Clinical dilemma and systemic treatment strategy of triple-negative breast cancer in the elderly

There is no specific biomarker for triple-negative breast cancer (TNBC), and chemotherapy remains as backbone but with limited efficacy and more side effects. 10%-21% TNBC are elderly patients with high prevalence of concomitant cardio-cerebrovascular and renal complications, which may lead to intolerance of chemotherapy. How to properly treat these elderly TNBC patients becomes a big challenge during daily clinical practice. To date, few clinical trials specifically focus on elderly TNBC patients, thus no enough evidence-based safety and efficacy data are provided to support the proper therapy to this population. There are also challenges and controversies in the diagnosis and treatment. Elderly TNBC patients have special age-related disease characteristics and high non-cancer related mortality. Therefore, it is very important to balance survival benefit and quality of life during the treatment. This paper summarized data of the epidemiology, tumor biological behavior, current diagnosis and treatment status and the huge unmet medical needs of elderly TNBC patients, and explored the benefits of novel antibody-drug conjugate (ADC), to provide certain guidance on systemic treatment strategies for elderly TNBC patients

Tetherin inhibits prototypic foamy virus release

Background: Tetherin (also known as BST-2, CD317, and HM1.24) is an interferon- induced protein that blocks the release of a variety of enveloped viruses, such as retroviruses, filoviruses and herpesviruses. However, the relationship between tetherin and foamy viruses has not been clearly demonstrated. Results: In this study, we found that tetherin of human, simian, bovine or canine origin inhibits the production of infectious prototypic foamy virus (PFV). The inhibition of PFV by human tetherin is counteracted by human immunodeficiency virus type 1 (HIV-1) Vpu. Furthermore, we generated human tetherin transmembrane domain deletion mutant (delTM), glycosyl phosphatidylinositol (GPI) anchor deletion mutant (delGPI), and dimerization and glycosylation deficient mutants. Compared with wild type tetherin, the delTM and delGPI mutants only moderately inhibited PFV production. In contrast, the dimerization and glycosylation deficient mutants inhibit PFV production as efficiently as the wild type tetherin. Conclusions: These results demonstrate that tetherin inhibits the release and infectivity of PFV, and this inhibition is antagonized by HIV-1 Vpu. Both the transmembrane domain and the GPI anchor of tetherin are important for the inhibition of PFV, whereas the dimerization and the glycosylation of tetherin are dispensable

Scalable and Programmable Phononic Network with Trapped Ions

Controllable bosonic systems can provide post-classical computational power with sub-universal quantum computational capability. A network that consists of a number of bosons evolving through beam-splitters and phase-shifters between different modes, has been proposed and applied to demonstrate quantum advantages. While the network has been implemented mostly in optical systems with photons, recently alternative realizations have been explored, where major limitations in photonic systems such as photon loss, and probabilistic manipulation can be addressed. Phonons, the quantized excitations of vibrational modes, of trapped ions can be a promising candidate to realize the bosonic network. Here, we experimentally demonstrate a minimal-loss phononic network that can be programmed and in which any phononic states are deterministically prepared and detected. We realize the network with up to four collective-vibrational modes, which can be straightforwardly extended to reveal quantum advantage. We benchmark the performance of the network with an exemplary algorithm of tomography for arbitrary multi-mode states with a fixed total phonon number. We obtain reconstruction fidelities of 94.5 $\pm$ 1.95 % and 93.4 $\pm$ 3.15 % for single-phonon and two-phonon states, respectively. Our experiment demonstrates a clear and novel pathway to scale up a phononic network for various quantum information processing beyond the limitations of classical and other quantum systems

Thiophene Disubstituted Benzothiadiazole Derivatives: An Effective Planarization Strategy Toward Deep-Red to Near-Infrared (NIR) Organic Light-Emitting Diodes

As one of the three primary colors that are indispensable in full-color displays, the development of red emitters is far behind the blue and green ones. Here, three novel orange-yellow to near-infrared (NIR) emitters based on 5,6-difluorobenzo[c][1,2,5]thiadiazole (BTDF) namely BTDF-TPA, BTDF-TTPA, and BTDF-TtTPA were designed and synthesized. Density functional theory analysis and photophysical characterization reveal that these three materials possess hybridized local and charge-transfer (HLCT) state feature and a feasible reverse intersystem crossing (RISC) from the high-lying triplet state to the singlet state may conduce to an exciton utilization exceeding the limit of 25% of traditional fluorescence materials under electrical excitation. The insertion of thiophene with small steric hindrance as π-bridge between the electron-donating (D) moiety triphenylamine (TPA) and the electron-accepting (A) moiety BTDF not only results in a remarkable 67 nm red-shift of the emission peak but also brings about a large overlap of frontier molecular orbitals to guarantee high radiative transition rate that is of great significance to obtain high photoluminescence quantum yield (PLQY) in the “energy-gap law” dominated long-wavelength emission region. Consequently, an attractive high maximum external quantum efficiency (EQE) of 5.75% was achieved for the doped devices based on these thiophene π-bridged emitters, giving a deep-red emission with small efficiency roll-off. Remarkably, NIR emission could be obtained for the non-doped devices, achieving an excellent maximum EQE of 1.44% and Commission Internationale de l'Éclairage (CIE) coordinates of (0.71, 0.29). These results are among the highest efficiencies in the reported deep-red to NIR fluorescent OLEDs and offer a new π-bridge design strategy in D-π-A and D-π-A-π-D red emitter design

School Climate, Loneliness, and Problematic Online Game Use Among Chinese Adolescents: The Moderating Effect of Intentional Self-Regulation

Evidently, the school climate is important in reducing adolescent problematic online game use (POGU); however, the mechanism accounting for this association remains largely unknown. This study examined whether loneliness mediated the link between school climate and adolescent POGU and whether this mediating process was moderated by adolescent intentional self-regulation. To this end, self-report questionnaires were distributed. Participants were 500 12–17-years-old Chinese adolescents (Meanage = 13.59 years, 50.60% male). After controlling for adolescents' gender, age, family socioeconomic status, and self-esteem, the results showed that the negative association between school climate and adolescent POGU was partially mediated by loneliness. Moreover, this indirect link was stronger for adolescents with low intentional self-regulation than for those with high intentional self-regulation. These findings highlight loneliness as a potential mechanism linking school climate to adolescent POGU and provide guidance for the development of effective interventions for addressing the adverse effects of a negative school climate

Characterization of starch structures isolated from the grains of waxy, sweet, and hybrid sorghum (Sorghum bicolor L. Moench)

In this study, starches were isolated from inbred (sweet and waxy) and hybrid (sweet and waxy) sorghum grains. Structural and property differences between (inbred and hybrid) sweet and waxy sorghum starches were evaluated and discussed. The intermediate fraction and amylose content present in hybrid sweet starch were lower than those in inbred sweet starch, while the opposite trend occurred with waxy starch. Furthermore, there was a higher A chain (30.93–35.73% waxy, 13.73–31.81% sweet) and lower B2 + B3 chain (18.04–16.56% waxy, 24.07–17.43% sweet) of amylopectin in hybrid sorghum starch. X-ray diffraction (XRD) and Fourier transform infrared reflection measurements affirm the relative crystalline and ordered structures of both varieties as follows: inbred waxy > hybrid waxy > hybrid sweet > inbred sweet. Small angle X-ray scattering and 13C CP/MAS nuclear magnetic resonance proved that the amylopectin content of waxy starch was positively correlated with lamellar ordering. In contrast, an opposite trend was observed in sweet sorghum starch due to its long B2 + B3 chain content. Furthermore, the relationship between starch granule structure and function was also concluded. These findings could provide a basic theory for the accurate application of existing sorghum varieties precisely

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival