Efficacy of natural products in preventing oral mucositis resulting from cancer therapies: A network meta-analysis of randomized controlled trials.

BACKGROUND: Oral mucositis significantly compromises the quality of life for patients undergoing cancer therapies. This study aimed to evaluate the effectiveness of natural products in either preventing or alleviating oral mucositis resulting from cancer treatments. METHODS: A systematic review and network meta-analysis were conducted, sourcing data from the Cochrane Library, PubMed, Embase, Airiti Library, and Wan Fang Data Knowledge Service Platform until August 2023. The study was registered in PROSPERO (CRD42021285433). Confidence in Network Meta-Analysis (CINeMA) and R software 4.1.3 were used for analysis. RESULTS: From 1556 identified articles, 36 randomized controlled trials (RCTs) were analyzed, involving 2083 patients. Honey, notably, was found to significantly reduce the overall incidence of oral mucositis compared to standard care, with a relative risk (RR) of 0.80 (95% CI: 0.67-0.96). It was particularly effective against moderate-to-severe oral mucositis (grade ≥ 2), reducing incidence with RR of 0.48 (95% CI: 0.30-0.75) versus placebo and 0.56 (95% CI: 0.34-0.93) against standard care. Other natural products, including propolis, chamomile, and P. major L., also demonstrated significant efficacy in reducing the incidence of oral mucositis. Regarding pain relief, honey, and P. major L. emerged as effective, significantly reducing pain severity with a mean difference (MD) of -2.96 (95% CI: -3.80 to -1.94) compared to placebo. CONCUSSION: This network meta-analysis supports the use of honey, propolis, chamomile, and P. major L. as effective natural products in the prevention and treatment of oral mucositis among cancer patients. Specifically, honey is highlighted for its significant impact on reducing both the overall incidence and the severity of moderate-to-severe oral mucositis. By leveraging their anti-inflammatory and antioxidant properties, integrating these natural products into the standard care regimen could markedly improve the well-being of individuals undergoing cancer therapy.

Peptide-Directed Synthesis of Aggregation-Induced Emission Enhancement-Active Gold Nanoclusters for Single- and Two-Photon Imaging of Lysosome and Expressed αvß3 Integrin Receptors.

This study explores the synthesis and characterization of aggregation-induced emission enhancement (AIEE)-active gold nanoclusters (AuNCs), focusing on their near-infrared luminescence properties and potential applications in biological imaging. These AIEE-active AuNCs were synthesized via the NaBH4-mediated reduction of HAuCl4 in the presence of peptides. We systematically investigated the influence of the peptide sequence on the optical features of the AuNCs, highlighting the role of glutamic acid in enhancing their quantum yield (QY). Among the synthesized peptide-stabilized AuNCs, EECEE-stabilized AuNCs exhibited the maximum QY and a pronounced AIEE effect at pH 5.0, making them suitable for the luminescence imaging of intracellular lysosomes. The AIEE characteristic of the EECEE-stabilized AuNCs was demonstrated through examinations using transmission electron microscopy, dynamic light scattering, zeta potential analysis, and single-particle imaging. The formation of the EECEE-stabilized AuNCs was confirmed by size-exclusion chromatography and mass spectrometry. Spectroscopic and electrochemical examinations uncover the formation process of EECEE-stabilized AuNCs, comprising EECEE-mediated reduction, NaBH4-induced nucleation, complex aggregation, and subsequent cluster growth. Furthermore, we demonstrated the utility of these AuNCs as luminescent probes for intracellular lysosomal imaging, leveraging their pH-responsive AIEE behavior. Additionally, cyclic arginylglycylaspartic acid (RGD)-modified AIEE dots, derived from cyclic RGD-linked peptide-induced aggregation of EECEE-stabilized AuNCs, were developed for single- and two-photon luminescence imaging of αvß3 integrin receptor-positive cancer cells.

Aptamer-based flares hybridized with single-stranded DNA-conjugated MoS2 nanosheets for ratiometric fluorescence sensing and imaging of potassium ions and adenosine triphosphate in human fluids and living cells.

Addressing the limitations observed in previous studies, where the quantitative range of nanoprobes for detecting K+ and adenosine triphosphate (ATP) did not cover concentrations found within living cells, the present study aimed to develop ratiometric nanoprobes that can accurately sense changes in K+ and ATP levels in living cells and quantify them in human fluids. The proposed nanoprobes consisted of recognition flares modified with 6-carboxyfluorescein (FAM) and 5-carboxytetramethylrhodamine (TAMRA), along with thiolate single-stranded DNA (ssDNA) and molybdenum disulfide nanosheets (MoS2 NSs). The thiolate ssDNA acts as a linker between the flares and the MoS2 NSs, directly forming a functional nanostructure at room temperature. The direct conjugation of labeled flares to the MoS2 NSs simplifies the fabrication process. In the absence of K+ and ATP, the hybridization of flares and thiolate ssDNA caused FAM to move away from TAMRA, suppressing the fluorescence resonance energy transfer (FRET) process. However, upon the introduction of K+ and ATP, the flares undergo a structural transformation via the formation of G-quadruplex formation and the generation of hairpin-shaped structures, respectively. This structural change leads to the release of the flares from the ssDNA-conjugated nanosheet surface. The release of the flares brings FAM and TAMRA into close proximity, allowing FRET to occur, leading to FRET and static quenching. By monitoring the ratio between the fluorescence intensities of FAM and TAMRA, the concentration of K+ (5-100 mM) and ATP (0.3-5 mM) can be accurately determined by the proposed nanoprobes. The advantages of these nanoprobes lie in their ability to provide ratiometric measurements, which enhance the accuracy and reliability of the quantification process. The proposed nanoprobes offer potential applications as ratiometric imaging probes for monitoring K+ and ATP-related reactions in living cells, providing valuable insights into cellular processes. Additionally, they can be employed for determining the levels of K+ and ATP in human fluids, offering potential diagnostic applications in various clinical settings.

EGFR-mediated hyperacetylation of tubulin induced docetaxel resistance by downregulation of HDAC6 and upregulation of MCAK and PLK1 in prostate cancer cells.

Docetaxel-based chemotherapy has generally been considered as one of the effective treatments for castration-resistant prostate cancer (PCa). However, clinical treatment with docetaxel often encounters a number of undesirable effects, including drug resistance. Tubulin isoforms have been previously examined for their resistance to docetaxel in many cancers, but their real mechanisms remained unclear. In this study, a series of docetaxel-resistant PC/DX cell sublines were established by chronically exposing PC3 to progressively increased concentrations of docetaxel. Western blotting results showed significantly higher expression of acetyl-tubulin, α-tubulin, ß-tubulin, γ-tubulin, and ßIII-tubulin in PC/DX25 than in parental PC3 cells. PC/DX25 with greater resistance to docetaxel had higher levels of acetyl-tubulin and mitotic centromere-associated kinesin (MCAK) than PC3 cells. This study found that docetaxel induced the expression of acetyl-tubulin and MCAK in PC3 cells at a dose- and time-dependent manner. Both mRNA and protein levels of histone deacetylase 6 (HDAC6) were significantly decreased in PC/DX25 compared with PC3 cells. PC3 increased the resistance to docetaxel by HDAC6 knockdown and Tubastatin A (HDAC6 inhibitor). Conversely, PC/DX25 reversed the sensitivity to docetaxel by MCAK knockdown. Notably, flow cytometry analysis revealed that MCAK knockdown induced significantly sub G1 fraction in PC/DX cells. Overexpression of polo-like kinase-1 increased the cell survival rate and resistance to docetaxel in PC3 cells. Moreover, epidermal growth factor receptor (EGFR) activation induced the upregulation of acetyl-tubulin in docetaxel-resistant PCa cells. These findings demonstrated that the EGFR-mediated upregulated expression of acetyl-tubulin played an important role in docetaxel-resistant PCa.

Application of response surface methodology and quantitative NMR for the optimum extraction, characterization, and quantitation of Antrodia cinnamomea triterpenoids.

Antrodia cinnamomea (AC) is a treasured Asian medicinal mushroom, which has attracted attention due to recent research on its effectiveness in targeting a variety of serious ailments such as cancer and liver diseases. Among different A. cinnamomea constituents, triterpenoids are regarded as the most therapeutically attractive components because of their anti-inflammatory and cytotoxic activities. In the present study, we proposed a mathematical and statistical extraction protocol to evaluate the concentrations of total ergostane and lanostane triterpenoid derivatives from the ethanolic extract of the wild fruiting bodies of A. cinnamomea (EEAC) by utilizing response surface methodology (RSM) and quantitative NMR (qNMR) approaches. The optimum response surface model showed that the variations of the investigated response variables reached more than 90%, suggesting that the developed model is accurate in explaining response variability. Furthermore, the EEAC major characteristic triterpenoids were quantified through the comparison of the HPLC-tandem MS results with those of the qNMR results. The precision of the used techniques was also evaluated. The experimental design of the EEAC optimum extraction procedure obtained by using RSM and qNMR enabled accurate characterization and quantitation of A. cinnamomea triterpenoids.

Effects of Walking Combined With Resistance Band Exercises on Alleviating Cancer-Related Fatigue: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Cancer-related fatigue (CRF) is a common symptom, and exercise has shown potential in alleviating CRF. However, there is a need for diverse exercise options tailored to individual patient needs. OBJECTIVE: To evaluate the overall effects of a combined walking and resistance band exercise intervention in relieving CRF among cancer patients through randomized controlled trials. METHODS: Comprehensive searches were conducted in multiple databases to identify relevant studies up until March 2023. Inclusion criteria required the intervention to involve walking combined with elastic band training, with a clear exercise protocol description. The primary outcome was CRF, and secondary outcomes included walking steps, distance, mood distress, and quality of life. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using random-effects models. RESULTS: Ten trials were included. The intervention group showed significant improvements in CRF (SMD, -0.40; 95% CI, -0.60 to -0.20), mood distress (SMD, -0.30; 95% CI, -0.53 to -0.07), and daily walking steps (SMD, 0.52; 95% CI, 0.07-0.96) compared with the control group. Although the 6-Minute Walk Test and quality of life did not show significant differences, a trend toward improvement was observed in the intervention group. Adverse events related to the intervention were infrequent. CONCLUSION: A combined walking and resistance band exercise intervention can effectively alleviate CRF and improve mood distress and daily walking steps among cancer patients. IMPLICATIONS FOR PRACTICE: This exercise option may provide an additional strategy to manage CRF. Further research is needed to explore the optimal exercise prescription for individual patients.

Simple and fast microderivatization method for determining formaldehyde using narrow-bore liquid chromatography with UV detection.

Formaldehyde is a harmful substance that can cause sick building syndrome and other diseases, such as contact allergy, asthma, leukemia, cancer, and brain/neuron disorders. Formaldehyde is a ubiquitous chemical owing to its use in many common products, including as a preservative in household and personal care products. To prevent overexposure to formaldehyde, a simple method for determining and controlling the formaldehyde content in commercial products is required. In this study, 3-aminoquinoline (3-AQ) was used to derivatize formaldehyde under mild conditions (2 min at 30 °C) without the use of catalysts or activators. The derivatized sample solutions were separated using narrow-bore liquid chromatography with an ultraviolet (UV) detector in a run time of only 5 min. All sample extraction and derivatization protocols were performed on the microliter scale to reduce the use of organic solvents. The linear range for the determination was 5-1000 µg mL-1, with a detection limit of approximately 1 µg mL-1 (2 ng per 2 µL injection). The proposed microscale method was successfully applied to the analysis of formaldehyde in commercial household products.

Cancer-related fatigue classification based on heart rate variability signals from wearables.

Background: Cancer-related fatigue (CRF) is the most distressing side effect in cancer patients and affects the survival rate. However, most patients do not report their fatigue level. This study is aimed to develop an objective CRF assessment method based on heart rate variability (HRV). Methods: In this study, patients with lung cancer who received chemotherapy or target therapy were enrolled. Patients wore wearable devices with photoplethysmography that regularly recorded HRV parameters for seven consecutive days and completed the Brief Fatigue Inventory (BFI) questionnaire. The collected parameters were divided into the active and sleep phase parameters to allow tracking of fatigue variation. Statistical analysis was used to identify correlations between fatigue scores and HRV parameters. Findings: In this study, 60 patients with lung cancer were enrolled. The HRV parameters including the low-frequency/high-frequency (LF/HF) ratio and the LF/HF disorder ratio in the active phase and the sleep phase were extracted. A linear classifier with HRV-based cutoff points achieved correct classification rates of 73 and 88% for mild and moderate fatigue levels, respectively. Conclusion: Fatigue was effectively identified, and the data were effectively classified using a 24-h HRV device. This objective fatigue monitoring method may enable clinicians to effectively handle fatigue problems.

Peptide-modified carbon dot aggregates for ultrasensitive detection of lipopolysaccharide through aggregation-induced emission enhancement.

This study fabricated yellow-emitting CDs (Y-CDs) by hydrothermal treatment of citric acid and urea and applied them as a fluorescence turn-on platform for sensitive and selective detection of lipopolysaccharide (LPS) based on the non-shifted AIEE of peptide-stabilized CD aggregates. The designed peptide (named K3) consisting of aggregation-active and LPS-recognition units triggered the aggregation of Y-CDs, switching on their fluorescence through the blue-shifted AIEE process. The formed K3-stabilized Y-CD aggregates (K3-YCDAs) specifically interacted with LPS at neutral pH, demonstrating that the sequence of the decorated peptide was highly connected with their selectivity and sensitivity. The K3-YCDAs provided a fast response time (within 5 min) to detect LPS with a quantification range of 0.5-100.0 nM and a limit of detection (LOD, signal-to-noise ratio of 3) of 300.0 pM. By integrating ultrafiltration membranes as a concentration device with K3-YCDAs as a sensing probe, the LOD for LPS was further reduced to 3.0 pM. The determination of picomolar levels of plasma LPS by the K3-YCDAs coupled to the centrifugation ultrafiltration was demonstrated to fall within the specificity range of clinical interest for sepsis patients. Also, the K3-YCDAs served as a fluorescent probe to selectively image and quantify E. coli cells. The distinct advantages of the K3-YCDAs for LPS include fast response time, wide linear range, low detection limit, and excellent selectivity compared to previously reported sensors.

3D Virtual Reality Smartphone Training for Chemotherapy Drug Administration by Non-oncology Nurses: A Randomized Controlled Trial.

Chemotherapy agents are cytotoxic materials. Thus, there is a need for the operators to be familiar with the knowledge and procedures before operation. We conducted a randomized controlled trial investigating the effectiveness of an immersive 3D VR teaching of chemotherapy administration operated in a smartphone coupled with a visual and audio device. We adopted a two-arm single-blind design and recruited 83 nurses, and they were randomized using a cluster approach. The VR group learned chemotherapy administration through VR, while the controlled group learned through document reading. The Knowledge and Attitude of Chemotherapy Administration (KACA) was administrated before the intervention, while the Objective Structured Clinical Examination (OSCE) and the Checklist of Action Accomplishment (CAA) were administrated one month after the intervention. The VR group scored higher than the controlled group in the CAA (95.69 ± 5.37 vs. 91.98 ± 9.31, p = 0.02) and the OSCE (73.07 ± 10.99 vs. 67.44 ±10.65, p = 0.02). Stepwise regression demonstrated that service years, an education level of undergraduate or above, and VR exposure contributed positively to the OSCE score (adjusted R2 = 0.194, p = 0.028). The use of VR improves the learning efficacy of chemotherapy administration in non-oncology nurses. We recommend using VR as a teaching tool for chemotherapy administration and other chemotherapy-related skills in a VR learning group with senior nurses with higher education levels as advisors. The study provides an approach to online training, especially during the COVID-19 pandemic. (CONSORT 2010 guidelines, registry number: NCT04840732).

An eco-friendly solvent-free reaction based on peptide probes: design an extraction-free method for analysis of acrylamide under microliter volume.

Acrylamide is a group 2A carcinogen and potential endocrine disruptor that can enter the ecosystem by various routes and has recently become a dangerous pollutant. This widely used chemical can enter the human body via air inhalation, food or water consumption, or skin contact. In this study, we developed a peptide probe for the detection of acrylamide by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) after its micro-tagging with a peptide. Direct detection of acrylamide by MALDI-TOF MS is not feasible due to its poor ionization in the MALDI interface, which hinders its analysis by the technique. After microwave irradiation for 2 min, the formed acrylamide-peptide derivative was detected easily by MALDI-TOF MS without the need for extraction procedures. The procedure does not involve organic solvents and a water-soluble peptide that allows detection of acrylamide in small sample volumes with a limit of detection (LOD) of 0.05 ng/µL. The relative standard deviation (RSD) and relative error (RE) of the measurements were < 6.7% for intra- and inter-day assays. Gel-washing solutions from a polyacrylamide gel experiment were used as a model to study the efficiency of the developed method. Finally, we used the proposed method for the detection of free acrylamide in small volumes of lung epithelial cells (a model to test the air inhalation of acrylamide under a tiny volume of sample) and human urine. The developed method will enable rapid acrylamide detection in environmental and biological samples via a green approach based on microwave-assisted derivatization in water alongside the use of a less toxic derivatization reagent, reusable target plate, and miniaturization protocols.

miR-29a-3p/THBS2 Axis Regulates PAH-Induced Cardiac Fibrosis.

Pulmonary artery hypertension (PAH) pathology involves extracellular matrix (ECM) remodeling in cardiac tissues, thus promoting cardiac fibrosis progression. miR-29a-3p reportedly inhibits lung progression and liver fibrosis by regulating ECM protein expression; however, its role in PAH-induced fibrosis remains unclear. In this study, we aimed to investigate the role of miR-29a-3p in cardiac fibrosis progression in PAH and its influence on ECM protein thrombospondin-2 (THBS2) expression. The diagnostic and prognostic values of miR-29a-3p and THBS2 in PAH were evaluated. The expressions and effects of miR-29a-3p and THBS2 were assessed in cell culture, monocrotaline-induced PAH mouse model, and patients with PAH. The levels of circulating miR-29a-3p and THBS2 in patients and mice with PAH decreased and increased, respectively. miR-29a-3p directly targets THBS2 and regulates THBS2 expression via a direct anti-fibrotic effect on PAH-induced cardiac fibrosis. The circulating levels of miR-29a-3p and THBS2 were correlated with PAH diagnostic parameters, suggesting their independent prognostic value. miR-29a-3p targeted THBS2 expression via a direct anti-fibrotic effect on PAH-induced cardiac fibrosis, indicating miR-29a-3p acts as a messenger with promising therapeutic effects.

Fluorescence sensing of heparin and heparin-like glycosaminoglycans by stabilizing intramolecular charge transfer state of dansyl acid-labeled AG73 peptides with glutathione-capped gold nanoclusters.

Sensors that can specifically and accurately detect glycosaminoglycans are rare. Here, a dual-mode platform for fluorescence intensity and lifetime sensing of plasma heparin and fluorescence imaging of heparan sulfate proteoglycan-expressed cancer cells was developed by stabilizing the intramolecular charge transfer (ICT) state of dansyl acid-labeling AG73 (DA-AG73) peptide with glutathione-capped gold nanoclusters (GSH-AuNCs). DA-AG73 peptides, including an electron-donor dimethylamino group and an electron-withdrawing sulfonamide moiety in the labeled DA molecules, emitted weak fluorescence due to the formation of the twisted ICT excited state. The complexation of heparin with DA-AG73 peptides followed by interacting with the GSH-AuNCs could restrict the rotation of the dimethylamino groups of the labeled DA molecules, triggering the transition from their twisted ICT state to ICT excited state. As a result, the fluorescence intensity and lifetime of the labeled DA molecules in DA-AG73 peptides were gradually enhanced with increasing the heparin concentration. The proposed platform provided excellent selectivity toward heparin and heparan sulfate and exhibited two linear calibration curves for quantifying 20-800 nM and 20-1000 nM heparin in the fluorescence intensity and lifetime modes, respectively. The proposed platform was practically applied for the fluorescence intensity and lifetime determination of plasma heparin and for the selective imaging of heparan sulfate proteoglycan-expressed cells.

High Mobility Group Box 1 Promotes Lung Cancer Cell Migration and Motility via Regulation of Dynamin-Related Protein 1.

High mobility group box 1 (HMGB1) has been demonstrated to promote the migration and invasion of non-small cell lung cancer (NSCLC). However, the mechanism of action of HMGB1 in regulating tumor mobility remains unclear. Therefore, we aimed to investigate whether HMGB1 affects mitochondria distribution and regulates dynamin-related protein 1 (DRP1)-mediated lamellipodia/filopodia formation to promote NSCLC migration. The regulation of mitochondrial membrane tension, dynamics, polarization, fission process, and cytoskeletal rearrangements in lung cancer cells by HMGB1 was analyzed using confocal microscopy. The HMGB1-mediated regulation of DRP1 phosphorylation and colocalization was determined using immunostaining and co-immunoprecipitation assays. The tumorigenic potential of HMGB1 was assessed in vivo and further confirmed using NSCLC patient samples. Our results showed that HMGB1 increased the polarity and mobility of cells (mainly by regulating the cytoskeletal system actin and microtubule dynamics and distribution), promoted the formation of lamellipodia/filopodia, and enhanced the expression and phosphorylation of DRP1 in both the nucleus and cytoplasm. In addition, HMGB1 and DRP1 expressions were positively correlated and exhibited poor prognosis and survival in patients with lung cancer. Collectively, HMGB1 plays a key role in the formation of lamellipodia and filopodia by regulating cytoskeleton dynamics and DRP1 expression to promote lung cancer migration.

Characterization and Proteomic Analysis of Endometrial Stromal Cell-Derived Small Extracellular Vesicles.

CONTEXT: Small extracellular vesicles (sEVs) have emerged as modulators of the disease microenvironment, thereby supporting disease progression. However, the potential role of EVs and their content to the pathophysiology of endometriosis remain unclear. OBJECTIVE: This work aimed to investigate whether the EVs from eutopic (Eu) and ectopic (Ec) endometrial stromal cells (ESCs) differ with respect to protein composition and role in endometriosis. METHODS: Human Eu and Ec endometrium-derived ESCs were isolated from samples of the same patients (n = 3). sEVs were isolated from ESCs via ultracentrifugation; these sEVs were characterized by Western blotting, transmission electron microscopy, and nanoparticle tracking analysis and analyzed using mass spectrometry. The potential role of EcESCs-derived sEVs (EcESCs-sEVs) in endometriosis was explored by assaying their effects on cell viability/proliferation, migration, and angiogenesis. RESULTS: In total, 105 ESCs-sEV-associated proteins were identified from EcESCs-sEVs and EuESCs-sEVs by mass spectrometry analysis. The protein content differed between EcESCs-sEVs and EuESCs-sEVs, with annexin A2 (ANXA2) being the most prominent difference-present in EcESCs-sEVs but not EuESCs-sEVs. We also found that sEVs-ANXA2 regulates the motility, proliferation, and angiogenesis of ESCs via the extracellularly regulated kinase (ERK)/STAT3 pathway. Notably, treatment of ESCs with sEVs-ANXA2 resulted in increased proliferation and motility, suggesting that sEVs-ANXA2 may be involved in regulating endometriosis. Our data suggest that EcESCs-sEVs-ANXA2 regulates the motility and the angiogenic potential of ESCs, implying a role for sEVs-ANXA2 in the pathogenesis of endometriosis. CONCLUSION: The study of sEVs-ANXA2 from Ec endometriotic cells uncovers a new mechanism of endometriosis progression and will inform the development of novel therapeutic strategies.

Phosphorescent MoS2 quantum dots as a temperature sensor and security ink.

Currently, few phosphorescent materials (PMs) possess a long phosphorescence lasting time and have potential for application in chemical sensors. Herein, we disclose that the incorporation of few-layer molybdenum disulfide quantum dots (FL-MoS2 QDs) into poly(vinyl alcohol) (PVA) matrices leads to the emission of bright green phosphorescence with a long lasting time of 3.0 s and a phosphorescence quantum yield of 20%. This enhanced phosphorescence originates from the formation of O-H⋯S hydrogen bonding networks between the rich sulfur sites of the FL-MoS2 QDs and the hydroxyl groups of the PVA molecules, which not only rigidifies the vibration modes of the FL-MoS2 QDs but also provides an oxygen barrier. Further investigations reveal that the FL-MoS2 QD/PVA composites exhibit a longer phosphorescence lasting time than N,S-doped carbon dots, few layer tungsten disulfide quantum dots, Rhodamine 6G, and Rhodamine B in PVA matrices. Since heat efficiently induced the removal of water moisture from PVA matrices, the FL-MoS2 QD/PVA composites could be implemented for phosphorescence turn-on and naked-eye detection of temperature variations ranging from 30 to 70 °C. By contrast, the carbon dot/PVA composites were incapable of sensing environmental temperature due to their weak hydrogen bonding with the hydroxyl groups of PVA matrices. Additionally, this study reveals the potential of the FL-MoS2 QD/PVA composites as an advanced security ink for anti-counterfeiting and encryption applications. The given results could open a new direction for potential application of two-dimensional quantum dots in phosphorescence-based sensors and security inks.

Thrombospondin 1-induced exosomal proteins attenuate hypoxia-induced paraptosis in corneal epithelial cells and promote wound healing.

Thrombospondin-1 (TSP1) is involved in corneal wound healing caused by chemical injury. Herein, we examined the effects of TSP1 on hypoxia-induced damages and wound-healing activity in human corneal epithelial (HCE) cells. Exosomal protein expression was determined using liquid chromatography-tandem mass spectrometry, and HCE cell migration and motility were examined through wound-healing assay and time-lapse microscopy. Reestablishment of cell junctions by TSP1 was assessed through confocal microscopy and 3D image reconstruction. Our results show that CoCl2 -induced hypoxia promoted HCE cell death by paraptosis. TSP1 protected these cells against paraptosis by attenuating mitochondrial membrane potential depletion, swelling and dilation of endoplasmic reticulum and mitochondria, and mitochondrial fission. Exosomes isolated from HCE cells treated with TSP1 contained wound healing-associated proteins that were taken up by HCE cells to promote tissue remodeling and repair. TSP1 protected HCE cells against hypoxia-induced damages and inhibited paraptosis progression by promoting cell migration, cell-cell adhesion, and extracellular matrix remodeling. These findings indicate that TSP1 ameliorates hypoxia-induced paraptosis in HCE cells and promotes wound healing and remodeling by regulating exosomal protein expression. TSP1 may, therefore, play important roles in the treatment of hypoxia-associated corneal diseases.

Sensitive detection of quinoline-derivatized sitagliptin in small volumes of human plasma by MALDI-TOF mass spectrometry.

Dipeptidyl peptidase 4 (DPP-4) inhibitors are incretin-based medications used as oral antidiabetic agents for the treatment of type 2 diabetes. However, DPP-4 inhibitors produce side effects like acute pancreatitis, upper respiratory tract infection, nasopharyngitis, urinary tract infection, serious allergies, cardiovascular diseases, hemolysis, and retinopathy. Hence, the development of a fast and simple method to detect DPP-4 inhibitors in body fluids is important. In this study, we developed a derivatization-assisted microextraction method to enhance the detection sensitivity for trace levels of a DPP-4 inhibitor, sitagliptin, from a small volume (10 µL) of human plasma by using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Subjecting the analyte to 100 W microwave irradiation after derivatization using a quinoline alkylating reagent (8-bromomethyl quinilone, BrMQ) shortened the reaction time to ~120 s and allowed the target analyte to be easily extracted to a small volume of the organic layer (20 µL). The analyte was then detected by MALDI-TOF MS using α-cyano-4-hydroxycinnamic acid as the matrix. The relative standard deviation and relative error were below 10% in intra- and inter-day assays. Using sitagliptin-d4 as an internal standard, the limits of quantitation and detection were found to be 0.03 µg/mL and 0.01 µg/mL, respectively. All the derivatization and extraction procedures described herein were of microliter grade. This method could effectively reduce the use of organic chemicals and solvents, thereby proving to be an eco-friendly strategy that will cause no harm to the environment.

Status of Asp29 and Asp40 in the Interaction of Naja atra Cardiotoxins with Lipid Bilayers.

It is widely accepted that snake venom cardiotoxins (CTXs) target the plasma membranes of cells. In the present study, we investigated the role of Asp residues in the interaction of Naja atra cardiotoxin 1 (CTX1) and cardiotoxin 3 (CTX3) with phospholipid bilayers using chemical modification. CTX1 contains three Asp residues at positions 29, 40, and 57; CTX3 contains two Asp residues at positions 40 and 57. Compared to Asp29 and Asp40, Asp57 was sparingly modified with semi-carbazide, as revealed by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass and mass/mass analyses. Thus, semi-carbazide-modified CTX1 (SEM-CTX1) mainly contained modified Asp29 and Asp40, while SEM-CTX3 contained modified Asp40. Compared to that of native toxins, trifluoroethanol easily induced structural transition of SEM-CTX1 and SEM-CTX3, suggesting that the structural flexibility of CTXs was constrained by Asp40. Modification of Asp29 and Asp40 markedly promoted the ability of CTX1 to induce permeability of cell membranes and lipid vesicles; CTX3 and SEM-CTX3 showed similar membrane-damaging activity. Modification of Asp residues did not affect the membrane-binding capability of CTXs. Circular dichroism spectra of SEM-CTX3 and CTX3 were similar, while the gross conformation of SEM-CTX1 was distinct from that of CTX1. The interaction of CTX1 with membrane was distinctly changed by Asp modification. Collectively, our data suggest that Asp29 of CTX1 suppresses the optimization of membrane-bound conformation to a fully active state and that the function of Asp40 in the structural constraints of CTX1 and CTX3 is not important for the manifestation of membrane-perturbing activity.

Galectin-9-like from Angiostrongylus cantonensis young adult worms modulates eosinophil chemotaxis in vitro.

BACKGROUND/PURPOSE: Eosinophils are recruited to the brain of mice after infection with Angiostrongylus canonensis. Several factors produced by infected mice are well known playing the role to chemoattract eosinophils from the blood into the brain. The purpose of this study is to investigate whether Angiostronylus cantonensis young-adult worms (AcYA) have components which have eosinophilic chemotactic activity. METHODS: Eosinophil chemotactic activity of AcYA was tested by Boyden blind-well chamber technique. The components of AcYA were analysed by SDS-PAGE and Mass spectrometry. Furthermore, galectin-9 in the cerebrospinal fluid (CSF) of infected mice and galectin-9-like in AcYA were measured by ELISA technic and also were recognized by western blot analysis respectively. RESULTS: Excretory-secretory products of AcYA did not show eosinophil chemotactic activity. However, the extracts of AcYA showed protein concentration-dependent eosinophil chemotactic activity and reached the peak at the 24 µg/ml. The eosinophil chemotactic activity was significantly reduced by lactose. The components of AcYA at molecular weights of approximatively 15 kDa and 35 kDa showed several galectins component in Mass spectrometric analysis. Furthermore, galectin-9-like in AcYA was recognized by ELISA and western blot analysis. In parallel with increase of galectin-9 in the CSF, eosinophils were also significantly increased in mouse after infected with A. cantonensis. CONCLUSION: Galectin-9-like in AcYA and galectin-9 in mouse CSF were confirmed demonstrating eosinophil chemotactic activity both in vitro study and in the infection of mouse in this study.