In recent years, stimulating the host immune system to create a promising antitumor immune therapy has been demonstrated to control metastatic tumor growth. [1] Research enthusiasm has been fueled by recent clinical successes in which antibodies were used to block immune inhibitory pathways, specifically the axis between programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1). [2] However, therapeutic antibodies exhibit several disadvantages, such as limited tissue and tumor penetration, very long half-life time, immunogenicity, and costly production. Moreover, the current PD-1/PD-L1 axis-directed monoclonal antibodies lead to a tumor response only in a fraction of cases and tumor types. [3] Therefore, the application of alternative, nonantibody-based agents to inhibit PD-1/ PD-L1 axis is currently a new goal within the field. [4] The development of organic smallmole cule inhibitors is expected to introduce a number of advantages in the field of PD-1/PD-L1 immune checkpoint 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.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.

We report on the preparation of N, P co-doped red carbon dots and their applications in bioimaging and photodynamic therapy of tumors.

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.

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 CO 2 (1000 latm, HCL, pH T : 7.70) for 1860 generations, showed significant differences in photosynthesis and growth from a population maintained in ambient CO 2 and then transferred to elevated CO 2 for 20 generations (HC). The HCL population had lower mitochondrial respiration, than did the control population maintained in ambient CO 2 (400 latm, LCL, pH T : 8.02) for 1860 generations. Although the cells had higher respiratory carbon loss within 20 generations under the elevated CO 2 , 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.