Structural mechanisms of TRPV2 modulation by endogenous and exogenous ligands.

The transient receptor potential vanilloid 2 (TRPV2) ion channel is a polymodal receptor widely involved in many physiological and pathological processes. Despite many TRPV2 modulators being identified, whether and how TRPV2 is regulated by endogenous lipids remains elusive. Here, we report an endogenous cholesterol molecule inside the vanilloid binding pocket (VBP) of TRPV2, with a 'head down, tail up' configuration, resolved at 3.2 Å using cryo-EM. Cholesterol binding antagonizes ligand activation of TRPV2, which is removed from VBP by methyl-ß-cyclodextrin (MßCD) as resolved at 2.9 Å. We also observed that estradiol (E2) potentiated TRPV2 activation by 2-aminoethoxydiphenyl borate (2-APB), a classic tool compound for TRP channels. Our cryo-EM structures (resolved at 2.8-3.3 Å) further suggest how E2 disturbed cholesterol binding and how 2-APB bound within the VBP with E2 or without both E2 and endogenous cholesterol, respectively. Therefore, our study has established the structural basis for ligand recognition of the inhibitory endogenous cholesterol and excitatory exogenous 2-APB in TRPV2.

Autologous liver transplantation for unresectable hepatobiliary malignancies in enhanced recovery after surgery model.

Ex vivo liver resection combined with autologous liver transplantation offers the opportunity to treat otherwise unresectable hepatobiliary malignancies and has been applied in clinic. The implementation of enhanced recovery after surgery (ERAS) program improves the outcome of surgical procedures. This is a retrospective single-center study including 11 cases of patients with liver cancer that underwent autologous liver transplantation and received ERAS: cholangiocarcinoma of the hilar region (n = 5), intrahepatic cholangiocarcinoma (n = 3), gallbladder cancer (n = 1), liver metastasis from colorectal cancer (n = 1), and liver metastasis from gastrointestinal mesenchymal tumor (n = 1). There were no deaths within 30 days and major complications occurred in two patients, and four patients were readmitted upon the first month after the surgery. Median hospital stay was 20 days (range 13-44) and median open diet was Day 4 (range 2-9) after surgery and median early post-operative activity was Day 5 (range 2-9) after surgery. In conclusion, autologous liver transplantation is feasible in the treatment of otherwise unresectable hepatobiliary malignancies, and our study showed favorable results with autologous liver transplantation in ERAS modality. ERAS modality provides a good option for some patients whose tumors cannot be resected in situ and offers a chance for rapid recovery.

A review on the structural dependent optical properties and energy transfer of Mn4+ and multiple ion-codoped complex oxide phosphors.

The tetravalent manganese Mn4+ ions with a 3d3 electron configuration as luminescence centers in solid-state inorganic compounds have been widely investigated because they emit bright light in the red to far-red region when they are excited by light with a wavelength in the UV to blue light region. Herein, we present an overview of the recent developments of Mn4+ and multiple ion such as Bi3+ and rare earth ion Dy3+, Nd3+, Yb3+, Er3+, Ho3+, and Tm3+ codoped complex oxide phosphors. Most of the specified host lattices of these complex oxide phosphors possess multiple metallic cations, which provide possible substitutions with different codopants and form various luminescence centers with diverse spectra. The luminescence of Mn4+ and multiple ion-codoped materials spans almost the whole visible light to near infrared (NIR) region. The crystal structures of complex oxide phosphors, the spectroscopic properties of Mn4+, and the energy transfer between Mn4+ and multiple ions are introduced and summarized in detail with regard to their practical applications. This review provides an insight into the optical properties of Mn4+ and the energy transfer process in multiple ion-codoped luminescence materials, which will be helpful in the development of novel excellent materials for applications in the lighting industry.