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Abstract Background Although low-dose computed tomography (LDCT) screening effectively reduces LC mortality in high-risk individuals with a history of smoking in China, the feasibility and efficacy of lung cancer screening (LCS) in individuals who never smoked versus individuals who smoked remains unclear. Methods We conducted a retrospective analysis of prospective cohort studies at the National Cancer Center (NCC) in China from January 2006 to December 2022. A comprehensive LCS initiative was undertaken, involving 30,468 participants (54.5% male). Participants underwent LCS using LDCT. Potential malignancies were managed through joint consensus between patients and their physicians. Epidemiology, screening eligibility criteria, and LC detection rates and survival outcomes were compared between individuals who smoked and individuals who never smoked. Results Among 30,468 participants, 339 LCs were pathologically confirmed in 289 patients. The LC detection rate was 0.9% (289/30,468) overall, 0.8% in individuals who smoked (71/9,042), and 1.0% in individuals who never smoked (218/21,426). In individuals who smoked, LC detection rates were 0.5% (21/4516) and 1.1% (50/4526) in the

Recent investigations indicate that high entropy alloys (HEAs) may exhibit distinctive thermal characteristics compared to traditional alloys. Through a blend of experiments and atomistic simulations, this study showcases that the lattice thermal conductivity of a highly distorted single-phase B2 alloy with the composition of (CoNi)50(TiZrHf)50 is as low as less than 1 W/(m·K), akin to that of ceramics like alumina, and remains stable across temperatures from 300 to 900 K. This remarkable thermal behavior is attributed to significant lattice distortion and atomic mass variation within this alloy. These findings suggest potential applications for distorted HEAs in thermal insulation technologies tailored for challenging environments.

Abstract High-entropy materials have been proposed for applications in nuclear systems recently due to their outstanding properties in extreme environments. Chemical complexity in these materials plays an important role in irradiation tolerance since it significantly affects energy dissipation and defect behaviors under particle bombardment. Indeed, better resistance to irradiation-induced amorphization was observed in the high-entropy MAX (HE-MAX) phase (Ti, M)2SnC (M = V, Nb, Zr, Hf). However, in this work, we report an opposite trend in another series of HE-MAX phases (Ti, M)2AlC (M = Nb, Ta, V, Zr). It is demonstrated that the amorphization resistance is sequentially reduced as the number of components increases from single-component Ti2AlC to (TiNbTa)2AlC and (TiNbTaVZr)2AlC. These phenomena are verified through AIMD simulations and interpreted by analyzing the underlying properties combining lattice distortion and bonding characteristics through the first-principle calculation. By developing a machine-learning (ML) model, we can directly predict lattice distortion to screen HE-MAX phases with excellent resistance to irradiation-induced amorphization. We highlight that the elemental species plays a more crucial role in the irradiation tolerance of these MAX phases than the number of constituent elements. Knowledge gained from this study will enable an improved understanding of the irradiation tolerance in HE-MAX phases and other multi-elemental ceramics.

Abstract Developing high-performance multicomponent ceramics, which are promising in solving challenges posed by emerging technologies, shows grand difficulties because of the immense compositional space and complex local distortions. In this work, an accurate machine learning (ML) model built upon an ab initio database is developed to predict the mechanical properties and structural distortions of multicomponent transition metal carbides (MTMCs). The compositional space of MTMCs is thoroughly explored by the well-trained model. Combined with electronic and geometrical analysis, we show that the elemental adaptability to the rock-salt structure elegantly elucidates the mechanical characteristics of MTMCs, and such adaptability can be quantified by local lattice distortions. We further establish new design principles for high-strength MTMCs, and V–Nb–Ta-based MTMCs are recommended, which are validated by the present experiments. The proposed model and design philosophy pave a broad avenue for the rational design of MTMCs with exceptional properties.

Abstract Background Evidence from observational studies indicates that lung cancer screening (LCS) guidelines with high rates of lung cancer (LC) underdiagnosis, and although current screening guidelines have been updated and eligibility criteria for screening have been expanded, there are no studies comparing the efficiency of LCS guidelines in Chinese population. Methods Between 2005 and 2022, 31,394 asymptomatic individuals were screened using low-dose computed tomography (LDCT) at our institution. Demographic data and relevant LC risk factors were collected. The efficiency of the LCS for each guideline criteria was expressed as the efficiency ratio (ER). The inclusion rates, eligibility rates, LC detection rates, and ER based on the different eligibility criteria of the four guidelines were comparatively analyzed. The four guidelines were as follows: China guideline for the screening and early detection of lung cancer (CGSL), the National Comprehensive Cancer Network (NCCN), the United States Preventive Services Task Force (USPSTF), and International Early Lung Cancer Action Program (I-ELCAP). Results Of 31,394 participants, 298 (155 women, 143 men) were diagnosed with LC. For CGSL, NCCN, USPSTF, and I-ELCAP guidelines, the eligibility rates for guidelines were 13.92%, 6.97%, 6.81%, and 53.46%; ERe for eligibility criteria were 1.46%, 1.64%, 1.51%, and 1.13%, respectively; and for the inclusion rates, they were 19.0%, 9.5%, 9.3%, and 73.0%, respectively. LCs which met the screening criteria of CGSL, NCCN, USPSTF, and I-ELCAP guidelines were 29.2%, 16.4%, 14.8%, and 86.6%, respectively. The age and smoking criteria for CGSL were stricter, hence resulting in lower rates of LC meeting the screening criteria. The CGSL, NCCN, and USPSTF guidelines showed the highest underdiagnosis in the 45–49 age group (17.4%), while the I-ELCAP guideline displayed the highest missed diagnosis rate (3.0%) in the 35–39 age group. Males and females significantly differed in eligibility based on the criteria of the four guidelines (P

Ordered L12 γ′ Ni3Al intermetallics are essential strengthening components to maintain the high strength of Ni-based superalloys and recently developed high entropy alloys at elevated temperatures. Under service conditions, structural disorder is usually encountered in these intermetallics, resulting in significant loss of their strengthening functionality. Thus, retaining the degree of order of the L12 intermetallics is vital for their long-term reliability and serviceability. In this study, atomistic simulations and rate equation analysis are employed to highlight a notable enhancement in the reordering ability of L12 intermetallics by incorporating multiple principal elements. Specifically, we examine the effects of Co and Ti addition on the irradiation-induced disordering and kinetic reordering process of L12 intermetallics. Our results reveal that the incorporation of Ti in the Al sublattice can maintain comparable disordering resistance as Ni3Al. Better yet, the introduction of Ti or Co fosters vacancy migration, which accelerates the kinetic reordering rate during the defect diffusion stage. A synergistic effect of Ti and Co in promoting kinetic reordering is also observed. Our work thus suggests a promising approach for designing irradiation-resistant multicomponent intermetallics, which can retain a high degree of structural order under irradiation with chemical disorder contributed by desirable compositions.

In order to quantitatively analyze the risk caused by each operational step of coal mine blasting and comprehensively and objectively assess its risk, with the help of Monte Carlo method, this paper establishes a risk assessment model of coal mine blasting operation steps, makes cumulative probability distribution of the behavioral risk consequence value of the operation process, and finally determines the risk size and risk level of each operation step based on the mean result of Monte Carlo simulation and the overall risk result of the operation process, and puts forward the measures for the control of the occurrence of such unsafe behaviors. The results of the study show that the order of risk of the blasting operation process is in the following order: clearing the items into the warehouse, loading, linkage, guarding, safety inspection after detonation, receiving and checking the blasting items, detonation, delivery of blasting items, acceptance of the task of blasting, preoperational safety inspection, pre-detonation safety inspection, sealing the holes.

Abstract Background The initial phase II stuty (NCT03215693) demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib‐refractory, anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC). Herein, we reported the updated data on overall survival (OS) and molecular profiling from the initial phase II study. Methods In this study, 180 patients received 225 mg of ensartinib orally once daily until disease progression, death or withdrawal. OS was estimated by Kaplan‒Meier methods with two‐sided 95% confidence intervals (CIs). Next‐generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib. Circulating tumor DNA (ctDNA) was detected to dynamically monitor the genomic alternations during treatment and indicate the existence of molecular residual disease, facilitating improvement of clinical management. Results At the data cut‐off date (August 31, 2022), with a median follow‐up time of 53.2 months, 97 of 180 (53.9%) patients had died. The median OS was 42.8 months (95% CI: 29.3‐53.2 months). A total of 333 plasma samples from 168 patients were included for ctDNA analysis. An inferior OS correlated significantly with baseline ALK or tumor protein 53 (TP53) mutation. In addition, patients with concurrent TP53 mutations had shorter OS than those without concurrent TP53 mutations. High ctDNA levels evaluated by variant allele frequency (VAF) and haploid genome equivalents per milliliter of plasma (hGE/mL) at baseline were associated with poor OS. Additionally, patients with ctDNA clearance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth, respectively. Furthermore, patients who had a lower tumor burden, as evaluated by the diameter of target lesions, had a longer OS. Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases, higher hGE, and elevated ALK mutation abundance at 6 weeks. Conclusion Ensartinib led to a favorable OS in patients with advanced, crizotinib‐resistant, and ALK‐positive NSCLC. Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.

Abstract Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution (SCRaMbLE) is a promising tool to study genomic rearrangements. However, the potential of SCRaMbLE to study genomic rearrangements is currently hindered, because a strain containing all 16 synthetic chromosomes is not yet available. Here, we construct SparLox83R, a yeast strain containing 83 loxPsym sites distributed across all 16 chromosomes. SCRaMbLE of SparLox83R produces versatile genome-wide genomic rearrangements, including inter-chromosomal events. Moreover, when combined with synthetic chromosomes, SCRaMbLE of hetero-diploids with SparLox83R leads to increased diversity of genomic rearrangements and relatively faster evolution of traits compared to hetero-diploids only with wild-type chromosomes. Analysis of the SCRaMbLEd strain with increased tolerance to nocodazole demonstrates that genomic rearrangements can perturb the transcriptome and 3D genome structure and consequently impact phenotypes. In summary, a genome with sparsely distributed loxPsym sites can serve as a powerful tool for studying the consequence of genomic rearrangements and accelerating strain engineering in Saccharomyces cerevisiae.

The Nishihara creep model is an extremely effective method in the field of sandstone creep model research. However, the Nishihara creep model curve for sandstone under the marine environment (the coupled effect of chemical corrosion and temperature) does not fit the actual creep test data well. Based on the Nishihara creep model, we discovered that, on the one hand, the viscoelastic elements in the Nishihara model are replaced by the viscoelastic elements containing temperature and pH factors, which can accurately describe the influence of temperature and pH on rock creep characteristics; on the other hand, the viscoplastic elements in the Nishihara model are replaced by nonlinear viscoplastic elements, which can accurately describe the accelerated creep stage of the rock mass. After modifying Nishihara’s creep model twice, a new temperature–pH damage nonlinear creep model is established. The creep curve of the temperature–pH damage nonlinear creep model is compared with the creep test data of sandstone. The comparison results indicate that the creep curve of the nonlinear creep model has a high degree of fit with the creep test data of sandstone (accuracy > 92%). This validates the correctness of the newly established temperature–pH damage nonlinear creep model presented in this paper, demonstrating that the new model can effectively reflect the influence of temperature and pH on the creep characteristics of sandstone.

Abstract The genome of an organism is inherited from its ancestor and continues to evolve over time, however, the extent to which the current version could be altered remains unknown. To probe the genome plasticity of Saccharomyces cerevisiae, here we replace the native left arm of chromosome XII (chrXIIL) with a linear artificial chromosome harboring small sets of reconstructed genes. We find that as few as 12 genes are sufficient for cell viability, whereas 25 genes are required to recover the partial fitness defects observed in the 12-gene strain. Next, we demonstrate that these genes can be reconstructed individually using synthetic regulatory sequences and recoded open-reading frames with a “one-amino-acid-one-codon” strategy to remain functional. Finally, a synthetic neochromsome with the reconstructed genes is assembled which could substitute chrXIIL for viability. Together, our work not only highlights the high plasticity of yeast genome, but also illustrates the possibility of making functional eukaryotic chromosomes from entirely artificial sequences.

Abstract Purpose To investigate the correlations between metabolic parameters (MPs) of 18F‐fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT), serum tumor markers (STMs), and tumor mutational burden (TMB) in patients with non‐small cell lung cancer (NSCLC). Materials and Methods In this retrospective study, we enrolled 129 patients with NSCLC (males, 78; females, 51) who underwent baseline TMB and STM tests and 18F‐FDG PET/CT scans before treatment between March 2018 and September 2022. Patients were categorized into TMB‐high (TMB ≥10 mutations/Mb; n = 27 [20.9%]) and non‐TMB‐high (TMB

Abstract Background In China, over 50% of lung cancer cases occur in nonsmokers. Thus, identifying high‐risk individuals for targeted lung cancer screening is crucial. Beyond age and smoking, determining other risk factors for lung cancer in the Asian population has become a focal point of research. Using 30,000 participants in the prospectively enrolled cohort at China's National Cancer Center (NCC) over the past 14 years, we categorized participants by risk, with an emphasis on nonsmoking females. Materials and Methods Between November 2005 and December 2019, 31,431 individuals voluntarily underwent low‐dose computed tomography (LDCT) scans for lung cancer screening at the NCC. We recorded details like smoking history, exposure to hazards, and family history of malignant tumors. Using the 2019 NCCN criteria, participants were categorized into high‐, moderate‐, and low‐risk groups. Additionally, we separated non‐high‐risk groups into female never smokers (aged over 40) exposed to second‐hand smoke (SHS) and others. Any positive results from initial scans were monitored per the I‐ELCAP protocol (2006), and suspected malignancies were addressed through collaborative decisions between patients and physicians. We analyzed and compared the detection rates of positive results, confirmed lung cancers, and cancer stages across risk, age, and gender groups. Results Out of 31,431 participants (55.9% male, 44.1% female), 3695 (11.8%) showed positive baseline LDCT scans with 197 (0.6%; 106 females, 91 males) confirmed as lung cancer cases pathologically. Malignancy rate by age was 0.1% among those aged under 40 years, 0.4% among those aged 40–49 years, 0.8% among those aged 50–59 years, and 1.2% among those aged 60 years and older. From the 25,763 participants (56.9% male, 43.1% female) who completed questionnaires, 1877 (7.3%) were categorized as high risk, 6500 (25.2%) as moderate risk, and 17,386 (67.5%) as low risk. Of the 23,886 in the non‐high‐risk category, 8041 (33.7%) were females over 40 years old exposed to SHS. The high‐risk group showed the highest lung cancer detection rate at 1.4%. However, females exposed to SHS had a notably higher detection rate than the rest of the non‐high‐risk group (1.1% vs. 0.5%; p

Summary: In eukaryotic genomes, rDNA generally resides as a highly repetitive and dynamic structure, making it difficult to study. Here, a synthetic rDNA array on chromosome III in budding yeast was constructed to serve as the sole source of rRNA. Utilizing the loxPsym site within each rDNA repeat and the Cre recombinase, we were able to reduce the copy number to as few as eight copies. Additionally, we constructed strains with two or three rDNA arrays and found that the presence of multiple arrays did not affect the formation of a single nucleolus. Although alteration of the position and number of rDNA arrays did impact the three-dimensional genome structure, the additional rDNA arrays had no deleterious influence on cell growth or transcriptomes. Overall, this study sheds light on the high plasticity of rDNA organization and opens up opportunities for future rDNA engineering.

Previous studies revealed that both Helicobacter pylori infection and some cytokine gene polymorphisms are risk factors for gastric diseases. The association between H. pylori and gene polymorphisms is worth exploring. Here we conducted a case–control study and systematically evaluate on association between H. pylori infection and IL4, TNFA, and IL10 polymorphisms in a Chinese Han population in northwestern China, where gastric cancer is the major burden on the health and the leading cause of death in local community. The Sequenom MassArray platform was used to screen the genotypes and 14C-urea breath test was employed to determine H. pylori infection status of 705 participants of the local rural residents. Significant association between H. pylori infection and the IL4 rs34142320 polymorphism was observed in the dominant model (OR = 0.57, 95% CI = 0.40–0.80, P = 0.030). No significant association was found between IL4 rs2243250, TNFA rs1800630, TNFA rs1800629, TNFA rs1799964, IL10 rs1800871, IL10 rs1800896 and H. pylori infection. Haplotype analysis showed that T-DEL and G-C haplotypes of the observed IL4 SNPs were significantly associated with H. pylori infection. Our analysis demonstrated that the IL4 rs34142320 polymorphism has a protective effect on H. pylori infection in Chinese Han population.

Single-phase concentrated solid-solution alloys (CSAs) have exhibited excellent mechanical and radiation tolerance properties, making them potential candidate materials for nuclear applications. These excellent properties are closely related to dislocation movements, which depend on the stacking fault energies (SFEs). In CSAs, SFEs show large fluctuations due to variations in the local atomic environments in the vicinity of the stacking faults. In this work, first-principle calculations were performed to investigate the origin of the fluctuations in the SFEs of the widely studied CSA, NiCoCr, which show a very wide distribution from about −200 mJ/m2 to 60 mJ/m2. Compared to the common understanding that only atoms in close proximity to the stacking fault influence the SFEs in pure metals and dilute alloys, charge redistribution can be observed in several nearby planes of the stacking fault in NiCoCr, indicating that atoms several atomic layers away from stacking fault also contribute to the SFEs. Our analysis shows that Cr plays a major role in the large fluctuation in the SFEs of NiCoCr based on both electronic and magnetic responses. The flexible electronic structure of Cr facilitates easier charge transfer with Cr in several nearby atomic planes near the stacking fault, leading to significant changes in the d-electron number, orbital occupation number, and magnetic moments of Cr.

Helium is the second most abundant element in the universe, and at low temperatures it becomes a quantum crystal with exotic physical properties such as second sound, superfluidity, and giant plasticity. Here authors prepare 2D solid helium at room temperature through diamond lattice confinement.

Imidazole ionic liquids (ILs) have good affinity and good solubility for carbon dioxide (CO2). Such ionic liquids, combined with polyimide membrane materials, can solve the problem that, today, CO2 is difficult to separate and recover. In this study, the ionic liquid (IL) of 1-ethyl-3-methylimidazolium tetrafluoroborate (IL1), 1-pentyl-3-methylimidazolium tetrafluoroborate (IL2), 1-octyl-3-methylimidazolium tetrafluoroborate (IL3), and 1-dodecylimidazolium tetrafluoroborate (IL4) with different contents were added to a polyimide matrix, and a series of polyimide membranes blended with ionic liquid were prepared using a high-speed mixer. The mechanical properties and gas separation permeability of the membranes were investigated. Among them, the selectivity of the PI/IL3 membrane for CO2/CH4 was 180.55, which was 2.5 times higher than the PI membrane, and its CO2 permeability was 16.25 Barrer, which exceeded the Robeson curve in 2008; the separation performance of the membrane was the best in this work.

Numerous studies have observed and analyzed the dynamics of language change from a diffusion perspective. As a complex and changeable system, the process of language change is characterized by a long memory that conforms to ultraslow diffusion. However, it is not perfectly suited for modeling with the traditional diffusion model. The Caputo nonlocal structural derivative is a further development of the classic Caputo fractional derivative. Its kernel function, characterized as an arbitrary function, proves highly effective in dealing with ultraslow diffusion. In this study, we utilized an extended logarithmic function to formulate a Caputo nonlocal structural derivative diffusion model for qualitatively analyzing the evolution process of language. The mean square displacement that grows logarithmically was derived through the Tauberian theorem and the Fourier–Laplace transform. Its effectiveness and credibility were verified by the appearance of already popular words on Japanese blogs. Compared to the random diffusion model, the Caputo nonlocal structural derivative diffusion model proves to be more precise in simulating the process of language change. The microscopic mechanism of ultraslow diffusion was explored using the continuous time random walk model, which involves a logarithmic function with a long tail. Both models incorporate memory effects, which can provide useful guidance for modeling diffusion behavior in other social phenomena.

The characterization and understanding of crack evolution in non-uniform geological structures are crucial for predicting the mechanical response of rock-like materials or structures under varying loading conditions. In this study, an improved Peridynamic model with a degree of heterogeneity characterized by random pre-breaking “bonds” coefficients is introduced to capture the intricacies of crack initiation, propagation, and branching behaviors in heterogeneous rock-like materials. MATLAB discrete programs for heterogeneous material models and PD simulation programs based on the FORTRAN language were developed. The effectiveness of the heterogeneous PD model in simulating crack propagation and branching patterns in heterogeneous materials has been verified through dynamic and static (quasi-static) loading cases with pre-notch. The different levels of heterogeneity not only affect the direction of crack propagation but also determine the crack deflection direction and branching patterns. The crack propagation path appears to possess obvious asymmetry in the crack propagation direction. As the load applied continues to increase, the asymmetric multi-crack branching phenomenon will occur. The higher the level of heterogeneity, the more complex the behaviors of crack propagation and branching become. This research provides valuable insights into the interplay of material heterogeneity and crack evolution, offering a foundation for improved numerical simulations and contributing to the broader field of geomechanics.

Nanoparticle strengthening provides a crucial basis for developing high-performance materials, which often fails to work due to poor thermal stability. Here, the authors achieve thermally stable nanoparticles at 800~1000 °C in chemically complex alloys via controllable sluggish lattice diffusion.

Abstract Objectives Whether curative‐intent radiotherapy could be safely applied to lung cancer patients with interstitial lung diseases (ILD) remains unclear. We aim to evaluate radiation induced lung toxicities (RILTs) and the efficacy of intensity‐modulated radiotherapy (IMRT) in these patients. ILD is characterized by inflammation or fibrosis in the interstitial tissue of the lung. Materials and Methods Stage III non–small cell lung cancer (NSCLC) and ILD patients treated with curative‐intent IMRT between 2010 and 2019 were retrospectively reviewed. Pre‐radiation computed tomography (CT) was scored according to a thin‐section CT scoring system for idiopathic pulmonary fibrosis. Results A total of 85 of 1261 stage III NSCLC patients were found with ILD. Seventeen (20%) of them developed G3+ (greater than or equal to grade 3) RILTs. The incidence abruptly dropped to 11.1%, 3.8%, and 0% for patients with honeycombing score ≤1, V20 1 and V20 ≥20% were independently associated with higher risk of G3+ RILTs. The median overall survival (OS) and progression‐free survival (PFS) were 14.0 months and 7.4 months in the whole group, whereas 26.5 months and 10.6 months in the low‐risk group (patients with honeycombing score 1 and V20 ≥20% were associated with high incidence of RILTs. However, patients with low risk might benefit from IMRT with acceptable toxicities and durable OS.

As a promising candidate material for the accident tolerant fuel cladding in light water reactors, the Nb-containing FeCrAl alloy has shown outstanding out-of-pile service performance due to the Laves phase precipitation. In this work, the radiation response in FeCrAl alloys with gradient Nb content under heavy ion radiation has been investigated. The focus is on the effect of the Laves phase on irradiation-induced defects and hardening. We found that the phase boundary between the matrix and Laves phase can play a critical role in capturing radiation defects, as verified by in-situ heavy-ion radiation experiments and molecular dynamic simulations. Additionally, the evolution of Laves phase under radiation is analyzed. Radiation-induced amorphization and segregations observed at high radiation doses will deepen the fundamental understanding of the stability of Laves phases in the radiation environment.

While (oxy)hydroxides are effective oxygen evolution electrocatalysts, the impacts of pre-catalyst properties on catalyst activities are challenging to assess. Here, authors find Mo dopants in Ni-Fe (oxyhydroxides) to promote lattice oxygen participation and to boost oxygen evolution activities.

Abstract High-entropy ceramics (HECs) have shown great application potential under demanding conditions, such as high stresses and temperatures. However, the immense phase space poses great challenges for the rational design of new high-performance HECs. In this work, we develop machine-learning (ML) models to discover high-entropy ceramic carbides (HECCs). Built upon attributes of HECCs and their constituent precursors, our ML models demonstrate a high prediction accuracy (0.982). Using the well-trained ML models, we evaluate the single-phase probability of 90 HECCs that are not experimentally reported so far. Several of these predictions are validated by our experiments. We further establish the phase diagrams for non-equiatomic HECCs spanning the whole composition space by which the single-phase regime can be easily identified. Our ML models can predict both equiatomic and non-equiatomic HECs based solely on the chemical descriptors of constituent transition-metal-carbide precursors, which paves the way for the high-throughput design of HECCs with superior properties.

Multi-principal elemental alloys (MPEAs) exhibit unusual mechanical properties and irradiation resistance. It has been reported that the irradiation tolerance of MPEAs originates from the long-term defect evolution stage rather than the ballistic collision phase. However, understanding the long-term evolution of MPEAs is exceptionally challenging due to intrinsic chemical disorder. In this work, we apply atomistically-informed cluster dynamics to study defect evolution in MPEAs for the first time, which enables us to elucidate the critical features responsible for the irradiation performance of MPEAs. With suitable irradiation parameters, our obtained cluster size distributions are in good agreement with experiments. We further discuss the influences of defect migration energy heterogeneity, cluster geometry, and temperature on the produced defect cluster forms. Our results suggest that the small clusters during the collision phase in MPEAs suppress the formation of large-sized defect clusters in the long term. Contrary to the common belief, a broader migration energy distribution due to chemical disorder cannot reduce the maximal defect cluster size but increase the proportion of small clusters. Our results thus reveal that the major role of chemical complexity in MPEAs is to modify the growth mechanism of clusters by promoting small cluster formation and suppressing overall defect diffusivities.

BackgroundScreening for lung cancer with LDCT detects a large number of nodules. However, it is unclear whether nodule number influences lung cancer probability. This study aimed to acquire deeply insight into the distribution characteristics of nodule number in the Chinese population and to reveal the association between the nodule number and the probability of lung cancer (LC).Methods10,167 asymptomatic participants who underwent LDCT LC screening were collected. Noncalcified nodules larger than 4 mm were included. The nodule number per participant was determined. We defined five categories according to the number of nodules (based on nodule type and size): one, two, three, four, and more than four nodules. We stratified the nodules as groups A, B, and C and participants as Amax, Bmax, and Cmax groups, and explored the association between nodule number and the probability of LC on nodule and participant levels.Results97 participants were confirmed to have LC. The probabilities of LC were 49/1719, 22/689, 11/327, 6/166, and 9/175 in participants with one, two, three, four, and more than four nodules (p>0.05), respectively. In the Bmax group, the probability of LC was significantly higher in participants with one nodule than those with >4 nodules (p4 nodules (p

Abstract Background Here, we aimed to assess the association of ALK variants and alterations with ensartinib response duration in NSCLC, and explore the potential value of computed tomography (CT) radiomic features in predicting progression‐free survival (PFS). Methods We enrolled 88 patients with identified ALK variant NSCLC in a multicenter phase 2 trial, and assessed the impact of ALK variants and secondary ALK alterations on the clinical outcome (response duration) of patients receiving ensartinib. We also established a multifactorial model of clinicopathological and quantitative CT radiomic features to predict PFS and risk stratification. Kaplan–Meier analysis was conducted to identify risk factors for tumor progression. Results Univariate analysis indicated a statistical difference (p = 0.035) in PFS among ALK variants in three classifications (V1, V3, and other variants). Secondary ALK alterations were adversely associated with PFS both in univariate (p = 0.008) and multivariate (p = 0.04) analyses and could identify patients at high risk for early progression in the Kaplan–Meier analysis (p = 0.002). Additionally, response duration to crizotinib

Multi-principal element alloys (MPEAs), including high entropy alloys, show exceptional mechanical properties and corrosion resistance. These unusual properties are mostly attributed to their particular diffusion behaviors, such as sluggish diffusion. However, this phenomenon is still controversial. Although state-of-the-art simulations report that the percolation effect plays a crucial role in triggering sluggish diffusion in binary alloys, whether this correlation could be generalized to a broad class of MPEAs is unknown. In this work, we combine machine learning (ML) with kinetic Monte Carlo (kMC) to accurately determine the diffusion coefficients in ternary CoCrNi MPEAs. Special care is taken to understand the effects of percolation on diffusion. We find that percolation does not always lead to sluggish diffusion. Instead, the diffusion properties are exclusively governed by the potential energy landscape (PEL) that the diffusing objects experience. By comparing the reduced systems of CoNi and FeNi, we reveal that the percolation effect on triggering the sluggish diffusion strongly depends on the diffusion properties of the slow-diffuser in these systems. These results shed light on the understanding of the complex diffusion behaviors in MPEAs, highlighting the importance of tunning species-dependent PEL in order to tailor their diffusion properties.

L-3-n-butylphthalide (NBP), which is used for treatment of mild and moderate acute ischemic stroke, exerts its effects by modulating the Nrf2 pathway. However, it has not been established whether NBP exerts its preventive effects in high-risk ischemic stroke patients through the Nrf2 pathway. We investigated whether NBP exerts its preventive effects through the Nrf2 pathway in long-term NBP pretreated dMCAO mice models. Nrf2+/+ wild-type and Nrf2−/− knockout mice were randomized into the vehicle group (equal volume vegetable oil), NBP-low-dose group (20 mg/kg) and NBP-high-dose group (60 mg/kg). The drug was administered once daily by gavage for a month. Then, a permanent distal middle cerebral artery occlusion model (dMCAO) was established after pretreatment with NBP. Neurological deficits, cerebral infarct volumes, brain water contents, activities of SOD, GSH-Px and MDA levels were determined. Further, axonal injury and demyelination, expression levels of Nrf2, HO-1 and NQO1 in ischemic brains were determined. Long-term NBP pretreatment significantly improved neurological functions, reduced cerebral infarction volumes, reduced brain water contents, increased SOD, GSH-Px activities, decreased MDA contents, reduced neurological injuries, axonal damage as well as demyelination, while increasing Nrf2, HO-1 and NQO1 mRNA as well as protein expressions in dMCAO mice models.

The ecological security of cultivated land critically depends on maintaining the quality of the land under cultivation. For the security of the nation’s grain supply, the evaluation and early warning of cultivated land quality (CLQ) are essential. However, previous studies on the assessment of the ecological safety of CLQ only rigidly standardized the assessment indicators and failed to investigate the positive and negative trends and spatiotemporal driving factors of the indicators. The main objective of this study was to develop a drive–pressure–state–response (DPSR) model to identify the hierarchical structure of indicators, using an improved matter–element model to assess the CLQ in the black soil region of northeastern China from 2001 to 2020. A panel data model was employed to explore the crucial drivers of CLQ warnings. The findings reveal that socioeconomic development has a potential impact on the improvement of CLQ. CLQ is generally in a secure state, with 69.71% of cities with no warnings and only 3.46% and 0.13% of cities under serious and extreme warnings, respectively. Compared with 2001, the CLQ in 2020 effectively improved by socioeconomic development and the conservation and reasonable utilization of arable land. According to the early warning results, the cultivated land in the northern regions was of higher quality than that in the southern regions. Moreover, the CLQ was significantly positively correlated with the agricultural GDP growth rate, grain yield per unit of cultivated land area, annual precipitation, and the habitat quality index, and was significantly negatively correlated with land carrying capacity. The findings of this study can provide a scientific and targeted basis for black soil conservation and utilization.

Abstract Background Redundancy is a common feature of genomes, presumably to ensure robust growth under different and changing conditions. Genome compaction, removing sequences nonessential for given conditions, provides a novel way to understand the core principles of life. The synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE) system is a unique feature implanted in the synthetic yeast genome (Sc2.0), which is proposed as an effective tool for genome minimization. As the Sc2.0 project is nearing its completion, we have begun to explore the application of the SCRaMbLE system in genome compaction. Results We develop a method termed SCRaMbLE-based genome compaction (SGC) and demonstrate that a synthetic chromosome arm (synXIIL) can be efficiently reduced. The pre-introduced episomal essential gene array significantly enhances the compacting ability of SGC, not only by enabling the deletion of nonessential genes located in essential gene containing loxPsym units but also by allowing more chromosomal sequences to be removed in a single SGC process. Further compaction is achieved through iterative SGC, revealing that at least 39 out of 65 nonessential genes in synXIIL can be removed collectively without affecting cell viability at 30 °C in rich medium. Approximately 40% of the synthetic sequence, encoding 28 genes, is found to be dispensable for cell growth at 30 °C in rich medium and several genes whose functions are needed under specified conditions are identified. Conclusions We develop iterative SGC with the aid of eArray as a generic yet effective tool to compact the synthetic yeast genome.

This work is concerned with the characterization of load-dependent dielectric loss and sensitivity analysis for CNT-based nanocomposite sensors (CNCSs) under AC loading. To this end, an electromechanically coupled microstructural theory is developed from the bottom up to quantitatively predict their overall dielectric loss change ratio and strain-sensitivity factor. In the theory, various categories of load-dependent functional interface effects, such as strain- and filler-dependent electron hopping and dielectric relaxation, are incorporated into it. The electric damage process under mechanical load is characterized through the principle of irreversible thermodynamics. The outcome is a microstructure-based coupled theory whose predictions of AC dielectric loss change ratio can be directly calibrated with the experimental data of MWCNT/PVDF nanocomposite sensor over a broad strain loading range from 0 to 10% and a wide frequency spectrum from 5 kHz to 500 kHz, where PVDF is a shape memory polymer. The theory further demonstrates the advantage of demarcating CNCSs via the dielectric loss over the traditional electric resistance. It can be used to rapidly determine the macroscopic dielectric loss change ratio by choosing a specific CNT volume concentration and AC working frequency, and further simplify the design procedure of highly sensitive strain sensors.

Recently, the oblique earth-space links (OELs) between satellite and earth station have been used for rainfall monitoring as a supplement to existing observation methods. Most recent studies achieved the rainfall measurement by OELs based on the empirical method such as power-law (PL) model. In practice, two crucial issues need to be addressed: 1) identification of rain and no-rain periods; and 2) determination of attenuation baseline. To solve these problems, this article adopts several machine learning algorithms based on the analysis of earth-space link signal characteristics. For the first issue, we choose the support vector machine as a classifier and the adaptive synthetic sampling algorithm is deployed to eliminate the effects caused by the data imbalance. For the second issue, the long short-term neural network is selected for the determination of attenuation baseline since it has a good ability to solve time-series problem. In terms of the rainfall inversion, we establish a new model by combining the back-propagation (BP) network and genetic algorithm (GA). The PL model is also used as a comparison. To validate the proposed method, we set up an earth-space link that receives the signal from AsiaSat5 in 12.32 GHz. The results demonstrate that the two issues are successfully addressed and the inversion of precipitation is also carried out. Compared to disdrometer, the correlation and mean absolute error of GA-BP model are 0.83 and 1.30 mm/h, respectively, indicating a great potential to use densely OELs for global precipitation monitoring.

Objectives: To investigate the predictive ability of clinical and chest computed tomography (CT) features to predict the severity of symptomatic immune checkpoint inhibitor-related pneumonitis (CIP). Methods: This study included 34 patients diagnosed with symptomatic CIP (grades 2–5) and divided into mild (grade 2) and severe CIP (grades 3–5) groups. The groups’ clinical and chest CT features were analyzed. Three manual scores (extent, image finding, and clinical symptom scores) were conducted to evaluate the diagnostic performance alone and in combination. Results: There were 20 cases of mild CIP and 14 cases of severe CIP. More severe CIP occurred within 3 months than after 3 months (11 vs. 3 cases, p = 0.038). Severe CIP was significantly associated with fever (p < 0.001) and the acute interstitial pneumonia/acute respiratory distress syndrome pattern (p = 0.001). The diagnostic performance of chest CT scores (extent score and image finding score) was better than that of clinical symptom score. The combination of the three scores demonstrated the best diagnostic value, with an area under the receiver operating characteristic curve of 0.948. Conclusions: The clinical and chest CT features have important application value in assessing the disease severity of symptomatic CIP. We recommend the routine use of chest CT in a comprehensive clinical evaluation.

Introduction: Sleep disorders can affect the overall health and quality of life of patients. This study was conducted to compare the differences of sleep disorders in vestibular migraine (VM) patients and benign paroxysmal positional vertigo (BPPV) patients.Methods: VM patients, BPPV patients, and healthy controls (HCs) were recruited. Pittsburgh sleep quality index and polysomnography monitoring were used as subjective and objective, respectively, evaluation methods to evaluate the sleep quality of participants in the latest month.Results: Fifty-seven BPPV patients, 48 VM patients, and 42 HCs were included in this study. There were 79.16% VM patients, 54.39% BPPV patients, and 14.28% HCs with sleep disorders. The difference in the incidence rate of sleep disorders was significant between VM patients and BPPV patients (p = 0.008) and significantly higher in both the VM group (p < 0.00001) and BPPV group (p = 0.00004) than in the HC groups (14.28%). Compared with BPPV patients, the VM patients had the significantly lower sleep efficiency (p < 0.001) and N3 (p < 0.001) and the significantly higher time of wake-up after sleep onset (p < 0.001), N1 (p < 0.001), and N2 (p < 0.001). Meanwhile, the VM patients had significantly higher incidence rates of severe obstructive sleep apnea hypoventilation syndrome (p = 0.001) and periodic leg movement in sleep (p = 0.016).Conclusion: The incidence rate of sleep disorders was significantly higher in both VM and BPPV patients than in the HC groups. To improve the curative effects, clinicians should pay more attention to the comorbidity of sleep disorders in treating VM and BPPV.

Purpose: Tirofiban administration to acute ischemic stroke patients undergoing mechanical thrombectomy with preceding intravenous thrombolysis remains controversial. The aim of the current study was to evaluate the safety and efficacy of low-dose tirofiban during mechanical thrombectomy in patients with preceding intravenous thrombolysis.Methods: Patients with acute ischemic stroke undergoing mechanical thrombectomy and preceding intravenous thrombolysis were derived from “ANGEL-ACT,” a multicenter, prospective registry study. The patients were dichotomized into tirofiban and non-tirofiban groups based on whether tirofiban was administered. Propensity score matching was used to minimize case bias. The primary safety endpoint was symptomatic intracerebral hemorrhage (sICH), defined as an intracerebral hemorrhage (ICH) associated with clinical deterioration as determined by the Heidelberg Bleeding Classification. All ICHs and hemorrhage types were recorded. Clinical outcomes included successful recanalization, dramatic clinical improvement, functional independence, and mortality at the 3-month follow-up timepoint. Successful recanalization was defined as a modified Thrombolysis in Cerebral Ischemia score of 2b or 3. Dramatic clinical improvement at 24 h was defined as a reduction in NIH stroke score of ≥10 points compared with admission, or a score ≤1. Functional independence was defined as a Modified Rankin Scale (mRS) score of 0–2 at 3-months.Results: The study included 201 patients, 81 in the tirofiban group and 120 in the non-tirofiban group, and each group included 68 patients after propensity score matching. Of the 201 patients, 52 (25.9%) suffered ICH, 15 (7.5%) suffered sICH, and 18 (9.0%) died within 3-months. The median mRS was 3 (0–4), 99 (49.3%) achieved functional independence. There were no statistically significant differences in safety outcomes, efficacy outcomes on successful recanalization, dramatic clinical improvement, or 3-month mRS between the tirofiban and non-tirofiban groups (all p > 0.05). Similar results were obtained after propensity score matching.Conclusion: In acute ischemic stroke patients who underwent mechanical thrombectomy and preceding intravenous thrombolysis, low-dose tirofiban was not associated with increased risk of sICH or ICH. Further randomized clinical trials are needed to confirm the effects of tirofiban in patients undergoing bridging therapy.

The unusual mechanical and radiation properties found in concentrated solid–solution alloys (CSAs) make them promising candidate materials in nuclear applications. In this work, He behavior in a typical CSA, NiCFeCr, is assessed by first-principles calculations. Our results suggest that the energy difference of He in substitutional and interstitial sites is greatly reduced. The energy barriers of He through both interstitial and substitutional diffusion are much higher than those in pure Ni, indicating slower He dynamics in CSAs. The calculated activation energies show that the dissociation mechanism is more favorable in NiCoFeCr, which helps to suppress He growth as observed experimentally.

Vascular calcification was an independent risk of cardiovascular and cerebrovascular diseases (CCDs). Studies reported that conditioned media of choroid plexus epithelium cells (CPECs-CM) showed potential neuroprotective effects. However, the protective effect of CPECs-CM against vascular calcification (VC) has not been reported yet. Herein, high phosphate (HPi)–induced calcification model in mouse aortic vascular smooth muscle cells (MOVAS) was established, and the protective effects and underlying mechanism of CPECs-CM against HPi-induced calcification were explored. The results indicated that CPEC cells were successfully isolated and cultured, and CPECs-CM co-treatment significantly inhibited HPi-induced calcification of MOVAS cells through blocking alkaline phosphatase activity and expression. CPECs-CM co-treatment also suppressed reactive oxide species–mediated DNA damage in HPi-treated MOVAS cells. Moreover, dysfunction of MAPKs and PI3K/AKT pathways both contributed to HPi-induced calcification of MOVAS cells, and CPECs-CM co-treatment attenuated HPi-induced calcification by normalizing MAPKs and PI3K/AKT expression. Taken together, our findings provide evidence that CPECs-CM had the potential to inhibit vascular calcification with potent application in chemoprevention and chemotherapy of human CCD.

Low-level wind shear is a vital weather process affecting aircraft safety while taking off and landing and is known as the “aircraft killer” in the aviation industry. As a result, effective monitoring and warning are required. Several ramps detection algorithms for low-level wind shear based on glide path scanning of lidar have been developed, including double and simple ramp detection, with the ramp length extension and contraction strategies corresponding to the algorithm. However, current algorithms must be improved to determine the maximum shear value and location. In this paper, a new efficient algorithm based on the shear intensity factor value is presented, in which wind speed changes and distance are both considered when calculating wind shear. Simultaneously, the effectiveness of the improved algorithm has been validated through numerical simulation experiments. Results reveal that the improved algorithm can determine the maximum intensity value and wind shear location more accurately than the traditional algorithm. In addition, the new algorithm improved the detection ability of lidar for weak wind shear.

Understanding the void swelling dependence on irradiation dose for structural materials is critical for the design and operation of advanced nuclear reactors. Due to their easy accessibility in high-voltage transmission electron microscopes, electron beams have been frequently employed to investigate the void swelling mechanisms. Here, we build a general model to describe the radiation-induced swelling produced by energetic electrons. Based on this model, we develop a quantitative relation between void swelling and irradiation dose, which is in good agreement with experimental data. By extrapolating to high-dose swelling in electron-irradiated alloys, our model validation is consistent with available experiments. Furthermore, the model is well supported by our phase-field simulations.

Abstract Background Mortality outcomes in trials of low-dose computed tomography (CT) screening for lung cancer are inconsistent. This study aimed to evaluate whether CT screening in urban areas of China could reduce lung cancer mortality and to investigate the factors that associate with the screening effect. Methods A decision tree model with three scenarios (low-dose CT screening, chest X-ray screening, and no screening) was developed to compare screening results in a simulated Chinese urban cohort (100,000 smokers aged 45–80 years). Data of participant characteristics were obtained from national registries and epidemiological surveys for estimating lung cancer prevalence. The selection of other tree variables such as sensitivities and specificities of low-dose CT and chest X-ray screening were based on literature research. Differences in lung cancer mortality (primary outcome), false diagnoses, and deaths due to false diagnosis were calculated. Sensitivity analyses were performed to identify the factors that associate with the screening results and to ascertain worst and optimal screening effects considering possible ranges of the variables. Results Among the 100,000 subjects, there were 448, 541, and 591 lung cancer deaths in the low-dose CT, chest X-ray, and no screening scenarios, respectively (17.2% reduction in low-dose CT screening over chest X-ray screening and 24.2% over no screening). The costs of the two screening scenarios were 9387 and 2497 false diagnoses and 7 and 2 deaths due to false diagnosis among the 100,000 persons, respectively. The factors that most influenced death reduction with low-dose CT screening over no screening were lung cancer prevalence in the screened cohort, low-dose CT sensitivity, and proportion of early-stage cancers among low-dose CT detected lung cancers. Considering all possibilities, reduction in deaths (relative numbers) with low-dose CT screening in the worst and optimal cases were 16 (5.4%) and 288 (40.2%) over no screening, respectively. Conclusions In terms of mortality outcomes, our findings favor conducting low-dose CT screening in urban China. However, approaches to reducing false diagnoses and optimizing important screening conditions such as enrollment criteria for screening are highly needed.

Deformation and fracture of brittle materials, especially crack propagation, have drawn wide attention in recent years. But dynamic crack propagation under impact loading was not well understood. In this paper, we experimentally tested Brazilian disk (BD) fine sandstone specimens containing pre-cracks under cyclic impact loading by the Φ 74 mm diameter split Hopkinson pressure bar (SHPB) test device. The pre-cracked specimens were named central straight through crack flattened Brazilian disk (CSCFBD). By using the low air-pressure loading conditions (0.1 MPa, equal to the impact velocity of 3.76 m/s), a series of dynamic impact tests were detected successfully, and the effects of pre-cracks on dynamic properties were analyzed. Experimental results show that the multiple cracks mostly initiate at/or near the pre-crack tips and then propagate in different paths and directions varying by inclination angles, leading to the ultimate failure. Compared to static or quasi-static loading, dynamic crack propagation and fracture behavior are obviously different. Furthermore, we characterized the crack propagation paths, directions, and fracture patterns and discussed the influences of the pre-cracks during the breakage process. We concluded that the results obtained are significant in investigating the failure mechanism and mechanical properties of brittle materials under impact loading.

This study aims to investigate the fracture behaviors of cracks and crack systems in Brazilian disk (BD) sandstone specimens under compressive line loading. We conduct a series of rock fracture experiments to investigate crack initiation, propagation, and coalescence in samples with one or more pre-existing flaws under radial compressive stress. The displacements and failure loads of the tested specimens are measured. Experimental results show that there are two main types of cracks growing from the pre-existing flaws: wing cracks and secondary cracks. Both initiate mostly from the tips of the pre-existing flaws and propagate in a stable manner. The results reveal that wing cracks appear first and propagate toward the loading direction. Secondary cracks can form in some multiple pre-cracked cases after wing cracks are already present. We also provide a characterization of the observed crack propagation paths and patterns and discuss the influence of pre-existing crack or crack systems. The results help in investigating the failure mechanisms and mechanical properties of rock or rock-like materials.

To ensure successful hosting of the 2022 Olympic Winter Games, a comprehensive understanding of the wind field characteristics in the Chongli Mountain region is essential. The purpose of this research was to accurately simulate the microscale wind in the Chongli Mountain region. Coupling the Weather Research and Forecasting (WRF) model with a computational fluid dynamics (CFD) model is a method for simulating the microscale wind field over complex terrain. The performance of the WRF-CFD model in the Chongli Mountain region was enhanced from two aspects. First, as WRF offers multiple physical schemes, a sensitivity analysis was performed to evaluate which scheme provided the best boundary condition for CFD. Second, to solve the problem of terrain differences between the WRF and CFD models, an improved method capable of coupling these two models is proposed. The results show that these improvements can enhance the performance of the WRF-CFD model and produce a more accurate microscale simulation of the wind field in the Chongli Mountain region.

The effect of silica fume (SF) in concrete on mechanical properties and dynamic behaviors was experimentally studied by split Hopkinson pressure bar (SHPB) device with pulse shaping technique. Three series of concrete with 0, 12%, and 16% SF as a cement replacement by weight were produced firstly. Then the experimental procedure for dynamic tests of concrete specimens with SF under a high loading rate was presented. Considering the mechanical performance and behaviors of the concrete mixtures, those tests were conducted under five different impact velocities. The experimental results clearly show concrete with different levels of SF is a strain-rate sensitive material. The tensile strength under impact loading of the tested specimens was generally improved with the increasing content of SF levels in concrete. Additionally, the tensile strength under impact loading of the concrete enhances with the increase of the strain rates. Finally, failure modes, dynamic tensile strength, dynamic increase factor (DIF), and critical strain are discussed and analyzed. These investigations are useful to improve the understanding of the effect of SF in concrete and guide the design of concrete structures.