Proton-Gradient-Driven Porphyrin-Based Liposome Remote-Loaded with Imiquimod as In Situ Nanoadjuvants for Synergistically Augmented Tumor Photoimmunotherapy.

Cancer immunotherapy is expected to achieve tumor treatment mainly by stimulating the patient's own immune system to kill tumor cells. However, the low immunogenicity of the tumor and the poor efficiency of tumor antigen presentation result in a variety of solid tumors that do not respond to immunotherapy. Herein, we designed a proton-gradient-driven porphyrin-based liposome (PBL) with highly efficient Toll-like receptor 7 (TLR7) agonist (imiquimod, R837) encapsulation (R837@PBL). R837@PBL rapidly released R837 in the acid microenvironment to activate the TLR in the endosome inner membrane to promote bone-marrow-derived dendritic cell maturation and enhance antigen presentation. R837@PBL upon laser irradiation triggered immunogenic cell death of tumor cells and tumor-associated antigen release after subcutaneous injection, activated TLR7, formed in situ tumor nanoadjuvants, and enhanced the antigen presentation efficiency. Photoimmunotherapy promoted the infiltration of cytotoxic T lymphocytes into tumor tissues, inhibited the growth of the treated and abscopal tumors, and exerted highly effective photoimmunotherapeutic effects. Hence, our designed in situ tumor nanoadjuvants are expected to be an effective treatment for treated and abscopal tumors, providing a novel approach for synergistic photoimmunotherapy of tumors.

Genome-wide analysis of gustatory receptor genes and identification of the fructose gustatory receptor in Arma chinensis.

Gustatory receptors (GRs) allow insects to sense tastes in their external environment. Gustatory perception is crucial for distinguishing between beneficial and harmful or toxic compounds, affecting survival. This study is the first to identify and classify the GR genes and investigate their expression in the predatory Arma chinensis. Thirteen GR genes (ArmaGr1-ArmaGr13) were identified and classified into four families via phylogenetic analysis. In the predacious developmental stages, ArmaGr7 expression gradually increased from the 2nd to 5th instar stages and then to adults. However, ArmaGr7 was also highly expressed in the non-predation 1st instar nymph and egg stages. ArmaGr7 expression was localized in the antennae, scalpella, forelegs, wings, head, and midgut of male and female adults, with wings displaying the highest expression. Furthermore, ArmaGr7 expression was positively correlated with fructose solution intake; molecular docking results showed that fructose could effectively dock withArmaGr7. A protein structure comparison revealed that the ArmaGr7 structure was different from that of other GR43a-like proteins, which may be related to the gene splicing of the A. chinensis GR gene. These results elucidate the crucial role of ArmaGr7 in fructose recognition by A. chinensis and provide a foundation for further studies on gustatory perception.

Thermal failure analysis and control algorithm improvement for the active controlled mount with consideration of thermal-magnetic coupling.

This paper proposes an improved narrowband filtered-x least mean square(FxLMS) algorithm to overcome the thermal failure problems of the active controlled mount(ACM). Firstly, the temperature-rising model and the thermal demagnetization model of the ACM are respectively developed. Combining these two models with the powertrain mounting system model, an analytical method is established for the thermal-magnetic coupling analysis of the ACM. Then a numerical simulation is carried out to obtain the permanent magnet(PM) temperature and the coil current. The ACM failure problem is discussed according to the working point trajectory. Finally, an improved algorithm is proposed. This algorithm is able to overcome the thermal failure problems by sacrificing part of the vibration isolation performance. The effectiveness of this algorithm is validated by numerical simulations and a comparison with conventional algorithms.

Charge reversal yolk-shell liposome co-loaded JQ1 and doxorubicin with high drug loading and optimal ratio for synergistically enhanced tumor chemo-immunotherapy via blockade PD-L1 pathway.

Antitumor immunotherapy has become a powerful therapeutic modality to identify and kill various malignant tumors by harnessing the immune system. However, it is hampered by the immunosuppressive microenvironment and poor immunogenicity in malignant tumors. Herein, in order to achieve multi-loading of drugs with different pharmacokinetic properties and targets, a charge reversal yolk-shell liposome co-loaded with JQ1 and doxorubicin (DOX) into the poly (D,L-lactic-co-glycolic acid) (PLGA) yolk and the lumen of the liposome respectively was engineered to increase hydrophobic drug loading capacity and stability under physiological conditions and further enhance tumor chemotherapy via blockade programmed death ligand 1 (PD-L1) pathway. This nanoplatform could release less JQ1 compared to traditional liposomes to avoid drug leakage under physiological conditions due to the protection of liposomes on JQ1 loaded PLGA nanoparticles while the release of JQ1 increased in an acidic environment. In the tumor microenvironment, released DOX promoted immunogenic cell death (ICD), and JQ1 blocked the PD-L1 pathway to strengthen chemo-immunotherapy. The in vivo antitumor results demonstrated the collaborative treatment of DOX and JQ1 in B16-F10 tumor-bearing mice models with minimized systemic toxicity. Furthermore, the orchestrated yolk-shell nanoparticle system could enhance the ICD effect, caspase 3 activation, and cytotoxic T lymphocyte infiltration while inhibiting PD-L1 expression, provoking a strong antitumor effect, whereas yolk-shell liposomes encapsulating only JQ1 or DOX showed modest tumor therapeutic effects. Hence, the cooperative yolk-shell liposome strategy provides a potential candidate for enhancement of hydrophobic drug loading and stability, showing potential for clinic application and synergistic cancer chemo-immunotherapy.

Pulmonary papillary adenoma with malignant potential: a case report and literature review.

BACKGROUND: Pulmonary papillary adenoma is a rare benign tumor in the periphery of the lung. We report a 66-year-old female patient with a tumor in the lower lobe of the right lung and present the clinicopathological features and review the literature. CASE PRESENTATION: A tumor in the lower lobe of the right lung was found incidentally on chest X-ray during the physical examination of the patient, and the patient occasionally had a dry cough that was not treated. The tumor was clearly demarcated and lobulated on CT scan. After 2 years of follow-up, the boundary of the tumor was still clear, with more lobulations and the enhanced scan showed uniform enhancement. Grossly, the tumor had a granular cut surface and was easy to fall off, which was helpful for the diagnosis of papillary adenoma during intraoperative frozen examination. Under the microscope, most areas of the tumor had the typical morphological structure of papillary adenoma. However, the tumor locally protruded into the surrounding lung tissue, accompanied by crowded cells and high cell proliferation index. It was suggested that this case of papillary adenoma had malignant potential and needed active intervention and treatment. CONCLUSION: Pulmonary papillary adenoma is a rare epithelial tumor with malignant potential. Surgical treatment should be performed as soon as possible after diagnosis to prevent malignant transformation.

The ballooning time in endoscopic papillary balloon dilation for removal of bile duct stones: A systematic review and meta-analysis.

BACKGROUND: So far, there was no consensus regarding balloon dilation time in endoscopic papillary balloon dilation (EPBD). Thus, we conducted a systematic review and meta-analysis to compare the stone removal and overall complication rates of dilation of short and long duration with EPBD. METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL; Cochrane Library), Web of Science, EMBASE Databases, and PubMed were searched from their inception to December 1, 2019 for all articles regarding balloon dilation time in EPBD for removal of bile duct stones. The data were extracted and the methodology quality was assessed. Meta-analysis was performed using RevMan5.3 software. RESULTS: Four studies involving a total of 1553 patients were included, 918 in the short dilation group and 635 in the long dilation group. The results of meta-analysis showed that there was no significant difference between the 2 different dilation groups in the complete stone removal in randomized controlled trails (RCTs) group (P = .10) and non-RCTs group (P = 0.45), mechanical lithotripsy requirement (RCTs: P = .92; non-RCTs: P = .47), pancreatitis (RCTs: P = .48; non-RCTs: P = .45), bleeding (RCTs: P = .95; non-RCTs: P = .60), infection of biliary (RCTs: P = .58; non-RCTs: P = .29), perforation (RCTs: P = .32; non-RCTs: P = .37). CONCLUSION: This systematic review suggests that there no significant difference in the efficacy and safety of dilation of short and long duration for removal of bile duct stones with EPBD.