Correlation of distribution characteristics and dynamic changes of gut microbiota with the efficacy of immunotherapy in EGFR-mutated non-small cell lung cancer.

BACKGROUND: The effects of gut microbiota and metabolites on the responses to immune checkpoint inhibitors (ICIs) in advanced epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) have been studied. However, their effects on EGFR-mutated (EGFR +) NSCLC remain unknown. METHODS: We prospectively recorded the clinicopathological characteristics of patients with advanced EGFR + NSCLC and assessed potential associations between the use of antibiotics or probiotics and immunotherapy efficacy. Fecal samples were collected at baseline, early on-treatment, response and progression status and were subjected to metagenomic next-generation sequencing and ultra-high-performance liquid chromatography-mass spectrometry analyses to assess the effects of gut microbiota and metabolites on immunotherapy efficacy. RESULTS: The clinical data of 74 advanced EGFR + NSCLC patients were complete and 18 patients' fecal samples were dynamically collected. Patients that used antibiotics had shorter progression-free survival (PFS) (mPFS, 4.8 vs. 6.7 months; P = 0.037); probiotics had no impact on PFS. Two dynamic types of gut microbiota during immunotherapy were identified: one type showed the lowest relative abundance at the response time point, whereas the other type showed the highest abundance at the response time point. Metabolomics revealed significant differences in metabolites distribution between responders and non-responders. Deoxycholic acid, glycerol, and quinolinic acid were enriched in responders, whereas L-citrulline was enriched in non-responders. There was a significant correlation between gut microbiota and metabolites. CONCLUSIONS: The use of antibiotics weakens immunotherapy efficacy in patients with advanced EGFR + NSCLC. The distribution characteristics and dynamic changes of gut microbiota and metabolites may indicate the efficacy of immunotherapy in advanced EGFR + NSCLC.

A Mechanism Study of Redox Reactions of the Ruthenium-oxo-polypyridyl Complex.

Over the years, RuIV(bpy)2(py)(O)2+([RuIVO]2+) has garnered considerable interest owing to its extensive use as a polypyridine mono-oxygen complex. However, as the active-site Ru=O bond changes during the oxidation process, [RuIVO]2+ can be used to simulate the reactions of various high-priced metallic oxides. In order to elucidate the hydrogen element transfer process between the Ruthenium-oxo-polypyridyl complex and organic hydride donor, the current study reports on the synthesis of [RuIVO]2+, a polypyridine mono-oxygen complex, in addition to 1H and 3H (organic hydride compounds) and 1H derivative: 2. Through 1H-NMR analysis and thermodynamics- and kinetics-based assessments, we collected data on [RuIVO]2+ and two organic hydride donors and their corresponding intermediates and established a thermodynamic platform. It was confirmed that a one-step hydride transfer reaction between [RuIVO]2+ and these organic hydride donors occurs, and here, the advantages and nature of the new mechanism approach are revealed. Accordingly, these findings can considerably contribute to the better application of the compound in theoretical research and organic synthesis.

Thermodynamics Evaluation of Selective Hydride Reduction for α,ß-Unsaturated Carbonyl Compounds.

The selective reduction of α,ß-unsaturated carbonyl compounds is one of the core reactions and also a difficult task for organic synthesis. We have been attempting to study the thermodynamic data of these compounds to create a theoretical basis for organic synthesis and computational chemistry. By electrochemical measurement method and titration calorimetry, in acetonitrile at 298 K, the hydride affinity of two types of unsaturated bonds in α,ß-unsaturated carbonyl compounds, their single-electron reduction potential, and the single-electron reduction potential of the corresponding radical intermediate are determined. Their hydrogen atom affinity, along with the hydrogen atom affinity and proton affinity of the corresponding radical anion, is also derived separately based on thermodynamic cycles. The above data are used to establish the corresponding "Molecule ID Card" (Molecule identity card) and analyze the reduction mechanism of unsaturated carbonyl compounds. Primarily, the mixture of any carbonyl hydride ions and Ac-tempo+ will stimulate hydride transfer process and create corresponding α,ß-unsaturated carbonyl compounds and Ac-tempoH from a thermodynamic point of view.

New Insight into the Mechanism of NADH Model Oxidation by Metal Ions in Nonalkaline Media.

For a long time, it has been controversial that the three-step (e-H+-e) or two-step (e-H•) mechanism was used for the oxidation of nicotinamide adenine dinucleotide coenzyme (NADH) and its models by metal ions in nonalkaline media. The latter mechanism has been accepted by the majority of researchers. In this work, 1-benzyl-1,4-dihydronicotinamide (BNAH) and 1-phenyl-l,4-dihydronicotinamide are used as NADH models and ferrocenium (Fc+) metal ion as an electron acceptor. The kinetics for oxidation of the NADH models by Fc+ in pure acetonitrile was monitored by using UV-vis absorption and a quadratic relationship between kobs and the concentrations of NADH models was found for the first time. The rate expression of the reactions developed according to the three-step mechanism is quite consistent with the quadratic curves. The rate constants, thermodynamic driving forces, and kinetic isotope effects of each elementary step for the reactions were estimated. All results supported the three-step mechanism. The intrinsic kinetic barriers of the proton transfer from BNAH+• to BNAH and the hydrogen-atom transfer from BNAH+• to BNAH+• were estimated by using Zhu equation; the results showed that the former is 11.8 kcal/mol and the latter is larger than 24.3 kcal/mol. It is the large intrinsic kinetic barrier of the hydrogen-atom transfer that makes the reactions choose the three-step rather than two-step mechanism. Further investigation of the factors affecting the intrinsic kinetic barrier of chemical reactions indicated that the large intrinsic kinetic barrier of the hydrogen-atom transfer originated from the repulsion of positive charges between BNAH+• and BNAH+•. The greatest contribution of this work is the discovery of the quadratic dependence of kobs on the concentrations of the NADH models, which is inconsistent with the conventional viewpoint of the "two-step mechanism" on the oxidation of NADH and its models by metal ions in the nonalkaline media.

[Blood Transfusion Selection in Patients with Autoimmune Hemolytic Anemia Producing Class Antibodies].

OBJECTIVE: To analyze the reasons for the incompatibility of cross matching in lymphoma patients complicated by autoimmune hemolytic anemia (AIHA), and to provide compatible blood to patients for multiple blood transfusion. METHODS: The test tube method was used for routine identification of ABO blood group, Rh typing and direct anti-globulin test; the patients antibody was identified by saline water method, micro column gel card; and the saline water method, Polybrene method and antiglobulin method were used for blood cross matching test of the patients. RESULTS: In the serum of the patient, positive autoantibodies were detected, in the elution, the Ce antibody was detected. After infusion of the corresponding antigen-negative blood, the patient's hemoglobin level was significantly improved. CONCLUSION: Only firstly accurately identifying antibodies existed in serum and elution, then selecting corresponding antigen negative blood, can ensure the safety and effectiveness of blood transfusion.

Controlling liquid crystal pretilt angle with photocurable prepolymer and vertically aligned substrate.

We demonstrate a new approach to control the pretilt angle of liquid crystals (LCs) with photocurable prepolymer in a cell fabricated with vertically aligned substrates. During UV exposure, prepolymer approaches and is polymerized on the substrate surfaces because of the vertical phase separation induced by differences in the surface tensions of the employed materials. After polymerization, the polymer structure formed on the substrate alters its surface polarity and changes the pretilt angle of the LC cell. The LC pretilt angle can be controlled from 87.3° to 2.5° when the prepolymer concentration ranges from 0 wt% to 2.5 wt%.

Design, synthesis, and biological evaluation of crenatoside analogues as novel influenza neuraminidase inhibitors.

Natural products, especially derived from TCMH, have been found to exert antiviral effects against influenza virus. Crenatoside, a phenylethanoid glycoside from Pogostemon cablin Benth, which has been shown as a novel effective NA inhibitor previously, is considered as the leading compound for our further SARs studies. This work presented design, synthesis of novel crenatoside analogues from readily available d-Glucose and l-rhamnose in a convergent manner. Furthermore, their biological activities and SARs were also investigated. Especially, compound 2 h showed impressive IC50 = 27.77 µg/mL against NAs, which is 3 folds more potent than the leading compound crenatoside (IC50 = 89.81 µg/mL). These results would promise their therapeutic potential for influenza disease.

Polarization-insensitive liquid crystal microlens array with dual focal modes.

We demonstrate a liquid crystal (LC) microlens array (MLA) fabricated by LCs possessing negative dielectric anisotropy, in conjunction with a cell with a three-electrode structure. The presented LC MLA is polarization-insensitive and can be operated in both concave and convex modes. The shortest focal length of the LC MLA is -2.54 and 2.22 mm in concave and convex mode, respectively. Disclination lines that are usually observed in conventional hole-patterned LC lens can also be avoided because of the vertical alignment treatment of LCs.

[Effect of five species of Epimedium on growth of cartilage and proliferation of cartilage cell in vitro].

OBJECTIVE: To observe the effect of Epimedium brevicornum, E. sagittatum, E. koreanum, E, wushanense and E. elongntum on the growth of cartilage and proliferation of cartilage cell in vitro. METHOD: According to the paired design method, either femur of each chichen embryo was put into the control tube with the medium containing no Epimedium injection, and the other was put into the treated tube with the medium containing 3% Epimedium injection. The length and weight of cultured cartilage and proliferation of cartilage cell (MTY method) were used as the indices to observe the cartilage biological activities of the five species of Epimedium in culture. RESULT: The results showed that the indices of length, weight and MTT in the E. brevicornum and E. sagittatum group were significantly higher than those in the contral group, but the above indices in groups E. koreanum, E. wushanens and E. elongntum were similar to those of the control with no statistical difference. CONCLUSION: E. brevicornum and E. sagittatum can improve the growth of cartilage and proliferation of cartilage cell in vitro, and other three Epimedium have not the same effect in this test.