer. Ca-Mg modified attapulgite with the optimal ratio (ACM-5:3) exhibited an exceptional adsorption quality, achieving a maximum adsorption capacity of 63.2 mg/g. The pseudo-second-order model and Langmuir model could well describe the adsorption kinetics and isotherms, respectively. The adsorption mechanism analyses suggested that the interaction between ACM-5:3 and phosphate depended mainly on ion exchange and electrostatic attraction. Moreover, phosphate-laden-ACM-5:3 demonstrated a significant potential as a phosphorus-releasing fertilizer. It could promote corn growth by ensuring a continuous supply of phosphorus and minimizing phosphorus runoff losses. The above results suggested that ACM-5:3 was a potential adsorbent for efficient phosphate removal and recovery.

Tailored chitosan integration in diatomaceous earth particles as a scaffold for fructosyltransferase immobilization in fructo-oligosaccharide production.

BACKGROUND: Fructo-oligosaccharide (FOS) belongs to the group of short inulin-type fructans and is one of the most important non-digestible bifid-oligosaccharides capable of biotransforming sucrose using fructosyltransferase (FTase). However, there are no immobilized FTase products that can be successfully used industrially. In this study, diatomite was subjected to extrusion, sintering and granulation to form diatomaceous earth particles that were further modified via chitosan aminomethylation for modification. FTase derived from Aspergillus oryzae was successfully immobilized on the modified support via covalent binding. RESULTS: The immobilized enzyme activity was 503 IU g-1 at an enzyme concentration of 0.6 mg mL-1, immobilization pH of 7.0 and contact time of 3 h. Additionally, the immobilization yield was 56.91%. Notably, the immobilized enzyme was more stable under acidic conditions. Moreover, the half-life of the immobilized enzyme was 20.80 and 10.96 times as long as that of the free enzyme at 45 and 60 °C, respectively. The results show good reusability, as evidenced by the 84.77% retention of original enzyme activity after eight cycles. Additionally, the column transit time of the substrate was 35.56 min when the immobilized enzyme was applied in a packed-bed reactor. Furthermore, a consistently high FOS production yield of 60.68% was achieved and maintained over the 15-day monitoring period. CONCLUSIONS: Our results suggest that immobilized FTase is a viable candidate for continuous FOS production on an industrial scale. © 2024 Society of Chemical Industry.

GW9508 ameliorates cognitive dysfunction via autophagy pathway in streptozotocin-induced mouse model of Alzheimer's disease.

BACKGROUND: G protein-coupled receptor 40 (GPR40) is a potential drug target for Alzheimer's disease (AD), and its agonist GW9508 ameliorates cognitive impairment by intravenous administration. OBJECTIVES: The present study was conducted to investigate the efficacy of GW9508 administered peripherally on cognitive dysfunction in streptozotocin (STZ)-induced AD mice. METHODS: Seventy male ICR mice were randomly divided into seven groups: vehicle sham group, model, Donepezil, GW9508-L, GW9508-M, GW9508-H, and GW1100 + GW9508-H groups, and administered either vehicle (artificial cerebrospinal fluid [aCSF]) or STZ (3 mg/kg in the vehicle) once a day (9:00 a.m.) by intracerebroventricular injection bilaterally on day 1 and day 3, respectively. After 2 weeks of recovery, all mice were given drug treatment. Behavioral experiments were applied to test the recognition and spatial memory of mice, while molecular biology experiments such as Western blot, ELISA, and Nissl staining were used to detect the corresponding changes of signaling pathways. RESULTS: Intraperitoneal administration of GW9508 prevented STZ-induced cognitive impairment as well as decreased the level of p-tau and Aß1-42 in plasma and brain. GW9508 upregulated the expression of gut-brain peptides like PYY, CCK, IGF-1, and GLP-1 both in blood circulation and brain and downregulated the expression level of autophagy-related proteins through activating Akt/mTOR signaling pathway. Meanwhile, the treatment effect of GW9508 was reversed by GPR40 antagonist GW1100 significantly. CONCLUSION: Peripheral administration of GW9508 exhibits neuroprotective effects, and it could be a promising therapy for AD. The neuroprotective mechanism of GW9508 was based on promoting gut-brain peptide secretion, activating Akt/mTOR signal pathway, and regulating neuronal autophagy.