A one-for-all organic agent for integrated triple-modality imaging-guided cancer surgery has been developed, in which the fluorescence, photoacoustic (PA), and Raman properties could be precisely tuned and boosted by tuning the molecular structure and intramolecular motions. By taking advantage of the merits of each mode, the organic nanoagent helps to decipher tumor information at different surgical stages and improve cancer surgery outcomes significantly. The preoperative fluorescence and PA imaging provide comprehensive information about tumors, while intraoperative fluorescence and Raman imaging accurately delineate tiny residual tumors.

Lysosome‐relevant cell death induced by lysosomal membrane permeabilization (LMP) has recently attracted increasing attention. However, nearly no studies show that currently available LMP inducers can evoke immunogenic cell death (ICD) or convert immunologically cold tumors to hot. Herein, we report a LMP inducer named TPE‐Py‐pYK(TPP)pY, which can respond to alkaline phosphatase (ALP), leading to formation of nanoassembies along with fluorescence and singlet oxygen turn‐on. TPE‐Py‐pYK(TPP)pY tends to accumulate in ALP‐overexpressed cancer cell lysosomes as well as induce LMP and rupture of lysosomal membranes to massively evoke ICD. Such LMP‐induced ICD effectively converts immunologically cold tumors to hot as evidenced by abundant CD8+ and CD4+ T cells infiltration into the cold tumors. Exposure of ALP‐catalyzed nanoassemblies in cancer cell lysosomes to light further intensifies the processes of LMP, ICD and cold‐to‐hot tumor conversion. This work thus builds a new bridge between lysosome‐relevant cell death and cancer immunotherapy.

Abstract:We articulate and apply the generalized Onsager principle to derive transport equations for active liquid crystals in a fixed domain as well as in a free surface domain adjacent to a passive fluid matrix. The Onsager principle ensures fundamental variational structure of the models as well as dissipative properties of the passive component in the models, irrespective of the choice of scale (kinetic to continuum) and of the physical potentials. Many popular models for passive and active liquid crystals in a fixed domain subject to consistent boundary conditions at solid walls, as well as active liquid crystals in a free surface domain with consistent transport equations along the free boundaries, can be systematically derived from the generalized Onsager principle. The dynamical boundary conditions are shown to reduce to the static boundary conditions for passive liquid crystals used previously.

We introduce a semi-perfect obstruction theory of a Deligne-Mumford stack X that consists of local perfect obstruction theories with a global obstruction sheaf. We construct the virtual cycle of a Deligne-Mumford stack with a semi-perfect obstruction theory. We use semi-perfect obstruction theory to construct virtual cycles of moduli of derived objects on Calabi-Yau threefolds.

Background:There has been no external validation of survival prediction models for severe adult respiratory distress syndrome (ARDS) with extracorporeal membrane oxygenation (ECMO) therapy in China. The aim of study was to compare the performance of multiple models recently developed for patients with ARDS undergoing ECMO based on Chinese single-center data.Methods:A retrospective case study was performed, including twenty-three severe ARDS patients who received ECMO from January 2009 to July 2015. The PRESERVE (Predicting death for severe ARDS on VV-ECMO), ECMOnet, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score, a center-specific model developed for inter-hospital transfers receiving ECMO, and the classical risk-prediction scores of Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) were calculated. In-hospital and six-month mortality were regarded as the endpoints and model performance was evaluated by comparing the area under the receiver operating characteristic curve (AUC).Results:The RESP and APACHE II scores showed excellent discriminate performance in predicting survival with AUC of 0.835 (95% confidence interval [CI], 0.659–1.010, P = 0.007) and 0.762 (95% CI, 0.558–0.965, P = 0.035), respectively. The optimal cutoff values were risk class 3.5 for RESP and 35.5 for APACHE II score, and both showed 70.0% sensitivity and 84.6% specificity. The excellent performance of these models was also evident for the pneumonia etiological subgroup, for which the SOFA score was also shown to be predictive, with an AUC of 0.790 (95% CI, 0.571–1.009, P = 0.038). However, the ECMOnet and the score developed for externally retrieved ECMO patients failed to demonstrate significant discriminate power for the overall cohort. The PRESERVE model was unable to be evaluated fully since only one patient died six months postdischarge.Conclusions:The RESP, APCHAE II, and SOFA scorings systems show good predictive value for intra-hospital survival of ARDS patients treated with ECMO in our single-center evaluation. Future validation should include a larger study with either more patients’ data at single-center or by integration of domestic multi-center data. Development of a scoring system with national characteristics might be warranted.

No abstract

Paclitaxel (Ptx), a type of microtubule depolymerization inhibitor, is one of the main components in gastric cancer chemotherapy. Some studies have demonstrated that tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, has potential antitumor effects in several cancers. Aside from the direct anticancer effect, Tet is proved to synergistically enhance the antitumor effect of Ptx in gastric cancer. However, the application of the combinational strategy is limited by the poor solubility of both drugs. Nanodrug delivery systems including polymeric nanoparticles, selfassembled nanofibers, hydrogels, etc., hold the potential to meet the need. Here, a novel supramolecular nanomaterial, based on the concept of "carrier-free nanodrugs", is reported as a feasible platform for synergistic drug delivery. Ptx−SA−RGD is obtained through the conjugation of Ptx and the tumor-specific peptide RGD (arginine−glycine−aspartic acid) with succinic acid (SA) as a linker. Ptx−SA−RGD could self-assemble into Ptx nanofibers (P-NFs) with high drugloading efficiency. Tet was then encapsulated into P-NFs to acquire novel Ptx and Tet coloaded self-assembled nanofibers (P/T-NFs). The uptake study shows the dynamic internalization of P/T-NFs by the gastric cancer cell line MGC-803. P/T-NFs significantly triggered the accumulation of reactive oxygen species (ROS) in gastric cancer cells MGC803 and further decreased the mitochondrial membrane potential, which led to the induction of mitochondrial apoptosis with superior cytotoxicity against free drugs. Moreover, P/T-NFs suppressed the expressions of p-STAT3 and p-JAK, initiated cytochrome-C release, and promoted caspase protein expression. Furthermore, P/T-NFs demonstrated the strongest tumor-delaying effect as well as the lowest toxicity. Therefore, self-assembled nanofibers of P/T-NFs demonstrated an increase of the mitochondrial apoptosis level and a stronger antitumor effect both in vitro and in vivo, which could be a potential way to enhance the clinical efficacy and reduce the side-effects of Ptx in gastric cancer.

A bioinspired synthesis of spirochensilide A from commercially available lanosterol is reported. The synthesis features a directed C–H oxidation, a Wagner–Meerwein-type double methyl migration, a Meinwald rearrangement, and a double-bond isomerization/spiroketal formation cascade. The proposed biosynthetic speculation was modified by this synthetic sequence, which also served as a platform for the synthesis of other lanostanes with migrating methyl groups.