Relationship Between Microstructural Alterations and Cognitive Decline After Whole-Brain Radiation Therapy for Brain Metastases: An Exploratory Whole-Brain MR Analysis Based on Neurite Orientation Dispersion and Density Imaging.

BACKGROUND: Cognitive impairment frequently occurs in patients with brain metastases (BM) after whole-brain radiotherapy (WBRT). It is crucial to explore the underlying mechanisms of cognitive impairment in BM patients receiving WBRT. PURPOSE: To detect brain microstructural alterations in patients after WBRT by neurite orientation dispersion and density imaging (NODDI), and evaluate the performance of microstructural alterations in predicting cognitive impairment. STUDY TYPE: Prospective. POPULATION: Twenty-six patients (seven female; mean age, 60.9 years). FIELD STRENGTH/SEQUENCE: 3-T, multi-shell diffusion-weighted single-shot echo-planar sequence. Three-dimensional magnetization-prepared rapid acquisition with gradient echo sequence. ASSESSMENT: Mini-mental state examination (MMSE) evaluations were conducted prior to, following, 1 and 3 months after WBRT. The diffusion data were collected twice, 1 week before and 1 week after WBRT. NODDI analysis was conducted to assess microstructural alterations in whole brain (orientation dispersion index, neurite density index, volume fraction of isotropic water molecules). Reliable change indices (RCI) of MMSE were used to measure cognitive decline. The performance of support vector machine models based on NODDI parameters and clinical features (prednisone usage, tumor volume, etc.) in predicting MMSE-RCI was evaluated. STATISTICAL TESTS: Paired t-test to assess alterations of NODDI measures and MMSE during follow-up. Statistical significance level of P-value <0.05. RESULTS: Significantly decreased MMSE score was found at 3 months after WBRT. After WBRT, corpus callosum, medial prefrontal cortex, limbic lobe, occipital lobe, parietal lobe, putamen, globus pallidus lentiform, and thalamus demonstrated damage in NODDI parameters. The predicted MMSE-RCI based on NODDI features was significantly associated with the measured MMSE-RCI at 1 month (R = 0.573; P = 0.003) and 3 months (R = 0.687; P < 0.0001) after WBRT. DATA CONCLUSION: Microstructural alterations in several brain regions including the middle prefrontal and limbic cortexes were observed in patients with BM following WBRT, which may contribute to subsequent cognitive decline. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Prokaryotic Expression, Purification, and Antibacterial Activity of the Hepcidin Peptide of Crescent Sweetlips (Plectorhinchus cinctus).

The hepcidin peptide of crescent sweetlips (Plectorhinchus cinctus) is a cysteine-rich, cationic antimicrobial peptide that plays a crucial role in the innate immune system's defense against invading microbes. The aim of this study was to identify the optimal parameters for prokaryotic expression and purification of this hepcidin peptide and characterize its antibacterial activity. The recombinant hepcidin peptides were expressed in Escherichia coli strain Arctic Express (DE3), with culture and induction conditions optimized using response surface methodology (RSM). The obtained hepcidin peptides were then purified before tag cleavage, and their antibacterial activity was determined. The obtained results revealed that induction temperature had the most significant impact on the production of soluble recombinant peptides. The optimum induction conditions were determined to be an isopropylthio-ß-galactoside (IPTG) concentration of 0.21 mmol/L, induction temperature of 18.81 °C, and an induction time of 16.01 h. Subsequently, the recombinant hepcidin peptide was successfully purified using Ni-IDA affinity chromatography followed by SUMO protease cleavage. The obtained hepcidin peptide (without His-SUMO tag) demonstrated strong antimicrobial activity in vitro against V. parahaemolyticus, E. coli, and S. aureus. The results showed prokaryotic (E. coli) expression is a feasible way to produce the hepcidin peptide of crescent sweetlips in a cost-effective way, which has great potential to be used as an antimicrobial agent in aquaculture.

Marine glycoproteins: a mine of their structures, functions and potential applications.

Many bioactive compounds are reported from marine organisms, which are significantly different from those found in terrestrial organisms regarding their chemical structures and pharmacological activities. Marine glycoproteins (MGs) have aroused increasing attention as a good nutrient source owing to their potential applications in medicine, cosmetics and food. However, there is a lack of a comprehensive study on MGs to help readers understand the current state of research on marine-derived glycoproteins. The current review compiles the recent progress made on the structures and functions of MGs with future perspectives to maximize their value and applications via bibliometric analysis methods for the first time. The current research on MGs appears mostly limited to the laboratory, with no large-scale production of marine glycoproteins developed. The sugar chains are bound to proteins through covalent bonds that can readily be cleaved leading to difficultly in their separation and purification. Health effects attributed to MGs include treatment of inflammatory diseases, as well as anti-oxidant, immune modulation, anti-tumor, hypolipidemic, hypoglycemic, anti-bacterial and anti-freeze activities. This review can not only deepen the understanding of the functions of MGs, but also lay an important foundation for the further development and utilization of marine resources.

Overview on isolation, structural and functional properties of marine glycoproteins (MGs) via bibliometric analysis methods for the first time.Marine glycoproteins (MGs) have various biological activities and potential health applications.glycoproteins from marine organisms (MGs) significantly enhanced anti-oxidant and anti-inflammatory activities.

Polyoxometalate K6[P2Mo18O62] Inactivates Escherichia coli O157:H7 by Inducing recA Expression and Apoptosis-like Bacterial Death.

Polyoxometalates have emerged as promising bactericidal agents. In the current study, the bactericidal activity of polyoxometalate K6[P2Mo18O62] against Escherichia coli (E. coli) O157:H7 and its possible underlying mechanisms were explored. The obtained results demonstrated that K6[P2Mo18O62] could effectively kill E. coli O157:H7 at millimolar levels. Moreover, K6[P2Mo18O62] treatment also induced significant increases in recA protein expression and further triggered characteristic apoptosis-like bacterial death events such as DNA fragmentation and phosphatidylserine exposure. In conclusion, polyoxometalate K6[P2Mo18O62] possesses a desirable antibacterial activity, and induction of bacterial apoptosis-like death might be involved in its underlying bactericidal mechanisms.

Anti-Aging Effects of R-Phycocyanin from Porphyra haitanensis on HUVEC Cells and Drosophila melanogaster.

Aging has become a global public health challenge. Many studies have revealed that the excessive generation of ROS and oxidative stress could be the major causative factors contributing to aging. In this study, R-phycocyanin (R-PC) was isolated from Porphyra haitanensis, and its anti-aging ability was explored by natural aging Drosophila melanogaster and H2O2-induced HUVEC cells as the aging model. Results showed that R-PC α and ß subunits expressed have antioxidant activity and can inhibit the generation of radicals, exhibiting a protective effect against H2O2-induced apoptotic HUVEC cells death. R-PC prevented the H2O2-induced HUVEC cell cycle phase arrest by regulating cell cycle-related protein. Furthermore, R-PC prevented the H2O2-induced HUVEC cell cycle phase arrest by regulating cell-cycle-related protein expression. In vivo study also indicated that R-PC significantly increased the survival time and alleviated the oxidative stress of Drosophila melanogaster. Moreover, R-PC notably decreased levels of ROS in natural aging flies and inhibited lipid peroxidation by enhancing the expressions of the endogenous stress marker genes (SOD1, SOD2, CAT of Drosophila melanogaster). Taken together, a study on the antioxidation extract from Porphyra haitanensis, such as R-PC, may open a new window for the prevention of anti-aging.

High-Amylose Corn Starch Regulated Gut Microbiota and Serum Bile Acids in High-Fat Diet-Induced Obese Mice.

High-amylose corn starch is well known for its anti-obesity activity, which is mainly based on the regulatory effects on gut microbiota. Recently, the gut microbiota has been reported to improve metabolic health by altering circulating bile acids. Therefore, in this study, the influence of high-amylose corn starch (HACS) on intestinal microbiota composition and serum bile acids was explored in mice fed with a high fat diet (HFD). The results demonstrated HACS treatment reduced HFD-induced body weight gain, hepatic lipid accumulation, and adipocyte hypertrophy as well as improved blood lipid profiles. Moreover, HACS also greatly impacted the gut microbiota with increased Firmicutes and decreased Bacteroidetes relative abundance being observed. Furthermore, compared to ND-fed mice, the mice with HFD feeding exhibited more obvious changes in serum bile acids profiles than the HFD-fed mice with the HACS intervention, showing HACS might restore HFD-induced alterations to bile acid composition in blood. In summary, our results suggested that the underlying mechanisms of anti-obesity activity of HACS may involve its regulatory effects on gut microbiota and circulating bile acids.

Identification of a Wells-Dawson polyoxometalate-based AP-2γ inhibitor with pro-apoptotic activity.

AP-2 gamma (AP-2γ) is a transcription factor that plays pivotal roles in breast cancer biology. To search for small molecule inhibitors of AP-2γ, we performed a high-throughput fluorescence anisotropy screen and identified a polyoxometalate compound with Wells-Dawson structure K6[P2Mo18O62] (Dawson-POM) that blocks the DNA-binding activity of AP-2γ. We showed that this blocking activity is due to the direct binding of Dawson-POM to AP-2γ. We also provided evidence to show that Dawson-POM decreases AP-2γ-dependent transcription similar to silencing the gene. Finally, we demonstrated that Dawson-POM contains anti-proliferative and pro-apoptotic effects in breast cancer cells. In summary, we identified the first small molecule inhibitor of AP-2γ and showed Dawson-POM-mediated inhibition of AP-2γ as a potential avenue for cancer therapy.

Curcumin-Based Photodynamic Sterilization for Preservation of Fresh-Cut Hami Melon.

Fresh-cut fruits and vegetables are the main sources of foodborne illness outbreaks with implicated pathogens such as Escherichia coli O157:H7, Salmonella, and Listeria monocytogenes. This study aimed at investigating the influence of two key parameters (concentration of curcumin and illumination time) on the effects of curcumin-based photodynamic sterilization on the preservation of fresh-cut Hami melons. The results indicated that illumination with 50 µmol/L curcumin for 60 min using a blue LED lamp reduced the total aerobic microorganism count by ~1.8 log CFU/g in fresh-cut Hami melons. Besides this, the effects of photodynamic sterilization on the soluble solids content, color, water content, firmness, and sensory indices of the fresh-cut Hami melons were also evaluated. Compared to the control group, photodynamic sterilization can effectively delay the browning rate and maintain the luminosity, firmness, water content, and soluble solids content of fresh-cut Hami melon. The sensory quality was indeed preserved well after 9 days of storage in a fridge. These results showed that photodynamic sterilization is an effective and promising technology to prolong the shelf life of fresh-cut Hami melons.

Short-chain fatty acids in control of energy metabolism.

Short-chain fatty acids (SCFAs), especially acetate, propionate and butyrate, are the end products from the intestinal microbial fermentation of dietary fibers and resistant starch. It has been well documented that plasma and colonic SCFAs are associated with metabolic syndromes. Recently, the involvement of SCFAs in energy homeostasis regulation has been extensively studied. The importance of SCFAs on energy metabolism has highlighted the potential of modulating SCFAs as a nutritional target to prevent and counteract metabolism disorders and its associated diseases such as obesity and type 2 diabetes. Here, we summarize the current knowledge about the biological properties of SCFAs with their impact on the energy homeostasis.

Circulatory changes of the novel adipokine adipolin/CTRP12 in response to metformin treatment and an oral glucose challenge in humans.

OBJECTIVE: Adipolin/CTRP12 is a novel adipokine with anti-inflammatory and glucose-lowering properties in rodents. We sought to investigate the effects of metformin treatment (850 mg twice daily for 6 months) and a 2 h 75 g oral glucose tolerance test (OGTT) on serum adipolin concentrations in humans. DESIGN: Cross-sectional study [PCOS (n = 83) and control (n = 39) subjects]. Serum adipolin was measured by ELISA. Metformin treatment (850 mg twice daily for 6 months) was offered to all women with PCOS, 34 women participated but 21 women completed 6 months of metformin therapy. Reasons for subjects not completing the study were nausea and gastrointestinal side effects (n = 4), pregnancies (n = 5), noncompliance (n = 2) and loss of contact (n = 2). RESULTS: Metformin treatment (850 mg twice daily for 6 months) substantially increased serum adipolin concentrations (P < 0·05) in women with polycystic ovary syndrome (PCOS), a pro-inflammatory state associated with obesity, diabetes, dyslipidaemia and atherosclerosis. Furthermore, changes in waist-hip ratio, glucose, triglycerides, CRP and carotid intima media thickness showed significant negative associations with changes in adipolin levels (P < 0·05, P < 0·01); in multiple regression analyses, only changes in glucose were predictive of changes in adipolin levels (ß = -0·570, P = 0·009). Serum adipolin decreased significantly in response to the OGTT in PCOS and control subjects at 90 min (P < 0·05) and 120 min (P < 0·01). CONCLUSIONS: Adipolin and/or novel pharmacologic agents that increase adipolin's circulating concentrations might constitute a novel approach in the treatment of insulin resistant states.

Comparison of anti-allergic activities of different types of lotus seed resistant starch in OVA-induced mouse model.

Currently, evidence from observational studies suggests dietary fiber intake may be associated with decreased risk of food allergy. As a type of dietary fiber, resistant starch was also widely reported to possess anti-allergic properties. However, there is a relative paucity of studies assessing the influence of resistant starch types on their anti-allergic activity and its possible underlying mechanisms. In the current study, the anti-allergic effects of RS3-type (retrograded starch), RS4-type (chemically modified starch, cross-bonded), and RS5-type (starch-palmitic acid complex) of lotus seed resistant starch were evaluated in the OVA (100 mg/kg)-induced food allergic mice model. The results showed that oral administration of RS3 or RS4 lotus seed resistant starch (0.3 g/100 g b.w.) for 25 days significantly improved adverse symptoms of food allergy such as weight loss, increases in allergy symptom score and diarrhea rate; with significant reduction of serum specific antibody IgE, TNF-α, IL-4 levels and improved Th1/Th2 balance being observed. The mechanism may involve the regulation of lotus seed resistant starch on intestinal flora and the metabolites short-chain fatty acids and bile acids. Taken together, the findings may enhance understanding towards ameliorative effects of resistant starch on food allergy, and offer valuable insights for the exploration of novel anti-allergic bioactive compounds.

Steam Explosion-Assisted Extraction of Polysaccharides from Pleurotus eryngii and Its Influence on Structural Characteristics and Antioxidant Activity.

Pleurotus eryngii (PE) has been sought after for its various health benefits and high content of phenolic compounds. This study explored the feasibility of steam explosion (SE)-assisted extraction of polysaccharides with high antioxidant capacities from PE. An orthogonal experimental design (OED) was used to optimize the SE-assisted extraction of PE. The influence of the optimized SE-assisted extraction on the physicochemical properties of PE polysaccharides was determined by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), monosaccharide compositional analysis and antioxidant capacity assays. Under optimal SE conditions, SE-assisted extraction increased the polysaccharide yield by 138% compared to extraction without SE-assistance. In addition, SEM demonstrated that SE-assisted extraction markedly altered the spatial structure of Pleurotus eryngii polysaccharides (PEP), and monosaccharide compositional analysis revealed that this pretreatment significantly increased the proportions of some monosaccharides, such as glucose, rhamnose and arabinose, in the isolated PEP. FTIR spectra indicated no change in the major chemical functional groups of PEP. PEP extracted by SE-assisted extraction had significantly increased free radical scavenging and antioxidant capacities. In conclusion, SE-assisted extraction appears to be a novel polysaccharide extraction technology, which markedly increases extraction yields and efficiency and can increase the biological activity of polysaccharide extracts.

Application of nano-radiosensitizers in non-small cell lung cancer.

Radiotherapy stands as a cornerstone in the treatment of numerous malignant tumors, including non-small cell lung cancer. However, the critical challenge of amplifying the tumoricidal effectiveness of radiotherapy while minimizing collateral damage to healthy tissues remains an area of significant research interest. Radiosensitizers, by methods such as amplifying DNA damage and fostering the creation of free radicals, play a pivotal role in enhancing the destructive impact of radiotherapy on tumors. Over recent decades, nano-dimensional radiosensitizers have emerged as a notable advancement. Their mechanisms include cell cycle arrest in the G2/M phase, combating tumor hypoxia, and others, thereby enhancing the efficacy of radiotherapy. This review delves into the evolving landscape of nanomaterials used for radiosensitization in non-small cell lung cancer. It provides insights into the current research progress and critically examines the challenges and future prospects within this burgeoning field.

R-phycocyanin from porphyra haitanensis influences drosophila melanogaster lifespan in a sex-specific manner.

Aging has become a major global public health challenge. Our previous research showed that R-phycocyanin (R-PC) possessed anti-aging activity. Notably, studies already revealed that gender may affect the responses to the anti-aging drug. Therefore, it is worth investigating whether the anti-aging effects and their underlying molecular mechanisms of R-PC differ between genders. Firstly, R-PC was isolated from porphyra haitanensis and its anti-aging mechanisms were explored using the nature aging male and female drosophila melanogaster as model. Next, the regulation pathway of longevity was analyzed by KEGG pathway analysis. The longevity pathways-associated molecules were also examined to explore anti-aging mechanisms of R-PC. The results showed that R-PC increased AMPK activity, thus enhanced the key regulatory factors of autophagy (Atg1, Atg8, Atg5), and consequently induced autophagy. Hence, the longevity activity of R-PC life was related with AMPK/mTOR/S6K autophagic signaling pathways in aging female drosophila melanogaster. Meanwhile, R-PC significantly down-regulated TNF-α, MMP3, IL-1ß, IL-6, IL-8 expression levels, and the anti-inflammatory and longevity was associated with R-PC-induced regulation of pI3k/AKT/FOXO3 signaling pathway in aging male drosophila melanogaster. These finding showed that R-PC from porphyra haitanensis might exert the anti-aging actions via different mechanisms in male and female drosophila melanogaste.

The emerging potential of quantitative MRI biomarkers for the early prediction of brain metastasis response after stereotactic radiosurgery: a scoping review.

Background: At present, the simple prognostic models based on clinical information for predicting the treatment outcomes of brain metastases (BMs) are subjective and delayed. Thus, we performed this systematic review of multiple studies to assess the potential of quantitative magnetic resonance imaging (MRI) biomarkers for the early prediction of treatment outcomes of brain metastases with stereotactic radiosurgery (SRS). Methods: We systematically searched the PubMed, Embase, Cochrane, Web of Science, and Clinical Trials.gov databases for articles published between February 1, 1991, and April 11, 2022, with no language restrictions. We included studies involving patients with BMs receiving SRS; the included patients were required to have definite pathology of a primary tumor and complete imaging data (pre- and post-SRS). We excluded the articles that included patients who had undergone previous surgery and those that did not include regular follow-up or corresponding MRI scans. Results: We identified 2,162 studies, of which 26 were included in our analysis, involving a total of 1,362 participants. All 26 studies explored the relevant MRI parameters to predict the prognosis of patients with BMs who received SRS. The outcomes were generalized according to the relationships between the anatomical/morphological, microstructural, vascular, and metabolic changes and SRS. Generally, with traditional MRI, there are several quantitative prognostic models based on preradiosurgical radiomics that predict the outcome of SRS treatment in local BM control. With the implementation of advanced MRI, the relative apparent diffusion coefficient (ADC), perfusion fraction (f), relative cerebral blood volume (rCBV), relative regional cerebral blood flow (rrCBF), interstitial fluid pressure (IFP), quadratic of time-dependent leakage (Ktrans 2), extracellular extravascular volume (ve), choline/creatine (Cho/Cr), nuclear Overhauser effect (NOE) peak, and intraextracellular water exchange rate constant (kIE ) were confirmed to be indicative of the therapeutic effect of SRS for BMs. Conclusions: Quantitative MRI biomarkers extracted from traditional or advanced MRI at different time points, which can represent the anatomical/morphological, microstructural, vascular, and metabolic changes, respectively, have been proposed as promising markers for the early prediction of SRS response in those with BMs. There are some limitations in this review, including the risk of selection bias, the limited number of study objects, the incomparability of the total data, and the subjectivity of the review process.

Oral Administration of Lotus-Seed Resistant Starch Protects against Food Allergy.

Food allergy is a serious food safety and public health issue. However, the medical interventions for allergy treatment are still suboptimal. Recently, the gut microbiome-immune axis has been considered as a promising target to reduce the symptoms of food allergy. In this study, we explore the oral administration of lotus-seed resistant starch as a means to protect against food allergy using an ovalbumin (OVA) sensitization and challenge rodent model. The results obtained showed that lotus-seed resistant starch intervention alleviated the food allergy symptoms (such as reductions in body temperature and allergic diarrhea). Furthermore, lotus-seed resistant starch also attenuated the increase in OVA-specific immunoglobulins and improved Th1/Th2 imbalance in OVA-sensitized mice. These anti-allergic effects might be associated with the actions of lotus-seed resistant starch on intestinal microbiota. Taken together, our findings suggest that daily ingestion of lotus-seed resistant starch might be effective for the alleviation of food allergy.

Current Perspectives on Viable but Non-Culturable Foodborne Pathogenic Bacteria: A Review.

Foodborne diseases caused by foodborne pathogens pose risks to food safety. Effective detection and efficient inactivation of pathogenic bacteria has always been a research hotspot in the field of food safety. Complicating these goals, bacteria can be induced to adopt a viable but non-culturable (VBNC) state under adverse external environmental stresses. When in the VBNC state, pathogens cannot form visible colonies during traditional culture but remain metabolically active and toxic. The resulting false negative results in growth-related assays can jeopardize food safety. This review summarizes the latest research on VBNC foodborne pathogens, including induction conditions, detection methods, mechanism of VBNC formation, and possible control strategies. It is hoped that this review can provide ideas and methods for future research on VBNC foodborne pathogenic bacteria.

Molecular cloning of the hepcidin gene from crescent sweetlips (Plectorhinchus cinctus) and characterization of its encoded antimicrobial peptide.

Hepcidin has been identified as an important antimicrobial peptide exerting important innate immunomodulatory activities in many fish species. In the present study, reverse transcription PCR coupled with the rapid amplification of cDNA ends was used to obtain the full-length cDNA of the crescent sweetlips hepcidin gene, which is 829 bp in length and includes an 273 bp ORF encoding a peptide with 90 amino acid residues. Sequence alignment showed a typical RXKR motif and eight conserved cysteine residues in the deduced amino acid sequences. Four disulfide bonds were predicted to form between these eight cysteines, which may stabilize the hairpin structure in hepcidin molecule. Furthermore, phylogenetic analysis showed that the deduced amino acid sequences of crescent sweetlips hepcidin had high sequence homology to hepcidins from fish species of Eupercaria. In addition, the crescent sweetlips hepcidin peptide demonstrated a strong antimicrobial activity in vitro against several types of pathogenic bacteria in fish. In conclusion, the obtained results suggested that crescent sweetlips hepcidin possessed the typical structure similar to other fish hepcidins and had strong antibacterial activity, which showed great potential in the prevention of fish diseases in aquaculture.

K6[P2Mo18O62] as DNase-Mimetic Artificial Nucleases to Promote Extracellular Deoxyribonucleic Acid Degradation in Bacterial Biofilms.

In the current study, the DNase-like activity of the Dawson-type polyoxometalate K6[P2Mo18O62] was explored. The obtained findings demonstrated that K6[P2Mo18O62] could effectively cleave phosphoester bonds in the DNA model substrate (4-nitrophenyl phosphate) and result in the degradation of plasmid DNA. Moreover, the application potential of this Dawson-type polyoxometalate as a DNase-mimetic artificial enzyme to degrade extracellular DNA (eDNA) in Escherichia coli (E. coli) bacterial biofilm was explored. The results demonstrated that K6[P2Mo18O62] exhibited high cleavage ability toward eDNA secreted by E. coli and thus eradicated the bacterial biofilm. In conclusion, Dawson-type polyoxometalate K6[P2Mo18O62] possessed desirable DNase-like activity, which could serve as a bacterial biofilm eradication agent by cleaving and degrading eDNA molecules.

Whole brain atlas-based diffusion kurtosis imaging parameters for the evaluation of multiple cognitive-related brain microstructure injuries after radiotherapy in lung cancer patients with brain metastasis.

Background: Whole brain radiation therapy (WBRT) can cause cognitive dysfunctions in lung cancer patients with brain metastasis (BM). Diffusion kurtosis imaging (DKI) can detect brain microstructural alterations sensitivly. We aimed to identify the potential of DKI parameters for early radiation-induced brain injury and investigate the association between microstructure changes and neurocognitive function (NCF) decline. Methods: Lung cancer patients with BM (n=35) who underwent WBRT in a single center in Zhejiang, China, were consecutively and prospectively enrolled between June 24th, 2020 and December 22nd, 2021, and the median follow-up time was 6.0 months (3.6-6.6 months). DKI and T1-weighted (T1W) MRI scans were acquired prior to and following WBRT. Diffusivity-based (mean diffusivity, MD; fractional anisotropy, FA) and kurtosis-based (mean kurtosis, MK; axial kurtosis, AK) parameters were calculated within the automated anatomical labeling (AAL) atlas-based regions. Reliable change indices practice effects (RCI-PE) scores of the Mini-Mental State Examination (MMSE) were calculated to determine significant neurocognitive decline by a one-sample t-test from baseline to 2-6 months post-WBRT. To assess the subacute induced effects within the whole brain, percentage changes of DKI parameters were evaluated at 170 atlas-based regions by a one-sample t-test. Linear regression analyses were used to evaluate the association between DKI parameter changes and RCI-PE scores. Results: Finally, the study included 19 patients in the longitudinal follow-up. RCI-PE scores declined at 2-6 months post-WBRT (mean RCI-PE =-0.842, 95% CI, -0.376 to -1.310; P=0.002). With the atlas-based analysis of subacute effects after post-WBRT, a total of 28 regions changed in at least one diffusion parameter, revealing region-wise microstructural alterations in the brain. Significant correlations of at least one diffusion parameters with RCI-PEs were observed in 9 regions, such as the right orbital part of the inferior frontal gyrus [right IFGorb, r(AK) =0.47, P=0.03] and left middle temporal gyrus [left MTG, r(MK) =-0.49, P=0.03]. Conclusions: DKI parameters can be used to detect early microstructure changes and represent important imaging predictors for cognitive decline. The reported 9 regions are more particularly vulnerable to neurocognitive radiation-induced impairment for lung cancer patients with BM, representing potential dose-avoidance targets for cognitive function preservation.