Search

Abstract Survival in host macrophages is an effective strategy for pathogenic bacterial transmission and pathogenesis. Our previous study found that viable but non-culturable (VBNC) Cronobacter Sakazakii (C. sakazakii) can survive in macrophages, but its survival mechanism is not clear. In this study, we investigated the possible mechanisms of VBNC C. sakazakii survival in macrophages in terms of environmental tolerance within macrophages and evasion of macrophages recognition. The results revealed that VBNC C. sakazakii survived under oxidative conditions at a higher rate than the culturable C. sakazakii. Moreover, the stringent response gene (relA and spoT) and the antioxidant-related genes (sodA, katG, and trxA) were up-regulated, indicating that VBNC C. sakazakii may regulate antioxidation through stringent response. On the other hand, compared with culturable C. sakazakii, VBNC C. sakazakii caused reduced response (Toll-like receptor 4) in macrophages, which was attributed to the suppression of biosynthesis of the lipopolysaccharides (LPS). Furthermore, we found that ellagic acid can reduce the survival rate of bacteria in macrophages by improving the immune TLR4 recognition ability of macrophages. In conclusion, VBNC C. sakazakii may survive in macrophages by regulating oxidative tolerance through stringent response and altering LPS synthesis to evade TLR4 recognition by macrophages, which suggests the pathogenic risk of VBNC C. sakazakii.

Background: Imbalances in Th1/Th2 and Th17/Treg immune axes, coupled with disruptions in the gut microbiota (GM), play a pivotal role in the pathogenesis of inflammatory bowel disease (IBD). Cordycepin, a natural anti-inflammatory compound, holds promise in mitigating IBD by rebalancing these immune axes in conjunction with modulating the GM. The aim of this experiment is to investigate the potential of cordycepin in mitigating enteritis and elucidate the underlying mechanisms associated with its ameliorative effects on enteritis. Methods: On the day of inducing experimental colitis with Dextran Sulfate Sodium (DSS), mice in the DSS + Cordycepin and Cordycepin groups received 50 mg/kg/day Cordycepin via intra-gastric administration (i.g.) for seven consecutive days, respectively. Mice in the DSS and control groups were treated with equal volumes of saline. On day 8, all mice were euthanized under pentobarbital sodium anesthesia. Results: In a DSS-induced colitis mouse model, Cordycepin treatment led to a significant reduction in the disease activity index (DAI), splenic weight, and colonic pathological injury while simultaneously improving body weight and colonic length. Furthermore, it positively impacted GM composition, resulting in decreased Th1 and Th17 cells, alongside an increase in Th2 and Treg cells. The contents of the mouse colon were extracted for microbial community analysis. Mouse blood was prepared into a single-cell suspension, and flow cytometry was used to assess the expressio of Treg, Th17, Th1, and Th2 immune cells. Conclusions: These results underscored the effective intervention of cordycepin in ameliorating DSS-induced colitis by harmonizing the interplay between GM and immune homeostasis.

ObjectivesThe competency of radiology directly affects the quality and equity of medical services. Due to their different occupational characteristics compared to other specialists, this study aims to evaluate the impacts of lifestyles on competency and burnout in radiology residents in China.Materials and methodsA nationwide, cross-sectional survey was conducted from December 1, 2020 to April 30, 2021. A total of 12,208 radiology residents during their standardized residency training in China were invited. Multivariate linear regression and logistic regression were conducted to identify perceived competency and burnout associated with lifestyles.ResultsOf the 3,666 participants, 58.02% were female, 82.24% were aged

BackgroundCompetency of health professionals stands as a fundamental element in ensuring the quality of care. Notably, work stress and resilience are found to be associated with competency of health professionals. However, the role of resilience between work stress and competency remains unexplored. This study aims to investigate competency, work stress and resilience of radiology residents, and to examine the mediating effect of resilience.MethodsA cross-sectional survey was conducted among 3,666 radiology residents from 31 provinces of China in 2021. The diagnostic radiology milestones were used to measure the competency. Results of work stress and resilience were derived from self-reports and assessment of the Connor Davidson Resilience Scale (CD-RISC) respectively. To examine the association between work stress, resilience, and competency, Spearman correlation analysis and hierarchical linear regression were employed. The mediating effect of resilience was tested by bootstrapping analysis.ResultsDescriptive statistics show that the average score (mean ± SD) of work stress, competency and resilience among radiology residents were 1.55 ± 1.53 (range from 0 to 6), 28.14 ± 13 (range from 0 to 81) and 5.97 ± 1.92 (range from 0 to 8), respectively. Work stress was negatively associated with competency (β = −0.51, p

Objective Pulmonary tuberculosis (PTB) is a critical challenge worldwide, particularly in China. This study aimed to explore the spatiotemporal transmission patterns and socioeconomic factors of PTB in Dongguan city, China.Methods/design An ecological study based on the reported new PTB cases between 2011 and 2020 was conducted in Dongguan city, China. The spatiotemporal analysis methods were used to explore the long-term trend, spatiotemporal transmission pattern and socioeconomic factors of PTB.Main outcome measures The number of new PTB cases.Participants We collected 35 756 new PTB cases, including 23 572 males and 12 184 females.Results The seasonal–trend decomposition indicated a significant downward trend for PTB with a significant peak in 2017 and 2018, and local spatial autocorrelation showed more and more high–high clusters in the central and north-central towns with high incidence. The multivariate spatial time series analysis revealed that the endemic component had a leading role in driving PTB transmission, with a high total effect value being 189.40 (95% CI: 171.65–207.15). A Bayesian spatiotemporal model revealed that PTB incidence is positively associated with the agricultural population ratio (relative risk (RR) =1.074), gender ratio (RR=1.104) and the number of beds in medical institutions (RR=1.028).Conclusions These findings revealed potential spatiotemporal variability and spatial aggregation of PTB, so targeted preventive strategies should be made in different towns based on spatiotemporal transmission patterns and risk factors.

Abstract Acute lung injury (ALI) is life-threatening. MicroRNAs (miRNAs) are often abnormally expressed in inflammatory diseases and are closely associated with ALI. This study investigates whether miRNA-206-3p attenuates pyroptosis in ALI and elucidates the underlying molecular mechanisms. ALI mouse and cell models were established through lipopolysaccharide (LPS) treatment for 24 h. Subsequently, the models were evaluated based on ultrasonography, the lung tissue wet/dry (W/D) ratio, pathological section assessment, electron microscopy, and western blotting. Pyroptosis in RAW264.7 cells was then assessed via electron microscopy, immunofluorescence, and western blotting. Additionally, the regulatory relationship between miRNA-206-3p and the Toll-like receptor (TLR)4/nuclear factor (NF)-κB/Nod-like receptor protein-3 (NLRP3) pathway was verified. Finally, luciferase reporter gene and RNA pull-down assays were used to verify the targeting relationship between miRNA-206-3p and TLR4. miRNA206-3p levels are significantly decreased in the LPS-induced ALI model. Overexpression of miRNA-206-3p improves ALI, manifested as improved lung ultrasound, improved pathological changes of lung tissue, reduced W/D ratio of lung tissue, release of inflammatory factors in lung tissue, and reduced pyroptosis. Furthermore, overexpression of miRNA-206-3p contributed to reversing the ALI-promoting effect of LPS by hindering TLR4, myeloid differentiation primary response 88 (MyD88), NF-κB, and NLRP3 expression. In fact, miRNA-206-3p binds directly to TLR4. In conclusion, miRNA-206-3p alleviates LPS-induced ALI by inhibiting inflammation and pyroptosis via TLR4/NF-κB/NLRP3 pathway modulation.

The abuse of nitrous oxide (N2O) poses a substantial public health challenge. In many countries, including China, regulations governing the utilization and accessibility to N2O remain ambiguous, particularly within the food industry. Here, we report a case of a 21-year-old female who presented with symptoms of subacute combined degeneration (SCD) of the spinal cord due to N2O abuse. The patient exhibited bilateral lower limb numbness and weakness, low serum vitamin B12 levels with elevated homocysteine levels, and lumbar spine magnetic resonance imaging (MRI) revealed abnormal signals of the spinal cord. Following cessation of N2O and comprehensive therapy including methylcobalamin and nerve growth factor, the symptoms significantly improved. A follow-up examination 3 months later showed good progress in gait stability. At a 5-year follow-up, the patient’s previous clinical symptoms had completely disappeared, and her quality of life had returned to normal. This case underscores the urgency of raising awareness and prevention of N2O abuse, emphasizing the importance of timely diagnosis and comprehensive treatment for patient recovery. Clear formulation and enforcement of relevant regulatory measures are equally crucial in reducing instances of abuse.

Abstract This study delves into the influence of green financing within the cultural industry on the green growth trajectories of China’s 32 provinces spanning the years 2010 to 2021. Employing the Common Correlated Effects Mean Group (CCEMG) estimator, the research comprehensively assesses the impact of various independent variables on green growth. The findings indicate that a 1% rise in cultural sustainability investment correlates with a 0.63% upswing in green growth, whereas a 1% increase in carbon dioxide emissions corresponds to a 0.14% decline in green growth. Additionally, the study posits that shifts in the scale of the financial market do not exert a significant influence on green growth. Moreover, the negative coefficient of −0.25% for the variable “ICT diffusion index” suggests that heightened use of ICT devices is associated with a reduction in green growth. Given these insights, proposed strategies involve advancing the digitalization of the cultural industry through fintech and big data, establishing supportive regulatory frameworks, and fostering collaborations between financial institutions and cultural organizations.

Abstract Natural course of perianal abscess (PA) in infancy remains obscure. This study aimed to investigate the natural course of infants with PA after conservative treatment. A retrospective cohort study was conducted in infants with PA who were treated conservatively (due to the parents’ refusal of surgery), for more than 2 months between 2014 and 2020 at a single tertiary center. 153 patients (149 boys and 4 girls) were identified. The median follow-up was 5.3 years (range 3–8.2 years). Initially, 119 patients (77.8%) were completely cured by conservative treatment, and 34 (22.2%) failed. Among the 34 patients, 23 continued conservative treatment (20 cure, 3 fistula formation) and 11 underwent surgery. After conservative treatment, the rate of fistula formation, abscess recurrence, and new-onset abscess were 15.0%, 4.6%, and 6.5%, respectively. Overall, 139 patients (90.8%) were cured conservatively without surgery, and 11 (7.2%) underwent surgical management. In addition, 3 (2.0%) patients developed fistula-in-ano (under observation). PA in infants may be a time-limited and self-limited condition. Conservative management should be the first choice of treatment in most cases. Longer periods of conservative treatment may achieve better clinical outcomes in selected cases. There will be a percentage of patients (about 10%) that would require surgical treatment.

Abstract The paper aims to evaluate the impact of cultural and creative industries (CCI) finance on green economic flourishing for 16 European Union countries from 2012 to 2021. The coefficients estimated by the Arellano-Bond dynamic GMM technique confirmed that the market size coefficient of the cultural and creative industries is positive. In the case of green innovation, this variable has a positive coefficient. In addition, a 1% increase in the index of openness of the financial markets improves the green economy index of the European Union countries by 0.015%. With a 1% increase in the volume of cultural goods trade in the studied countries, the green economy index increases by 0.184%. The primary policy implications are developing green financing tools, using green cryptocurrencies in the cultural industry, developing the policy of trade multilateralism in cultural goods, promoting mutual learning of civilizations and cross-cultural literary exchange and innovation, and green government support for small and medium enterprises active in the culture industry.

The interaction between microbes and drugs encompasses the sourcing of pharmaceutical compounds, microbial drug degradation, the development of drug resistance genes, and the impact of microbial communities on host drug metabolism and immune modulation. These interactions significantly impact drug efficacy and the evolution of drug resistance. In this study, we propose a novel predictive model, termed GCGACNN. We first collected microbe, disease, and drug association data from multiple databases and the relevant literature to construct three association matrices and generate similarity feature matrices using Gaussian similarity functions. These association and similarity feature matrices were then input into a multi-layer Graph Neural Network for feature extraction, followed by a two-dimensional Convolutional Neural Network for feature fusion, ultimately establishing an effective predictive framework. Experimental results demonstrate that GCGACNN outperforms existing methods in predictive performance.

Background The objective of this study was to investigate the prognostic significance of total metabolic tumor volume (TMTV) derived from baseline 18F-2-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT), in conjunction with epidermal growth factor receptor (EGFR) mutation status, among patients with lung adenocarcinoma (LUAD). Methods We performed a retrospective analysis on 141 patients with LUAD (74 males, 67 females, median age 67 (range 34–86)) who underwent 18F-FDG PET/CT and had their EGFR mutation status determined. Optimal cutoff points for TMTV were determined using time-dependent receiver operating characteristic curve analysis. The survival difference was compared using Cox regression analysis and Kaplan‒Meier curves. Results The EGFR mutant patients (n = 79, 56.0%) exhibited significantly higher 2-year progression-free survival (PFS) and overall survival (OS) rates compared to those with EGFR wild-type (n = 62, 44.0%), with rates of 74.2% vs 69.2% (P = 0.029) and 86.1% vs 67.7% (P = 0.009), respectively. The optimal cutoff values of TMTV were 36.42 cm3 for PFS and 37.51 cm3 for OS. Patients with high TMTV exhibited significantly inferior 2-year PFS and OS, with rates of 22.4% and 38.1%, respectively, compared to those with low TMTV, who had rates of 85.8% and 95.0% (both P < 0.001). In both the EGFR mutant and wild-type groups, patients exhibiting high TMTV demonstrated significantly inferior 2-year PFS and OS compared to those with low TMTV. In multivariate analysis, EGFR mutation status (hazard ratio, HR, 0.41, 95% confidence interval, CI [0.18–0.94], P = 0.034) and TMTV (HR 8.08, 95% CI [2.34–28.0], P < 0.001) were independent prognostic factors of OS, whereas TMTV was also an independent prognosticator of PFS (HR 2.59, 95% CI [1.30–5.13], P = 0.007). Conclusion Our study demonstrates that the integration of TMTV on baseline 18F-FDG PET/CT with EGFR mutation status improves the accuracy of prognostic evaluation for patients with LUAD.

AbstractFibroblast growth factor receptor 2 (FGFR2), as a transmembrane receptor tyrosine kinase, is implicated in a plethora of human cancers, including intrahepatic cholangiocarcinomas, breast cancers, and non-small cell lung cancer. The clinically relevant V564F gatekeeper mutation conferred resistance to current FGFR2 drug − Infigratinib. In this study, the protein − ligand interactions between FGFR2 kinase domain (wild-type and V564F) and Infigratinib were compared through an integrated computational method. The multiple, large-scale molecular dynamics (MD) simulations, together with dynamic cross-correlation analysis and binding free energy calculations suggested that the resistant mutation may not trigger the conformational changes of the FGFR2 kinase domain. The simulation results also indicated that the driving force to decrease the binding affinity of Infigratinib to the FGFR2 V564F variant derived from the difference in the protein − ligand hydrogen bonding interactions. Moreover, the per-residue free energy decomposition analysis revealed that the reduced contributions from several residues in the ATP-binding site of FGFR2, especially Glu565 and Ala567 located at the kinase hinge domain, were the key residues responsible for the loss of binding affinity of Infigratinib to the V564F variant. This study may offer useful information for the design of novel selective kinase inhibitors targeting FGFR2.

Abstract Background The high incidence of epidermal growth factor receptor (EGFR) mutations is usually found in female patients with lung adenocarcinoma who have never-smoked. However, reports concerning male patients are scarce. Thus, this study aimed to explore a novel approach based on 18F-fluoro-2-deoxy-2-deoxyglucose (18F-FDG) PET/CT and serum tumor markers (STMs) to determine EGFR mutation status in male patients with non-small-cell lung cancer (NSCLC). Methods A total of 121 male patients with NSCLC were analyzed between October 2019 and March 2022. All patients underwent 18F-FDG PET/CT scan before treatment and monitored 8 STMs (cytokeratin 19 fragment [CYFRA21-1], squamous cell carcinoma-related antigen [SCC-Ag], carcinoembryonic antigen [CEA], neuron-specific enolase [NSE], carbohydrate antigen [CA] 50, CA125, CA72-4, and ferritin). A comparison was done between EGFR mutant and wild-type patients in terms of the maximum standardized uptake value of primary tumors (pSUVmax) and 8 STMs. We performed receiver operating characteristic (ROC) curve and multiple logistic regression analyses to determine predictors for EGFR mutation status. Results EGFR mutations were detected in 39 patients (32.2%). Compared with patients with EGFR wild-type, EGFR-mutant patients had lower concentrations of serum CYRFA21-1 (2.65 vs. 4.01, P = 0.002) and SCC-Ag (0.67 vs. 1.05, P = 0.006). No significant differences of CEA, NSE, CA 50, CA125, CA72-4 and ferritin were found between the two groups. The presence of EGFR mutations was significantly associated with low pSUVmax (

Variability in musculoskeletal and lower leg structure has the potential to influence hopping height. Achilles tendon moment arm length and plantarflexor muscle strength can influence ankle joint torque development and, consequently, hopping performance. While most studies have examined the connection of the Achilles tendon moment arm with hopping performance including the resting length, in this study we attempted to explore how the changes in Achilles tendon moment arm are related to hopping performance. Therefore, the purpose of this study was to test for correlations between foot and lower leg muscle structure parameters (i.e., muscle mass, volume, cross-sectional area and Achilles tendon moment arm length) and hopping height performance in relation to changes in Achilles tendon moment arm length. Eighteen participants (10 males 8 female) performed repetitive bilateral hopping on a force platform while sagittal plane kinematics of the lower leg were recorded. Additionally, maximal isometric plantarflexion was measured. To obtain structural parameters of the lower leg, the right lower leg of each participant was scanned with magnetic resonance imaging. The cross-sectional areas of the Achilles tendon, soleus, lateral and medial gastrocnemius were measured, while muscle volumes, muscle mass, and Achilles tendon moment arm length were calculated. Contrary to our initial assumption, longer Achilles tendon moment arm did not result in superior hopping performance. Interestingly, neither maximal isometric plantarflexion force nor muscle size correlated with repetitive bilateral hopping performance. We can assume that the mechanical characteristics of the tendon and the effective utilization of the stored strain energy in the tendon may play a more important role in repetitive hopping than the structural parameters of the lower leg.

BackgroundArtificial intelligence (AI) is transforming various fields, with health care, especially diagnostic specialties such as radiology, being a key but controversial battleground. However, there is limited research systematically examining the response of “human intelligence” to AI. ObjectiveThis study aims to comprehend radiologists’ perceptions regarding AI, including their views on its potential to replace them, its usefulness, and their willingness to accept it. We examine the influence of various factors, encompassing demographic characteristics, working status, psychosocial aspects, personal experience, and contextual factors. MethodsBetween December 1, 2020, and April 30, 2021, a cross-sectional survey was completed by 3666 radiology residents in China. We used multivariable logistic regression models to examine factors and associations, reporting odds ratios (ORs) and 95% CIs. ResultsIn summary, radiology residents generally hold a positive attitude toward AI, with 29.90% (1096/3666) agreeing that AI may reduce the demand for radiologists, 72.80% (2669/3666) believing AI improves disease diagnosis, and 78.18% (2866/3666) feeling that radiologists should embrace AI. Several associated factors, including age, gender, education, region, eye strain, working hours, time spent on medical images, resilience, burnout, AI experience, and perceptions of residency support and stress, significantly influence AI attitudes. For instance, burnout symptoms were associated with greater concerns about AI replacement (OR 1.89; P

Exercise-derived exosomes have been identified as novel players in mediating cell-to-cell communication in the beneficial effects of improving cardiovascular disease (CVD). This review aimed to systematically investigate exosomes as delivery tools for the benefits of exercise in the prevention and treatment of CVD and summarize these outcomes with an overview of their therapeutic implications. Among the 1417 articles obtained in nine database searches (PubMed, EBSCO, Embase, Web of Science, CENTRAL, Ovid, Science Direct, Scopus, and Wiley), 12 articles were included based on eligibility criteria. The results indicate that exercise increases the release of exosomes, increasing exosomal markers (TSG101, CD63, and CD81) and exosome-carried miRNAs (miR-125b-5p, miR-122-5p, miR-342-5p, miR-126, miR-130a, miR-138-5p, and miR-455). These miRNAs mainly regulate the expression of MAPK, NF-kB, VEGF, and Caspase to protect the cardiovascular system. Moreover, the outcome indicators of myocardial apoptosis and myocardial infarction volume are significantly reduced following exercise-induced exosome release, and angiogenesis, microvessel density and left ventricular ejection fraction are significantly increased, as well as alleviating myocardial fibrosis following exercise-induced exosome release. Collectively, these results further confirm that exercise-derived exosomes have a beneficial role in potentially preventing and treating CVD and support the use of exercise-derived exosomes in clinical settings.

Abstract Objective To evaluate the diagnostic value of a multiparameter model based on 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) metabolic parameters and clinical variables in differentiating nonmetastatic gallbladder cancer (GBC) from cholecystitis. Patients and methods In total, 122 patients (88 GBC nonmetastatic patients and 34 cholecystitis patients) with gallbladder space-occupying lesions who underwent 18F-FDG PET/CT were included. All patients received surgery and pathology, and baseline characteristics and clinical data were also collected. The metabolic parameters of 18F-FDG PET, including SUVmax (maximum standard uptake value), SUVmean (mean standard uptake value), SUVpeak (peak standard uptake value), MTV (metabolic tumour volume), TLG (total lesion glycolysis) and SUVR (tumour-to-normal liver standard uptake value ratio), were evaluated. The differential diagnostic efficacy of each independent parameter and multiparameter combination model was evaluated using the receiver operating characteristic (ROC) curve. The improvement in diagnostic efficacy using a combination of the above multiple parameters was evaluated by integrated discriminatory improvement (IDI), net reclassification improvement (NRI) and bootstrap test. Decision curve analysis (DCA) was used to evaluate clinical efficacy. Results The ROC curve showed that SUVR had the highest diagnostic ability among the 18F-FDG PET metabolic parameters (area under the curve [AUC] = 0.698; sensitivity = 0.341; specificity = 0.971; positive predictive value [PPV] = 0.968; negative predictive value [NPV] = 0.363). The combined diagnostic model of cholecystolithiasis, fever, CEA > 5 ng/ml and SUVR showed an AUC of 0.899 (sensitivity = 0.909, specificity = 0.735, PPV = 0.899, NPV = 0.758). The diagnostic efficiency of the model was improved significantly compared with SUVR. The clinical efficacy of the model was confirmed by DCA. Conclusions The multiparameter diagnostic model composed of 18F-FDG PET metabolic parameters (SUVR) and clinical variables, including patient signs (fever), medical history (cholecystolithiasis) and laboratory examination (CEA > 5 ng/ml), has good diagnostic efficacy in the differential diagnosis of nonmetastatic GBC and cholecystitis.

Key points The radiology residents at all levels in China were systematically landscaped. 68.6% of the 3666 residents reported satisfaction with the residency training. Radiation protection was significantly associated with residency satisfaction. Satisfaction significantly impacts radiology residents’ well-being, professional identity and self-reported competency. The findings provide new insights into sustaining and improving the radiology residency.

Robust and high capacity optical coding will be at the base of future developments of information transfer and storage. Here the authors develop a topological all-optical coding scheme, which possesses good stability and a high capacity, using nested vortex knots and links.

Airway mucus dysfunction and impaired immunological defenses are hallmarks of several lung diseases, including asthma, cystic fibrosis, and chronic obstructive pulmonary diseases, and are mostly causative factors in bacterial-biofilm-associated respiratory tract infections. Bacteria residing within the biofilm architecture pose a complex challenge in clinical settings due to their increased tolerance to currently available antibiotics and host immune responses, resulting in chronic infections with high recalcitrance and high rates of morbidity and mortality. To address these unmet clinical needs, potential anti-biofilm therapeutic strategies are being developed to effectively control bacterial biofilm. This review focuses on recent advances in the development and application of nanoparticulate drug delivery systems for the treatment of biofilm-associated respiratory tract infections, especially addressing the respiratory barriers of concern for biofilm accessibility and the various types of nanoparticles used to combat biofilms. Understanding the obstacles facing pulmonary drug delivery to bacterial biofilms and nanoparticle-based approaches to combatting biofilm may encourage researchers to explore promising treatment modalities for bacterial-biofilm-associated chronic lung infections.

This work presents a free-breathing dynamic contrast-enhanced (DCE) MRI reconstruction method called low-rank plus sparse (L+S) with joint sparsity. The proposed method improved dynamic contrast performance by integrating an additional temporal Fast Fourier Transform (FFT) constraint into the standard L+S decomposition method. In the proposed method, both temporal total variation (TV) sparsity constraint and temporal FFT constraint are integrated into a standard L+S decomposition model, forming L+S with joint sparsity. Temporal TV and Temporal FFT aim to suppress under-sampling artifacts and improve dynamic contrast in DCE-MRI, respectively. A fast composite splitting algorithm (FCSA) is adopted for solving the L+S model with multiple sparsity constraints, maintaining the reconstruction efficiency. A computer simulation framework was developed to compare the performance of L+S with joint sparsity and other reconstruction schemes. The performance of L+S with joint sparsity was tested using computer simulation and several liver DCE-MRI datasets. The proposed L+S based method achieved around four times faster reconstruction speed than the GRASP method. With the support of an additional sparsity constraint, the peak DCE signal in the proposed method was increased by more than 20% over that of a standard L+S decomposition.

BackgroundThis study aimed to establish an effective model for preoperative prediction of tumor deposits (TDs) in patients with rectal cancer (RC). MethodsIn 500 patients, radiomic features were extracted from magnetic resonance imaging (MRI) using modalities such as high-resolution T2-weighted (HRT2) imaging and diffusion-weighted imaging (DWI). Machine learning (ML)-based and deep learning (DL)-based radiomic models were developed and integrated with clinical characteristics for TD prediction. The performance of the models was assessed using the area under the curve (AUC) over five-fold cross-validation.ResultsA total of 564 radiomic features that quantified the intensity, shape, orientation, and texture of the tumor were extracted for each patient. The HRT2-ML, DWI-ML, Merged-ML, HRT2-DL, DWI-DL, and Merged-DL models demonstrated AUCs of 0.62 ± 0.02, 0.64 ± 0.08, 0.69 ± 0.04, 0.57 ± 0.06, 0.68 ± 0.03, and 0.59 ± 0.04, respectively. The clinical-ML, clinical-HRT2-ML, clinical-DWI-ML, clinical-Merged-ML, clinical-DL, clinical-HRT2-DL, clinical-DWI-DL, and clinical-Merged-DL models demonstrated AUCs of 0.81 ± 0.06, 0.79 ± 0.02, 0.81 ± 0.02, 0.83 ± 0.01, 0.81 ± 0.04, 0.83 ± 0.04, 0.90 ± 0.04, and 0.83 ± 0.05, respectively. The clinical-DWI-DL model achieved the best predictive performance (accuracy 0.84 ± 0.05, sensitivity 0.94 ± 0. 13, specificity 0.79 ± 0.04).ConclusionsA comprehensive model combining MRI radiomic features and clinical characteristics achieved promising performance in TD prediction for RC patients. This approach has the potential to assist clinicians in preoperative stage evaluation and personalized treatment of RC patients.

The RET protein is a transmembrane receptor tyrosine kinase (RTK) whose oncogenic mutations or fusions are closely related to human cancers such as thyroid and non-small cell lung cancer. Vandetanib as a clinical-approved protein-tyrosine kinase inhibitor (TKI) exhibits anti-cancer efficacy by blocking the RET ATP-binding site, but drug resistance was observed for the RETG810A mutant. Recent studies have identified another TKI nintedanib as an effective molecule to inhibit vandetanib-resistant RETG810A. However, there is no clear evidence of why nintedanib and vandetanib displayed different inhibitory activities towards RETG810A. Here, we exploited molecular dynamic (MD) simulations to compare the interactions of the RETG810A mutant with nintedanib and vandetanib. A higher structural flexibility of the activation loop was observed in the nintedanib-bound RETG810A, which may result in discrepant autophosphorylation activity in the nintedanib- and vandetanib-bound RET kinase, causing differentiated pharmacological effects of the two compounds. Molecular mechanics/Poisson-Bolzmann surface area method suggested that nintedanib had a higher affinity towards RETG810A over vandetanib, accounting for its better inhibitory effect as an ATP-competitive compound. These results depicted the underlying mechanism for the different inhibitory efficacy of nintedanib and vandetanib on RETG810A from both conformational and energetic aspects. Furthermore, we also found that both compounds maintained the ‘DFG-in, αC-helix-in, and activation loop-open’ conformation of RETG810A, which is the characteristic of the active state. Together, our results provide comprehensive mechanistic insights into nintedanib’s capability in inhibiting vandetanib-resistant RET mutant and enlighten future structural-based optimisation of RET TKIs to overcome drug resistance.

The WRKY proteins are a family of plant-specific transcription factors (TFs) that are widely involved in plant development and anti-stress responses. Arabidopsis WRKY11 (AtWRKY11) functions in regulating plant defense against abiotic stress and belongs to the IId subgroup of WRKY TFs. We herein report the expression, purification and preliminary structural characterization of AtWRKY11 DNA-binding domain (DBD) using solution NMR. Almost complete backbone chemical shift assignments of AtWRKY11-DBD have been obtained. Chemical shift-based secondary structure analysis suggests that AtWRKY11-DBD may exhibit local conformational differences from the X-ray structure of the C-terminal WRKY domain of AtWRKY1, particularly in the β1 and β5 strands. Our current study provides the basis for further structural and interactional studies.

Free radicals, including reactive oxygen species (ROS) and reactive nitrogen species (RNS), play critical roles in various physiological activities such as cell differentiation, apoptosis, and vascular tension when existing in cells at low levels. However, excessive amounts of free radicals are harmful, causing DNA damage, lipid peroxidation, protein degeneration, and abnormal cell death. Certain viral infections induce cells to produce excessive free radicals, which in multiple ways help the virus to replicate, mature, and exit. Iron is a necessary element for many intracellular enzymes, involved in both cellular activities and viral replication. Ferroptosis, a programmed cell death mode distinct from apoptosis, necrosis, and pyroptosis, is characterized by lipid peroxide accumulation and damage to the antioxidant system, affecting many cellular processes. Viral infection commonly manifests as decreased glutathione (GSH) content and down-regulated glutathione peroxidase 4 (GPX4) activity, similar to ferroptosis. Recent studies have suggested a possible relationship among free radicals, viral infections and ferroptosis. This review aims to elucidate the molecular mechanism linking free radicals and ferroptosis during viral infections and provide a new theoretical basis for studying viral pathogenesis and control.

This paper forms a set of three-dimensional temperature field simulation methods considering the influence of sunshine shadow based on the DFLUX subroutine and FILM subroutine interface provided by the Abaqus platform to simulate the three-dimensional temperature field of concrete bridge towers and study its distribution law. The results show that the method has high accuracy for shadow recognition and temperature field calculation. The maximum difference between the shadow recognition results and the theoretical calculation value was only 19.1 mm, and the maximum difference between the simulated temperature and the measured temperature was 3.3 °C. The results of analyzing the temperature field of the concrete bridge tower using this algorithm show that the temperature difference between the opposite external surface of the tower column can reach 11.6 °C, which is significantly greater than the recommended temperature difference value of 5 °C in the specifications. For the concrete bridge tower, in the thickness direction of the tower wall, the temperature change was obvious only at a range of 0.3 m from the external surface of the tower wall, and the temperature change in the remaining range was small. In addition, the temperature gradient distribution of the sunshine temperature field in the direction of wall thickness conformed to the exponential function T(x) = T0e−αx + C. Additionally, the data fitting results indicate that using the temperature data at a distance of 0.8 m from the external surface as the calculation parameter in the function can achieve the ideal fitting result.

Avian influenza virus (AIV) subtype H9N2 is the most widespread AIV in poultry worldwide, causing great economic losses in the global poultry industry. Chickens and ducks are the major hosts and play essential roles in the transmission and evolution of H9N2 AIV. Vaccines are considered an effective strategy for fighting H9N2 infection. However, due to the differences in immune responses to infection, vaccines against H9N2 AIV suitable for use in both chickens and ducks have not been well studied. This study developed an inactivated H9N2 vaccine based on a duck-origin H9N2 AIV and assessed its effectiveness in the laboratory. The results showed that the inactivated H9N2 vaccine elicited significant haemagglutination inhibition (HI) antibodies in both chickens and ducks. Virus challenge experiments revealed that immunization with this vaccine significantly blocked virus shedding after infection by both homogenous and heterologous H9N2 viruses. The vaccine was efficacious in chicken and duck flocks under normal field conditions. We also found that egg-yolk antibodies were produced by laying birds immunized with the inactivated vaccine, and high levels of maternal antibodies were detected in the serum of the offspring. Taken together, our study showed that this inactivated H9N2 vaccine could be extremely favourable for the prevention of H9N2 in both chickens and ducks.

PET/CT with 18F-2-fluoro-2-deoxyglucose (18F-FDG) has been proposed as a promising modality for diagnosing and monitoring treatment response and evaluating prognosis for patients with non-small cell lung cancer (NSCLC). The status of epidermal growth factor receptor (EGFR) mutation is a critical signal for the treatment strategies of patients with NSCLC. Higher response rates and prolonged progression-free survival could be obtained in patients with NSCLC harboring EGFR mutations treated with tyrosine kinase inhibitors (TKIs) when compared with traditional cytotoxic chemotherapy. However, patients with EGFR mutation treated with TKIs inevitably develop drug resistance, so predicting the duration of resistance is of great importance for selecting individual treatment strategies. Several semiquantitative metabolic parameters, e.g., maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), measured by PET/CT to reflect 18F-FDG metabolic activity, have been demonstrated to be powerful in predicting the status of EGFR mutation, monitoring treatment response of TKIs, and assessing the outcome of patients with NSCLC. In this review, we summarize the biological and clinical correlations between EGFR mutation status and 18F-FDG metabolic activity in NSCLC. The metabolic activity of 18F-FDG, as an extrinsic manifestation of NSCLC, could reflect the mutation status of intrinsic factor EGFR. Both of them play a critical role in guiding the implementation of treatment modalities and evaluating therapy efficacy and outcome for patients with NSCLC.

Background Never-smokers with lung cancer usually have a higher survival rate than that of smokers. The high metabolic activity of lung cancer on 18F-2-Fluoro-2-deoxyglucose (18F-FDG) PET/CT generally indicates a poor outcome. However, there is a lack of reports on the association between cigarette smoking and 18F-FDG metabolic activity in patients with lung cancer. In this study, we aimed to investigate the effects of cigarette smoking on metabolic activity of lung cancer on 18F-FDG PET/CT. Materials and Methods A total of 338 patients (230 males, 108 females; mean age: 66.3, range 34–86) with pathologically diagnosed lung cancer were enrolled from September 2019 to April 2021. All patients underwent baseline 18F-FDG PET/CT and the maximum standard uptake value (SUVmax) of the primary tumor (pSUVmax), lymph node (nSUVmax) and distant metastasis (mSUVmax) were measured. The associations between cigarette smoking status, clinical stage, pathological subtypes and metabolic parameters on 18F-FDG PET/CT were analyzed. Results Of the 338 patients, cigarette smoking was identified in 153 patients (45.3%) and the remaining 185 (54.7%) were never-smokers. Smoking was found more frequently in males, squamous cell carcinoma (SCC) and stage III–IV diseases. The pSUVmax in smokers was significantly higher than that in never-smokers (t = 3.386, P

Several mutations identified in phospholamban (PLN) have been linked to familial dilated cardiomyopathy (DCM) and heart failure, yet the underlying molecular mechanism remains controversial. PLN interacts with sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) and regulates calcium uptake, which is modulated by the protein kinase A (PKA)-dependent phosphorylation of PLN during the fight-or-flight response. Here, we present the crystal structures of the catalytic domain of mouse PKA in complex with wild-type and DCM-mutant PLNs. Our structures, combined with the results from other biophysical and biochemical assays, reveal a common disease mechanism: the mutations in PLN reduce its phosphorylation level by changing its conformation and weakening its interactions with PKA. In addition, we demonstrate that another more ubiquitous SERCA-regulatory peptide, called another-regulin (ALN), shares a similar mechanism mediated by PKA in regulating SERCA activity.

ObjectiveTo develop an accurate and rapid computed tomography (CT)-based interpretable AI system for the diagnosis of lung diseases.BackgroundMost existing AI systems only focus on viral pneumonia (e.g., COVID-19), specifically, ignoring other similar lung diseases: e.g., bacterial pneumonia (BP), which should also be detected during CT screening. In this paper, we propose a unified sequence-based pneumonia classification network, called SLP-Net, which utilizes consecutiveness information for the differential diagnosis of viral pneumonia (VP), BP, and normal control cases from chest CT volumes.MethodsConsidering consecutive images of a CT volume as a time sequence input, compared with previous 2D slice-based or 3D volume-based methods, our SLP-Net can effectively use the spatial information and does not need a large amount of training data to avoid overfitting. Specifically, sequential convolutional neural networks (CNNs) with multi-scale receptive fields are first utilized to extract a set of higher-level representations, which are then fed into a convolutional long short-term memory (ConvLSTM) module to construct axial dimensional feature maps. A novel adaptive-weighted cross-entropy loss (ACE) is introduced to optimize the output of the SLP-Net with a view to ensuring that as many valid features from the previous images as possible are encoded into the later CT image. In addition, we employ sequence attention maps for auxiliary classification to enhance the confidence level of the results and produce a case-level prediction.ResultsFor evaluation, we constructed a dataset of 258 chest CT volumes with 153 VP, 42 BP, and 63 normal control cases, for a total of 43,421 slices. We implemented a comprehensive comparison between our SLP-Net and several state-of-the-art methods across the dataset. Our proposed method obtained significant performance without a large amount of data, outperformed other slice-based and volume-based approaches. The superior evaluation performance achieved in the classification experiments demonstrated the ability of our model in the differential diagnosis of VP, BP and normal cases.