Targeting antioxidant factor Nrf2 by raffinose ameliorates lipid dysmetabolism-induced pyroptosis, inflammation and fibrosis in NAFLD.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a persistent liver condition that affects both human health and animal productive efficiency on a global scale. A number of naturally occurring compounds activate nuclear factor erythroid 2-related factor 2 (Nrf2) as a transcription factor with important protective effects against many liver diseases, including NAFLD. Raffinose (Ra), an oligosaccharide extracted from several plants, exhibits diverse biological functions. However, the uncertainty lies in determining whether the activation of Nrf2 by Ra can provide a preventive effect on liver lipotoxicity. PURPOSE: The aim of this study was to shed light on the molecular pathways by which Ra possesses its protective benefits against NAFLD. METHODS: Experimental protocols were established using WT and Nrf2-null (Nrf2-/-) mice. Liver samples from each group were collected for Western blot, RT-qPCR, H & E, Sirius red and Oil red O staining. Additionally, serums were processed for ELISA. ALM12 cells were gathered for Western blot and immunofluorescence. Moreover, to elucidate the molecular mechanism of Ra, molecular docking was performed. RESULTS: Our results indicated that Ra remarkably alleviated liver lipotoxic in vivo and in vitro. Ra treatment effectively corrected hepatic steatosis, the release of AST, ALT, TG, and TC, as well as the depletion of HDL and LDL. Meanwhile, Ra efficiently prevented inflammation by inhibiting the TLR4-MyD88-NF-κB pathway and pyroptosis. Additionally, these findings implied that Ra reduced the production of fibrosis-related proteins, which enhanced collagen deposition. Molecular docking revealed that Ra possessed the ability to bind specific regions of Nrf2, resulting in the enhancement of Nrf2 activation and nuclear translocation. Ra treatment restored serum redox factors and antioxidant enzymes to normal levels; however, these alterations were clearly reversed in Nrf2-/- mice. CONCLUSION: This study reveals novel information on Ra's protective benefits against liver injury caused by abnormal lipid metabolism; these effects are mostly mediated by Nrf2 activation, suggesting a potential new medicine or treatment strategy for NAFLD.

Genome-wide identification of the SAUR gene family and screening for SmSAURs involved in root development in Salvia miltiorrhiza.

KEY MESSAGE: SmSAUR4, SmSAUR18, SmSAUR28, SmSAUR37, and SmSAUR38 were probably involved in the auxin-mediated root development in Salvia miltiorrhiza. Salvia miltiorrhiza is a widely utilized medicinal plant in China. Its roots and rhizomes are the main medicinal portions and are closely related to the quality of this herb. Previous studies have revealed that auxin plays pivotal roles in S. miltiorrhiza root development. Whether small auxin-up RNA genes (SAURs), which are crucial early auxin response genes, are involved in auxin-mediated root development in S. miltiorrhiza is worthy of investigation. In this study, 55 SmSAUR genes in S. miltiorrhiza were identified, and their physical and chemical properties, gene structure, cis-acting elements, and evolutionary relationships were analyzed. The expression levels of SmSAUR genes in different organs of S. miltiorrhiza were detected using RNA-seq combined with qRT‒PCR. The root development of S. miltiorrhiza seedlings was altered by the application of indole-3-acetic acid (IAA), and Pearson correlation coefficient analysis was conducted to screen SmSAURs that potentially participate in this physiological process. The diameter of primary lateral roots was positively correlated with SmSAUR4. The secondary lateral root number was positively correlated with SmSAUR18 and negatively correlated with SmSAUR4. The root length showed a positive correlation with SmSAUR28 and SmSAUR37 and a negative correlation with SmSAUR38. The fresh root biomass exhibited a positive correlation with SmSAUR38 and a negative correlation with SmSAUR28. The aforementioned SmSAURs were likely involved in auxin-mediated root development in S. miltiorrhiza. Our study provides a comprehensive overview of SmSAURs and provides the groundwork for elucidating the molecular mechanism underlying root morphogenesis in this species.

Epsilon-poly-l-lysine microneedle patch loaded with amorphous doxycycline nanoparticles for synergistic treatment of skin infection.

The development of antibiotic-loaded microneedles has been hindered for years by limited excipient options, restricted drug-loading space, poor microneedle formability, and short-term drug retention. Therefore, this study proposes a dissolving microneedle fabricated from the host-defense peptide ε-poly-l-lysine (EPL) as an antibacterial adjuvant system for delivering antibiotics. EPL serves not only as a major matrix material for the microneedle tips, but also as a broad-spectrum antibacterial agent that facilitates the intracellular accumulation of the antibiotic doxycycline (DOX) by increasing bacterial cell membrane permeability. Furthermore, the formation of physically crosslinked networks of EPL affords microneedle tips with improved formability, good mechanical properties, and amorphous nanoparticles (approximately 7.2 nm) of encapsulated DOX. As a result, a high total loading content of both antimicrobials up to 2319.1 µg/patch is achieved for efficient transdermal drug delivery. In a Pseudomonas aeruginosa-induced deep cutaneous infection model, the EPL microneedles demonstrates potent and long-term effects by synergistically enhancing antibiotic activities and prolonging drug retention in infected lesions, resulting in remarkable therapeutic efficacy with 99.91 % (3.04 log) reduction in skin bacterial burden after a single administration. Overall, our study highlights the distinct advantages of EPL microneedles and their potential in clinical antibacterial practice when loaded with amorphous DOX nanoparticles.

Effect of bone mass density and alveolar bone resorption on stress in implant restoration of free-end edentulous posterior mandible: Finite element analysis of double-factor sensitivity.

BACKGROUND: Osseous condition of the mandible was regarded as a key factor influencing stability of implants in the early stage. Finite element analysis was used to assess the effect of bone mass density and alveolar bone resorption (double factors) on stress in a four-unit implant restoration of a free-end edentulous posterior mandible. METHODS: A 3D finite element model was constructed for a single-sided free-end edentulous mandible (from mandibular first premolar to mandibular second molar) containing threaded dental implants. Mandible sensitivity modes were constructed with different alveolar bone resorption levels for normal conditions as well as mild, moderate and severe periodontitis, respectively. Based on the mass density of cancellous bone for four types of bones as the sensitivity parameter, two implant design modes were constructed: Model A (four-unit fixed bridge supported by three implants, implant positions were 34, 36 and 37) and model B: 34 × 36, 37 (37: a single implant crown) (34 × 36: three-unit fixed bridge supported by two implants, implant positions were 34 and 36). A total of 32 sensitivity-based finite element models, grouped in two groups, were constructed. Stress distribution and maximum von Mises stress on cortical bone and cancellous bone around the implant, as well as the surface of implant were investigated by using ABAQUS when vertical loading and 45° oblique loading were applied, respectively. RESULTS: When vertical loading was applied on the implant, maximum von Mises stress on the cortical bone around the implant was assessed to be 4.726 MPa - 13.15 MPa and 6.254 MPa - 13.79 MPa for groups A and B, respectively; maximum stress on the cancellous bone around the implant was 2.641 MPa - 3.773 MPa and 2.864 MPa - 4.605 MPa, respectively; maximum stress on the surface of implant was 14.7 MPa - 21.17 MPa and 21.64 MPa - 30.70 MPa, respectively. When 45° oblique loading was applied on the implant restoration, maximum von Mises stress on the cortical bone around the implant was assessed to be 42.08 MPa - 92.71 MPa and 50.84 MPa - 102.5 MPa for groups A and B, respectively; maximum stress on the cancellous bone around the implant was 4.88 MPa - 25.95 MPa and 5.227 MPa - 28.43 MPa, respectively; maximum stress on the surface of implant was 77.91 MPa - 124.8 MPa and 109.2 MPa - 150.7 MPa, respectively. Stress peak on the cortical bone and that on cancellous bone around the implant increased and decreased with the decrease in bone mass density, respectively. Stress peak on alveolar bone increased with alveolar bone resorption when oblique loading was applied. CONCLUSION: 1. Both alveolar bone resorption and bone mass density (double factors) are critical to implant restoration. Bone mass density may exhibit a more pronounced impact than alveolar bone resorption. 2. From the biomechanical perspective, types I and II bones are preferred for implant restoration, while implantation should be considered carefully in the case of type III bones, or those with less bone mass density accompanied by moderate to severe alveolar bone loss. 3. Splinting crowns restoration is biomechanically superior to single crown restoration.

S-Wave Accelerates Optimization-based Photoacoustic Image Reconstruction in vivo.

OBJECTIVE: Photoacoustic imaging has undergone rapid development in recent years. To simulate photoacoustic imaging on a computer, the most popular MATLAB toolbox currently used for the forward projection process is k-Wave. However, k-Wave suffers from significant computation time. Here we propose a straightforward simulation approach based on superposed Wave (s-Wave) to accelerate photoacoustic simulation. METHODS: In this study, we consider the initial pressure distribution as a collection of individual pixels. By obtaining standard sensor data from a single pixel beforehand, we can easily manipulate the phase and amplitude of the sensor data for specific pixels using loop and multiplication operators. The effectiveness of this approach is validated through an optimization-based reconstruction algorithm. RESULTS: The results reveal significantly reduced computation time compared with k-Wave. Particularly in a sparse 3-D configuration, s-Wave exhibits a speed improvement >2000 times compared with k-Wave. In terms of optimization-based image reconstruction, in vivo imaging results reveal that using the s-Wave method yields images highly similar to those obtained using k-Wave, while reducing the reconstruction time by approximately 50 times. CONCLUSION: Proposed here is an accelerated optimization-based algorithm for photoacoustic image reconstruction, using the fast s-Wave forward projection simulation. Our method achieves substantial time savings, particularly in sparse system configurations. Future work will focus on further optimizing the algorithm and expanding its applicability to a broader range of photoacoustic imaging scenarios.

Effect of M-type reactive dyes on dyeing properties of twisted bamboo fiber bundles.

The dyeing properties of twisted bamboo fiber bundles were studied by using the combination of three primary colors in M-type reactive dyes. The study found that the three dyes of red, yellow and blue have good color rendering in the actual dyeing process, and because the molecular structures of the three are similar, the chemical reactions during the fixation are the same, so the final dyeing rate results are similar, which were 29-32%. Compared with the undyed twisted bamboo fiber bundle, the mechanical properties of the three-color twisted bamboo fiber bundle also changed significantly, and the tensile strength increased by 13.79% on average. The changes of elastic modulus and elongation at break showed that the three-color twisted bamboo fiber bundle had excellent flexibility. In addition, there are significant color differences between the samples of each color. When the color indexes of DB are used as the benchmark, the ΔE* of other dyed samples varies from 40 to 80, and the color of each sample is relatively uniform, without an obvious color flower phenomenon. This indicates that twisted bamboo fiber bundles with richer colors can be prepared by different combinations of three primary dyes, which can improve the ornamental value of bamboo fiber bundles after processing into large blocks and their application potential in home textiles, interior decoration and other fields.

Comparative transcriptome analysis reveals the regulatory effects of exogenous auxin on lateral root development and tanshinone accumulation in Salvia miltiorrhiza.

MAIN CONCLUSION: The physiological and transcriptome analysis revealed that auxin was a positive regulator of lateral root development and tanshinone accumulation in Salvia miltiorrhiza. Roots of S. miltiorrhiza are widely used as medicinal materials in China, and the root morphology and content of bioactive compounds [such as phenolic acids and diterpenoid quinones (tanshinones)] are the main factors to determine the quality of this herb. Auxin regulates root development and secondary metabolism in many plant species, but little is known about its function in S. miltiorrhiza. In this study, S. miltiorrhiza seedlings were treated (exogenous application) with the auxin indole-3-acetic acid (IAA) and the polar auxin transport inhibitor N-1-naphthylphthalamic acid (NPA) to investigate the regulatory roles of auxin in S. miltiorrhiza. The results indicated that exogenous IAA promoted both lateral root development and tanshinones biosynthesis in S. miltiorrhiza. The NPA application suppressed the lateral root development but showed no obvious effects on tanshinones accumulation. Based on the RNA-seq analysis, expressions of genes related to auxin biosynthesis and signaling transduction were altered in both treated groups. Coincidental with the enhanced content of tanshinones, transcripts of several key enzyme genes in the tanshinones biosynthetic pathway were stimulated after the exogenous IAA application. The expression profiles of seven common transcription factor domain-containing gene families were analyzed, and the results implied that some AP2/ERF genes were probably responsible for the auxin-induced lateral root development in S. miltiorrhiza. These findings shed new light on the regulatory roles of auxin on root development and bioactive compounds biosynthesis in S. miltiorrhiza, and lay the groundwork for future research into the detailed molecular mechanism underlying these biological functions.

Effect of Low Temperature Reactive Dye Reactive Red 2 on Dyeing and Tensile Properties of Twisted Bamboo Fibers.

This study employed bamboo as the raw material and employed the sodium chlorite method to remove most of the chromogenic groups in bamboo. The low-temperature reactive dyes were then utilized as the dyeing agents in combination with the one-bath method to dye the decolorized bamboo bundles. The dyed bamboo bundles were subsequently twisted into bamboo fiber bundles with high flexibility. The effects of various factors, including dye concentration, dyeing promoter concentration, and fixing agent concentration, on the dyeing properties, mechanical properties, and other properties of the twisted bamboo bundles were investigated using a tensile test, dyeing rate test, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and scanning electron microscopy. The results indicate that the macroscopic bamboo fibers prepared by the top-down method have excellent dyeability. The dyeing treatment not only improves the aesthetics of bamboo fibers but also improves their mechanical properties to a certain extent. When the concentration of dye is 1.0% (o.w.f.), the concentration of dye promoter is 30 g/L, and the concentration of color fixing agent is 10 g/L, the comprehensive mechanical properties of the dyed bamboo fiber bundles are the best. At this time, the tensile strength is 95.1 MPa, 2.45 times that of undyed bamboo fiber bundles. XPS analysis results show that the relative content of C-O-C in the fiber is significantly increased compared with that before dyeing, which indicates that the formed dye fiber covalent bond can strengthen the cross-linking between fibers, thus improving its tensile performance. The covalent bond is stable, and the dyed fiber bundle can retain its mechanical strength even after high temperature soaping.

Analysis of the correlation between biomechanical properties and corneal densitometry in myopic eyes.

Background: To investigate the correlation between corneal biomechanical characteristics (in vitro and in vivo) and corneal densitometry in myopia. Methods: The Pentacam (Oculus, Wetzlar, Germany) corneal densitometry (CD) and Corvis ST (Oculus, Wetzlar, Germany) exams were conducted prior to surgery for myopic patients who were intended to undergo small-incision lenticule extraction (SMILE). CD values (grayscale units, GSUs), and in vivo biomechanical parameters were obtained. The stromal lenticule was subjected to a uniaxial tensile test to obtain the elastic modulus E in vitro. We exam the correlations among in vivo, in vitro biomechanical characteristics and CD values. Results: In this study, 37 myopic patients (63 eyes) were included. The mean age of participants was 25.14 ± 6.74 years (range:16-39 years). The mean CD values of the total cornea, anterior layer, intermediate layer, posterior layer, 0-2 mm region and 2-6 mm region were 15.03 ± 1.23 GSU, 20.35 ± 1.98 GSU, 11.76 ± 1.01 GSU, 10.95 ± 0.83 GSU, 15.57 ± 1.12 GSU and 11.94 ± 1.77 GSU, respectively. Elastic modulus E (in vitro biomechanical indicator) was negatively correlated with intermediate layer CD (r = -0.35, p = 0.01) and 2-6 mm region CD (r = -0.39, p = 0.00). A negative correlation was also found between 0-2 mm central region CD and in vivo biomechanical indicator SP-HC (r = -0.29, p = 0.02). Conclusion: In myopic patients, densitometry is negatively correlated with biomechanical properties both in vivo and in vitro. With an increase in CD, the cornea deformed more easily.

Intestinal BMP-9 locally upregulates FGF19 and is down-regulated in obese patients with diabetes.

Bone morphogenetic protein (BMP)-9, a member of the TGFß-family of cytokines, is believed to be mainly produced in the liver. The serum levels of BMP-9 were reported to be reduced in newly diagnosed diabetic patients and BMP-9 overexpression ameliorated steatosis in the high fat diet-induced obesity mouse model. Furthermore, injection of BMP-9 in mice enhanced expression of fibroblast growth factor (FGF)21. However, whether BMP-9 also regulates the expression of the related FGF19 is not clear. Because both FGF21 and 19 were described to protect the liver from steatosis, we have further investigated the role of BMP-9 in this context. We first analyzed BMP-9 levels in the serum of streptozotocin (STZ)-induced diabetic rats (a model of type I diabetes) and confirmed that BMP-9 serum levels decrease during diabetes. Microarray analyses of RNA samples from hepatic and intestinal tissue from BMP-9 KO- and wild-type mice (C57/Bl6 background) pointed to basal expression of BMP-9 in both organs and revealed a down-regulation of hepatic Fgf21 and intestinal Fgf19 in the KO mice. Next, we analyzed BMP-9 levels in a cohort of obese patients with or without diabetes. Serum BMP-9 levels did not correlate with diabetes, but hepatic BMP-9 mRNA expression negatively correlated with steatosis in those patients that did not yet develop diabetes. Likewise, hepatic BMP-9 expression also negatively correlated with serum LPS levels. In situ hybridization analyses confirmed intestinal BMP-9 expression. Intestinal (but not hepatic) BMP-9 mRNA levels were decreased with diabetes and positively correlated with intestinal E-Cadherin expression. In vitro studies using organoids demonstrated that BMP-9 directly induces FGF19 in gut but not hepatocyte organoids, whereas no evidence of a direct induction of hepatic FGF21 by BMP-9 was found. Consistent with the in vitro data, a correlation between intestinal BMP-9 and FGF19 mRNA expression was seen in the patients' samples. In summary, our data confirm that BMP-9 is involved in diabetes development in humans and in the control of the FGF-axis. More importantly, our data imply that not only hepatic but also intestinal BMP-9 associates with diabetes and steatosis development and controls FGF19 expression. The data support the conclusion that increased levels of BMP-9 would most likely be beneficial under pre-steatotic conditions, making supplementation of BMP-9 an interesting new approach for future therapies aiming at prevention of the development of a metabolic syndrome and liver steatosis.

Impact of chronic cold exposure on lung inflammation, pyroptosis and oxidative stress in mice.

Chronic cold exposure, which is the main inducer of lung diseases in high latitudes, affects production efficiency and restricts the development of aquaculture. Although the relationship between cold exposure and susceptibility to the lungs is widely accepted, but the influence between them has not been fully explored. The aim of this study is to understand the underlying mechanism. In the present study, the mice, which are used to establish cold stress (CS)-induced lung injury model, are exposed to cold temperature (4 °C) for 3 h each day for 4 weeks. The results indicate that the expression of heat shock protein 70 (HSP70) is augmented by cold exposure. In addition, chronic cold exposure aggravate the formation of malondialdehyde (MDA) and lead to a significant decrease in the contents of micrococcus catalase (CAT) and glutathione (GSH). Moreover, chronic cold exposure significantly exacerbates the expression of inflammation- and apoptosis-related proteins. The activation of Bax and caspase-3 are significantly augmented. However, that of Bcl-2 is decreased. These results are different from those in room team. The results show that chronic cold exposure plays an important roles in the activation of multiple signaling pathways, such as pyroptosis-related, inflammation-related and oxidative stress-regulated signaling pathways. In summary, these investigations support that chronic cold exposure increase the risk of lung injury by activating inflammation, oxidative stress and pyroptosis.

Mining Therapeutic Efficacy from Treasure Chest of Biodiversity and Chemodiversity: Pharmacophylogeny of Ranunculales Medicinal Plants.

Ranunculales, comprising of 7 families that are rich in medicinal species frequently utilized by traditional medicine and ethnomedicine, represents a treasure chest of biodiversity and chemodiversity. The phylogenetically related species often have similar chemical profile, which makes them often possess similar therapeutic spectrum. This has been validated by both ethnomedicinal experiences and pharmacological investigations. This paper summarizes molecular phylogeny, chemical constituents, and therapeutic applications of Ranunculales, i.e., a pharmacophylogeny study of this representative medicinal order. The phytochemistry/metabolome, ethnomedicine and bioactivity/pharmacology data are incorporated within the phylogenetic framework of Ranunculales. The most studied compounds of this order include benzylisoquinoline alkaloid, flavonoid, terpenoid, saponin and lignan, etc. Bisbenzylisoquinoline alkaloids are especially abundant in Berberidaceae and Menispermaceae. The most frequent ethnomedicinal uses are arthritis, heat-clearing and detoxification, carbuncle-abscess and sore-toxin. The most studied bioactivities are anticancer/cytotoxic, antimicrobial, and anti-inflammatory activities, etc. The pharmacophylogeny analysis, integrated with both traditional and modern medicinal uses, agrees with the molecular phylogeny based on chloroplast and nuclear DNA sequences, in which Ranunculales is divided into Ranunculaceae, Berberidaceae, Menispermaceae, Lardizabalaceae, Circaeasteraceae, Papaveraceae, and Eupteleaceae families. Chemical constituents and therapeutic efficacy of each taxonomic group are reviewed and the underlying connection between phylogeny, chemodiversity and clinical uses is revealed, which facilitate the conservation and sustainable utilization of Ranunculales pharmaceutical resources, as well as developing novel plant-based pharmacotherapy.

Peripheral lymphocyte populations in ovarian cancer patients and correlations with clinicopathological features.

BACKGROUND: To investigate the alterations of peripheral lymphocyte subpopulations in ovarian cancer patients compared to benign or borderline counterparts. The possible clinicopathological implications were also evaluated. METHODS: We enrolled 112 treatment-naive ovarian cancer patients, 14 borderline tumor patients and 44 benign tumor patients between 09/2016 and 01/2019. Flow cytometry was used to measure the peripheral lymphocyte subsets consisting of T cells (CD3+, CD3+CD4+, CD3+CD8+ and CD8+CD28+), regulatory T cells (Tregs, CD4+CD25+CD127-), natural killer cells (NK cells, CD3-CD56+) and B cells (CD19+). RESULTS: Most ovarian cancer patients were high-grade serous carcinoma (84.8%), followed by clear cell carcinoma (8.03%). Late-stage tumor (FIGO III + IV) accounted for 82.1%. The study showed that the proportions of peripheral lymphocyte subsets underwent apparent changes in ovarian cancer patients. We observed elevated levels of Treg cells in patients with both ovarian borderline and malignant tumor compared to those with benign tumors, which achieved statistic significance. In contrast, CD3+CD8+ T and CD8+CD28+ T cells were significantly lower in ovarian cancer patients. Interestingly, low level of B cells was correlated to clear cell carcinoma (P = 0.024), advanced tumor (P = 0.028) and platinum-resistant recurrence (P = 0.014). Regarding the changes of lymphocyte subsets after surgery, CD8+CD28+ T cells had a significant decreasing tendency (P = 0.007) while B cells were the opposite (P < 0.001). CONCLUSIONS: Ovarian cancer patients have altered circulating lymphocyte profile (elevated Treg cell, depressed CD3+CD8+ T and CD8+CD28+ T cells). Low level of B cells might be related to disease aggressiveness, and it recovered after the removal of tumor, which merits further study.

Titanium carbide MXene-based hybrid hydrogel for chemo-photothermal combinational treatment of localized bacterial infection.

With the increased emergence and threat of multi-drug resistant microorganisms, MXenes have become not only an emerging class of two-dimensional functional nanomaterials, but also potential nanomedicines (i.e., antimicrobial agents) that deserve further exploration. Very recently, Ti3C2 MXene was observed to offer a unique membrane-disruption effect and superior light-to-heat conversion efficiency, but its antibacterial property remains unsatisfactory due to poor MXene-bacteria interactions, low photothermal therapy efficiency, and occurrence of bacterial rebound in vivo. Herein, the cationic antibiotic ciprofloxacin (Cip) is combined with Ti3C2 MXene, and a hybrid hydrogel was constructed by incorporating Cip-Ti3C2 nanocomposites into the network structure of a Cip-loaded hydrogels to effectively trap and kill bacteria. We found that the Cip-Ti3C2 nanocomposites achieved an impressive in vitro bactericidal efficiency of >99.99999% (7.03 log10) for the inhibition of methicillin-resistant Staphylococcus aureus (MRSA) by combining chemotherapy with photothermal therapy. In an MRSA-induced murine abscess model, the hybrid hydrogel simultaneously achieved high-efficiency sterilization and long-term inhibition effects, avoiding the rebound of bacteria after photothermal therapy, and thus maximized the in vivo therapeutic efficacy of Ti3C2 MXene-based systems. Overall, this work provides a strategy for efficiently combating localized bacterial infection by rationally designing MXene-based hybrid hydrogels. STATEMENT OF SIGNIFICANCE: Two-dimensional Ti3C2 MXene was recently regarded as a promising functional nanomaterial, however, its antibacterial applications are limited by the poor MXene-bacteria interactions, low photothermal therapy efficiency, and the occurrence of bacterial rebound in vivo. This work aims to construct a Ti3C2 MXene-based hybrid hydrogel for chemo-photothermal therapy and enhance the antimicrobial performance via a combination of the high-efficiency sterilization of ciprofloxacin-Ti3C2 nanocomposites with the long-term inhibition effect of ciprofloxacin hydrogel. The present study provides an example of efficient MXene-based antimicrobials to treat localized bacterial infection such as methicillin-resistant Staphylococcus aureus (MRSA)-induced skin abscess.

Effects of Light on Secondary Metabolite Biosynthesis in Medicinal Plants.

Secondary metabolites (SMs) found in medicinal plants are one of main sources of drugs, cosmetics, and health products. With the increase in demand for these bioactive compounds, improving the content and yield of SMs in medicinal plants has become increasingly important. The content and distribution of SMs in medicinal plants are closely related to environmental factors, especially light. In recent years, artificial light sources have been used in controlled environments for the production and conservation of medicinal germplasm. Therefore, it is essential to elucidate how light affects the accumulation of SMs in different plant species. Here, we systematically summarize recent advances in our understanding of the regulatory roles of light quality, light intensity, and photoperiod in the biosynthesis of three main types of SMs (polyphenols, alkaloids, and terpenoids), and the underlying mechanisms. This article provides a detailed overview of the role of light signaling pathways in SM biosynthesis, which will further promote the application of artificial light sources in medicinal plant production.

Membrane-disruptive peptides/peptidomimetics-based therapeutics: Promising systems to combat bacteria and cancer in the drug-resistant era.

Membrane-disruptive peptides/peptidomimetics (MDPs) are antimicrobials or anticarcinogens that present a general killing mechanism through the physical disruption of cell membranes, in contrast to conventional chemotherapeutic drugs, which act on precise targets such as DNA or specific enzymes. Owing to their rapid action, broad-spectrum activity, and mechanisms of action that potentially hinder the development of resistance, MDPs have been increasingly considered as future therapeutics in the drug-resistant era. Recently, growing experimental evidence has demonstrated that MDPs can also be utilized as adjuvants to enhance the therapeutic effects of other agents. In this review, we evaluate the literature around the broad-spectrum antimicrobial properties and anticancer activity of MDPs, and summarize the current development and mechanisms of MDPs alone or in combination with other agents. Notably, this review highlights recent advances in the design of various MDP-based drug delivery systems that can improve the therapeutic effect of MDPs, minimize side effects, and promote the co-delivery of multiple chemotherapeutics, for more efficient antimicrobial and anticancer therapy.

Clinical implication of serum CA125 for the prediction of malignancy in mucinous cystic neoplasms of the pancreas.

Mucinous cystic neoplasms (MCNs) of the pancreas have malignant potential. Carbohydrate antigen 125 (CA125) is a common widely used biomarker for cancers. However, the role of CA125 in predicting the malignant change of MCNs is currently unidentified. Patients with resected and pathologically confirmed MCN were identified from a prospectively maintained database. The predictive role of serum CA125 in assessing malignant change of MCNs was analyzed and compared with serum carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA). This study included 164 patients with MCN (low/moderate grade, 153 cases; high grade and invasive, 11 cases). The serum levels of CA125 in the high grade and invasive group (45.1±42.1 U/ml) was significantly higher than those in the low/moderate grade group (21.0±46.2 U/ml, P=0.006). The area under the receiver operating characteristic (ROC) curve of CA125 (0.75) for predicting malignancy of MCNs was higher than that of CA19-9 (0.68) or CEA (0.72). The prediction value of CA125 was improved when combined with CEA (CA125 alone, sensitivity 36.4%, specificity 90.6%, accuracy 86.6%; combined with CEA, sensitivity 45.5%, specificity 88.2%, accuracy 85.0%). It was concluded that serum CA125 shows value in predicting the malignant change of MCNs, especially when combined with serum CEA.

Value of multi-parameter flow cytometry immunophenotyping in T/NK-cell neoplasms in cytology specimens: A retrospective study in Chinese patients.

BACKGROUND: Innate limitations of morphological diagnosis of T/NK-cell neoplasms mean that they can be misdiagnosed or missed, especially when mixed with a variety of benign and reactive conditions. The aim of this study was to investigate the application value of multiparameter flow cytometry immunophenotyping (MFCI) in screening and diagnosing T/NK-cell neoplasms with cytology specimens. MATERIAL AND METHODS: The clinical and pathological characteristics of 1028 newly diagnosed cases from Fudan University Shanghai Cancer Center who provided a cytology specimen between June 2010 and January 2016 with correlated histology diagnosis and clinical confirmation were retrospectively reviewed. MFCI was used for screening, diagnosis and typing. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in diagnosis of T/NK-cell neoplasms were calculated. RESULTS: There were 606 males and 422 females in 1028cases, with a mean age of 47.5 years (range 9-86 years). Specimens used for cytologic diagnosis included 996 FNAs, 2 US-FNAs, 13 EUS-FNAs and 17 effusions. Screening for types of lymphoma of MFCI, 139 (13.52 %) cases were T/NK cell lymphoma, 3 (0.29 %) cases were B cell lymphoma T-NHL and B-NHL coexist. A total of 146 suspected T/NK-cell neoplasms were screened out (sensitivity = 94.64 %, specificity = 95.63 % PPV = 72.60 %, NPV = 99.32 %) by MFCI, with 112 (76.71 %) histologically confirmed cases and 6 (4.11 %) false-negative cases identified (3 cases diagnosed as B-cell neoplasms and 1 case as T-cell neoplasm with B-cell neoplasm, which also were confirmed by gene rearrangement. 2 cases were suspicious T-cell-immunophenotypic abnormalities). When used at the diagnostic level, a total of 88 T/NK-cell neoplasms were identified (sensitivity = 68.75 %, specificity = 98.80 %, PPV = 87.50 %, NPV = 96.28 %) with 11 false-positive cases recognized, 9 of which showed typical immunophenotypic T-cell neoplasms features, and 2 exhibited aberrant T immunophenotype. CONCLUSIONS: MFCI has high sensitivity and specificity in the screening and diagnosis of T/NK-cell neoplasms and may be useful as an alternative diagnosis method in cytology specimens.

The improvement effect of gastrodin on LPS/GalN-induced fulminant hepatitis via inhibiting inflammation and apoptosis and restoring autophagy.

Fulminant hepatitis (FH), characterized by overwhelmed inflammation and massive hepatocyte apoptosis, is a life-threatening and high mortality rate. Gastrodin (GTD), a phenolic glucoside extracted from Gastrodiaelata Blume, exerts anti-apoptosis, and anti-inflammatory activities. In the present study, we aimed to evaluate whether GTD treatment could alleviate lipopolysaccharide and d-galactosamine (LPS/GalN)-induced FH in mice and its potential mechanisms. These data suggested that GTD treatment remarkably protected against LPS/GalN-induced FH by enhancing the survival rate of mice, reducing ALT and AST levels, attenuating histopathological changes, and suppressing interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α secretion. In addition, GTD treatment relieved hepatic apoptosis by the regulation of peroxisome proliferator-activated receptors (PPARs), P53 and caspase-3/9. Furthermore, GTD treatment could significantly inhibit inflammation-related signaling pathways activated by LPS/GalN, including the suppression of nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) and nuclear factor-kappa B (NF-κB) activation. Importantly, GTD treatment effectively restored but not induced LPS/GalN-reduced the expression of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, as well as the level of pro-autophagy proteins. Taken together, our investigation indicated that GTD played an essential role in liver protection by relieving hepatocyte apoptosis and inflammation reaction, which may be closely involved in the inhibition of NLRP3 inflammasome and NF-κB activation, regulation of apoptosis-related proteins expression, and the recovery of AMPK/ACC/autophagy.

Kinematic Modeling of a Combined System of Multiple Mecanum-Wheeled Robots with Velocity Compensation.

In industry, combination configurations composed of multiple Mecanum-wheeled mobile robots are adopted to transport large-scale objects. In this paper, a kinematic model with velocity compensation of the combined mobile system is created, aimed to provide a theoretical kinematic basis for accurate motion control. Motion simulations of a single four-Mecanum-wheeled virtual robot prototype on RecurDyn and motion tests of a robot physical prototype are carried out, and the motions of a variety of combined mobile configurations are also simulated. Motion simulation and test results prove that the kinematic models of single- and multiple-robot combination systems are correct, and the inverse kinematic correction model with velocity compensation matrix is feasible. Through simulations or experiments, the velocity compensation coefficients of the robots can be measured and the velocity compensation matrix can be created. This modified inverse kinematic model can effectively reduce the errors of robot motion caused by wheel slippage and improve the motion accuracy of the mobile robot system.