Phycocyanin from microalgae: A comprehensive review covering microalgal culture, phycocyanin sources and stability.

As food safety continues to gain prominence, phycocyanin (PC) is increasingly favored by consumers as a natural blue pigment, which is extracted from microalgae and serves the dual function of promoting health and providing coloration. Spirulina-derived PC demonstrates exceptional stability within temperature ranges below 45 °C and under pH conditions between 5.5 and 6.0. However, its application is limited in scenarios involving high-temperature processing due to its sensitivity to heat and light. This comprehensive review provides insights into the efficient production of PC from microalgae, covers the metabolic engineering of microalgae to increase PC yields and discusses various strategies for enhancing its stability in food applications. In addition to the most widely used Spirulina, some red algae and Thermosynechococcus can serve as good source of PC. The genetic and metabolic manipulation of microalgae strains has shown promise in increasing PC yield and improving its quality. Delivery systems including nanoparticles, hydrogels, emulsions, and microcapsules offer a promising solution to protect and extend the shelf life of PC in food products, ensuring its vibrant color and health-promoting properties are preserved. This review highlights the importance of metabolic engineering, multi-omics applications, and innovative delivery systems in unlocking the full potential of this natural blue pigment in the realm of food applications, provides a complete overview of the entire process from production to commercialization of PC, including the extraction and purification.

A feasibility study to predict 3D dose delivery accuracy for IMRT using DenseNet with log files.

OBJECTIVE: This study aims to explore the feasibility of DenseNet in the establishment of a three-dimensional (3D) gamma prediction model of IMRT based on the actual parameters recorded in the log files during delivery. METHODS: A total of 55 IMRT plans (including 367 fields) were randomly selected. The gamma analysis was performed using gamma criteria of 3% /3 mm (Dose Difference/Distance to Agreement), 3% /2 mm, 2% /3 mm, and 2% /2 mm with a 10% dose threshold. In addition, the log files that recorded the gantry angle, monitor units (MU), multi-leaf collimator (MLC), and jaws position during delivery were collected. These log files were then converted to MU-weighted fluence maps as the input of DenseNet, gamma passing rates (GPRs) under four different gamma criteria as the output, and mean square errors (MSEs) as the loss function of this model. RESULTS: Under different gamma criteria, the accuracy of a 3D GPR prediction model decreased with the implementation of stricter gamma criteria. In the test set, the mean absolute error (MAE) of the prediction model under the gamma criteria of 3% /3 mm, 2% /3 mm, 3% /2 mm, and 2% /2 mm was 1.41, 1.44, 3.29, and 3.54, respectively; the root mean square error (RMSE) was 1.91, 1.85, 4.27, and 4.40, respectively; the Sr was 0.487, 0.554, 0.573, and 0.506, respectively. There was a correlation between predicted and measured GPRs (P <  0.01). Additionally, there was no significant difference in the accuracy between the validation set and the test set. The accuracy in the high GPR group was high, and the MAE in the high GPR group was smaller than that in the low GPR group under four different gamma criteria. CONCLUSIONS: In this study, a 3D GPR prediction model of patient-specific QA using DenseNet was established based on log files. As an auxiliary tool for 3D dose verification in IMRT, this model is expected to improve the accuracy and efficiency of dose validation.

Bismuth-Containing Quadruple Therapy for Helicobacter pylori Eradication: A Randomized Clinical Trial of 10 and 14 Days.

BACKGROUND: Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. METHODS: Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication. RESULTS: The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups. CONCLUSION: Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).

Real-Time Monitoring of Tyrosine Hydroxylase Activity with a Ratiometric Fluorescent Probe.

Parkinson's disease (PD) represents the second most widespread neurodegenerative disease, and early monitoring and diagnosis are urgent at present. Tyrosine hydroxylase (TH) is a key enzyme for producing dopamine, the levels of which can serve as an indicator for assessing the severity and progression of PD. This renders the specific detection and visualization of TH a strategically vital way to meet the above demands. However, a fluorescent probe for TH monitoring is still missing. Herein, three rationally designed wash-free ratiometric fluorescent probes were proposed. Among them, TH-1 exhibited ideal photophysical properties and specific dual-channel bioimaging of TH activity in SH-SY5Y nerve cells. Moreover, the probe allowed for in vivo imaging of TH activity in zebrafish brain and living striatal slices of mice. Overall, the ratiometric fluorescent probe TH-1 could serve as a potential tool for real-time monitoring of PD in complex biosystems.

Development strategies and application of antimicrobial peptides as future alternatives to in-feed antibiotics.

The use of in-feed antibiotics has been widely restricted due to the significant environmental pollution and food safety concerns they have caused. Antimicrobial peptides (AMPs) have attracted widespread attention as potential future alternatives to in-feed antibiotics owing to their demonstrated antimicrobial activity and environment friendly characteristics. However, the challenges of weak bioactivity, immature stability, and low production yields of natural AMPs impede practical application in the feed industry. To address these problems, efforts have been made to develop strategies for approaching the AMPs with enhanced properties. Herein, we summarize approaches to improving the properties of AMPs as potential alternatives to in-feed antibiotics, mainly including optimization of structural parameters, sequence modification, selection of microbial hosts, fusion expression, and industrially fermentation control. Additionally, the potential for application of AMPs in animal husbandry is discussed. This comprehensive review lays a strong theoretical foundation for the development of in-feed AMPs to achieve the public health globally.

The Gene vepN Regulated by Global Regulatory Factor veA That Affects Aflatoxin Production, Morphological Development and Pathogenicity in Aspergillus flavus.

Velvet (VeA), a light-regulated protein that shuttles between the cytoplasm and the nucleus, serves as a key global regulator of secondary metabolism in various Aspergillus species and plays a pivotal role in controlling multiple developmental processes. The gene vepN was chosen for further investigation through CHIP-seq analysis due to significant alterations in its interaction with VeA under varying conditions. This gene (AFLA_006970) contains a Septin-type guanine nucleotide-binding (G) domain, which has not been previously reported in Aspergillus flavus (A. flavus). The functional role of vepN in A. flavus was elucidated through the creation of a gene knockout mutant and a gene overexpression strain using a well-established dual-crossover recombinational technique. A comparison between the wild type (WT) and the ΔvepN mutant revealed distinct differences in morphology, reproductive capacity, colonization efficiency, and aflatoxin production. The mutant displayed reduced growth rate; dispersion of conidial heads; impaired cell wall integrity; and decreased sclerotia formation, colonization capacity, and aflatoxin levels. Notably, ΔvepN exhibited complete growth inhibition under specific stress conditions, highlighting the essential role of vepN in A. flavus. This study provides evidence that vepN positively influences aflatoxin production, morphological development, and pathogenicity in A. flavus.

Methylation entropy landscape of Chinese long-lived individuals reveals lower epigenetic noise related to human healthy aging.

The transition from ordered to noisy is a significant epigenetic signature of aging and age-related disease. As a paradigm of healthy human aging and longevity, long-lived individuals (LLI, >90 years old) may possess characteristic strategies in coping with the disordered epigenetic regulation. In this study, we constructed high-resolution blood epigenetic noise landscapes for this cohort by a methylation entropy (ME) method using whole genome bisulfite sequencing (WGBS). Although a universal increase in global ME occurred with chronological age in general control samples, this trend was suppressed in LLIs. Importantly, we identified 38,923 genomic regions with LLI-specific lower ME (LLI-specific lower entropy regions, for short, LLI-specific LERs). These regions were overrepresented in promoters, which likely function in transcriptional noise suppression. Genes associated with LLI-specific LERs have a considerable impact on SNP-based heritability of some aging-related disorders (e.g., asthma and stroke). Furthermore, neutrophil was identified as the primary cell type sustaining LLI-specific LERs. Our results highlight the stability of epigenetic order in promoters of genes involved with aging and age-related disorders within LLI epigenomes. This unique epigenetic feature reveals a previously unknown role of epigenetic order maintenance in specific genomic regions of LLIs, which helps open a new avenue on the epigenetic regulation mechanism in human healthy aging and longevity.

Eukaryotic translation initiation factor EIF4G1 p.Ser637Cys mutation in a family with Parkinson's disease with antecedent essential tremor.

Essential tremor (ET) and Parkinson's disease (PD) are common chronic movement disorders that can cause a substantial degree of disability. However, the etiology underlying these two conditions remains poorly understood. In the present study, Whole-exome sequencing of peripheral blood samples from the proband and Sanger sequencing of the other 18 family members, and pedigree analysis of four generations of 29 individuals with both ET and PD in a nonconsanguineous Chinese family were performed. Specifically, family members who had available medical information, including historical documentation and physical examination records, were included. A novel c.1909A>T (p.Ser637Cys) missense mutation was identified in the eukaryotic translation initiation factor 4γ1 (EIF4G1) gene as the candidate likely responsible for both conditions. In total, 9 family members exhibited tremor of the bilateral upper limbs and/or head starting from ages of ≥40 years, 3 of whom began showing evidence of PD in their 70s. Eukaryotic initiation factor 4 (eIF4)G1, a component of the translation initiation complex eIF4F, serves as a scaffold protein that interacts with many initiation factors and then binds to the 40S ribosomal subunit. The EIF4G1 (p.Ser637Cys) might inhibit the recruitment of the mRNA to the ribosome. In conclusion, the results from the present study suggested that EIF4G1 may be responsible for the hereditary PD with 'antecedent ET' reported in the family assessed.

High-dose dual therapy versus bismuth-containing quadruple therapy for the eradication of Helicobacter pylori: A systematic review and meta-analysis.

OBJECTIVE: To update evidence-based data comparing the efficacy and safety of high-dose dual therapy (HDDT) and bismuth-containing quadruple therapy (BQT) in eradicating Helicobacter pylori infection through meta-analysis. METHODS: Multiple databases were systematically searched for randomized controlled trials (RCTs) published up to May 18, 2023. Dichotomous data were evaluated using risk ratio (RR) and 95% confidence interval (CI). Subgroup analysis, sensitivity analysis, risk of bias assessment, and quality of evidence evaluation were performed. RESULTS: Twenty RCTs containing 7891 subjects were included in the analysis. There was no statistically significant difference in H. pylori eradication rate between HDDT and BQT in the intention-to-treat (ITT) analysis (86.31% vs 84.88%; RR 1.02, 95% CI 1.00-1.04, P = 0.12). In the per-protocol (PP) analysis, the eradication rates for HDDT and BQT were 90.27% and 89.94%, respectively (RR 1.01, 95% CI 0.99-1.03, P = 0.44). Adverse events were significantly lower with HDDT than with BQT (RR 0.44, 95% CI 0.38-0.51, P < 0.00001). Patient adherence was significantly different between the two groups (RR 1.01, 95% CI 1.00-1.03, P = 0.02). Subgroup analysis based on antibiotic combinations within the BQT group showed a significantly higher eradication rate for HDDT than for BQT only when BQT used amoxicillin combined with clarithromycin (P = 0.0009). CONCLUSIONS: HDDT showed comparable efficacy with BQT for H. pylori eradication, with fewer adverse effects and higher compliance. Due to regional differences, antibiotic resistance rates, and combined BQT antibiotics, more studies are needed for further validation and optimization of HDDT.

Predicting the error magnitude in patient-specific QA during radiotherapy based on ResNet.

BACKGROUND: The error magnitude is closely related to patient-specific dosimetry and plays an important role in evaluating the delivery of the radiotherapy plan in QA. No previous study has investigated the feasibility of deep learning to predict error magnitude. OBJECTIVE: The purpose of this study was to predict the error magnitude of different delivery error types in radiotherapy based on ResNet. METHODS: A total of 34 chest cancer plans (172 fields) of intensity-modulated radiation therapy (IMRT) from Eclipse were selected, of which 30 plans (151 fields) were used for model training and validation, and 4 plans including 21 fields were used for external testing. The collimator misalignment (COLL), monitor unit variation (MU), random multi-leaf collimator shift (MLCR), and systematic MLC shift (MLCS) were introduced. These dose distributions of portal dose predictions for the original plans were defined as the reference dose distribution (RDD), while those for the error-introduced plans were defined as the error-introduced dose distribution (EDD). Different inputs were used in the ResNet for predicting the error magnitude. RESULTS: In the test set, the accuracy of error type prediction based on the dose difference, gamma distribution, and RDD + EDD was 98.36%, 98.91%, and 100%, respectively; the root mean squared error (RMSE) was 1.45-1.54, 0.58-0.90, 0.32-0.36, and 0.15-0.24; the mean absolute error (MAE) was 1.06-1.18, 0.32-0.78, 0.25-0.27, and 0.11-0.18, respectively, for COLL, MU, MLCR and MLCS. CONCLUSIONS: In this study, error magnitude prediction models with dose difference, gamma distribution, and RDD + EDD are established based on ResNet. The accurate prediction of the error magnitude under different error types can provide reference for error analysis in patient-specific QA.

Electroencephalogram findings in 10 patients with post-stroke epilepsy: A retrospective study.

BACKGROUND: Post-stroke epilepsy is a common and easily overlooked complication of acute cerebrovascular disease. Long-term seizures can seriously affect the prognosis and quality of life of patients. Electroencephalogram (EEG) is the simplest way to diagnose epilepsy, and plays an important role in predicting seizures and guiding medication. AIM: To explore the EEG characteristics of patients with post-stroke epilepsy and improve the detection rate of inter-seizure epileptiform discharges. METHODS: From January 2017 to June 2020, 10 patients with post-stroke epilepsy in our hospital were included. The clinical, imaging, and EEG characteristics were collected. The stroke location, seizure type, and ictal and interictal EEG manifestations of the patients with post-stroke epilepsy were then retrospectively analyzed. RESULTS: In all 10 patients, epileptiform waves occurred in the side opposite to the stroke lesion during the interictal stage; these manifested as sharp wave, sharp-wave complex, or spike discharges in the anterior head lead of the side opposite to the lesion. CONCLUSION: In EEG, epileptiform waves can occur in the side opposite to the stroke lesion in patients with post-stroke epilepsy.

Dosimetry and treatment efficiency of SBRT using TaiChiB radiotherapy system for two-lung lesions with one overlapping organs at risk.

Purpose: This study aims to assess the dosimetry and treatment efficiency of TaiChiB-based Stereotactic Body Radiotherapy (SBRT) plans applying to treat two-lung lesions with one overlapping organs at risk. Methods: For four retrospective patients diagnosed with two-lung lesions each patient, four treatment plans were designed including Plan Edge, TaiChiB linac-based, RGS-based, and a linac-RGS hybrid (Plan TCLinac, Plan TCRGS, and Plan TCHybrid). Dosimetric metrics and beam-on time were employed to evaluate and compare the TaiChiB-based plans against Plan Edge. Results: For Conformity Index (CI), Plan TCRGS outperformed all other plans with an average CI of 1.06, as opposed to Plan Edge's 1.33. Similarly, for R50 %, Plan TCRGS was superior with an average R50 % of 3.79, better than Plan Edge's 4.28. In terms of D2 cm, Plan TCRGS also led with an average of 48.48%, compared to Plan Edge's 56.25%. For organ at risk (OAR) sparing, Plan TCRGS often displayed the lowest dosimetric values, notably for the spinal cord (Dmax 5.92 Gy) and lungs (D1500cc 1.00 Gy, D1000cc 2.61 Gy, V10 Gy 15.14%). However, its high Dmax values for the heart and great vessels sometimes exceeded safety thresholds. Plan TCHybrid presented a balanced approach, showing doses comparable to or better than Plan Edge without crossing safety limits. In terms of beam-on time, Plan TCLinac emerged as the most efficient treatment option in three out of four cases, followed closely by Plan Edge in one case. Plan TCRGS, despite its dosimetric advantages, was the least efficient, recording notably longer beam-on times, with a peak at 33.28 minutes in Case 2. Conclusion: For patients with two-lung lesions treated by SBRT whose one lesion overlaps with OARs, the Plan TCHybrid delivered by TaiChiB digital radiotherapy system can be recommended as a clinical option.

Improved viability of probiotics by encapsulation in chickpea protein matrix during simulated gastrointestinal digestion by succinylated modification.

The potential application of succinylated chickpea protein (SCP) as a wall material for spray-dried microencapsulated probiotics was investigated. The results showed that succinylation increased the surface charge of chickpea proteins (CP) and reduced the particle size of the proteins. Meanwhile, succinylated modification decreased the solubility of protein under acidic conditions and increased the solubility in alkaline conditions. The effects of spray drying and in vitro gastrointestinal digestion on probiotics were investigated by microencapsulating chickpea protein with different degrees of N-succinylation. The results showed that all microcapsules had similar morphology, particle size and low water content. The microcapsules prepared by succinylated chickpea protein showed better stability and viability during spray drying and gastrointestinal digestion. The protective effect of probiotics was better as the degree of N-succinylation increased. In particular, the SCP-3-P sample (10 % succinic anhydride modified CP and maltodextrin) lost only 0.29 Log CFU/g throughout gastrointestinal digestion. The superior protective effect provided by succinylated CP in simulated gastric fluid (SGF) was mainly attributed to the reaction of succinic anhydride with protein to cause protein aggregation under gastric acidic conditions, reducing the infiltration of gastric acid and pepsin and maintaining the structural integrity of the microcapsules. Therefore, these findings provide a new strategy for probiotic intestinal delivery and application of chickpea protein.

Investigation of PET image quality with acquisition time/bed and enhancement of lesion quantification accuracy through deep progressive learning.

OBJECTIVE: To improve the PET image quality by a deep progressive learning (DPL) reconstruction algorithm and evaluate the DPL performance in lesion quantification. METHODS: We reconstructed PET images from 48 oncological patients using ordered subset expectation maximization (OSEM) and deep progressive learning (DPL) methods. The patients were enrolled into three overlapped studies: 11 patients for image quality assessment (study 1), 34 patients for sub-centimeter lesion quantification (study 2), and 28 patients for imaging of overweight or obese individuals (study 3). In study 1, we evaluated the image quality visually based on four criteria: overall score, image sharpness, image noise, and diagnostic confidence. We also measured the image quality quantitatively using the signal-to-background ratio (SBR), signal-to-noise ratio (SNR), contrast-to-background ratio (CBR), and contrast-to-noise ratio (CNR). To evaluate the performance of the DPL algorithm in quantifying lesions, we compared the maximum standardized uptake values (SUVmax), SBR, CBR, SNR and CNR of 63 sub-centimeter lesions in study 2 and 44 lesions in study 3. RESULTS: DPL produced better PET image quality than OSEM did based on the visual evaluation methods when the acquisition time was 0.5, 1.0 and 1.5 min/bed. However, no discernible differences were found between the two methods when the acquisition time was 2.0, 2.5 and 3.0 min/bed. Quantitative results showed that DPL had significantly higher values of SBR, CBR, SNR, and CNR than OSEM did for each acquisition time. For sub-centimeter lesion quantification, the SUVmax, SBR, CBR, SNR, and CNR of DPL were significantly enhanced, compared with OSEM. Similarly, for lesion quantification in overweight and obese patients, DPL significantly increased these parameters compared with OSEM. CONCLUSION: The DPL algorithm dramatically enhanced the quality of PET images and enabled more accurate quantification of sub-centimeters lesions in patients and lesions in overweight or obese patients. This is particularly beneficial for overweight or obese patients who usually have lower image quality due to the increased attenuation.

Efficacy and safety of cold snare polypectomy versus cold endoscopic mucosal resection for resecting 3-10 mm colorectal polyps: Systematic review and meta-analysis of randomized controlled trials.

Introduction The safety and efficacy of cold snare polypectomy (CSP) compared to those of cold endoscopic mucosal resection (CEMR) have been reported. This meta-analysis compared the efficacy and safety of CEMR and CSP. Methods PubMed, EMBASE, Web of Science, and Cochrane Library databases were systematically searched to identify randomized controlled trials comparing the efficacy and safety of CEMR and CSP in removing 3-10 mm polyps. The outcomes assessed included complete resection rate, intraoperative bleeding rate, delayed bleeding rate, perforation, and polyp removal time. The results are reported as risk ratios (RR) and 95% confidence intervals (CI) derived from a Mantel-Haenszel random effects model. Results Seven studies comprising 1,911 polyps were included in the analysis. The complete resection rate of CEMR was comparable to that of CSP (RR: 1.01, 95% CI: 0.99-1.04, P = 0.32). Comparable results were also demonstrated for intraoperative bleeding rate (polyp-based analysis: RR: 1.22, 95% CI: 0.33-4.43, P = 0.77), delayed bleeding rate (polyp-based analysis: RR: 1.34, 95% CI: 0.44-4.15, P = 0.61), and polyp removal time (mean difference: 28.31 s, 95% CI: -21.40~78.02, P=0.26). No studies reported cases of perforation. Conclusion CEMR has comparable efficacy and safety to CSP in removing 3-10 mm polyps. Further randomized controlled trials with long-term follow-up are warranted to compare and validate efficacy.

Chemical constituents from the aerial parts of Rubia cordifolia L. with their NO inhibitory activity.

A new naphthoquinone derivative (1) together with twenty-three known compounds (2-24), were isolated from the aerial parts of Rubia cordifolia L. Their structures were elucidated on the basis of NMR and HR-ESIMS data. Compounds 1-13 were assessed for their inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophage cells. Compounds 2-6 exhibited significant inhibitory activities with IC50 values of 21.37, 13.81, 24.56, 20.32, and 30.08 µmol·L-1, respectively.

Scrutiny of genome-wide somatic mutation profiles in centenarians identifies the key genomic regions for human longevity.

Somatic mutations accumulate with age and are associated closely with human health, their characterization in longevity cohorts remains largely unknown. Here, by analyzing whole genome somatic mutation profiles in 73 centenarians and 51 younger controls in China, we found that centenarian genomes are characterized by a markedly skewed distribution of somatic mutations, with many genomic regions being specifically conserved but displaying a high function potential. This, together with the observed more efficient DNA repair ability in the long-lived individuals, supports the existence of key genomic regions for human survival during aging, with their integrity being of essential to human longevity.

Modified Bushen Yiqi Formula mitigates pulmonary inflammation and airway remodeling by inhibiting neutrophils chemotaxis and IL17 signaling pathway in rats with COPD.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic obstructive pulmonary disease (COPD) is a major global health concern characterized by pulmonary inflammation and airway remodeling. Traditional Chinese medicine, such as Modified Jiawei Bushen Yiqi Formula (MBYF), has been used as a complementary therapy for COPD in China. AIM OF THE STUDY: To investigate the therapeutic potential of MBYF in a rat model of COPD induced by cigarette smoke (CS) exposure and explore the underlying mechanism. MATERIALS AND METHODS: The COPD rat model was established through 24 weeks of CS exposure, with MBYF administration starting in the 9th week. Pulmonary function, histological analysis, inflammatory cell count and molecular assays were employed to assess the effects of MBYF on airway remodeling, pulmonary inflammation, neutrophils chemotaxis and the IL17 signaling pathway. RESULTS: MBYF treatment effectively delayed airway remodeling, as evidenced by improved pulmonary function parameters. Histological examination and bronchoalveolar lavage fluid analysis revealed that MBYF mitigated CS-induced pulmonary inflammation by reducing inflammatory cell infiltration. Pharmacological network analysis suggested that MBYF may act through the IL17 signaling pathway to regulate inflammatory responses. RNA-sequencing and molecular assays indicated that MBYF inhibited neutrophils chemotaxis through downregulating the CXCL1/CXCL5/CXCL8-CXCR2 axis, and suppressed IL17A, IL17F and its downstream cytokines, including IL6, TNFα, IL1ß, and COX2. Furthermore, MBYF inhibited the activation of NF-κB and MAPKs in the IL17 signaling pathway. CONCLUSION: MBYF exhibits potential as an adjunct or alternative treatment for COPD, effectively mitigating CS-induced pulmonary inflammation and airway remodeling through the inhibition of neutrophil chemotaxis and IL17 signaling pathway.

AS-NeSt: A Novel 3D Deep Learning Model for Radiation Therapy Dose Distribution Prediction in Esophageal Cancer Treatment With Multiple Prescriptions.

PURPOSE: Implementing artificial intelligence technologies allows for the accurate prediction of radiation therapy dose distributions, enhancing treatment planning efficiency. However, esophageal cancers present unique challenges because of tumor complexity and diverse prescription types. Additionally, limited data availability hampers the effectiveness of existing artificial intelligence models. This study developed a deep learning model, trained on a diverse data set of esophageal cancer prescriptions, to improve dose prediction accuracy. METHODS AND MATERIALS: We retrospectively collected data from 530 patients with esophageal cancer, including single-target and simultaneous integrated boost prescriptions, for model building. The proposed Asymmetric ResNeSt (AS-NeSt) model features novel 3-dimensional (3D) ResNeSt blocks and an asymmetrical architecture. We constructed a loss function targeting global and local doses and validated the model's performance against existing alternatives. Model-assisted experiments were used to validate its clinical benefits. RESULTS: The AS-NeSt model maintained an absolute prediction error below 5% for each dosimetric metric. The average Dice similarity coefficient for isodose volumes was 0.93. The model achieved an average relative prediction error of 2.02%, statistically lower than Hierarchically Densely Connected U-net (4.17%), DoseNet (2.35%), and Densely Connected Network (3.65%). It also demonstrated significantly fewer parameters and shorter prediction times. Clinically, the AS-NeSt model raised physicians' ability to accurately preassess appropriate treatment methods before planning from 95.24% to 100%, reduced planning time by over 61% for junior dosimetrists and 52% for senior dosimetrists, and decreased both inter- and intra-dosimetrist discrepancies by more than 50%. CONCLUSIONS: The AS-NeSt model, developed with innovative 3D ResNeSt blocks and an asymmetrical encoder-decoder structure, has been validated using clinical esophageal cancer patient data. It accurately predicts 3D dose distributions for various prescriptions, including simultaneous integrated boost, showing potential to improve the management of esophageal cancer treatment in a clinical setting.