Multiple pathways for licensing human replication origins.

The loading of replicative helicases constitutes an obligatory step in the assembly of DNA replication machineries. In eukaryotes, the MCM2-7 replicative helicase motor is deposited onto DNA by the origin recognition complex (ORC) and co-loader proteins as a head-to-head MCM double hexamer to license replication origins. Although extensively studied in the budding yeast model system, the mechanisms of origin licensing in higher eukaryotes remain poorly defined. Here, we use biochemical reconstitution and electron microscopy (EM) to reconstruct the human MCM loading pathway. Unexpectedly, we find that, unlike in yeast, ORC's Orc6 subunit is not essential for human MCM loading but can enhance loading efficiency. EM analyses identify several intermediates en route to MCM double hexamer formation in the presence and absence of Orc6, including an abundant DNA-loaded, closed-ring single MCM hexamer intermediate that can mature into a head-to-head double hexamer through different pathways. In an Orc6-facilitated pathway, ORC and a second MCM2-7 hexamer are recruited to the dimerization interface of the first hexamer through an MCM-ORC intermediate that is architecturally distinct from an analogous intermediate in yeast. In an alternative, Orc6-independent pathway, MCM double hexamer formation proceeds through dimerization of two independently loaded single MCM2-7 hexamers, promoted by a propensity of human MCM2-7 hexamers to dimerize without the help of other loading factors. This redundancy in human MCM loading pathways likely provides resilience against replication stress under cellular conditions by ensuring that enough origins are licensed for efficient DNA replication. Additionally, the biochemical reconstitution of human origin licensing paves the way to address many outstanding questions regarding DNA replication initiation and replication-coupled events in higher eukaryotes in the future.

Degradable Nanohydroxyapatite-Reinforced Superglue for Rapid Bone Fixation and Promoted Osteogenesis.

Bone glue with robust adhesion is crucial for treating complicated bone fractures, but it remains a formidable challenge to develop a "true" bone glue with high adhesion strength, degradability, bioactivity, and satisfactory operation time in clinical scenarios. Herein, inspired by the hydroxyapatite and collagen matrix composition of natural bone, we constructed a nanohydroxyapatite (nHAP) reinforced osteogenic backbone-degradable superglue (O-BDSG) by in situ radical ring-opening polymerization. nHAP significantly enhances adhesive cohesion by synergistically acting as noncovalent connectors between polymer chains and increasing the molecular weight of the polymer matrix. Moreover, nHAP endows the glue with bioactivity to promote osteogenesis. The as-prepared glue presented a 9.79 MPa flexural adhesion strength for bone, 4.7 times that without nHAP, and significantly surpassed commercial cyanoacrylate (0.64 MPa). O-BDSG exhibited degradability with 51% mass loss after 6 months of implantation. In vivo critical defect and tibia fracture models demonstrated the promoted osteogenesis of the O-BDSG, with a regenerated bone volume of 75% and mechanical function restoration to 94% of the native tibia after 8 weeks. The glue can be flexibly adapted to clinical scenarios with a curing time window of about 3 min. This work shows promising prospects for clinical application in orthopedic surgery and may inspire the design and development of bone adhesives.

Loss of CHCHD2 Stability Coordinates with C1QBP/CHCHD2/CHCHD10 Complex Impairment to Mediate PD-Linked Mitochondrial Dysfunction.

Novel CHCHD2 mutations causing C-terminal truncation and interrupted CHCHD2 protein stability in Parkinson's disease (PD) patients were previously found. However, there is limited understanding of the underlying mechanism and impact of subsequent CHCHD2 loss-of-function on PD pathogenesis. The current study further identified the crucial motif (aa125-133) responsible for diminished CHCHD2 expression and the molecular interplay within the C1QBP/CHCHD2/CHCHD10 complex to regulate mitochondrial functions. Specifically, CHCHD2 deficiency led to decreased neural cell viability and mitochondrial structural and functional impairments, paralleling the upregulation of autophagy under cellular stresses. Meanwhile, as a binding partner of CHCHD2, C1QBP was found to regulate the stability of CHCHD2 and CHCHD10 proteins to maintain the integrity of the C1QBP/CHCHD2/CHCHD10 complex. Moreover, C1QBP-silenced neural cells displayed severe cell death phenotype along with mitochondrial damage that initiated a significant mitophagy process. Taken together, the evidence obtained from our in vitro and in vivo studies emphasized the critical role of CHCHD2 in regulating mitochondria functions via coordination among CHCHD2, CHCHD10, and C1QBP, suggesting the potential mechanism by which CHCHD2 function loss takes part in the progression of neurodegenerative diseases.

Single-cell landscape of undifferentiated pleomorphic sarcoma.

Undifferentiated pleomorphic sarcoma (UPS) is a highly aggressive malignant soft tissue tumor with a poor prognosis; however, the identity and heterogeneity of tumor populations remain elusive. Here, eight major cell clusters were identified through the RNA sequencing of 79,569 individual cells of UPS. UPS originates from mesenchymal stem cells (MSCs) and features undifferentiated subclusters. UPS subclusters were predicted to exist in two bulk RNA datasets, and had a prognostic value in The Cancer Genome Atlas (TCGA) dataset. The functional heterogeneity of malignant UPS cells and the immune microenvironment were characterized. Additionally, the fused cells were innovatively detected by expressing both monocyte/macrophage markers and other subcluster-associated genes. Based on the ligand-receptor interaction analysis, cellular interactions with epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) were abundant. Furthermore, 73% of patients with UPS (48/66) showed positive EGFR expression, which was associated with a poor prognosis. EGFR blockade with cetuximab inhibited tumor growth in a patient-derived xenograft model. Our transcriptomic studies delineate the landscape of UPS intratumor heterogeneity and serve as a foundational resource for further discovery and therapeutic exploration.

Tackling the water solubility dilemma of spiroring-closing rhodamine: Sulfone-functionalization enabling rational designing water-soluble probe for rapid visualizing mercury ions in cosmetics.

Rhodamine derivatives possessing spiroring-closing structures exhibit colorlessness, while the induction of spiroring-opening by metal ions results in notable color changes, rendering them as ideal platform for the development of functional probes with broad applications. However, the spiroring-closing form of rhodamine-based probes exhibits limited water solubility due to its neutral character, necessitating the incorporation of organic solvents to enhance solubility, which may adversely affect the natural system. Designing rhodamine probes with high solubility in both the zwitterionic and neutral form is of utmost importance and presents a significant challenge. This study presents a sulfone-rhodamine-based probe that exhibits good water solubility both in the spiroring opening and closing for detecting Hg2+. Upon the presence of Hg2+, the color undergoes a noticeable change from colorless to pink, with a response time of less than 1 min. probe 1 demonstrates an excellent linear relationship with Hg2+ concentrations within the range of 0-8 µM, and achieves a detection limit is 17.26 nM. The effectiveness of probe 1 was confirmed through the analysis of mercury ions in cosmetic products. Utilizing this probe, test paper strips have been developed to enhance the portability of Hg2+ detection naked eyes.

The potential mechanism of Aidi injection against neuroblastoma-an investigation based on network pharmacology analysis.

Background: Aidi injection, a classic traditional Chinese medicine (TCM) formula, has been used on a broader scale in treating a variety of cancers. In this study, we aimed to explore the potential anti-tumor effects of Aidi injection in the treatment of neuroblastoma (NB) using network pharmacology (NP). Methods: To elucidate the anti-NB mechanism of Aidi injection, an NP-based approach and molecular docking validation were employed. The compounds and target genes were collected from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) database. The protein-protein interaction network was constructed using the STRING database. clusterProfiler (R package) was utilized to annotate the bioinformatics of hub target genes. The gene survival analysis was performed on R2, a web-based genomic analysis application. iGEMDOCK was used for molecular docking validation, and GROMACS was utilized to validate molecular docking results. Furthermore, we investigated the anticancer effects of gomisin B and ginsenoside Rh2 on human NB cells using a cell viability assay. The Western blot assay was used to validate the protein levels of target genes in gomisin B- and ginsenoside Rh2-treated NB cells. Results: A total of 2 critical compounds with 16 hub target genes were identified for treating NB. All 16 hub genes could potentially influence the survival of NB patients. The top three genes (EGFR, ESR1, and MAPK1) were considered the central hub genes from the drug-compound-hub target gene-pathway network. The endocrine resistance and estrogen signaling pathways were identified as the therapeutic pathways using the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Gomisin B and ginsenoside Rh2 showed a good binding ability to the target protein in molecular docking. The results of cell experiments showed the anti-NB effect of gomisin B and ginsenoside Rh2. In addition, the administration of gomisin B over-regulated the expression of ESR1 protein in MYCN-amplified NB cells. Conclusion: In the present study, we investigated the potential pharmacological mechanisms of Aidi against NB and revealed the anti-NB effect of gomisin B, providing clinical evidence of Aidi in treating NB and establishing baselines for further research.

Rapid quantitative evaluation of total polar materials (TPM) in frying oil based on an "off-on" fluorescence viscosity response probe.

The content of total polar material (TPM) is considered as a comprehensive indicator to evaluate the quality of edible oils which should be discarded and no longer be used when TPM content exceeding 27 %. Nevertheless, there is currently a lack of a convenient and efficient TPM detection method, which is a meaningful challenge. With the increase of TPM content, the viscosity of frying oil grows, and the two maintain a satisfactory positive correlation. Consequently, an "off-on" fluorescence probe TCF-PR method based on viscosity-response has been developed. There exists a good linear relationship between the fluorescence intensity of the probe and the TPM content of soybean oil ((R2 = 0.9936) and salad oil (R2 = 0.9878), accompanying with the advantage of fast response (3 s), which means the rapid detection of TPM can be realized to determine the quality of frying oil in the field of food safety.

The Identification of a Strain for the Biological Purification of Soy Molasses to Produce Functional Soy Oligosaccharides and Optimize Purification Conditions.

Soy molasses is rich in oligosaccharides like sucrose, stachyose, and raffinose, with stachyose and raffinose being functional oligosaccharides. Harnessing soy molasses for the production of functional soy oligosaccharides (FSO) can significantly elevate its value. Biological purification, a method leveraging the selective utilization of different carbon sources by microorganisms, allows for the specific removal of sucrose from soy molasses while preserving stachyose and raffinose, thereby increasing the FSO content. This research identified a yeast named YT312 with strong purification capabilities for soy molasses and optimized the purification conditions. The study revealed that yeast YT312 was Wickerhamomyces anomalus, exhibiting a broad range of growth temperatures and pH levels alongside a high tolerance to glucose, sucrose, and NaCl. Through single-factor and orthogonal experiments, it was established that under specific conditions-0.375% inoculum size, 30 °C fermentation temperature, 150 rpm shaking speed, 10-fold dilution ratio, pH of 7, and 12 h of fermentation-sucrose was completely removed from soy molasses, while functional raffinose and stachyose were retained at rates of 96.1% and 90.2%, respectively. Consequently, W. anomalus YT312 displayed exceptional characteristics for the biological purification of soy molasses and the production of FSO.

Derivation of human primordial germ cell-like cells in an embryonic-like culture.

Primordial germ cells (PGCs) are the embryonic precursors of sperm and eggs. They transmit genetic and epigenetic information across generations. Given the prominent role of germline defects in diseases such as infertility, detailed understanding of human PGC (hPGC) development has important implications in reproductive medicine and studying human evolution. Yet, hPGC specification remains an elusive process. Here, we report the induction of hPGC-like cells (hPGCLCs) in a bioengineered human pluripotent stem cell (hPSC) culture that mimics peri-implantation human development. In this culture, amniotic ectoderm-like cells (AMLCs), derived from hPSCs, induce hPGCLC specification from hPSCs through paracrine signaling downstream of ISL1. Our data further show functional roles of NODAL, WNT, and BMP signaling in hPGCLC induction. hPGCLCs are successfully derived from eight non-obstructive azoospermia (NOA) participant-derived hPSC lines using this biomimetic platform, demonstrating its promise for screening applications.

Salvianolic acid A provides neuroprotective effects on cerebral ischemia-reperfusion injury in rats via PKA/CREB/c-Fos signaling pathway.

BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI) is a phenomenon that pathological injury of ischemic brain tissue is further aggravated after the restoration of blood supply. The complex pathological mechanism of CIRI has led to the failure of multiple neuroprotective agents in clinical studies. Salvianolic acid A (SAA) is a neuroprotective extract from Salvia miltiorrhiza Bge., with significant pharmacological activities in the treatment of brain injury. However, the neuroprotective mechanisms of SAA remain unclear. PURPOSE: To explore the potential protective effect of SAA on CIRI and its mechanism, and to provide experimental basis for the research of new drugs for CIRI. STUDY DESIGN: A model of transient middle cerebral artery occlusion (tMCAO) in rats was used to simulate clinical CIRI, and the neuroprotective effect of SAA on tMCAO rats was investigated within 14 days after reperfusion. The improvement effects of SAA on cognitive impairment of tMCAO rats were investigated by behavioral tests from days 7-14. Finally, the neuroprotective mechanism of SAA was investigated on day 14. METHODS: The neuroprotective effects and mechanism of SAA were investigated by behavioral tests, HE and TUNEL staining, RNA sequence (RNA-seq) analysis and Western blot in tMCAO rats. RESULTS: The brain protective effects of SAA were achieved by alleviating cerebral infarction, cerebral edema, cerebral atrophy and nerve injury in tMCAO rats. Meanwhile, SAA could effectively improve the cognitive impairment and pathological damage of hippocampal tissue, and inhibit cell apoptosis in tMCAO rats. Besides, SAA could provide neuroprotective effects by up-regulating the expression of Bcl-2, inhibiting the activation of Caspase 3, and regulating PKA/CREB/c-Fos signaling pathway. CONCLUSION: SAA can significantly improve brain injury and cognitive impairment in CIRI rats, and this neuroprotective effect may be achieved through the anti-apoptotic effect and the regulation of PKA/CREB/c-Fos signaling pathway.

A novel amidine-based fluorescent probe TPE-4+ for rapid detection of anionic surfactant sodium dodecyl sulfate.

An accurate, fast, and simple surfactant detection method is of great significance for monitoring surfactants pollution. Sodium dodecyl sulfate (SDS) is one of the most commonly used anionic surfactants and has been listed as an important monitoring pollutant for surfactant residues. Herein, a novel fluorescent probe named TPE-4+ with four amidines as the recognition functional group and tetraphenylethene as the fluorophore was fabricated. Due to the special intramolecular environment, the probe showed selectively identification towards SDS which made an aggregation induced fluorescence enhencement. Under the optimum conditions, the fluorescence enhencement of TPE-4+ is linearly related to the concentration of SDS in the range of 5.0-60.0 µM with limit of detection (LOD) of 0.010 µM and limit of quantification (LOQ) of 0.034 µM. Relative to the reported methods, the probe in our work showed better selectivity and sensitivity. The proposed method was successfully applied for the SDS determination of disinfecting bowls.

Quality evaluation of Lonicerae Japonicae Flos from different origins based on high-performance liquid chromatography (HPLC) fingerprinting and multicomponent quantitative analysis combined with chemical pattern recognition.

INTRODUCTION: Lonicerae Japonicae Flos (LJF) is widely used in food and traditional Chinese medicine. To meet demand, Lonicera japonica Thunb. is widely cultivated in many provinces of China. However, reported studies on the quality evaluation of LJF only used a single or a few active components as indicators, which could not fully reflect the quality of LJF. OBJECTIVES: In the present study, we aimed to develop a methodology for comprehensively evaluating the quality of LJF from different origins based on high-performance liquid chromatography (HPLC) fingerprinting and multicomponent quantitative analysis combined with chemical pattern recognition. MATERIALS AND METHODS: The HPLC method was developed for fingerprint analysis and was used to determine the contents of 19 components of LJF. To distinguish between samples and identify differential components, similarity analysis, hierarchical cluster analysis, principal component analysis, and orthogonal partial least squares discriminant analysis were performed. RESULTS: The HPLC fingerprint was established. Using the developed method, the contents of 19 components recognized in the fingerprint analysis were determined. Samples from different origins could be effectively distinguished. CONCLUSIONS: HPLC fingerprinting and multicomponent quantitative analysis combined with chemical pattern recognition is an efficient method for evaluating LJF.

Comparison of the Utility of PI-RADS 2.1, ADC Values, and Combined Use of Both, for the Diagnosis of Transition Zone Prostate Cancers.

OBJECTIVE: To assess the performance of apparent diffusion coefficient (ADC; values or category) alone, Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1) scoring alone, and the two in combination, to diagnose transition zone prostate cancers (PCas). METHODS: This retrospective study included 222 patients who underwent multiparametric magnetic resonance imaging of the prostate between May 2020 and December 2022 and who had pathologically confirmed PCa or benign prostatic hyperplasia (BPH). Prostate Imaging Reporting and Data System version 2.1 and ADC (values or category) were used in the assessment of suspicious findings identified in the transition zone. The interobserver agreements for region-of-interest measurements were calculated by intraclass correlation coefficients. Logistic regression analyses were used to determine the performance of PI-RADS v2.1 alone and in combination with ADC (values or category) to diagnose PCa. Receiver operating characteristic curve and DeLong test were used to evaluate the diagnostic performance of the quantitative parameters. RESULTS: A total of 152 patients had BPH, and 70 patients had PCa. For BPH versus PCa, the ADC values of PCa (0.64 × 10 -3 ± 0.16 × 10 -3 mm 2 /s) were significantly lower than BPH (1.06 ± 0.18 × 10 -3 mm 2 /s; P < 0.001). The PI-RADS scores for PCa (5 [interquartile range, 5-5]) were significantly higher than BPH (2 [interquartile range, 2-3]; P < 0.001). For all patients who had PI-RADS 1-5, the combined use of ADC (values or category) together with PI-RADS v2.1 did not perform significantly better than the use of PI-RADS v2.1 alone. The receiver operating characteristic of ADC category in combination with PI-RADS v2.1 score, 0.756 (95% confidence interval, 0.646-0.846), was significantly higher than that for PI-RADS 2.1 alone, 0.631 (95% confidence interval, 0.514-0.738), in PI-RADS 3-4 lesions ( P = 0.047). CONCLUSION: The ADC category can help to improve the diagnostic performance of PI-RADS v2.1 category 3-4 lesions in diagnosing PCa.

Heating performance of dual-source microwave heating using different frequency shifting strategies in a solid-state system.

Solid-state microwave heating holds potential in mitigating the issue of nonuniform heating commonly observed in magnetron-based microwave ovens. Previous work on solid-state application primarily focused on single-source microwave heating and modeling of dual-source heating with fixed frequency combinations. This study experimentally investigated the port interactions and heating performance of four different frequency shifting approaches (in range of 2.4 and 2.5 GHz, at an interval of 0.01 GHz), i.e., Fixed-frequency without shifting, Synchronized-shifting, Inverse-shifting and Distinct-shifting, in a dual-source microwave system under both stationary and rotatory conditions. Results showed that port interactions were dependent on the microwave frequency and load position, both of which significantly affected the microwave power efficiency. All three shifting strategies significantly improved heating performance compared to the Fixed-frequency heating. Additionally, the use of a turntable in our dual-source microwave configuration did not improve the heating uniformity in the context of various frequency shifting processes, suggesting that the inclusion of a turntable might be dispensable in solid-state microwave systems if proper multi-port frequency shifting strategy could deliver more uniform heating.

TAD evolutionary and functional characterization reveals diversity in mammalian TAD boundary properties and function.

Topological associating domains (TADs) are self-interacting genomic units crucial for shaping gene regulation patterns. Despite their importance, the extent of their evolutionary conservation and its functional implications remain largely unknown. In this study, we generate Hi-C and ChIP-seq data and compare TAD organization across four primate and four rodent species and characterize the genetic and epigenetic properties of TAD boundaries in correspondence to their evolutionary conservation. We find 14% of all human TAD boundaries to be shared among all eight species (ultraconserved), while 15% are human-specific. Ultraconserved TAD boundaries have stronger insulation strength, CTCF binding, and enrichment of older retrotransposons compared to species-specific boundaries. CRISPR-Cas9 knockouts of an ultraconserved boundary in a mouse model lead to tissue-specific gene expression changes and morphological phenotypes. Deletion of a human-specific boundary near the autism-related AUTS2 gene results in the upregulation of this gene in neurons. Overall, our study provides pertinent TAD boundary evolutionary conservation annotations and showcases the functional importance of TAD evolution.

Diagnostic value of plasma circular RNA based on droplet digital polymerase chain reaction in lung adenocarcinoma.

BACKGROUND: Plasma circular (circ)RNAs detected by droplet digital polymerase chain reaction (ddPCR) may be ideal markers for liquid biopsy. However, ddPCR detection of circRNAs in plasma for diagnosis of lung adenocarcinoma has been rarely reported. METHODS: An RNA sequencing analysis was performed in plasma from patients with early lung adenocarcinoma and healthy individuals. Droplet digital PCR was used to verify the differentially expressed genes. RESULTS: The copy numbers of circle RNALZIC (circLZIC)and circle RNACEP350 (circCEP350) in the plasma of lung adenocarcinoma patients were significantly higher than in plasma of healthy people, and the copy numbers in postoperative plasma of the same patients were significantly lower than those in preoperative plasma. CircLZIC and circCEP350 alone and in combination had diagnostic value in lung adenocarcinoma and early lung adenocarcinoma. CircLZIC and circCEP350 had more binding sites with multiple microRNAs. Their target genes were enriched in several signaling pathways. CONCLUSION: The copy numbers of circLZIC and circCEP350 were higher in plasma of lung adenocarcinoma patients than in plasma of healthy controls, significantly correlated with tumor size and TNM stage, and closely related to the occurrence and development of tumors. These circRNAs may serve as molecular markers for the diagnosis of lung adenocarcinoma.

[Spatio-temporal Variations in PM2.5and Its Influencing Factors in the Yangtze River Delta Urban Agglomeration].

To coordinate the contradiction between economic development and environmental pollution and achieve the sustainable development of the economy and society, the spatio-temporal variations in PM2.5 were analyzed based on PM2.5 concentration and meteorological data of the Yangtze River Delta (YRD) urban agglomeration. Wavelet transform coherence (WTC), partial wavelet coherence (PWC), and multiple wavelet coherence (MWC) were used to analyze the multi-scale coupling oscillation between PM2.5 and meteorological factors in the time-frequency domain. The results showed that:① the concentration of PM2.5 in the YRD decreased from northwest to southeast, and the spatial range with high PM2.5 concentration decreased annually. The spatial distribution characteristics of the seasonal average PM2.5 concentration were similar to those of the annual average PM2.5 concentration. PM2.5 concentration exhibited the seasonal variation characteristics of high in winter, low in summer, and transitioning between spring and autumn. ② PM2.5 concentration decreased from 2015 to 2021, and the compliance rate increased. The difference in annual average PM2.5 concentration was decreased with dynamic convergence characteristics. The convergence of PM2.5 concentration in summer was greater than that in winter. During the whole study period, the daily average PM2.5 concentration showed a "U" distribution, and the proportion of days with excellent and good PM2.5 levels were 49.72% and 41.45%, respectively. ③ The wavelet coherence between PM2.5 and meteorological factors was different in different time-frequency domains. The main factors affecting PM2.5 were different in different time-frequency scales. At all time-frequency scales, WTC and PWC showed that wind speed and temperature were the best explanatory variables of PM2.5 variation, respectively. ④ The larger the time-frequency scale, the stronger the interaction of multi-factor combinations to explain PM2.5 variations. The synergistic effect of temperature and wind speed could better explain the variation in PM2.5. These results can provide reference for air pollution control in the YRD.

Delta-radiomics features for predicting the major pathological response to neoadjuvant chemoimmunotherapy in non-small cell lung cancer.

OBJECTIVES: To investigate if delta-radiomics features have the potential to predict the major pathological response (MPR) to neoadjuvant chemoimmunotherapy in non-small cell lung cancer (NSCLC) patients. METHODS: Two hundred six stage IIA-IIIB NSCLC patients from three institutions (Database1 = 164; Database2 = 21; Database3 = 21) who received neoadjuvant chemoimmunotherapy and surgery were included. Patients in Database1 were randomly assigned to the training dataset and test dataset, with a ratio of 0.7:0.3. Patients in Database2 and Database3 were used as two independent external validation datasets. Contrast-enhanced CT scans were obtained at baseline and before surgery. The delta-radiomics features were defined as the relative net change of radiomics features between baseline and preoperative. The delta-radiomics model and pre-treatment radiomics model were established. The performance of Immune-Related Response Evaluation Criteria in Solid Tumors (iRECIST) for predicting MPR was also evaluated. RESULTS: Half of the patients (106/206, 51.5%) showed MPR after neoadjuvant chemoimmunotherapy. For predicting MPR, the delta-radiomics model achieved a satisfying area under the curves (AUCs) values of 0.768, 0.732, 0.833, and 0.716 in the training, test, and two external validation databases, respectively, which showed a superior predictive performance than the pre-treatment radiomics model (0.644, 0.616, 0.475, and 0.608). Compared with iRECIST criteria (0.624, 0.572, 0.650, and 0.466), a mixed model that combines delta-radiomics features and iRECIST had higher AUC values for MPR prediction of 0.777, 0.761, 0.850, and 0.670 in four sets. CONCLUSION: The delta-radiomics model demonstrated superior diagnostic performance compared to pre-treatment radiomics model and iRECIST criteria in predicting MPR preoperatively in neoadjuvant chemoimmunotherapy for stage II-III NSCLC. CLINICAL RELEVANCE STATEMENT: Delta-radiomics features based on the relative net change of radiomics features between baseline and preoperative CT scans serve a vital support tool in accurately identifying responses to neoadjuvant chemoimmunotherapy, which can help physicians make more appropriate treatment decisions. KEY POINTS: • The performances of pre-treatment radiomics model and iRECIST model in predicting major pathological response of neoadjuvant chemoimmunotherapy were unsatisfactory. • The delta-radiomics features based on relative net change of radiomics features between baseline and preoperative CT scans may be used as a noninvasive biomarker for predicting major pathological response of neoadjuvant chemoimmunotherapy. • Combining delta-radiomics features and iRECIST can further improve the predictive performance of responses to neoadjuvant chemoimmunotherapy.

Research Progress on Cu-15Ni-8Sn Alloys: The Effect of Microalloying and Heat Treatment on Microstructure and Properties.

Cu-15Ni-8Sn alloy is the best choice to replace beryllium bronze alloy. This alloy has unparalleled application value in aerospace, ocean engineering, electronic information, equipment manufacturing, and other fields. However, the application of Cu-15Ni-8Sn alloy is challenged and limited because of a series of problems in its preparation and processing, such as easy segregation, difficult deformation, and discontinuous precipitation. It is an effective way to improve the comprehensive properties of Cu-15Ni-8Sn alloy using alloying design and process optimization to control the as-cast, deformed, and heat-treated microstructures. At present, it is a hot spot for scholars to study. In this paper, the grade generation, system evolution, and preparation technology development of Cu-15Ni-8Sn alloy are comprehensively reviewed. The phase transformation sequence of the Cu-15Ni-8Sn alloy is discussed. The influence of the type, amount, and existing form of alloying elements on the strength of Cu-15Ni-8Sn alloy and its mechanism are systematically summarized. Furthermore, the latest research progress on the effects of solid solution, cold deformation, and aging on the phase structure transformation and mechanical properties of Cu-15Ni-8Sn alloy is summarized. Finally, the future development trend of the Cu-15Ni-8Sn alloy is projected. The research results of this paper can provide a reference for the control of the microstructure and properties of high-performance Cu-15Ni-8Sn alloys used in key fields, as well as the optimization of the preparation process and alloy composition.