Biomimetic delivery of emodin via macrophage membrane-coated UiO-66-NH2 nanoparticles for acute pancreatitis treatment.

Acute pancreatitis (AP) is a severe inflammatory condition with a rising incidence and high mortality rates, especially in severe cases. Emodin (ED), known for its potent anti-inflammatory properties, holds promise in addressing AP. However, its clinical application is hindered by limitations such as low bioavailability and insufficient target specificity. Herein, we developed a novel drug delivery system using macrophage membrane-coated UiO-66-NH2 nanoparticles loaded with ED (MVs-UiO-ED). UiO-66-NH2 was successfully synthesized and characterized, revealing an octahedral structure with a suitable size distribution. The successful loading of ED onto UiO-66-NH2 was confirmed by ultraviolet and infrared spectroscopy. Subsequently, MVs-UiO-ED was prepared by coating macrophage membrane-derived vesicles onto UiO-ED, resulting in a biomimetic delivery system. In vitro release studies demonstrated that MVs-UiO-ED exhibited a sustained-release profile, indicating its potential for prolonged drug circulation. An AP mouse model was established to evaluate the therapeutic efficacy of MVs-UiO-ED. Compared with the model group, MVs-UiO-ED significantly reduced serum levels of α-amylase and lipase, two indicators of pancreatitis severity. Furthermore, histopathological examinations revealed that MVs-UiO-ED ameliorated pancreatic tissue damage. This study underscores the potential of MVs-UiO-ED as an effective therapeutic approach for AP.

Microplastics' toxic effects and influencing factors on microorganisms in biological wastewater treatment units.

Prior to entering the water body, microplastics (MPs) are mostly collected at the sewage treatment plant and the biological treatment unit is the sewage treatment facility's central processing unit. This review aims to present a comprehensive analysis of the detrimental impacts of MPs on the biological treatment unit of a sewage treatment plant and it covers how MPs harm the effluent quality of biological treatment processes. The structure of microbial communities is altered by MPs presence and additive release, which reduces functional microbial activity. Extracellular polymers, oxidative stress, and enzyme activity are explored as micro views on the harmful mechanism of MPs on microorganisms, examining the toxicity of additives released by MPs and the harm caused to microorganisms by harmful compounds that have been adsorbed in the aqueous environment. This article offers a theoretical framework for a thorough understanding of the potential problems posed by MPs in sewage treatment plants and suggests countermeasures to mitigate those risks to the aquatic environment.

A data-driven framework for learning hybrid dynamical systems.

The existing data-driven identification methods for hybrid dynamical systems such as sparse optimization are usually limited to parameter identification for coefficients of pre-defined candidate functions or composition of prescribed function forms, which depend on the prior knowledge of the dynamical models. In this work, we propose a novel data-driven framework to discover the hybrid dynamical systems from time series data, without any prior knowledge required of the systems. More specifically, we devise a dual-loop algorithm to peel off the data subject to each subsystem of the hybrid dynamical system. Then, we approximate the subsystems by iteratively training several residual networks and estimate the transition rules by training a fully connected neural network. Several prototypical examples are presented to demonstrate the effectiveness and accuracy of our method for hybrid models with various dimensions and structures. This method appears to be an effective tool for learning the evolutionary governing laws of hybrid dynamical systems from available data sets with wide applications.

GC-MS Analysis of the Essential Oil from Seseli mairei H. Wolff (Apiaceae) Roots and Their Nematicidal Activity.

The essential oil (EO) was extracted from aerial parts with insecticidal and fungicidal activity. Herein, the hydro-distilled essential oils of Seseli mairei H. Wolff roots were determined by GC-MS. A total of 37 components were identified, (E)-beta-caryophyllene (10.49%), ß-geranylgeranyl (6.64%), (E)-2-decenal (6.17%) and germacrene-D (4.28%). The essential oil of Seseli mairei H. Wolff had nematicidal toxicity against Bursaphelenchus xylophilus with a LC50 value of 53.45 µg/mL. The subsequent bioassay-guided investigation led to the isolation of three active constituents: falcarinol, (E)-2-decenal, and octanoic acid. The falcarinol demonstrated the strongest toxicity against B. Xylophilus (LC50 = 8.52 µg/mL). The octanoic acid and (E)-2-decenal also exhibited moderate toxicity against B. xylophilus (LC50 = 65.56 and 176.34 µg/mL, respectively). The LC50 of falcarinol for the toxicity of B. xylophilus was 7.7 and 21 times than that of octanoic acid and (E)-2-decenal, respectively. Our findings demonstrate that the essential oil from Seseli mairei H. Wolff roots and their isolates may be developed as a promising natural nematicide.

Effects of sulfamethoxazole on nitrogen removal and molecular ecological network in integrated vertical-flow constructed wetland.

Response of nitrogen removal efficiency and microbial interactions to organic pollution has been a major issue in wastewater treatment system. However, the nitrogen removal efficiency and interactions among microbial community under antibiotics press is still unclear. Thus, the effect of sulfamethoxazole (SMX) on nitrogen removal and microbial responses of IVCWs was investigated through recorded the nitrogen removal efficiency before and after adding SMX and random matrix theory (RMT)-based network analysis. Results showed that better NH4+-N removal (>90%) after a long period of operation were achieved in IVCWs, but NO3--N was accumulated. However, nitrate removal rates were significantly increased after long-term exposure (60 d) to 100 µgL-1 SMX (from 27.35% to 35.57%) with relatively high SMX removal (53.50%). Surprisingly, the ammonia nitrogen removal rate (90.07-92.70%) were not significantly affected by SMX in IVCWs. Moreover, the bacterial richness was decreased and the bacterial community structures were altered by the presence of SMX, especially those of nitrogen-transforming microorganisms. Molecular ecological network analysis suggested that SMX had positive influences on denitrifying bacteria interactions but reduced the network complexity and microbial interactions on whole molecular network, and among-module connections were weakened obviously at SMX.

Bifurcation of singularities of fluctuational paths for a noise-driven overdamped two-well system.

Noise-induced escape in a 2D generalized Maier-Stein model with two parameters µ and α is investigated in the weak noise limit. With the WKB approximation, the patterns of extreme paths and singularities are displayed. By employing the Freidlin-Wentzell action functional and the asymptotic series, critical parameters α inducing singularity bifurcation are determined analytically for µ=1. The switching line will appear with singularities and is equivalent to the sliding set in the Filippov system. The pseudo-saddle-node bifurcation on the switching line is found. Then, when -1<µ<1, it is found that all bifurcation values α will decrease as µ decreases and the second-order bifurcation values are bigger than all first-order ones. In addition, the variation of the switching line is also analyzed and a new switching line will emerge when the location of the minimum quasi-potential on the boundary changes. At last, when the noise is anisotropic, only the noise intensity ratio will affect the bifurcation value α.

Effect of parametric excitation on a bifractional-order damped system with a fractional-power nonlinearity.

Investigation on linear/nonlinear resonance phenomena and supercritical/subcritical pitchfork bifurcation mechanism is reported in a complex bifractional-order damped system which endures a high-frequency parametric excitation and contains fractional-power nonlinearity. The approximate theoretical expression of the linear response amplitude at the primary frequency and the superharmonic response amplitude at the second and third harmonic frequencies are obtained by utilizing an analytical method and an iterative formula. A numerical approximation scheme based on the Caputo derivative for the simulation of the system is introduced, showing sufficient precision. Due to the parametric excitation, analytical approximation expressions of the stable equilibrium points are given explicitly when the exponent is not an integer so that the pitchfork bifurcation, nonlinear resonance can be studied in an analytical way, exhibiting much more operability than the external excitation case. It is found that the fractional-order derivative may bring new multibifurcation and new multiresonance phenomena, which have not yet been reported before. With the variation of different control parameters of the system, the equivalent slow-varying system can be converted from bistability to monostability and finally to bistability. Unlike the cases of the system excited by bifrequency external excitation, the optimum response amplitude of the parametric excited system is not monotonous with respect to the values of the exponent. For a range of parameters of the system, it is also found that the superharmonic resonance at the second and third harmonic frequencies is affected deeply by the parametric excitation.

Most probable dynamics of stochastic dynamical systems with exponentially light jump fluctuations.

The emergence of the exit events from a bounded domain containing a stable fixed point induced by non-Gaussian Lévy fluctuations plays a pivotal role in practical physical systems. In the limit of weak noise, we develop a Hamiltonian formalism under the Lévy fluctuations with exponentially light jumps for one- and two-dimensional stochastic dynamical systems. This formalism is based on a recently proved large deviation principle for dynamical systems under non-Gaussian Lévy perturbations. We demonstrate how to compute the most probable exit path and the quasi-potential by several examples. Meanwhile, we explore the impacts of the jump measure on the quasi-potential quantitatively and on the most probable exit path qualitatively. Results show that the quasi-potential can be well estimated by an approximate analytical expression. Moreover, we discover that although the most probable exit paths are analogous to the Gaussian case for the isotropic noise, the anisotropic noise leads to significant changes in the structure of the exit paths. These findings shed light on the underlying qualitative mechanism and quantitative feature of the exit phenomenon induced by non-Gaussian noise.

Single and joint oxidative stress of cadmium and phenanthrene on the Bivalve Anadara subcrenata.

Single and joint oxidative stress of cadmium (Cd) and phenanthrene (Phe) on Anadara subcrenata were investigated under laboratory conditions with biomarkers such as reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and total antioxidant capacity (TAOC). The results indicated that the ROS level in Anadara subcrenata exposed to Cd and Phe significantly (P < 0.05) increased during the early exposure stage, and the TAOC level and SOD activity were induced as the response of the antioxidant defense system, and this followed a damage, recovery or acclimation event. The MDA content was negatively correlated with SOD activity. As the time went on, the ROS level decreased gradually and was close to that in the control after 9 days; the TAOC level decreased accordingly, but the recovery rate of the SOD activity was slower than that of the TAOC level. High concentrations of Cd or Phe had a stronger oxidative stress effect on Anadara subcrenata. Phe had a stronger effect on the SOD activity of Anadara subcrenata. The joint effects of Cd and Phe on the levels of ROS and TAOC, SOD activity and MDA content in Anadara subcrenata are dependent on their concentration combination, which were called the double-dose dependent effects and time-dependent effects, respectively. The binary mixture treatments of 477.33 µg/L Cd and 48.08 µg/L Phe had the highest oxidative stress on Anadara subcrenata.

Effects of Moist Exposed Burn Therapy and Ointment (MEBT/MEBO) on the autophagy mTOR signalling pathway in diabetic ulcer wounds.

Context: Burn therapy (MEBT)/moist exposed burn ointment (MEBO) is an effective traditional Chinese medicine method to treat diabetic wound, but the mechanism is unclear. Autophagy has been proved to be closely related with wound healing, so MEBO/MEBT is hypothesized to promote diabetic wound healing by regulating autophagy.Objective: To explore the mechanism of moist exposed MEBT/MEBO promoting diabetic wound repair.Materials and methods: Eighty male Wistar rats were randomly assigned to control (n = 20) and diabetic group induced by intraperitoneal injection of STZ (n = 60), which were further randomly assigned to MEBO, Kangfuxin and model groups (n = 20 each). All rats underwent full-thickness skin resection in the back. Wound healing was dynamically observed and wound tissues were collected at five time points for pathological examination, autophagosome and the expression of PI3K, Akt and mTOR.Results: The healing time in the control group was the shortest, no statistically significant difference was found between the MEBO and the Kangfuxin group (p = 0.76). The morphology of autophagosomes ranged large to small, which was the most obvious in the MEBO group. The mRNA and protein expression of PI3K, Akt and mTOR in each group reached the peak on Day 5, the levels in the MEBO group were the highest (F = 18.43, 19.97, 15.36, p < 0.05). On Day 11, the expression levels in each group began to decline.Discussion and conclusions: In this study, we discussed the molecular mechanism of MEBT/MEBO promoting the repair of diabetic ulcer wounds through autophagy and PI3K-Akt-mTOR signalling pathway, which provides a new way for drug design in the future.

Sp1 promotes cell migration and invasion in oral squamous cell carcinoma by upregulating Annexin A2 transcription.

Oral squamous cell carcinoma (OSCC) is a common malignant tumor with high metastatic potential in head and neck. Revealing the mechanism of OSCC metastasis will benefit the prognosis and prevention of OSCC. Sp1 is a transcription factor involved in the progression of several tumors. Annexin A2 functions as an oncogene, and there are three putative Sp1 binding sites in the Annexin A2 promoter region. Therefore, we hypothesized that Sp1 could regulate OSCC metastasis by regulating Annexin A2 expression. Quantitative real-time PCR (qRT-PCR) and Western blot were used to evaluate Sp1 or Annexin A2 expression. Transwell assays were used to evaluate the migration and invasion capacity of OSCC cells. Luciferase assays and Chromatin immunoprecipitation assays were used to verify whether Sp1 regulate Annexin A2 at the transcriptional level. We found that the expression of Sp1 increased in OSCC tissues compared to paired adjacent normal tissues, and the overexpression of Sp1 was associated with tumor metastasis. Furthermore, Sp1 promoted cell migration and invasion through Annexin A2. In addition, we verified that Sp1 controls Annexin A2 expression at the transcriptional level and identified the binding sites involved. Our study suggests that Sp1/Annexin A2 expression could be a promising prognostic biomarker and therapeutic target for OSCC metastasis.

Noise induced escape in one-population and two-population stochastic neural networks with internal states.

In the present paper, the escapes from the basins of fixed points induced by intrinsic noise are investigated in both one- and two-population stochastic hybrid neural networks. In the weak noise limit, the quasipotentials are computed through the application of WKB approximation to the original hybrid system and the results of quasi-steady-state (QSS) diffusion approximation. It is seen that the two results are consistent with each other within the neighborhood of a fixed point and an obvious discrepancy arises in the other area, of which the reason is then explored and revealed. Furthermore, the relationship between the fluctuational paths and the relaxational ones is analyzed, based on which some specific results for the hybrid system is obtained. Besides, for the two-population model, the phenomenon of saddle point avoidance is investigated by using both theoretical and numerical methods. Finally, the topological structure of Lagrangian manifold is analyzed, and its particular features and something analogous to the stochastic differential equation are found according to the accuracy of QSS within the vicinity of the saddle point.

Ultrahigh-Energy Density Lithium-Ion Cable Battery Based on the Carbon-Nanotube Woven Macrofilms.

Moore's law predicts the performance of integrated circuit doubles every two years, lasting for more than five decades. However, the improvements of the performance of energy density in batteries lag far behind that. In addition, the poor flexibility, insufficient-energy density, and complexity of incorporation into wearable electronics remain considerable challenges for current battery technology. Herein, a lithium-ion cable battery is invented, which is insensitive to deformation due to its use of carbon nanotube (CNT) woven macrofilms as the charge collectors. An ultrahigh-tap density of 10 mg cm-2 of the electrodes can be obtained, which leads to an extremely high-energy density of 215 mWh cm-3 . The value is approximately seven times than that of the highest performance reported previously. In addition, the battery displays very stable rate performance and lower internal resistance than conventional lithium-ion batteries using metal charge collectors. Moreover, it demonstrates excellent convenience for connecting electronics as a new strategy is applied, in which both electrodes can be integrated into one end by a CNT macrorope. Such an ultrahigh-energy density lithium-ion cable battery provides a feasible way to power wearable electronics with commercial viability.

The efficacy of polidocanol sclerotherapy in mucocele of the minor salivary gland.

OBJECTIVES: Mucocele of the minor salivary gland is usually caused when the duct is injured, mucus leaks into the tissue space and the mucous gland are obstructed, which lead to cystic lesion formation and dilatation. Currently, there are multiple therapeutic methods available with various outcomes. This study aims to provide clinical evidence of polidocanol sclerotherapy for the treatment of mucocele of the minor salivary gland. METHODS: In this study, we injected polidocanol into 112 patients who were diagnosed with mucocele of the minor salivary gland and evaluated the treatment efficacy and safety systematically. RESULTS: Of the 122 cases, 102 cases were cured, eight cases showed remarkable remission, and two cases had partial remission. No recurrence was found during follow-up, and none of the cases showed an invalid effect, resulting in a total cure rate of 91.07%. No severe side effects were observed during treatment or the follow-up period. No significant difference in efficacy between different genders was found (P = 0.490). Polidocanol sclerotherapy for mucocele on the lower lip was more effective compared to mucocele on the inferior surface of the lingual apex (P = 0.035). CONCLUSION: Polidocanol sclerotherapy showed satisfying curative effects for mucocele of the minor salivary gland without causing side effects of anesthesia, trauma, or severe pain.

Delay-induced locking in bursting neuronal networks.

In this paper, the collective behaviors for ring structured bursting neuronal networks with electrical couplings and distance-dependent delays are studied. Each neuron is modeled by the Hindmarsh-Rose neuron. Through changing time delays between connected neurons, different spatiotemporal patterns are obtained. These patterns can be explained by calculating the ratios between the bursting period and the delay which exhibit clear locking relations. The holding and the failure of the lockings are investigated via bifurcation analysis. In particular, the bursting death phenomenon is observed for large coupling strengths and small time delays which is in fact the result of the partial amplitude death in the fast subsystem. These results indicate that the collective behaviors of bursting neurons critically depend on the bifurcation structure of individual ones and thus the variety of bifurcation types for bursting neurons may create diverse behaviors in similar neuronal ensembles.

Noise induced escape from a nonhyperbolic chaotic attractor of a periodically driven nonlinear oscillator.

Noise induced escape from the domain of attraction of a nonhyperbolic chaotic attractor in a periodically excited nonlinear oscillator is investigated. The general mechanism of the escape in the weak noise limit is studied in the continuous case, and the fluctuational path is obtained by statistical analysis. Selecting the primary homoclinic tangency as the initial condition, the action plot is presented by parametrizing the set of escape trajectories and the global minimum gives rise to the optimal path. Results of both methods show good agreements. The entire process of escape is discussed in detail step by step using the fluctuational force. A structure of hierarchical heteroclinic crossings of stable and unstable manifolds of saddle cycles is found, and the escape is observed to take place through successive jumps through this deterministic hierarchical structure.

Controllable Preparation of Polyaniline-Graphene Nanocomposites using Functionalized Graphene for Supercapacitor Electrodes.

In order to explore the effect of graphene surface chemistry on electrochemical performance based on polyaniline-graphene hybrid material electrodes, four different polyaniline-graphene nanocomposites were fabricated with graphene oxide, reduced graphene oxide, aminated graphene and sulfonated graphene as carriers, respectively. The nanocomposites feature various structures and morphologies, which could be used to more deeply understand the morphology and structure effects caused by surface chemistry on electrochemical performance. The experimental results reveal that functionalized electronegative graphene was conducive to the vertical and neat growth of polyaniline (PANI) nanorods. The array architecture endowed the PANI-GS nanocomposite with a large ion-accessible surface area and high-efficiency electron- and ion-transport pathways. Meanwhile, the introduction of sulfonic acid functional groups accelerated the redox reaction with doping and dedoping of the PANI. Thereby, the PANI-GS nanocomposite exhibited a high specific capacitance of 863.2 F g(-1) at a current density of 0.2 A g(-1) and the excellent rate capability of 67.4 % (581.6 F g(-1) at 5 A g(-1) ), which were much better than the other three nanocomposites produced.

Inhibition of autophagy augments apoptosis in human oral squamous cell carcinoma under nutrient depletion.

There has been little research conducted regarding autophagy in oral squamous cell carcinoma (OSCC). Given the prevalence of oral cancers which are OSCC and the severe side effects of current treatments, there is a pressing need to develop effective alternative therapies. In this study, we have endeavored to explore the biological characteristics of oral squamous cell carcinoma cell line KB cells, in particular with regard to the role played by autophagy in their survival. Autophagy was activated by nutrient depletion via culturing cells in Earle's balanced salts (EBSS) and was measured via indices relating to Beclin 1, microtubule-associated protein light chain 3 (MAPLC3, LC3), p62, and Green fluorescent protein-light chain 3 plasmid transfection (GFP-LC3). Cell death and apoptosis induced by nutrient depletion was measured using both MTT assay and flow cytometry (FCM). Compared to initial levels at 0 h, Beclin 1 density in EBSS-treated cells was found to have increased at 6, 12, and 18 h in a time-dependent manner and was found to have subsequently declined at 24 and 48 h. p62 levels, LC3-II/LC3-I ratio, and GFP-LC3 levels increased at 6, 12, 18, 24, and 48 h in a time-dependent manner. 3-methyladenine (3-MA) was found to inhibit autophagy and the expression of Beclin 1 and significantly enhanced nutrient depletion-induced apoptosis and death. We concluded that nutrient depletion enhances OSCC cell autophagy in time-course patterns and that the inhibition of autophagy augments apoptosis in OSCC cells. We also deduced that Beclin 1 takes part in the development and progression of autophagy, potentially playing an important role in the crosstalk between apoptosis and autophagy in OSCC cells. These findings suggest that nutrient depletion may be an effective way to explore autophagy and that autophagy inhibitors should be investigated as a potential novel agent for the adjuvant treatment of human OSCC.

Uptake, accumulation and translocation mechanisms of organophosphate esters in cucumber (Cucumis sativus) following foliar exposure.

Organophosphate esters (OPEs) have been frequently detected in crops. However, few studies have focused on the uptake and translocation of OPEs in plants following foliar exposure. Herein, to investigate the foliar uptake, accumulation and translocation mechanisms of OPEs in plant, the cucumber (Cucumis sativus) was selected as a model plant for OPEs exposure via foliar application under control conditions. The results showed that the content of OPEs in the leaf cuticle was higher than that in the mesophyll on exposed leaf. Significant positive correlations were observed between the content of OPEs in the leaf cuticle and their log Kow and log Kcw values (P < 0.01), suggesting that OPEs with high hydrophobicity could not easily move from the cuticle to the mesophyll. The moderately hydrophobic OPEs, such as tris (2-chloroisopropyl) phosphate (TCPP, log Kow = 2.59), were more likely to move not only from the cuticle to the mesophyll but also from the mesophyll to the phloem. The majority of the transported OPEs accumulated in younger leaves (32-45 %), indicating that younger tissue was the primary target organ for OPEs accumulation after foliar exposure. Compared to chlorinated OPEs (except TCPP) and aryl OPEs, alkyl OPEs exhibited the strongest transport capacity in cucumber seedling due to their high hydrophilicity. Interestingly, tri-p-cresyl phosphate was found to be more prone to translocation compared to tri-m-cresyl phosphate and tri-o-cresyl phosphate, despite having same molecular weight and similar log Kow value. These results can contribute to our understanding of foliar uptake and translocation mechanism of OPEs by plant.

Recent Advances in Targeted Therapies for Infantile Hemangiomas.

Targeted therapy for infantile hemangiomas (IHs) has been extensively studied as they can concentrate drugs, increase therapeutic efficacy and reduce drug dosage. Meanwhile, they can extend drug release times, enhance drug stability, decrease dosing frequency, and improve patient compliance. Moreover, carriers made from biocompatible materials reduced drug immunogenicity, minimizing adverse reactions. However, current targeted formulations still face numerous challenges such as the non-absolute safety of carrier materials; the need to further increase drug loading capacity; the limitation of animal hemangioma models in fully replicating the biological properties of human infantile hemangiomas; the establishment of models for deep-seated hemangiomas with high incidence rates; and the development of more specific targets or markers. In this review, we provided a brief overview of the characteristics of IHs and summarized the past decade's advances, advantages, and targeting strategies of targeted drug delivery systems for IHs and discussed their applications in the treatment of IHs. Furthermore, the goal is to provide a reference for further research and application in this field.