Warming and UV Radiation Alleviate the Effect of Virus Infection on the Microalga Emiliania huxleyi.

The marine microalga Emiliania huxleyi is widely distributed in the surface oceans and is prone to infection by coccolithoviruses that can terminate its blooms. However, little is known about how global change factors like solar UV radiation (UVR) and ocean warming affect the host-virus interaction. We grew the microalga at 2 temperature levels with or without the virus in the presence or absence of UVR and investigated the physiological and transcriptional responses. We showed that viral infection noticeably reduced photosynthesis and growth of the alga but was less harmful to its physiology under conditions where UVR influenced viral DNA expression. In the virus-infected cells, the combination of UVR and warming (+4°C) led to a 13-fold increase in photosynthetic carbon fixation rate, with warming alone contributing a change of about 5-7-fold. This was attributed to upregulated expression of genes related to carboxylation and light-harvesting proteins under the influence of UVR, and to warming-reduced infectivity. In the absence of UVR, viral infection downregulated the metabolic pathways of photosynthesis and fatty acid degradation. Our results suggest that solar UV exposure in a warming ocean can reduce the severity of viral attack on this ecologically important microalga, potentially prolonging its blooms.

Immune Checkpoint Blockade Mediated by a Small-Molecule Nanoinhibitor Targeting the PD-1/PD-L1 Pathway Synergizes with Photodynamic Therapy to Elicit Antitumor Immunity and Antimetastatic Effects on Breast Cancer.

Targeting programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) immunologic checkpoint blockade with monoclonal antibodies has achieved recent clinical success in antitumor therapy. However, therapeutic antibodies exhibit several issues such as limited tumor penetration, immunogenicity, and costly production. Here, Bristol-Myers Squibb nanoparticles (NPs) are prepared using a reprecipitation method. The NPs have advantages including passive targeting, hydrophilic and nontoxic features, and a 100% drug loading rate. BMS-202 is a small-molecule inhibitor of the PD-1/PD-L1 interaction that is developed by BMS. Transfer of BMS-202 NPs to 4T1 tumor-bearing mice results in markedly slower tumor growth to the same degree as treatment with anti-PD-L1 monoclonal antibody (α-PD-L1). Consistently, the combination of Ce6 NPs with BMS-202 NPs or α-PD-L1 in parallel shows more efficacious antitumor and antimetastatic effects, accompanied by enhanced dendritic cell maturation and infiltration of antigen-specific T cells into the tumors. Thus, inhibition rates of primary and distant tumors reach >90%. In addition, BMS-202 NPs are able to attack spreading metastatic lung tumors and offer immune-memory protection to prevent tumor relapse. These results indicate that BMS-202 NPs possess effects similar to α-PD-L1 in the therapies of 4T1 tumors. Therefore, this work reveals the possibility of replacing the antibody used in immunotherapy for tumors with BMS-202 NPs.

PSCA regulates IL-6 expression through p38/NF-κB signaling in prostate cancer.

BACKGROUND: Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein. We previously reported that PSCA involved in proliferation and invasion of PCa cells, however, the underlying mechanisms are unknown. In this study, we aimed to explore the regulating role of PSCA gene expression in interleukin-6 (IL-6) autocrine of PCa cells. METHODS: The stable knockdown-PSCA and ectopically overexpressed-PSCA vector were constructed and transfected into human PCa DU145 and PC-3M cells. The effects of PSCA overexpression or knockdown were determined in proliferation, invasion, and metastasis assays. The effect of PSCA on the expression and secretion of IL-6 was evaluated by immunoblotting and ELISA. Subcellular localization and expression pattern of PSCA and IL-6 protein were examined by immunohistochemistry. Its clinical significance was statistically analyzed. RESULTS: The results showed that stable knockdown of PSCA delayed proliferation, migration, and invasion while overexpressing PSCA enhanced the proliferation, migration, and invasion in vitro and the lung metastasis in vivo of PCa cells. Importantly, the PSCA involved in the IL-6 secretion and positively regulated p38/NF-κB/IL-6 signaling, leading to enhanced PCa cell invasion and metastasis. Both the expression of PSCA and IL-6 were significantly associated with poor biochemical recurrence-free survival of patients with PCa. PSCA protein expression showed a prognostic value in overall survival as indicated by Kaplan-Meier analysis. CONCLUSIONS: These results indicate that PSCA regulates the expression and secretion of IL-6 in human PCa cells through p38/NF-κB signaling pathways. PSCA may be a potential diagnostic marker and therapeutic target for PSCA-positive PCa.

PSCA promotes prostate cancer proliferation and cell-cycle progression by up-regulating c-Myc.

BACKGROUND: The Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored protein. Increasing evidence has indicated PSCA plays an important role in tumorigenesis. However, its function and the underlying molecular mechanisms in prostate cancer (PCa) are still not fully elucidated. In this study, we aimed to explore the effect of PSCA on cell cycle of PCa cells and its mechanism research. METHODS: Immunohistochemistry, quantitative reverse transcription-PCR (qRT-PCR) and Western blotting were used to quantify PSCA expression pattern in PCa tissues and cell lines. The association of PSCA expression with the biochemical recurrence (BCR)-free survival and overall survival (OS) of PCa patients were analyzed using Kaplan-Meier method. The roles of PSCA in PCa were confirmed based on both in vitro and in vivo systems. RESULTS: Immunohistochemistry results showed that PSCA was upregulated in PCa tissue. PSCA overexpression were significantly associated with high Gleason score (GS) (P = 0.028), positive BCR (P = 0.002), and poor OS (P = 0.032) and high c-Myc expression (P = 0.019). PSCA promoted PCa cell cycle progression and tumor growth via increased c-Myc expression. Additional, PI3K/AKT signaling pathways was involved in PSCA-mediated c-Myc expression and cell proliferation. CONCLUSIONS: PSCA is a novel cell cycle regulator with a key role in mediating c-Myc-induced proliferation. PSCA may be a potential diagnostic marker and therapeutic target for patients with PCa.

Decreased photosynthesis and growth with reduced respiration in the model diatom Phaeodactylum tricornutum grown under elevated CO2 over 1800 generations.

Studies on the long-term responses of marine phytoplankton to ongoing ocean acidification (OA) are appearing rapidly in the literature. However, only a few of these have investigated diatoms, which is disproportionate to their contribution to global primary production. Here we show that a population of the model diatom Phaeodactylum tricornutum, after growing under elevated CO2 (1000 µatm, HCL, pHT : 7.70) for 1860 generations, showed significant differences in photosynthesis and growth from a population maintained in ambient CO2 and then transferred to elevated CO2 for 20 generations (HC). The HCL population had lower mitochondrial respiration, than did the control population maintained in ambient CO2 (400 µatm, LCL, pHT : 8.02) for 1860 generations. Although the cells had higher respiratory carbon loss within 20 generations under the elevated CO2 , being consistent to previous findings, they downregulated their respiration to sustain their growth in longer duration under the OA condition. Responses of phytoplankton to OA may depend on the timescale for which they are exposed due to fluctuations in physiological traits over time. This study provides the first evidence that populations of the model species, P. tricornutum, differ phenotypically from each other after having been grown for differing spans of time under OA conditions, suggesting that long-term changes should be measured to understand responses of primary producers to OA, especially in waters with diatom-dominated phytoplankton assemblages.

Association Between HIV Infection and Prevalence of Erectile Dysfunction: A Systematic Review and Meta-Analysis.

BACKGROUND: The prevalence of erectile dysfunction (ED) in men positive for HIV has been reported to exceed the baseline of the general population. However, no meta-analysis or conclusive review has investigated whether individuals with HIV infection have a significantly higher prevalence of ED. AIM: To explore the exact association between HIV infection and the prevalence of ED. METHODS: The PubMed, Embase, Medline, and Cochrane Library databases were searched to identify studies concerning the association between HIV infection and the prevalence of ED that were published up to December 2016. Manual searches also were performed. Relative risks and corresponding 95% confidence intervals were used to estimate the strength of association between HIV infection and the prevalence of ED. The methodologic quality of the included cohort studies was assessed through the Newcastle-Ottawa Scale. The cross-sectional study quality methodology checklist was used to assess the quality of cross-sectional studies. Sensitivity analyses were conducted to assess potential bias. This study was conducted according to the guidelines for Meta-Analyses and Systematic Reviews of Observational Studies (MOOSE). OUTCOMES: The strength of association between HIV infection and the prevalence of ED was evaluated using summarized unadjusted pooled relative risks and 95% confidence intervals. RESULTS: Two cohort studies and three cross-sectional studies involving 4,252 participants were included. Mean age of patients ranged from 35.2 to 52 years in the included studies. Based on the random-effects model, analyses of all studies showed that HIV infection was significantly associated with an increased prevalence of ED (relative risk = 2.32, 95% confidence interval = 1.52-3.55, P < .001). There was significant heterogeneity among included studies (I2 = 84%, P < .001). Estimates of total effects were generally consistent with the sensitivity. CLINICAL IMPLICATIONS: Individuals with HIV infection had a significantly increased prevalence of ED, which suggests that ED should be of concern to clinicians when managing men with HIV infection. STRENGTHS AND LIMITATIONS: A strength of this study is that it is the first meta-analysis to explore the relation between HIV infection and the prevalence of ED. A limitation is that all included studies were observational studies, which can induce recall bias or selection bias. CONCLUSION: Evidence from the observational studies suggested that individuals with HIV infection had a significantly increased prevalence of ED despite significant heterogeneity. More research is warranted to clarify the relation between HIV infection and the prevalence of ED. Luo L, Deng T, Zhao S, et al. Association Between HIV Infection and Prevalence of Erectile Dysfunction: A Systematic Review and Meta-Analysis. J Sex Med 2017;14:1125-1132.

Association Between Opioid Use and Risk of Erectile Dysfunction: A Systematic Review and Meta-Analysis.

BACKGROUND: Opioid analgesics have been widely used to relieve chronic pain conditions; however, a connection between opioid analgesic administration and increased susceptibility to erectile dysfunction (ED) has been hypothesized. AIM: To evaluate whether opioid use was a risk factor for ED in a systematic review and meta-analysis. METHODS: The PubMed, Cochrane Library, and Embase databases were searched to identify eligible studies concerning opioid use and risk of ED from inception to April 2017. The association between opioid use and risk of ED was summarized using the relative risk with 95% CI. Sensitivity analyses were conducted to assess potential bias. The Begg and Egger tests were used for publication bias analysis. The GRADE evidence profile tool was used to assess the quality of the evidence. OUTCOMES: The overall combined risk estimates for the effect of opioid use on ED were calculated using a random-effects model. RESULTS: This meta-analysis included 8,829 men (mean age = 41.6 years) from 10 studies, 2,456 of whom received opioid management (duration of intervention = 4 months to 9.5 years). Pooled results demonstrated that the use of opioids was significantly associated with an increased risk of ED (relative risk = 1.96, 95% CI = 1.66-2.32, P < .001). Estimates of the total effects were generally consistent in the sensitivity analysis. No evidence of publication bias was observed. The overall quality of evidence was rated as low. CLINICAL IMPLICATIONS: We found that men with opioid use had a significantly increased prevalence of ED, which suggests that patients and clinicians should be aware of the potential role played by opioid administration in the development of ED. STRENGTHS AND LIMITATIONS: This is the first meta-analysis performed to describe the relation between opioid use and ED risk based on all available epidemiologic studies. However, the direction of causality between opioid use and risk of ED should be interpreted with caution because most included studies used a cross-sectional design. CONCLUSION: Evidence from the included observational studies indicated that men with opioid use had a significantly increased risk of ED. Further randomized controlled trials are still needed to confirm this relation. Zhao S, Deng T, Luo L, et al. Association Between Opioid Use and Risk of Erectile Dysfunction: A Systematic Review and Meta-Analysis. J Sex Med 2017;14:1209-1219.

Absolute detector-based spectrally tunable radiant source using digital micromirror device and supercontinuum fiber laser.

High-accuracy absolute detector-based spectroradiometric calibration techniques traceable to cryogenic absolute radiometers have made progress rapidly in recent decades under the impetus of atmospheric quantitative spectral remote sensing. A high brightness spectrally tunable radiant source using a supercontinuum fiber laser and a digital micromirror device (DMD) has been developed to meet demands of spectroradiometric calibrations for ground-based, aeronautics-based, and aerospace-based remote sensing instruments and spectral simulations of natural scenes such as the sun and atmosphere. Using a supercontinuum fiber laser as a radiant source, the spectral radiance of the spectrally tunable radiant source is 20 times higher than the spectrally tunable radiant source using conventional radiant sources such as tungsten halogen lamps, xenon lamps, or LED lamps, and the stability is better than ±0.3%/h. Using a DMD, the spectrally tunable radiant source possesses two working modes. In narrow-band modes, it is calibrated by an absolute detector, and in broad-band modes, it can calibrate for remote sensing instrument. The uncertainty of the spectral radiance of the spectrally tunable radiant source is estimated at less than 1.87% at 350 nm to 0.85% at 750 nm, and compared to only standard lamp-based calibration, a greater improvement is gained.

RNA interference targeting PSCA suppresses primary tumor growth and metastasis formation of human prostate cancer xenografts in SCID mice.

BACKGROUND AND OBJECTIVES: Prostate stem cell antigen (PSCA) is a cell surface, glycosylphosphatidylinositol (GPI)-anchored glycoprotein. Its overexpression has been detected in both local and metastatic prostate cancer (PCa), making it a potential therapeutic target. We previously reported that silencing PSCA by small interfering RNA targeting human PSCA (siRNA-PSCA) inhibited biological activity of PSCA-positive PCa cells leading to reduced proliferation, motility and invasion in vitro. In this study, we extended this in vitro findings to in vivo settings in order to investigate the effects of this specific siRNA on the tumor growth and metastasis development of PCa in vivo. MATERIALS AND METHODS: The siRNA-PSCA and ectopically overexpressed-PSCA vector were constructed and transfected into human PCa PC-3M and LNCaP cells, respectively, and were subcutaneously inoculated into the male SCID mice. Tumor growth was measured with a caliper, and formation of metastasis in mice bearing xenograft tumors was studied by magnetic resonance imaging (MRI) and autopsy analysis. Western blot and immunohistochemistry were used to assess the expression levels of PSCA protein in tumor tissues from xenograft and distant metastases. RESULTS: Consistent with our previous in vitro findings, the subcutaneous xenografts of PC-3M-siPSCA exhibited the almost completely inhibited expression of PSCA protein in their tumors tissues (P < 0.001 and P < 0.001, respectively), and consequently had a significant reduction in tumor growth volumes (P < 0.05 for all), and metastasis onset and sites (P < 0.001 for all) compared to those of PC-3M and PC-3M-siScrm. Conversely, LNCaP-PSCA showed significantly enhanced primary tumor growth and metastasis formation of xenografts compared to LNCaP-vehicle and LNCaP cells (P < 0.001 for all). Moreover, the up-regulated expression of PSCA protein was detected in the distant metastases of xenograft tumors from all groups. CONCLUSIONS: Taken together, these observations suggest that PSCA has a promoting role in the growth and metastasis of PCa and siRNA-PSCA may be a potential therapeutic strategy for PSCA-positive PCa.

Knockdown of PSCA induces EMT and decreases metastatic potentials of the human prostate cancer DU145 cells.

BACKGROUND: Prostate stem cell antigen (PSCA) expression has been shown to correlate with prostatic carcinogenesis and prostate cancer (PCa) progression. The underlying mechanisms for these processes are currently unknown. Epithelial to mesenchymal transition (EMT) has been associated with the invasiveness and the distant metastasis of PCa. In this study, we investigated the effects of knocking down the PSCA on the cell migration, the invasiveness, and the EMT of the PCa cell line DU145 in vitro and in vivo. METHODS: Four target sequences of the small hairpin RNA for PSCA were designed, and the best effect knockdown sequence shRNA#1 was screened to construct the stable transfected DU145 cell line (DU145 shRNA#1), the scramble sequence was also designed to construct the stable transfected DU145 cell line(DU145 scramble). Cell migration and invasion were studied using Transwell assay. Quantitative RT-PCR, Western blot (WB) were used to quantify PSCA, E-cadherin, ß-catenin, Vimentin, Fibronectin expression in DU145, DU145 scramble, DU145 shRNA#1 in vitro and in vivo. RT-PCR, immunofluorescent staining were used to quantify PSCA, E-cadherin, and Vimentin expression in vitro. EMT-related genes Snail, Slug, and Twist, were quantified by quantitative RT-PCR in vitro. RESULTS: The constructed stable knockdown of the PSCA in the DU145 cell had a silencing effect up to 90.5 %. DU145 shRNA#1 became scattered from the tightly packed colonies. It was associated with decreased cell migration and invasion. There was also an increased Vimentin and Fibronectin expression, an inhibited E-cadherin and ß-catenin expression at both the mRNA and the protein levels when compared to the DU145 and the DU145 scramble in vitro and vivo. Furthermore, with the exception of the Snail, the expression of EMT-related Slug and Twist genes were upregulated. CONCLUSIONS: Our data indicated that knockdown of PSCA induced EMT and reduced metastatic potentials of the DU145 cells, suggesting that PSCA played an important role in prostatic carcinogenesis and progression.

Effect of 5α-Reductase Inhibitors on Sexual Function: A Meta-Analysis and Systematic Review of Randomized Controlled Trials.

INTRODUCTION: 5α-Reductase inhibitors (5ARIs) are widely used for the treatment of benign prostatic hyperplasia (BPH) and androgenetic alopecia (AGA). AIM: To review all the available data on the effect of 5ARIs on sexual function and assess whether 5ARIs increase the risk of sexual dysfunction. METHODS: A systematic search of the literature was conducted using the Medline, Embase, and Cochrane databases. The search was limited to articles published in English and up to October 2015. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. Data were analyzed using Stata 12.0. A fixed- or a random-effects model was used to calculate the overall combined risk estimates. Publication bias was assessed using Begg and Egger tests. MAIN OUTCOME MEASURES: Sexual dysfunction, erectile dysfunction, and decreased libido. RESULTS: After screening 493 articles, 17 randomized controlled trials with 17,494 patients were included. Nine studies evaluated the efficacy of 5ARIs in men with BPH. The other eight reported using 5ARIs in the treatment of men with AGA. The mean age of participants was 60.10 years across all studies. We included 10 trials (6,779 patients) on the efficacy and safety of finasteride, 4 trials (6,222 patients) on the safety and tolerability of dutasteride, and 3 trials (4,493 patients) using finasteride and dutasteride for AGA. The pooled relative risks for sexual dysfunction were 2.56 (95% CI = 1.48-4.42) in men with BPH and 1.21 (95% CI = 0.85-1.72) in men with AGA; those for erectile dysfunction were 1.55 (95% CI = 1.14-2.12) in men with BPH and 0.66 (95% CI = 0.20-2.25) in men with AGA; and those for decreased libido were 1.69 (95% CI = 1.03-2.79) in men with BPH and 1.16 (95% CI = 0.50-2.72) in men with AGA. Estimates of the total effects were generally consistent with the sensitivity analysis. No evidence of publication bias was observed. CONCLUSION: Evidence from the randomized controlled trials suggested that 5ARIs were associated with increased adverse effects on sexual function in men with BPH compared with placebo. However, the association was not statistically significant in men with AGA. Well-designed randomized controlled trials are indicated to study further the mechanism and effects of 5ARIs on sexual function.

Sexual Dysfunction in Patients with Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis.

INTRODUCTION: Sexual dysfunction is an under-recognized problem in men and women with obstructive sleep apnea (OSA). Epidemiologic findings were inconclusive regarding the risk for sexual dysfunction associated with OSA. AIM: The aim of this study was to examine the association between OSA and sexual dysfunction. METHODS: The PubMed, Cochrane Library, and Embase databases were searched for observational studies on the OSA and the risk of sexual dysfunction. The methodologic quality of the case-control and cohort studies was assessed with Newcastle-Ottawa Scale (NOS). The cross-sectional study quality methodology checklist was used for cross-sectional study. Data were pooled for the random-effects model. Sensitivity analyses were conducted to assess potential bias. MAIN OUTCOME MEASURE: The association between OSA and sexual dysfunction was summarized using relative risk (RR) with a 95% confidence interval (CI). RESULTS: This meta-analysis included 1,275 participants from nine studies. Five studies reported the incidence of erectile dysfunction (ED); the remaining four studies reported the incidence of female sexual dysfunction (FSD). Pooled results demonstrated that OSA was associated with increased risk of ED (pooled RR = 1.82, 95% CI: 1.12-2.97) as well as FSD (pooled RR = 2.00, 95% CI: 1.29-3.08). Estimates of the total effects were generally consistent in the sensitivity analysis. No evidence of publication bias was observed. CONCLUSIONS: Evidence from the observational studies suggested that OSA individuals might have an increased incidence of sexual dysfunction despite significant heterogeneity. More researches are warranted to clarify the relationship between OSA and the increased risk of sexual dysfunction.

Predicting Survival Using Whole-Liver MRI Radiomics in Patients with Hepatocellular Carcinoma After TACE Refractoriness.

PURPOSE: To develop a model based on whole-liver radiomics features of pre-treatment enhanced MRI for predicting the prognosis of hepatocellular carcinoma (HCC) patients undergoing continued transarterial chemoembolization (TACE) after TACE-resistance. MATERIALS AND METHODS: Data from 111 TACE-resistant HCC patients between January 2014 and March 2018 were retrospectively collected. At a ratio of 7:3, patients were randomly assigned to developing and validation cohorts. The whole-liver were manually segmented, and the radiomics signature was extracted. The tumor and liver radiomics score (TLrad-score) was calculated. Models were trained by machine learning algorithms and their predictive efficacies were compared. RESULTS: Tumor stage, tumor burden, body mass index, alpha-fetoprotein, and vascular invasion were revealed as independent risk factors for survival. The model trained by Random Forest algorithms based on tumor burden, whole-liver radiomics signature, and clinical features had the highest predictive efficacy, with c-index values of 0.85 and 0.80 and areas under the ROC curve of 0.96 and 0.83 in the developing cohort and validation cohort, respectively. In the high-rad-score group (TLrad-score > - 0.34), the median overall survival (mOS) was significantly shorter than in the low-rad-score group (17 m vs. 37 m, p < 0.001). A shorter mOS was observed in patients with high tumor burden compared to those with low tumor burden (14 m vs. 29 m, p = 0.007). CONCLUSION: The combined radiomics model from whole-liver signatures may effectively predict survival for HCC patients continuing TACE after TACE refractoriness. The TLrad-score and tumor burden are potential prognostic markers for TACE therapy following TACE-resistance.

The tolerance of two marine diatoms to diurnal pH fluctuation under dynamic light condition and ocean acidification scenario.

Coastal waters undergo dynamic changes in seawater carbonate chemistry due to natural and anthropogenic factors. Despite this, our current understanding of how coastal phytoplankton respond to fluctuating pH is limited. In the present study, we investigated the physiological responses of two coastal diatoms Thalassiosira pseudonana and Thalassiosira weissflogii to seawater acidification and diurnally fluctuating pH under natural solar irradiance. Seawater acidification did not significantly impact the growth, maximum and effective quantum yield of PSII, and photosynthetic rates of the two species. However, it did increase the maximum relative electron transport rate of T. weissflogii by 11%. Overall, fluctuating pH had neutral or positive effects on both species. It enhanced the light-saturated photosynthetic rate of T. weissflogii by 20% compared to cells grown under seawater acidification condition. Results from the short-term pH exposure experiment revealed that the photosynthetic rates of both species remained unaffected by acute pH changes, indicating their tolerance to varying pH. Nevertheless, it is crucial to consider dynamic pH when predicting changes in primary production in coastal waters, given the interplay of various environmental drivers.

Stimulatory and inhibitory effects of phenanthrene on physiological performance of Chlorella vulgaris and Skeletonema costatum.

The effects of polycyclic aromatic hydrocarbons on phytoplankton have been extensively documented, but there is limited knowledge about the physiological responses of marine primary producers to phenanthrene at environmentally relevant levels. Here, we investigated the toxicity of phenanthrene (0, 1, and 5 or 10 µg L-1) to the physiological performance of two cosmopolitan phytoplankton species: the green alga Chlorella vulgaris and bloom-forming diatom Skeletonema costatum. The specific growth rates of both species were remarkably inhibited at both low (1 µg L-1) and high phenanthrene concentrations (5 or 10 µg L-1), while their tolerance to phenanthrene differed. At the highest phenanthrene concentration (10 µg L-1), the growth of C. vulgaris was inhibited by 69%, and no growth was observed for S. costatum cells. The superoxide dismutase activity of both species was enhanced at high phenanthrene concentration, and increased activity of catalase was only observed at high phenanthrene concentration in C. vulgaris. Interestingly, the low phenanthrene concentration stimulated the photosynthetic and relative electron transport rates of S. costatum, whereas hormetic effects were not found for growth. Based on our results, phenanthrene could be detrimental to these two species at a environmentally relevant level, while different tolerance levels were detected.

Comparative study of the physiological responses of Skeletonema costatum and Thalassiosira weissflogii to initial pCO2 in batch cultures, with special reference to bloom dynamics.

Extensive studies have documented the responses of diatoms to environmental drivers in the context of climate change. However, bloom dynamics are usually ignored in most studies. Here, we investigated the effects of the initial pCO2 on the bloom characteristics of two cosmopolitan diatoms, Skeletonema costatum and Thalassiosira weissflogii. Batch cultures with two initial pCO2 conditions (LC: 400 µatm; HC: 1000 µatm) were used to investigate bloom dynamics under current and ocean acidification scenarios. The simulated S. costatum bloom was characterized by fast accumulation, a rapid decline in biomass, and a shorter stationary phase. The T. weissflogii bloom had a longer stationary phase, and cell density remained at high levels after culturing for 19 days. The physiological performances of the two diatoms varied significantly in the different bloom phases. We found that the initial pCO2 has modulating effects on biomass accumulation and bloom dynamics for these two diatoms. The higher initial pCO2 enhanced the specific growth rate of T. weissflogii by 6% in the exponential phase, leading to higher cell densities, while 86% higher decay rates were observed in the HC cultures of S. costatum. Overall, ocean acidification may alter the dynamics of diatom blooms and may have profound impacts on the biological carbon pump.

DTX@VTX NPs synergy PD-L1 immune checkpoint nanoinhibitor to reshape immunosuppressive tumor microenvironment for enhancing chemo-immunotherapy.

Immunosuppressed tumor microenvironment (TME) is a major cause of the low response rate in solid tumor patients during PD-1/PD-L1 checkpoint blockade therapy. In this study, a series of small molecule nanomedicines with a 100% drug loading rate were prepared via the nanoprecipitation method. They were used in synergistic chemo-immunotherapy for 4T1 tumors. Among four PD-L1 small-molecule nanoinhibitors, BMS-1 NP with the best anti-tumor performance was selected to replace the therapeutic PD-L1 antibody. The core-shell small-molecule nanomedicine DTX@VTX NP (DTX: Docetaxel and VTX: VTX-2337 or Motolimod) was used to reverse immunosuppressed TME through the depletion of myeloid-derived suppressor cells (MDSCs) and the polarization of macrophages from an M2-like phenotype to M1-like phenotype. Thus, the frequency of cytotoxic CD8+ T cells was significantly increased, resulting in an effective attack on cancer cells. Combining BMS-1 NPs with DTX@VTX NPs, synergistic chemo-immunotherapy of 4T1 tumors was performed, and the results indicate that the inhibition rates of primary and rechallenge tumors achieved 90.5% and 94.3%, respectively. These results indicate that DTX@VTX NPs can synergize PD-L1 nanoinhibitor BMS-1 NPs to reshape the immunosuppressive tumor microenvironment for enhancing the anti-tumor effect of chemo-immunotherapy for breast.

Combined effects of seawater acidification and benzo(a)pyrene on the physiological performance of the marine bloom-forming diatom Skeletonema costatum.

The combined effects of polycyclic aromatic hydrocarbons and seawater acidification are poorly understood. Hence, we exposed the bloom-forming diatom Skeletonema costatum to four concentrations (0, 0.1, 1 and 10 µg L-1) of benzo(a)pyrene and two pCO2 levels (400 and 1000 µatm) to investigate its physiological performance. The growth and photosynthesis of S. costatum were tolerant to low and moderate benzo(a)pyrene concentrations regardless of the pCO2 level. However, the highest benzo(a)pyrene concentration had remarkably adverse effects on most parameters, decreasing the growth rate by 69%. Seawater acidification increased the sensitivity to high light stress, as shown by the lower maximum relative electron transport rate and light saturation point at the highest benzo(a)pyrene concentration. Our results suggested that benzo(a)pyrene could be detrimental to diatoms at a habitat-relevant level, and seawater acidification might further decrease its light tolerance, which would have important ramifications for the community structure and primary production in coastal waters.

Lipid Remodeling Reveals the Adaptations of a Marine Diatom to Ocean Acidification.

Ocean acidification is recognized as a major anthropogenic perturbation of the modern ocean. While extensive studies have been carried out to explore the short-term physiological responses of phytoplankton to ocean acidification, little is known about their lipidomic responses after a long-term ocean acidification adaptation. Here we perform the lipidomic analysis of a marine diatom Phaeodactylum tricornutum following long-term (∼400 days) selection to ocean acidification conditions. We identified a total of 476 lipid metabolites in long-term high CO2 (i.e., ocean acidification condition) and low CO2 (i.e., ambient condition) selected P. tricornutum cells. Our results further show that long-term high CO2 selection triggered substantial changes in lipid metabolites by down- and up-regulating 33 and 42 lipid metabolites. While monogalactosyldiacylglycerol (MGDG) was significantly down-regulated in the long-term high CO2 selected conditions, the majority (∼80%) of phosphatidylglycerol (PG) was up-regulated. The tightly coupled regulations (positively or negatively correlated) of significantly regulated lipid metabolites suggest that the lipid remodeling is an organismal adaptation strategy of marine diatoms to ongoing ocean acidification. Since the composition and content of lipids are crucial for marine food quality, and these changes can be transferred to high trophic levels, our results highlight the importance of determining the long-term adaptation of lipids in marine producers in predicting the ecological consequences of climate change.

[Analysis and experimental validation of signal-to-noise for limb imaging spectrometer].

Limb imaging spectrometer is an important new remote sensor for research and application. Signal-to-noise ratio (SNR) is one of the key parameters to quantitatively evaluate the image quality and radiometric performance of an imaging spectrometer. The estimation and testing of SNR are very important for developing an imaging spectrometer. From the perspectives of radiative transmission and energy conversion, the SNR model is proposed, and the SNR equation of dispersive-type limb imaging spectrometer is derived, and the SNR values under several observing conditions for an limb imaging spectrometer prototype developed are theoretically evaluated based on atmospheric radiative transfer code MODTRAN 4.0. The results show that the SNR of the prototype under typical viewing geometry is not less than 8. As experimental validation, SNR testing was performed using an internally illuminated integrating sphere, and the experimental results have proved the correctness of this theoretical model.