Treatment and survival status of patients with EGFR mutation-positive stage Ⅳ lung adenocarcinoma: five-year follow-up results in the Ordos Area of Inner Mongolia, China

Objective We aimed to determine the epidermal growth factor receptor(EGFR) mutation status and treatment survival of patients with stage Ⅳ lung adenocarcinoma living in the Ordos area of Inner Mongolia, China.Methods EGFR testing and first-line tyrosine kinase inhibitor(TKI) treatment rates of patients with stage Ⅳ lung adenocarcinoma were analyzed from June 2012 to June 2016. Kaplan-Meier survival curves were constructed to compare patients who received different treatment strategies and those harboring different EGFR mutation statuses.Results EGFR testing and mutation rates were 65.60% and 52.90%, respectively, and improved continuously from June 2012 to June 2016. Among patients with EGFR mutations, 38.9% had EGFR 19 del, 48.2% had L858 R, 4.2% had co-existing mutations in exons 19 and 21, and 8.4% had uncommon mutations. The median overall survival(OS) was 29.5, 26.5, and 16.0 months for patients receiving both TKI and chemotherapy, TKI alone, and chemotherapy alone, respectively(P = 0.047). The OS was 26.5 and 30.0 months for patients harboring EGFR 19 del and L858 R mutations, respectively(P = 0.096).Conclusion The high OS rates of stage Ⅳ lung adenocarcinoma patients living in the Ordos area may be attributed to continuous improvements in EGFR testing and first-line TKI treatment rates. In the era of TKIs, chemotherapy for increasing OS times should be emphasized.

Dynamical and allosteric regulation of photoprotection in light harvesting complex Ⅱ

Major light-harvesting complex of photosystemⅡ(LHCⅡ)plays a dual role in light-harvesting and excited energy dissipation to protect photodamage from excess energy.The regulatory switch is induced by increased acidity,temperature or both.However,the molecular origin of the protein dynamics at the atomic level is still unknown.We carried out temperature-jump time-resolved infrared spectroscopy and molecular dynamics simulations to determine the energy quenching dynamics and conformational changes of LHCⅡtrimers.We found that the spontaneous formation of a pair of localα-helices from the 310-helix E/loop and the C-terminal coil of the neighboring monomer,in response to the increased environmental temperature and/or acidity,induces a scissoring motion of transmembrane helices A and B,shifting the conformational equilibrium to a more open state,with an increased angle between the associated carotenoids.The dynamical and allosteric conformation change leads to close contacts between carotenoid lutein 1 and chlorophyll pigment 612,facilitating the fluorescence quenching.Based on these results,we suggest a unified mechanism by which the LHCⅡtrimer controls the dissipation of excess excited energy in response to increased temperature and acidity,as an intrinsic result of intense sun light in plant photosynthesis.

Minimal-active-space multistate density functional theory for excitation energy involving local and charge transfer states

Multistate density functional theory(MSDFT)employing a minimum active space(MAS)is presented to determine charge transfer(CT)and local excited states of bimolecular complexes.MSDFT is a hybrid wave function theory(WFT)and density functional theory,in which dynamic correlation is first incorporated in individual determinant configurations using a Kohn–Sham exchangecorrelation functional.Then,nonorthogonal configuration-state interaction is performed to treat static correlation.Because molecular orbitals are optimized separately for each determinant by including Kohn–Sham dynamic correlation,a minimal number of configurations in the active space,essential to representing low-lying excited and CT states of interest,is sufficient to yield the adiabatic states.We found that the present MAS-MSDFT method provides a good description of covalent and CT excited states in comparison with experiments and high-level computational results.Because of the simplicity and interpretive capability through diabatic configuration weights,the method may be useful in dynamic simulations of CT and nonadiabatic processes.