Molecular crowding facilitates bundling of IMPDH polymers and cytoophidium formation.

The cytoophidium is a unique type of membraneless compartment comprising of filamentous protein polymers. Inosine monophosphate dehydrogenase (IMPDH) catalyzes the rate-limiting step of de novo GTP biosynthesis and plays critical roles in active cell metabolism. However, the molecular regulation of cytoophidium formation is poorly understood. Here we show that human IMPDH2 polymers bundle up to form cytoophidium-like aggregates in vitro when macromolecular crowders are present. The self-association of IMPDH polymers is suggested to rely on electrostatic interactions. In cells, the increase of molecular crowding with hyperosmotic medium induces cytoophidia, while the decrease of that by the inhibition of RNA synthesis perturbs cytoophidium assembly. In addition to IMPDH, CTPS and PRPS cytoophidium could be also induced by hyperosmolality, suggesting a universal phenomenon of cytoophidium-forming proteins. Finally, our results indicate that the cytoophidium can prolong the half-life of IMPDH, which is proposed to be one of conserved functions of this subcellular compartment.

Efficacy of epi-1 modified epirubicin and curcumin encapsulated liposomes targeting-EpCAM in the inhibition of epithelial ovarian cancer cells.

Treatment of epithelial ovarian cancer (EOC) is a challenge because it still leads to unsatisfactory clinical prognosis. This is due to the toxicity and poor targeting of chemotherapeutic agents, as well as metastasis of the tumor. In this study, we designed a targeted liposome with nanostructures to overcome these problems. In the liposomes, epirubicin and curcumin were encapsulated to achieve their synergistic antitumor efficacy, while Epi-1 was modified on the liposomal surface to target epithelial cell adhesion molecule (EpCAM). Epi-1, a macrocyclic peptide, exhibits active targeting for enhanced cellular uptake and potent cytotoxicity against tumor cells. The encapsulation of epirubicin and curcumin synergistically inhibited the formation of neovascularization and vasculogenic mimicry (VM) channels, thereby suppressing tumor metastasis on SKOV3 cells. The dual drug loaded Epi-1-liposomes also induced apoptosis and downregulated metastasis-related proteins for effective antitumor in vitro. In vivo studies showed that dual drug loaded Epi-1-liposomes prolonged circulation time in the blood and increased the selective accumulation of drug at the tumor site. H&E staining and immunohistochemistry with Ki-67 also showed that targeted liposomes elevated antitumor activity. Also, targeted liposomes downregulated angiogenesis-related proteins to inhibit angiogenesis and thus tumor metastasis. In conclusion, the production of dual drug loaded Epi-1-liposomes is an effective strategy for the treatment of EOC.

Halitosis: etiology, prevention, and the role of microbiota.

OBJECTIVES: This study aims to review halitosis research, discuss its various causes, and propose effective interventions based on the underlying etiologies and mechanisms. The main research question is to identify the primary factors contributing to halitosis and appropriate strategies to address them. MATERIALS AND METHODS: A comprehensive literature review was conducted on halitosis and its associated causes, including oral pathological factors, oral microbial influences, microbial metabolic pathways, gastrointestinal diseases, and gut microbiota dysbiosis. RESULTS: Unhealthy eating habits and an imbalance of microorganisms in the oral cavity and gastrointestinal tract were identified as primary causes of halitosis. Dental caries, periodontal disease, xerostomia, and digestive disorders like gastritis and irritable bowel syndrome were also found to be related to the development of halitosis. Due to poor oral hygiene or antibiotic use, disruption of microbial communities can result in dysbiosis, inflammation, and halitosis. CONCLUSIONS: Halitosis is a multifactorial condition with various underlying causes, including oral and systemic diseases. Effective interventions should be tailored based on the specific etiologies and mechanisms involved. CLINICAL RELEVANCE: Understanding the factors contributing to halitosis is crucial for developing appropriate treatment strategies. Enhancing oral hygiene habits, using antimicrobial drugs, or administering probiotics may help regulate oral or intestinal flora, thereby improving halitosis and overall oral health.

Investigation of periodontal status and bacterial composition aroundmini-implants.

INTRODUCTION: Mini-implants are now widely used in orthodontic treatment. Soft-tissue inflammation around the mini-implant is an important factor affecting its stability. This study aimed to investigate the periodontal status and the bacterial composition around mini-implants. METHODS: A total of 79 mini-implants in 40 patients (aged 18-45 years) were evaluated in this study. The mini-implant probing depth (mPD), mini-implant gingival sulcus bleeding index (mBI), mini-implant plaque index (mPLI), and the composition of the supragingival and subgingival plaque around the mini-implants were recorded. After Congo red staining, the bacteria were classified and counted under a light microscope. RESULTS: The mPLI and mBI around mini-implants in the infrazygomatic crest were higher than those in the buccal shelf and interradicular area. The mPD was higher on the coronal site of the mini-implant than on the mesial, distal, and apical sites in the infrazygomatic crest. The mPLI around the mini-implant was positively correlated with the mBI, and the mBI was positively correlated with the mPD. The supragingival and subgingival bacterial composition around the mini-implants was similar to that of natural teeth. Compared with supragingival bacterial composition, the subgingival bacteria of mini-implants had a significantly lower proportion of cocci and a higher proportion of bacilli and spirochetes. CONCLUSIONS: The bacteria composition of the plaque and the location are important factors in the inflammation around mini-implants. Similar to natural teeth, mini-implants require health maintenance to prevent inflammation of the surrounding soft tissue and maintain stability.

Feasibility of mini-implant insertion between mesial and distal buccal roots of a maxillary first molar: A cone-beam computed tomography imaging study.

INTRODUCTION: Mini-implant insertion in the maxillary posterior region can be influenced by anatomic limitations, thus increasing the failure rate. We explored the feasibility of a new implantation site: the region between the mesial and distal buccal roots of the maxillary first molar. METHODS: Cone-beam computed tomography data from 177 patients were collected from a database. The maxillary first molars were morphologically classified by analyzing the angle and morphology of the mesial and distal buccal roots. Next, 77 subjects were randomly selected from the 177 patients to measure and analyze the hard-tissue morphology in the maxillary posterior region. RESULTS: We devised the Morphological Classification on the Mesial and Distal Buccal Roots of Maxillary First Molar (MCBRMM), divided into 3 types: MCBRMM-I, II, and III. In all subjects, MCBRMM-I, II, and III accounted for 43%, 25%, and 32%, respectively. At 8 mm from the mesial cementoenamel junction of maxillary first molars, the interradicular distance between the maxillary first molar's mesiodistal buccal roots of MCBRMM-I was 2.6 mm, showing an upward trend from the cementoenamel junction to the apex. The distance from the buccal bone cortex to the palatal root was >9 mm. The buccal cortical thickness was >1 mm. CONCLUSIONS: This study provided a potential site for mini-implant insertion in the maxillary posterior region: the alveolar bone of maxillary first molars in MCBRMM-I.

Robust Hydrogel Adhesion by Harnessing Bioinspired Interfacial Mineralization.

Hydrogels have gained intensive interest in biomedical and flexible electronics, and adhesion of hydrogels to substrates or devices is indispensable in these application scenarios. Although numerous hydrogel adhesion strategies have been developed, it is still challenging to achieve a hydrogel with robust adhesion interface through a universal yet simple method. Here, a strategy for establishing strong interfacial adhesion between various hydrogels and a wide variety of substrates (i.e., soft hydrogels and rigid solids, including glass, aluminum, PET, nylon and PDMS) even under wet conditions, is reported. This strong interfacial adhesion is realized by constructing a bioinspired mineralized transition layer through ion diffusion and subsequent mineral deposition. This strategy is not only generally applicable to a broad range of substrates and ionic pairs, but also compatible with various fabrication approaches without compromising their interfacial robustnesses. This strategy is further demonstrated in the application of single-electrode triboelectric nanogenerators (TENG), where a robust interface between the hydrogel and elastomer layers is enabled to ensure a reliable signal generation and output.

Migratory pharyngeal foreign bodies and related complications: Analysis of 20 cases.

PURPOSE: To explore the diagnostic approach and therapeutic method of migratory pharyngeal foreign bodies and related complications, to improve the understanding of such disease and to reduce misdiagnosis and missed diagnosis. MATERIAL AND METHODS: A retrospective study was performed by collecting patients who were treated because of the related complications caused by migratory pharyngeal foreign bodies from 2012 to 2020. RESULTS: A total of 20 patients were admitted to hospital due to the related complications. 14 cases showed cervical mass; 3 cases showed abscess of the mouth floor; 1 cases showed retropharyngeal abscess; 1 cases showed laryngeal granuloma; 1 cases showed mass of tongue. All patients received imaging examination of B-ultrasonography or computed tomography (CT). 19 patients were treated by surgery, and 1 patient was taken conservative treatment. All foreign bodies was successfully removed. As for the type of foreign bodies, there have 15 cases of fishbone, 2 cases of crabshell, 2 cases of shrimp shell, 1 cases of duck bone. CONCLUSIONS: Migrating foreign bodies and related complications are rare in clinic, much attention should be paid to avoid missed diagnosis or misdiagnosis.

DNAzyme-Catalyzed Cellular Oxidative Stress Amplification for Pro-protein Activation in Living Cells.

The conditional control of protein function in response to the physiological change of cells is of great interest for studying protein function in biological settings and developing protein therapeutics. We report herein that catalase (CAT) DNAzyme can potentiate the generation of reactive oxygen species (ROS) in living cells by knocking down catalase expression, which could further activate a reactive oxygen species (ROS)-responsive pro-protein, RNase A-NBC, in situ. Using an optimized lipid nanoparticle delivery system to simultaneously introduce CAT DNAzyme and RNase A-NBC into cells, we show that the pro-protein, RNase A-NBC, could be activated in a significantly enhanced manner to prohibit tumor cell growth in different types of cancer cells. We believe the methodology of regulating pro-protein activity using DNAzyme biocatalysis to differentiate intracellular environment could further be extended to other functional proteins, and even fundamental investigations in living systems to develop pro-protein therapeutics.

[Purification and component identification of total proanthocyanidins in Choerospondias axillaris pericarp].

The present study determined the quantitative markers of total proanthocyanidins in the purification of the industrial waste Choerospondias axillaris pericarp based on the comparison results of high-performance liquid chromatography(HPLC) and mass spectrometry(MS) and optimized the purification process with two stable procyanidins as markers. The adsorption and desorption of five different macroporous adsorption resins, the static adsorption kinetics curve of NKA-Ⅱ resin, the maximum sample load, and the gradient elution were investigated. The UPLC-Q-TOF-MS/MS was employed for qualitative analysis of the newly-prepared total proanthocyanidins of C. axillaris pericarp. As revealed by the results, NKA-Ⅱ resin displayed strong adsorption and desorption toward total proanthocyanidins. The sample solution(50 mg·mL~(-1)) was prepared from 70% ethanol crude extract of C. axillaris pericarp dissolved in water and 7-fold BV of the sample solution was loaded, followed by static adsorption for 12 h. After 8-fold BV of distilled water and 6-fold BV of 10% ethanol were employed to remove impurities, the solution was eluted with 8-fold BV of 50% ethanol, concentrated, and dried under reduced pressure, and purified total proanthocyanidin powder was therefore obtained. Measured by vanillin-hydrochloric acid method, the purity and transfer rate of total proanthocyanidins were 47.67% and 59.92%, respectively, indicating the feasibi-lity of the optimized process. UPLC-Q-TOF-MS/MS qualitative analysis identified 16 procyanidins in C. axillaris total proanthocyanidins. The optimized purification process is simple in operation and accurate in component identification, and it can be applied to the process investigation of a class of components that are difficult to be separated and purified. It can also provide technical support and research ideas for the comprehensive utilization of industrial waste.

Hierarchical Self-assembly of Discrete Metal-Organic Cages into Supramolecular Nanoparticles for Intracellular Protein Delivery.

Hierarchical self-assembly (HAS) is a powerful approach to create supramolecular nanostructures for biomedical applications. This potency, however, is generally challenged by the difficulty of controlling the HAS of biomacromolecules and the functionality of resulted HAS nanostructures. Herein, we report a modular approach for controlling the HAS of discrete metal-organic cages (MOC) into supramolecular nanoparticles, and its potential for intracellular protein delivery and cell-fate specification. The hierarchical coordination-driven self-assembly of adamantane-functionalized M12 L24 MOC (Ada-MOC) and the host-guest interaction of Ada-MOC with ß-cyclodextrin-conjugated polyethylenimine (PEI-ßCD) afford supramolecular nanoparticles in a controllable manner. HAS maintains high efficiency and orthogonality in the presence of protein, enabling the encapsulation of protein into the nanoparticles for intracellular protein delivery for therapeutic application and CRISPR/Cas9 genome editing.

Tetraphenylethylene-Featured Fluorescent Supramolecular Nanoparticles for Intracellular Trafficking of Protein Delivery and Neuroprotection.

The delivery of protein into mammalian cells enables the dissection and manipulation of biological processes; however, this potency is challenged by the lack of an efficient protein delivery tool and a means to monitor its intracellular trafficking. Herein, we report that the hierarchical self-assembly of tetraphenylethylene (TPE)-featured metal-organic cages (MOCs) and ß-cyclodextrin-conjugated polyethylenimine can generate fluorescent supramolecular nanoparticles (FSNPs) to deliver protein into neural cells, a cell line that is hard to transfect using conventional strategy. Further, the aggregation-induced emission (AIE) of TPE enabled the fluorescent monitoring of cytosolic protein release. It is found that FSNPs can deliver and release protein into cytosol for subcellular targeting as fast as 18 h post-delivery. Moreover, the delivery of molecular chaperone DJ-1 using FSNPs activates MAPK/ERK signaling of neural cells to protect cells from oxidative stress.

Rapid and sensitive detection of NGAL for the prediction of acute kidney injury via a polydopamine nanosphere/aptamer nanocomplex coupled with DNase I-assisted recycling amplification.

Early detection of acute kidney injury (AKI) is important, as early intervention and treatment can prevent further kidney injury and improve kidney health. Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as the earliest and promising non-invasive biomarker of AKI in urine, and has been used as a new predictive biomarker of AKI in the bench-to-bedside journey. In this work, a nanocomplex composed of a polydopamine nanosphere (PDANS) and a fluorophore-labelled aptamer has been constructed for the detection of NGAL using a DNase I-assisted recycling amplification strategy. After the addition of NGAL, the fluorescence intensity increases linearly over the NGAL concentration range from 12.5 to 400 pg mL-1. The limit of detection of this strategy is found to be 6.25 pg mL-1, which is almost 5 times lower than that of the method that does not involve DNase I. The process can be completed within 1 h, indicating a fast fluorescence response. Furthermore, the method using the nanocomplex coupled with DNase I has been successfully utilized for the detection of NGAL in the urine from cisplatin-induced AKI and five-sixths nephrectomized mice, demonstrating its promising ability for the early prediction of AKI. This method also demonstrates the protective effect of the Huangkui capsule on AKI, and provides an effective way to screen potentially protective drugs for renal disease.

Optimization, characterization and evaluation of liposomes from Malus hupehensis (Pamp.) Rehd. extracts.

The Malus hupehensis (Pamp.) Rehd. is a traditional medicine and edible plant. The previous study found that the extracts of M. hupehensis (Pamp.) Rehd. had a good antioxidant activity in vivo and in vitro. But its clinical application was limited by its poor solubility, rapidly metabolized and poor bioavailability. Hence, this article aimed at developing liposomes as a novel transdermal system for delivering M. hupehensis extracts efficiently. The prepared liposomes were characterized regarding their entrapment efficiency percentage (EE%), vesicle size (VS), polydispersity index (PDI), zeta potential (ZP) and drug loading (DL). Box-Behnken design response surface methodology and factorial design were used to optimize formulation and preparation process, respectively. The optimized liposomes had an EE of 77.29 ± 0.99%, VS of 102.74 ± 1.61 nm, ZP of -21.79 ± 1.43 mV, PDI of 0.291 ± 0.005 and DL was 6.68 ± 0.49%. Transmission electron microscopy showed liposomes had a regular spherical surface. In addition, liposomes exhibited superior skin permeation potential and retention capacity compared with solution. Histopathological study ensured the safety of liposome application. Meanwhile, the optimized liposome has a good stability. Hence, M. hupehensis extracts liposomes could be considered a promising vehicle for transdermal delivery.

Losartan loaded liposomes improve the antitumor efficacy of liposomal paclitaxel modified with pH sensitive peptides by inhibition of collagen in breast cancer.

The dense collagen network in tumors restricts the penetration of drugs into tumors. Free losartan could inhibit collagen, but it would cause hypotension at the dosage of 10 mg/kg/d. In this study, losartan was encapsulated in liposomes (LST-Lip) and the collagen inhibition ability of LST-Lip was investigated. Our results showed the blood pressure was not affected by LST-Lip at the dosage of 2.5 mg/kg every other day. The amount of Evans Blue in tumor in LST-Lip group was 1.98 times of that in control group. Confocal laser scanning microscopy images showed that prior injection of LST-Lip could inhibit collagen and further improve the tumorous accumulation of liposomes modified with TH peptides (AGYLLGHINLHHLAHL(Aib)HHIL-NH2) (TH-Lip) in 4T1 tumors. Compared with control group, the tumor inhibition rate of combined strategy of LST-Lip and paclitaxel loaded TH-Lip (PTX-TH-Lip) was 41.73%, while that of group only treated with PTX-TH-Lip was 14.94%. Masson's trichrome staining confirmed that collagen was inhibited in LST-Lip group. Thus, the administration of LST-Lip in advance could inhibit the collagen in tumors effectively and did not affect the blood pressure, then PTX-TH-Lip injected subsequently could exert enhanced antitumor efficacy. In conclusion, this combined strategy might be promising for breast cancer therapy.

Dynamic Interfacial Adhesion through Cucurbit[n]uril Molecular Recognition.

Supramolecular building blocks, such as cucurbit[n]uril (CB[n])-based host-guest complexes, have been extensively studied at the nano- and microscale as adhesion promoters. Herein, we exploit a new class of CB[n]-threaded highly branched polyrotaxanes (HBP-CB[n]) as aqueous adhesives to macroscopically bond two wet surfaces, including biological tissue, through the formation of CB[8] heteroternary complexes. The dynamic nature of these complexes gives rise to adhesion with remarkable toughness, displaying recovery and reversible adhesion upon mechanical failure at the interface. Incorporation of functional guests, such as azobenzene moieties, allows for stimuli-activated on-demand adhesion/de-adhesion. Macroscopic interfacial adhesion through dynamic host-guest molecular recognition represents an innovative strategy for designing the next generation of functional interfaces, biomedical devices, tissue adhesives, and wound dressings.

Dominant, toxic gain-of-function mutations in gars lead to non-cell autonomous neuropathology.

Charcot-Marie-Tooth (CMT) neuropathies are collectively the most common hereditary neurological condition and a major health burden for society. Dominant mutations in the gene GARS, encoding the ubiquitous enzyme, glycyl-tRNA synthetase (GlyRS), cause peripheral nerve degeneration and lead to CMT disease type 2D. This genetic disorder exemplifies a recurring motif in neurodegeneration, whereby mutations in essential, widely expressed genes have selective deleterious consequences for the nervous system. Here, using novel Drosophila models, we show a potential solution to this phenomenon. Ubiquitous expression of mutant GlyRS leads to motor deficits, progressive neuromuscular junction (NMJ) denervation and pre-synaptic build-up of mutant GlyRS. Intriguingly, neuronal toxicity is, at least in part, non-cell autonomous, as expression of mutant GlyRS in mesoderm or muscle alone results in similar pathology. This mutant GlyRS toxic gain-of-function, which is WHEP domain-dependent, coincides with abnormal NMJ assembly, leading to synaptic degeneration, and, ultimately, reduced viability. Our findings suggest that mutant GlyRS gains access to ectopic sub-compartments of the motor neuron, providing a possible explanation for the selective neuropathology caused by mutations in a widely expressed gene.

A Comprehensive Study on Pyrolysis Mechanism of Substituted ß-O-4 Type Lignin Dimers.

In order to understand the pyrolysis mechanism of ß-O-4 type lignin dimers, a pyrolysis model is proposed which considers the effects of functional groups (hydroxyl, hydroxymethyl and methoxyl) on the alkyl side chain and aromatic ring. Furthermore, five specific ß-O-4 type lignin dimer model compounds are selected to investigate their integrated pyrolysis mechanism by density functional theory (DFT) methods, to further understand and verify the proposed pyrolysis model. The results indicate that a total of 11 pyrolysis mechanisms, including both concerted mechanisms and homolytic mechanisms, might occur for the initial pyrolysis of the ß-O-4 type lignin dimers. Concerted mechanisms are predominant as compared with homolytic mechanisms throughout unimolecular decomposition pathways. The competitiveness of the eleven pyrolysis mechanisms are revealed via different model compounds, and the proposed pyrolysis model is ranked in full consideration of functional groups effects. The proposed pyrolysis model can provide a theoretical basis to predict the reaction pathways and products during the pyrolysis process of ß-O-4 type lignin dimers.

Recent developments in ureteral stent: Substrate material, coating polymer and technology, therapeutic function.

The ureteral stent is an effective treatment for clinical ureteral stricture following urological surgery, and the functional coating of the stent could effectively inhibit bacterial colonization and other complications. The present review provides an analysis and description of the materials used in ureteral stents and their coatings. Emphasis is placed on the technological advancements of functional coatings, taking into consideration the characteristics of these materials and the properties of their active substances. Furthermore, recent advances in enhancing the therapeutic efficacy of functional coatings are also reviewed. It is anticipated that this article will serve as a valuable reference providing insights for future research development on new drug-loaded ureteral stents.

A Mendelian Randomisation Analysis Reveals No Relationship Between Periodontitis and Coronary Atherosclerosis.

OBJECTIVES: Growing evidence appears to intimate a profound connection between periodontitis and coronary atherosclerosis (CA), yet the existence of a causal relationship remains unclear. Through the implementation of Mendelian randomization analysis, we further evaluated the potential causal link between chronic/acute periodontitis (CP/AP) and CA. METHODS: Utilizing genome-wide association study (GWAS) summary statistics, we incorporated periodontitis data derived from European samples (n1 = 198,441; n2 = 195,762) and CA data from 61,194 cases. We conducted a 2 sample, bidirectional Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW) method as the main analytical approach. Supplementary analyses were executed through MR Egger, Weighted median (WM), IVW, Simple mode, and Weighted mode approaches. RESULTS: The IVW analysis revealed no significant causal relationship between CA and periodontitis (CA-CP: OR = 2.110, 95% CI = 0.208-21.317, P = .527; CA-AP: OR = 0.414, 95% CI = 0.051-3.384, P = .644). Similarly, the bidirectional analysis did not identify impact of periodontitis on CA (OR = 1.000, 95% CI = 0.999-1.001, P = .953). The supplementary analyses corroborated these findings. CONCLUSIONS: While studies highlighting a correlation between periodontitis and CA, our comprehensive analysis does not corroborate a causal association between periodontitis and CA. Further research is needed to elucidate other potential shared mechanisms and causal evidence between periodontitis and CA.

Amine response smartphone-based portable and intelligent polyvinyl alcohol films for real-time detection of shrimp freshness.

Food freshness monitoring is an important component in ensuring food safety for consumers and the food industry. Therefore, there is an urgent need for a portable, low-cost, and efficient detection method to determine the freshness. In this study, polyvinyl alcohol (PVA) was used as polymer carrier to prepare electrospinning film containing curcumin (Cur) and gardenia blue (GB) as intelligent indicator label on food packaging for real-time nondestructive detection of freshness of shrimp. The detection limit of ammonia response is less than or equal to 20 ppm, and the detection time is about 1 min, indicating that it has a sensitive response effect. At the same time, a smartphone application that can identify amines in response to color changes has been developed, and consumers can understand freshness by scanning the label. This study demonstrates the huge potential of smart indicator labels for food freshness monitoring.