Critical role of TPRN rings in the stereocilia for hearing.

Inner ear hair cells detect sound vibration through the deflection of mechanosensory stereocilia. Cytoplasmic protein TPRN has been shown to localize at the taper region of the stereocilia, and mutations in TPRN cause hereditary hearing loss through an unknown mechanism. Here, using biochemistry and dual stimulated emission depletion microscopy imaging, we show that the TPRN, together with its binding proteins CLIC5 and PTPRQ, forms concentric rings in the taper region of stereocilia. The disruption of TPRN rings, triggered by the competitive inhibition of the interaction of TPRN and CLIC5 or exogenous TPRN overexpression, leads to stereocilia degeneration and severe hearing loss. Most importantly, restoration of the TPRN rings can rescue the damaged auditory function of Tprn knockout mice by exogenously expressing TPRN at an appropriate level in HCs via promoter recombinant adeno-associated virus (AAV). In summary, our results reveal highly structured TPRN rings near the taper region of stereocilia that are crucial for stereocilia function and hearing. Also, TPRN ring restoration in stereocilia by AAV-Tprn effectively repairs damaged hearing, which lays the foundation for the clinical application of AAV-mediated gene therapy in patients with TPRN mutation.

Bioinspired Three-Mode Photosensitive Synaptic LED for Optical Information Processing.

Inspired by human sense organs, AI is advancing toward multimodal perception, with display technology evolving into intelligent human-computer interaction tools. However, hardware networks with multimodal responses connected by different devices bring problems such as delayed information transfer and inefficiency. Thus, an innovative three-mode photosensitive synaptic LED (PSSL) is first proposed by adding a photosensitive layer indacenodithiophene-benzothiadiazole (IDTBT) to the quantum-dot light-emitting diode (QLED), switched by changing the bias voltage. The self-powered PSSL has a photoresponse range from 310 nm to 808 nm (ultraviolet-near-infrared, UV-NIR). The device exhibits a bipolar response under red and UV light at 1 V. When the voltage reaches the turn-on voltage, the PSSL device turns into a neuromorphic LED, exhibiting conductivity enhancement under red-light irradiation and suppression under UV-light irradiation. As a result, the PSSLs are expected to be applied in the field of optical encryption communication and in neuromorphic display.

Stimulating cardiac glucose oxidation lessens the severity of heart failure in aged female mice.

Heart failure is a prevalent disease worldwide. While it is well accepted that heart failure involves changes in myocardial energetics, what alterations that occur in fatty acid oxidation and glucose oxidation in the failing heart remains controversial. The goal of the study are to define the energy metabolic profile in heart failure induced by obesity and hypertension in aged female mice, and to attempt to lessen the severity of heart failure by stimulating myocardial glucose oxidation. 13-Month-old C57BL/6 female mice were subjected to 10 weeks of a 60% high-fat diet (HFD) with 0.5 g/L of Nω-nitro-L-arginine methyl ester (L-NAME) administered via drinking water to induce obesity and hypertension. Isolated working hearts were perfused with radiolabeled energy substrates to directly measure rates of myocardial glucose oxidation and fatty acid oxidation. Additionally, a series of mice subjected to the obesity and hypertension protocol were treated with a pyruvate dehydrogenase kinase inhibitor (PDKi) to stimulate cardiac glucose oxidation. Aged female mice subjected to the obesity and hypertension protocol had increased body weight, glucose intolerance, elevated blood pressure, cardiac hypertrophy, systolic dysfunction, and decreased survival. While fatty acid oxidation rates were not altered in the failing hearts, insulin-stimulated glucose oxidation rates were markedly impaired. PDKi treatment increased cardiac glucose oxidation in heart failure mice, which was accompanied with improved systolic function and decreased cardiac hypertrophy. The primary energy metabolic change in heart failure induced by obesity and hypertension in aged female mice is a dramatic decrease in glucose oxidation. Stimulating glucose oxidation can lessen the severity of heart failure and exert overall functional benefits.

AAV-Net1 facilitates the trans-differentiation of supporting cells into hair cells in the murine cochlea.

Mechanosensitive hair cells (HCs) in the cochlear sensory epithelium are critical for sound detection and transduction. Mammalian HCs in the cochlea undergo cytogenesis during embryonic development, and irreversible damage to hair cells postnatally is a major cause of deafness. During the development of the organ of Corti, HCs and supporting cells (SCs) originate from the same precursors. In the neonatal cochlea, damage to HCs activates adjacent SCs to act as HC precursors and to differentiate into new HCs. However, the plasticity of SCs to produce new HCs is gradually lost with cochlear development. Here, we delineate an essential role for the guanine nucleotide exchange factor Net1 in SC trans-differentiation into HCs. Net1 overexpression mediated by AAV-ie in SCs promoted cochlear organoid formation and HC differentiation under two and three-dimensional culture conditions. Also, AAV-Net1 enhanced SC proliferation in Lgr5-EGFPCreERT2 mice and HC generation as indicated by lineage tracing of HCs in the cochleae of Lgr5-EGFPCreERT2/Rosa26-tdTomatoloxp/loxp mice. We further found that the up-regulation of Wnt/ß-catenin and Notch signaling in AAV-Net1-transduced cochleae might be responsible for the SC proliferation and HC differentiation. Also, Net1 overexpression in SCs enhanced SC proliferation and HC regeneration and survival after HC damage by neomycin. Taken together, our study suggests that Net1 might serve as a potential target for HC regeneration and that AAV-mediated gene regulation may be a promising approach in stem cell-based therapy in hearing restoration.

Investigation of the Inhibitory Effects of Illicium verum Essential Oil Nanoemulsion on Fusarium proliferatum via Combined Transcriptomics and Metabolomics Analysis.

Fusarium proliferatum is the main pathogen that causes Panax notoginseng root rot. The shortcomings of strong volatility and poor water solubility of Illicium verum essential oil (EO) limit its utilization. In this study, we prepared traditional emulsion (BDT) and nanoemulsion (Bneo) of I. verum EO by ultrasonic method with Tween-80 and absolute ethanol as solvents. The chemical components of EO, BDT, and Bneo were identified by gas chromatography-mass spectrometry (GC-MS) and the antifungal activity and mechanism were compared. The results show that Bneo has good stability and its particle size is 34.86 nm. The contents of (-) -anethole and estragole in Bneo were significantly higher than those in BDT. The antifungal activity against F. proliferatum was 5.8-fold higher than BDT. In the presence of I. verum EO, the occurrence of P. notoginseng root rot was significantly reduced. By combining transcriptome and metabolomics analysis, I. verum EO was found to be involved in the mutual transformation of pentose and glucuronic acid, galactose metabolism, streptomycin biosynthesis, carbon metabolism, and other metabolic pathways of F. proliferatum, and it interfered with the normal growth of F. proliferatum to exert antifungal effects. This study provide a theoretical basis for expanding the practical application of Bneo.

Virtual Reality-Based Exercise Rehabilitation in Cancer-Related Dysfunctions: Scoping Review.

BACKGROUND: Virtual reality-based exercise rehabilitation (VRER) is a promising intervention for patients with cancer-related dysfunctions (CRDs). However, studies focusing on VRER for CRDs are lacking, and the results are inconsistent. OBJECTIVE: We aimed to review the application of VRER in patients with CRDs. METHODS: This scoping review was conducted following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) checklist framework. Publications were included from the time of database establishment to October 14, 2023. The databases were PubMed, Embase, Scopus, Cochrane, Web of Science, ProQuest, arXiv, IEEE Xplore, MedRxiv, CNKI, Wanfang Data, VIP, and SinoMed. The population included patients with cancer. A virtual reality (VR) system or device was required to be provided in exercise rehabilitation as an intervention. Eligible studies focused on VRER used for CRDs. Study selection and data extraction were performed by 2 reviewers independently. Extracted data included authors, year, country, study type, groups, sample size, participant age, cancer type, existing or potential CRDs, VR models and devices, intervention programs and durations, effectiveness, compliance, satisfaction, and safety. RESULTS: We identified 25 articles, and among these, 12 (48%) were randomized clinical trials, 11 (44%) were other experimental studies, and 2 (8%) were observational studies. The total sample size was 1174 (range 6-136). Among the 25 studies, 22 (88%), 2 (8%), and 1 (4%) included nonimmersive VR, immersive VR, and augmented reality, respectively, which are models of VRER. Commercial game programs (17/25, 68%) were the most popular interventions of VRER, and their duration ranged from 3 to 12 weeks. Using these models and devices, VRER was mostly applied in patients with breast cancer (14/25, 56%), leukemia (8/25, 32%), and lung cancer (3/25, 12%). Furthermore, 6 CRDs were intervened by VRER, and among these, postmastectomy syndromes were the most common (10/25, 40%). Overall, 74% (17/23) of studies reported positive results, including significant improvements in limb function, joint range of motion, edema rates, cognition, respiratory disturbance index, apnea, activities of daily living, and quality of life. The compliance rate ranged from 56% to 100%. Overall, 32% (8/25) of studies reported on patient satisfaction, and of these, 88% (7/8) reported satisfaction with VRER. Moreover, 13% (1/8) reported mild sickness as an adverse event. CONCLUSIONS: We found that around half of the studies reported using VRER in patients with breast cancer and postmastectomy dysfunctions through nonimmersive models and commercial game programs having durations of 3-12 weeks. In addition, most studies showed that VRER was effective owing to virtualization and interaction. Therefore, VRER may be an alternate intervention for patients with CRDs. However, as the conclusions were drawn from data with acknowledged inconsistencies and limited satisfaction reports, studies with larger sample sizes and more outcome indictors are required.

Accurate Robot Arm Attitude Estimation Based on Multi-View Images and Super-Resolution Keypoint Detection Networks.

Robot arm monitoring is often required in intelligent industrial scenarios. A two-stage method for robot arm attitude estimation based on multi-view images is proposed. In the first stage, a super-resolution keypoint detection network (SRKDNet) is proposed. The SRKDNet incorporates a subpixel convolution module in the backbone neural network, which can output high-resolution heatmaps for keypoint detection without significantly increasing the computational resource consumption. Efficient virtual and real sampling and SRKDNet training methods are put forward. The SRKDNet is trained with generated virtual data and fine-tuned with real sample data. This method decreases the time and manpower consumed in collecting data in real scenarios and achieves a better generalization effect on real data. A coarse-to-fine dual-SRKDNet detection mechanism is proposed and verified. Full-view and close-up dual SRKDNets are executed to first detect the keypoints and then refine the results. The keypoint detection accuracy, PCK@0.15, for the real robot arm reaches up to 96.07%. In the second stage, an equation system, involving the camera imaging model, the robot arm kinematic model and keypoints with different confidence values, is established to solve the unknown rotation angles of the joints. The proposed confidence-based keypoint screening scheme makes full use of the information redundancy of multi-view images to ensure attitude estimation accuracy. Experiments on a real UR10 robot arm under three views demonstrate that the average estimation error of the joint angles is 0.53 degrees, which is superior to that achieved with the comparison methods.

Carbazolyl-Modified Neutral Ir(III) Complexes for Efficient Detection of Picric Acid in Aqueous Media.

Based on the electron-deficient property of picric acid (PA), two neutral Ir(III) complexes 1 and 2 modified with the electron-rich carbazolyl groups were synthesized and characterized. Both 1 and 2 exhibit aggregation-induced phosphorescence emission (AIPE) properties in THF/H2O. Among them, 2 is extremely sensitive for detecting PA with a limit of detection of 0.15 µM in THF/H2O. Furthermore, the selectivity for PA is significantly higher compared to other analytes, enabling the efficient detection of PA in four common water samples. The density functional theory calculations and the spectroscopic results confirm that the sensing mechanism is photo-induced electron transfer (PET).

Robust Point Cloud Registration for Aircraft Engine Pipeline Systems.

Aircraft engine systems are composed of numerous pipelines. It is crucial to regularly inspect these pipelines to detect any damages or failures that could potentially lead to serious accidents. The inspection process typically involves capturing complete 3D point clouds of the pipelines using 3D scanning techniques from multiple viewpoints. To obtain a complete and accurate representation of the aircraft pipeline system, it is necessary to register and align the individual point clouds acquired from different views. However, the structures of aircraft pipelines often appear similar from different viewpoints, and the scanning process is prone to occlusions, resulting in incomplete point cloud data. The occlusions pose a challenge for existing registration methods, as they can lead to missing or wrong correspondences. To this end, we present a novel registration framework specifically designed for aircraft pipeline scenes. The proposed framework consists of two main steps. First, we extract the point feature structure of the pipeline axis by leveraging the cylindrical characteristics observed between adjacent blocks. Then, we design a new 3D descriptor called PL-PPFs (Point Line-Point Pair Features), which combines information from both the pipeline features and the engine assembly line features within the aircraft pipeline point cloud. By incorporating these relevant features, our descriptor enables accurate identification of the structure of the engine's piping system. Experimental results demonstrate the effectiveness of our approach on aircraft engine pipeline point cloud data.

Disaster literacy in disaster emergency response: a national qualitative study among nurses.

BACKGROUND: As the largest group of healthcare professionals, nurses play an indispensable and crucial role in disaster response. The enhancement of nurses' disaster literacy is imperative for effective disaster emergency management. However, there is currently a lack of knowledge regarding nurses' disaster literacy. This study represents the first attempt to explore the key components and characteristics of disaster literacy among nurses. METHODS: A qualitative descriptive design was employed, and the reporting followed the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines (refer to File S1). The purposive sampling method was utilized. Thirty-one rescue nurses from 31 medical institutions across 25 provinces and regions in China were recruited to participate in the study. The respondents were requested to share their experiences and insights regarding disaster rescue operations. Inductive content analysis was employed for data examination. RESULTS: The results indicated that rescue nurses universally recognized that there was a pressing need to enhance the level of disaster literacy among nurses. The disaster literacy of nurses encompasses nine dimensions: physical and mental quality, disaster rescue general knowledge, professional and technical competence, professional ethics, teamwork, emotional ability, information literacy, leadership, and knowledge transformation. CONCLUSIONS: To ensure national sustainability, government departments, healthcare organizations, and hospital administrators can accurately evaluate the disaster literacy of individual clinical nurses, groups, and the workforce as a whole through nine dimensions, which also can provide evidence to support the development of precision strategies to strengthen the disaster literacy of nurses.

Improve disaster literacy in nurses: a qualitative descriptive study.

BACKGROUND: The enhancement of nurses' disaster literacy is crucial for effective disaster emergency management, especially for clinical nurses with no prior experience in disaster rescue. This study aims to explore the perspectives of nurses who have been involved in disaster rescue operations on strategies to advance nurses' disaster literacy. METHODS: A qualitative descriptive study, which follows unified qualitative study reporting guidelines. Thirty disaster rescue nurses were recruited to participate in this study, who came from 30 third-class hospitals in China. From October to December 2021, information was acquired by conducting semi-structured telephone interviews with participants. Qualitative content analysis was used to examine the data. RESULTS: Six categories and eleven subcategories were created. Strengthening disaster education and training was the main focus, and its subcategories included continuing education, nursing curriculum development, and disaster rescue experience guide. The second focus, which included scene simulation, actual combat/military simulation, and virtual reality simulation, was strengthening disaster simulation and drill. The third focus was on providing psychosocial support, which included improving self-psychological adjustment, developing resilience, and engaging in active coping. The fourth category was to strengthen nurse/hospital managers roles and leadership, which included enhancing professional identity and policies/leadership support. The fifth category was disaster preparedness, and the sixth was enhancing knowledge transformation. CONCLUSIONS: Government agencies or healthcare organizations should actively promote the formation of nurses' disaster literacy from multiple viewpoints. Disaster education and training, simulation exercises, and psychosocial support should be prioritized.

Learning technology for detection and grading of cancer tissue using tumour ultrasound images1.

BACKGROUND: Early diagnosis of breast cancer is crucial to perform effective therapy. Many medical imaging modalities including MRI, CT, and ultrasound are used to diagnose cancer. OBJECTIVE: This study aims to investigate feasibility of applying transfer learning techniques to train convoluted neural networks (CNNs) to automatically diagnose breast cancer via ultrasound images. METHODS: Transfer learning techniques helped CNNs recognise breast cancer in ultrasound images. Each model's training and validation accuracies were assessed using the ultrasound image dataset. Ultrasound images educated and tested the models. RESULTS: MobileNet had the greatest accuracy during training and DenseNet121 during validation. Transfer learning algorithms can detect breast cancer in ultrasound images. CONCLUSIONS: Based on the results, transfer learning models may be useful for automated breast cancer diagnosis in ultrasound images. However, only a trained medical professional should diagnose cancer, and computational approaches should only be used to help make quick decisions.

Virulence gene distribution and molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae in the ICU. / ICUç¢³é’éœ‰çƒ¯è€è¯è‚ºç‚Žå ‹é›·ä¼¯èŒçš„æ¯’åŠ›åŸºå› åˆ†å¸ƒåŠåˆ†å­æµè¡Œç— å­¦ç‰¹å¾.

OBJECTIVES: The drug-resistant genes carried by carbapenem-resistant Klebsiella pneumoniae (CRKP) limit clinical treatment options, and its virulence genes severely affect patient prognosis. This study aims to investigate the distribution of virulence genes, capsular serotypes, and molecular epidemiological characteristics of CRKP in ICU, to understand the characteristics of CRKP infections in ICU, and to provide a scientific basis for effective monitoring and control of CRKP infections in ICU. METHODS: A total of 40 non-duplicate strains of CRKP isolated from the ICU of Guangdong Provincial People's Hospital between January 2021 and December 2022 were collected and analyzed. Whole-genome sequencing was used to analyze the distribution of resistance genes, virulence genes, and capsular serotypes of the strains. The sequences of 7 housekeeping genes of CRKP genome were uploaded to the Klebsiella pneumoniae (KPN)multilocus sequence typing (MLST) database to determine the sequence types (STs) of the strains. RESULTS: The age of the 40 ICU CRKP-infected patients was (69.03±17.82) years old, with various underlying diseases, and there were 20 patients with improved clinical outcome and 20 patients with death. The isolated strains primarily originated from mid-stream urine and bronchoalveolar lavage fluid. Whole-genome sequencing results revealed that the strains predominantly carried blaKPC-1 (29 strains, 72.5%) and blaNDM-1 (6 strains, 15.0%), with 5 strains carrying both blaKPC-1 and blaNDM-1. Various virulence genes were detected, among which the carriage rates of genes such as entA, entB, entE, entS, fepA, fepC, fepG, yag/ecp, and ompA reached 100%, while the carriage rates of genes such as entD, fimB, iroB, iroD, fes,and pla were low. The CRKP strains isolated from ICU were predominantly ST11 (27 cases, 67.5%), with KL64 being the main capsular serotype (29 cases, 72.5%). A total of 23 ST11-KL64 CRKP strains were detected, accounting for 57.5%. CONCLUSIONS: The main type of ICU CRKP is ST11-KL64, carrying various virulence genes, primarily those related to iron absorption. Furthermore, blaKPC has shifted from blaKPC-2 to blaKPC-1. Therefore, close monitoring of the molecular epidemiological changes of CRKP is necessary, and strict control measures should be implemented to effectively curb the occurrence of CRKP infections.

Cucurbit[8]uril-Mediated Supramolecular Heterodimerisation and Photoinduced [2+2] Heterocycloaddition to Generate Unexpected [2]Rotaxanes.

In contrast to the self-assembly of homosupramolecules, the self-assembly of heterosupramolecules is more challenging and significant in various fields. Herein, we design and investigate a cucurbit[8]uril-mediated heterodimerisation based on an arene-fluoroarene strategy. Furthermore, the heteroternary complex is found to be able to undergo a photoinduced [2+2] heterocycloaddition, resulting in the formation of an unexpected [2]rotaxane. This work demonstrates a novel supramolecular heterodimerisation system that not only contributes to the development of photoisomerisation systems, but also enriches synthetic methods for mechanically interlocked molecules.

Red-Light Activation of a Microtubule Polymerization Inhibitor via Amide Functionalization of the Ruthenium Photocage.

Photoactivated chemotherapy (PACT) is a promising cancer treatment modality that kills cancer cells via photochemical uncaging of a cytotoxic drug. Most ruthenium-based photocages used for PACT are activated with blue or green light, which penetrates sub-optimally into tumor tissues. Here, we report amide functionalization as a tool to fine-tune the toxicity and excited states of a terpyridine-based ruthenium photocage. Due to conjugation of the amide group with the terpyridine π system in the excited state, the absorption of red light (630 nm) increased 8-fold, and the photosubstitution rate rose 5-fold. In vitro, red light activation triggered inhibition of tubulin polymerization, which led to apoptotic cell death both in normoxic (21 % O2 ) and hypoxic (1 % O2 ) cancer cells. In vivo, red light irradiation of tumor-bearing mice demonstrated significant tumor volume reduction (45 %) with improved biosafety, thereby demonstrating the clinical potential of this compound.

Cyclic Ruthenium-Peptide Conjugates as Integrin-Targeting Phototherapeutic Prodrugs for the Treatment of Brain Tumors.

To investigate the potential of tumor-targeting photoactivated chemotherapy, a chiral ruthenium-based anticancer warhead, Λ/Δ-[Ru(Ph2phen)2(OH2)2]2+, was conjugated to the RGD-containing Ac-MRGDH-NH2 peptide by direct coordination of the M and H residues to the metal. This design afforded two diastereoisomers of a cyclic metallopeptide, Λ-[1]Cl2 and Δ-[1]Cl2. In the dark, the ruthenium-chelating peptide had a triple action. First, it prevented other biomolecules from coordinating with the metal center. Second, its hydrophilicity made [1]Cl2 amphiphilic so that it self-assembled in culture medium into nanoparticles. Third, it acted as a tumor-targeting motif by strongly binding to the integrin (Kd = 0.061 µM for the binding of Λ-[1]Cl2 to αIIbß3), which resulted in the receptor-mediated uptake of the conjugate in vitro. Phototoxicity studies in two-dimensional (2D) monolayers of A549, U87MG, and PC-3 human cancer cell lines and U87MG three-dimensional (3D) tumor spheroids showed that the two isomers of [1]Cl2 were strongly phototoxic, with photoindexes up to 17. Mechanistic studies indicated that such phototoxicity was due to a combination of photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) effects, resulting from both reactive oxygen species generation and peptide photosubstitution. Finally, in vivo studies in a subcutaneous U87MG glioblastoma mice model showed that [1]Cl2 efficiently accumulated in the tumor 12 h after injection, where green light irradiation generated a stronger tumoricidal effect than a nontargeted analogue ruthenium complex [2]Cl2. Considering the absence of systemic toxicity for the treated mice, these results demonstrate the high potential of light-sensitive integrin-targeted ruthenium-based anticancer compounds for the treatment of brain cancer in vivo.

Prediction of Antibiotic Resistance Evolution by Growth Measurement of All Proximal Mutants of Beta-Lactamase.

The antibiotic resistance crisis continues to threaten human health. Better predictions of the evolution of antibiotic resistance genes could contribute to the design of more sustainable treatment strategies. However, comprehensive prediction of antibiotic resistance gene evolution via laboratory approaches remains challenging. By combining site-specific integration and high-throughput sequencing, we quantified relative growth under the respective selection of cefotaxime or ceftazidime selection in ∼23,000 Escherichia coli MG1655 strains that each carried a unique, single-copy variant of the extended-spectrum ß-lactamase gene blaCTX-M-14 at the chromosomal att HK022 site. Significant synergistic pleiotropy was observed within four subgenic regions, suggesting key regions for the evolution of resistance to both antibiotics. Moreover, we propose PEARP and PEARR, two deep-learning models with strong clinical correlations, for the prospective and retrospective prediction of blaCTX-M-14 evolution, respectively. Single to quintuple mutations of blaCTX-M-14 predicted to confer resistance by PEARP were significantly enriched among the clinical isolates harboring blaCTX-M-14 variants, and the PEARR scores matched the minimal inhibitory concentrations obtained for the 31 intermediates in all hypothetical trajectories. Altogether, we conclude that the measurement of local fitness landscape enables prediction of the evolutionary trajectories of antibiotic resistance genes, which could be useful for a broad range of clinical applications, from resistance prediction to designing novel treatment strategies.

Aldose reductase inhibition alleviates diabetic cardiomyopathy and is associated with a decrease in myocardial fatty acid oxidation.

BACKGROUND: Cardiovascular diseases, including diabetic cardiomyopathy, are major causes of death in people with type 2 diabetes. Aldose reductase activity is enhanced in hyperglycemic conditions, leading to altered cardiac energy metabolism and deterioration of cardiac function with adverse remodeling. Because disturbances in cardiac energy metabolism can promote cardiac inefficiency, we hypothesized that aldose reductase inhibition may mitigate diabetic cardiomyopathy via normalization of cardiac energy metabolism. METHODS: Male C57BL/6J mice (8-week-old) were subjected to experimental type 2 diabetes/diabetic cardiomyopathy (high-fat diet [60% kcal from lard] for 10 weeks with a single intraperitoneal injection of streptozotocin (75 mg/kg) at 4 weeks), following which animals were randomized to treatment with either vehicle or AT-001, a next-generation aldose reductase inhibitor (40 mg/kg/day) for 3 weeks. At study completion, hearts were perfused in the isolated working mode to assess energy metabolism. RESULTS: Aldose reductase inhibition by AT-001 treatment improved diastolic function and cardiac efficiency in mice subjected to experimental type 2 diabetes. This attenuation of diabetic cardiomyopathy was associated with decreased myocardial fatty acid oxidation rates (1.15 ± 0.19 vs 0.5 ± 0.1 µmol min-1 g dry wt-1 in the presence of insulin) but no change in glucose oxidation rates compared to the control group. In addition, cardiac fibrosis and hypertrophy were also mitigated via AT-001 treatment in mice with diabetic cardiomyopathy. CONCLUSIONS: Inhibiting aldose reductase activity ameliorates diastolic dysfunction in mice with experimental type 2 diabetes, which may be due to the decline in myocardial fatty acid oxidation, indicating that treatment with AT-001 may be a novel approach to alleviate diabetic cardiomyopathy in patients with diabetes.

Trefoil-Shaped Metal-Organic Cages as Fluorescent Chemosensors for Multiple Detection of Fe3+, Cr2O72-, and Antibiotics.

The construction of metal-organic cages (MOCs) with specific structures and fluorescence sensing properties is of much importance and challenging. Herein, a novel phenanthroline-based metal-organic cage, [Cd3L3·6MeOH·6H2O] (1), was synthesized by metal-directed assembly of the ligand 3,3'-[(1E,1'E)-(1,10-phenanthroline-2,9-diyl)bis(ethene-2,1-diyl)]dibenzoic acid (H2L) and CdI2 using a solvothermal method. According to single-crystal X-ray analysis, cage 1 exhibits a rare trefoil-shaped structure. Meanwhile, the discrete MOCs are further stacked into a 3D porous supramolecular structure through abundant intermolecular C-H···O interactions. Additionally, through exploration of fluorescence sensing on cations, anions, and antibiotics in aqueous solution, the experimental results indicate that cage 1 has excellent fluorescence sensing abilities for Fe3+, Cr2O72-, and nitrofuran and nitroimidazole antibiotics. The sensing ability of 1 remains unaltered for five cycles toward all analytes. The above results suggested that cage 1 can be considered a potential multiple sensor for the detection of Fe3+, Cr2O72-, and some antibiotics.

Isolation and biological activity of natural chalcones based on antibacterial mechanism classification.

Bacterial infection, which is still one of the leading causes of death in humans, poses an enormous threat to the worldwide public health system. Antibiotics are the primary medications used to treat bacterial diseases. Currently, the discovery of antibiotics has reached an impasse, and due to the abuse of antibiotics resulting in bacterial antibiotic resistance, researchers have a critical desire to develop new antibacterial agents in order to combat the deteriorating antibacterial situation. Natural chalcones, the flavonoids consisting of two phenolic rings and a three-carbon α, ß-unsaturated carbonyl system, possess a variety of biological and pharmacological properties, including anti-cancer, anti-inflammatory, antibacterial, and so on. Due to their potent antibacterial properties, natural chalcones possess the potential to become a new treatment for infectious diseases that circumvents existing antibiotic resistance. Currently, the majority of research on natural chalcones focuses on their synthesis, biological and pharmacological activities, etc. A few studies have been conducted on their antibacterial activity and mechanism. Therefore, this review focuses on the antibacterial activity and mechanisms of seventeen natural chalcones. Firstly, seventeen natural chalcones have been classified based on differences in antibacterial mechanisms. Secondly, a summary of the isolation and biological activity of seventeen natural chalcones was provided, with a focus on their antibacterial activity. Thirdly, the antibacterial mechanisms of natural chalcones were summarized, including those that act on bacterial cell membranes, biological macromolecules, biofilms, and quorum sensing systems. This review aims to lay the groundwork for the discovery of novel antibacterial agents based on chalcones.