Comparison of Efficacy and Safety of First-Line Treatment Options for Unresectable Stage III Non-Small Cell Lung Cancer: A Retrospective Analysis.

Background: Based on PACIFIC trial, durvalumab as consolidation therapy following concurrent chemoradiotherapy (cCRT) has been a new standard treatment for unresectable stage III non-small cell lung cancer (NSCLC). In clinical applications, there are heterogeneous adjustments or novel strategies following specialized discussions in experienced multidisciplinary teams. This study retrospectively compared the efficacy and safety of different first-line treatments for unresectable stage III NSCLC. Methods: We retrospectively analyzed 397 patients who received first-line treatment for unresectable stage III NSCLC. Comparisons and statistical analyses of treatment were made in terms of efficacy and safety. Adverse events and responses were assessed using CTCAE v5.0 and RECIST v1.1. The progression-free survival (PFS) was estimated using the Kaplan-Meier method or the Cox survival regression model and compared using the log-rank test. Results: In wild-type driver genes group, the objective response rate (ORR), disease control rate (DCR), and median PFS (mPFS) were prolonged in the radiotherapy group compared to those in the nonradiotherapy group (ORR: 50.94% vs. 30.06%, p < 0.001; DCR: 98.11% vs. 80.37%, p < 0.001; and mPFS: 21.00 vs. 8.20 months, p < 0.001). The incidence of pneumonia at any grade in the radiotherapy group was higher than that in the nonradiotherapy group (9.43% vs. 2.45%, p = 0.008). In the radiotherapy group, the chemoradiotherapy (CRT) plus immunotherapy subgroup had longer mPFS than the CRT subgroup, with increased toxicity at any grade (24.60 vs. 17.90 months, p = 0.025, and 83.17% vs. 65.52%, p = 0.011). In the nonradiotherapy group, the DCR and mPFS were higher in the chemotherapy plus immunotherapy subgroup than in the chemotherapy subgroup, with increased toxicity at any grade (DCR: 93.67% vs. 67.86%, p < 0.001; mPFS: 13.53 vs. 5.07 months, p < 0.001; and 68.35% vs. 41.67%, p = 0.001). In the mutant driver genes group, the efficacy did not significantly differ among the radiotherapy subgroup, targeted therapy subgroup, and radiotherapy plus targeted therapy subgroup (ORR: p = 0.633; mPFS: p = 0.450). Conclusions: For unresectable stage III NSCLC patients with wild-type driver genes, the combination of radiotherapy and immunotherapy in the initial treatment was essential to significantly improve the efficacy. For patients with mutant driver genes, radiotherapy, targeted therapy, and the combination of radiotherapy and targeted therapy showed similar short-term efficacy.

Biochar amendment reduces biological nitrogen fixation and nitrogen use efficiency in cadmium-contaminated paddy fields.

Cadmium (Cd) contamination poses a considerable threat to human health through grain enrichment and limits biological nitrogen fixation (BNF) in paddy fields. Biochar has shown great potential for agricultural soil remediation because it inactivates Cd, but uncertainties remain as to how biochar amendments affect BNF and grain N use efficiency in paddies. To elucidate these issues, we investigated the effects of biochar amendment on the structure and function of diazotrophic bacterial communities in different rice growth stages in Cd-contaminated paddy fields, and evaluated the contribution of BNF to grain N use efficiency under biochar amendment. The results showed that biochar amendment significantly increased the abundance of diazotrophic bacteria in the tillering and jointing stages. Furthermore, the community structure of soil diazotrophic bacteria markedly changed with biochar amendment, with a significant reduction in the abundances of Euryarchaeota, Desulfobacterales (Proteobacteria), and Sphingomonadales (Bacteroidetes) in the tillering stage. Changes in the soil carbon/nitrogen (C/N) ratio was the main factor driving diazotrophic microbial community characteristics caused by the release of available C from biochar at the tillering stage, rather than the Cd. Moreover, biochar amendment increased the efficiency of BNF (especially for autotrophic N2 fixation) in the vegetative phase of rice growth. Notably, biochar amendment significantly decreased BNF efficiency during the filling stage and reduced grain N use efficiency. The limited available nutrients in biochar and the toxicity of polycyclic aromatics and phenols in biochar-derived dissolved organic matter were responsible for the varied impacts of biochar on BNF in different rice growth stages. For the first time, we report that biochar amendment in paddy soils reduces Cd toxicity but also inhibits BNF and thereby decreases N use efficiency. Therefore, before applying biochar to inactivate Cd in paddy fields, there should be a trade-off between agricultural production and ecological safety to achieve sustainable agriculture.

Comparison of Efficacy and Safety of Second-Line Treatment Options for Advanced Small-Cell Lung Cancer: A Retrospective Analysis.

OBJECTIVE: As monotherapy such as topotecan has reached a plateau of effectiveness, new second-line treatments based on experience have been used in clinical application. This study compared the efficacy and safety of different second-line treatments for advanced small-cell lung cancer (SCLC). METHODS: A total of 380 patients with advanced SCLC were screened selectively in the retrospective study. Adverse events and patient responses were assessed using Common Terminology Criteria for Adverse Events v5.0 and Response Evaluation Criteria for Solid Tumors v1.1. The progression-free survival (PFS) was estimated using the Kaplan-Meier method or Cox survival regression model and compared using the log-rank test. RESULTS: In the platinum-resistant group, disease control rate (DCR) and median PFS (mPFS) were prolonged in the combination group versus single-agent group (DCR: 49.24% vs 24.39%, P = .004; mPFS: 3.73 vs 1.90 months, P < .001). Grade 3/4 toxicity was similar between the 2 groups (P = .683). The mPFS did not differ among single-agent groups (P = .380). No significant difference was observed in mPFS of different combination therapy groups (P = .170). In terms of platinum-based chemotherapy, the DCR and mPFS were prolonged in irinotecan-platinum group versus taxol-platinum group (DCR: 56.14% vs 9.09%, P = .004; mPFS: 3.87 vs 1.93 months, P = .012). Grade 3/4 toxicity was similar between the 2 groups (P = .614). The mPFS was prolonged in the chemotherapy plus immunotherapy group versus single-agent chemotherapy group (P = .003). In the platinum-sensitive group, the mPFS did not differ between the combination group and single-agent group (P = .200). The mPFS did not differ among different single-agent groups (P = .260) or combination groups (P = .150). There was no difference in mPFS among different platinum-based chemotherapy groups (P = .830). CONCLUSIONS: For patients with platinum-resistant SCLC, combination therapy has shown better efficacy and acceptable toxicity profile than monotherapy. Among combination therapies, irinotecan-platinum has shown better efficacy than taxol-platinum. For patients with platinum-sensitive SCLC, the efficacy of different single-agent or combination therapies was similar.

Enhancing Water Resistance and Mechanical Properties of Cemented Soil with Graphene Oxide.

Although cemented soil as a subgrade fill material can meet certain performance requirements, it is susceptible to capillary erosion caused by groundwater. In order to eliminate the hazards caused by capillary water rise and to summarize the relevant laws of water transport properties, graphene oxide (GO) was used to improve cemented soil. This paper conducted capillary water absorption tests, unconfined compressive strength (UCS) tests, softening coefficient tests, and scanning electron microscope (SEM) tests on cemented soil using various contents of GO. The results showed that the capillary water absorption capacity and capillary water absorption rate exhibited a decreasing and then increasing trend with increasing GO content, while the UCS demonstrated an increasing and then decreasing trend. The improvement effect is most obvious when the content is 0.09%. At this content, the capillary absorption and capillary water absorption rate were reduced by 25.8% and 33.9%, respectively, and the UCS at 7d, 14d, and 28d was increased by 70.32%, 57.94%, and 61.97%, respectively. SEM testing results demonstrated that GO reduces the apparent void ratio of cemented soil by stimulating cement hydration and promoting ion exchange, thereby optimizing the microstructure and improving water resistance and mechanical properties. This research serves as a foundation for further investigating water migration and the appropriate treatment of GO-modified cemented soil subgrade.

Efficacy and safety analysis of immune checkpoint inhibitor rechallenge therapy in locally advanced and advanced non-small cell lung cancer: a retrospective study.

Background: Immune checkpoint inhibitors (ICIs) have dramatically changed the first-line treatment pattern of non-small cell lung cancer (NSCLC) without driver gene alterations. However, the optimal choice for second-line treatment after initial treatment with ICIs is unclear. This study aimed to clarify the efficacy and safety of ICI rechallenge therapy in locally advanced and advanced NSCLC. Methods: We retrospectively analyzed the histories of 224 patients with locally advanced or advanced NSCLC treated with programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors alone or in combination with chemotherapy and/or antiangiogenic therapy in first-line treatment. Progression-free survival 2 (PFS2) was the time from the first defined progress disease (PD) to the second disease progression or death. Efficacy evaluation was performed directly in accordance with RECIST v1.1 criteria. Adverse events (AEs) were graded following the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Survival data were estimated using the Kaplan-Meier method or Cox survival regression model and compared using the log-rank test in overall cohort and other subgroups. Results: There were no significant differences in objective response rate (ORR) and median PFS2 (mPFS2) between the ICI rechallenge group and non-rechallenge group (ORR: 10.3% vs. 15.3%, P=0.308; mPFS2: 5.33 vs. 4.40 months, P=0.715). And the ICI rechallenge group showed no new safety signals compared with non-rechallenge group. In ICI rechallenge group, patients resistant to first-line immunotherapy had a lower ORR and shorter PFS2 compared with those who responded to initial ICIs treatment (ORR: 7.0% vs. 17.6%, P=0.038; mPFS2: 3.68 vs. 5.91 months, P=0.014). No significant difference in mPFS2 was observed among different second-line treatment groups (P=0.362). Radiotherapy in second-line treatment and ICI rechallenge therapy were not the main factors affecting PFS2. Conclusions: ICI rechallenge therapy beyond disease progression did not improve clinical outcomes in patients with NSCLC, but no new safety signals emerged. However, patients with favorable response to initial ICIs treatment still showed significant efficacy of subsequent ICI rechallenge therapy.

Synthesis of well-defined star, star-block, and miktoarm star biodegradable polymers based on PLLA and PCL by one-pot azide-alkyne click reaction.

Based on the "arm-first" strategy, ring-opening polymerization (ROP) and one-pot azide-alkyne click reaction, well-defined star-shaped polymers with different architectures have been successfully synthesized, including the star homopolymers four-arm star-shaped polycaprolactone (4sPCL) and four-arm star-shaped poly(l-lactic acid) (4sPLLA), star-block copolymer 4sPCL-b-PLLA and miktoarm star-shaped copolymer PCL2PLLA2. The star homopolymers 4sPCL and 4sPLLA were synthesized by a click reaction of an azide small molecule initiator and HC[triple bond, length as m-dash]C-PCL or HC[triple bond, length as m-dash]C-PLLA. The star-block copolymer 4sPCL-b-PLLA was synthesized by a click reaction of an azide small molecule initiator and the block copolymer HC[triple bond, length as m-dash]C-PCL-b-PLLA. The miktoarm star polymer PCL2PLLA2 was synthesized by a one-pot azide-alkyne click reaction of simultaneous addition of equal proportions of HC[triple bond, length as m-dash]C-PCL and HC[triple bond, length as m-dash]C-PLLA. The structures of these star-shaped polymers have been confirmed by NMR, FT-IR and GPC. Furthermore, the melting and crystallization behaviors investigated using DSC and WXRD also confirm the formation of star-shaped polymers with different architectures.

[Influence of inert nuclei (La3+, Y3+ and Gd3+) on fluorescence of europium complex with phenylglyoxylic acid and phenathroline].

Three series of dinuclear complexes (Eux RE(1-x) L3 phen) of phenylglyoxylic acid and phenathroline with different molar ratios of Eu3+ to inert nuclei (RE = La3+, Y3+ and Gd3+) were synthesized. Their excitation and emission spectra were studied. The excitation spectra showed that the optimum excitation wavelengths of the complexes are all in the range of 350-360 nm, which belong to the excitation peaks of ligands, and the weak excitation peak of Eu3+ is at about 398 nm; The emission spectra showed that there are five emission bands at about 583, 595, 617, 654 and 703 nm respectively for all the complexes, due to (5)D0 - (7)F0, (5)D0 - (7)F1, (5)D0 - (7)F2, (5)D0 - (7)F3 and (5)D0 - (7)F4 transitions of Eu3+ respectively. The authors also found that the emission peak positions of Eu3+ shift the most in the complexes Eu(x) La(1-x) L3 phen, the position of (5)D0 - (7)F2 transition shifts 5.2 nm when the molar ratio of Eu3+:La3+ is 0.3: 0.7, but the addition of Y3+ and Gd3+ makes the emission peak positions of Eu3+ change less than that of La3+. Meanwhile the luminescence intensity of Eu3+ can be most enhanced by La3+ in all the complexes. The conclusion we found in the present paper could help search the luminescence materials with low cost and good luminescence properties.

3D Navigation on Impossible Figures via Dynamically Reconfigurable Maze.

Previous research on impossible figures focuses extensively on single view modeling and rendering. Existing computer games that employ impossible figures as navigation maze for gaming either use a fixed third-person view with axonometric projection to retain the figure's impossibility perception, or simply break the figure's impossibility upon view changes. In this paper, we present a new approach towards 3D gaming with impossible figures, delivering for the first time navigation in 3D mazes constructed from impossible figures. Such result cannot be achieved by previous research work in modeling impossible figures. To deliver seamless gaming navigation and interaction, we propose i) a set of guiding principles for bringing out subtle perceptions and ii) a novel computational approach to construct 3D structures from impossible figure images and then to dynamically construct the impossible-figure maze subjected to user's view. In the end, we demonstrate and discuss our method with a variety of generic maze types.

[Synthesis, structure characterization and, fluorescence studies of the complexes of europium with phenylglyoxylic acid, 1,10-phenanthroline and triphenyl phosphine oxide].

Three novel europium complexes, Eu-L, EuL3phen and EuL2 (TPPO)2NO3, were synthesized (HL = phenylglyoxylic, phen= 1,10-phenanthroline, and TPPO = triphenyl phosphine oxide). The complexes were characterized by elemental analysis, conductivity, IR, and 1H NMR. The IR spectra indicated that all the complexes have a larger deltaupsilon(upsilon(as) (CO2-) - upsilon(s)(CO2-) than that of NaL, and carboxylate ions in the phenylglyoxyate coordinated as unidentate ligands. And alpha-aeto also coordinated with the europium ions. In 1H NMR, the signals of hydrogens in the phenylglyoxyate shifted toward upfield, and those in phen or TPPO slightly shifted. The excitation and emission spectra were recorded at room temperature, and the excitation spectra showed that the optimum excitation wavelengths were 374.0, 358.2 and 383.4 nm, Five emission bands of the complexes due to 5D(0)-7F(0), 5D(0)-7F(1), 5D(0)-7F(2), 5D(0)-7F(3) and 5D(0)-7F(4) transitions were observed in the region of 550-720 nm (Eu-L: 577.8, 590.2, 614.0, 648.4 and 695.4 nm; EuL3phen: 578.0, 588.4, 591.6, 611.2, 617.0, 649.4, 687.6 and 698.6 nm; EuL2 (TPPO)2NO3: 577.8, 590.4, 614.6, 649.2 and 697.6 nm). The emission intensities of europium ions were obviously sensitized by TPPO.

[Study on the synthesis, characterization of structure and fluorescence properties of the solid complex of europium ion with 1,10-phenanthroline and 2-thiopheneglyoxylic acid].

The complex of europium with 1,10-phenanthroline and 2-thiopheneglyoxylic acid (HL) was synthesized. Its chemical formula was determined to be [EuL2 x phen x (H2O)3]NO3 by elemental analysis, electrical conductivity, IR and 1H NMR. It was found that the europium ion coordinated to the O atoms of 2-thiopheneglyoxylic acid and H2O, and to the N atoms of 1,10-phenanthroline. Its fluorescence property was determined by the excitation and emission spectra at room temperature, the emission peaks at 592 and 618 nm were assigned to the 5D0-7F1 and 5D0-7F2, respectively. It was also observed that the title complex emits strong red fluorescence under ultraviolet light at room temperature. In the IR spectrum, the characteristic absorption nu(C=O) (1719 cm(-1)), nu(C-O) (1232 cm(-1)), delta(O-H) (909 cm(-1)) of 2-thiopheneglyoxylic acid disappeared in the complex, the nu(as) and nu(s) of -COO- appeared at 1642 and 1408 cm(-1) in the complex respectively. In 1H NMR, the signals of 2-thiopheneglyoxylic acid were shifted upfield, and those of 1,10-phenanthroline downfield. It is proved by the TG curve that the complex is stable from ambient temperature to 250 degrees C.