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The models used to describe the light response of electron transport rate in photosynthesis play a crucial role in determining two key parameters i.e., the maximum electron transport rate (Jmax) and the saturation light intensity (Isat). However, not all models accurately fit J–I curves, and determine the values of Jmax and Isat. Here, three models, namely the double exponential (DE) model, the non-rectangular hyperbolic (NRH) model, and a mechanistic model developed by one of the coauthors (Z-P Ye) and his coworkers (referred to as the mechanistic model), were compared in terms of their ability to fit J–I curves and estimate Jmax and Isat. Here, we apply these three models to a series of previously collected Chl a fluorescence data from seven photosynthetic organisms, grown under different conditions. Our results show that the mechanistic model performed well in describing the J–I curves, regardless of whether photoinhibition/dynamic down-regulation of photosystem II (PSII) occurs. Moreover, both Jmax and Isat estimated by this model are in very good agreement with the measured data. On the contrary, although the DE model simulates quite well the J–I curve for the species studied, it significantly overestimates both the Jmax of Amaranthus hypochondriacus and the Isat of Microcystis aeruginosa grown under NH4+-N supply. More importantly, the light intensity required to achieve the potential maximum of J (Js) estimated by this model exceeds the unexpected high value of 105 μmol photons m−2 s−1 for Triticum aestivum and A. hypochondriacus. The NRH model fails to characterize the J-I curves with dynamic down-regulation/photoinhibition for Abies alba, Oryza sativa and M. aeruginosa. In addition, this model also significantly overestimates the values of Jmax for T. aestivum at 21% O2 and A. hypochondriacus grown under normal condition, and significantly underestimates the values of Jmax for M. aeruginosa grown under NO3–N supply. Our study provides evidence that the ‘mechanistic model’ is much more suitable than both the DE and NRH models in fitting the J–I curves and in estimating the photosynthetic parameters. This is a powerful tool for studying light harvesting properties and the dynamic down-regulation of PSII/photoinhibition.

A new human-based heuristic optimization method, named the Snooker-Based Optimization Algorithm (SBOA), is introduced in this study. The inspiration for this method is drawn from the traits of sales elites—those qualities every salesperson aspires to possess. Typically, salespersons strive to enhance their skills through autonomous learning or by seeking guidance from others. Furthermore, they engage in regular communication with customers to gain approval for their products or services. Building upon this concept, SBOA aims to find the optimal solution within a given search space, traversing all positions to obtain all possible values. To assesses the feasibility and effectiveness of SBOA in comparison to other algorithms, we conducted tests on ten single-objective functions from the 2019 benchmark functions of the Evolutionary Computation (CEC), as well as twenty-four single-objective functions from the 2022 CEC benchmark functions, in addition to four engineering problems. Seven comparative algorithms were utilized: the Differential Evolution Algorithm (DE), Sparrow Search Algorithm (SSA), Sine Cosine Algorithm (SCA), Whale Optimization Algorithm (WOA), Butterfly Optimization Algorithm (BOA), Lion Swarm Optimization (LSO), and Golden Jackal Optimization (GJO). The results of these diverse experiments were compared in terms of accuracy and convergence curve speed. The findings suggest that SBOA is a straightforward and viable approach that, overall, outperforms the aforementioned algorithms.

Abstract The crystal‐structure symmetry in real space can be inherited in the reciprocal space, making high‐symmetry materials the top candidates for thermoelectrics due to their potential for significant electronic band degeneracy. A practical indicator that can quantitatively describe structural changes would help facilitate the advanced thermoelectric material design. In face‐centered cubic structures, the spatial environment of the same crystallographic plane family is isotropic, such that the distances between the close‐packed layers can be derived from the atomic distances within the layers. Inspired by this, the relationship between inter‐ and intra‐layer geometric information can be used to compare crystal structures with their desired cubic symmetry. The close‐packed layer spacing was found to be a practical guideline of crystal structure symmetry in IV‐VI chalcogenides and I‐V‐VI2 ternary semiconductors, both of which are historically important thermoelectrics. The continuous structural evolution toward high symmetry can be described by the layer spacing when temperature or/and composition change, which is demonstrated by a series of pristine and alloyed thermoelectric materials in this work. The layer‐spacing‐based guideline provides a quantitative pathway for manipulating crystal structures to improve the electrical and thermal properties of thermoelectric materials.

Objectives Radiofrequency catheter ablation is the first-line treatment for idiopathic premature ventricular complexes (PVCs) and ventricular tachycardias (VTs). However, the outcomes were less compared among the categories. The study aims to assess the effectiveness and safety of catheter ablation for idiopathic PVC/VTs in a single high-volume centre, using the right ventricular outflow tract (RVOT) as a reference.Design Retrospective cohort study.Setting Patient data were collected from a tertiary hospital in Guizhou, China.Participants Between September 2013 and September 2022, 1028 patients (male: 41.3%; age: 46.5±15.6 years) who underwent the first catheter ablation for idiopathic monomorphic PVC/VTs were enrolled.Outcome measures Acute success, procedure-related complications, and long-term recurrence were assessed. Antiarrhythmic drugs (AADs) were not administrated after procedures unless recurrence was identified.Results The overall acute success rate was 90.3%, with 368 patients (35.8%) experiencing left ventricular PVC/VTs. No cases of third-degree atrioventricular block or death were reported. Complications were more common in patients with left ventricular PVC/VTs than those with right-sided ones (4.6% vs 0.1%, p

Abstract Recently, relaxation linear regression has received increasing attention in image analysis. However, the current relaxation linear regression methods fail to consider the local geometrical structure and spatial information while they are applied for hyperspectral image (HSI) classification. To address the above problems, this letter proposes a novel relaxation linear regression with spectral–spatial constrained locality adaptive regularization (SSLA‐RLR) method for HSI classification. The SSLA‐RLR method not only integrates the locality adaptive graph with relaxation linear regression to adaptively exploit the local geometrical structure for relieving the side effects of noise corruptions, but also takes the spatial correlations between each data point and its neighbours into consideration via spectral–spatial constraint. Finally, extensive experiments are conducted on three benchmark HSI datasets to demonstrate the effectiveness of the proposed method.

The cerebellum has been implicated in the regulation of social behavior. Its influence is thought to arise from communication, via the thalamus, to forebrain regions integral in the expression of social interactions, including the anterior cingulate cortex (ACC). However, the signals encoded or the nature of the communication between the cerebellum and these brain regions is poorly understood. Here, we describe an approach that overcomes technical challenges in exploring the coordination of distant brain regions at high temporal and spatial resolution during social behavior. We developed the E-Scope, an electrophysiology-integrated miniature microscope, to synchronously measure extracellular electrical activity in the cerebellum along with calcium imaging of the ACC. This single coaxial cable device combined these data streams to provide a powerful tool to monitor the activity of distant brain regions in freely behaving animals. During social behavior, we recorded the spike timing of multiple single units in cerebellar right Crus I (RCrus I) Purkinje cells (PCs) or dentate nucleus (DN) neurons while synchronously imaging calcium transients in contralateral ACC neurons. We found that during social interactions a significant subpopulation of cerebellar PCs were robustly inhibited, while most modulated neurons in the DN were activated, and their activity was correlated with positively modulated ACC neurons. These distinctions largely disappeared when only non-social epochs were analyzed suggesting that cerebellar-cortical interactions were behaviorally specific. Our work provides new insights into the complexity of cerebellar activation and co-modulation of the ACC during social behavior and a valuable open-source tool for simultaneous, multimodal recordings in freely behaving mice.

Cytisine is a naturally occurring bioactive compound, an alkaloid mainly isolated from legume plants. In recent years, various biological activities of cytisine have been explored, showing certain effects in smoking cessation, reducing drinking behavior, anti-tumor, cardiovascular protection, blood sugar regulation, neuroprotection, osteoporosis prevention and treatment, etc. At the same time, cytisine has the advantages of high efficiency, safety, and low cost, has broad development prospects, and is a drug of great application value. However, a summary of cytisine's biological activities is currently lacking. Therefore, this paper summarizes the pharmacological action, mechanism, and pharmacokinetics of cytisine by referring to numerous databases, and analyzes the new and core targets of cytisine with the help of computer simulation technology, to provide reference for doctors.

Urban agglomerations are sophisticated territorial systems at the mature stage of city development that are concentrated areas of production and economic activity. Therefore, the study of vulnerability from the perspective of production-living-ecological space is crucial for the sustainable development of the Yellow River Basin and global urban agglomerations. The relationship between productivity, living conditions, and ecological spatial quality is fully considered in this research. By constructing a vulnerability evaluation index system based on the perspectives of production, ecology, and living space, and adopting the entropy value method, comprehensive vulnerability index model, and obstacle factor diagnostic model, the study comprehensively assesses the vulnerability of the urban agglomerations along the Yellow River from 2001 to 2020. The results reveal that the spatial differentiation characteristics of urban agglomeration vulnerability are significant. A clear three-level gradient distribution of high, medium, and low degrees is seen in the overall vulnerability; these correspond to the lower, middle, and upper reaches of the Yellow River Basin, respectively. The percentage of cities with higher and moderate levels of vulnerability did not vary from 2001 to 2020, while the percentage of cities with high levels of vulnerability did. The four dimensions of economic development, leisure and tourism, resource availability, and ecological pressure are the primary determinants of the urban agglomeration's vulnerability along the Yellow River. And the vulnerability factors of various urban agglomerations showed a significant evolutionary trend; the obstacle degree values have declined, and the importance of tourism and leisure functions has gradually increased. Based on the above conclusions, we propose several suggestions to enhance the quality of urban development along the Yellow River urban agglomeration. Including formulating a three-level development strategy, paying attention to ecological and environmental protection, developing domestic and foreign trade, and properly planning and managing the tourism industry.

Objective Cardiac CT (CCT) is an emerging non-invasive modality for assessing left atrial appendage (LAA) thrombus, but the results were conflicting. Our study aims to evaluate the accuracy of CCT for detecting LAA thrombus in patients undergoing catheter ablation of atrial fibrillation, using trans-oesophageal echocardiography (TEE) as the reference standard.Design Case-control study.Setting Patient data were collected from a tertiary hospital in China between 2017 and 2022.Participants The study enrolled 726 patients (male: 60.2%, age: 61±11 years) who had both TEE and CCT before catheter ablation of atrial fibrillation.Measures The CCT protocol consisted of one angiographic phase and one delayed scan 30 s later. LAA thrombi were defined as solid masses on TEE or persistent defects on CCT. The thrombus dimension and location, the LAA filling and emptying flow velocity were assessed by TEE.Results Of the 57 (7.9%) patients with LAA thrombi identified by TEE, 29 (50.9%) were located at the LAA ostium, and 28 (49.1%) were in the LAA. The former showed higher motility following blood flow and heartbeats than the latter. The CCT detected 14 (48.3%) of the LAA-ostium thrombi but 25 (89.3%) of those in the LAA (p=0.001). The LAA-ostium thrombi with the LAA mean flow velocity >0.35 m/s and maximum diameters

Avulsion fracture of the anterior superior iliac crest (ASIC) following autogenous bone grafting for anterior lumbar fusion (ALF) is an extremely rare complication. We describe a very rare case of avulsion fracture of the ASIC following autograft for ALF in a revision surgery for treating lumbar tuberculosis. A 68-year-old woman with lumbar tuberculosis underwent posterior debridement and posterior iliac crest bone graft fusion; however, her lumbar tuberculosis recurred 9 months after surgery. She then underwent a lumbar revision surgery, including removal of the posterior instrumentation and debridement, followed by anterior L2 corpectomy, debridement, anterior left iliac crest bone graft fusion, and internal fixation. When walking for the first time on postoperative day 3, she experienced a sharp, sudden-onset pain in the anterior iliac crest harvest area. X-ray revealed an avulsion fracture of the ASIC. Considering her failure to respond to conservative treatment for one week and large displacement of the fracture ends, an open reduction and internal fixation surgery was scheduled. Her pain symptoms were significantly relieved after the operation. Although rare, fracture of the ASIC following autograft for ALF should not be ignored. Fracture of the ASIC is usually treated conservatively. Additional surgical treatment is required only when intractable pain fails to respond to conservative treatment or when there is a large displacement of fracture ends that are not expected to heal spontaneously.

Salt stress inhibits plant growth by disturbing plant intrinsic physiology. The application of exogenous plant growth regulators to improve the plant tolerance against salt stress has become one of the promising approaches to promote plant growth in saline environment. Eugenol (4-allyl-2- methoxyphenol) is the main ingredient in clove oil and it is known for its strong antioxidant and anti-microbial activities. Eugenol also has the ability of inhibiting several plant pathogens, implying the potential use of eugenol as an environmental friendly agrichemical. However, little is known about the possible role of eugenol in the regulation of plant tolerance against abiotic stress. Therefore, here we investigated the effectiveness of phytochemical eugenol in promoting salt tolerance in tobacco seedlings through physiological, histochemical, and biochemical method. The seedling roots were exposed to NaCl solution in the presence or absence of eugenol. Salt stress inhibited seedling growth, but eugenol supplementation effectively attenuated its effects in a dose-dependent manner, with an optimal effect at 20 µM. ROS (reactive oxygen species) accumulation was found in seedlings upon salt stress which was further resulted in the amelioration of lipid peroxidation, loss of membrane integrity, and cell death in salt-treated seedlings. Addition of eugenol highly suppressed ROS accumulation and reduced lipid peroxidation generation. Both enzymatic and non-enzymatic antioxidative systems were activated by eugenol treatment. AsA/DHA and GSH/GSSG were also enhanced upon eugenol treatment, which helped maintain redox homeostasis upon salinity. Eugenol treatment resulted in an increase in the content of osmoprotectants (e.g. proline, soluble sugar and starch) in salt-treated seedlings. Na+ levels decreased significantly in seedlings upon eugenol exposure. This may result from the upregulation of the expression of two ionic transporter genes, SOS1 (salt-hypersensitive 1) and NHX1 (Na+/H+ anti-transporter 1). Hierarchical cluster combined correlation analysis uncovered that eugenol induced salt tolerance was mediated by redox homeostasis and maintaining ionic balance in tobacco seedlings. This work reveals that eugenol plays a crucial role in regulating plant resistant physiology. This may extend its biological function as a novel biostimulant and opens up new possibilities for improving crop productivity in the saline agricultural environment.

The fungal Gβ-like protein has been reported to be involved in a variety of biological processes, such as mycelial growth, differentiation, conidiation, stress responses and infection. However, molecular mechanisms of the Gβ-like protein in regulating fungal development and pathogenicity are largely unknown. Here, we show that the Gβ-like protein gene Bcgbl1 in the gray mold fungus Botrytis cinerea plays a pivotal role in development and pathogenicity by regulating the mitogen-activated protein (MAP) kinases signaling pathways. The Bcgbl1 deletion mutants were defective in mycelial growth, sclerotial formation, conidiation, macroconidial morphogenesis, plant adhesion, and formation of infection cushions and appressorium-like structures, resulting in a complete loss of pathogenicity. Bcgbl1 interacted with BcSte50, the adapter protein of the cascade of MAP kinase (MAPK). Bcgbl1 mutants had reduced phosphorylation levels of two MAPKs, namely Bmp1 and Bmp3, thereby reducing infection. However, deletion of Bcgbl1 did not affect the intracellular cAMP level, and exogenous cAMP could not restore the defects. Moreover, Bcgbl1 mutants exhibited defects in cell wall integrity and oxidative stress tolerance. Transcriptional profiling revealed that Bcgbl1 plays a global role in regulation of gene expression upon hydrophobic surface induction. We further uncovered that three target genes encoding the hydrophobic surface binding proteins (HsbAs) contributed to the adhesion and virulence of B. cinerea. Overall, these findings suggest that Bcgbl1 had multiple functions and provided new insights for deciphering the Bcgbl1-mediated network for regulating development and pathogenicity of B. cinerea.

Primary liver cancer (PLC) is one of the most commonly diagnosed cancers worldwide and a leading cause of cancer-related deaths. However, traditional liver cancer models fail to replicate tumor heterogeneity and the tumor microenvironment, limiting the study and personalized treatment of liver cancer. To overcome these limitations, scientists have introduced three-dimensional (3D) culture models as an emerging research tool. These 3D models, utilizing biofabrication technologies such as 3D bioprinting and microfluidics, enable more accurate simulation of the in vivo tumor microenvironment, replicating cell morphology, tissue stiffness, and cell-cell interactions. Compared to traditional two-dimensional (2D) models, 3D culture models better mimic tumor heterogeneity, revealing differential sensitivity of tumor cell subpopulations to targeted therapies or immunotherapies. Additionally, these models can be used to assess the efficacy of potential treatments, providing guidance for personalized therapy. 3D liver cancer models hold significant value in tumor biology, understanding the mechanisms of disease progression, and drug screening. Researchers can gain deeper insights into the impact of the tumor microenvironment on tumor cells and their interactions with the surrounding milieu. Furthermore, these models allow for the evaluation of treatment responses, offering more accurate guidance for clinical interventions. In summary, 3D models provide a realistic and reliable tool for advancing PLC research. By simulating tumor heterogeneity and the microenvironment, these models contribute to a better understanding of the disease mechanisms and offer new strategies for personalized treatment. Therefore, 3D models hold promising prospects for future PLC research.

ABSTRACT The vertical wall attached jet ventilation has the advantages of good air supply quality, low energy consumption and uniform air distribution, which can improve the environmental quality, reduce heating energy consumption and increase the healthy brood rate when applied to the gosling house in cold region. In order to investigate the distribution of the air flow field and the temperature field in the gosling barn by the computational fluid dynamics method, the three-dimensional steady state simulation of the air flow field and the temperature field is carried out in this study. The results show that the maximum air velocity in the living area of goslings exceeds 0.5m/s when the air supply velocity is greater than 1.8m/s, and goslings feel blowing. When the air supply velocity is lower than 0.8m/s, the average air velocity in the gosling living area is lower than 0.2m/s, and the ventilation is insufficient. When the air supply velocity v=1.5m/s and temperature t=305.15k, the average air velocity in the gosling living area was 0.40m/s, the average temperature was 305.20k, the horizontal sticking range of the air supply air was 7.0m, the Air Diffusion Performance Index of the gosling house was 100%. Ventilation is the best.

Abstract Both iodine concentration and protein intake are important nutritional factors that may influence the development of depressive symptoms. However, there are no studies on the effect of protein intake on the relationship between iodine concentration and the risk of depression. The study aimed to explore the relationship between iodine and the risk of clinically relevant depression (CRD) according to protein intake. This study analyzed the adults (≥18 years) who participated in the 2007–2018 National Health and Nutrition Cross‐sectional Survey (N = 10,462). CRD was assessed using the Patient Health Questionnaire (PHQ‐9). Protein intake was assessed using two 24‐h dietary recalls and urinary iodine concentration (UIC) was measured using inductively coupled plasma dynamic response cell mass spectrometry. Weighted multivariate logistic regression and restrictive cubic splines were performed to assess the relationship between UIC and CRD according to protein category (low protein intake

Abstract Recent studies have shown an inconsistent association between dietary niacin and cognitive function. And this remains unclear in the American outpatient population. The aim of this study was to assess whether there is an association between dietary niacin and cognitive performance in an older American population aged ≥60 years. A total of 2523 participants from the National Health and Nutrition Examination Survey (NHANES) 2011–2014 were enrolled. Cognitive function was assessed by the CERAD Word Learning (CERAD‐WL) test, the CERAD Delayed Recall (CERAD‐DR) test, the Animal Fluency test (AFT), and the Digit Symbol Substitution test (DSST). Cognitive impairment that meets one of the four scoring conditions listed above is defined as low cognitive function. Dietary niacin intake was obtained from 2 days of a 24‐h recall questionnaire. Based on the quartiles of dietary niacin intake, they were divided into four groups: Q1 (26.91 mg). The stability of the results was assessed using multifactorial logistic regression, restricted cubic spline (RCS) models, and sensitivity stratified analysis. More than half of the participants had cognitive impairment (52.52%). In the fully adjusted model, niacin was associated with a significantly reduced risk of cognitive impairment in Q3 and Q4 compared with the Q1 group (OR: 0.610, 95% CI: 0.403, 0.921, p = .022; OR: 0.592, 95% CI: 0.367, 0.954, p = .034). Meanwhile, niacin was negatively associated with poor cognition as assessed by the CERAD‐WL test, CERAD test, AFT, and DSST. An L‐shaped dose–response relationship between dietary niacin and cognitive function was observed in all participants (nonlinear p

Abstract In this study, the competitive failure mechanism of bolt loosening and fatigue is elucidated via competitive failure tests on bolts under composite excitation. Based on the competitive failure mechanism, the mode prediction model and “load ratio—life prediction curve” (ξ–N curve) of the bolt competitive failure are established. Given the poor correlation of the ξ–N curve, an evaluation model of the bolt competitive failure life is proposed based on Miner’s linear damage accumulation theory. Based on the force analysis of the thread surface and simulation of the bolt connection under composite excitation, a theoretical equation of the bolt competitive failure life is established to validate the model for evaluating the bolt competitive failure life. The results reveal that the proposed model can accurately predict the competitive failure life of bolts under composite excitation, and thereby, it can provide guidance to engineering applications.

AIM: To compare the efficacy of aflibercept and ranibizumab in the treatment of diabetic macular edema(DME).METHODS: Prospective randomized controlled trial. A total of 35 patients(60 eyes)with non-proliferative diabetic retinopathy complicated with DME confirmed in our hospital from June 2020 to September 2021 were included. Intravitreal injection was performed using the 3+PRN protocol in all cases, of which 17 cases(30 eyes)received aflibercept treatment(aflibercept group)and 18 cases(30 eyes)received ranibizumab(ranibizumab group). The two groups were followed up for 12mo, observing the central macular thickness(CMT)and the best corrected visual acuity(BCVA)of the two groups, and recording the number of intravitreal injections and the occurrence of complications.RESULTS: After treatment, CMT and BCVA in the aflibercept group were significantly better than that in the ranibizumab group at 1, 3, 6 and 12 mo(all P

Abstract Background Long terminal repeat (LTR)-retrotransposons (LTR-RTs) are ubiquitous and make up the majority of nearly all sequenced plant genomes, whereas their pivotal roles in genome evolution, gene expression regulation as well as their epigenetic regulation are still not well understood, especially in a large number of closely related species. Results Here, we analyzed the abundance and dynamic evolution of LTR-RTs in 54 species from an economically and agronomically important family, Fabaceae, and also selected two representative species for further analysis in expression of associated genes, transcriptional activity and DNA methylation patterns of LTR-RTs. Annotation results revealed highly varied proportions of LTR-RTs in these genomes (5.1%~68.4%) and their correlation with genome size was highly positive, and they were significantly contributed to the variance in genome size through species-specific unique amplifications. Almost all of the intact LTR-RTs were inserted into the genomes 4 Mya (million years ago), and more than 50% of them were inserted in the last 0.5 million years, suggesting that recent amplifications of LTR-RTs were an important force driving genome evolution. In addition, expression levels of genes with intronic, promoter, and downstream LTR-RT insertions of Glycine max and Vigna radiata, two agronomically important crops in Fabaceae, showed that the LTR-RTs located in promoter or downstream regions suppressed associated gene expression. However, the LTR-RTs within introns promoted gene expression or had no contribution to gene expression. Additionally, shorter and younger LTR-RTs maintained higher mobility and transpositional potential. Compared with the transcriptionally silent LTR-RTs, the active elements showed significantly lower DNA methylation levels in all three contexts. The distributions of transcriptionally active and silent LTR-RT methylation varied across different lineages due to the position of LTR-RTs located or potentially epigenetic regulation. Conclusion Lineage-specific amplification patterns were observed and higher methylation level may repress the activity of LTR-RTs, further influence evolution in Fabaceae species. This study offers valuable clues into the evolution, function, transcriptional activity and epigenetic regulation of LTR-RTs in Fabaceae genomes.

Abstract Background Recurrences are the main reasons for unfavorable outcomes for patients with stage II colorectal cancer (CRC). To obtain a clear understanding of the high-risk factors, further investigation is warranted. The present study aimed to analyze the risk factors associated with postoperative recurrence in patients with stage II CRC. Methods Eligible patients with pathologically confirmed stage II CRC were enrolled in the study retrospectively based on a prospectively maintained database from April 2008 to March 2019. The Kaplan–Meier method were used to calculate the overall survival (OS) rate and the cumulative recurrence rate. Univariate and multivariable Cox regression analyses were performed to identify risk factors for recurrence. Results There were 2515 patients included, of whom 233 (9.3%) developed local or distant recurrence. Recurrence was associated with a significantly worse 5-year OS (45.4% vs. 95.5%, p < 0.0001). The 5-year cumulative recurrence rate was 13.0% in patients with stage II CRC. On multivariable Cox analysis, tumor size (Hazard Ratio (HR) [95% confidence interval (CI)] = 1.79[1.38, 2.33]), preoperative carbohydrate antigen (CA) 125 level (HR [95% CI] = 1.78[1.17, 2.70]), preoperative CA 199 level (HR [95% CI] = 1.56[1.09, 2.22]), and ulcerating tumor (HR [95% CI] = 1.61[1.19, 2.17]) were found to be associated with postoperative recurrence. Adjuvant chemotherapy was associated with a lower cumulative recurrence rate in patients with these risk factors (p = 0.00096). Conclusion The tumor diameter, preoperative CA125 level, preoperative CA199 level, and an ulcerative tumor can predict postoperative recurrence in patients with stage II CRC, and postoperative chemotherapy could reduce the cumulative recurrence rate in patients with these high-risk factors.

Abstract Laser plasma-based particle accelerators attract great interest in fields where conventional accelerators reach limits based on size, cost or beam parameters. Despite the fact that particle in cell simulations have predicted several advantageous ion acceleration schemes, laser accelerators have not yet reached their full potential in producing simultaneous high-radiation doses at high particle energies. The most stringent limitation is the lack of a suitable high-repetition rate target that also provides a high degree of control of the plasma conditions required to access these advanced regimes. Here, we demonstrate that the interaction of petawatt-class laser pulses with a pre-formed micrometer-sized cryogenic hydrogen jet plasma overcomes these limitations enabling tailored density scans from the solid to the underdense regime. Our proof-of-concept experiment demonstrates that the near-critical plasma density profile produces proton energies of up to 80 MeV. Based on hydrodynamic and three-dimensional particle in cell simulations, transition between different acceleration schemes are shown, suggesting enhanced proton acceleration at the relativistic transparency front for the optimal case.

Abstract The incidence of bladder cancer (BLCA) in men is higher than that in women. Differences in androgen levels between men and women are considered the main causes of incidence rate differences. In this study, dihydrotestosterone (DHT) significantly increased the proliferation and invasion of BLCA cells. In addition, BLCA formation and metastatic rates were higher in N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-treated male mice than in female and castrated male mice in vivo. However, immunohistochemistry showed that androgen receptor (AR) was expressed at low levels in normal and BLCA tissues of men and women. The classical AR pathway considers that DHT binds to AR and induces it to enter the nucleus, where it functions as a transcription factor. Here, a non-AR combination pathway of androgen that promoted BLCA development was investigated. The EPPK1 protein was bombarded with DHT, as determined by biotinylated DHT-binding pull-down experiments. EPPK1 was highly expressed in BLCA tissues, and EPPK1 knockdown significantly inhibited BLCA cell proliferation and invasion promoted by DHT. Moreover, JUP expression was elevated in DHT-treated high-EPPK1 expressing cells, and JUP knockdown inhibited cell proliferation and invasion. EPPK1 overexpression increased tumour growth and JUP expression in nude mice. Furthermore, DHT increased the expression of the MAPK signals p38, p-p38, and c-Jun, and c-Jun could bind to the JUP promoter. However, the promotion of p38, p-p38, and c-Jun expression by DHT was not observed in EPPK1 knockdown cells, and a p38 inhibitor suppressed the DHT-induced effects, indicating that p38 MAPK may be involved in the regulation of DHT-dependent EPPK1-JUP-promoted BLCA cell proliferation and invasion. The growth of bladder tumours in BBN-treated mice was inhibited by the addition of the hormone inhibitor goserelin. Our findings indicated the potential oncogenic role and mechanism of DHT in BLCA pathogenesis through a non-AR pathway, which may serve as a novel therapeutic target for BLCA.