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Cognitive and behavioral symptoms of major depressive disorder (MDD) are linked to aberrant changes in the controllability of brain networks. However, previous studies examined network controllability using white matter tractography, neglecting the contributions of gray matter. We aimed to examine differences in the controllability of morphometric networks between patients with MDD and demographic-matched healthy controls and identify the associated neurobiological signatures.
Methods
Based on the structural and diffusion MRI data from two independent cohorts, we calculated the controllability of morphometric similarity networks for each participant. A generalized additive model was used to investigate the case–control differences in regional controllability and their cognitive and behavioral associations. We investigated the associations between imaging-derived controllability and neurotransmitters, brain metabolism, and gene transcription profiles using multivariate linear regression and partial least squares regression analyses.
Results
In both cohorts, depression-related abnormalities of morphometric network controllability were primarily located in the prefrontal, cingulate, and visual cortices, contributing to memory, sensation, and perception processes. These abnormalities in network controllability were spatially aligned with the distributions of serotonergic transmission pathways as well as with altered oxygen and glucose metabolism. In addition, these abnormalities spatially overlapped with differentially expressed genes enriched in annotations related to protein catabolism and mitochondria in neuronal cells and were disproportionately located on chromosome 22.
Conclusions
Collectively, neuroimaging evidence revealed aberrant morphometric network controllability underlying MDD-related cognitive and behavioral deficits, and the associated genetic and molecular signatures may help identify the neurobiological mechanisms underlying MDD and provide feasible therapeutic targets.
To synthesize the available experimental study evidence to estimate the effects of ketamine on suicide ideation (SI) in high-risk individuals.
Methods
We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Double-blind randomized controlled trials and open-label studies investigating the safety and effectiveness of ketamine on SI published up to October 2025 were identified. Data were pooled using random-effects meta-analysis. The main outcome was standardized mean difference on SI in high-risk individuals. Secondary outcomes were the percentage of adverse events and the moderator effects.
Results
We identified 21 studies with a total of 927 participants meeting our inclusion criteria. The pooled effect size for the reduction of SI after ketamine treatment was significant and clinically meaningful (large effect size of −1.40, 95% confidence interval: −2.15 to −0.66, P < 0.001, low–quality evidence). Dissociation (38.8%, P = 0.014), nausea (31.6%, P < 0.001), dizziness (24.7%, P = 0.003), headache (22.0%, P = 0.011) and anxiety (15.8%, P < 0.001) were the frequently reported adverse events. Moderator analyses indicated that the effect was higher in younger individuals and those with severe SI.
Conclusions
Our findings highlight the effectiveness of ketamine in reducing SI in high-risk individuals, especially younger individuals and those with severe ideation. Nonetheless, additional research is required to better understand optimal dosing regimens and the potential long-term effects of ketamine treatment.
This study aimed to determine the optimal Biological Effective Dose (BED)-based compensation strategy for treatment interruptions in left-sided breast cancer radiotherapy, with a focus on evaluating cardiac substructures to address a previously unmet clinical need.
Methods:
Twenty patients with left-sided breast cancer who had received radiotherapy were retrospectively enrolled.
Simulations assumed treatment interruptions (number of interruption days) occurred after the first week, ranging from 1 to 10 days. Three BED-based compensation strategies were evaluated: (A) maintaining total fractions and days while delivering twice-daily treatments; (B) maintaining total days while increasing the dose per fraction; and (C) keeping the dose per fraction constant while extending the overall treatment course. Original uninterrupted plans served as the baseline. BEDs for the planning target volume (PTV), simultaneous integrated boost (SIB), cardiac substructures and other organs at risk (OARs) were calculated. Physical and BED differences among the schemes were systematically compared.
Results:
Compared to the original scheme, physical doses to PTV and SIB were lower in Scheme B but higher in Scheme C. As interruptions increased from 1 to 10 days, PTV and SIB doses in Scheme B decreased to minimum values of 42.71 Gy and 50.58 Gy, respectively, while Scheme C resulted in maximum values of 58.60 Gy and 67.15 Gy. Analysis of BED changes (ΔBED) in OARs revealed that the left anterior descending artery (LAD) was the most affected cardiac substructure, with ΔBED values of 0.41, –1.20 and 0.60 for Schemes A, B and C, respectively, at 10 interruption days. Among other OARs, the left lung showed the highest ΔBED changes (0.39, –0.30 and 0.32, respectively). Most OAR comparisons reached statistical significance (ANOVA, p < 0.05).
Conclusion:
Compensation strategies for radiotherapy interruptions significantly influence the BED of OARs, particularly in the LAD and left lung. Scheme B most effectively reduced the BED of OARs but requires replanning. Schemes A and C offer clinical convenience at the cost of a higher BED of OARs. The choice of compensation strategy should be individualised based on clinical priorities and patient-specific anatomy.
The conventional design method for high-performance concrete (HPC) mixture proportion requires a large amount of trial mixing work to obtain the desired HPC mixture proportion, which consumes a lot of manpower, material resources, and time resources during the trial mixing process. In recent years, an intelligent scheme for HPC mixture proportion design has been developed. To more effectively optimize HPC mixture proportions, this article proposes a novel intelligent HPC mixture proportion design method. Firstly, this article establishes a hybrid multi-objective optimization (MOO) method for HPC mixture proportion design problem, called CNN–NSDBO–EWTOPSIS. In this MOO framework, there are three objective functions, namely the compressive strength (CS) of concrete, cost, and carbon dioxide emissions. Among them, based on the various components of concrete, this article constructs a convolutional neural network (CNN) regression prediction model for predicting the CS of concrete. The calculation of cost and carbon dioxide emissions involves the utilization of two polynomials. Additionally, dung beetle optimizer (DBO) is used to optimize the hyperparameters of the CNN. Furthermore, this article incorporates the constructed CNN regression prediction model and two polynomials as the three objective functions for HPC mixture proportion design problem. This three-objective optimization problem is solved using a non-dominated sorting dung beetle optimizer (NSDBO). Finally, based on the obtained Pareto front, this article obtains a good solution using the entropy weight technique for order preference by similarity to an ideal solution (EWTOPSIS) method. The experimental results indicate that the proposed CNN–NSDBO–EWTOPSIS approach can achieve HPC mixture proportion design.
To investigate the characteristics of a turbulent boundary layer (TBL) over the curved edge of the bow of submarine technology program office (SUBOFF) model, wall-resolved large-eddy simulation is conducted at a Reynolds number of $\mathop {\textit{Re}}\nolimits _L = 1.1 \times {10^6}$ based on the model length and free-stream velocity. Instead of using a trip wire at the bow surface, turbulent inflow is added to the simulation to induce boundary layer transition. The effects of geometric curvature and inflow turbulence intensity (ITI) are examined. With a low ITI level, natural transition takes place at the rear end of the straight section. With higher ITI levels, turbulence emerges immediately and evolves gradually, following a strong favourable-pressure-gradient (FPG) region near the forehead, which is significantly influenced by the large streamwise curvature. Within the FPG region, the root mean square of the wall pressure fluctuation (WPF) decreases rapidly, with the frequency spectra of WPF exhibiting good scalability with outer variables. Moreover, higher turbulence intensity levels lead to larger skin friction, which is related to the development of the TBL. To elucidate the generation mechanism of skin friction, the dynamic decomposition is derived in the curvilinear coordinate system. The mean convection and streamwise pressure gradient make the largest contributions to the local skin friction. Furthermore, an analysis of the energy transfer process based on the Reynolds stress transport equations in the curvilinear coordinate system is presented, highlighting the significant impact of geometric effects, particularly on the production term.
In this study, HFRS data were obtained from China CDC and ECDC, while monthly meteorological data and GDP were extracted from the National Bureau of Statistics of China website. Descriptive epidemiology, time series decomposition, and spatial autocorrelation analyses were employed to evaluate HFRS incidence patterns. A spatial panel data model was used to estimate the effects of meteorological and socio-economic variables on HFRS incidence. The average annual incidence rate of HFRS was 0.90/100000 in China, compared to 29.3/100000 in Finland. The incidence level in China was comparable to that in Belgium and the EU/EEA (excluding the UK), the high-incidence age group was 45–64 years, which was similar to Finland and the EU/EEA. HFRS in China exhibited marked seasonality. Three north-eastern provinces, Shaanxi, Shandong, and Jiangxi reported higher incidence rates. After adjusting for spatial individual effects and spatial autocorrelation, HFRS incidence was negatively associated with precipitation during the same period, per capita GDP showed no significant effect on HFRS incidence. Continued surveillance and prevention of HFRS remain necessary in China, particularly in Shaanxi. Additional disease prevention and control efforts should be directed towards individuals aged 45–64 years during the high-risk period from October to December.
Butachlor is a herbicide extensively employed in rice (Oryza sativa L.) cultivation but historically under-investigated for its toxicological impacts on terrestrial vegetation. This study examines the dose-dependent effects of butachlor on the germination and antioxidant defense mechanisms in the seeds of Asian tape grass [Vallisneria natans (Lour.) H. Hara], an important submerged plant species widely distributed in the agricultural ponds. In a hydroponic setup, seeds were exposed to four concentrations of butachlor (0, 20, 200, and 2,000 μg ai L−1), and cultivated under controlled light conditions to quantify germination rates and assess oxidative stress responses. Our findings showed that butachlor concentrations up to 20 μg L−1 had no effect on the germination rate of V. natans seeds, while germination rates decreased by 6.0% and 8.7% at 200 and 2,000 μg L−1, respectively. At 2,000 μg L−1, malondialdehyde (MDA) content increased by 5.7 nmol g−1 FW, and catalase (CAT) activity declined by 21%, indicating oxidative damage. Additionally, the antioxidants proline (Pro) and glutathione (GSH) were upregulated under 20 μg L−1 butachlor treatment after 12 h, contributing to reactive oxygen species (ROS) scavenging and cellular stability. This study highlights the nuanced interactions between butachlor exposure and the antioxidant defenses in V. natans, providing valuable insights into the ecological impacts of herbicide pollution. Understanding these interactions is crucial for development of sustainable agricultural practices and management of herbicide resistance in aquatic systems.
Antimicrobial resistance (AMR) is a global health crisis exacerbated by policies like China’s Volume-Based Procurement (VBP), which may inadvertently increase antimicrobial overuse. This study evaluates a clinical pharmacist-led Antimicrobial Stewardship (AMS) program with prospective audit for special-restricted antimicrobials under VBP.
Methods:
A retrospective quasi-experimental interrupted time-series analysis compared pre-intervention (2022) and post-intervention (2023–2024) data at Tongji Hospital, a tertiary hospital in Wuhan, China. Key metrics included Antimicrobial Use Density (AUD), prescription rationality, antimicrobial costs, and multidrug-resistant infection rates.
Results:
The intervention significantly improved prescription appropriateness for special-restricted antimicrobials (80.24% vs. 93.83%, P < 0.005) and reduced AUD (47.87 vs. 34.25, P < 0.001). Total antimicrobial costs decreased by 41.26%, with a reduction in the incidence of multidrug-resistant infections from 0.084% to 0.062% (P < 0.05). Carbapenem use correlated with CRKP isolation rates (R = 0.62, P < 0.05). Clinical pharmacists rejected 10.24% of prescriptions, all accepted by physicians.
Conclusion:
Pharmacist-led prospective audits optimize antimicrobial use under VBP, mitigate resistance risks, and reduce costs, while acknowledging that concurrent infection control measures may have contributed to these trends. This model may inform similar interventions in other institutions, particularly those in resource-limited settings.
Dispersion of microswimmers is widespread in environmental and biomedical applications. In the category of continuum modelling, the present study investigates the dispersion of microswimmers in a confined unidirectional flow under a diffuse reflection boundary condition, instead of the specular reflection and the Robin boundary conditions prevailing in existing studies. By the moment analysis based on the Smoluchowski equation, the asymptotic and transient solutions are directly obtained, as validated against random walk simulations, to illustrate the effects of mean flow velocity, swimming velocity and gyrotaxis on the migration and distribution patterns of elongated microswimmers. Under the diffuse reflection boundary condition, microswimmers are found more likely to exhibit M-shaped low-shear trapping and even pronounced centreline aggregation, and elongated shape affects depletion at the centreline. Along the flow direction, they readily form unimodal distributions oriented downstream, resulting in prominent downstream migration. Near the centreline, the migration is almost entirely downstream, while upstream and vertical migrations are confined near the boundaries. When the mean flow velocity and swimming velocity are comparable, the system undergoes a temporal transition from M-shaped low-shear trapping to M-shaped high-shear trapping and ultimately to centreline aggregation. The downstream migration continuously strengthens over time, while the upstream first strengthens and then weakens. Moreover, the coupling between swimming-induced diffusion and convective dispersion leads to non-monotonic, fluctuating trends in both drift velocity and dispersivity over time. These results contribute to a deeper understanding of the underlying mechanisms governing the locomotion and control of natural and synthetic microswimmers.
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.
To assess the association between coffee consumption and life expectancy among the US adults.
Design:
Prospective cohort.
Setting:
National representative survey in the United States, 2001–2018.
Participants:
A total of 43 114 participants aged 20 years or older with complete coffee consumption data were included from National Health and Nutrition Examination Survey 2001–2018.
Results:
Over a median follow-up of 8·7 years, 6234 total deaths occurred, encompassing 1929 deaths from CVD and 1411 deaths from cancer. Based on the nationally representative survey, we found that coffee consumption is associated with longer life expectancy. The estimated life expectancy at age 50 was 30·06 years (95 % CI, 29·68, 30·44), 30·82 years (30·12, 31·57), 32·08 years (31·52, 32·70), 31·24 years (30·29, 32·19), and 31·45 years (30·39, 32·60) in participants consuming 0, ≤ 1, 1 to ≤ 2, 2 to ≤ 3, and > 3 cups of coffee per day, respectively. Consequently, compared with non-coffee drinkers, participants who consumed 1 to ≤ 2 cups/day had a gain of 2·02 years (1·17, 2·85) in life expectancy on average, attributable to a 0·61-year (29·72 %) reduction in CVD deaths. Similar benefits were found in both males and females.
Conclusion:
Our findings suggest that moderate coffee consumption (approximately 2 cups per day) could be recommended as a valuable component of a healthy diet and may be an adjustable effective intervention measure to increase life expectancy.
Weeds significantly reduce sugarcane (Saccharum officinarum L.) production by 30% to 50% and cause complete crop loss in severe cases. Guangxi, a central sugarcane-growing region in southern China, faces significant challenges due to the proliferation of weeds severely impacting crop tillering, yield, and quality. In this study, we surveyed and identified 35 weed species belonging to 16 families in Longzhou, Nongqin, and Qufeng, with significant threats posed by purple nutsedge (Cyperus rotundus L.), bermudagrass [Cynodon dactylon (L.) Pers.], hairy crabgrass [Digitaria sanguinalis (L.) Scop.], black nightshade (Solanum nigrum L.), white-edge morningglory [Ipomoea nil (L.) Roth], and ivy woodrose [Merremia hederacea (Burm. f.) Hallier f.]. The application of 81% MCPA-ametryn-diuron achieved greater than 90% control within 15 d. Although herbicides are effective, they can unintentionally harm sugarcane, indicating a need for tolerant genotypes. Therefore, we comprehensively evaluated herbicide-induced phytotoxic responses and identified tolerant sugarcane genotypes over 3 yr of trials conducted on 222 genotypes across Guangxi. We quantified phytotoxicity by counting the number and severity of affected leaves. The ANOVA revealed statistically significant main and interaction effects among genotype, crop cycle, and location. Cluster and discriminant analyses classified the genotypes into five groups: 21 highly tolerant (HT), 68 tolerant, 75 moderately tolerant, 18 susceptible, and 40 highly susceptible. The 21 HT genotypes demonstrated strong potential to be used as parental lines for breeding herbicide-tolerant varieties, to inform precision breeding strategies, and to increase tolerance to herbicide stress in sugarcane.
The pulse duration is a critical parameter of picosecond-petawatt laser systems because it directly affects the results of high-energy-density physics experiments. This study systematically investigated the effects of the spectral width, central wavelength and beam-pointing deviations on pulse duration stability at the SG-II facility. A theoretical analysis of the relationship between spectra and pulse duration is conducted to quantify the impact on pulse duration stability, and the results are further validated through experimental measurements. In addition, beam-pointing deviations at the stretcher significantly affect the pulse duration. For example, a 27 μrad deviation can induce a 30% pulse duration variation. In contrast, the compressor exhibits greater robustness. Based on simulation and experimental results, we identify operational tolerance ranges for spectral width and beam-pointing deviation to maintain pulse duration stability within 5% at the SG-II facility. These findings provide critical guidance for optimizing the performance and reliability of chirped-pulse amplification/optical parametric chirped-pulse amplification-based high-power laser systems.
The heating effect of electromagnetic waves in ion cyclotron range of frequencies (ICRFs) in magnetic confinement fusion device is different in different plasma conditions. In order to evaluate the ICRF heating effect in different plasma conditions, we conducted a series of experiments and corresponding TRANSP simulations on the EAST tokamak. Both simulation and experimental results show that the effect of ICRF heating is poor at low core electron density. The decrease in electron density changes the left-handed electric field near the resonant layer, resulting in a significant decrease in the power absorbed by the hydrogen fundamental resonance. However, quite a few experiments must be performed in plasma conditions with low electron density. It is necessary to study how to make ICRF heating best in low electron density plasma. Through a series of simulation scans of the parallel refractive index (n//) of the ICRF antenna, it is concluded that the change of the ICRF antenna n// will lead to the change of the left-handed electric field, which will change the fundamental absorption of ICRF power by the hydrogen minority ions. Fully considering the coupling of ion cyclotron wave at the tokamak boundary and the absorption in the plasma core, optimizing the ICRF antenna structure and selecting appropriate parameters such as parallel refractive index, minority ion concentration, resonance layer position, plasma current and core electron temperature can ensure better heating effect in the ICRF heating experiments in the future EAST upgrade. These results have important implications for the enhancement of the auxiliary heating effect of EAST and other tokamaks.
Rare earth elements (REEs) preserved in speleothems have garnered increasing attention as ideal proxies for the paleoenvironmental reconstruction. However, due to their typically low contents in stalagmites, the availability of stalagmite-based REE records remains limited. Here we present high-resolution REEs alongside oxygen isotope (δ18O) records in stalagmite SX15a from Sanxing Cave, southwestern China (110.1–103.3 ka). This study demonstrates that REE records could provide useful information for the provenance and formation process of the stalagmite, due to consistent distribution pattern across different periods indicating stable provenance. More interestingly, the total REE (ΣREE) record could serve as an effective indicator to reflect local hydrological processes associated with monsoonal precipitation. During Marine Isotopic Stage (MIS) 5d, a relatively low ΣREE content is consistent with the positive SX15a δ18O and negative NGRIP δ18O, reflecting a dry-cold environment; while during MIS 5c, a generally high ΣREE content suggests a humid-warm circumstance. Furthermore, the ΣREE record captured four prominent sub-millennial fluctuations within the Greenland interstadial 24 event, implying a combined influence by the regional climate and local soil redox conditions. Our findings indicate that the stalagmite-based REE records would be a useful proxy for better understanding of past climate and environment changes.
We report the first shock-tube experiments on Richtmyer–Meshkov instability at a single-mode light–heavy interface accelerated by a strong shock wave with Mach number higher than 3.0. Under the proximity effect of the transmitted shock and its induced secondary compression effect, the interface profile is markedly different from that in weakly compressible flows. For the first time, the validity of the compressible linear theory and the failure of the impulsive model in predicting the linear amplitude evolution in highly compressible flows are verified through experiments. Existing nonlinear and modal models fail to accurately describe the perturbation evolution, as they do not account for the shock proximity and secondary compression effects on interface evolution. The shock proximity effect manifests mainly in the early stages when the transmitted shock remains close to the interface, while the effect of secondary compression manifests primarily at the period when interactions of transverse shocks occur at the bubble tips. Based on these findings, we propose an empirical model capable of predicting the bubble evolution in highly compressible flows.
The propagation of multiple ultraintense femtosecond lasers in underdense plasmas is investigated theoretically and numerically. We find that the energy merging effect between two in-phase seed lasers can be improved by using two obliquely incident guiding lasers whose initial phase is $\pi$ and $\pi /2$ ahead of the seed laser. Particle-in-cell simulations show that due to the repulsion and energy transfer of the guiding laser, the peak intensity of the merged light is amplified by more than five times compared to the seed laser. The energy conversion efficiency from all incident lasers to the merged light is up to approximately 60$\%$. The results are useful for many applications, including plasma-based optical amplification, charged particle acceleration and extremely intense magnetic field generation.
The betatron radiation source features a micrometer-scale source size, a femtosecond-scale pulse duration, milliradian-level divergence angles and a broad spectrum exceeding tens of keV. It is conducive to the high-contrast imaging of minute structures and for investigating interdisciplinary ultrafast processes. In this study, we present a betatron X-ray source derived from a high-charge, high-energy electron beam through a laser wakefield accelerator driven by the 1 PW/0.1 Hz laser system at the Shanghai Superintense Ultrafast Laser Facility (SULF). The critical energy of the betatron X-ray source is 22 ± 5 keV. The maximum X-ray flux reaches up to 4 × 109 photons for each shot in the spectral range of 5–30 keV. Correspondingly, the experiment demonstrates a peak brightness of 1.0 × 1023 photons·s−1·mm−2·mrad−2·0.1%BW−1, comparable to those demonstrated by third-generation synchrotron light sources. In addition, the imaging capability of the betatron X-ray source is validated. This study lays the foundation for future imaging applications.