Low beauvericin concentrations promote PC-12 cell survival under oxidative stress by regulating lipid metabolism and PI3K/AKT/mTOR signaling.

Beauvericin (BEA), a naturally occurring cyclic peptide with good pharmacological activity, has been widely explored in anticancer research. Although BEA is toxic, studies have demonstrated its antioxidant activity. However, to date, the antioxidant mechanisms of BEA remain unclear. Herein, we conducted a comprehensive and detailed study of the antioxidant mechanism of BEA using an untargeted metabolomics approach, subsequently validating the results. BEA concentrations of 0.5 and 1 µM significantly inhibited H2O2-induced oxidative stress (OS), decreased reactive oxygen species levels in PC-12 cells, and restored the mitochondrial membrane potential. Untargeted metabolomics indicated that BEA was primarily involved in lipid-related metabolism, suggesting its role in resisting OS in PC-12 cells by participating in lipid metabolism. BEA combated OS damage by increasing phosphatidylcholine, phosphatidylethanolamine, and sphingolipid levels. In the current study, BEA upregulated proteins related to the PI3K/AKT/mTOR pathway, thereby promoting cell survival. These findings support the antioxidant activity of BEA at low concentrations, warranting further research into its pharmacological effects.

A Cross-Sectional Study of Clostridium Difficile Infection in Inpatients with Antibiotic Associated Diarrhea.

BACKGROUND: Clostridium difficile (C. difficile) is a Gram-positive, anaerobic, spore-forming bacillus that can cause pseudomembranous colitis and other C. difficile-associated diseases, resulting in significant morbidity and mortality. The incidence and clinical features vary by geography. METHODS: In this cross-sectional study, we examined the incidence and clinical features of C. difficile infection (CDI) within a 2,900-bed academic medical center in a southern area of China from January 1, 2017, to December 31, 2020. All adult inpatients (aged ≥ 18 years) who submitted loose stool samples for C. difficile testing over this period were considered for the study. RESULTS: This cross-sectional study showed that the average incidence of CDI was 2.07 cases/100,000 hospital patient-days. The mean age of these inpatients was 71.21 ± 2.83 years (range 30 - 93 years), and 83.61% (51/61) were treated in medical units. We found that 85.25% (52/61) of inpatients with CDI were aged > 60 years. Multivariate logistic regression analysis revealed that age > 60 years, and admission to the geriatric treatment unit or neurosurgery treatment unit were indeed independent risk factors for CDI in inpatients. CONCLUSIONS: The incidence of CDI in the southern area of China was low. Age > 60 years, and treatment in geriatric or neurosurgery units were independent risk factors for CDI inpatients.

A Novel Clustering Method Based on Adjacent Grids Searching.

Clustering is used to analyze the intrinsic structure of a dataset based on the similarity of datapoints. Its widespread use, from image segmentation to object recognition and information retrieval, requires great robustness in the clustering process. In this paper, a novel clustering method based on adjacent grid searching (CAGS) is proposed. The CAGS consists of two steps: a strategy based on adaptive grid-space construction and a clustering strategy based on adjacent grid searching. In the first step, a multidimensional grid space is constructed to provide a quantization structure of the input dataset. The noise and cluster halo are automatically distinguished according to grid density. Moreover, the adaptive grid generating process solves the common problem of grid clustering, in which the number of cells increases sharply with the dimension. In the second step, a two-stage traversal process is conducted to accomplish the cluster recognition. The cluster cores with arbitrary shapes can be found by concealing the halo points. As a result, the number of clusters will be easily identified by CAGS. Therefore, CAGS has the potential to be widely used for clustering datasets with different characteristics. We test the clustering performance of CAGS through six different types of datasets: dataset with noise, large-scale dataset, high-dimensional dataset, dataset with arbitrary shapes, dataset with large differences in density between classes, and dataset with high overlap between classes. Experimental results show that CAGS, which performed best on 10 out of 11 tests, outperforms the state-of-the-art clustering methods in all the above datasets.

Efficacy and Safety of Apatinib in Patients with Recurrent or Refractory Melanoma.

BACKGROUND: The prognosis of patients with metastatic malignant melanoma is very poor and partly due to resistance to conventional chemotherapies. The study's objectives were to assess the activity and tolerability of apatinib, an oral small molecule anti-angiogenesis inhibitor, in patients with recurrent advanced melanoma. METHODS: This was a single-arm, single-center phase II trial. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Eligible patients had received at least one first-line therapy for advanced melanoma and experienced recurrence. Apatinib (500 mg) was orally administered daily. RESULTS: Fifteen patients (V660E BRAF status: 2 mutation, 2 unknown, 11 wild type) were included in the analysis. The median PFS was 4.0 months. There were two major objective responses, for a 13.3% response rate. Eleven patients had stable disease, with a DCR of 86.7%. The median OS was 12.0 months. The most common treatment-related adverse events of any grade were hypertension (80.0%), mucositis oral (33.3%), hand-foot skin reaction (26.7%), and liver function abnormalities, hemorrhage, diarrhea (each 20%). The only grade ≥3 treatment-related adverse effects that occurred in 2 patients was hypertension (6.7%) and mucositis (6.7%). No treatment-related deaths occurred. CONCLUSION: Apatinib showed antitumor activity as a second- or above-line therapy in patients with malignant melanoma. The toxicity was manageable. CLINICALTRIALS.GOV IDENTIFIER: NCT03383237.

Direction-sensitive detection of a spinning object using dual-frequency vortex light.

Rotational Doppler effect (RDE) has attracted much attention in recent years which opens new avenues to angular velocity measurement. However, most previous studies used single-frequency vortex light as the detection beam so that the rotational Doppler signal is in the low frequency domain where most of noise signals exist. In this article, we use the dual-frequency 2-fold multiplexed vortex light as the probe beam and transform the Doppler signals from the low frequency domain to the high frequency domain successfully. The results show hardly any noise compared with the measurement in the low frequency domain. More importantly, the direction of rotation can be obtained directly by comparing the modulated signal and the reference signal. Our work demonstrates a new detection method for the RDE and provides a reference for its practical application.

Rotational Doppler effect detection by LG beams with a nonzero radial index.

The capability to detect the rotational speed of non-cooperative targets in a long distance is a difficult problem to be solved. In recent years, vortex light provides a feasible solution for the measurement of rotational speed for its spiral phase and the orbital angular momentum. Laguerre-Gaussian (LG) mode, as the typical vortex beam, has been widely employed in rotational Doppler effect (RDE) experiments. Here, we show that the nonzero radial index LG beam not only has a specific physical meaning but also can enhance the light intensity and the amplitude of RDE frequency signal relative to a zero radial index LG beam. To this end, we theoretically analyze the reason of intensity enhancement of a nonzero radial index beam and verify the conclusion in a variable control experiment. Our study provides a new aspect of LG beams that can be considered in rotational speed detection based on RDE. It may produce an improvement of the detection range of rotating targets in practical applications.

Generating a new type of polygonal perfect optical vortex.

We generate a new type of perfect optical vortex called the polygonal perfect optical vortex (PPOV) by combining the Bessel-Gauss beam with the high-order cross-phase (HOCP) at the plane of a spatial light modulator (SLM). This is the first time that the HOCP is applied to the Fourier plane of an optical field (POV) instead of directly acting on an optical field itself. Experimentally, the symmetrical PPOV is generated, and the capability of asymmetric distribution is demonstrated. Furthermore, we discuss the influence of parameters on a PPOV. On this basis, we show a novel function of the PPOV that can adjust the energy distribution at the vertices while maintaining the orbital angular momentum as much as possible, which facilitates applications in optical micro-manipulation.

Analysis of misaligned optical rotational Doppler effect by modal decomposition.

The optical rotational Doppler effect (RDE) is closely related to the unique orbital angular momentum (OAM) carried by optical vortex, whose topological charge means the mode of OAM. Compared with the coaxial incidence, the rotational Doppler frequency shift spectrum of a misaligned optical vortex (misaligned RDE) widens according to a certain law. In this paper, an OAM modal decomposition method of the misaligned optical RDE is proposed and the relative intensity of different OAM modes, namely the OAM spectrum, is derived based on an inner product computation. Analyses show that lateral displacements and angular deflections change the distribution of OAM modes relative to the rotation axis of the object. A misaligned Laguerre-Gaussian (LG) vortex can be represented as a specific combination of coaxial LG modes, and the difference between the topological charge of two adjacent modes is 1 or 2 with lateral displacements or angular deflections respectively. An experiment of misaligned optical RDE using a superimposed LG vortex is executed, and the obtained frequency shift spectrum with misaligned incidence expands into a set of discrete signals, which agrees well with the theoretical results. Moreover, we can get the rotation frequency of the object from an expanded frequency spectrum more quickly and accurately based on the difference between two adjacent signal peaks. The proposed method contributes to analyze the misaligned optical RDE comprehensively, which is significant in remote sensing and optical metrology.

A Hybrid Differential Symbiotic Organisms Search Algorithm for UAV Path Planning.

Unmanned aerial vehicle (UAV) path planning is crucial in UAV mission fulfillment, with the aim of finding a satisfactory path within affordable time and moderate computation resources. The problem is challenging due to the complexity of the flight environment, especially in three-dimensional scenarios with obstacles. To solve the problem, a hybrid differential symbiotic organisms search (HDSOS) algorithm is proposed by combining the mutation strategy of differential evolution (DE) with the modified strategies of symbiotic organism search (SOS). The proposed algorithm preserves the local search capability of SOS, and at the same time has impressive global search ability. The concept of traction function is put forward and used to improve the efficiency. Moreover, a perturbation strategy is adopted to further enhance the robustness of the algorithm. Extensive simulation experiments and comparative study in two-dimensional and three-dimensional scenarios show the superiority of the proposed algorithm compared with particle swarm optimization (PSO), DE, and SOS algorithm.

Detection of spinning objects at oblique light incidence using the optical rotational Doppler effect: erratum.

An erratum is presented to correct funding section of [Opt. Express 27(17), 24781-24792 (2019)].

Polygonal shaping and multi-singularity manipulation of optical vortices via high-order cross-phase.

Increasing demand for practical applications is forcing more in-depth research into optical vortices (OVs): from the generation and measurement to the shaping and multi-singularity manipulation of OVs. Herein, we propose a new type of phase structure called the high-order cross-phase (HOCP), which can be employed to modulate OVs to implement polygonal shaping and multi-singularity manipulation simultaneously at far-field. Theoretically, we investigate the propagation characteristics of OVs modulated by a HOCP. In experiments, we achieve the polygonal shaping and multi-singularity manipulation of OVs via HOCPs. On this basis, we discuss the relationship between shapes and the orders of HOCPs, where we find that the order of a HOCP is exactly equal to the number of sides of polygonal OVs. This work provides a novel method to achieve polygonal shaping and multi-singularity manipulation simultaneously, which facilitate applications in optical micro-manipulation and optical communication.

Generation and measurement of high-order optical vortices by using the cross phase.

We investigate a method for the generation and measurement of high-order optical vortices (OVs) by using the cross phase (CP), which is applied to implement interconversion between Laguerre-Gauss (LG) beams and Hermite-Gaussian beams in the far-field. Experimentally, we generate LG beams, which are a kind of typical OVs, with 20 radial nodes, and measure OVs with topological charges up to 200 via the CP. On this basis, we discuss the relationship between intensity distributions and the waist radius of initial light beams. This work provides an alternative method to generate and measure high-order OVs, which is useful in the fields of optical micro-manipulation, high-dimensional quantum entanglement, and remote sensing of the angular rotation of structured objects.

A Novel Simulated Annealing Based Strategy for Balanced UAV Task Assignment and Path Planning.

The unmanned aerial vehicle (UAV) has drawn increasing attention in recent years, especially in executing tasks such as natural disaster rescue and detection, and battlefield cooperative operations. Task assignment and path planning for multiple UAVs in the above scenarios are essential for successful mission execution. But, effectively balancing tasks to better excavate the potential of UAVs remains a challenge, as well as efficiently generating feasible solutions from the current one in constrained explosive solution spaces with the increase in the scale of optimization problems. This paper proposes an efficient approach for task assignment and path planning with the objective of balancing the tasks among UAVs and achieving satisfactory temporal resolutions. To be specific, we add virtual nodes according to the number of UAVs to the original model of the vehicle routing problem (VRP), thus make it easier to form a solution suitable for heuristic algorithms. Besides, the concept of the universal distance matrix is proposed to transform the temporal constraints to spatial constraints and simplify the programming model. Then, a Swap-and-Judge Simulated Annealing (SJSA) algorithm is therefore proposed to improve the efficiency of generating feasible neighboring solutions. Extensive experimental and comparative studies on different scenarios demonstrate the efficiency of the proposed algorithm compared with the exact algorithm and meta-heuristic algorithms. The results also inspire us about the characteristics of a population-based algorithm in solving combinatorial discrete optimization problems.

Novel Sulfolobus Virus with an Exceptional Capsid Architecture.

A novel archaeal virus, denoted Sulfolobus ellipsoid virus 1 (SEV1), was isolated from an acidic hot spring in Costa Rica. The morphologically unique virion of SEV1 contains a protein capsid with 16 regularly spaced striations and an 11-nm-thick envelope. The capsid exhibits an unusual architecture in which the viral DNA, probably in the form of a nucleoprotein filament, wraps around the longitudinal axis of the virion in a plane to form a multilayered disk-like structure with a central hole, and 16 of these structures are stacked to generate a spool-like capsid. SEV1 harbors a linear double-stranded DNA genome of ∼23 kb, which encodes 38 predicted open reading frames (ORFs). Among the few ORFs with a putative function is a gene encoding a protein-primed DNA polymerase. Sixfold symmetrical virus-associated pyramids (VAPs) appear on the surface of the SEV1-infected cells, which are ruptured to allow the formation of a hexagonal opening and subsequent release of the progeny virus particles. Notably, the SEV1 virions acquire the lipid membrane in the cytoplasm of the host cell. The lipid composition of the viral envelope correlates with that of the cell membrane. These results suggest the use of a unique mechanism by SEV1 in membrane biogenesis.IMPORTANCE Investigation of archaeal viruses has greatly expanded our knowledge of the virosphere and its role in the evolution of life. Here we show that Sulfolobus ellipsoid virus 1 (SEV1), an archaeal virus isolated from a hot spring in Costa Rica, exhibits a novel viral shape and an unusual capsid architecture. The SEV1 DNA wraps multiple times in a plane around the longitudinal axis of the virion to form a disk-like structure, and 16 of these structures are stacked to generate a spool-like capsid. The virus acquires its envelope intracellularly and exits the host cell by creating a hexagonal hole on the host cell surface. These results shed significant light on the diversity of viral morphogenesis.

Detection of spinning objects at oblique light incidence using the optical rotational Doppler effect.

The optical rotational Doppler effect of light beams with angular momentum has recently found applications in the remote sensing of spinning objects. However, most of the reported experimental demonstrations rely on the particular condition of normal incidence, while the general case of oblique incidence has not been addressed yet. Herein, we investigate the optical rotational Doppler effect at oblique incidence based on a local scattering model and formulate the quantitative relation between the Doppler frequency shift and the tilt angle. The analytic results indicate that even if the rotational axis of the spinning object is oriented at a specific tilt angle relative to the light propagation direction, the rotational speed can still be extracted from an asymmetrically broadened Doppler signal. The geometric mean value of the extreme frequency shift is a constant despite the variation of the incident angle. An experiment with obliquely incident and superimposed optical vortices is executed to verify our theoretical predictions, achieving a successful detection of the rotational speed at relatively large tilt angles with a relative error less than 2%. The scheme proposed in this study may be useful for practical applications of rotational Doppler effect in remote sensing and metrology.

Influence of lateral misalignment on the optical rotational Doppler effect.

The discovery of the optical rotational Doppler effect associated with orbital angular momentum of light paves a new way to detect the rotational speed of spinning objects. In this paper, we investigate the influence of lateral misalignment, i.e., the distance between the beam axis of a probe light and the rotation axis of a spinning object, on the rotational Doppler effect. First, we analyze the mechanism of the rotational Doppler effect of optical vortices based on the linear Doppler effect. Specifically, we consider the general case where the center of the optical vortex does not coincide with the rotation axis, and deduce the generalized formula of rotational Doppler shift based on a local scattering model. It is found that the bandwidth of the rotational Doppler signal depends proportionally on the amount of lateral misalignment, whereas the value of rotational Doppler shift remains constant. A proof-of-concept experiment is performed, and the measured results agree well with theoretical predictions. These findings may be useful for practical application of the optical rotational Doppler effect in remote sensing and metrology.

Synergy of Raddeanin A and cisplatin induced therapeutic effect enhancement in human hepatocellular carcinoma.

Cisplatin is a main compound for human hepatocellular carcinoma (HCC) chemotherapies, but it has certain cytotoxicity during applications. To release that, combining with other drugs are being as a regular plan in clinic. In our present study, we are focusing on one of active monomers extracted from Anemone Raddeana Regel, Raddeanin A (RA), which is on behalf of the same character like cisplatin in the tumor remedies. In order to investigate whether combination usage of RA and cisplatin can be priority to the later drug's effect development and its toxicity reduction in HCC, both of two drugs were treated 24 h or 48 h in QGY-7703 cells for estimating their abilities in tumor cell proliferation inhibition. Results show RA makes synergistic functions with cisplatin after measuring and analyzing their combination index (CI) values. Meanwhile it can strengthen cisplatin's effect through arresting the tumor cells in G0/G1 cycle and further promoting their apoptosis. Interestingly, the molecule signals correlated to tumor cell apoptosis containing both of p53 and bax are simultaneously activated, but bcl-2 and survivin are all depressed in mRNA level. Meanwhile, combining usage with RA can even raise the intracellular productions of reactive oxygen species (ROS). All these consequences reflect RA plays an important role in enhancing the therapeutic effect of cisplatin in HCC. This finding may guide for the drug usage of cisplatin in clinic practice.

BDNF-GSK-3ß-ß-Catenin Pathway in the mPFC Is Involved in Antidepressant-Like Effects of Morinda officinalis Oligosaccharides in Rats.

Background: Morinda officinalis oligosaccharides have been reported to exert neuroprotective and antidepressant-like effects in the forced swim test in mice. However, the mechanisms that underlie the antidepressant-like effects of Morinda officinalis oligosaccharides are unclear. Methods: Chronic unpredictable stress and forced swim test were used to explore the antidepressant-like effects of Morinda officinalis oligosaccharides and resilience to stress in rats. The phosphoinositide-3 kinase inhibitor LY294002 was microinjected in the medial prefrontal cortex to explore the role of glycogen synthase kinase-3ß in the antidepressant-like effects of Morinda officinalis oligosaccharides. The expression of brain-derived neurotrophic factor, phosphorylated-Ser9-glycogen synthase kinase 3ß, ß-catenin, and synaptic proteins was determined in the medial prefrontal cortex and the orbitofrontal cortex by western blot. Results: We found that Morinda officinalis oligosaccharides effectively ameliorated chronic unpredictable stress-induced depression-like behaviors in the sucrose preference test and forced swim test. The Morinda officinalis oligosaccharides also significantly rescued chronic unpredictable stress-induced abnormalities in the brain-derived neurotrophic factor-glycogen synthase kinase-3ß-ß-catenin pathway and synaptic protein deficits in the medial prefrontal cortex but not orbitofrontal cortex. The activation of glycogen synthase kinase-3ß by the phosphoinositide-3 kinase inhibitor LY294002 abolished the antidepressant-like effects of Morinda officinalis oligosaccharides in the forced swim test. Naïve rats that were treated with Morinda officinalis oligosaccharides exhibited resilience to chronic unpredictable stress, accompanied by increases in the expression of brain-derived neurotrophic factor, phosphorylated-Ser9-glycogen synthase kinase-3ß, and ß-catenin in the medial prefrontal cortex. Conclusion: Our findings indicate that the brain-derived neurotrophic factor-glycogen synthase kinase-3ß-ß-catenin pathway in the medial prefrontal cortex may underlie the antidepressant-like effect of Morinda officinalis oligosaccharides and resilience to stress.

Force sensor based tool condition monitoring using a heterogeneous ensemble learning model.

Tool condition monitoring (TCM) plays an important role in improving machining efficiency and guaranteeing workpiece quality. In order to realize reliable recognition of the tool condition, a robust classifier needs to be constructed to depict the relationship between tool wear states and sensory information. However, because of the complexity of the machining process and the uncertainty of the tool wear evolution, it is hard for a single classifier to fit all the collected samples without sacrificing generalization ability. In this paper, heterogeneous ensemble learning is proposed to realize tool condition monitoring in which the support vector machine (SVM), hidden Markov model (HMM) and radius basis function (RBF) are selected as base classifiers and a stacking ensemble strategy is further used to reflect the relationship between the outputs of these base classifiers and tool wear states. Based on the heterogeneous ensemble learning classifier, an online monitoring system is constructed in which the harmonic features are extracted from force signals and a minimal redundancy and maximal relevance (mRMR) algorithm is utilized to select the most prominent features. To verify the effectiveness of the proposed method, a titanium alloy milling experiment was carried out and samples with different tool wear states were collected to build the proposed heterogeneous ensemble learning classifier. Moreover, the homogeneous ensemble learning model and majority voting strategy are also adopted to make a comparison. The analysis and comparison results show that the proposed heterogeneous ensemble learning classifier performs better in both classification accuracy and stability.

Laser Synthesis of PtMo Single-Atom Alloy Electrode for Ultralow Voltage Hydrogen Generation.

Maximizing atom-utilization efficiency and high current stability are crucial for the platinum (Pt)-based electrocatalysts for hydrogen evolution reaction (HER). Herein, the Pt single-atom anchored molybdenum (Mo) foil (Pt-SA/Mo-L) as a single-atom alloy electrode is synthesized by the laser ablation strategy. The local thermal effect with fast rising-cooling rate of laser can achieve the single-atom distribution of the precious metals (e.g., Pt, Rh, Ir, and Ru) onto the Mo foil. The synthesized self-standing Pt-SA/Mo-L electrode exhibits splendid catalytic activity (31 mV at 10 mA cm-2 ) and high-current-density stability (≈850 mA cm-2 for 50 h) for HER in acidic media. The strong coordination of Pt-Mo bonding in Pt-SA/Mo-L is critical for the efficient and stable HER. In addition, the ultralow electrolytic voltage of 0.598 V to afford the current density of 50 mA cm-2 is realized by utilization of the anodic molybdenum oxidation instead of the oxygen evolution reaction (OER). Here a universal synthetic strategy of single-atom alloys (PtMo, RhMo, IrMo, and RuMo) as self-standing electrodes is provided for ultralow voltage and membrane-free hydrogen production.