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.

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.

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.

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.

Multifunctional Tetracene/Pentacene Host/Guest Nanorods for Enhanced Upconversion Photodynamic Tumor Therapy.

The tissue penetration depth of light and the singlet oxygen (1O2) generation efficiency of photosensitizers (PSs) are the two main factors that determine the effectiveness of photodynamic therapy for tumors. Herein, we report a novel strategy to prepare a multifunctional upconversion photosensitizer (UCPS) based on the host/guest nanoarchitecture. By a simple reprecipitation method, host/guest tetracene/pentacene nanorods (Tc/Pc NRs) were synthesized for enhancing triplet-triplet annihilation-upconversion (TTA-UC) or two-photon excited emission and 1O2 generation efficiency upon 650 or 808 nm excitation. Tc/Pc NRs had higher 1O2 quantum yield (74%) than Tc NRs (28%) upon 650 nm laser irradiation. The proposed mechanism is that doping Pc molecules into Tc NRs induces intermediate states between S0 and S1, shortening the energy gap for 1O2 generation and resulting in TTA-UC emission. Equally important, with 808 nm fs laser excitation, Tc/Pc NRs showed an enhanced 1O2 generation efficiency and two-photon absorption cross section (σ) compared with Tc NRs. In addition, when the tumors in mice were exposed to Tc/Pc NRs with 650 or 808 nm wavelength irradiation, the tumor inhibition rates achieved 99 and 95%, respectively. This work opens new perspectives for exploring novel nano-UCPSs for biomedical applications.

Functional responses of smaller and larger diatoms to gradual CO2 rise.

Diatoms and other phytoplankton groups are exposed to abrupt changes in pCO2, in waters in upwelling areas, near CO2 seeps, or during their blooms; or to more gradual pCO2 rise through anthropogenic CO2 emissions. Gradual CO2 rises have, however, rarely been included in ocean acidification (OA) studies. We therefore compared how small (Thalassiosira pseudonana) and larger (Thalassiosira weissflogii) diatom cell isolates respond to gradual pCO2 rises from 180 to 1000 µatm in steps of ~40 µatm with 5-10 generations at each step, and whether their responses to gradual pCO2 rise differ when compared to an abrupt pCO2 rise imposed from ambient 400 directly to 1000 µatm. Cell volume increased in T. pseudonana but decreased in T. weissflogii with an increase from low to moderate CO2 levels, and then remained steady under yet higher CO2 levels. Growth rates were stimulated, but Chl a, particulate organic carbon (POC) and cellular biogenic silica (BSi) decreased from low to moderate CO2 levels, and then remained steady with further CO2 rise in both species. Decreased saturation light intensity (Ik) and light use efficiency (α) with CO2 rise in T. pseudonana indicate that the smaller diatom becomes more susceptible to photoinhibition. Decreased BSi/POC (Si/C) in T. weissflogii indicates the biogeochemical cycles of both silicon and carbon may be more affected by elevated pCO2 in the larger diatom. The different CO2 modulation methods resulted in different responses of some key physiological parameters. Increasing pCO2 from 180 to 400 µatm decreased cellular POC and BSi contents, implying that ocean acidification to date has already altered diatom contributions to carbon and silicon biogeochemical processes.

The fatty acid content of plankton is changing in subtropical coastal waters as a result of OA: Results from a mesocosm study.

Ocean Acidification (OA) effects on marine plankton are most often considered in terms of inorganic carbon chemistry, but decreasing pH may influence other aspects of cellular metabolism. Here we present the effects of OA on the fatty acid (FA) content and composition of an artificial phytoplankton community (Phaeodactylum tricornutum, Thalassiosira weissflogii, and Emiliania huxleyi) in a fully replicated, ∼4 m3 mesocosm study in subtropical coastal waters (Wuyuan Bay, China, 24.52°N, 117.18°E) at present day (400 µatm) and elevated (1000 µatm) pCO2 concentrations. Phytoplankton growth occurred in three phases during the 33-day experiment: an initial exponential growth leading to senescence and a subsequent decline phase. Phytoplankton sampled from these mesocosms were fed to mesozooplankton collected by net haul from Wuyuan Bay. Concentrations of saturated fatty acids (SFA) in both phytoplankton and mesozooplankton remained high under acidified and non-acidified conditions. However, polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA) increased significantly more under elevated pCO2 during the late exponential phase (Day 13), indicating increased nutritional value for zooplankton and higher trophic levels. Indeed, uptake rates of the essential FA docosahexaenoic acid (C20:5n3, DHA) increased in mesozooplankton under acidified conditions. However, mesozooplankton grazing rates decreased overall with elevated pCO2. Our findings show that these selected phytoplankton species have a relatively high tolerance to acidification in terms of FA production, and local mesozooplankton in these subtropical coastal waters can maintain their FA composition under end of century ocean acidification conditions.

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.

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.

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.

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.

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.

Carbon assimilation and losses during an ocean acidification mesocosm experiment, with special reference to algal blooms.

A mesocosm experiment was conducted in Wuyuan Bay (Xiamen), China, to investigate the effects of elevated pCO2 on bloom formation by phytoplankton species previously studied in laboratory-based ocean acidification experiments, to determine if the indoor-grown species performed similarly in mesocosms under more realistic environmental conditions. We measured biomass, primary productivity and particulate organic carbon (POC) as well as particulate organic nitrogen (PON). Phaeodactylum tricornutum outcompeted Thalassiosira weissflogii and Emiliania huxleyi, comprising more than 99% of the final biomass. Mainly through a capacity to tolerate nutrient-limited situations, P. tricornutum showed a powerful sustained presence during the plateau phase of growth. Significant differences between high and low CO2 treatments were found in cell concentration, cumulative primary productivity and POC in the plateau phase but not during the exponential phase of growth. Compared to the low pCO2 (LC) treatment, POC increased by 45.8-101.9% in the high pCO2 (HC) treated cells during the bloom period. Furthermore, respiratory carbon losses of gross primary productivity were found to comprise 39-64% for the LC and 31-41% for the HC mesocosms (daytime C fixation) in phase II. Our results suggest that the duration and characteristics of a diatom bloom can be affected by elevated pCO2. Effects of elevated pCO2 observed in the laboratory cannot be reliably extrapolated to large scale mesocosms with multiple influencing factors, especially during intense algal blooms.

The acclimation process of phytoplankton biomass, carbon fixation and respiration to the combined effects of elevated temperature and pCO2 in the northern South China Sea.

We conducted shipboard microcosm experiments at both off-shore (SEATS) and near-shore (D001) stations in the northern South China Sea (NSCS) under three treatments, low temperature and low pCO2 (LTLC), high temperature and low pCO2 (HTLC), and high temperature and high pCO2 (HTHC). Biomass of phytoplankton at both stations were enhanced by HT. HTHC did not affect phytoplankton biomass at station D001 but decreased it at station SEATS. HT alone increased net primary productivity by 234% at station SEATS and by 67% at station D001 but the stimulating effect disappeared when HC was combined. HT also increased respiration rate by 236% at station SEATS and by 87% at station D001 whereas HTHC reduced it by 61% at station SEATS and did not affect it at station D001. Overall, our findings indicate that the positive effect of ocean warming on phytoplankton assemblages in NSCS could be damped or offset by ocean acidification.

Effect of Testosterone on the Phenotypic Modulation of Corpus Cavernosum Smooth Muscle Cells in a Castrated Rat Model.

OBJECTIVE: To investigate the effect of testosterone (T) on the phenotypic modulation of corpus cavernosum smooth muscle (CCSM) cells in a castrated rat model. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were randomly divided into 3 groups: control, castration, and castration with T supplementation (castration + T). Erectile function, histologic change, and biochemical markers were assessed for phenotypic modulation of CCSM cells in corporal tissue. Moreover, the primary rat CCSM cells were isolated and examined by Western blot analysis. RESULTS: Our data showed that serum T level, mean weight of the body, erectile function, and smooth muscle-to-collagen ratio were significantly decreased in the castration group compared with those in the control and castration + T groups. The expressions of CCSM cells' phenotypic markers, such as α-smooth muscle actin, calponin, and smooth muscle myosin heavy chain 11, were markedly lower, whereas osteopontin protein expression was significantly higher in castrated rats than in control and castrated + T rats. In addition, the immunofluorescence staining of α-smooth muscle actin and calponin markedly decreased in the primary CCSM cells of the castrated rats compared with the intensity of the control and the castration + T rats. CONCLUSION: CCSM cells undergo phenotype modulation in castrated rats, whereas T reversed the alterations. T may play a key role in the phenotype modulation of CCSM cells.

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.

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.