New Sight of Renal Toxicity Caused by UV-Aged Polystyrene Nanoplastics: Induced Ferroptosis via Adsorption of Transferrin.

Secondary nanoplastics (NPs) caused by degradation and aging due to environmental factors are the main source of human exposure, and alterations in the physicochemical and biological properties of NPs induced by environmental factors cannot be overlooked. In this study, pristine polystyrene (PS) NPs to obtain ultraviolet (UV)-aged PS NPs (aPS NPs) as secondary NPs is artificially aged. In a mouse oral exposure model, the nephrotoxicity of PS NPs and aPS NPs is compared, and the results showed that aPS NPs exposure induced more serious destruction of kidney tissue structure and function, along with characteristic changes in ferroptosis. Subsequent in vitro experiments revealed that aPS NPs-induced cell death in human renal tubular epithelial cells involved ferroptosis, which is supported by the use of ferrostatin-1, a ferroptosis inhibitor. Notably, it is discovered that aPS NPs can enhance the binding of serum transferrin (TF) to its receptor on the cell membrane by forming an aPS-TF complex, leading to an increase in intracellular Fe2+ and then exacerbation of oxidative stress and lipid peroxidation, which render cells more sensitive to ferroptosis. These findings indicated that UV irradiation can alter the physicochemical and biological properties of NPs, enhancing their kidney biological toxicity risk by inducing ferroptosis.

iFLAS: positive-unlabeled learning facilitates full-length transcriptome-based identification and functional exploration of alternatively spliced isoforms in maize.

The advent of full-length transcriptome sequencing technologies has accelerated the discovery of novel splicing isoforms. However, existing alternative splicing (AS) tools are either tailored for short-read RNA-Seq data or designed for human and animal studies. The disparities in AS patterns between plants and animals still pose a challenge to the reliable identification and functional exploration of novel isoforms in plants. Here, we developed integrated full-length alternative splicing analysis (iFLAS), a plant-optimized AS toolkit that introduced a semi-supervised machine learning method known as positive-unlabeled (PU) learning to accurately identify novel isoforms. iFLAS also enables the investigation of AS functions from various perspectives, such as differential AS, poly(A) tail length, and allele-specific AS (ASAS) analyses. By applying iFLAS to three full-length transcriptome sequencing datasets, we systematically identified and functionally characterized maize (Zea mays) AS patterns. We found intron retention not only introduces premature termination codons, resulting in lower expression levels of isoforms, but may also regulate the length of 3'UTR and poly(A) tail, thereby affecting the functional differentiation of isoforms. Moreover, we observed distinct ASAS patterns in two genes within heterosis offspring, highlighting their potential value in breeding. These results underscore the broad applicability of iFLAS in plant full-length transcriptome-based AS research.

POU6F1 promotes ferroptosis by increasing lncRNA-CASC2 transcription to regulate SOCS2/SLC7A11 signaling in gastric cancer.

OBJECTIVE: This study investigated the effect and mechanism of POU6F1 and lncRNA-CASC2 on ferroptosis of gastric cancer (GC) cells. METHODS: GC cells treated with erastin and RSL3 were detected for ferroptosis, reactive oxygen species (ROS) level, and cell viability. The expression levels of POU6F1, lncRNA-CASC2, SOCS2, and ferroptosis-related molecules (GPX4 and SLC7A11) were also measured. The regulations among POU6F1, lncRNA-CASC2, FMR1, SOCS2, and SLC7A11 were determined. Subcutaneous tumor models were established, in which the expressions of Ki-67, SOCS2, and GPX4 were detected by immunohistochemistry. RESULTS: GC patients with decreased expressions of POU6F1 and lncRNA-CASC2 had lower survival rate. Overexpression of POU6F1 or lncRNA-CASC2 decreased cell proliferation and GSH levels in GC cells, in addition to increasing total iron, Fe2+, MDA, and ROS levels. POU6F1 directly binds to the lncRNA-CASC2 promoter to promote its transcription. LncRNA-CASC2 can target FMR1 and increase SOCS2 mRNA stability to promote SLC7A11 ubiquitination degradation and activate ferroptosis signaling. Knockdown of SOCS2 inhibited the ferroptosis sensitivity of GC cells and reversed the effects of POU6F1 and lncRNA-CASC2 overexpression on ferroptosis in GC cells. CONCLUSION: Transcription factor POU6F1 binds directly to the lncRNA-CASC2 promoter to promote its expression, while upregulated lncRNA-CASC2 increases SOCS2 stability and expression by targeting FMR1, thereby inhibiting SLC7A11 signaling to promote ferroptosis in GC cells and inhibit GC progression.

[18F]FAPI PET/CT in the evaluation of focal liver lesions with [18F]FDG non-avidity.

PURPOSE: This prospective study was aimed to investigate the potential utility of [18F]fibroblast activation protein inhibitor (FAPI) PET/CT for evaluating focal liver lesions (FLLs) with [18F]FDG non-avidity. METHODS: From January 2021 to March 2022, this prospective study included 80 FLLs that were not avid on [18F]FDG PET/CT from 37 patients, then underwent [18F]FAPI PET/CT. All patients with FLL(s) with biopsy-proof or follow-up confirmation were categorized into four subgroups (20 hepatocellular carcinomas [HCCs]/5 non-HCC malignancies/4 inflammatory FLLs/8 benign noninflammatory FLLs). The diagnostic value of [18F]FAPI for detecting liver malignancy was determined by visual evaluation. Differences in the maximum standardized uptake value (SUVmax) and lesion-to-background ratio (LBR) obtained from [18F]FAPI PET/CT among the four subgroups were analyzed by semiquantitative analysis. RESULTS: Among the thirty-seven enrolled participants (34 males; median age 57 years, range 48-67 years), on visual evaluation, the sensitivity, specificity, and accuracy of [18F]FAPI PET for detecting liver malignancy in the patient-based analysis were 96.0% (24/25), 58.3% (7/12), and 83.8% (31/37), respectively. On semiquantitative analysis, the SUVmax and LBR of [18F]FAPI PET in liver malignancy (33 HCC lesions; 19 non-HCC malignant lesions) were significantly higher than those in 11 benign noninflammatory FLLs [HCC: SUVmax: 6.4 vs. 4.5, P = 0.017; LBR: 5.1 vs. 1.5, P = 0.003; non-HCC: SUVmax: 5.5 vs. 4.5, P = 0.008; LBR: 4.4 vs. 1.5, P = 0.042]. Notably, there was no significant difference in the SUVmax of [18F]FAPI PET between 33 HCC lesions and 17 inflammatory FLLs (6.4 vs. 8.2, P = 0.37), but the LBR of [18F]FAPI PET in HCC were significantly lower than that in inflammatory FLLs (5.1 vs. 9.1, P = 0.003). CONCLUSIONS: [18F]FAPI PET/CT shows high sensitivity in detecting HCC and non-HCC malignancy with [18F]FDG non-avidity. [18F]FAPI might be a promising radiopharmaceutical for the differential diagnosis of benign noninflammatory FLLs and liver malignancy with [18F]FDG non-avidity.

Integrative analysis of γδT cells and dietary factors reveals predictive values for autism spectrum disorder in children.

BACKGROUND: Autism spectrum disorder (ASD) includes a range of multifactorial neurodevelopmental disabilities characterized by a variable set of neuropsychiatric symptoms. Immunological abnormalities have been considered to play important roles in the pathogenesis of ASD, but it is still unknown which abnormalities are more prominent. METHODS: A total of 105 children with ASD and 105 age and gender-matched typically developing (TD) children were recruited. An eating and mealtime behavior questionnaire, dietary habits, and the Bristol Stool Scale were investigated. The immune cell profiles in peripheral blood were analyzed by flow cytometry, and cytokines (IFN-γ, IL-8, IL-10, IL-17A, and TNF-α) in plasma were examined by Luminex assay. The obtained results were further validated using an external validation cohort including 82 children with ASD and 51 TD children. RESULTS: Compared to TD children, children with ASD had significant eating and mealtime behavioral changes and gastrointestinal symptoms characterized by increased food fussiness and emotional eating, decreased fruit and vegetable consumption, and increased stool astriction. The proportion of γδT cells was significantly higher in children with ASD than TD children (ß: 0.156; 95% CI: 0.888 âˆ¼ 2.135, p < 0.001) even after adjusting for gender, eating and mealtime behaviors, and dietary habits. In addition, the increased γδT cells were evident in all age groups (age < 48 months: ß: 0.288; 95% CI: 0.420 âˆ¼ 4.899, p = 0.020; age ≥ 48 months: ß: 0.458; 95% CI: 0.694 âˆ¼ 9.352, p = 0.024), as well as in boys (ß: 0.174; 95% CI: 0.834 âˆ¼ 2.625, p < 0.001) but not in girls. These findings were also confirmed by an external validation cohort. Furthermore, IL-17, but not IFN-γ, secretion by the circulating γδT cells was increased in ASD children. Machine learning revealed that the area under the curve in nomogram plots for increased γδT cells combined with eating behavior/dietary factors was 0.905, which held true in both boys and girls and in all the age groups of ASD children. The decision curves showed that children can receive significantly higher diagnostic benefit within the threshold probability range from 0 to 1.0 in the nomogram model. CONCLUSIONS: Children with ASD present with divergent eating and mealtime behaviors and dietary habits as well as gastrointestinal symptoms. In peripheral blood, γδT cells but not αßT cells are associated with ASD. The increased γδT cells combined with eating and mealtime behavior/dietary factors have a high value for assisting in the diagnosis of ASD.

Divergent selection and genetic introgression shape the genome landscape of heterosis in hybrid rice.

The successful application of heterosis in hybrid rice has dramatically improved rice productivity, but the genetic mechanism for heterosis in the hybrid rice remains unclear. In this study, we generated two populations of rice F1 hybrids with present-day commercial hybrid parents, genotyped the parents with 50k SNP chip and genome resequencing, and recorded the phenotype of ∼2,000 hybrids at three field trials. By integrating these data with the collected genotypes of ∼4,200 rice landraces and improved varieties that were reported previously, we found that the male and female parents have different levels of genome introgressions from other rice subpopulations, including indica, aus, and japonica, therefore shaping heterotic loci in the hybrids. Among the introgressed exogenous genome, we found that heterotic loci, including Ghd8/DTH8, Gn1a, and IPA1 existed in wild rice, but were significantly divergently selected among the rice subpopulations, suggesting these loci were subject to environmental adaptation. During modern rice hybrid breeding, heterotic loci were further selected by removing loci with negative effect and fixing loci with positive effect and pyramid breeding. Our results provide insight into the genetic basis underlying the heterosis of elite hybrid rice varieties, which could facilitate a better understanding of heterosis and rice hybrid breeding.

The hybrid protein interactome contributes to rice heterosis as epistatic effects.

Heterosis is the phenomenon in which hybrid progeny exhibits superior traits in comparison with those of their parents. Genomic variations between the two parental genomes may generate epistasis interactions, which is one of the genetic hypotheses explaining heterosis. We postulate that protein-protein interactions specific to F1 hybrids (F1 -specific PPIs) may occur when two parental genomes combine, as the proteome of each parent may supply novel interacting partners. To test our assumption, an inter-subspecies hybrid interactome was simulated by in silico PPI prediction between rice japonica (cultivar Nipponbare) and indica (cultivar 9311). Four-thousand, six-hundred and twelve F1 -specific PPIs accounting for 20.5% of total PPIs in the hybrid interactome were found. Genes participating in F1 -specific PPIs tend to encode metabolic enzymes and are generally localized in genomic regions harboring metabolic gene clusters. To test the genetic effect of F1 -specific PPIs in heterosis, genomic selection analysis was performed for trait prediction with additive, dominant and epistatic effects separately considered in the model. We found that the removal of single nucleotide polymorphisms associated with F1 -specific PPIs reduced prediction accuracy when epistatic effects were considered in the model, but no significant changes were observed when additive or dominant effects were considered. In summary, genomic divergence widely dispersed between japonica and indica rice may generate F1 -specific PPIs, part of which may accumulatively contribute to heterosis according to our computational analysis. These candidate F1 -specific PPIs, especially for those involved in metabolic biosynthesis pathways, are worthy of experimental validation when large-scale protein interactome datasets are generated in hybrid rice in the future.

Resveratrol inhibits bile acid-induced gastric intestinal metaplasia via the PI3K/AKT/p-FoxO4 signalling pathway.

Gastric intestinal metaplasia (GIM) is the essential pre-malignancy of gastric cancer. Chronic inflammation and bile acid reflux are major contributing factors. As an intestinal development transcription factor, caudal-related homeobox 2 (CDX2) is key in GIM. Resveratrol has potential chemopreventive and anti-tumour effects. The aim of the study is to probe the effect of resveratrol in bile acid-induced GIM. We demonstrated that resveratrol could reduce CDX2 expression in a time- and dose-dependent manner in gastric cell lines. A Cignal Finder 45-Pathway Reporter Array and TranSignal Protein/DNA Array Kit verified that resveratrol could increase Forkhead box O4 (FoxO4) activity and that Chenodeoxycholic acid (CDCA) could reduce FoxO4 activity. Furthermore, bioinformatics analysis showed that FoxO4 could bind to the CDX2 promoter, and these conjectures were supported by chromatin-immunoprecipitation (ChIP) assays. Resveratrol can activate FoxO4 and decrease CDX2 expression by increasing phospho-FoxO4 nucleus trans-location. Resveratrol could increase FoxO4 phosphorylation through the PI3K/AKT pathway. Ectopic FoxO4 expression can up-regulate FoxO4 phosphorylation and suppress CDCA-induced GIM marker expression. Finally, we found a reverse correlation between p-FoxO4 and CDX2 in tissue arrays. This study validates that resveratrol could reduce bile acid-induced GIM through the PI3K/AKT/p-FoxO4 signalling pathway and has a potential reversing effect on GIM, especially that caused by bile acid reflux.

DKK1 is epigenetically downregulated by promoter methylation and inhibits bile acid-induced gastric intestinal metaplasia.

Dickkopf-related protein 1 (DKK1) is essential to gastric cancer as an inhibitor of Wnt signaling. Gastric intestinal metaplasia (GIM) is an important precancerous lesion of gastric cancer that can be activated by bile acid reflux and chronic inflammation. However, the exact mechanism of DKK1 in bile acid-induced GIM has not been completely elucidated. We aimed to explore the epigenetic alterations and biological functions of DKK1 in the development of GIM. In the present study, bile acid was found to induce the expression of intestinal markers in gastric epithelial cells, whereas DKK1 was downregulated in response to bile acid stimulation. The mRNA and protein expression levels of DKK1 were decreased in GIM tissues as evidenced by qRT-PCR and immunohistochemical staining. Surprisingly, the methylation of the DKK1 promoter increased in GIM tissues, and we discovered 28 differential methylation sites of the DKK1 promoter in GIM tissues. Bile acid was able to induce the partial methylation of the DKK1 promoter, while 5-aza could increase DKK1 expression as well as decrease intestinal markers expression in gastric epithelial cells. In conclusion, the promoter methylation and downregulation of DKK1 might play important roles in the development of GIM, especially bile acid-induced GIM.

Genome optimization for improvement of maize breeding.

KEY MESSAGE: We propose a new model to improve maize breeding that incorporates doubled haploid production, genomic selection, and genome optimization. Breeding 4.0 has been considered the next era of plant breeding. It is clear that the Breeding 4.0 era for maize will feature the integration of multi-disciplinary technologies including genomics and phenomics, gene editing and synthetic biology, and Big Data and artificial intelligence. The breeding approach of passively selecting ideal genotypes from designated genetic pools must soon evolve to virtual design of optimized genomes by pyramiding superior alleles using computational simulation. An optimized genome expressing optimal phenotypes, which may never actually be created, can function as a blueprint for breeding programs to use minimal materials and hybridizations to achieve maximum genetic gain. We propose a new breeding pipeline, "genomic design breeding," that incorporates doubled haploid production, genomic selection, and genome optimization and is facilitated by different scales of trait predictions and decision-making models. Successful implementation of the proposed model will facilitate the evolution of maize breeding from "art" to "science" and eventually to "intelligence," in the Breeding 4.0 era.

The role of 99mTc-MIBI SPECT/CT in patients with secondary hyperparathyroidism: comparison with 99mTc-MIBI planar scintigraphy and ultrasonography.

BACKGROUND: This study aimed to compare the sensitivity of 99mTc-MIBI SPECT/CT, 99mTc-MIBI planar scintigraphy and ultrasonography (US) in patients with secondary hyperparathyroidism (SHPT), and to explore the factors that affect the sensitivity of 99mTc-MIBI SPECT/CT. METHODS: In this retrospective study, forty-six patients with SHPT who underwent 99mTc-MIBI planar scintigraphy, 99mTc-MIBI SPECT/CT and US were enrolled. They underwent surgery within 1 month. We compared the sensitivity of the different imaging methods based on the lesions according to the pathological results. The parathyroid lesions on 99mTc-MIBI SPECT/CT images were divided into missed diagnosis group (MDG) and non-missed diagnosis group (NMDG). We compared the lesion to background ratio (LBR), maximum diameter, volume, the mean CT Hounsfield unit values (CTmean) and location of lesions between MDG and NMDG. RESULTS: The sensitivity of 99mTc-MIBI SPECT/CT, 99mTc-MIBI planar scintigraphy and US were 70.30% versus 48.48% versus 61.82%, respectively. The sensitivity of 99mTc-MIBI SPECT/CT combined US was 79.39%, which was higher than 99mTc-MIBI SPECT/CT with significant difference (P = 0.000). On 99mTc-MIBI SPECT/CT images, the LBR, maximum diameter and volume of lesions in MDG was smaller than those in NMDG with significant difference (P < 0.001). The average LBR, maximum diameter and volume of lesions in MDG and NMDG were 3.42 ± 1.28, 9.32 ± 2.69 mm, 208.51 ± 163.22 mm3 versus 6.75 ± 5.08, 15.03 ± 4.94 mm and 863.85 ± 1216.0 mm3, respectively. CONCLUSIONS: 99mTc-MIBI SPECT/CT exhibited the highest sensitivity among the three methods. When 99mTc-MIBI SPECT/CT combined with US, the sensitivity can be further improved. Lesions with lower MIBI uptake and smaller lesions on 99mTc-MIBI SPECT/CT images were easily missed.

Amorphous calcium phosphate phase-mediated crystal nucleation kinetics and pathway.

Generally, a solution nucleation model is used to study biomineralization kinetics. However, we found that the amorphous calcium phosphate (ACP)-mediated hydroxyapatite (HAP) nucleation in simulated body fluids (SBF) had a different profile from the linear relationship between ln J and ln(-2) S (J, nucleation rate; S, supersaturation). This behaviour was alternatively explained by a developed heterogeneous nucleation theory, which indicated that HAP was nucleated at the ACP-solution interface via a polymorph transformation. Based upon this new model, we demonstrated experimentally that the embedded polymer molecules inside ACP were inert on HAP nucleation kinetics; rather, the polymers adsorbed on ACP surface could inhibit HAP nucleation from ACP. It further confirmed the heterogeneous nucleation pathway of HAP on the precursor phase. The present study provides an in-depth understanding of HAP formation for ACP-mediated crystallization.

Application of T-DNA activation tagging to identify glutamate receptor-like genes that enhance drought tolerance in plants.

KEY MESSAGE: A high-quality rice activation tagging population has been developed and screened for drought-tolerant lines using various water stress assays. One drought-tolerant line activated two rice glutamate receptor-like genes. Transgenic overexpression of the rice glutamate receptor-like genes conferred drought tolerance to rice and Arabidopsis. Rice (Oryza sativa) is a multi-billion dollar crop grown in more than one hundred countries, as well as a useful functional genetic tool for trait discovery. We have developed a population of more than 200,000 activation-tagged rice lines for use in forward genetic screens to identify genes that improve drought tolerance and other traits that improve yield and agronomic productivity. The population has an expected coverage of more than 90 % of rice genes. About 80 % of the lines have a single T-DNA insertion locus and this molecular feature simplifies gene identification. One of the lines identified in our screens, AH01486, exhibits improved drought tolerance. The AH01486 T-DNA locus is located in a region with two glutamate receptor-like genes. Constitutive overexpression of either glutamate receptor-like gene significantly enhances the drought tolerance of rice and Arabidopsis, thus revealing a novel function of this important gene family in plant biology.

18 F-FDG PET/CT Versus 18 F-FAPI PET/CT in a Case of Recurrent Malignant Phyllodes Breast Tumor.

ABSTRACT: A 52-year-old woman with medical history of surgery for left malignant phyllodes breast tumor found a mass on the left chest 3 months ago. A suspicion of recurrent malignant phyllodes breast tumor was made. The patient was enrolled in the clinical trial of 18 F-FAPI PET/CT in recurrent sarcoma (no. NCT05485792). 18 F-FAPI PET/CT and 18 F-FDG PET/CT were performed, and the images demonstrated intense uptake in a huge mass in the left anterior chest wall. Then the patient underwent extended resection of left chest wall tumor. The tumor proved to be recurrent malignant phyllodes breast tumor pathologically.

Phycoremediation and valorization of hypersaline pickled mustard wastewater via Chaetoceros muelleri and indigenous bacteria.

Hypersaline pickled mustard wastewater (PMW), a typical food wastewater with high nutrient content, was successfully bioremediated via the co-treatment of Chaetoceros muelleri and indigenous bacteria in this study. Chemical oxygen demand, ammonia nitrogen, total nitrogen and total phosphorus in 10 % PMW could be effectively reduced by 82 %, 90 %, 94 % and 96 %, respectively, after 12 days treatment. Oxygen species activities, malondialdehyde content, microalgal biomass, photosynthesis and extracellular polymeric substances were characterized during the treatment to determine the responses of the consortium when exposed to different concentration of PMW. Microbial community analysis demonstrated a significant increase in the relative abundance of Halomonas and Marinobacter in the 10 % PMW after 12 days treatment, which was beneficial for nutrients recycling by the diatoms. Meanwhile, C. muelleri was effective in reducing the relative abundance of potentially pathogenic bacteria Malaciobacter. In conclusion, the work here offers a promising and environmentally friendly approach for hypersaline wastewater treatment.

UV-aged polystyrene nanoplastics aggravate intestinal barrier damage by overproduction of ROS.

UV irradiation significantly alters nanoplastics (NPs) physicochemical properties, thus affecting their biological toxicity. This study is the first to assess the influence of virgin and UV-aged polystyrene NPs (v-PS NPs, a-PS NPs) on the intestinal barrier of ICR mice. We found that a-PS NPs can cause more severe intestinal barrier damage compared with v-PS NPs. The reason may be attributed to that a-PS NPs produced more ROS in intestinal tissue. Moreover, the strong oxidizing property of hydroxyl radicals (·OH) generated from the a-PS NPs can damage cell membranes through lipid peroxidation, thereby leading to a low clearance rate of ·OH due to the impaired intestinal tissue function, in turn, causing more ROS to accumulate and inducing severe oxidative damage. This research underscores the crucial role of ·OH in mediating oxidative damage from UV-aged nanoparticles, emphasizing the need to consider environmental factors in assessing NPs toxicity.

Correlation between serum vitamin D level and uterine volume in girls with idiopathic central precocious puberty.

OBJECTIVES: Investigate serum vitamin D (vit D) levels' relation to uterine volume in idiopathic central precocious puberty (ICPP) girls and compare findings with normal peers. METHODS: Analyzed 278 ICPP cases from January 2017 to September 2022 alongside 239 normally developing girls. Collected clinical data and lab markers and performed subgroup analysis based on vit D levels. Correlation and regression analyses were conducted. RESULTS: The ICPP group exhibited elevated uterine volume and lower serum vit D compared to controls (p<0.05). A weak negative correlation was noted between vit D and uterine volume in ICPP (r=-0.193, p=0.004), and no such correlation in controls (r=-0.073, p=0.319). The ICPP vit D deficiency subgroup displayed higher uterine volume than the insufficiency and sufficiency subgroups (p<0.05). Uterine volume in the insufficiency subgroup exceeded the sufficiency subgroup (p<0.05). After adjusting for confounders, lower vit D is linked to increased ICPP uterine volume (non-standardized regression coefficient ß=-25.55, 95 % CI= -46.23, -4.87, p=0.016). A Limited correlation between vit D and uterine volume was seen in girls with normal pubertal timing. CONCLUSIONS: We demonstrated a correlation between vit D and uterine volume in ICPP girls, absent in normal peers. ICPP girls often exhibit lower vit D levels and increased uterine volume. Further research is vital for understanding vit D's role in ICPP pathogenesis and guiding prevention and treatment strategies.

Role of [18F]FAPI-04 in staging and therapeutic management of intrahepatic cholangiocarcinoma: prospective comparison with [18F]FDG PET/CT.

BACKGROUND: Fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has some limitations in diagnosis of Intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: Patients with histologically confirmed ICC who underwent both [18F]FDG and 18F-labeled fibroblast-activation protein inhibitors ([18F]FAPI)-04 PET/CT were prospectively analyzed. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), [18F]FAPI-avid tumor volume (FTV), total lesion fibroblast activation protein expression (TLF) were compared between the two modalities by paired Wilcoxon signed-rank test and Mann-Whitney U test, and McNemar's test was used to assess the diagnostic accuracy between the two techniques. RESULTS: In total, 23 patients with 389 lesions were included. Compared to [18F]FDG, [18F]F-FAPI-04 PET/CT demonstrated a higher detection rate for intrahepatic lesions (86.3% vs. 78.2% P = 0.040), lymph node metastases (85.2% vs. 68.2%, P = 0.007), peritoneal metastases (100% vs. 93.8%), and bone metastases (100% vs. 70.5%, P < 0.001). [18F]FAPI-04 PET showed higher SUVmax, TBR and greater tumor burden values than [18F]FDG PET in non-cholangitis intrahepatic lesions (SUVmax: 8.7 vs. 6.4, P < 0.001; TBR: 8.0 vs. 3.5, P < 0.001; FTV vs. MTV: 41.3 vs. 12.4, P < 0.001; TLF vs. TLG: 223.5 vs. 57.0, P < 0.001), lymph node metastases (SUVmax: 6.5 vs. 5.5, P = 0.042; TBR: 5.4 vs. 3.9, P < 0.001; FTV vs. MTV: 2.0 vs. 1.5, P = 0.026; TLF vs. TLG: 9.0 vs. 7.8 P = 0.024), and bone metastases (SUVmax: 9.7 vs. 5.25, P < 0.001; TBR: 10.8 vs. 3.0, P < 0.001; TLF vs. TLG: 9.8 vs. 4.2, P < 0.001). However, [18F]FDG showed higher radiotracer uptake (SUVmax: 14.7 vs. 8.4, P < 0.001; TBR: 7.4 vs. 2.8, P < 0.001) than [18F]FAPI-04 PET/CT for 6 patients with obstructive cholangitis. [18F]FAPI-04 PET/CT yielded a change in planned therapy in 6 of 23 (26.1%) patients compared with [18F]FDG. CONCLUSIONS: [18F]FAPI-04 PET/CT had higher detection rate and radiotracer uptake than [18F]FDG PET/CT in intrahepatic lesions, lymph node metastases, and distant metastases, especially in bone. Therefore, [18F]FAPI-04 PET/CT may be a promising technique for diagnosis and staging of ICC. TRIAL REGISTRATION: Clinical Trials, NCT05485792. Registered 1 August 2022, retrospectively registered, https//clinicaltrials.gov/study/NCT05485792?cond=NCT05485792&rank=1.

Faster nucleation at lower pH: amorphous phase mediated nucleation kinetics.

Faster nucleation of hydroxyapatite (HAP) at lower pH (with lower supersaturation) contradicts classical understanding. We find that the residue calcium ion in the mother liquor is the key to trigger ACP phase transformation, which gives an understanding of nonclassical nucleation kinetics of ACP-mediated crystallization and sheds light on biomineralization.

Increased 18F-FAPI Uptake in Radiation-Induced Liver Injury.

ABSTRACT: A 51-year-old woman with breast cancer underwent a complete surgical resection and chemoradiotherapy approximately 3 months ago. Follow-up abdominal ultrasound detected a new lesion with decreased echogenicity in the hepatic segment IV/VIII. 18F-FDG PET/CT showed the hepatic lesion without abnormal uptake. The patient was subsequently enrolled in a clinical trial of 18F-FAPI PET/CT to assess the hepatic lesion. An intense 18F-FAPI activity was identified in the hepatic lesion. Finally, pathological analysis combined with imaging follow-up confirmed the diagnosis of radiation-induced liver injury.