Motivated by the superlinear behavior of the Barzilai-Borwein (BB) method for two-dimensional quadratics, we propose two gradient methods which adaptively choose a small step-size or a large step-size at each iteration. The small step-size is primarily used to induce a favorable descent direction for the next iteration, while the large step-size is primarily used to produce a sufficient reduction. Although the new algorithms are still linearly convergent in the quadratic case, numerical experiments on some typical test problems indicate that they compare favorably with the BB method and some other efficient gradient methods.

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BackgroundWearable devices have attracted much attention from the market in recent years for their fitness monitoring and other health-related metrics; however, the accuracy of fitness tracking results still plays a major role in health promotion.ObjectiveThe aim of this study was to evaluate the accuracy of a host of latest wearable devices in measuring fitness-related indicators under various seminatural activities.MethodsA total of 44 healthy subjects were recruited, and each subject was asked to simultaneously wear 6 devices (Apple Watch 2, Samsung Gear S3, Jawbone Up3, Fitbit Surge, Huawei Talk Band B3, and Xiaomi Mi Band 2) and 2 smartphone apps (Dongdong and Ledongli) to measure five major health indicators (heart rate, number of steps, distance, energy consumption, and sleep duration) under various activity states (resting, walking, running, cycling, and sleeping), which were then compared with the gold standard (manual measurements of the heart rate, number of steps, distance, and sleep, and energy consumption through oxygen consumption) and calculated to determine their respective mean absolute percentage errors (MAPEs).ResultsWearable devices had a rather high measurement accuracy with respect to heart rate, number of steps, distance, and sleep duration, with a MAPE of approximately 0.10, whereas poor measurement accuracy was observed for energy consumption (calories), indicated by a MAPE of up to 0.44. The measurements varied for the same indicator measured by different fitness trackers. The variation in measurement of the number of steps was the highest (Apple Watch 2: 0.42; Dongdong: 0.01), whereas it was the lowest for heart rate (Samsung Gear S3: 0.34; Xiaomi Mi Band 2: 0.12). Measurements differed insignificantly for the same indicator measured under different states of activity; the MAPE of distance and energy measurements were in the range of 0.08 to 0.17 and 0.41 to 0.48, respectively. Overall, the Samsung Gear S3 performed the best for the measurement of heart rate under the resting state (MAPE of 0.04), whereas Dongdong performed the best for the measurement of the number of steps under the walking state (MAPE of 0.01). Fitbit Surge performed the best for distance measurement under the cycling state (MAPE of 0.04), and Huawei Talk Band B3 performed the best for energy consumption measurement under the walking state (MAPE of 0.17).ConclusionsAt present, mainstream devices are able to reliably measure heart rate, number of steps, distance, and sleep duration, which can be used as effective health evaluation indicators, but the measurement accuracy of energy consumption is still inadequate. Fitness trackers of different brands vary with regard to measurement of indicators and are all affected by the activity state, which indicates that manufacturers of fitness trackers need to improve their algorithms for different activity states.

Effective cancer therapy depends not only on destroying the primary tumor but also on conditioning the host immune system to recognize and eliminate residual tumor cells and prevent metastasis. In this study, a tumor integrin αvβ6-targeting peptide (the HK peptide)-functionalized graphene oxide (GO) was coated with a photosensitizer (HPPH). The resulting GO conjugate, GO(HPPH)-PEG-HK, was investigated whether it could destroy primary tumors and boost host antitumor immunity. We found that GO(HPPH)-PEG-HK exhibited significantly higher tumor uptake than GO(HPPH)-PEG and HPPH. Photodynamic therapy (PDT) using GO(HPPH)-PEG suppressed tumor growth in both subcutaneous and lung metastatic mouse models. Necrotic tumor cells caused by GO(HPPH)-PEG-HK PDT activated dendritic cells and significantly prevented tumor growth and lung metastasis by increasing the infiltration of cytotoxic CD8 T lymphocytes within tumors as evidenced by in vivo optical and single-photon emission computed tomography (SPECT)/CT imaging. These results demonstrate that tumor-targeted PDT using GO(HPPH)-PEG-HK could effectively ablate primary tumors and destroy residual tumor cells, thereby preventing distant metastasis by activating host antitumor immunity and suppressing tumor relapse by stimulation of immunological memory.

“Training” the host immune system to recognize and systemically eliminate residual tumor lesions and micrometastases is a promising strategy for cancer therapy. In this study, we investigated whether integrin αvβ6-targeted photodynamic therapy (PDT) of tumors using a phthalocyanine dye-labeled probe (termed DSAB-HK) could trigger the host immune response, and whether PDT in combination with anti-PD-1 immune checkpoint inhibition could be used for the effective therapy of primary tumors and metastases. By near-infrared fluorescence imaging, DSAB-HK was demonstrated to specifically target either subcutaneous tumors in a 4T1 mouse breast cancer model or firefly luciferase stably transfected 4T1 (4T1-fLuc) lung metastatic tumors. Upon light irradiation, PDT by DSAB-HK significantly inhibited the growth of subcutaneous 4T1 tumors, and in addition promoted the maturation of dendritic cells and their production of cytokines, which subsequently stimulated the tumor recruitment of CD8+ cytotoxic T lymphocytes. Furthermore, DSAB-HK PDT of the first tumor followed by PD-1 blockade markedly suppressed the growth of a second subcutaneous tumor, and also slowed the growth of 4T1-fLuc lung metastasis as demonstrated by serial bioluminescence imaging. Together, our results demonstrated the synergistic effect of tumor-targeted PDT and immune checkpoint inhibition for improving anti-tumor immunity and suppressing tumor growth/metastasis.

Hematologic malignancies such as acute and chronic myeloid leukemia are characterized by the malignant transformation of immature CD34+ progenitor cells. Transformation is associated with elevated expression of the Wilm's tumor gene encoded transcription factor (WT1). Here we demonstrate that WT1 can serve as a target for cytotoxic T lymphocytes (CTL) with exquisite specificity for leukemic progenitor cells. HLA-A0201– restricted CTL specific for WT1 kill leukemia cell lines and inhibit colony formation by transformed CD34+ progenitor cells isolated from patients with chronic myeloid leukemia (CML), whereas colony formation by normal CD34+ progenitor cells is unaffected. Thus, the tissue-specific transcription factor WT1 is an ideal target for CTL-mediated purging of leukemic progenitor cells in vitro and for antigen-specific therapy of leukemia and other WT1-expressing malignancies in vivo.

Interleukin-2 (IL-2), originally described as a growth factor required for sustained proliferation of T cells in vitro is a glycoprotein hormone of known structure which appears to be important for the generation of immune responses in vivo. As well as T lymphocytes, B lymphocytes and large granular lymphocytes with natural killer activity (NK cells) can also respond to IL-2. The action of IL-2 seemed to be limited specifically to lymphocytes, however, and the term 'T-lymphocytotrophic hormone' was used. Here we provide evidence that human monocytes display a substantially increased cytotoxic activity as a direct and rapid response to human recombinant IL-2 but not to human recombinant glycosylated interferon-gamma (IFN-gamma) or lipopolysaccharide. Our results reveal a previously unknown function of IL-2 and suggest its possible involvement in monocyte-T cell interactions.

Tumor relapse after initial regression post-chemotherapy is a major challenge in cancer treatment, as it usually leads to local-regional recurrence or inoperable distant metastasis. M2 macrophages diminish the tumor-inhibitory effect of chemotherapy and correlate with distant metastasis and poor prognosis. In this study, we investigated whether molecular imaging of M2 macrophages could serve as an early biomarker for tumor relapse after chemotherapy and tumor lymph node metastasis in preclinical mouse models. Methods: We developed M2 macrophage-targeted probes for near-infrared fluorescence (NIRF) imaging and single-photon emission computed tomography (SPECT) using an anti-CD206 monoclonal antibody. The specific targeting capacity and potential applications of the NIRF and SPECT probes were investigated in subcutaneous tumor and lymph node metastasis models of 4T1 murine breast cancer. Results: M2 macrophage infiltration was significantly increased in the 4T1 tumors that later underwent relapse but not in non-relapsing 4T1 tumors after cyclophosphamide treatment. Through NIRF imaging and SPECT using our synthesized probes, the infiltration of M2 macrophages in relapsing tumors and tumor lymph node metastasis could be sensitively detected. Importantly, early prediction of tumor relapse by molecular imaging of M2 macrophages resulted in an effective eradication of tumors upon combination with additional radiotherapy. Conclusion: Our findings demonstrate that M2 macrophage-targeted imaging allows for noninvasively predicting post-chemotherapy tumor relapse and sensitively detecting the metastatic lymph nodes in vivo. This imaging strategy could provide a better understanding of cancer progression, enable early prediction of tumor resistance, and have implications on the rational design of cancer therapeutics.