Controlled release characteristics of alkyl gallates and gallic acid from ß-cyclodextrin inclusion complexes of alkyl gallates.

The freeze-drying approach was used to create inclusion complexes utilizing alkyl gallates and ß-cyclodextrin, namely dodecyl gallate, octyl gallate, butyl gallate, and ethyl gallate, which are exemplary examples of phenolic esters. The everted-rat-gut-sac model demonstrated that the inclusion complexes released alkyl gallates, which were subsequently hydrolyzed to generate free gallic acid, as evidenced by HPLC-UV analysis. Both gallic acid and short-chain alkyl gallates were capable of permeating the small intestinal membrane. The transport rate of gallic acid (or alkyl gallates) exhibited an initial rise followed by a drop when the carbon-chain lengths varied. The inclusion complex groups exhibited a superior sustained-release effect compared to the comparable alkyl gallates groups, thus possibly leading to higher bioavailability and stronger bioactivity. Moreover, altering the length of the carbon chain will allow for the effortless achievement of regulated release of phenolic compounds and short-chain phenolic esters from such ß-cyclodextrin inclusion complexes.

The Light-Intensity-Affected Aroma Components of Green Tea during Leaf Spreading.

Leaf spreading is a key processing step that affects the aroma formation of green tea. The effects of a single-light wavelength on the aroma and taste of tea have been extensively studied. Less attention has been paid to the effect of different complex light intensities on the formation of green tea's volatile aroma during leaf spreading. The current study was designed to evaluate how leaf spreading under different complex light intensities relates to the quality of green tea. Using headspace solid-phase micro-extraction and gas chromatography-mass spectrometry (HS-SPME/GC-MS), volatile flavor compounds in green tea were analyzed during leaf spreading in five different light conditions. Multivariate statistical analysis and odor activity values (OAVs) were used to classify these samples and identify key odors. Eight distinct groups, including ninety volatile compounds, were detected. The most prevalent volatile compounds found in green tea samples were hydrocarbons and alcohols, which accounted for 29% and 22% of the total volatile compounds, respectively. Fourteen volatile compounds (OAV > 1) were identified as key active differential odorants. The chestnut-like aroma in green tea was mostly derived from 3-methyl-butanal and linalool, which were significantly accumulated in medium-intensity light (ML).

Synergistic and Antagonistic Activity of Selected Dietary Phytochemicals against Oxidative Stress-Induced Injury in Cardiac H9c2 Cells via the Nrf2 Signaling Pathway.

The antioxidant activities of lycopene (LY), lutein (LU), chlorogenic acid (CA), and delphinidin (DP) were tested in vitro on H9c2 cell-based models. Some indicators, such as the generation of reactive oxygen (ROS), the quantification of cell antioxidant activity (CAA), and the expressions of SOD, GSH-Px, and CAT, were calculated to examine their antioxidant interactions. From our results, the phytochemical mixtures (M1: CA-LU: F3/10, M2: DP-CA: F7/10, M3: DP-LY: F5/10) displayed strong synergistic effects based on the generation of ROS and the quantification of CAA. However, great antagonistic bioactivities were seen in the combinations of LY-LU: F5/10 (M4), CA-LU: F9/10 (M5), and DP-LY: F7/10 (M6). Western blotting analysis indicated that the possible mechanism underlying the synergistic antioxidant interactions among phytochemical combinations was to enhance the accumulation of Nrf2 in the nucleus and the expression of its downstream antioxidant enzymes, HO-1 and GCLC. The combinations (M1-M3 groups) showed significant protection against the loss of mitochondrial membrane potential than individual groups to avoid excessive ROS production. The M4-M6 groups exerted antagonistic protective effects compared with the individual groups. In addition, lutein and lycopene absorption was improved more because of the presence of chlorogenic acid and delphinidin in the M1 and M3 groups, respectively. However, delphinidin significantly reduced the cellular uptake of lycopene in the M6 group. It appeared that antioxidant interactions of phytochemical combinations may contribute to the restoration of cellular redox homeostasis and lead to an improvement in diet quality and collocation.

In situ deposition of bismuth on pre-anodized screen-printed electrode for sensitive determination of Cd2+ in water and rice with a portable device.

Electrochemical detection is favorable for the rapid and sensitive determination of heavy metal cadmium. However, the detection sensitivity needs to be further improved, and a portable, low-cost device is needed for on-site detection. Herein, an in-situ bismuth modified pre-anodized screen-printed carbon electrode (SPCE) was developed for Cd2+ determination by square wave anodic stripping voltammetry (SWASV). The in-situ bismuth modification enhances the enrichment of Cd2+, and together with pre-anodization improve the electron transfer rate of electrode, thus enhancing the detection sensitivity. The electrode modification method combines pre-anodization and in-situ bismuth deposition, which is very easy and effective. Furthermore, a self-made PSoC Stat potentiostat coupled with a stirring device was fabricated for portable and low-cost electrochemical detection. After comprehensive optimization, the developed method can reach a testing time of 3 min, a detection limit of 3.55 µg/L, a linear range of 5-100 µg/L, and a recovery rate of 91.7-107.1% in water and rice samples for Cd2+ determination. Therefore, our method holds great promise for the rapid, sensitive and on-site determination of Cd2+ in food samples.

An acridone based fluorescent dye for lipid droplet tracking and cancer diagnosis.

Lipid droplets (LDs) are spherical organelles that localize in the cytosol of eukaryotic cells. Different proteins are embedded on the surface of LDs, so LDs play a vital role in the physiological activities of cells. The dysregulation of LDs is associated with various human diseases, such as diabetes and obesity. Therefore, it is essential to develop a fluorescent dye that labels LDs to detect and monitor illnesses. In this study, we developed the compound BDAA12C for staining LDs in cells. BDAA12C exhibits excellent LD specificity and low toxicity, enabling us to successfully stain and observe the fusion of LDs in A549 cancer cells. Furthermore, we also successfully distinguished A549 cancer cells and MRC-5 normal cells in a co-culture experiment and in normal and tumour tissues. Interestingly, we found different localizations of BDAA12C in well-fed and starved A549 cancer cells and consequently illustrated the transfer of fatty acids (FAs) from LDs to mitochondria to supply energy for ß-oxidation upon starvation. Therefore, BDAA12C is a promising LD-targeted probe for cancer diagnosis and tracking lipid trafficking within cells.

Modulation of Interlayer Nanochannels via the Moderate Heat Treatment of Graphene Oxide Membranes.

In response to the phenomenon of interlayer transport channel swelling caused by the hydration of oxygen-containing functional groups on the GO membrane surface, a moderate heat treatment method was employed to controllably reduce the graphene oxide (GO) membrane and prepare a reduced GO composite nanofiltration membrane (mixed cellulose membrane (MCE)/ethylenediamine (EDA)/reduced GO-X (RGO-X)). The associations of different heat treatment temperatures with the hydrophilicity, interlayer structure, permeability and dye/salt rejection properties of GO membranes were systematically explored. The results indicated that the oxygen-containing groups of the GO membrane were partially eliminated after heat treatment, and the hydrophilicity was weakened. This effectively weakened the hydration between the GO membrane and the water molecules and inhibited the swelling of the oxidized graphene membrane. In the dye desalination test, the MCE/EDA/RGO membrane exhibited an ultra-high rejection rate of over 97% for methylene blue (MB) dye molecules. In addition, heat treatment increased the structural defects of the GO membrane and promoted the fast passage of water molecules via the membrane. In pure water flux testing, the water flux of the membrane remained above 46.58 Lm-2h-1bar-1, while the salt rejection rate was relatively low.

Polyphenol (-)-Epigallocatechin Gallate (EGCG) mitigated kidney injury by regulating metabolic homeostasis and mitochondrial dynamics involvement with Drp1-mediated mitochondrial fission in mice.

The study aimed to examine effects of (-)-epigallocatechin-3-gallate (EGCG) on energy metabolism and mitochondrial dynamics in mouse model of renal injury caused by doxorubicin (DOX). Here, mice were divided into Control group, EGCG-only treated group, DOX group, and three doses of EGCG plus DOX groups. Our results showed that EGCG behaved beneficial effects against kidney injury via attenuation of pathological changes in kidney tissue, which was confirmed by reducing serum creatinine (SCr), blood urea nitrogen (BUN), and apoptosis. Subsequently, changes in reactive oxygen species generation, malondialdehyde content, and activities of antioxidant enzymes were considerably ameliorated in EGCG + DOX groups when compared to DOX group. Furthermore, EGCG-evoked renal protection was associated with increases of mitochondrial membrane potential and decreases of mitochondrial fission protein Dynamin-related protein 1 (Drp1). Moreover, changing glycolysis into mitochondrial oxidative phosphorylation was observed, evidenced by controlling activities of malate dehydrogenase (MDH) and hexokinase (HK) in EGCG + DOX groups when compared to DOX group, indicating that reprogramming energy metabolism was linked to EGCG-induced renal protection in mice. Therefore, EGCG was demonstrated to have a protective effect against kidney injury by reducing oxidative damage, metabolic disorders, and mitochondrial dysfunction, suggesting that EGCG has potential as a feasible strategy to prevent kidney injury.

Self-healing and injectable chitosan/konjac glucomannan hydrogel with pH response for controlled protein release.

Dynamic hydrogels with the features of injection, self-healing, and remodeling at the target site have been developed as smart multifunctional biomaterials for drug delivery. However, most self-healing injectable hydrogels are difficult to control protein release after implantation, owing to the deficiency of pH responsiveness, which reduces the bioavailability of proteins. Herein, we propose a facile strategy to endow pH responsiveness into a dynamic hydrogel with both self-healing and injectable capabilities, by crosslinking biomacromolecular backbones via dual pH sensitive dynamic covalent bond. Particularly, oxidized konjac glucomannan (OKGM) can be crosslinked with poly (aspartic hydrazide) (PAHy) and N-carboxyethyl chitosan (CEC) to form dynamic acylhydrazone bonds and imide bonds, respectively, endowing the hydrogel with pH responsiveness and dynamic behaviors. Specifically, PAHy facilitates the formation of acylhydrazone bonds, improving the mechanical properties and pH sensitivity while reducing the degradation behavior of the hydrogels under physiological conditions. Kinetics indicate that the release of bovine serum albumin follows Fick diffusion under different pH conditions. The pH responsive hydrogel with self-healing injectable capabilities has the potential to be used as a controllable and sustain release carrier for protein drugs.

MOF-Derived Zn/N-Doped Porous Carbon Film on a Carbon Nanotube for High-Performance Supercapacitors.

Designing high-performance binder-free electrochemical electrodes is crucially important toward supercapacitors. In this paper, a Zn/N-doped porous carbon film coating on flexible carbon nanotubes (ZIF-8@CT-800) derived from the epitaxial Zn-MOF film growth on cotton textile was successfully fabricated via a combination of the liquid-phase epitaxial (LPE) method and calcination treatments. The ZIF-8@CT-800 serves directly as a self-supported electrode for supercapacitors and exhibits a high areal capacitance of 930 mF·cm-2 at a current density of 1 mA·cm-2 and a good recyclability of 86% after 2000 cycles. The excellent supercapacitor property is ascribed to the unique structural design of ZIF-8@CT-800, which provides appropriate channels for enhanced electronic and ionic transport as well as increased surface area for accessing more electrolyte ions. This work will provide significant guidance for designing MOF-derived porous carbon to construct flexible binder-free electrode materials with high electrochemical performance.

Abnormal genes and pathways that drive muscle contracture from brachial plexus injuries: Towards machine learning approach.

In order to clarify the pathways closely linked to denervated muscle contracture, this work uses IoMT-enabled healthcare stratergies to examine changes in gene expression patterns inside atrophic muscles following brachial plexus damage. The gene expression Omnibus (GEO) database searching was used to locate the dataset GSE137606, which is connected to brachial plexus injuries. Strict criteria (|logFC|≥2 & adj.p < 0.05) were used to extract differentially expressed genes (DEGs). To identify dysregulated activities and pathways in denervated muscles, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and Gene Set Enrichment Analysis (GSEA) were used. Hub genes were found using Cytoscape software's algorithms, which took into account parameters like as proximity, degree, and MNC. Their expression, enriched pathways, and correlations were then examined. The results showed that 316 DEGs were predominantly concentrated in muscle-related processes such as tissue formation and contraction pathways. Of these, 297 DEGs were highly expressed in denervated muscles, whereas 19 DEGs were weakly expressed. GSEA showed improvements in the contraction of striated and skeletal muscles. In addition, it was shown that in denervated muscles, Myod1, Myog, Myh7, Myl2, Tnnt2, and Tnni1 were elevated hub genes with enriched pathways such adrenergic signaling and tight junction. These results point to possible therapeutic targets for denervated muscular contracture, including Myod1, Myog, Myh7, Myl2, Tnnt2, and Tnni1. This highlights treatment options for this ailment which enhances the mental state of patient.

Comprehensive insights into berberine's hypoglycemic mechanisms: A focus on ileocecal microbiome in db/db mice.

The efficacy of berberine in managing diabetes through modulation of gut microbiome has been established through fecal sample analyses. However, relying solely on fecal materials constrains our comprehension of berberine's effects on diverse gastrointestinal locations. This study specifically explores the ileocecal region, a segment characterized by higher microbial diversity than fecal samples. Berberine exhibits a robust hypoglycemic impact by significantly reducing glucose levels in blood and urine. Beyond glycemic control, berberine ameliorates various diabetes-related symptoms in serum, including increased insulin and leptin, but decreased NEFA and MDA. Notably, berberine demonstrates liver-protective functions by alleviating oxidative stress and enhancing hepatic glycogen abundance. These outcomes prompted a high-throughput sequencing analysis of the ileocecal microbiome, revealing an augmentation of beneficial bacterial genera (four genera in the Lachnospiraceae family, Erysipelatoclostridium, and Escherichia-Shigella), along with a reduction in harmful bacterial genera (Romboutsia). Additionally, we predicted the impact of the ileocecal microbiome on clinically relevant factors associated with diabetes. These findings elucidate the multi-pathway mechanisms of berberine in treating T2D, underscoring its potential as a natural anti-diabetic agent or functional food, particularly through the modulation of the gut microbiota.

Organophosphate flame retardants in air from formal e-waste recycling workshops in China: Size-distribution, gas-particle partitioning and exposure assessment.

In order to understand the organophosphate flame retardants (OPFRs) pollution and evaluate the inhalation exposure risk in formal e-waste recycling facilities, the air concentrations, particle size distribution and gas-particle partitioning of OPFRs in four typical workshops were investigated. The total Σ15OPFR concentrations inside workshops were in the range of 64.7-682 ng/m3, with 5.80-23.4 ng/m3 in gas phase and 58.8-658 ng/m3 in particle phase. Triphenyl phosphate (TPHP) and tris(2-chloroisopropyl) phosphate (TCIPP) were main analogs, both of which contributed to 49.0-85.7% of total OPFRs. In the waste printed circuit boards thermal treatment workshop, the OPFRs concentration was the highest, and particle-bound OPFRs mainly distributed in 0.7-1.1 µm particles. The proportions of TPHP in different size particles increased as the decrease of particle size, while TCIPP presented an opposite trend. The gas-particle partitioning of OPFR analogs was dominated by absorption process, and did not reach equilibrium state due to continuous emission of OPFRs from the recycling activities. The deposition fluxes of OPFRs in respiratory tract were 65.7-639 ng/h, and the estimated daily intake doses of OPFRs were 8.52-76.9 ng/(kg·day) in four workshops. Inhalation exposure was an important exposure pathway for e-waste recycling workers, and deposition fluxes of size-segregated OPFRs were mainly in head airways region.

Inhibition of FBP1 expression by KMT5A through TWIST1 methylation is one of the mechanisms leading to chemoresistance in breast cancer.

Lysine methyltransferase 5A (KMT5A) is the sole mammalian enzyme known to catalyse the mono­methylation of histone H4 lysine 20 and non­histone proteins such as p53, which are involved in the occurrence and progression of numerous cancers. The present study aimed to determine the function of KMT5A in inducing docetaxel (DTX) resistance in patients with breast carcinoma by evaluating glucose metabolism and the underlying mechanism involved. The upregulation or downregulation of KMT5A­related proteins was examined after KMT5A knockdown in breast cancer (BRCA) cells by Tandem Mass Tag proteomics. Through differential protein expression and pathway enrichment analysis, the upregulated key gluconeogenic enzyme fructose­1,6­bisphosphatase 1 (FBP1) was discovered. Loss of FBP1 expression is closely related to the development and prognosis of cancers. A dual­luciferase reporter gene assay confirmed that KMT5A inhibited the expression of FBP1 and that overexpression of FBP1 could enhance the chemotherapeutic sensitivity to DTX through the suppression of KMT5A expression. The KMT5A inhibitor UNC0379 was used to verify that DTX resistance induced by KMT5A through the inhibition of FBP1 depended on the methylase activity of KMT5A. According to previous literature and interaction network structure, it was revealed that KMT5A acts on the transcription factor twist family BHLH transcription factor 1 (TWIST1). Then, it was verified that TWSIT1 promoted the expression of FBP1 by using a dual­luciferase reporter gene experiment. KMT5A induces chemotherapy resistance in BRCA cells by promoting cell proliferation and glycolysis. After the knockdown of the KMT5A gene, the FBP1 related to glucose metabolism in BRCA was upregulated. KMT5A knockdown expression and FBP1 overexpression synergistically inhibit cell proliferation and block cells in the G2/M phase. KMT5A inhibits the expression of FBP1 by methylating TWIST1 and weakening its promotion of FBP1 transcription. In conclusion, KMT5A was shown to affect chemotherapy resistance by regulating the cell cycle and positively regulate glycolysis­mediated chemotherapy resistance by inhibiting the transcription of FBP1 in collaboration with TWIST1. KMT5A may be a potential therapeutic target for chemotherapy resistance in BRCA.

Prediction of early-phase cytomegalovirus pneumonia in post-stem cell transplantation using a deep learning model.

BACKGROUND: Diagnostic challenges exist for CMV pneumonia in post-hematopoietic stem cell transplantation (post-HSCT) patients, despite early-phase radiographic changes. OBJECTIVE: The study aims to employ a deep learning model distinguishing CMV pneumonia from COVID-19 pneumonia, community-acquired pneumonia, and normal lungs post-HSCT. METHODS: Initially, 6 neural network models were pre-trained with COVID-19 pneumonia, community-acquired pneumonia, and normal lung CT images from Kaggle's COVID multiclass dataset (Dataset A), then Dataset A was combined with the CMV pneumonia images from our center, forming Dataset B. We use a few-shot transfer learning strategy to fine-tune the pre-trained models and evaluate model performance in Dataset B. RESULTS: 34 cases of CMV pneumonia were found between January 2018 and December 2022 post-HSCT. Dataset A contained 1681 images of each subgroup from Kaggle. Combined with Dataset A, Dataset B was initially formed by 98 images of CMV pneumonia and normal lung. The optimal model (Xception) achieved an accuracy of 0.9034. Precision, recall, and F1-score all reached 0.9091, with an AUC of 0.9668 in the test set of Dataset B. CONCLUSIONS: This framework demonstrates the deep learning model's ability to distinguish rare pneumonia types utilizing a small volume of CT images, facilitating early detection of CMV pneumonia post-HSCT.

Curcumin Nanocapsules based on carbon dots for photodynamic sterilization towards Listeria monocytogenes and Staphylococcus aureus.

Curcumin (Cur) as a natural food additive and photosensitizer has been widely applied on photodynamic sterilization and preservation for food, but the poor aqueous solubility and light stability restrict its extensive application. In this study, we report a Cur nanocapsules (Cur-CDs) made by carbon dots (CDs). Attributing to the hydrogen bonds formed between Cur and CDs, Cur-CDs exhibits excellent Cur aqueous solubility each to 9286.98 ng/mL (enhanced by 246.27 times) and light stability (enhanced by 1.51 times). The photogenerated electron transmission from Cur to CDs in addition resulted in >1.23 and 1.60 times generation of •O2- and •OH, compared to that of bare Cur. Accordingly, 5.73 × 103 CFU L. monocytogenes, and 5.43 × 103 CFU S. aureus were killed by 0.06 mg/mL Cur-CDs within 20 mins of blue light, showing the promising potential in the development and application of safe and environmentally friendly non-thermal sterilization technology based on Cur-CDs.

Potential association of rheumatic diseases with bone mineral density and fractures: a bi-directional mendelian randomization study.

BACKGROUND: Previous studies have implicated rheumatoid arthritis as an independent risk factor for bone density loss. However, whether there is a causal relationship between rheumatic diseases and bone mineral density (BMD) and fractures is still controversial. We employed a bidirectional Mendelian analysis to explore the causal relationship between rheumatic diseases and BMD or fractures. METHODS: The rheumatic diseases instrumental variables (IVs) were obtained from a large Genome-wide association study (GWAS) meta-analysis dataset of European descent. Analyses were performed for the three rheumatic diseases: ankylosing spondylitis (AS) (n = 22,647 cases, 99,962 single nucleotide polymorphisms [SNPs]), rheumatoid arthritis (RA) (n = 58,284 cases, 13,108,512 SNPs), and systemic lupus erythematosus (SLE) (n = 14,267 cases, 7,071,163 SNPs). Two-sample Mendelian randomization (MR) analyses were carried out by using R language TwoSampleMR version 0.5.7. The inverse-variance weighted (IVW), MR-Egger, and weighted median methods were used to analyze the causal relationship between rheumatic diseases and BMD or fracture. RESULTS: The MR results revealed that there was absence of evidence for causal effect of AS on BMD or fracture. However, there is a positive causal relationship of RA with fracture of femur (95% CI = 1.0001 to 1.077, p = 0.046), and RA and fracture of forearm (95% CI = 1.015 to 1.064, p = 0.001). SLE had positive causal links for fracture of forearm (95% CI = 1.004 to 1.051, p = 0.020). Additionally, increasing in heel bone mineral density (Heel-BMD) and total bone mineral density (Total-BMD) can lead to a reduced risk of AS without heterogeneity or pleiotropic effects. The results were stable and reliable. There was absence of evidence for causal effect of fracture on RA (95% CI = 0.929 to 1.106, p = 0.759), and fracture on SLE (95% CI = 0.793 to 1.589, p = 0.516). CONCLUSIONS: RA and SLE are risk factors for fractures. On the other hand, BMD increasing can reduce risk of AS. Our results indicate that rheumatic diseases may lead to an increased risk of fractures, while increased BMD may lead to a reduced risk of rheumatic diseases. These findings provide insight into the risk of BMD and AS, identifying a potential predictor of AS risk as a reduction in BMD.

Possible toxification mechanisms of acute and chronic pentachlorophenol to Montipora digitata: Limitation of energy supply and immunotoxicity.

Pentachlorophenol (PCP) is widely found in coastal environments and has various adverse effects, and its potential impact on coral reef ecosystems concerning. The scleractinian coral Montipora digitata was used for PCP stress experiments in this study. Phenotypes, physiological indicators, microbial diversity analysis and RNA sequencing were used to investigate the mechanisms underlying the responses of corals to acute and chronic PCP exposure. After 96 h of acute exposure, coral bleaching occurred at 1000 µg/LPCP and there was a significant decrease in Symbiodiniaceae density, Fv/Fm, and chlorophyll a content. Exposure to different concentrations of PCP significantly increased the content of malondialdehyde (MDA), leading to oxidative stress in corals. Chronic PCP exposure resulted in bleaching at 60 days, with the Fv/Fm significantly reduced to 0.461. Microbial diversity analysis revealed an increase in the abundance of potential pathogens, such as Vibrio, during acute PCP exposure and the emergence of the degrading bacterium Delftia during chronic PCP exposure. Transcriptional analysis showed that PCP exposure caused abnormal carbohydrate and amino acid metabolism in zooxanthella, which affected energy supply, induced immune responses, and disrupted symbiotic relationships. Corals respond to injury by boosting the expression of genes associated with signal transduction and immune response. Additionally, the expression of genes associated with environmental adaptation increased with chronic PCP exposure, which is consistent with the results of the microbial diversity analysis. These results indicate that PCP exposure might affect the balance of coral- zooxanthellae symbiosis in the stony coral M. digitata, impairing coral health and leading to bleaching.

Targeted next-generation sequencing reveals the genetic mechanism of Chinese Marfan syndrome cohort with ocular manifestation.

BACKGROUND: Marfan syndrome (MFS) is a hereditary connective tissue disorder involving multiple systems, including ophthalmologic abnormalities. Most cases are due to heterozygous mutations in the fibrillin-1 gene (FBN1). Other associated genes include LTBP2, MYH11, MYLK, and SLC2A10. There is significant clinical overlap between MFS and other Marfan-like disorders. PURPOSE: To expand the mutation spectrum of FBN1 gene and validate the pathogenicity of Marfan-related genes in patients with MFS and ocular manifestations. METHODS: We recruited 318 participants (195 cases, 123 controls), including 59 sporadic cases and 88 families. All patients had comprehensive ophthalmic examinations showing ocular features of MFS and met Ghent criteria. Additionally, 754 cases with other eye diseases were recruited. Panel-based next-generation sequencing (NGS) screened mutations in 792 genes related to inherited eye diseases. RESULTS: We detected 181 mutations with an 84.7% detection rate in sporadic cases and 87.5% in familial cases. The overall detection rate was 86.4%, with FBN1 accounting for 74.8%. In cases without FBN1 mutations, 23 mutations from seven Marfan-related genes were identified, including four pathogenic or likely pathogenic mutations in LTBP2. The 181 mutations included 165 missenses, 10 splicings, three frameshifts, and three nonsenses. FBN1 accounted for 53.0% of mutations. The most prevalent pathogenic mutation was FBN1 c.4096G>A. Additionally, 94 novel mutations were detected, with 13 de novo mutations in 14 families. CONCLUSION: We expanded the mutation spectrum of the FBN1 gene and provided evidence for the pathogenicity of other Marfan-related genes. Variants in LTBP2 may contribute to the ocular manifestations in MFS, underscoring its role in phenotypic diversity.

Disentangling the "tip-effects" enhanced antibacterial mechanism of Ag nanoparticles.

Silver nanoparticles (Ag NPs) exhibit strong antibacterial activity and are widely used in industries such as medical, food and cosmetics. In this study, Ag nanospheres and Ag nanotriangles are selected as antibacterial agents to reveal the distinct mechanism of tip effects towards their antibacterial performance. A series of antibacterial experiments were implemented, including in situ monitoring as well as studying and determining the evolution of the inhibition zone, minimum inhibitory concentration (MIC)/minimum bactericidal concentration (MBC) values, growth kinetics, bactericidal curve, bacterial morphologies and intracellular reactive oxygen species (ROS). Ag nanotriangles can eradicate E. coli and S. aureus at extremely low concentrations in comparison to Ag nanospheres, in particular under sunlight irradiation. The destroyed bacterial cell walls were examined by scanning electron microscopy. Through the investigation of ROS production, the generation efficiency of ROS is improved by the merit of sunlight irradiation thanks to the localized surface plasmon resonance (LSPR) properties of Ag NPs. However, a more significant improvement in ROS generation efficiency occurred in the presence of Ag nanotriangles contributed by the pronounced "tip effects". This study sheds light on the structure-performance relationship for the rational design of antibacterial agents.

Potential Role of Dipeptidyl Peptidase-4 in Regulating Mitochondria and Oxidative Stress in Cardiomyocytes.

Oxidative stress causes mitochondrial damage and bioenergetic dysfunction and inhibits adenosine triphosphate production, contributing to the pathogenesis of cardiac diseases. Dipeptidyl peptidase 4 (DPP4) is primarily a membrane-bound extracellular peptidase that cleaves Xaa-Pro or Xaa-Ala dipeptides from the N terminus of polypeptides. DPP4 inhibitors have been used in patients with diabetes and heart failure; however, they have led to inconsistent results. Although the enzymatic properties of DPP4 have been well studied, the substrate-independent functions of DPP4 have not. In the present study, we knocked down DPP4 in cultured cardiomyocytes to exclude the effects of differential alteration in the substrates and metabolites of DPP4 then compared the response between the knocked-down and wild-type cardiomyocytes during exposure to oxidative stress. H2O2 exposure induced DPP4 expression in both types of cardiomyocytes. However, knocking down DPP4 substantially reduced the loss of cell viability by preserving mitochondrial bioenergy, reducing intracellular reactive oxygen species production, and reducing apoptosis-associated protein expression. These findings demonstrate that inhibiting DPP4 improves the body's defense against oxidative stress by enhancing Nrf2 and PGC-1α signaling and increasing superoxide dismutase and catalase activity. Our results indicate that DPP4 mediates the body's response to oxidative stress in individuals with heart disease.