Ultrafast and temperature-insensitive strain interrogation using a PM-PCF based Sagnac loop interferometer and wavelength-to-time mapping.

A novel approach for ultrafast and temperature-insensitive strain interrogation using a polarization-maintaining photonic crystal fiber (PM-PCF) based Sagnac loop interferometer (SLI) and linear wavelength-to-time (WTT) mapping is proposed and experimentally demonstrated. The PM-PCF incorporated in the SLI is used as the sensing element to achieve stable strain sensing with ultra-low temperature-dependence due to its intrinsic thermal insensitivity, which can be used to eliminate the cross-sensitivity effect and increase the measurement accuracy. A dispersive element is employed to realize the WTT mapping and real-time strain interrogation is obtained by converting the strain-encoded wavelength shift to time shift in the temporal domain, which can be directly monitored by a real-time oscilloscope. The proposed system offers an ultrafast interrogation speed of 100 MHz and a strain sensitivity of -0.17 ps/µÎµ.

MMS2plot: An R Package for Visualizing Multiple MS/MS Spectra for Groups of Modified and Non-Modified Peptides.

A large number of post-translational modifications (PTMs) in proteins are buried in the unassigned mass spectrometric (MS) spectra in shot-gun proteomics datasets. Because the modified peptide fragments are low in abundance relative to the corresponding non-modified versions, it is critical to develop tools that allow facile evaluation of assignment of PTMs based on the MS/MS spectra. Such tools will preferably have the ability to allow comparison of fragment ion spectra and retention time between the modified and unmodified peptide pairs or group. Herein, MMS2plot, an R package for visualizing peptide-spectrum matches (PSMs) for multiple peptides, is described. MMS2plot features a batch mode and generates the output images in vector graphics file format that facilitate evaluation and publication of the PSM assignment. MMS2plot is expected to play an important role in PTM discovery from large-scale proteomics datasets generated by liquid chromatography-MS/MS. The MMS2plot package is freely available at https://github.com/lileir/MMS2plot under the GPL-3 license.

Four-wavelength-switchable SLM fiber laser with sub-kHz linewidth using superimposed high-birefringence FBG and dual-coupler ring based compound-cavity filter.

We propose and demonstrate a four-wavelength-switchable erbium-doped fiber laser (4WS-EDFL) with a four-channel superimposed high-birefringence fiber Bragg grating (SI-HBFBG) and a dual-coupler ring based compound-cavity (DCR-CC) filter. Both for the first time, a SI-HBFBG as a four-channel reflective filter is used in a multi-wavelength switchable fiber laser to define wavelength channels and a DCR-CC filter is used to select a single mode from dense longitudinal-modes in a fiber laser. We present in detail how to design, fabricate, and characterize the DCR-CC filter with both theoretical analysis and experimental results, which we believe is the first systematic approach for making a compound-cavity based filter used for selecting single-longitudinal mode (SLM) in a fiber laser. The enhanced polarization hole burning effect in a 2.9 m long erbium-doped fiber, coiled inside a three-loop polarization controller, and the polarization-mismatch-induced losses are introduced into the laser cavity to achieve wavelength-switching operations. We show that the 4WS-EDFL can be switched among fifteen lasing states, including four single-wavelength operations, six dual-wavelength operations, four three-wavelength operations and one four-wavelength operation, all with high stability. For demonstration, in switchable single-wavelength operations, the four SLM lasing outputs measured are all with an optical signal to noise ratio of >80 dB, a linewidth of <700 Hz, a relative intensity noise of ≤-156.7 dB/Hz at frequencies over 3 MHz, an output power fluctuation of ≤0.555 dB and excellent polarization characteristics.

Water table decline alters arthropod community structure by shifting plant communities and leaf nutrients in a Tibetan peatland.

Water table decline is one of the most serious environmental problems in the peatland in the Qinghai-Tibetan Plateau. However, the effect of water table decline on the structure of aboveground arthropod communities is still not clear. We investigated changes in the abundance of different arthropod groups, and estimated the abundance, height, and biomass of the plant community in a soil water table reduction experiment to reveal the effect of water table decline on the arthropod community structure. The effect of water level decline on herbivorous arthropods varied according to the feeding habits. Specifically, water table decline treatment decreased the abundance of grass-preferring herbivores but increased the abundance of forb-preferring herbivores. However, the density of predators (e.g., spiders) did not change significantly. The variations in arthropod communities were correlated with the increase in forbs and leaf nitrogen content in the water table decline treatments. Our experiment demonstrated that the effect of water table decline on plant communities cascades upwardly to alter the arthropod community. Such trophic interactions should be considered in studies aimed at predicting shifts in the arthropods communities in a changing climate.

Differences in Phenotypic Plasticity between Invasive and Native Plants Responding to Three Environmental Factors.

The phenotypic plasticity hypothesis suggests that exotic plants may have greater phenotypic plasticity than native plants. However, whether phenotypic changes vary according to different environmental factors has not been well studied. We conducted a multi-species greenhouse experiment to study the responses of six different phenotypic traits, namely height, leaf number, specific leaf area, total biomass, root mass fraction, and leaf mass fraction, of native and invasive species to nutrients, water, and light. Each treatment was divided into two levels: high and low. In the nutrient addition experiment, only the leaf mass fraction and root mass fraction of the plants supported the phenotypic plasticity hypothesis. Then, none of the six traits supported the phenotypic plasticity hypothesis in the water or light treatment experiments. The results show that, for different environmental factors and phenotypes, the phenotypic plasticity hypothesis of plant invasion is inconsistent. When using the phenotypic plasticity hypothesis to explain plant invasion, variations in environmental factors and phenotypes should be considered.

Tumor-associated macrophages in multiple myeloma: advances in biology and therapy.

Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow (BM) and represents the second most common hematological malignancy in the world. The MM tumor microenvironment (TME) within the BM niche consists of a wide range of elements which play important roles in supporting MM disease progression, survival, proliferation, angiogenesis, as well as drug resistance. Together, the TME fosters an immunosuppressive environment in which immune recognition and response are repressed. Macrophages are a central player in the immune system with diverse functions, and it has been long established that macrophages play a critical role in both inducing direct and indirect immune responses in cancer. Tumor-associated macrophages (TAMs) are a major population of cells in the tumor site. Rather than contributing to the immune response against tumor cells, TAMs in many cancers are found to exhibit protumor properties including supporting chemoresistance, tumor proliferation and survival, angiogenesis, immunosuppression, and metastasis. Targeting TAM represents a novel strategy for cancer immunotherapy, which has potential to indirectly stimulate cytotoxic T cell activation and recruitment, and synergize with checkpoint inhibitors and chemotherapies. In this review, we will provide an updated and comprehensive overview into the current knowledge on the roles of TAMs in MM, as well as the therapeutic targets that are being explored as macrophage-targeted immunotherapy, which may hold key to future therapeutics against MM.

Short-term phosphorus addition augments the effects of nitrogen addition on soil respiration in a typical steppe.

Soil respiration is one of the largest carbon (C) sources in terrestrial ecosystems and is sensitive to soil nutrient variation. Although nitrogen (N) availability affects soil respiration, other nutrients, such as phosphorous (P), which play pivotal roles in plant growth and microbial activity, may also affect soil respiration. In addition, N and P have been widely reported to interactively affect plant growth; however, their interactive effects on soil respiration have rarely been studied. Therefore, we conducted a short-term, two-factor experiment (from 2013 to 2015) to determine whether N and P addition can interactively affect soil respiration in a northern Chinese steppe. Nitrogen addition elevated soil respiration by 9.5%, whereas P addition did not affect soil respiration in the studied steppe across all treatments. However, neither N nor P addition significantly affected soil respiration alone in the experiment. Furthermore, N and P interactively affected soil respiration. Nitrogen addition did not affect soil respiration in the ambient P plots, but significantly elevated soil respiration (by 17.7%) in P addition plots across the three growing seasons. The effects of N addition on soil respiration were primarily correlated with the responses of vegetation cover and litter biomass to N addition in the experiment. Our results demonstrate that P addition augments the effects of N addition on soil respiration. Soil nutrient contents should be incorporated into predictive models for terrestrial C cycle response to N addition.

A simple and selective electrochemical magneto-assay for sea lice eDNA detection developed with a Quality by Design approach.

Environmental DNA (eDNA) is a novel, non-invasive sampling procedure that allows the obtaining of genetic material directly from environmental samples without any evidence of biological sources. The eDNA methodology can greatly benefit from coupling it to reliable, portable and cost-effective tools able to perform decentralized measurements directly at the site of need and in resource-limited settings. Herein, we report a simple method for the selective analysis of eDNA using a magneto-assay with electrochemical detection. The proposed method involves the polymerase chain-reaction (PCR) amplification of mitochondrial eDNA of parasitic Salmon lice (Lepeophtheirus salmonis), extracted from seawater samples. The eDNA sequence was targeted via sandwich hybridization onto magnetic beads and enzymatic labeling was performed to obtain an electroactive product measured by differential pulse voltammetry. Quality by Design (QbD), a recent concept of science- and risk-oriented quality paradigm, was used for the optimization of the different parameters of the assay. Response surface methodology and Monte Carlo simulations were performed to define the method operable design region. The optimized electrochemical magneto-assay attained a limit of detection of 2.9 amol µL-1 of the short synthetic sea louse DNA analogue (43 bp). In addition, robustness testing using a further experimental design approach was performed for monitoring eDNA amplicons. Seawater samples spiked with individuals of free-swimming L. salmonis copepodite stages and seawater collected from tanks with sea lice-infested fish were analyzed.

Effects of Cannabinoids on Female Sexual Function.

INTRODUCTION: With the legalization of both medical and recreational marijuana in some countries and a few US states, its use has become more widely prevalent. Both exogenous cannabinoids such as tetrahydrocannabinol (THC) and endogenous cannabinoids (endocannabinoids) have been shown to affect female gonadotropin pathways and female sexuality. Yet, our understanding of the mechanisms and effects on female sexual function is limited. AIM: To review the literature regarding the effects of both endogenous and exogenous cannabinoids on female sexual function in both animals and humans. METHODS: We performed a PubMed search for English-language articles in peer-reviewed journals between 1970 and 2019. We used the following search terms: "cannabinoids," "endocannabinoids," "marijuana," "cannabis," and "female sexual function" or "sexual function." The main outcomes of the papers were reviewed. MAIN OUTCOME MEASURE: The main outcome measure was sexual function in females. RESULTS: A total of 12 human studies and 8 animal studies that evaluated the relationship between cannabinoids and female sexual function were included. Study types in animals were blinded, prospective, placebo-controlled trials. Human studies were based primarily on questionnaire data. The data indicate dose-dependent effects on female sexual desire and receptivity, such that low doses generally facilitate or have no effect but high doses inhibit. CONCLUSIONS: More research is needed to develop a better understanding of the effects of cannabinoids on female sexual function. There does appear to be an effect on both animals and humans, but whether the effect is positive or negative along dose and species lines requires more study. With the legalization of marijuana occurring in more countries and more US states, there needs to be more well-controlled studies evaluating the effects. Lynn B, Gee A, Zhang L, et al. Effects of Cannabinoids on Female Sexual Function. Sex Med Rev 2020;8:18-27.

DeepKhib: A Deep-Learning Framework for Lysine 2-Hydroxyisobutyrylation Sites Prediction.

As a novel type of post-translational modification, lysine 2-Hydroxyisobutyrylation (K hib ) plays an important role in gene transcription and signal transduction. In order to understand its regulatory mechanism, the essential step is the recognition of K hib sites. Thousands of K hib sites have been experimentally verified across five different species. However, there are only a couple traditional machine-learning algorithms developed to predict K hib sites for limited species, lacking a general prediction algorithm. We constructed a deep-learning algorithm based on convolutional neural network with the one-hot encoding approach, dubbed CNN OH . It performs favorably to the traditional machine-learning models and other deep-learning models across different species, in terms of cross-validation and independent test. The area under the ROC curve (AUC) values for CNN OH ranged from 0.82 to 0.87 for different organisms, which is superior to the currently available K hib predictors. Moreover, we developed the general model based on the integrated data from multiple species and it showed great universality and effectiveness with the AUC values in the range of 0.79-0.87. Accordingly, we constructed the on-line prediction tool dubbed DeepKhib for easily identifying K hib sites, which includes both species-specific and general models. DeepKhib is available at http://www.bioinfogo.org/DeepKhib.

Tumor microenvironment-targeted nanoparticles loaded with bortezomib and ROCK inhibitor improve efficacy in multiple myeloma.

Drug resistance and dose-limiting toxicities are significant barriers for treatment of multiple myeloma (MM). Bone marrow microenvironment (BMME) plays a major role in drug resistance in MM. Drug delivery with targeted nanoparticles have been shown to improve specificity and efficacy and reduce toxicity. We aim to improve treatments for MM by (1) using nanoparticle delivery to enhance efficacy and reduce toxicity; (2) targeting the tumor-associated endothelium for specific delivery of the cargo to the tumor area, and (3) synchronizing the delivery of chemotherapy (bortezomib; BTZ) and BMME-disrupting agents (ROCK inhibitor) to overcome BMME-induced drug resistance. We find that targeting the BMME with P-selectin glycoprotein ligand-1 (PSGL-1)-targeted BTZ and ROCK inhibitor-loaded liposomes is more effective than free drugs, non-targeted liposomes, and single-agent controls and reduces severe BTZ-associated side effects. These results support the use of PSGL-1-targeted multi-drug and even non-targeted liposomal BTZ formulations for the enhancement of patient outcome in MM.

Physiologically stable F127-GO supramolecular hydrogel with sustained drug release characteristic for chemotherapy and photothermal therapy.

A synthetic method for preparing a Pluronic F127 (F127)-stabilized graphene (GO) supramolecular hydrogel as a safe nanovehicle for combination treatment has been studied. Doxorubicin (DOX) as a model drug is non-covalently bound on the great surface area of GO due to strong π-π interaction, hydrophobic interaction, and the strongest hydrogen bonding. In vitro drug release experiments revealed that this F127-stabilized GO supramolecular hydrogel has a sustained drug release characteristic. Furthermore, the supramolecular hydrogel showed better in vitro antitumor ability under NIR (near infrared) laser irradiation because of the excellent photothermal effect of GO. Moreover, we evaluated its antitumor ability in vivo and the results show that the hydrogel system can also markedly inhibit the growth of a tumor when administered individually, especially under laser irradiation. All these findings make the supramolecular hydrogel system promising for combination therapy with good bioavailability and minimal side effects.

Interferon-dependent immunoproteasome activity during mouse adenovirus type 1 infection.

The immunoproteasome is an inducible host mechanism that aids in the clearance of damaged proteins. The immunoproteasome also influences immune function by enhancing peptide presentation by MHC class I and promotes inflammation via IκB degradation and activation of NF-κB. We used mouse adenovirus type 1 (MAV-1) to characterize the role of the immunoproteasome in adenovirus pathogenesis. Following intranasal infection of mice, immunoproteasome activity in the heart and lung was significantly increased in an IFN-γ-dependent manner. Absence of the ß5i immunoproteasome subunit and pharmacological inhibition of ß5i activity had minimal effects on viral replication, virus-induced cellular inflammation, or induction of cytokine expression. Likewise, the establishment of protective immunity following primary infection was not significantly altered by ß5i deficiency. Thus, although immunoproteasome activity is robustly induced during acute infection with MAV-1, our data suggest that other mechanisms are capable of compensating for immunoproteasome activity to maintain antiviral immunity and appropriate inflammatory responses.

A stable and practical etoposide-containing intravenous long-/medium-chain triglycerides-based lipid emulsion formulation: pharmacokinetics, biodistribution, toxicity, and antitumor efficacy.

OBJECTIVES: This work aimed to evaluate pharmacokinetics, biodistribution, toxicity, and antitumor activities of a highly stable long-/medium-chain triglycerides (LCT/MCT)-based etoposide parenteral emulsion (EPE) in comparison to etoposide parenteral solution (EPS). METHODS: Using high-pressure homogenization method, EPE was prepared and sterilized at 121°C for 10 min by autoclaving. The biological samples were analyzed using the UPLC-ESI-MS/MS method. RESULTS: Superior stability of EPE was verified with no significant changes in physicochemical properties in the accelerating and long-term stability tests. Similar pharmacokinetic behavior in beagle dogs was obtained and the AUC 0 - 12h values were 1196.73 ± 320.85 and 1505.56 ± 617.93 µg.h/L for EPE and EPS (p > 0.5), respectively. Likewise, no remarkable difference in biodistribution profiles in mice was found for both formulations. Safety assessment studies including hemolysis test, rabbit ear vein test and injection anaphylaxis were undertaken and the EPE was proven to be safe for intravenous administration. Specifically, after consecutive 12 weeks administration in rats, systematic and local toxicity induced by EPE were alleviated relative to that of EPS. Furthermore, significant and comparable antitumor activities to EPS were also demonstrated by EPE with tumor suppression rate (TSR) of 66.63, 55.94, and 60.16% against H460, Hep G2, and BCAP-37 human cancer cell lines in nude mice at the dose of 15 mg/kg, respectively. CONCLUSION: These results suggest that this LCT/MCT-based lipid emulsion is a promising alternative intravenous carrier for etoposide with high stability, improved convenience, alleviated toxicity, and noncompromised antitumor efficacy.