Cysteine (Cys) not only plays an indispensable role in maintaining the redox balance in organisms, but is also an important nutrient in the food industry. Fluorescence-based detection systems have emerged as an effective method to track the locations and concentrations of different species. To achieve efficient monitoring of Cys in both food samples and biological systems, a novel lipid droplet (LD) targeted fluorescent probe (namely NIT-Cys) was constructed for the turn-on detection of Cys, characterized by a large Stokes shift (142 nm), a short response time (<8 min), and a low Cys detection limit (39 nM). Furthermore, the NIT-Cys probe has been successfully used not only to quantify the amounts of Cys in selected food samples, but also to enable the visualization of endogenous Cys in acetaminophen (APAP)-induced drug-induced liver injury cells, zebrafish larvae and mice models. Consequently, the work presented here provides an efficient tool for monitoring Cys.
Tissue engineering involves implanting grafts into damaged tissue sites to guide and stimulate the formation of new tissue, which is an important strategy in the field of tissue defect treatment. Scaffolds prepared in vitro meet this requirement and are able to provide a biochemical microenvironment for cell growth, adhesion, and tissue formation. Scaffolds made of piezoelectric materials can apply electrical stimulation to the tissue without an external power source, speeding up the tissue repair process. Among piezoelectric polymers, poly(vinylidene fluoride) (PVDF) and its copolymers have the largest piezoelectric coefficients and are widely used in biomedical fields, including implanted sensors, drug delivery, and tissue repair. This paper provides a comprehensive overview of PVDF and its copolymers and fillers for manufacturing scaffolds as well as the roles in improving piezoelectric output, bioactivity, and mechanical properties. Then, common fabrication methods are outlined such as 3D printing, electrospinning, solvent casting, and phase separation. In addition, the applications and mechanisms of scaffold-based PVDF in tissue engineering are introduced, such as bone, nerve, muscle, skin, and blood vessel. Finally, challenges, perspectives, and strategies of scaffold-based PVDF and its copolymers in the future are discussed.
Polyvinyls , Tissue Engineering , Tissue Scaffolds , Polyvinyls/chemistry , Tissue Scaffolds/chemistry , Tissue Engineering/methods , Humans , Printing, Three-Dimensional , Biocompatible Materials/chemistry , Polymers/chemistry , Animals , Fluorocarbon Polymers
The complex genomics, immunosuppressive tumor microenvironment (TME), and chemotherapeutic resistance of osteosarcoma (OS) have resulted in limited therapeutic effects in the clinic. Ferroptosis is involved in tumor progression and is regulated mainly by glutathione peroxidase 4 (GPX4). Small interfering RNA (siRNA)-based RNA interference (RNAi) can precisely target any gene. However, achieving effective siRNA delivery is highly challenging. Here, we fabricated a TME-responsive metal-organic framework (MOF)-based biomimetic nanosystem (mFeP@si) with siGPX4 delivery and sonodynamic therapy (SDT) to treat OS by targeting ferroptosis. Under ultrasound (US) irradiation, mFeP@si achieves lysosomal escape via singlet oxygen (1O2)-mediated lysosomal membrane disruption and then accelerates ROS generation and glutathione (GSH) depletion. Meanwhile, siGPX4 silences GPX4 expression by binding to GPX4 mRNA and leads to the accumulation of toxic phospholipid hydroperoxides (PL-OOH), further magnifying the ROS storm and triggering ferroptosis. Notably, synergistic therapy remarkably enhances antitumor effects, improves the immunosuppressive TME by inducing potent immunogenic cell death (ICD), and increases the sensitivity of chemotherapy-resistant OS cells to cisplatin. Overall, this novel nanosystem, which targets ferroptosis by integrating RNAi and SDT, exhibits strong antitumor effects both in vitro and in vivo, providing new insights for treating OS.
Objective: This experiment aimed to obtain the relatively rare cis-crocetin isomer from natural plants, which predominantly exist in the more stable all-trans configuration. This was achieved through iodine-induced isomerization, followed by purification and structural identification. The study also aimed to compare the pharmacokinetic differences between cis- and trans-crocetin in vivo. Methods: Trans-crocetin of high purity was extracted by hydrolysis from gardenia yellow pigment. Cis-crocetin was then synthesized through an optimized electrophilic addition reaction induced by elemental iodine, and subsequently separated and purified via silica gel column chromatography. Structural identification of cis-crocetin was determined using IR, UV, and NMR techniques. In vivo pharmacokinetic studies were conducted for both cis- and trans-crocetin. In addition to this, we have conducted a comparative study on the in vivo anti-hypoxic activity of trans- and cis-crocetin. Results: Under the selected reaction conditions using DMF as the solvent, with a concentration of 2.5 mg/mL for both trans-crocetin and the iodine solution, and adjusting the illumination time according to the amount of trans-crocetin, the rate of iodine-induced isomerization was the fastest. Cis-crocetin was successfully obtained and, after purification, its structure was identified and found to be consistent with reported data. Cis-crocetin exhibited a faster absorption rate and higher bioavailability, and despite its shorter half-life, it could partially convert to trans-crocetin in the body, thereby extending the duration of the drug's action within the body to some extent. Conclusion: This study accomplished the successful preparation and structural identification of cis-crocetin. Additionally, through pharmacokinetic studies, it uncovered notable variations in bioavailability between cis- and trans-crocetin. These findings serve as a solid scientific foundation for future functional research and practical applications in this field.
An ultra-compact and efficient acousto-optic modulator based on a thin-film lithium niobate-chalcogenide (ChG) hybrid platform was designed and realized. In this approach, π phase-shift Bragg grating has an ultra-short effective interaction length of only â¼ 300 µm and a compact footprint of 200 × 300 µm2. The strong microwave-acoustic coupling and superior photo-elastic property of the ChG allow us to achieve a half-wave voltage of Vπ = 1.08â V (4.07â V) for the π phase-shift Bragg grating (waveguide Bragg grating), corresponding to VπL = 0.03â V·cm (0.09â V·cm). This acousto-optic modulator exhibits a compact size, and low power consumption, and can be used for on-chip optical interconnects and microwave photonics.
This paper reports an optical strain sensor that integrates a self-powered mechanoluminescent (ML) elastic fiber with a flexible circuit. The inclusion of an alumina nanoparticle as the additive results in seven-fold enhancement of ML intensity while maintaining flexibility of 120% strain. The sensor facilitates the detection of strain and stretching speed. It attains a sensitivity of 0.0022â lx/(1% strain) and a resolution of 0.2% strain, respectively. We have successfully applied it to detect bending motions of the finger, wrist, and elbow. This wearable strain sensor holds promise for diverse applications in wearable technology.
Background and Aims: Elevated eosinophils typically indicate hypersensitive inflammation; however, their involvement in cardiovascular events remains incompletely understood. We investigated the association between the absolute eosinophil count (AEC) and major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Additionally, we determine whether the integration of AEC with the SYNTAX II score could improve predictive ability. Methods and Results: The AECs of 1711 patients with ACS undergoing PCI from June 2016 to November 2017 were analyzed on admission. All recruitments were splitted into three groups based on AEC tertiles and 101 participants underwent one or more noteworthy outcomings. The association between AEC and MACCEs (defined as a composite of cardiovascular death, myocardial infarction [MI], and stroke) was tested by Cox proportional-hazards regression analysis. After adjusting for confounders, AEC was independently associated with MACCEs (HR 11.555, 95% CI: 3.318-40.239). Patients in the lowest AEC tertile (T1) as a reference, those in the higher tertiles had an incrementally higher risk of MACCEs (T3: HR 1.848 95% CI: 1.157-2.952; P for trend=0.008). Inclusion of AEC enhanced the predictive accuracy of the SYNTAX II score for MACCEs (AUC: from 0.701 [95% CI: 0.646-0.756] to 0.728 [95% CI: 0.677-0.780]; DeLong's test, P = 0.020). Conclusion: AEC is independently linked to MACCEs in ACS patients who underwent PCI, and adds incremental predictive information to the SYNTAX II score.
Metal nanoclusters (MNCs) represent a promising class of materials for catalytic carbon dioxide and proton reduction as well as dihydrogen oxidation. In such reactions, multiple proton-coupled electron transfer (PCET) processes are typically involved, and the current understanding of PCET mechanisms in MNCs has primarily focused on the sequential transfer mode. However, a concerted transfer pathway, i.e., concerted electron-proton transfer (CEPT), despite its potential for a higher catalytic rate and lower reaction barrier, still lacks comprehensive elucidation. Herein, we introduce an experimental paradigm to test the feasibility of the CEPT process in MNCs, by employing Au18(SR)14 (SR denotes thiolate ligand), Au22(SR)18, and Au25(SR)18- as model clusters. Detailed investigations indicate that the photoinduced PCET reactions in the designed system proceed via an CEPT pathway. Furthermore, the rate constants of gold nanoclusters (AuNCs) have been found to be correlated with both the size of the cluster and the flexibility of the Au-S framework. This newly identified PCET behavior in AuNCs is prominently different from that observed in semiconductor quantum dots and plasmonic metal nanoparticles. Our findings are of crucial importance for unveiling the catalytic mechanisms of quantum-confined metal nanomaterials and for the future rational design of more efficient catalysts.
A cocrystallization strategy is used through incorporation of 1,2,4,5-tetracyanobenzene (TCNB) as an acceptor with halogen-substituent thioxanthone (TX) derivatives as donors. The resulting cocrystals TT-R (R = H, F, Cl, Br, or I) transform the thermally activated delayed fluorescence emission in the TT-H, TT-F, and TT-Cl cocrystals to room-temperature phosphorescence in the TT-Br and TT-I cocrystals. Definite crystal packing structures demonstrate a 1:1 alternative donor-acceptor stacking in the TT-H cocrystal, a 2:1 alternative donor-acceptor stacking in the TT-F and TT-Cl cocrystals, and a separate stacking of donor and acceptor in the TT-Br and TT-I cocrystals. A transformation law can be revealed that with an increase in atomic number from H, F, Cl, Br, to I, the cocrystals show the structural transformation of the number of aggregated TX-R molecules from monomers to dimers and finally to multimers. This work will facilitate an understanding of the effect of halogen substituents on the crystal packing structure and luminescence properties in the cocrystals.
OBJECTIVES: To investigate the effects of low tube voltage on coronary plaques and pericoronary fat assessment, and to compare their extent among various levels of low voltage. MATERIALS AND METHODS: Patients were recommended for high-pitch low-tube voltage coronary computed tomography angiography (CCTA), and they were included if they had poor image quality and were referred to a conventional CCTA. The patients were classified into a low-voltage group (with 70-kV, 80-kV, and 90-kV subgroups) and a conventional group (100/120 kV). Their total plaque and subcomponent volumes and pericoronary fat attenuation index (FAI) were measured. RESULTS: A total of 1002 image slices (from 65 patients and 74 plaques) were included, including 21, 31, 13, 4, and 61 patients in the 70-kV, 80-kV, 90-kV, 100-kV, and 120-kV groups respectively. The CT values of noncalcified plaques in the conventional and low-voltage groups were 54.6 ± 21.3 HU and 31.5 ± 22.6 HU, respectively (p < 0.05). Compared with the conventional group, the necrotic core and calcification volume were increased, and the fibrolipid volume, periplaque, and right coronary artery FAI were decreased in the low-voltage group and its subgroups (p < 0.001). The magnitude of changes in fibrous and calcification volumes increased in the 70-kV subgroup compared with that in the 90-kV subgroup (p < 0.05). CONCLUSION: Low tube voltages, particularly of 70 kV, have a significant effect on coronary plaque and FAI. The effect of low voltage on plaque composition is characterized by a polarization pattern, i.e., a decrease in fibrolipid (medium density) and an increase in necrotic core (low density) and calcification (high density). CLINICAL RELEVANCE STATEMENT: Our results highlight the comparability and repeatability of plaque and pericoronary fat assessments facilitated by the same or a similar tube voltage. It is necessary to carry out studies on the specificity threshold of low tube voltage at each level. KEY POINTS: ⢠Low tube voltage had a significant effect on coronary plaque and pericoronary fat, particularly 70 kV. ⢠The effect of low tube voltage on plaque composition shows the shift from medium-density mixed components to low- and high-density components. ⢠It is necessary to correct the specificity threshold or attenuation difference for low tube voltage at each level.
OBJECTIVE: This study aimed to explore the characteristics of abdominal aortic blood flow in patients with heart failure (HF) using 99mTc-diethylenetriaminepentaacetic acid (DTPA) renal scintigraphy. We investigated the ability of renal scintigraphy to measure the cardiopulmonary transit time and assessed whether the time-to-peak of the abdominal aorta (TTPa) can distinguish between individuals with and without HF. METHODS: We conducted a retrospective study that included 304 and 37 patients with and without HF (controls), respectively. All participants underwent 99mTc-DTPA renal scintigraphy. The time to peak from the abdominal aorta's first-pass time-activity curve was noted and compared between the groups. The diagnostic significance of TTPa for HF was ascertained through receiver operating characteristic (ROC) analysis and logistic regression. Factors influencing the TTPa were assessed using ordered logistic regression. RESULTS: The HF group displayed a significantly prolonged TTPa than controls (18.5 [14, 27] s vs. 11 [11, 13] s). Among the HF categories, HF with reduced ejection fraction (HFrEF) exhibited the longest TTPa compared with HF with mildly reduced (HFmrEF) and preserved EF (HFpEF) (25 [17, 36.5] s vs. 17 [15, 23] s vs. 15 [11, 17] s) (P < 0.001). The ROC analysis had an area under the curve of 0.831, which underscored TTPa's independent diagnostic relevance for HF. The diagnostic precision was enhanced as left ventricular ejection fraction (LVEF) declined and HF worsened. Independent factors for TTPa included the left atrium diameter, LVEF, right atrium diameter, velocity of tricuspid regurgitation, and moderate to severe aortic regurgitation. CONCLUSIONS: Based on 99mTc-DTPA renal scintigraphy, TTPa may be used as a straightforward and non-invasive tool that can effectively distinguish patients with and without HF.
Aorta, Abdominal , Heart Failure , Kidney , Technetium Tc 99m Pentetate , Humans , Heart Failure/diagnostic imaging , Heart Failure/physiopathology , Male , Female , Retrospective Studies , Aged , Middle Aged , Aorta, Abdominal/diagnostic imaging , Aorta, Abdominal/physiopathology , Kidney/diagnostic imaging , Kidney/blood supply , Kidney/physiopathology , Radionuclide Imaging/methods , ROC Curve
It is important to improve the production of bioactive secondary products for drug development. The Escherichia coli-Streptomyces shuttle vector pSET152 and its derived vector pIB139 containing a strong constitutive promoter ermEp* are commonly used as integrative vectors in actinomycetes. Four new integrative vectors carrying the strong constitutive promoter kasOp*, hrdBp, SCO5768p, and SP44, respectively, were constructed and proven to be functional in different mangrove-derived Streptomyces host strains by using kanamycin resistance gene neo as a reporter. Some biosynthetic genes of elaiophylins, azalomycin Fs, and armeniaspirols were selected and inserted into these vectors to overexpress in their producers including Streptomyces sp. 219807, Streptomyces sp. 211726, and S. armeniacus DSM 43125, resulting in an approximately 1.1-1.4-fold enhancement of the antibiotic yields.
Actinobacteria , Streptomyces , Streptomyces/genetics , Anti-Bacterial Agents , Promoter Regions, Genetic/genetics , Genetic Vectors , Actinobacteria/genetics , Plasmids
Halide-based solid electrolytes are promising candidates for all solid-state lithium-ion batteries (ASSLBs) due to their high ionic conductivity, wide electrochemical window, and excellent chemical stability with cathode materials. However, when tested in practice, their intrinsic electrochemical stability windows do not well match the conditions for stable operation of ASSBs. Existing literature reports halide-based ASSBs that still operate well outside the electrochemical stability window, while ASSBs that do not operate within the window are not well studied or the studies are based on the cathode material interface. In this study, we aim to elucidate the mechanism behind all-solid-state battery failure by investigating how the reduction potential of Li3YCl6 solid-state electrolyte itself changes under overcharging conditions. Our findings demonstrate that in Li-In|Li3YCl6|Li3YCl6-C half-cells during the first state of charge, Cl ions participate in charge compensation, resulting in a depletion of ligands. This phenomenon significantly affects the reduction potential of Y3+, causing it to be reduced to Y2Cl3 and ultimately to Y0 at conditions far exceeding its actual reduction potential. Furthermore, we analyze the interfacial impedance induced by this process and propose a novel perspective on battery failure.
Background: Given the differential expression and biological functions of protein arginine methylation (PAM) regulators in lung adenocarcinoma (LUAD), it may be of great value in the diagnosis, prognosis, and treatment of LUAD. However, the expression and function of PAM regulators in LUAD and its relationship with prognosis are unclear. Methods: 8 datasets including 1798 LUAD patients were selected. During the bioinformatic study in LUAD, we performed (i) consensus clustering to identify clusters based on 9 PAM regulators related expression profile data, (ii) to identify hub genes between the 2 clusters, (iii) principal component analysis to construct a PAM.score based on above genes, and (iv) evaluation of the effect of PAM.score on the deconstruction of tumor microenvironment and guidance of immunotherapy. Results: We identified two different clusters and a robust and clinically practicable prognostic scoring system. Meanwhile, a higher PAM.score subgroup showed poorer prognosis, and was validated by multiple cohorts. Its prognostic effect was validated by ROC (Receiver operating characteristic curve) curve and found to have a relatively good prediction efficacy. High PAM.score group exhibited lower immune score, which associated with an immunosuppressive microenvironment in LUAD. Finally, patients exhibiting a lower PAM.score presented noteworthy therapeutic benefits and clinical advantages. Conclusion: Our PAM.score model can help clinicians to select personalized therapy for LUAD patients, and PAM.score may act a part in the development of LUAD.
α-Glucosidase (α-Glu) is implicated in the progression and pathogenesis of type II diabetes (T2D). In this study, we developed a rapid colorimetric technique using platinum nanoparticles stabilized by chitosan (Ch-PtNPs) to detect α-Glu activity and its inhibitor. The Ch-PtNPs facilitate the conversion of 3,3',5,5'-tetramethylbenzidine (TMB) into oxidized TMB (oxTMB) in the presence of dissolved O2. The catalytic hydrolysis of 2-O-α-D-glucopyranosyl-L-ascorbic acid (AA-2G) by α-Glu produces ascorbic acid (AA), which reduces oxTMB to TMB, leading to the fading of the blue color. However, the presence of α-Glu inhibitors (AGIs) hinders the generation of AA, allowing Ch-PtNPs to re-oxidize colorless TMB back to blue oxTMB. This unique phenomenon enables the colorimetric detection of α-Glu activity and AGIs. The linear range for α-Glu was found to be 0.1-1.0 U mL-1 and the detection limit was 0.026 U mL-1. Additionally, the half-maximal inhibition value (IC50) for acarbose, an α-Glu inhibitor, was calculated to be 0.4769 mM. Excitingly, this sensing platform successfully detected α-Glu activity in human serum samples and effectively screened AGIs. These promising findings highlight the potential application of the proposed strategy in clinical diabetes diagnosis and drug discovery.
Tuberculosis (TB), as one of the leading causes of death, poses a serious predicament to the world. MicroRNAs (miRNAs) play a role in the post-transcriptional regulation of gene expression. It has been reported that the expression of miRNAs changes upon mycobacterial infection; the screening and identification of miRNAs regulating the expression of genes could benefit our understanding of TB pathogenesis and generate effective strategies for its control and prevention. In this study, luciferase assays showed that miR-4687-5p is bound to the 3'-untranslated region of natural resistance-associated macrophage protein 1 (NRAMP1). Additionally, we found a significant increase in miR-4687-5p expression in Mycobacterium tuberculosis (Mtb)-infected A549 cells. Concomitantly, we detected a reduced level of NRAMP1 expression, suggesting that NRAMP1 is one of the targets of miR-4687-5p. Infection experiments evidenced that the transfection of miR-4687-5p induced a decrease in NRAMP1 expression and increased intracellular Mtb loads post-infection, indicating that miR-4687-5p promotes the intracellular survival of Mtb through its downregulation of the NRAMP1 protein level. We also found that the transfection of miR-4687-5p induced increased apoptosis and decreased cell proliferation post-infection with Mtb. The results presented in our study suggest that miR-4687-5p may be indicative of the susceptibility of Mtb infection to humans and could act as a potential therapeutic target for tuberculosis treatment.
Supramolecular peptide nanofiber hydrogels are emerging biomaterials for tissue engineering, but it is difficult to fabricate multi-functional systems by simply mixing several short-motif-modified supramolecular peptides because relatively abundant motifs generally hinder nanofiber cross-linking or the formation of long nanofiber. Coupling bioactive factors to the assembling backbone is an ideal strategy to design multi-functional supramolecular peptides in spite of challenging synthesis and purification. Herein, a multi-functional supramolecular peptide, P1R16, is developed by coupling a bioactive factor, parathyroid hormone related peptide 1 (PTHrP-1), to the basic supramolecular peptide RADA16-â via solid-phase synthesis. It is found that P1R16 self-assembles into long nanofibers and co-assembles with RADA16-â to form nanofiber hydrogels, thus coupling PTHrP-1 to hydrogel matrix. P1R16 nanofiber retains osteoinductive activity in a dose-dependent manner, and P1R16/RADA16-â nanofiber hydrogels promote osteogenesis, angiogenesis and osteoclastogenesis in vitro and induce multi-functionalized osteoregeneration by intramembranous ossification and bone remodeling in vivo when loaded to collagen (Col) scaffolds. Abundant red blood marrow formation, ideal osteointegration and adapted degradation are observed in the 50% P1R16/Col scaffold group. Therefore, this study provides a promising strategy to develop multi-functional supramolecular peptides and a new method to topically administrate parathyroid hormone or parathyroid hormone related peptides for non-healing bone defects.
A new series of complex anion ionic liquids (ILs) [Emim][BF3X] (X = CH3SO3, EtSO4, HSO4, Tosylate) were synthesized and characterized by nuclear magnetic resonance, elemental analysis, differential scanning calorimetry analysis, and thermogravimetry. The physicochemical properties of these ILs, such as density, viscosity, conductivity, and surface tension, were measured and correlated with thermodynamic and empirical equations in the temperature range of 293.15-358.15 K under ambient conditions, and the thermal expansion coefficient, standard molar entropy, lattice potential energy, viscosity activation energy, surface enthalpy, and surface entropy were further calculated from experimental values. According to the temperature-dependent viscosity and conductivity, [Emim][BF3X] ILs follow the Walden rule, and they are classified as "good (or super) ionic liquids".
