Regeneratable bioinspired nanochannels for highly sensitive electrochemical detection of glycated albumin.

Glycated albumin (GA) has been proposed as a reliable diabetes mellitus marker particularly useful in assessing intermediate glycemic control. Herein, we designed a bioinspired nanochannels for biochemical detection based on the host-guest interaction between ß-cyclodextrin and azobenzene. Cyclodextrin was grafted on the inner surface of nanochannels of a nanoporous membrane and azobenzene was tagged to the terminal of GA aptamer, thereby facilitating the orientation of GA aptamer in the nanochannels. The presence of GA was monitored by recording the voltammetric signal of ferricyanide that transported across the nanochannel array. The peak current exhibited a linearity relationship with the GA concentration across a broad range of 1.0 ng mL-1 to 100 µg mL-1, along with a detection limit of 0.18 ng mL-1. Notably, the aptamer could be offloaded under ultraviolet light, regenerating the cyclodextrin functionalized nanochannels for subsequent re-immobilization of the fresh aptamer. The relative standard deviation for seven cycles of regeneration treatment was no more than 1.8 %. The remarkable reusability of the nanochannels offered a cost-effective, sensitive and reproducible aptasensing platform.

ART26.12, a novel fatty acid-binding protein 5 inhibitor, shows efficacy in multiple preclinical neuropathy models.

BACKGROUND: Painful neuropathy is a pathological condition caused by numerous factors including diabetes, chemotherapy or cancer. ART26.12 is a novel fatty acid-binding protein 5 inhibitor, which our group showed could prevent and treat persistent pain in a preclinical model of oxaliplatin-induced peripheral neuropathy. METHODS: In the current study, the efficacy of orally dosed ART26.12 was tested in multiple neuropathy models of different aetiology. Paw withdrawal threshold to von Frey monofilaments and latency to escape a cold plate were used as measurements of mechanical and cold sensitivity. RESULTS: ART26.12 (25 and 50 mg/kg BID), dosed prior to the induction of paclitaxel-induced peripheral neuropathy (PIPN), reversed mechanical allodynia induced by paclitaxel in both male and female rats, and ART26.12 (50 mg/kg BID) prevented the induction of PIPN in female rats. ART26.12 (50 mg/kg BID) also had a protective effect on body weight in the PIPN model. ART26.12 (25 and 100 mg/kg BID) reversed mechanical allodynia when treating established streptozotocin-induced diabetic neuropathy in male rats. In a model of breast cancer-induced bone pain in female rats, ART26.12 (100 mg/kg BID) reversed mechanical allodynia within 1 h of dosing. In the same model, ART26.12 (25 mg/kg BID) reversed mechanical allodynia from day 4 of treatment. CONCLUSION: Overall, these preclinical data suggest that ART26.12 is a safe and efficacious therapeutic drug for continued development towards the prevention and treatment of peripheral neuropathy. SIGNIFICANCE STATEMENT: This work now shows that ART26.12, a novel and selective inhibitor of FABP5, can prevent and treat multiple preclinical models of peripheral neuropathy. Given its excellent safety profile, further work is warranted to develop ART26.12 as a potential therapeutic tool for pain management.

Correlation between pupillary size and depth of focus after the implantation of extended depth of focus intraocular lenses.

PURPOSE: To evaluate whether depth of focus after the implantation of extended depth of focus (EDoF) intraocular lenses (IOLs) correlates with pupillary size. METHODS: This retrospective case series study evaluated eyes undergoing cataract surgery with implantation of EDoF IOLs. At least one month postoperatively, the depth of focus (DoF) was measured to determine the correlation with pupillary size, age, anterior chamber depth (ACD), axial length (AXL), and corneal spherical aberrations (SA). RESULTS: The study evaluated 64 eyes of 49 patients. The mean depth of focus was 2.67 diopters (D). The mean preoperative photopic pupil size was 3.36 mm. A significant negative association was found between preoperative photopic pupil size and depth of focus (r = 0.30, Pearson's correlation coefficient) and between preoperative mesopic pupil size and depth of focus (r = 0.274, Pearson's correlation coefficient).

The antimicrobial property of JY-1, a complex mixture of Traditional Chinese Medicine, is linked to it abilities to suppress biofilm formation and disrupt membrane permeability.

The substantial increase of infections, caused by novel, sudden, and drug-resistant pathogens, poses a significant threat to human health. While numerous studies have demonstrated the antibacterial and antiviral effects of Traditional Chinese Medicine, the potential of a complex mixture of traditional Chinese Medicine with a broad-spectrum antimicrobial property remains underexplored. This study aimed to develop a complex mixture of Traditional Chinese Medicine (TCM), JY-1, and investigate its antimicrobial properties, along with its potential mechanism of action against pathogenic microorganisms. Antimicrobial activity was assessed using a zone of inhibition assay and the drop plate method. Hyphal induction of Candida albicans was conducted using RPMI1640 medium containing 10% FBS, followed by microscopic visualization. Quantitative real-time PCR (RT-qPCR) was employed to quantify the transcript levels of hyphal-specific genes such as HWP1 and ALS3. The impact of JY-1 on biofilm formation was evaluated using both the XTT reduction assay and scanning electron microscopy (SEM). Furthermore, the cell membrane integrity was assessed by protein and nucleic acid leakage assays. Our results clearly showed that JY-1 significantly inhibits the vegetative growth of Candida spp. and Cryptococcus spp. In addition, this complex mixture is effectively against a wide range of pathogenic bacteria, including Staphylococcus aureus, Vancomycin-resistant enterococci, Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae. More interestingly, JY-1 plays a direct anti-viral role against the mammalian viral pathogen vesicular stomatitis virus (VSV). Further mechanistic studies indicate that JY-1 acts to reduce the expression of hyphal specific genes HWP1 and ALS3, resulting in the suppression of the hyphal formation of C. albicans. The antimicrobial property of JY-1 could be attributed to its ability to reduce biofilm formation and disrupt the cell membrane permeability, a process resulting in microbial cell death and the release of cellular contents. Taken together, our work identified a potent broad-spectrum antimicrobial agent, a complex mixture of TCM which might be developed as a potential antimicrobial drug.

Identification, characterisation and expression analysis of peanut sugar invertase genes reveal their vital roles in response to abiotic stress.

KEY MESSAGE: Sucrose invertase activity is positively related to osmotic and salt stress resistance in peanut. Sucrose invertases (INVs) have important functions in plant growth and response to environmental stresses. However, their biological roles in peanut are still not fully revealed. In this research, we identified 42 AhINV genes in the peanut genome. They were highly conserved and clustered into three groups with 24 segmental duplication events occurred under purifying selection. Transcriptional expression analysis exhibited that they were all ubiquitously expressed, and most of them were up-regulated by osmotic and salt stresses, with AhINV09, AhINV23 and AhINV19 showed the most significant up-regulation. Further physiochemical analysis showed that the resistance of peanut to osmotic and salt stress was positively related to the high sugar content and sucrose invertase activity. Our results provided fundamental information on the structure and evolutionary relationship of INV gene family in peanut and gave theoretical guideline for further functional study of AhINV genes in response to abiotic stress.

Breast cancer cells have an increased ferroptosis risk induced by system xc- blockade after deliberately downregulating CYTL1 to mediate malignancy.

Cytokine-like protein 1 (CYTL1) expression is deliberately downregulated during the progression of multiple types of cancers, especially breast cancer. However, the metabolic characteristics of cancer progression remain unclear. Here, we uncovered a risk of breast cancer cells harboring low CYTL1 expression, which is metabolically controlled during malignant progression. We performed metabolism comparison and revealed that breast cancer cells with low CYTL1 expression have highly suppressed transsulfuration activity that is driven by cystathionine ß-synthase (CBS) and contributes to de novo cysteine synthesis. Mechanistically, CYTL1 activated Nrf2 by promoting autophagic Keap1 degradation, and Nrf2 subsequently transactivated CBS expression. Due to the lack of cellular cysteine synthesis, breast cancer cells with low CYTL1 expression showed hypersensitivity to system xc- blockade-induced ferroptosis in vitro and in vivo. Silencing CBS counteracted CYTL1-mediated ferroptosis resistance. Our results show the importance of exogeneous cysteine in breast cancer cells with low CYTL1 expression and highlight a potential metabolic vulnerability to target.

Lifestyle-based nomogram for identifying the Chaoshan inhabitants of China at high risk of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori (HP) infection is associated with various diseases. Early detection can prevent the onset of illness. We constructed a nomogram to predict groups at high risk of HP infection. METHODS: Patients who underwent regular medical check-ups at hospital in Chaoshan, China from March to September 2022 were randomly allocated to the training and validation cohorts. Risk factors including basic characteristics and lifestyle habits associated with HP infection were analyzed by logistic regression analyses. The independent varieties were calculated and plotted into a nomogram. The nomogram was internally validated by receiver operating characteristic curve, calibration, and decision curve analyses (DCAs). RESULTS: Of the 945 patients, 680 were included in the training cohort and 265 in the validation cohort. 356 patients in training cohort with positive 13 C-UBT results served as the infected group, and 324 without infection were the control group. The multivariate regression analyses showed that the risk factors for HP infection included alcohol consumption (OR = 1.29, 95%CI = 0.78-2.13, P = 0.03), family history of gastric disease (OR = 4.35, 95%CI = 1.47-12.84, P = 0.01), living with an HP-positive individual (OR = 18.09, 95%CI = 10.29-31.82, P < 0.0001), drinking hot tea (OR = 1.58, 95%CI = 1.05-2.48, P = 0.04), and infection status of co-drinkers unknown (OR = 2.29, 95%CI = 1.04-5.06, P = 0.04). However, drinking tea > 3 times per day (OR = 0.56, 95%CI = 0.33-0.95, P = 0.03), using serving chopsticks (OR = 0.30, 95%CI = 0.12-0.49, P < 0.0001) were protective factors for HP infection. The nomogram had an area under the curve (AUC) of 0.85 in the training cohort. The DCA was above the reference line within a large threshold range, indicating that the model was better. The calibration analyses showed the actual occurrence rate was basically consistent with the predicted occurrence rate. The model was validated in the validation cohort, and had a good AUC (0.80), DCA and calibration curve results. CONCLUSIONS: This nomogram, which incorporates basic characteristics and lifestyle habits, is an efficient model for predicting those at high risk of HP infection in the Chaoshan region.

Deep learning-based analysis of infrared fundus photography for automated diagnosis of diabetic retinopathy with cataracts.

PURPOSE: To develop deep learning-based networks for the diagnosis of diabetic retinopathy (DR) with cataracts based on infrared fundus images. SETTING: Shanghai General Hospital, Shanghai Eye Disease Prevention & Treatment Center, Shanghai, China. DESIGN: Development and evaluation of an artificial intelligence (AI) diagnostic method. METHODS: A total of 10 665 infrared fundus images from 4553 patients with diabetes were used to train and test the model. For image quality assessment, left and right eye classification, DR diagnosis and grading, and segmentation of 3 DR lesions, an end-to-end software using EfficientNet and UNet was developed. The accuracy and performance of the software in comparison to human experts was evaluated. RESULTS: The model achieved an accuracy of 75.31% for left and right eye classification, 100% for DR grading and diagnosis tasks, and 73.67% for internal test set, with corresponding areas under the curve (AUCs) of 0.88, 1.00, and 0.89, respectively. For DR lesion segmentation, the AUCs of hemorrhagic, microangioma, and exudative lesions were 0.86, 0.66, and 0.84, respectively. In addition, a contrast test of human-machine film reading confirmed the software's high sensitivity (96.3%) and specificity (90.0%) and consistency with the manual film reading group (κ = 0.869, P < .001). This easily deployable software generated reports quickly and promoted efficient DR screening with cataracts in clinical and community settings. CONCLUSIONS: AI-assisted software can perform automatic analysis of infrared fundus images and has substantial application value for the diagnosis of DR patients with cataracts.

Suppression of cAMP/PKA/CREB signaling ameliorates retinal injury in diabetic retinopathy.

The blood-retinal barrier (BRB), homeostasis, neuronal integrity, and metabolic processes are all directly influenced by Müller cells, the most important retinal glial cells. We isolated primary Müller cells from Sprague-Dawley (SD) neonatal rats and treated them with glucose at varying doses. CCK-8 was used to quantify cellular viability, and a TUNEL assay was performed to detect cell apoptosis. ELISA, immunofluorescence, and western blotting were used to assess cAMP/PKA/CREB signaling, Kir4.1, AQP4, GFAP, and VEGF levels, respectively. H&E staining was used to examine histopathological alterations in diabetic retinopathy (DR)-affected retinal tissue in rats. As glucose concentration increases, gliosis of Müller cells became apparent, as evidenced by a decline in cell activity, an increase in apoptosis, downregulation of Kir4.1 level, and overexpression of GFAP, AQP4, and VEGF. Treatments with low, intermediate, and high glucose levels led to aberrant activation of cAMP/PKA/CREB signaling. Interestingly, blocking cAMP and PKA reduced high glucose-induced Müller cell damage and gliosis by a significant amount. Further in vivo results suggested that cAMP or PKA inhibition significantly improved edema, bleeding, and retinal disorders. Our findings showed that high glucose exacerbated Müller cell damage and gliosis via a mechanism involving cAMP/PKA/CREB signaling.

Construction of Ternary Bismuth-Based Heterojunction by Using (BiO)2 CO3 as Electron Bridge for Highly Efficient Degradation of Phenol.

Inspired by nature, it has been considered an effective approach to design artificial photosynthetic system by fabricating Z-scheme photocatalysts to eliminate environmental issues and alleviate the global energy crisis. However, the development of low cost, environment-friendly, and high-efficient photocatalysts by utilizing solar energy still confronts huge challenge. Herein, we constructed a Bi2 O3 /(BiO)2 CO3 /Bi2 MoO6 ternary heterojunction via a facile solvothermal method and calcination approach and used it as a photocatalyst for the degradation of phenol. The optimized Bi2 O3 /(BiO)2 CO3 /Bi2 MoO6 heterojunction delivers a considerable activity for phenol photodegradation with an impressive removal efficiency of 98.8 % and about total organic carbon (TOC) of 68 % within 180 min under visible-light irradiation. The excellent photocatalytic activity was ascribed to the formation of a Z-scheme heterojunction, more importantly, the presence of (BiO)2 CO3 as an electron bridge greatly shortens the migration distance of photogenerated electron from ECB of Bi2 O3 to EVB of Bi2 MoO6 , thus prolonging the lifetime of photogenerated electrons, which is verified by trapping experiments, electron spin-resonance spectroscopy (ESR) results, and density functional theory (DFT) calculations. This work provides a potential strategy to fabricate highly efficient Bi-based Z-scheme photocatalysts with wide application prospects in solar-to-fuel conversion and environmental protection.