Despite its revolutionary success in hematological malignancies, chimeric antigen receptor (CAR) T cell therapy faces disappointing clinical results in solid tumors. The poor efficacy has been partially attributed to the lack of understanding in how CAR-T cells function in a solid tumor microenvironment. Hypoxia plays a critical role in cancer progression and immune editing, which potentially results in solid tumors escaping immunosurveillance and CAR-T cell-mediated cytotoxicity. Mechanistic studies of CAR-T cell biology in a physiological environment has been limited by the complexity of tumor-immune interactions in clinical and animal models, as well as by a lack of reliable in vitro models. We have engineered a microdevice platform that recapitulates a three-dimensional tumor section with a gradient of oxygen and integrates fluidic channels surrounding the tumor for CAR-T cell delivery. Our design allows for the evaluation of CAR-T cell cytotoxicity and infiltration in the heterogeneous oxygen landscape of in vivo solid tumors at a previously unachievable scale in vitro.

Raman spectra of individual carbon nanotubes are measured by scanning a focused laser spot ͑0.5 m diameter͒ over a large area ͑100 m 2 ͒ before and after depositing silver nanoparticles. Local regions exhibiting surface enhanced Raman spectroscopy ͑SERS͒ were located with respect to a lithographically patterned grid, allowing subsequent scanning electron microscopy to be performed. The uniquely large aspect ratio of carbon nanotubes enables imaging of the nanoparticle geometry together with the SERS active molecule. By measuring the same individual carbon nanotube before and after metal nanoparticle deposition, the SERS enhancement factor is determined unambiguously. The data reveals SERS enhancement factors up to 134 000, a consistent upshift in the G band Raman frequency and nanoparticle heating in excess of 600°C.

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Phytophthora pathogens secrete many effector proteins to manipulate host innate immunity. PsAvh238 is a Phytophthora sojae N-terminal Arg-X-Leu-Arg (RXLR) effector, which evolved to escape host recognition by mutating one nucleotide while retaining plant immunity-suppressing activity to enhance infection. However, the molecular basis of the PsAvh238 virulence function remains largely enigmatic.By using coimmunoprecipitation and liquid chromatography-tandem mass spectrometry analysis, we identified the 1-aminocyclopropane-1-carboxylate synthase (ACS) isoforms, the key enzymes in ethylene (ET) biosynthesis, as a host target of PsAvh238.We show that PsAvh238 interacts with soybean ACSs (GmACSs) in vivo and in vitro. By destabilizing Type2 GmACSs, PsAvh238 suppresses Type2 ACS-catalyzed ET biosynthesis and facilitates Phytophthora infection. Silencing of Type2 GmACSs, and inhibition of ET biosynthesis or signaling, increase soybean susceptibility to P. sojae infection, supporting a role for Type2 GmACSs and ET in plant immunity against P. sojae. Moreover, wild-type P. sojae but not the PsAvh238-disrupted mutants, inhibits ET induction and promotes P. sojae infection in soybean.Our results highlight the ET biosynthesis pathway as an essential part in plant immunity against P. sojae and a direct effector target.

Broadband near-infrared (NIR) emitting phosphors have attracted many studies due to their potential applications in non-destructive examination and bioimaging. However, most of the reported broadband NIR phosphors emit in NIR-I...

The adverse effects of high environmental temperature exposure on animal reproductive functions have been concerned for many decades. However, the molecular basis of heat stress (HS)-induced decrease of sperm motility has not been entirely elucidated. We hypothesized that the deteriorate effects of HS may be mediated by damage of mitochondrial function and ATP synthesis. To test this hypothesis, we use mature boar sperm as model to explore the impacts of HS on mitochondrial function and sperm motility. A 6 h exposure to 42°C (HS) induced significant decrease in sperm progressive motility. Concurrently, HS induced mitochondrial dysfunction that is indicated by decreased of membrane potential, respiratory chain complex I and IV activities and adenosine triphosphate (ATP) contents. Exogenous ATP abolished this effect suggesting that reduced of ATP synthesis is the committed step in HS-induced reduction of sperm motility. At the molecular level, the mitochondrial protein contents were significantly decreased in HS sperm. Notably, the cytochrome c oxidase subunit 4, which was synthesized in cytoplasm and translocated into mitochondria, was significantly lower in mitochondria of HS sperm. Glycogen synthase kinase-3α (GSK3α), a negative regulator of sperm motility that is inactivated by Ser21 phosphorylation, was dephosphorylated after HS. The GSK3α inhibitor CHIR99021 was able to abolish the effects of HS on sperm and their mitochondria. Taken together, our results demonstrate that HS affects sperm motility through downregulation of mitochondrial activity and ATP synthesis yield, which involves dephosphorylation of GSK3α and interference of mitochondrial remodeling.

Micro/nanorobots have attracted significant interest in the biomedical field due to their micro/nano scale sizes and autonomously untethered motions. Meanwhile, stem cell‐based therapy has emerged as a promising approach to cure previously irreparable degenerative diseases by virtue of the stem cells’ differentiation and regeneration. To ensure the efficiency of the stem cell delivery, developing suitable and reliable cell‐transport systems is essential. Micro/nanorobots aimed at cell transport have progressed in recent years, which can perform this crucial step of cell delivery accurately and noninvasively during cell‐based therapy. Herein, a review of the design and fabrication technologies and actuation mechanisms of cell‐transport microrobots is presented. The applications of the micro/nanorobotic cell‐manipulation and cell‐transport platforms are discussed, as well as the current challenges and the future perspectives in translation of microrobots from research stage to clinical applications.