Immunoregulation of Shenqi Fuzheng Injection Combined with Chemotherapy in Cancer Patients: A Systematic Review and Meta-Analysis

Background. Immunosuppression is a well-recognised complication of chemotherapy in cancer patients. We assemble the clinical evidence that SQI, an adjuvant drug for lung cancer and gastric cancer which was widely prescribed in China, interventions could increase objective tumour response and regulate immunity in cancer patients undergoing chemotherapy. Methods. We undertook a systemic review of the clinical data from randomised controlled trials up to September 2015 in which a SQI intervention was compared with a control arm in patients undergoing conventional chemotherapy. Revman 5.0 Software was used for the data analysis. Results. 49 randomised controlled trials were included in the systematic review. The meta-analysis results demonstrated that the SQI intervention with conventional chemotherapy exhibited better therapeutic efficacy than the conventional chemotherapy group with a statistically significant higher objective tumour response. Cotreatment with SQI could enhance NK, CD3+, CD4+ level, and CD4+/CD8+ ratio comparing with the conventional chemotherapy group. Conclusions. The conclusions of this review might suggest a high risk of bias due to the low quality and the limitation of cancer types in the included trials. A more reliable conclusion regarding the immunoregulation of SQI could be reached based on more trials of higher quality

Self‐Assembly of Therapeutic Peptide into Stimuli‐Responsive Clustered Nanohybrids for Cancer‐Targeted Therapy

Clinical translation of therapeutic peptides, particularly those targeting intracellular protein–protein interactions (PPIs), has been hampered by their inefficacious cellular internalization in diseased tissue. Therapeutic peptides engineered into nanostructures with stable spatial architectures and smart disease targeting ability may provide a viable strategy to overcome the pharmaceutical obstacles of peptides. This study describes a strategy to assemble therapeutic peptides into a stable peptide–Au nanohybrid, followed by further self‐assembling into higher‐order nanoclusters with responsiveness to tumor microenvironment. As a proof of concept, an anticancer peptide termed β‐catenin/Bcl9 inhibitors is copolymerized with gold ion and assembled into a cluster of nanohybrids (pCluster). Through a battery of in vitro and in vivo tests, it is demonstrated that pClusters potently inhibit tumor growth and metastasis in several animal models through the impairment of the Wnt/β‐catenin pathway, while maintaining a highly favorable biosafety profile. In addition, it is also found that pClusters synergize with the PD1/PD‐L1 checkpoint blockade immunotherapy. This new strategy of peptide delivery will likely have a broad impact on the development of peptide‐derived therapeutic nanomedicine and reinvigorate efforts to discover peptide drugs that target intracellular PPIs in a great variety of human diseases, including cancer.A strategy for clinical translation of therapeutic peptides by assembling them into a stable peptide–Au nanohybrid, followed by further self‐assembling into higher‐order nanoclusters with responsiveness to the tumor microenvironment, is presented. An anticancer peptide termed β‐catenin/Bcl9 inhibitor is assembled into a cluster of nanohybrids termed pCluster, which potently inhibits tumor growth as well as metastasis, and synergizes with immunotherapy, while maintaining a highly favorable biosafety profile.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148246/1/adfm201807736.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148246/2/adfm201807736-sup-0001-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148246/3/adfm201807736_am.pd

Seasonal changes in sea ice kinematics and deformation in the Pacific sector of the Arctic Ocean in 2018/19

Arctic sea ice kinematics and deformation play significant roles in heat and momentum exchange between the atmosphere and ocean, and at the same time they have profound impacts on biological processes and biogeochemical cycles. However, the mechanisms regulating their changes on seasonal scales and their spatial variability remain poorly understood. Using position data recorded by 32 buoys in the Pacific sector of the Arctic Ocean (PAO), we characterized the spatiotemporal variations in ice kinematics and deformation for autumn–winter 2018/19, during the transition from a melting sea ice regime to a nearly consolidated ice pack. In autumn, the response of the sea ice drift to wind and inertial forcing was stronger in the southern and western PAO compared to the northern and eastern PAO. These spatial heterogeneities gradually weakened from autumn to winter, in line with the seasonal increases in ice concentration and thickness. Correspondingly, ice deformation became much more localized as the sea ice mechanical strength increased, with the area proportion occupied by the strongest (15 %) ice deformation decreasing by about 50 % from autumn to winter. During the freezing season, ice deformation rate in the northern PAO was about 2.5 times higher than in the western PAO and probably related to the higher spatial heterogeneity of oceanic and atmospheric forcing in the north. North–south and east–west gradients in sea ice kinematics and deformation within the PAO, as observed especially during autumn in this study, are likely to become more pronounced in the future as a result of a longer melt season, especially in the western and southern parts

Distribution of Shallow Isochronous Layers in East Antarctica Inferred from Frequency-Modulated Continuous-Wave (FMCW) Radar

During the 32nd Chinese National Antarctic Research Expedition, the Frequency-Modulated Continuous-Wave (FMCW) radar was used for the first time to obtain the distribution of shallow isochronous layers within the East Antarctic region extending from Zhongshan Station to Kunlun Station. Taking a typical area as a case study, this article describes the complete workflow used in radar data processing, including signal processing and extraction of isochronous layers. The wave velocity model is established according to an empirical formula to calculate the depth of the layer, and the result is compared and corrected with the volcanic record in ice core DT263; the relative error of depth is only approximately 5%. The echograms of the isochronous layers in three regions are presented, including the area around the Dome A, the area 100 km from the Dome A and the area in the Lambert Glacier. A comparison of the echograms within the three regions shows that the isochronous layers are relatively stable in the Dome A and change more intensely in the Lambert Glacier, while the folding of the layer occurs in a concentrated area near Dome A. This folding may be due to the local layer mixing and compression caused by the ice flow and wind-driven processes. The analysis of the distribution of the shallow isochronous layers and age-depth information from different regions provides important data that support the calculation of large-scale accumulation rates and flow history in the Antarctic

A New Machine Learning Algorithm for Numerical Prediction of Near-Earth Environment Sensors along the Inland of East Antarctica

Accurate short-term small-area meteorological forecasts are essential to ensure the safety of operations and equipment operations in the Antarctic interior. This study proposes a deep learning-based multi-input neural network model to address this problem. The newly proposed model is predicted by combining a stacked autoencoder and a long- and short-term memory network. The self-stacking autoencoder maximises the features and removes redundancy from the target weather station’s sensor data and extracts temporal features from the sensor data using a long- and short-term memory network. The proposed new model evaluates the prediction performance and generalisation capability at four observation sites at different East Antarctic latitudes (including the Antarctic maximum and the coastal region). The performance of five deep learning networks is compared through five evaluation metrics, and the optimal form of input combination is discussed. The results show that the prediction capability of the model outperforms the other models. It provides a new method for short-term meteorological prediction in a small inland Antarctic region

DataSheet_1_A d-peptide-based oral nanotherapeutic modulates the PD-1/PD-L1 interaction for tumor immunotherapy.docx

BackgroundPD-1/PD-L1 immune checkpoint inhibitors are currently the most commonly utilized agents in clinical practice, which elicit an immunostimulatory response to combat malignancies. However, all these inhibitors are currently administered via injection using antibody-based therapies, while there is a growing need for oral alternatives.MethodsThis study has developed and synthesized exosome-wrapped gold–peptide nanocomplexes with low immunogenicity, which can target PD-L1 and activate antitumor immunity in vivo through oral absorption. The SuperPDL1exo was characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), and gel silver staining. The transmembrane ability of SuperPDL1exo was evaluated by flow cytometry and immunofluorescence. Cell viability was determined using the Cell Counting Kit-8 (CCK-8) assay. ELISA experiments were conducted to detect serum and tissue inflammatory factors, as well as serum biochemical indicators. Tissue sections were stained with H&E for the evaluation of the safety of SuperPDL1exo. An MC38 colon cancer model was established in immunocompetent C56BL/6 mice to evaluate the effects of SuperPDL1exo on tumor growth in vivo. Immunohistochemistry (IHC) staining was performed to detect cytotoxicity factors such as perforin and granzymes.ResultsFirst, SuperPDL1 was successfully synthesized, and milk exosome membranes were encapsulated through ultrasound, repeated freeze–thaw cycles, and extrusion, resulting in the synthesis of SuperPDL1exo. Multiple characterization results confirmed the successful synthesis of SuperPDL1exo nanoparticles. Furthermore, our data demonstrated that SuperPDL1exo exhibited excellent colloidal stability and superior cell transmembrane ability. In vitro and in vivo experiments revealed that SuperPDL1exo did not cause damage to multiple systemic organs, demonstrating its good biocompatibility. Finally, in the MC38 colon cancer mouse model, it was discovered that SuperPDL1exo could inhibit the progression of colon cancer, and this tumor-suppressive effect was mediated through the activation of tumor-specific cytotoxic T lymphocyte (CTL)-related immune responses.ConclusionThis study has successfully designed and synthesized an oral nanotherapeutic, SuperPDL1exo, which demonstrates small particle size, excellent colloidal stability, transmembrane ability in tumor cells, and biocompatibility. In vivo experiments have shown that it effectively activates T-cell immunity and exerts antitumor effects.</p

ERK-mediated phosphorylation regulates SOX10 sumoylation and targets expression in mutant BRAF melanoma

In BRAF mutant melanoma, inhibition of ERK1/2 induces FOXD3 and mediates RAF inhibitor resistance. Here, the authors show that ERK1/2 mediated phosphorylation regulates sumoylation of SOX10 which activates FOXD3, and depletion of SOX10 sensitises BRAF mutant melanoma cells to RAF inhibitors