Repeated dynamic [18F]FDG PET/CT imaging using a high-sensitivity PET/CT scanner for assessing non-small cell lung cancer patients undergoing induction immuno-chemotherapy followed by hypo-fractionated chemoradiotherapy and consolidative immunotherapy: report from a prospective observational study (GASTO-1067).

OBJECTIVE: The study aims to investigate the role of dynamic [18F]FDG PET/CT imaging by high-sensitivity PET/CT scanner for assessing patients with locally advanced non-small cell lung cancer (LA-NSCLC) who undergo induction immuno-chemotherapy, followed by concurrent hypo-fractionated chemoradiotherapy (hypo-CCRT) and consolidative immunotherapy. METHODS: Patients with unresectable LA-NSCLC are prospectively recruited. Dynamic [18F]FDG PET/CT scans are conducted at four timepoints: before treatment (Baseline), after induction immuno-chemotherapy (Post-IC), during hypo-CCRT (Mid-hypo-CCRT) and after hypo-CCRT (Post-hypo-CCRT). The primary lung tumors (PTs) are manually delineated, and the metabolic features, including the Patlak-Ki (Ki), maximum SUV (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have been evaluated. The expressions of CD3, CD8, CD68, CD163, CD34 and Ki67 in primary lung tumors at baseline are assayed by immunohistochemistry. The levels of blood lymphocytes at four timepoints are analyzed with flow cytometry. RESULTS: Fifteen LA-NSCLC patients are enrolled between December 2020 and December 2022. Baseline Ki of primary tumor yields the highest AUC values of 0.722 and 0.796 for predicting disease progression and patient death, respectively. Patients are classified into the High FDG Ki group (n = 8, Ki > 2.779 ml/min/100 g) and the Low FDG Ki group (n = 7, Ki ≤ 2.779 ml/min/100 g). The High FDG Ki group presents better progression-free survival (P = 0.01) and overall survival (P = 0.025). The High FDG Ki group exhibits more significant reductions in Ki after hypo-CCRT compared to the Low FDG Ki group. Patients with a reduction in Ki > 73.1% exhibit better progression-free survival than those with a reduction ≤ 73.1% in Ki (median: not reached vs. 7.33 months, P = 0.12). The levels of CD3+ T cells (P = 0.003), CD8+ T cells (P = 0.002), CD68+ macrophages (P = 0.071) and CD163+ macrophages (P = 0.012) in primary tumor tissues are higher in the High FDG Ki group. The High FDG Ki group has higher CD3+CD8+ lymphocytes in blood at baseline (P = 0.108), post-IC (P = 0.023) and post-hypo-CCRT (P = 0.041) than the Low FDG Ki group. CONCLUSIONS: The metabolic features in the High FDG Ki group significantly decrease during the treatment, particularly after induction immuno-chemotherapy. The Ki value of primary tumor shows significant relationship with the treatment response and survival in LA-NSCLC patients by the combined immuno-chemoradiotherapy regimen. TRIAL REGISTRATION: ClinicalTrials.gov. NCT04654234. Registered 4 December 2020.

Corrosion-Induced Cracking Model of Concrete Considering a Transverse Constraint.

The performance of corrosion-induced cracking of reinforced concrete members under transverse constraints was studied. Based on the theory of elastic-plastic mechanics and the hypothesis of uniform corrosion of a steel bar, a three-layer hollow cylinder model was established to predict the critical corrosion of the steel bar at the time of the cracking of the concrete cover. Taking the constraint of stirrups on surrounding concrete into consideration, it can be used to predict the corrosion rate of members with stirrups at the time of the cracking of the concrete cover, which further expands the application range of the corrosion-induced cracking models of concrete. On this basis, the critical corrosion rate of concrete under different stirrup ratios at the time of cracking was measured. The calculated results of the model are in accordance with experimental data. For corner steel bars, when the stirrup spacing is less than 100 mm, the existence of stirrups can effectively delay the occurrence of rust expansion cracks and enhance the durability of the structure. On the basis of this study, the problem of corrosion expansion and cracking of the concrete cover caused by non-uniform corrosion of steel bars along longitudinal and radial directions needs to be further studied in the future.

Pt-Cluster-Embedded Metal-Organic Frameworks-Derived Fe@C as Dual-Enzyme Mimics for NADH Detection in Serum.

Dihydro-nicotinamide adenine dinucleotide (NADH) detection is crucial since it is a vital coenzyme in organism metabolism. Compared to the traditional method based on natural NADH oxidase (NOX), nanozymes with multienzyme-like activity can catalyze multistage reactions in a singular setup, simplifying detection processes and enhancing sensitivity. In this study, an innovative NADH detection method was developed using iron-doped carbon (Fe@C) nanozyme synthesized from metal-organic frameworks with in situ reduced Pt clusters. This nanozyme composite (Pt/Fe@C) demonstrated dual NOX and peroxidase-like characteristics, significantly enhancing the catalytic efficiency and enabling NADH conversion to NAD+ and H2O2 with subsequent detection. The collaborative research involving both experimental and theoretical simulations has uncovered the catalytic process and the cooperative effect of Fe and Pt atoms, leading to enhanced oxygen adsorption and activation, as well as a decrease in the energy barrier of the key step in the H2O2 decomposition process. These findings indicate that the catalytic performance of Pt/Fe@C in NOX-like and POD-like reactions can be significantly improved. The colorimetric sensor detects NADH with a limit of detection as low as 0.4 nM, signifying a breakthrough in enzyme-mimicking nanozyme technology for precise NADH measurement.

Correlation of Ktrans derived from dynamic contrast-enhanced MRI with treatment response and survival in locally advanced NSCLC patients undergoing induction immunochemotherapy and concurrent chemoradiotherapy.

PURPOSE: This study aimed to investigate the prognostic significance of pretreatment dynamic contrast-enhanced (DCE)-MRI parameters concerning tumor response following induction immunochemotherapy and survival outcomes in patients with locally advanced non-small cell lung cancer (NSCLC) who underwent immunotherapy-based multimodal treatments. MATERIAL AND METHODS: Unresectable stage III NSCLC patients treated by induction immunochemotherapy, concurrent chemoradiotherapy (CCRT) with or without consolidative immunotherapy from two prospective clinical trials were screened. Using the two-compartment Extend Tofts model, the parameters including Ktrans, Kep, Ve, and Vp were calculated from DCE-MRI data. The apparent diffusion coefficient was calculated from diffusion-weighted-MRI data. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to assess the predictive performance of MRI parameters. The Cox regression model was used for univariate and multivariate analysis. RESULTS: 111 unresectable stage III NSCLC patients were enrolled. Patients received two cycles of induction immunochemotherapy and CCRT, with or without consolidative immunotherapy. With the median follow-up of 22.3 months, the median progression-free survival (PFS) and overall survival (OS) were 16.3 and 23.8 months. The multivariate analysis suggested that Eastern Cooperative Oncology Group score, TNM stage and the response to induction immunochemotherapy were significantly related to both PFS and OS. After induction immunochemotherapy, 67 patients (59.8%) achieved complete response or partial response and 44 patients (40.2%) had stable disease or progressive disease. The Ktrans of primary lung tumor before induction immunochemotherapy yielded the best performance in predicting the treatment response, with an AUC of 0.800. Patients were categorized into two groups: high-Ktrans group (n=67, Ktrans＞164.3×10-3/min) and low-Ktrans group (n=44, Ktrans≤164.3×10-3/min) based on the ROC analysis. The high-Ktrans group had a significantly higher objective response rate than the low-Ktrans group (85.1% (57/67) vs 22.7% (10/44), p<0.001). The high-Ktrans group also presented better PFS (median: 21.1 vs 11.3 months, p=0.002) and OS (median: 34.3 vs 15.6 months, p=0.035) than the low-Ktrans group. CONCLUSIONS: Pretreatment Ktrans value emerged as a significant predictor of the early response to induction immunochemotherapy and survival outcomes in unresectable stage III NSCLC patients who underwent immunotherapy-based multimodal treatments. Elevated Ktrans values correlated positively with enhanced treatment response, leading to extended PFS and OS durations.

Effects of different pickling methods on physicochemical properties and flavor profiles of Tongling white ginger: Dry-salting, brine-pickling, and inoculation-pickling.

Tongling white ginger is a Chinese fermented vegetable with unique flavors. However, little is known about its physicochemical properties, flavor characteristics, and sensory evaluation. The study examined the physicochemical (pH, titratable acidity [TA], nitrite, soluble protein, and color) and flavor characteristics (organic acids, free amino acids, and volatiles) of white ginger during fermentation. The results showed that the pH value and soluble protein in the dry-salted, brine-pickled, and inoculation-pickled decreased significantly while the TA value increased significantly, inoculation-pickled can effectively reduce the content of nitrite. After fermentation, inoculation-pickled produced the highest content of organic acids, while dry-salted produced the highest total amount of free amino acids. A total of 70, 68, 70, and 69 volatile compounds were identified in fresh, dry-salted, brine-pickled, and inoculation-pickled white ginger. The total contents of terpenoids of Tongling white ginger by three fermentation methods decreased; the total contents of alcohols and aldehydes were the highest in brine-pickled, and esters and ketones were more abundant in inoculation-pickled. The results showed that inoculation-pickled could shorten the fermentation time of Tongling white ginger, produce a unique flavor, and have the highest sensory score.

Fraction Dose Escalation of Hypofractionated Radiotherapy with Concurrent Chemotherapy and Subsequent Consolidation Immunotherapy in Locally Advanced Non-Small Cell Lung Cancer: A Phase I Study.

PURPOSE: This phase I trial aimed to determine the maximum tolerated fraction dose (MTFD) of hypofractionated radiotherapy (hypo-RT) combined with concurrent chemotherapy and subsequent consolidation immune checkpoint inhibitors (cICI) for patients with locally advanced non-small cell lung cancer. PATIENTS AND METHODS: Split-course hypo-RT and hypoboost combined with concurrent chemotherapy was administered at three dose levels (DL), using a stepwise dose-escalation protocol. The sophisticated esophagus-sparing technique was implemented to restrict the dose to the esophagus. Patients who did not experience disease progression or unresolved ≥grade 2 (G2+) toxicities after RT received cICI. Each DL aimed to treat six patients. The MTFD was defined as the highest DL at which ≤2 patients of the six who were treated experienced treatment-related G3+ toxicity and ≤1 patient experienced G4+ toxicity within 12 months post-RT. RESULTS: Eighteen patients were enrolled, with six patients in each DL. All patients completed hypo-RT and concurrent chemotherapy, and 16 (88.9%) received at least one infusion of cICI, with a median of 10 infusions. Within the 12-month assessment period, one patient in DL1 experienced G3 pneumonitis, and one patient in DL3 developed G3 tracheobronchitis. The MTFD was not reached. The objective response rate was 100%. With a median follow-up of 20.9 months, the 1-year overall survival and progression-free survival rates were 94.4% and 83.3%, respectively. CONCLUSIONS: Utilizing the split-course hypo-RT and hypoboost approach, a fraction dose of 5 Gy to a total dose of 60 Gy, combined with concurrent chemotherapy and subsequent cICI, was well tolerated and yielded a promising objective response rate and survival outcomes.

Conformal Conversion of Polyphosphazene@Sb2MoO6 Nanowires to N/S-Doped/Carbon-Coated SbPO4/MoOx for High-performance Lithium Storage.

Alloy-type antimony (Sb) and conversion-type molybdenum (Mo) anodes have attracted extensive attention in the application of lithium-ion batteries (LIBs) owing to their high theoretical capacity. In this study, Sb2MoO6 nanowires are prepared via a hydrothermal method and assessed their thermal behavior upon heat treatment, observing an intriguing transformation from nanowire to Sb2O3/MoOx nanosheets. To enhance structure stability, the Sb2MoO6 nanowires are successfully coated with a polyphosphazene layer (referred to as PZS@Sb2MoO6), which not only preserved the nanowires form but also yielded N/S co-doped carbon-coated SbPO4/MoOx (NS-C@SbPO4/MoOx) nanowires following annealing in an inert environment. This composite benefits from the stable PO4 3- anion that serve as a buffer against volume expansion and form a Li3PO4 matrix during cycling, both of which substantially bolster ion transport and cycle endurance. Doping with heteroatoms introduces numerous oxygen vacancies, augmenting the number of electrochemically active sites, and carbon integration considerably enhances the electronic conductivity of the electrode and alleviates the volume-change-induced electrode pulverization. Employed as anode materials in LIBs, the NS-C@SbPO4/MoOx electrode exhibits remarkable cycling performance (449.8 mA h g-1 at 1000 mA g-1 over 700 cycles) along with superior rate capability (394.2 mA h g-1 at 2000 mA g-1).

Expression of concern: Intelligent nanoflowers: a full tumor microenvironment-responsive multimodal cancer theranostic nanoplatform.

Expression of concern for 'Intelligent nanoflowers: a full tumor microenvironment-responsive multimodal cancer theranostic nanoplatform' by Xunan Jing et al., Nanoscale, 2019, 11, 15508-15518, https://doi.org/10.1039/C9NR04768A.

Expression of Concern: One-pot synthesis of acid-degradable polyphosphazene prodrugs for efficient tumor chemotherapy.

Expression of Concern for 'One-pot synthesis of acid-degradable polyphosphazene prodrugs for efficient tumor chemotherapy' by Na Zhou et al., J. Mater. Chem. B, 2020, 8, 10540-10548, https://doi.org/10.1039/D0TB01992E.

The time-series behavior of systemic inflammation-immune status in predicting survival of locally advanced non-small cell lung cancer treated with chemoradiotherapy.

Background: Systematic inflammation is believed to play a crucial role in tumorigenesis and metastasis. This study aims at evaluating the prognostic value of time-series behavior of systematic inflammation-immune status before and after definitive chemoradiotherapy (dCRT) in patients with locally advanced non-small cell lung cancer (LA-NSCLC). Methods: The relationship between systematic inflammation-immune score (SIS, defined as pretreatment peripheral platelet count × neutrophil count/lymphocyte count) and the prognosis was tested in a retrospective study of 386 consecutive LA-NSCLC patients (Group A) with pretreatment SIS and 161 patients (Group B) with SIS before and one month after the dCRT. Results: SIS of 1400 × 109 was found to be an optimal cutoff point to stratify the patients into high (>1400 × 109) and low (≤1400 × 109) SIS groups. Univariate and multivariate analyses revealed that the SIS, whether before or after dCRT, was an independent predictor for overall survival (OS), progress-free survival (PFS), and distant metastasis-free survival (DMFS). High SIS (>1400 × 109) was shown to predict poor 3-year OS (P=0.006, hazard ratio [HR]=2.427), PFS (P=0.001, HR=2.442) and DMFS (P=0.015, HR=2.119). However, SIS was not related to local regional recurrence-free survival in either Group A (P=0.346) or Group B (P=0.486). Further, the area under the receiver operating characteristic curve of the SIS for OS was higher than the neutrophil count/lymphocyte count ratio, platelet count/lymphocyte count ratio, and other conventional clinic-pathological indices. Conclusions: The SIS is a stable and more sensitive survival predictor than other inflammation-based factors and conventional clinical indices, which may aid in more accurately stratifying patients for risk assessment and treatment decisions.