Highly Effective Pyroelectric Catalysis for Simultaneous Tumor-Targeted Dynamic Therapy and Gentle Photothermal Therapy by Oxygen-Vacancy-Rich CeO2-BaTiO3 Nanorods.

Pyroelectric nanostructures could effectively generate temperature-mediated reactive oxygen species (ROS) through the pyroelectric effect, providing promise for treating hypoxic tumors, and therefore, the synergistic application of photothermal therapy (PTT) and pyroelectric dynamic therapy (PEDT) presents an intriguing approach for cancer therapy. However, this method still faces challenges in improving pyroelectric catalysis and achieving precise tumor localization. In this study, a nano-heterojunction based on CeO2-BaTiO3 nanorods (IR1061@PCBNR) is reported, which exhibits highly effective pyroelectric catalysis for simultaneous tumor-targeted dynamic therapy and gentle photothermal therapy through the utilization of the rich oxygen vacancies. The oxygen vacancies create active sites that facilitate the migration of pyroelectrically-induced charge carriers, improving charge separation and ROS generation. IR1061@PCBNR also demonstrates high tumor penetration while minimizing damage to normal cells. This precise nanomedicine strategy holds great potential for advancing dynamic cancer therapies by overcoming the limitations of conventional approaches. This article is protected by copyright. All rights reserved.

Comprehensive quality evaluation of fermented-steaming Fructus Aurantii based on chemical composition, flavor characteristics, and intestinal microbial community.

Fructus Aurantii (FA) is an edible and medicinal functional food used worldwide that enhances digestion. Since raw FA (RFA) possesses certain side effects for some patients, processed FA (PFA) is commonly used in clinical practice. This study aimed to establish an objective and comprehensive quality evaluation of the PFA that employed the technique of steaming and fermentation. Combined with the volatile and non-volatile components, as well as the regulation of gut microbiota, the differentiation between RFA and PFA was analyzed. The results showed that the PFA considerably reduced the contents of flavonoid glycosides while increasing hesperidin-7-O-glucoside and flavonoid aglycones. The electronic nose and GC-MS (Gas chromatography/mass spectrometry) effectively detected the variation in flavor between RFA and PFA. Correlation analysis revealed that eight volatile components (relative odor activity value [ROAV] ≥ 0.1) played a key role in inducing odor modifications. The original floral and woody notes were subdued due to decreased levels of linalool, sabinene, α-terpineol, and terpinen-4-ol. After processing, more delightful flavors such as lemon and fruity aromas were acquired. Furthermore, gut microbiota analysis indicated a significant increase in beneficial microbial taxa. Particularly, Lactobacillus, Akkermansia, and Blautia exhibited higher abundance following PFA treatment. Conversely, a lower presence of pathogenic bacteria, including Proteobacteria, Flexispira, and Clostridium. This strategy contributes to a comprehensive analysis technique for the quality assessment of FA, providing scientific justifications for processing FA into high-value products with enhanced health benefits. PRACTICAL APPLICATION: This study provided an efficient approach to Fructus Aurantii quality evaluation. The methods of fermentation and steaming showed improved quality and safety.

Chemokines and Their Receptors: Predictors of Therapeutic Potential in Tumor Microenvironment on Esophageal Cancer.

Esophageal carcinoma (ESCA) is an aggressive solid tumor. The 5-year survival rate for patients with ESCA is estimated to be less than 20%, mainly due to tumor invasion and metastasis. Therefore, it is urgent to improve early diagnostic tools and effective treatments for ESCA patients. Tumor microenvironment (TME) enhances the ability of tumor cells to proliferate, migrate, and escape from the immune system, thus promoting the occurrence and development of tumor. TME contains chemokines. Chemokines consist of four major families, which are mainly composed of CC and CXC families. The main purpose of this review is to understand the CC and CXC chemokines and their receptors in ESCA, to improve the understanding of tumorigenesis of ESCA and determine new biomarkers for the diagnosis and prognosis of ESCA. We reviewed the literature on CC and CXC chemokines and their receptors in ESCA identified by PubMed database. This article introduces the general structures and functions of CC, CXC chemokines and their receptors in TME, as well as their roles in the progress of ESCA. Chemokines are involved in the development of ESCA, such as cancer cell invasion, metastasis, angiogenesis, and radioresistance, and are key determinants of disease progression, which have a great impact on patient prognosis and treatment response. In addition, a full understanding of their mechanism of action is essential to further verify that these chemokines and their receptors may serve as biomarkers or therapeutic targets of ESCA.

Understanding PI3K/Akt/mTOR signaling in squamous cell carcinoma: mutated PIK3CA as an example.

Compared with those in adenocarcinoma, PIK3CA mutations are more common in squamous cell carcinoma (SCC), which arises from stratified squamous epithelia that are usually exposed to adverse environmental factors. Although hotspot mutations in exons 9 and 20 of PIK3CA, including E542K, E545K, H1047L and H1047R, are frequently encountered in the clinic, their clinicopathological meaning remains to be determined in the context of SCC. Considering that few reviews on PIK3CA mutations in SCC are available in the literature, we undertook this review to shed light on the clinical significance of PIK3CA mutations, mainly regarding the implications and ramifications of PIK3CA mutations in malignant cell behavior, prognosis, relapse or recurrence and chemo- or radioresistance of SCC. It should be noted that only those studies regarding SCC in which PIK3CA was mutated were cherry-picked, which fell within the scope of this review. However, the role of mutated PIK3CA in adenocarcinoma has not been discussed. In addition, mutations occurring in other main members of the PI3K-AKT-mTOR signaling pathway other than PIK3CA were also excluded.

Impulsive consensus algorithms for vector second-order Lipschitz nonlinear multi-agent systems using only velocity regulation.

The existing impulsive consensus algorithms for second-order Lipschitz nonlinear multi-agent systems require to apply the impulsive control to both position and velocity vectors at the same time. Such a requirement cannot be met in most of the real-world applications. To overcome the limitations of these impulsive algorithms, two kinds of new second-order impulsive consensus algorithms using only velocity regulation are proposed. Through developing a weighted discontinuous Lyapunov function-based approach that is able to leverage the spectral property of Laplacian matrix, impulse-dwell-time-dependent sufficient conditions for solving second-order impulsive consensus are derived in the form of linear matrix inequalities. Further, it is shown that if the impulsively controlled velocity subsystems are globally exponentially stable, the impulsive static consensus algorithm is able to ensure that all agents tend to an agreed position. Based on the consensus conditions, two convex optimization problems are formulated, by which the impulsive gain matrices for ensuring a prescribed exponential convergence rate can be designed. Finally, the effectiveness of the proposed distributed impulsive consensus algorithms is certified through numerical simulations.

A Novel Splicing Mutation Leading to Wiskott-Aldrich Syndrome from a Family.

Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive genetic disease characterized by clinical symptoms such as eczema, thrombocytopenia with small platelets, immune deficiency, prone to autoimmune diseases, and malignant tumors. This disease is caused by mutations of the WAS gene encoding WASprotein (WASP). The locus and type of mutations of the WAS gene and the expression quantity of WASP were strongly correlated with the clinical manifestations of patients. We found a novel mutation in the WAS gene (c.931 + 5G > C), which affected splicing to produce three abnormal mRNA, resulting in an abnormally truncated WASP. This mutation led to a reduction but not the elimination of the normal WASP population, resulting in causes X-linked thrombocytopenia (XLT) with mild clinical manifestations. Our findings revealed the pathogenic mechanism of this mutation.

In silico analyses of pan-squamous cell carcinoma unveiled the immunological implications of MRPL13, which had previously been under-recognized.

The involvement of the mitochondrial ribosomal protein 13 (MRPL13) gene in the development of adenocarcinoma has been previously reported. However, the clinicopathological significance of MRPL13 in squamous cell carcinoma (SCC) remains poorly understood. To gain insight into the clinicopathological and immunological implications of MRPL13 expression in SCC, we conducted a bioinformatic analysis utilizing various available databases, including TIMER 2.0, Xiantao academic tool and TISIDB, attempting to evaluate the abnormal expression, prognosis and immunological correlation of MRPL13 in the pan-SCC setting. Subsequently, we conducted experimental verification using an esophageal squamous cell carcinoma (ESCC) tissue array subjected to multiplexed immunofluorescent (mIF) staining. The ESCC tissue array we used consists of 93 dots of ESCC and 86 dots of matched adjacent normal tissues (ANT). Data from in silico analyses showed that MRPL13 mRNA is significantly up-regulated and correlated with infiltration of CD8+ T cells in pan-SCC. However, in silico analyses did not support the prognostic role of MRPL13 in SCC. Consistently, data from the ESCC tissue array showed that MRPL13 was remarkably elevated in ESCC tissues relative to ANT in stroma, which was controlled by pan-cytokeratin (pan-CK) staining. In the epithelia, no significant difference was identified between ESCC and ANT. Furthermore, MRPL13 expression markedly correlated with the infiltration of CD8+ T cells in the stromal region but not in the epithelial region. Prognostically, no significant association was observed between MRPL13 expression and overall survival, regardless of epithelial or stromal section. Through these pan-SCC analyses, we have expanded the understanding of MRPL13 previously reported, in particular, underscoring the immunological involvement of MRPL13 in the tumor microenvironment of SCC that has been under-recognized before, suggesting that MRPL13 may regulate the infiltration of CD8+ T cells into the SCC microenvironment.

Shh-Gli2-Runx2 inhibits vascular calcification.

BACKGROUND: In patients with chronic kidney disease (CKD), vascular calcification (VC) is common and is associated with a higher risk of all-cause mortality. Shh, one ligand for Hedgehog (Hh) signaling, participates in osteogenesis and several cardiovascular diseases. However, it remains unclear whether Shh is implicated in the development of VC. METHODS: Inorganic phosphorus 2.6 mM was used to induce vascular smooth muscle cells (VSMCs) calcification. Mice were fed with adenine diet supplement with 1.2% phosphorus to induce VC. RESULTS: Shh was decreased in VSMCs exposed to inorganic phosphorus, calcified arteries in mice fed with an adenine diet, as well as radial arteries from patients with CKD presenting VC. Overexpression of Shh inhibited VSMCs ostosteoblastic differentiation and calcification, whereas its silencing accelerated these processes. Likewise, mice treated with smoothened agonist (SAG; Hh signaling agonist) showed alleviated VC, and mice treated with cyclopamine (CPN; Hh signaling antagonist) exhibited severe VC. Additionally, overexpression of Gli2 significantly reversed the pro-calcification effect of Shh silencing on VSMCs, suggesting that Shh inhibited VC via Gli2. Mechanistically, Gli2 interacted with Runx2 and promoted its ubiquitin proteasomal degradation, therefore protecting against VC. Of interest, the pro-degradation effect of Gli2 on Runx2 was independent of Smurf1 and Cullin4B. CONCLUSIONS: Our study provided deeper insight to the pathogenesis of VC, and Shh might be a novel potential target for VC treatment.

Hypoxic Preconditioning Attenuates Neuroinflammation via Inhibiting NF-κB/NLRP3 Axis Mediated by p-MLKL after Transient Global Cerebral Ischemia.

Hypoxic preconditioning (HPC) has been reported to alleviate neuronal damage and microglial activation in hippocampal CA1 after transient global cerebral ischemia (tGCI). However, the molecular mechanism is unclear. Recent studies identified that nuclear factor-kappa-B (NF-κB)/oligomerization domain-like receptors protein (NLRP) 3 inflammasome pathway is mainly involved in the activation of microglia and that phosphorylated (p)-mixed lineage kinase domain-like (MLKL) is related to the regulation of NF-κB/NLRP3 axis. Hence, in this study, we set out to investigate whether HPC attenuates neuronal damage and microglial activation through inhibiting NF-κB/NLRP3 axis mediated by p-MLKL after tGCI in CA1 of male rats. We found that HPC decreased NLRP3 inflammasome in microglia and inhibited M1 polarization of microglia in CA1 after tGCI. Mechanistically, HPC inhibited the activation of NF-κB signaling pathway and reduced the mRNA and protein levels of NLRP3 inflammasome after tGCI. Additionally, the knockdown of p-MLKL by short hairpin RNA (shRNA) administration inhibited the activation of the NF-κB signaling pathway and reduced the formation of NLRP3 inflammasome, thus attenuating M1 polarization of microglia and decreasing the release of interleukin 1 beta (IL-1ß) and necrosis factor alpha (TNF-α) in CA1 post ischemia. We consider that p-MLKL in microglia may be derived from necroptotic neurons after tGCI. In conclusion, the new finding in this study is that HPC-induced neuroprotection against tGCI through inhibiting NF-κB/NLRP3 pathway mediated by p-MLKL.

Targeted genome engineering based on CRISPR/Cas9 system to enhance FVIII expression in vitro.

BACKGROUND: Hemophilia A is caused by a deficiency of coagulation factor VIII in the body due to a defect in the F8 gene. The emergence of CRISPR/Cas9 gene editing technology will make it possible to alter the expression of the F8 gene in hemophiliacs, while achieving a potential cure for the disease. METHODS: Initially, we identified high-activity variants of FVIII and constructed donor plasmids using enzymatic digestion and ligation techniques. Subsequently, the donor plasmids were co-transfected with sgRNA-Cas9 protein into mouse Neuro-2a cells, followed by flow cytometry-based cell sorting and puromycin selection. Finally, BDD-hF8 targeted to knock-in the mROSA26 genomic locus was identified and validated for FVIII expression. RESULTS: We identified the p18T-BDD-F8-V3 variant with high FVIII activity and detected the strongest pX458-mROSA26-int1-sgRNA1 targeted cleavage ability and no cleavage events were found at potential off-target sites. Targeted knock-in of BDD-hF8 cDNA at the mROSA26 locus was achieved based on both HDR/NHEJ gene repair approaches, and high level and stable FVIII expression was obtained, successfully realizing gene editing in vitro. CONCLUSIONS: Knock-in of exogenous genes based on the CRISPR/Cas9 system targeting genomic loci is promising for the research and treatment of a variety of single-gene diseases.

Research ReportDiurnal global ocean surface pCO2 and air-sea CO2 flux reconstructed from spaceborne LiDAR data.

The ocean absorbs a significant amount of carbon dioxide (CO2) from the atmosphere, helping regulate Earth's climate. However, our knowledge of ocean CO2 sink levels remains limited. This research focused on assessing daily changes in ocean CO2 sink levels and air-sea CO2 exchange, using a new technique. We used LiDAR technology, which provides continuous measurements during day and night, to estimate global ocean CO2 absorption over 23 years. Our model successfully reproduced sea surface partial pressure of CO2 data. The results suggest the total amount of CO2 absorbed by oceans is higher at night than during the day. This difference arises from a combination of factors like temperatures, winds, photosynthesis, and respiration. Understanding these daily fluctuations can improve predictions of ocean CO2 uptake. It may also help explain why current carbon budget calculations are not fully balanced-an issue scientists have grappled with. Overall, this pioneering study highlights the value of LiDAR's unique day-night ocean data coverage. The findings advance knowledge of ocean carbon cycles and their role in climate regulation. They underscore the need to incorporate day-night variability when assessing the ocean's carbon sink capacity.

Positioning determines function: Wandering PKM2 performs different roles in tumor cells.

Short for pyruvate kinase M2 subtype, PKM2 can be said of all-round player that is notoriously known for its metabolic involvement in glycolysis. Holding a dural role as a metabolic or non-metabolic (kinase) enzyme, PKM2 has drawn extensive attention over its biological roles implicated in tumor cells, including proliferation, migration, invasion, metabolism, and so on. wandering PKM2 can be transboundary both intracellularly and extracellularly. Specifically, PKM2 can be nuclear, cytoplasmic, mitochondrial, exosomal, or even circulate within the body. Importantly, PKM2 can function as an RNA-binding protein (RBP) to self-support its metabolic function. Despite extensive investigations or reviews available surrounding the biological roles of PKM2 from different angles in tumor cells, little has been described regarding some novel role of PKM2 that has been recently found, including, for example, acting as RNA-binding protein, protection of Golgi apparatus, and remodeling of microenvironment, and so forth. Given these findings, in this review, we summarize the recent advancements made in PKM2 research, mainly from non-metabolic respects. By the way, PKM1, another paralog of PKM2, seems to have been overlooked or under-investigated since its discovery. Some recent discoveries made about PKM1 are also preliminarily mentioned and discussed.

Small-Molecule Phototheranostic Agent with Extended π-Conjugation for Efficient NIR-II Photoacoustic-Imaging-Guided Photothermal Therapy.

Photoacoustic imaging (PAI) and photothermal therapy (PTT) conducted over the near-infrared-II (NIR-II) window offer the benefits of noninvasiveness and deep tissue penetration. This necessitates the development of highly effective therapeutic agents with NIR-II photoresponsivity. Currently, the predominant organic diagnostic agents used in NIR-II PAI-guided PTT are conjugated polymeric materials. However, they exhibit a low in vivo clearance rate and long-term biotoxicity, limiting their clinical translation. In this study, an organic small molecule (CY-1234) with NIR-II absorption and nanoencapsulation (CY-1234 nanoparticles (NPs)) for PAI-guided PTT is reported. Extended π-conjugation is achieved in the molecule by introducing donor-acceptor units at both ends of the molecule. Consequently, CY-1234 exhibits a maximum absorption peak at 1234 nm in tetrahydrofuran. Nanoaggregates of CY-1234 are synthesized via F-127 encapsulation. They exhibit an excellent photothermal conversion efficiency of 76.01% upon NIR-II light irradiation. After intravenous injection of CY-1234 NPs into tumor-bearing mice, strong PA signals and excellent tumor ablation are observed under 1064 nm laser irradiation. This preliminary study can pave the way for the development of small-molecule organic nanoformulations for future clinical applications.

miR-133b Promotes Esophageal Squamous Cell Carcinoma Metastasis.

Background: Evaluation of biological changes at the molecular level has important clinical implications for improving the survival rate of esophageal squamous cell carcinoma (ESCC). Therefore, we plan to analyze and elucidate the expression of microRNA-133b (miR-133b), M2 pyruvate kinase (PKM2), and signal transducer and activator of transcription 3 (STAT3) in ESCC and their associated clinicopathological significance. Methods: The 72 patients with ESCC were selected as the experimental study group. Normal adjacent tissues (NAT) were matched as the control group. In this study, in situ hybridization was used to detect the expression of miR-133b in ESCC, and tissue expressions of PKM2 and STAT3 were detected by immunohistochemistry, and literature review was conducted. Results: Studies had shown that the positive expression of miR-133b in NAT was significantly higher than that in ESCC (χ2 = 9.007, P = .003). PKM2 and STAT3 in ESCC had a significantly higher positive expression levels than those of NAT (χ2 = 56.523, P = .000; χ2 = 72.939, P = .000). From correlation analysis, there was a negative correlation between miR-133b and PKM2(r = -0.515, P < .001), a negative correlation between miR-133b and STAT3(r = -0.314, P = .007), and a positive correlation between PKM2 and STAT3(r = 0.771, P < .001). Conclusions: In ESCC, our study demonstrated that downregulation of miR-133b and upregulation of PKM2 and STAT3. We predict that miR-133b may inhibit the STAT3 pathway by downregulating PKM2.

A new isoflavone from the stems of Derris eriocarpa How.

A preliminary screening test was performed to discover new antihyperlipidaemic active compounds from the leguminous plant Derris eriocarpa How. A new compound, derris-isoflavone F (1), and derrubone dimethyl ether (6), a known synthetic compound of natural origin, were isolated from the stems of D. eriocarpa alongside eight recognised compounds. To our knowledge, this is the first instance of documenting the identification of compounds 1-10 from this plant. The new compound were evaluated for their antihyperlipidemic and antiproliferative properties. Compound 1 evidently reduced the triglyceride (TG) content in oleic acid-treated HepG2 cells, which validated its efficacy as a potential TG-lowering agent.

Cullin7 induces docetaxel resistance by regulating the protein level of the antiapoptotic protein Survivin in lung adenocarcinoma cells.

Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC). Chemotherapy resistance is the main cause of chemotherapy failure. Cullin7 (Cul7) is highly expressed in LUAD and is associated with poor prognosis. Moreover, Cul7 is abnormally overexpressed in docetaxel-resistant LUAD cells. Therefore, further exploration of the role and molecular mechanism of Cul7 in LUAD docetaxel resistance is necessary. Methods: We established docetaxel-resistant cell lines (A549DTX and H358DTX cell lines) by exposing cells to gradually increasing concentrations of docetaxel. Cell (A549, A549DTX, H358, and H358DTX cell lines) sensitivity to docetaxel was determined via a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymmethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. And then quantitative polymerase chain reaction (qPCR) and Western blotting were performed to measure the expression of Cul7 and Survivin in A549, A549DTX, H358, and H358DTX cell lines. Subsequently, we knocked down Cul7 in docetaxel-resistant cells and overexpressed Cul7 in parental cells via lentiviral transduction to further validate the correlation between Cul7 and docetaxel resistance, while exploring the molecular mechanism of docetaxel resistance it caused. Immunofluorescence and immunohistochemical (IHC) staining were also used to evaluate the expression and cellular localization of Cul7. To confirm the effect of Cul7 expression on cell apoptosis, we used flow cytometry to detect the apoptosis rate of A549 and A549DTX cells with the same drug concentration. Results: Cul7 was highly expressed in A549DTX and H358DTX cells. However, when Cul7 expression was knocked down in A549DTX and H358DTX cells, cell sensitivity to docetaxel was significantly increased. In addition, we found that Cul7 was coexpressed with Survivin. Silencing Survivin reversed the docetaxel insensitivity caused by Cul7 overexpression. High expression of Cul7 and Survivin in docetaxel-resistant LUAD cells inhibited the intrinsic apoptosis pathway and promoted cell proliferation. Therefore, the Cul7/Survivin axis may play a role in inducing LUAD docetaxel chemoresistance. Conclusions: Cul7 and Survivin were both highly expressed in docetaxel-resistant LUAD cells. Our results suggest that Cul7 may inhibit apoptosis and promote the proliferation of LUAD cells by increasing the Survivin protein level, which in turn contributes to docetaxel chemoresistance in LUAD.

Femtosecond-laser-assisted high-aspect-ratio nanolithography in lithium niobate.

We report the successful fabrication of high-aspect-ratio lithium niobate (LN) nanostructures by using femtosecond-laser-assisted chemical etching. In this technique, a 1 kHz femtosecond laser is first used to induce local modifications inside the LN crystal. Then, selective chemical wet etching is conducted using a buffered oxide etch (BOE) solution. The etching rate in the laser-modified area reaches 2 µm h-1, which is enhanced by a factor of ∼660 in comparison to previous reports without laser irradiation. Such high selectivity in chemical etching helps realize high-performance maskless nanolithography in lithium niobate. In the experiment, we have fabricated high-quality LN nanohole arrays. The nanohole size reaches ∼100 nm and its aspect ratio is above 40 : 1. The minimal period of the LN hole array is 300 nm. Our work paves a way to fabricate LN nano-integrated devices for advanced optic and electronic applications.

Lidar attenuation coefficient in the global oceans: insights from ICESat-2 mission.

The attenuation coefficient of natural waters plays a significant role in our understanding of hydrology from both the oceanographic and biological point of view. The advent of near-continuous observations by sophisticated space-based lidars now offers an unprecedented opportunity to characterize attenuation coefficients over open oceans on global and regional scales. At present, however, literature reports of lidar-derived attenuation coefficient estimates (klidar, m-1) in oceanic waters are very limited. In this study, we present a global survey of klidar derived from ATLAS/ICESat-2 nighttime measurements. Our results augment the existing passive sensor ocean color data set with a new diurnal component and extend the record to now include previously unavailable polar nighttime observations. The values of ATLAS measured klidar at 532 nm are between 0.045 and 0.39 m-1 with the higher values (>0.15 m-1) correlated with coastal waters and sea ice covered oceans. The average klidar in clearest oligotrophic ocean gyres is ∼0.058 ± 0.012 m-1 at 532 nm. The results reported here demonstrate the feasibility of using ATLAS/ICESat-2 lidar measurements for global klidar studies, which will in turn provide critical insights that enable climate models to correctly describe the amount of light present under sea ice, and for heat deposition studies in the upper ocean.

Ultra-low-dose spectral-detector computed tomography for the accurate quantification of pulmonary nodules: an anthropomorphic chest phantom study.

PURPOSE: To assess the quantification accuracy of pulmonary nodules using virtual monoenergetic images (VMIs) derived from spectral-detector computed tomography (CT) under an ultra-low-dose scan protocol. METHODS: A chest phantom consisting of 12 pulmonary nodules was scanned using spectral-detector CT at 100 kVp/10 mAs, 100 kVp/20 mAs, 120 kVp/10 mAs, and 120 kVp/30 mAs. Each scanning protocol was repeated three times. Each CT scan was reconstructed utilizing filtered back projection, hybrid iterative reconstruction, iterative model reconstruction (IMR), and VMIs of 40-100 keV. The signal-to-noise ratio and air noise of images, absolute differences, and absolute percentage measurement errors (APEs) of the diameter, density, and volume of the four scan protocols and ten reconstruction images were compared. RESULTS: With each fixed reconstruction image, the four scanning protocols exhibited no significant differences in APEs for diameter and density (all P > 0.05). Of the four scan protocols and ten reconstruction images, APEs for nodule volume had no significant differences (all P > 0.05). At 100 kVp/10 mAs, APEs for density using IMR were the lowest (APE-mean: 6.69), but no significant difference was detected between VMIs at 50 keV (APE-mean: 11.69) and IMR (P = 0.666). In the subgroup analysis, at 100 kVp/10 mAs, there were no significant differences between VMIs at 50 keV and IMR in diameter and density (all P > 0.05). The radiation dose at 100 kVp/10 mAs was reduced by 77.8% compared with that at 120 kVp/30 mAs. CONCLUSION: Compared with IMR, reconstruction at 100 kVp/10 mAs and 50 keV provides a more accurate quantification of pulmonary nodules, and the radiation dose is reduced by 77.8% compared with that at 120 kVp/30 mAs, demonstrating great potential for ultra-low-dose spectral-detector CT.