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A multi-objective evolutionary algorithm based on decomposition with an improved hybrid particle swarm optimization (MOEA/D-IHPSO) method is proposed, which aims to enhance the efficiency of automated optimization for antenna geometry. The optimization process includes two stages: optimization problem modeling and algorithm application. In the first stage, the topology optimization regions are selected according to the surface current distribution of the antenna, and a differential grid division strategy is employed to characterize the selected regions, ensuring the modeling accuracy of the key topology areas. By combining the encoded topological parameters of the selected regions with the key size parameters, a hybrid solution vector is formed and subsequently used to generate the initial population. In the second stage, the proposed framework uses new crossover and adaptive mutation operators to accelerate the process of reaching the target solution. Furthermore, MOEA/D-IHPSO incorporates a novel transfer learning-based recombination strategy that directly leverages historical optimization data without requiring surrogate model training, thereby intelligently guiding the search direction. To validate the effectiveness of the method, a dual-polarized omnidirectional antenna is optimized. Experimental results show that the optimization efficiency is improved by 31.8% and 26% compared to IBPSO and MOEA/D-GO algorithms, respectively.
In laser-produced plasma (LPP) extreme ultraviolet (EUV) sources, deformation of a tin droplet into an optimal target shape is determined by its interaction with a pre-pulse laser-generated plasma. This interaction is mediated by a transient ablation pressure, whose complex spatio-temporal evolution remains experimentally inaccessible. Existing modelling approaches are limited: empirical pressure–impulse models neglect dynamic plasma feedback, while advanced radiation hydrodynamics codes often fail to resolve late-time droplet hydrodynamics. To bridge this gap, we propose a radiation two-phase flow model based on a diffuse interface approach. The model integrates radiation hydrodynamics for the plasma with the Euler equations for a weakly compressible liquid, extending a five-equation diffuse interface formulation to incorporate radiation transport, thermal conduction, ionisation and surface tension. This formulation enforces pressure and velocity equilibrium across the diffuse interface region, with closure models constructed to ensure correct jump conditions at interfaces and asymptotically recover the pure-phase equations in bulk regions. Then we apply the model to simulate a benchmark pre-pulse scenario, where a $50\ \unicode{x03BC} \mathrm{m}$ tin droplet is irradiated by a $10\ \mathrm{ns}$ laser pulse. Our axisymmetric simulations capture the rapid plasma expansion and subsequent inertial flattening of the droplet into a thin, curved sheet over microsecond time scales. Notably, the model reproduces experimentally observed features such as an axial jet – rarely replicated in prior simulations. Quantitative agreement with experimental data for sheet dimensions and velocity validates the approach. The proposed model self-consistently couples laser–plasma physics with compressible droplet dynamics, providing a powerful tool for studying plasma–liquid interactions in LPP-EUV source optimisation.
Prior observational studies have reported conflicting results regarding whether antidepressant treatment reduces long-term dementia risk, likely due to confounding by indication and reverse causation. We aimed to investigate the association between baseline antidepressant use and incident dementia, incorporating cognitive and neuroimaging outcomes.
Methods
We conducted a prospective cohort study using UK Biobank participants free of dementia at baseline. Antidepressant use was self-reported at baseline (2006–2010). Incident dementia was identified through linked electronic health records until December 19, 2022. Cox proportional hazards models estimated hazard ratios (HRs) for all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VD), adjusting for sociodemographic, lifestyle, health-related, antidepressant indication factors, and co-medication of other anticholinergics. In subsamples, cognitive performance (n = 57,330) and structural brain imaging (n = 42,276) were examined as intermediate outcomes.
Results
Among 461,464 participants, 33,721 (7.3%) reported baseline antidepressant use. Over a mean follow-up of 13.4 years, 7,922 (1.7%) developed incident dementia. Baseline antidepressant use was associated with higher risks of all-cause dementia (adjusted HR: 1.47, 95% CI 1.36–1.60), AD (1.53, 1.36–1.73), and VD (1.44, 1.23–1.70). Users performed worse on fluid intelligence and prospective memory tasks and showed lower total and gray matter volume, regional reductions in the hippocampal gray matter and basal nucleus, and greater white matter hyperintensity volume.
Conclusions
Baseline antidepressant use was linked to a higher risk of dementia, poorer cognitive performance, and adverse brain structural changes. These findings underscore the importance of judicious prescribing, regular cognitive monitoring, and consideration of non-pharmacological approaches in clinical care.
Schizophrenia (SCZ) and bipolar disorder (BD) are severe psychiatric conditions with overlapping clinical presentations, genetic risk factors, and brain network dysfunction. Whether alterations in large-scale intrinsic brain networks reflect shared or disorder-specific genetic influences remains poorly understood. Clarifying this distinction is essential for refining etiological models and improving diagnostic precision.
Methods
Genome-wide inferred statistics (GWIS) were applied to decompose the genetic architecture of SCZ and BD into shared and unique components. Using resting-state network (RSN) data from the UK Biobank, functional connectivity (FC) and structural connectivity (SC) were extracted as neuroimaging phenotypes. Causal inference approaches were subsequently employed to infer potential directional relationships between brain network connectivity and each disorder.
Results
Analyses revealed both common and distinct patterns of brain network connectivity associated with SCZ and BD. Notably, SC within the default mode network (DMN) exhibited opposing effects across the two disorders, suggesting divergent structural underpinnings despite clinical overlap. Additionally, SC within the limbic network (LN) and frontotemporal control network demonstrated potential causal relationships with both conditions, implicating these circuits astransdiagnostic neural substrates.
Conclusion
These findings illuminate the shared and disorder-specific genetic and neural architecture underlying SCZ and BD. Integrating genome-wide genetic methods with large-scale neuroimaging data offers a powerful framework for disentangling psychiatric comorbidity and may inform more targeted diagnostic criteria and individualized treatment strategies.
This work presents an integrated modelling study of fast-proton distributions generated by ion cyclotron range of frequency (ICRF) minority heating in the Experimental Advanced Superconducting Tokamak (EAST). Using a series of high-confinement (H-mode) discharges with increasing ICRF power levels from 0.8 to 2.4 MW, fast protons were produced via minority heating mechanisms and analysed through simulations using the ASCOT code. The results reveal that the fast protons are primarily concentrated near the fundamental cyclotron resonance layer and exhibit strong power-dependent behaviour in both real-space (R–Z) distribution and velocity space, where R is the major radius and Z is the vertical coordinate. As the ICRF power increases, the energetic proton population shows significant spatial broadening and energy enhancement, reaching up to 1 MeV. The fast-ion pitch-angle distribution becomes increasingly anisotropic, with high-energy ions concentrated around $|\textit{v}_{\|}/\textit{v}| \lt 0.5$, where $\nu$ is the magnitude (speed) of the full velocity vector of the particle. Furthermore, the energy density of fast ions aligns well with the ICRF power deposition profile, confirming efficient central-core heating. These findings, which provide insight into fast-ion behaviour and ICRF heating characteristics in EAST plasmas, also support future fast-ion diagnostics and performance control strategies in EAST and similar experimental conditions.
The mechanisms governing generation and amplification of laser-driven electromagnetic pulses (EMPs) in the picosecond (ps) regime remain insufficiently understood. Here, we present a unified theoretical and experimental framework that demonstrates dual-picosecond laser irradiation of solid targets can synergistically enhance EMP emission. By integrating particle-in-cell simulations with three-dimensional electromagnetic modeling, we reveal that the increasing laser focal power density amplifies hot electron emission and strengthens neutralization currents, leading to giant EMP radiations. Experimentally, we validate these predictions at the XG-III and SG-II U picosecond petawatt laser facilities, achieving a record-breaking EMP field strength of 3.08 MV/m – substantially exceeding previously reported values from ps-laser–solid interactions. Furthermore, we demonstrate that EMP characteristics can be precisely tuned via laser and target parameters, enabling controllable, high-field electromagnetic sources. Our findings provide deep insight into the physics of laser-driven EMP amplification and establish a robust platform for developing next-generation high-intensity electromagnetic emitters.
Pronounced variations in suicide mortality persist across Europe. Understanding long-term temporal patterns through age, period and cohort (APC) effects, alongside suicide means, is essential for tailored prevention. This study aims to determine how suicide mortality rates in Europe have changed across APC dimensions at national and subregional levels.
Methods
Our analysis was restricted to European countries with complete age- and sex-specific suicide mortality data from 1990 to 2019 within the World Health Organization mortality database. The analysis comprised two components. The first component disentangled long-term suicide mortality trends (1990–2019) into APC dimensions using an age-period-cohort model via the National Cancer Institute’s APC Web Tool. The second component involved an assessment of suicide means, restricted to 2010–2019 and to countries with detailed International Classification of Diseases, 10th Revision (ICD-10) cause-of-death data.
Results
In 2019, Europe recorded 47,793 male and 13,111 female suicide deaths. Overall suicide mortality rates declined in most subregions from 1990 to 2019, with the largest reductions among Eastern European men, from 77.81 (95% CI: 77.17–78.45) per 100,000 in the mid-1990s to 22.93 (95% CI: 22.58–23.28) per 100,000 by 2019, although this region retained the highest male suicide burden. Age-specific risk patterns differed markedly: among men, risk peaked in early adulthood and then declined in Eastern Europe, while in Western and Southern Europe, it was lower and more stable but rose after age 60; for women, risk was generally lower, with peaks in early adulthood in Eastern Europe and in midlife elsewhere. Period reflected continued improvement, especially in Eastern Europe where the period risk in 2015–2019 was approximately 60% lower than 2000–2004. Cohort effects similarly showed progressive declines. However, upward trends emerged among younger generations. In Northern Europe, the cohort relative risk for females increased from 0.73 (95% CI: 0.68–0.78) in the 1980 cohort to 0.90 (95% CI: 0.70–1.04) in the 2000 cohort. While the completeness of suicide means analysis varied by subregion, the primary data indicated that hanging was the predominant means for both sexes during 2010–2019.
Conclusions
Despite an overall decline, suicide mortality in Europe exhibits persistent regional and demographic differences. This study reveals emerging risks among younger cohorts, specifically Northern European women and Southern European men, signalling shifting patterns that are not apparent from overall temporal trends alone. This evolving risk profile calls for sustained surveillance and research to investigate the drivers of these population-specific vulnerabilities.
The objective of this study was to investigate the gene-breastfeeding interaction on BMI based on the Chinese National Twin Register (CNTR). The study included 4,573 pairs of same-sex twins aged 2–18 from CNTR. Data were collected using a self-reported questionnaire, and a structural equation model was used to analyze the gene-environment interaction of breastfeeding with BMI in six age groups. Our findings indicate that as age increases, the heritability of BMI shows an increasing trend, being the lowest (h2: 0.08; 95% CI [0.00, 0.19]) in the 6- to 8-year age group and the highest (h2: 0.57, 95% CI [0.44, 0.72]) in the 12- to 14-year age group. Additionally, breastfeeding significantly modified the additive genetic component of BMI in the 6- to 8-year age group and 12- to 14-year age group. In the 6- to 8-year age group, breastfeeding decreased the impact of genes on BMI, with a genetic effect modification coefficient (βa) of −0.19 (−0.25, −0.13). In the 12- to 14-year age group, breastfeeding increased the impact of genes on BMI, with a genetic effect modification coefficient (βa) of 0.08 (0.02, 0.15). In conclusion, as age increases, the genetic influence on children’s BMI becomes more pronounced. Breastfeeding may modulate genetic effects at the ages of 6–8 and 12–14. Given the metabolic diversity of obesity, our findings offer insight into how breastfeeding interacts with genetic background, helping to unravel the complex gene–environment interplay influencing obesity.
Direct-seeding of rice by sowing dry seeds on dry soils often results in poor seedling emergence due to erratic rainfall. Adjusting the sowing depth to a given rainfall pattern may improve rice emergence. To assess risks of crop failure in direct-seeded rice, we developed a platform for modelling and simulation of rice emergence at different sowing depths. We combined the HYDRUS-1D soil simulation model, which simulates the surface soil’s moisture dynamics, with two rice emergence models recently developed by our research group. The platform used 48 years of daily weather data (1977–2024) for the study site as inputs for the soil model to simulate soil moisture and temperature at designated depths. We then input the simulated values and sowing depths into the emergence models to simulate final emergence and the emergence date. The simulated soil water tension at a depth of 1 cm showed huge interannual variation, reaching 10 MPa in dry years. The simulation showed that relative to a 1-cm sowing depth, depths of 4 and 6 cm greatly reduce the probability of crop failure under rainfed conditions (from 8 % to between 1 % and 2 %). Our novel platform for risk assessment should therefore facilitate the use of direct-seeded rice in suboptimal environments. The platform also fills a knowledge gap for simulation of crop establishment in direct-seeded rice under future climate scenarios.
Streptococcus agalactiae, a major bovine mastitis pathogen, poses significant economic and antimicrobial resistance (AMR) challenges. This study evaluated AMR in 128 isolates from Shandong, Hebei and Inner Mongolia using the broth microdilution method. Results showed high sensitivity to most antibiotics (e.g. 100% resistance to penicillin, ceftiofur, amoxicillin, cefquinome and vancomycin) but significant resistance to tetracycline (80.7%) and daptomycin (99.3%). Inner Mongolia isolates exhibited higher resistance and mimimum inhibitory concentrations (MIC) values, reflecting regional antibiotic usage differences, guiding mastitis treatment and antibiotic stewardship in China's dairy industry.
The consumption of ultra-processed food (UPF) has been linked to bone metabolism in adults, but its impact on bone mineral density (BMD) in children and adolescents remains unclear. This study analysed data from 4809 children and adolescents aged 8–19 years, drawn from the National Health and Nutrition Examination Survey (NHANES) 2011–2018. UPF intake was categorised according to the NOVA classification system, with the percentage of energy derived from UPF divided into quartiles (Q1–Q4). A weighted multiple linear regression model was used to examine the relationship between UPF intake and lumbar spine BMD (LSBMD) and subtotal BMD (SBMD). Stratified analyses were conducted to explore associations across various subgroups. The results indicated that UPF intake was positively associated with LSBMD. This association was significant in girls for both LSBMD and SBMD. Positive correlations with LSBMD also emerged in 12–15 years old and specific subgroups. Moreover, mediation analysis showed total cholesterol mediated 4·8 % of the UPF–LSBMD link, and HDL-cholesterol mediated 0·9 % of the UPF–SBMD one. These findings indicate that UPF intake is associated with increased BMD in children and adolescents. Future research should further investigate the complex effects of UPF on the health of this population.
Extending the concept of economic interdependence to the subnational level, this paper explores how the foreign commercial ties of non-state actors can introduce geopolitical risks to advanced democracies. We examine this phenomenon through the lens of US–China higher education partnerships. Facing budget constraints, public universities in the United States often rely on revenue from international tuition and fees. Due to trade barriers in China, American universities frequently recruit fee-paying Chinese students through joint degree programs (JDPs) established with Chinese partner institutions. These transnational partnerships create asymmetric market dependencies that the Chinese government can exploit. Using newly compiled panel data from the United States, we find that the extensive pre-existing JDP network is significantly correlated with the proliferation of Confucius Institutes (CIs) – a flagship soft power initiative of the Chinese government – on American college campuses. Preliminary evidence from other countries aligns with the patterns observed in the USA. Our findings highlight how China employs a decentralized approach to advance its soft power strategy through higher education ties.
Multi-plane light conversion (MPLC) is a versatile technique that enables arbitrary manipulation of optical fields, and is numerically investigated as a novel avenue for coherent beam combining (CBC) applications. The optical parameters have been investigated to guide the MPLC design, indicating that the number of phase planes and plane spacing serve as pivotal factors. The channel scalability is simulated, revealing that the plane spacing should be increased in a larger array to maintain high performance under a few-plane limit. CBC of up to 1027 lasers has been numerically demonstrated with near-diffraction-limited beam quality (M2 of 1.16 and combining efficiency close to 100%) with only seven phase plates. Beam steering is investigated, revealing that steering capability is related to both the number of multiplexed modes in MPLC and their mode fidelities, and the main-lobe power ratio of 87.1% at one divergence angle is achieved in a 10-mode MPLC with five phase plates.
Although extensive research has been conducted on the impact of the COVID-19 pandemic on global mental health, a systematic synthesis of the cross-time dynamics of suicidal ideation (SI) remains lacking. This study aims to systematically synthesise the global aggregated prevalence of SI before and after the pandemic, investigate the potential association between pandemic exposure and the SI risk through meta-regression analysis of longitudinal studies, and explore key moderating factors.
Methods
A systematic search was conducted in Web of Science, PubMed, PsycINFO and ProQuest databases up to August 2025. Observational studies were included if they employed cross-sectional or longitudinal designs and reported the prevalence of SI before and after the pandemic across global regions.
Results
The analysis included 354 cross-sectional studies (N = 8,247,875) and 27 longitudinal studies. In cross-sectional studies, the pooled prevalence of SI was 13.20% [95% CI 12.06%–14.42%]. Pre-pandemic prevalence was 12.52% [95% CI 8.46%–18.14%], and post-pandemic prevalence was 13.24% [95% CI 12.07%–14.50%], with no significant difference. Meta-regression analysis identified three moderators. Specifically, larger sample sizes (n) were associated with lower prevalence (β = −0.232, P < 0.0001); higher study quality predicted lower prevalence (β = −0.278, P < 0.001); and studies on adults reported significantly lower prevalence than adolescents (β = −0.366, P < 0.05). Conversely, time progression during the pandemic, development level, geographical area, gender and measurement method did not show significant independent effects. Interaction analyses also found no significant moderating effect of economic development level or geographical area on the temporal trend of SI prevalence. Longitudinal analysis found no significant increase in prevalence from the pre-pandemic to the post-pandemic period (P = 0.101). However, a small but significant increase occurred between early and late stages within the pandemic (β = 0.265, P = 0.021). Subgroup analyses showed no significant moderation of these temporal changes.
Conclusions
The COVID-19 pandemic’s impact on SI was dynamic. While no significant prevalence change was found between pre- and post-pandemic periods, a significant increase occurred as the crisis progressed. This deteriorating trend was more pronounced in adolescents, identifying them as a key vulnerable group. Methodologically, findings were moderated by the measurement instrument, study quality and sample size, with evidence suggesting potential small-study effects. These findings underscore the need for robust mental health surveillance and targeted interventions for at-risk populations during prolonged public health crises.
The protocol was registered on PROSPERO (CRD42024603151).
How psychotic symptoms, depressive symptoms, cognitive deficits, and functional impairment may interact with one another in schizophrenia or bipolar disorder is unclear.
Methods
This study explored these interactions in a discovery sample of 339 Chinese, of whom 146 had first-episode schizophrenia and 193 had bipolar disorder. Psychotic symptoms were assessed using the Positive and Negative Symptom Scale; depressive symptoms, using the Hamilton Depression Rating Scale; cognitive deficits, using tests of processing speed, executive function, and logical memory; and functional impairment, using clinical assessments. Network models connecting the four types of variables were developed and compared between men and women and between disorders. Potential causal relationships among the variables were explored through directed acyclic graphing. The results in the discovery sample were compared to those obtained for a validation sample of 235 Chinese, of whom 138 had chronic schizophrenia and 97 had bipolar disorder.
Results
In the discovery and validation cohorts, schizophrenia and bipolar disorder showed similar networks of associations, in which the central hubs included ‘disorganized’ symptoms, depressive symptoms, and deficits in processing speed during the digital symbol substitution test. Directed acyclic graphing suggested that disorganized symptoms were upstream drivers of cognitive impairment and functional decline, while core depressive symptoms (e.g. low mood) drove somatic and anxiety symptoms.
Conclusions
Our study advocates for transdiagnostic, network-informed strategies prioritizing the mitigation of disorganization and depressive symptoms to disrupt symptom cascades and improve functional outcomes in schizophrenia and bipolar disorder.
Previous studies highlighted the health benefits of coffee and tea, but they only focused on the comparisons between different consumptions. Consequently, the association estimate lacked a clear interpretation, as the substitution of beverages and distribution of doses were not explicitly prescribed. We focused on the ‘relative association’ to ascertain the optimal consumption strategy (including total intake and optimal allocation strategy) for coffee, tea and plain water associated with decreased mortality. Self-reported coffee, tea and plain water intake were used from the UK Biobank. Within a compositional data analysis framework, a multivariate Cox model was used to assess the relative associations after adjusting for a range of potential confounders. The lower mortality risk was observed with at least approximately 7–8 drinks/d of total consumption. When the total intake > 4 drinks/d, substituting plain water with coffee or tea was linked to reduced mortality; nevertheless, the benefit was not seen for ≤ 4 drinks/d. Besides, a balanced consumption of coffee and tea (roughly a ratio of 2:3) associated with the lowest hazard ratios of 0·55 (95 % CI 0·47, 0·64) for all-cause mortality, 0·59 (95 % CI 0·48, 0·72) for cancer mortality, 0·69 (95 % CI 0·49, 0·99) for CVD mortality, 0·28 (95 % CI 0·15, 0·52) for respiratory disease mortality and 0·35 (95 % CI 0·15, 0·82) for digestive disease mortality than other combinations. These results highlight the importance of the rational combination of coffee, tea and plain water, with particular emphasis on ensuring adequate total intake, offering more comprehensive and explicit guidance for individuals.
The current study aims to assess associations between trimethylamine N-oxide (TMAO) levels and mortality and to investigate modification effects of genetics. A total of 500 participants from a family-based cohort study were enrolled from 2005 to 2017 and followed up until 2020 in Fangshan District, Beijing, China. Serum TMAO levels were measured using the ELISA kit. The primary outcomes were all-cause mortality and deaths from CVD and stroke. During a median follow-up time of 7·38 years, thirty-eight deaths were recorded, including twenty deaths due to CVD and nineteen deaths due to stroke. Compared with the lowest TMAO quartile group, the HR for all-cause mortality was 1·35 (95 % CI: 0·44, 4·15), 1·65 (95 % CI: 0·58, 4·64) and 2·45 (95 % CI: 0·91, 6·57), respectively, in higher groups. No association was observed between TMAO and CVD mortality. However, compared with the lowest TMAO concentration group, the HR for stroke mortality was 1·93 (95 % CI: 0·40, 9·39), 1·91 (95 % CI: 0·41, 8·96) and 4·16 (95 % CI: 0·94, 18·52), respectively, in higher groups (Pfor trend = 0·046). Furthermore, polygenic risk score (PRS) for longevity modified the association of TMAO with all-cause mortality (Pfor interaction = 0·008). The risk of mortality (HR = 2·20, 95 % CI: 1·06, 4·57) was higher among participants with lower PRS compared with higher PRS (HR = 1·00, 95 % CI: 0·71, 1·40). The study indicates that elevated serum TMAO levels are potentially associated with long-term mortality risk in rural areas of northern China, especially for stroke deaths. Additionally, it provides novel evidence that genetic variations might modify the association.
MicroRNAs (miRNAs) alterations in patients with bipolar disorder (BD) are pivotal to the disease’s pathogenesis. Since obtaining brain tissue is challenging, most research has shifted to analyzing miRNAs in peripheral blood. One innovative solution is sequencing miRNAs in plasma extracellular vesicles (EVs), particularly those neural-derived EVs emanating from the brain.
Methods
We isolated plasma neural-derived EVs from 85 patients with BD and 39 healthy controls (HC) using biotinylated antibodies targeting a neural tissue marker, followed by miRNA sequencing and expression analysis. Furthermore, we conducted bioinformatic analyses and functional experiments to delve deeper into the underlying pathological mechanisms of BD.
Results
Out of the 2,656 neural-derived miRNAs in EVs identified, 14 were differentially expressed between BD patients and HC. Moreover, the target genes of miR-143-3p displayed distinct expression patterns in the prefrontal cortex of BD patients versus HC, as sourced from the PsychENCODE database. The functional experiments demonstrated that the abnormal expression of miR-143-3p promoted the proliferation and activation of microglia and upregulated the expression of proinflammatory factors, including IL-1β, IL-6, and NLRP3. Through weighted gene co-expression network analysis, a module linking to the clinical symptoms of BD patients was discerned. Enrichment analyses unveiled these miRNAs’ role in modulating the axon guidance, the Ras signaling pathway, and ErbB signaling pathway.
Conclusions
Our findings provide the first evidence of dysregulated plasma miRNAs within neural-derived EVs in BD patients and suggest that neural-derived EVs might be involved in the pathophysiology of BD through related biological pathways, such as neurogenesis and neuroinflammation.
High gain greater than 106 is crucial for the preamplifiers of joule-class high-energy lasers. In this work, we present a specially designed compact amplifier using 0.5%Nd,5%Gd:SrF2 and 0.5%Nd,5%Y:SrF2 crystals. The irregular crystal shape enhances the gain length of the laser beam and helps suppress parasitic oscillations. The amplified spontaneous emission (ASE) induced by the high gain is analyzed through ray tracing. The balance between gain and ASE is estimated via numerical simulation. The gain spectral characteristics of the two-stage two-pass amplifier are examined, demonstrating the advantages of using different crystals, with bandwidths up to 8 nm and gains over 106. In addition, the temperature and stress distributions in the Nd,Gd:SrF2 crystal are simulated. This work is expected to contribute to the development of high-peak-power ($\ge$terawatt-class) high-energy (joule-class) laser devices.