Ultra-flat bands at large twist angles in group-V twisted bilayer materials.

Flat bands in 2D twisted materials are key to the realization of correlation-related exotic phenomena. However, a flat band often was achieved in the large system with a very small twist angle, which enormously increases the computational and experimental complexity. In this work, we proposed group-V twisted bilayer materials, including P, As, and Sb in the ß phase with large twist angles. The band structure of twisted bilayer materials up to 2524 atoms has been investigated by a deep learning method DeepH, which significantly reduces the computational time. Our results show that the bandgap and the flat bandwidth of twisted bilayer ß-P, ß-As, and ß-Sb reduce gradually with the decreasing of twist angle, and the ultra-flat band with bandwidth approaching 0 eV is achieved. Interestingly, we found that a twist angle of 9.43° is sufficient to achieve the band flatness for ß-As comparable to that of twist bilayer graphene at the magic angle of 1.08°. Moreover, we also find that the bandgap reduces with decreasing interlayer distance while the flat band is still preserved, which suggests interlayer distance as an effective routine to tune the bandgap of flat band systems. Our research provides a feasible platform for exploring physical phenomena related to flat bands in twisted layered 2D materials.

Serum exosomal miR-16-5p functions as a tumor inhibitor and a new biomarker for PD-L1 inhibitor-dependent immunotherapy in lung adenocarcinoma by regulating PD-L1 expression.

OBJECTIVES: We aimed at investigating whether serum exosomal miR-16-5p could be utilized as an immunotherapy biomarker in lung adenocarcinoma (LUAD) patients administered by programmed cell death ligand-1 (PD-L1) inhibitors, and to evaluate its functions in LUAD progression. METHODS: Sixty LUAD sufferers and 20 healthy controls (HCs) were covered in this work. We applied both IHC and WB to examine PD-L1 level in clinical tissue samples and utilized WB to quantify PD-L1 expression in LUAD cells and LUAD xenograft tissues, respectively. Transmission electron microscopy (TEM), WB, and nanoparticle tracking analysis (NTA) were executed to confirm the exosomes isolated from serum specimens and cell culture media. To quantify of exosomal miR-16-5p level from serum and culture medium of cultured cell, qRT-PCR experiment was utilized. The connection between tissue PD-L1 level and serum exosomal miR-16-5p expression in PD-L1-positive sufferers administered by PD-L1 inhibitors was verified using Spearman correlation coefficient analysis. In addition, the overall survival (OS) and progression-free survival (PFS) rates among PD-L1 inhibitor managed sufferers were acquired through a follow-up visit. Finally, we used a group of assays, including 5-bromo-2'-dexoyuridine (BrdU) and colony formation test, wound healing experiment, flow cytometry, and nude mice xenograft experiment, to explore the functions of circulating exosomal miR-16-5p on LUAD cell proliferation, apoptosis, and migration, as well as tumor development, respectively. RESULTS: PD-L1 expression was positively related to T stage (tumor size stage), and PD-L1 inhibitor treatment reduced the PD-L1 expression and mitigated T stage in PD-L1-positive LUAD sufferers. For PD-L1-positive LUAD sufferers, elevated PD-L1 expression or reduced serum exosomal miR-16-5p level were linked to longer PFS and OS upon PD-L1 inhibitor treatment. The number of exosomes in patient's serum was more than that in the serum of healthy individuals, and PD-L1 inhibitor treatment decreased the number of serum-derived exosomes in PD-L1-positive LUAD sufferers. Exosome-derived miR-16-5p was downregulated in patient's serum and cell culture medium, and this was negatively linked to tumor stage and PD-L1 expression. Meanwhile, PD-L1 inhibitor treatment could increase the serum exosomal miR-16-5p expression, and the expression change of serum exosomal miR-16-5p was diametrically related to PD-L1 after the treatment. Moreover, the overexpression of PD-L1 accelerated tumor growth and decreased the exosomal miR-16-5p content in cell culture media, while exosomal miR-16-5p overexpression in cell culture media inhibited tumor development by decreasing the PD-L1 expression. Exosomal miR-16-5p overexpression in cell culture media also depressed LUAD cell proliferation and migration, and stimulated cell apoptosis, especially in the cells which cultured in the mediums with PD-L1 inhibitor in vitro. CONCLUSIONS: Serum exosomal miR-16-5p may be a latent tumor inhibitor and a new biomarker for PD-L1 inhibitor-dependent immunotherapy in LUAD by regulating the PD-L1 expression.

Development of Dipolarophiles for Catalytic Asymmetric Cycloadditions through Pd-π-Allyl Zwitterions.

The development of new and efficient methodology for the construction of optically active molecules is of great interest in both synthetic organic and medicinal chemistry fields. To this end, the personal account summarizes our studies on the development of electron-deficient alkenes, allenes, and alkynes containing single activator as new dipolarophiles for Pd-catalyzed asymmetric cycloaddition reactions. These new dipolarophiles can participate in Pd-catalyzed asymmetric [3+2] and [4+2] cycloadditions through Pd-π-allyl 1,3- and 1,4-zwitterions in-situ generated by the reaction of Pd(0) catalyst with vinyl aziridines, vinyl epoxides, vinyl cyclopropanes, 4-vinyl-1,3-dioxan-2-ones, and vinyl benzoxazinanones. These [3+2] and [4+2] cycloadditions provide efficient approaches to a wide range of enantiomerically enriched five- and six-membered ring compounds containing contiguous chiral centers with high to excellent chemo-, diastereo-, and enantioselectivities. The utilities of these protocols are demonstrated by transformation of the cycloadducts into other useful chiral building blocks. DFT calculations reveal the dissimilar reactivity of different electron deficient alkenes and rationalize the mechanism and stereo-control of the reaction. A Pd-catalyzed inverse [3+2] cycloaddition is disclosed.

Survival Benefit and Genetic Profile of Pemetrexed as Initial Chemotherapy in Selected Chinese Patients With Advanced Lung Adenocarcinoma.

Objective: This study investigated survival in selected Chinese patients with advanced lung adenocarcinoma who received initial chemotherapy with pemetrexed. We also explored the relationship between genetic biomarkers and pemetrexed efficacy. Methods: We retrospectively collected patients (n = 1,047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed. Results: The median DOT was 9.1 months (95% CI: 8.5-9.8), and the median OS was 26.2 months (95% CI: 24.2-28.1). OS was positively correlated with DOT (r = 0.403, P < 0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and EGFR/ALK/ROS1 status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: TP53 (54.5%), EGFR (50.0%), MYC (18.2%), and PIK3CA (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT > 6.9 months set was associated with PIK3CA, ALK, BRINP3, CDKN2A, CSMD3, EPHA3, KRAS, and RB1 mutations, while ERBB2 mutation was observed only in the DOT ≤ 6.9 months set. Conclusion: This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration.

[Correlation of CD4+CD29+ regulatory T cells with recurrence and survival time in patients with non-small cell lung cancer].

OBJECTIVE: To investigate the correlation of CD4+CD29+ regulatory T cells (Treg) with tumor recurrence and survival time in patients with non-small cell lung cancer (NSCLC). METHODS: Fifty-nine patients with NSCLC treated with radical surgery were followed up for 5 years. Blood Treg cells were examined during the follow-up using flow cytometry (FCM). The sensitivity and specificity of Treg cells to predict recurrence of NSCLC were analyzed using receiver-operating characteristic (ROC) curve and compared with those of carcinoembryonic antigen (CEA) and cytokeratin21-1 (Cyfra21-1). The influences of gender, age, occupation and radiotherapy on survival time of the patients were analyzed with Kaplan-Meier method. RESULTS: Among the 59 patients, the shortest survival time was 23 months while the longest time was over 67 months. Nineteen patients had NSCLC recurrence, and 17 (28.81%) of them died of metastasis during the follow-up. The frequencies of blood Treg cells in patients who did not receive radiotherapy and in patients with tumor recurrence were significantly higher than those in patients receiving radiotherapy and in patients free of recurrence (P=0.000). ROC curves showed that the area under curve (AUC) lowered in the order of Treg cells, Cyfra21-1, CEA (P=0.002, 0.006 and 0.013, respectively) with 95% confidence interval (CI) of 0.649-0.981, 0.621-0.936 and 0.584-0.944, respectively. At the cut-off value of 7.53%, the sensitivity and specificity of Treg cells to predict NSCLC recurrence was 91.42% and 87.59%, respectively. The five-year survival rate of the 59 patients was 71.18% (42/59), and Kaplan-Meier analysis revealed a longer survival time in female patients (P=0.038), in patients below 50 years of age (P=0.013), in patients not engaging in mental work (P=0.029), and in patients receiving radiotherapy (P=0.003). CONCLUSION: Treg cells has a better efficiency than Cyfra21-1 and CEA to predict tumor recurrence in patients with NSCLC following radical surgery. The male gender, an age beyond 50 years, an occupation of mental work, and failure to receive radiotherapy are all risk factors for recurrence of NSCLC.

Research on Ground-Based LWIR Hyperspectral Imaging Remote Gas Detection.

The new progress of ground-based long-wave infrared remote sensing is presented, which describes the windowing spatial and temporal modulation Fourier spectroscopy imaging in details. The prototype forms the interference fringes based on the corner-cube of spatial modulation of Michelson interferometer, using cooled long-wave infrared photovoltaic staring FPA (focal plane array) detector. The LWIR hyperspectral imaging is achieved by the process of collection, reorganization, correction, apodization, FFT etc. from data cube. Noise equivalent spectral radiance (NESR), which is the sensitivity index of CHIPED-1 LWIR hyperspectral imaging prototype, can reach 5.6 x 10⁻8 W · (cm⁻¹ · sr · cm²)⁻¹ at single sampling. The data is the same as commercial temporal modulation hyperspectral imaging spectrometer. It can prove the advantage of this technique. This technique still has space to be improved. For instance, spectral response range of CHIPED-1 LWIR hyperspectral imaging prototype can reach 11. 5 µm by testing the transmission curve of polypropylene film. In this article, choosing the results of outdoor high-rise and diethyl ether gas experiment as an example, the authors research on the detecting method of 2D distribution chemical gas VOC by infrared hyperspectral imaging. There is no observed diethyl ether gas from the infrared spectral slice of the same wave number in complicated background and low concentration. By doing the difference spectrum, the authors can see the space distribution of diethyl ether gas clearly. Hyperspectral imaging is used in the field of organic gas VOC infrared detection. Relative to wide band infrared imaging, it has some advantages. Such as, it has high sensitivity, the strong anti-interference ability, identify the variety, and so on.

MMP-14 overexpression correlates with poor prognosis in non-small cell lung cancer.

Matrix metalloproteinase-14 (MMP-14) has been demonstrated to play an important role in tumor progression. The aim of this study was to analyze the correlation between MMP-14 expression and clinicopathologic features and its prognostic significance in non-small cell lung cancer (NSCLC). Immunohistochemical staining for MMP-14 protein was performed in 104 patients with NSCLC. High levels of MMP-14 protein were positively correlated with the status of clinical stage (I-II vs. III-IV; P < 0.001), N classification (N0-N1 vs. N2-N3; P < 0.001), distant metastasis (no vs. yes; P = 0.014), and differentiated degree (high vs. low or undifferentiated; P = 0.001). The patients with higher MMP-14 expression of protein had shorter survival time than patients with low MMP-14 expression. Multivariate analysis indicated that the level of MMP-14 expression was an independent prognostic indicator (P < 0.001) for the survival of patients with NSCLC. In conclusion, MMP-14 is a potential unfavorable prognostic factor for patients with NSCLC.

[Application of nonlinear mixed models in Logistic regression with random effect in clinical trials].

OBJECTIVE: To explore the application of nonlinear mixed models fitting logistic regression in clinical trials. METHODS: Two clinical trials were selected to exemplify the method for fitting nonlinear logistic regression using nonlinear mixed models by running NLMIXED procedure in SAS. RESULTS: All the parameters and their standard errors were estimated, and each factor could be properly interpreted. CONCLUSION: Nonlinear mixed models in which both fixed and random effects enter nonlinearly can fit nonlinear logistic regression. These models provide effective methods to analyze the binary data in clinical trials.

[Variation patterns of Coptis teeta biomass and its major active compounds along an altitude gradient].

An investigation was made on the biomass and major active compounds of wild and cultivated Coptis teeta along an altitude gradient in Nujiang of Yunnan. The results showed that the rhizome and root biomass of wild C. teeta increased from the altitude 2100 m to 2700 m, but the difference was not significant. The rhizome biomass of cultivated C. teeta was 87.5 kg x hm(-2) at 2600 m and 97.0 kg x hm(-2) at 2700 m, being much higher than 34.8 kg x hm(-2) at 2300 m (P < 0.05). At the same altitudes (2300 m, 2600 m, and 2700 m), cultivated C. teeta had higher rhizome and root biomass than wild C. teeta, but the difference was not significant. There was a significant positive correlation between the rhizome and root biomass and the whole plant biomass of wild C. teeta. Wild C. teeta had the highest content of berberine in rhizome (4.60%) and root (1.93%) at 2700 m, plamatinein in rhizome, and jatrorrhizine in rhizome and root at 2600-2700 m, and plamatinein in root at 2 300 m; while cultivated C. teeta had the highest content of berberine in rhizome (4.41%) and root (1.90%) at 2600 m, plamatinein in rhizome and root, and berberine and jatrorrhizine in root at 2600-2700 m, and jatrorrhizine in rhizome at 2300 m. The content of major active compounds in wild C. teeta rhizome and root were significantly higher at 2600 m and 2700 m than at 2100 m and 2300 m (P < 0.05), and the rhizome biomass, root biomass, leaf biomass, total biomass, height, and canopy diameter of wild C. teeta ramet increased first and decreased then from the altitude 2100 m to 2700 m. Increasing planting density and enhancing artificial management could improve the biomass of C. teeta and its major active compounds concentrations.

[Late course conformal radiotherapy combined with chemotherapy for stage III and IV a nasopharyngeal carcinoma].

OBJECTIVE: To evaluate the effect and acute toxicity of late course conformal radiotherapy combined with chemotherapy for stage III and IV a nasopharyngeal carcinoma (NPC). METHODS: Ninety-six patients with stage III and IV a NPC were randomly divided into 2 groups: test group (n = 46, undergoing late course conformal radiotherapy combined with chemotherapy) and control group (n = 50, undergoing conventional radiotherapy). Both groups were treated with one-period chemotherapy, including cisplantin, 5-fluouracil, and calcium folinate, before and after the radiotherapy. The radiotherapy of the test group consisted of 2 phases: 36.0 approximately 40.0 Gy in 18 approximately 20 fractions over 3.5-4 weeks as the first phase using conventional technique was delivered with 2 lateral opposing faciocervical fields, and then 30.0-46.0 Gy in 15-23 fractions over 3-4.5 weeks as the second phase using three-dimensional conformal radiotherapy (3D-CRT). RESULTS: The rates of complete remission (CR), partial remission (PR), and no change (NC) of the test group were 95.65%, 4.35%, and 0, not significantly different from those in the control group (90.00%, 10.00%, and 0, P = 0.287). The 1-year survival rate of the test group was 100%, not significantly different from that of the control group (96.00%, P = 0.170). The nasopharyngeal 1 year control rate of the test group was 97.83%, significantly higher than that of the control group (78.00%, P = 0.03). The distant metastasis rate of the test group was 8.70%, not significantly different from that of the control group (12.00%, P = 0.596). The incidence rates of radiological caries and irradiation-induced otitis media in the test group was 4.25% and 17.39% respectively, both significantly lower than those in the control group (26.00% and 42.00% respectively, P = 0.004 and P = 0.000). There was no significant difference in the incidence of nausea, vomiting, leukopenia, and severity of acute mucositis between these 2 groups. CONCLUSION: Late course conformal radiotherapy combined with chemotherapy effectively improves the disease control, delays the distant metastasis, and alleviates radioactivity damnification.

[Efficacy of concurrent radio-chemotherapy and chemotherapy alone in the treatment of locally advanced non-small-cell lung cancer].

OBJECTIVE: To evaluate the effect and acute toxicity of concurrent radio-chemotherapy, by NVB and DDP, plus concurrent radiotherapy in comparison with chemotherapy alone in the treatment of inoperable locally advanced non-small-cell lung cancer (LANSCLC). METHODS: Sixty-four patients with inoperable LANSCLC were randomly divided by envelope method into two groups: concurrent radio-chemotherapy group (n = 33) and conventional chemotherapy group (n = 31). The patients in conventional chemotherapy group were treated by NP regimen (NVB + DDP): NVB 25 mg/m(2), d1, 8 and DDP 25-30 mg/m(2) d1-3. In the radio-chemotherapy group by NP regimen plus conventional radiotherapy by (60)Co: 64-68 Gy/2 Gy x 5/w x 6-7w. RESULTS: All patients completed the treatment schedule. The overall response rate (CR + PR) in the radio-chemotherapy group was significantly higher than that in the conventional chemotherapy group: 81.8% vs 45.2%, (P < 0.01) with 1- and 2-year survival rates of 69.7% vs 38.7% (P < 0.05) and 39.4% vs 16.1% (P < 0.05). without any significant difference in the acute toxicity between two groups (P > 0.05). CONCLUSION: Compared with conventional chemotherapy (NVP and DDP), concurrent radio-chemotherapy (NVP and DDP plus concurrent radiotherapy) is more effective and tolerable for the inoperable locally advanced non-small-cell lung cancer.