A rare complex structural variant of novel intragenic inversion combined with reciprocal translocation t(X;1)(p21.2;p13.3) in Duchenne muscular dystrophy.

Structural variants (SVs) are infrequently observed in Duchenne muscular dystrophy (DMD), a condition mainly marked by deletions and point mutations in the DMD gene. SVs in DMD remain difficult to reliably detect due to the limited SV-detection capacity of conventionally used short-read sequencing technology. Herein, we present a family, a boy and his mother, with clinical signs of muscular dystrophy, elevated creatinine kinase levels, and intellectual disability. A muscle biopsy from the boy showed dystrophin deficiency. Routine molecular techniques failed to detect abnormalities in the DMD gene, however, dystrophin mRNA transcripts analysis revealed an absence of exons 59 to 79. Subsequent long-read whole-genome sequencing identified a rare complex structural variant, a 77 kb novel intragenic inversion, and a balanced translocation t(X;1)(p21.2;p13.3) rearrangement within the DMD gene, expanding the genetic spectrum of dystrophinopathy. Our findings suggested that SVs should be considered in cases where conventional molecular techniques fail to identify pathogenic variants.

Gallium-68 labeled somatostatin receptor antagonist PET/CT in over 500 patients with neuroendocrine neoplasms: experience from a single center in China.

PURPOSE: Somatostatin receptor antagonists have shown promising performance for imaging neuroendocrine neoplasms. However, there is a lack of studies exploring the diagnostic performance of SSTR antagonists or comparing them with agonists in a large cohort of patients with NENs. This study aimed to retrospectively review all SSTR antagonist PET/CT scans conducted at Peking Union Medical College Hospital since November 2018 in patients with confirmed or suspected NENs. METHODS: Four types of SSTR antagonists were utilized, including [68Ga]Ga-NODAGA-LM3, [68Ga]Ga-DOTA-LM3, [68Ga]Ga-NODAGA-JR11, and [68Ga]Ga-DOTA-JR11. The reference standard was based on a combination of histopathology, clinical evaluation, imaging results, and follow-up. Patient-based sensitivity, specificity, and accuracy were evaluated. The SUVmax and tumor-to-liver ratio (TLR) of the hottest lesions was recorded and compared between antagonists and [68Ga]Ga-DOTATATE. RESULTS: A total of 622 antagonist scans from 549 patients were included in the analysis. The patient-level sensitivity, specificity, and accuracy of antagonist imaging (all tracers combined) were 91.0% (443/487), 91.9% (57/62), and 91.1% (500/549), respectively. In 181 patients with a comparative [68Ga]Ga-DOTATATE PET/CT scan, the patient-level sensitivity, specificity, and accuracy were 87.5% (147/168), 76.9% (10/13), and 86.7% (157/181), respectively. For the hottest lesions, SSTR antagonists all tracers combined demonstrated an overall comparable SUVmax to [68Ga]Ga-DOTATATE (40.1 ± 32.5 vs. 39.4 ± 23.8, p = 0.772). While [68Ga]Ga-NODAGA-LM3 showed significantly higher uptake than [68Ga]Ga-DOTATATE (57.4 ± 38.5 vs. 40.0 ± 22.8, p<0.001), [68Ga]Ga-NODAGA-JR11 (39.7 ± 26.5 vs. 34.3 ± 23.9, p = 0.108) and [68Ga]Ga-DOTA-LM3 (38.9 ± 32.1 vs. 37.2 ± 22.1, p = 0.858) showed comparable uptake to [68Ga]Ga-DOTATATE, and [68Ga]Ga-DOTA-JR11 showed lower uptake (28.9 ± 26.1 vs. 44.0 ± 25.7, p = 0.001). All antagonists exhibited significantly higher TLR than [68Ga]Ga-DOTATATE (12.1 ± 10.8 vs. 5.2 ± 4.5, p<0.001). CONCLUSION: Gallium-68 labeled SSTR antagonists could serve as alternatives to SSTR agonists for imaging of NENs. Among various antagonists, [68Ga]Ga-NODAGA-LM3 seems to have the best imaging profile.

Environmental factors affecting the risk of generalization for ocular-onset myasthenia gravis: a nationwide cohort study.

BACKGROUND: The environmental effects on the prognosis of ocular myasthenia gravis (OMG) remain largely unexplored. AIM: To investigate the association between specific environmental factors and the generalization of OMG. DESIGN: The cohort study was conducted in China based on a nationwide multicenter database. METHODS: Adult patients with OMG at onset, who were followed up for at least 2 years until May 2022, were included. We collected data on demographic and clinical factors, as well as environmental factors, including latitude, socioeconomic status (per capita disposable income [PDI] at provincial level and education) and smoking. The study outcome was the time to the development of generalized myasthenia gravis (GMG). Cox models were employed to examine the association between environmental exposures and generalization. Restricted cubic spline was used to model the association of latitude with generalization risk. RESULTS: A total of 1396 participants were included. During a median follow-up of 5.15 (interquartile range [IQR] 3.37-9.03) years, 735 patients developed GMG within a median of 5.69 (IQR 1.10-15.66) years. Latitude of 20-50°N showed a U-shaped relation with generalization risk, with the lowest risk at around 30°N; both higher and lower latitudes were associated with the increased risk (P for non-linearity <0.001). Living in areas with lower PDI had 1.28-2.11 times higher risk of generalization. No significant association was observed with education or smoking. CONCLUSIONS: Latitude and provincial-level PDI were associated with the generalization of OMG in China. Further studies are warranted to validate our findings and investigate their potential applications in clinical practice and health policy.

Distinct FDG PET/CT avidity among newly diagnosed intravascular large B-cell lymphoma patients: a descriptive observational study.

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of aggressive B-cell non-Hodgkin lymphoma that poses a great diagnostic challenge due to its highly heterogenous clinical manifestations. Although 18F-fluorodeoxyglucose (FDG) is widely used as a diagnostic tool for patients suspected of having lymphoma, as it reveals FDG-avid lesions, the FDG avidity of IVLBCL has not been extensively characterized. Here, we present a comprehensive report of FDG avidity in IVLBCL and its association with clinicopathological features and survival. This descriptive observational study included consecutive patients aged at least 18 years diagnosed with IVLBCL in Peking Union Medical Hospital across 9 years. Among 50 screened IVLBCL patients, 42 had undergone 18F-FDG PET/CT to detect possible lesions for biopsy before pathological diagnosis; their FDG PET/CT (positron emission computed tomography, PET/CT) reports were retrospectively reviewed. The primary endpoint was the clinical description of FDG avidity of newly diagnosed intravascular large B-cell lymphoma and frequency. A total of 73.8% patients showed FDG-avid lesions, with a median SUVmax of 7.4 (range 1-27.7), which was lower than that for other aggressive lymphomas. Clinicopathological features were the same between the FDG-avid group and the non-FDG-avid group, except that the latter had a higher Ki-67 index (median 90% in the nonavid group vs. 80% in the avid group, P = 0.043). The overall survival rate was not different between the PET/CT groups. Our findings demonstrate that FDG PET/CT is a useful diagnostic tool for detecting FDG-avid lesions in IVLBCL patients. A random skin biopsy is essential for assisting in the diagnosis of IVLBCL, even for those with negative PET/CT.

Alterations in regional homogeneity and functional connectivity in the cerebellum of patients with sporadic amyotrophic lateral sclerosis.

OBJECTIVE: The purpose of this study was to examine the cerebellum's local and global functional characteristics in individuals with sporadic amyotrophic lateral sclerosis (sALS) and their correlation with clinical data. METHODS: Resting-state functional magnetic resonance imaging was performed on 39 patients with sALS and on 23 healthy controls. Regional homogeneity (ReHo) in the cerebellum of all participants was analyzed, and the cerebellar regions with differences in ReHo were considered regions of interest (ROIs). In addition, the functional connectivity between the ROIs and other brain regions was analyzed. RESULTS: In patients with sALS, ReHo increased in parts of the posterior cerebellar lobe. Then, the two regions with increased ReHo of the cerebellum were used as seeds, and further analysis revealed that the connectivity of the right cerebellum to the right medial superior frontal gyrus, left lingual gyrus (calcarine sulcus), left precentral gyrus, left supplementary motor area, and right Crus II was significantly increased. CONCLUSION: The results demonstrate that resting-state functional connectivity changes in both motor and extra-motor regions of the cerebellum in patients with sALS, and that the cerebellum plays a pathophysiological role in sALS.

Mesenteric Castleman Disease Misdiagnosed as Lymph Node Metastasis of Rectal Cancer on 18 F-FDG PET/CT.

ABSTRACT: Two years ago, a 64-year-old man underwent an 18 F-FDG PET/CT for staging rectal cancer. Besides the hypermetabolic rectal lesion, the image revealed a mesenteric lymph node with intense activity and multiple lung nodules with slight FDG uptake, which were highly suspected of metastases. After surgery and multiple cycles of chemotherapy, the follow-up 18 F-FDG PET/CT showed remission of all lesions except for the enlarged mesenteric lymph node with higher metabolic activity. Serum CEA remained normal during the follow-up. Postoperative pathology of the mesenteric lymph node confirmed Castleman disease.

Analysis of Fatty Acid Metabolism in Fetal and Failing Hearts by Single-Cell RNA Sequencing Revealed SLC27A6 as a Critical Gene in Heart Maturation.

Background: Heart failure is associated with shifts in substrate preferences and energy insufficiency. Although cardiac metabolism has been explored at the organ level, the metabolic changes at the individual cell level remain unclear. This study employed single-cell ribonucleic acid (RNA) sequencing to investigate the cell-type-specific characteristics of gene expression related to fatty acid metabolism. Methods: Single-cell RNA sequencing data from fetal hearts were processed to analyze gene expression patterns related to fatty acid metabolism. Immunofluorescence staining and Western blotting techniques were employed to validate the expression of specific proteins. Additionally, calcium recording and contractility measurements were performed to assess the functional implications of fatty acid metabolism in cardiomyocytes. Results: Based on single-cell RNA sequencing data analysis, we found that a decrease in overall energy requirements underlies the downregulation of fatty acid oxidation-related genes in the later period of heart maturation and the compensatory increase of fatty acid metabolism in individual cardiomyocytes during heart failure. Furthermore, we found that solute carrier family 27 member 6 (SLC27A6), a fatty acid transport protein, is involved in cardiac maturation. SLC27A6 knockdown in human induced pluripotent stem cell-derived cardiomyocytes resulted in an immature cardiomyocyte transcriptional profile, abnormal morphology, impaired Ca2+ handling activity, and contractility. Conclusions: Overall, our study offers a novel perspective for exploring cardiac fatty acid metabolism in fetal and failing hearts along with new insights into the cellular mechanism underlying fatty acid metabolic alterations in individual cardiac cells. It thus facilitates further exploration of cardiac physiology and pathology.

Head-to-Head Comparison of 68Ga-NODAGA-JR11 and 68Ga-DOTATATE PET/CT in Patients with Metastatic, Well-Differentiated Neuroendocrine Tumors: Interim Analysis of a Prospective Bicenter Study.

The current study aimed to compare 68Ga-NODAGA-Cpa-cyclo(d-Cys-amino-Phe-hydroorotic acid-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)-d-Tyr-NH2 (JR11) and 68Ga-DOTATATE PET/CT in patients with metastatic, well-differentiated neuroendocrine tumors. Methods: A prospective bicenter study aimed at enrolling 100 patients with histologically proven, metastatic or unresectable, well-differentiated neuroendocrine tumors was conducted. The first 48 patients represented the study cohort. Each patient received 68Ga-DOTATATE on the first day and 68Ga-NODAGA-JR11 on the second day. Whole-body PET/CT scans were performed at 40-60 min after injection. Normal-organ uptake, lesion numbers, lesion uptake, and sensitivity were compared. The potential impact on clinical management was also determined. Results: Overall, 68Ga-NODAGA-JR11 demonstrated lower background uptake in normal organs. Compared with 68Ga-DOTATATE, 68Ga-NODAGA-JR11 detected significantly more liver lesions (673 vs. 584, P = 0.002). The target-to-background ratio of liver lesions was significantly higher on 68Ga-NODAGA-JR11 (6.4 ± 8.7 vs. 3.1 ±2.6, P = 0.000). Comparable uptake was observed for primary tumors, bone lesions, and lymph node metastases. In total, 180 lesions were detected on conventional imaging in 15 patients; 165 and 139 lesions of them were positive on 68Ga-NODAGA-JR11 and 68Ga-DOTATATE, leading to a sensitivity of 91.7% and 77.2%, respectively. In 14.5% (7/48) of patients, 68Ga-NODAGA-JR11 PET might have a potential impact on clinical management. Conclusion: 68Ga-NODAGA-JR11 shows better sensitivity and a higher target-to-background ratio than 68Ga-DOTATATE. The detection of more lesions by the antagonist may have a potential impact on clinical management in a subgroup of patients.

Prediction of metformin adsorption on subsurface sediments based on quantitative experiment and artificial neural network modeling.

Metformin (MET), a widely employed hypoglycemic pharmaceutical agent, has been frequently detected within groundwater, which has posed a threat to ecosystems and human health. However, the adsorption behavior of MET onto distinct constituent aquitards and aquifers sediments remains shrouded in uncertainty. To reveal the adsorption capacities and mechanisms of diverse sedimentary matrices, we delved into a series of adsorption experiments involving MET on 37 subsurface sediment samples obtained from four boreholes (ranging from 0 to 30 m in depth) in the Jianghan Plain. The quantitative analysis revealed that a majority of the sedimentary compositions consisted of clay minerals (mainly chlorite, montmorillonite and albite), with MET exhibiting considerable variability in across different sediment components (ranging from 15.5 to 489.4 mg/kg). In general, MET adsorption declined in proportion to an increase in quartz composition and depth. Consequently, an artificial neural network model was constructed (R2 = 0.971) to assess the influence of sediment composition on MET adsorption, and thereby elucidating the dominant roles played by chlorite and montmorillonite in this process. Notably, electrostatic attraction, cation exchange, and chemical bonding emerged as the primary mechanisms governing MET adsorption on sediments, particularly those rich in clay minerals. By shedding light on the adsorption mechanism of MET on clay-dominated subsurface sediments, our findings have contributed to a quantitative understanding of MET's adsorption capacity and have highlighted the associated environmental risks.

Changes in brain gray matter volume in nasopharyngeal carcinoma patients after radiotherapy in long-term follow-up

Abstract Objectives The aim of this study was to examine the changes in gray matter in nasopharyngeal carcinoma patients with normal hearing (Group 1) and nasopharyngeal carcinoma patients with hearing loss (Group 2) after radiotherapy using voxel-based morphological analysis and to analyze the relationship with the radiation doses of the temporal lobe. Methods 21 patients in Group 1, 14 patients in Group 2, and 21 healthy volunteers were selected. All participants underwent an otologic examination and three-dimensional magnetization preparatory rapid acquisition gradient echo sequence scan. The correlation between the variation of whole brain gray matter volume and the doses of the temporal lobe was analyzed by Data Processing & Analysis for Brain Imaging software. Results Compared with the normal control group, the brain areas with reduced gray matter volume in nasopharyngeal carcinoma patients after radiotherapy were mainly in the left posterior cerebellar lobe (T = −8.797), left insular lobe (T = −7.96), and the right insular lobe (T = −6.632). Compared to Group 1, the brain areas of Group 2 patients with reduced gray matter volume were mainly in the left superior temporal gyrus (T = −2.366), left olfactory bulb (T = −2.52), left Rolandic operculum (T = −2.431), and right olfactory bulb (T = −3.100). Compared with Group 1, the brain areas of Group 2 patients with increased gray matter volume were mainly in the left calcarine sulcus (T = 3.425) and right calcarine sulcus (T = 3.169). There were no correlations between the changes of brain gray matter volume and the radiation doses of the temporal lobe in both Group 1 and Group 2. Conclusions The radiotherapy may cause the changes of brain areas associated with cognitive function in nasopharyngeal carcinoma in a long-term follow-up. At the same time, nasopharyngeal carcinoma patients with the radiation-induced hearing loss had abnormal gray matter volumes in the auditory center and other sensory centers. Our findings might provide new understanding into the pathogenesis of radiation-induced brain damage in normal-appearing brain tissue. Yet this exploratory study should be taken with caution.

What learning strategies influence higher-order learning behaviours of medical students?

AIMS: The aim of this study was to explore the relationship between the application of learning strategies and the emergence of higher-order learning behaviours among medical students in Chinese provincial undergraduate colleges, while also examining the impact of social demographic variables on the development of higher-order learning behaviours and learning strategy preferences. METHODOLOGY: We conducted a relevant cross-sectional study using the Chinese College Student Survey (CCSS) online questionnaire to evaluate higher-order learning behaviours and learning strategies in medical undergraduate students attending provincial colleges in China. A total of 992 valid questionnaires were collected and analysed using SPSS 22.0 (SPSS Inc., Chicago, IL). We performed statistical analysis using one-sample t-tests to compare the results with the national norm score for medical subjects in undergraduate colleges. We also conducted variance analysis and regression analysis. RESULTS: The study found that the average scores for higher-order learning behaviours, enquiry-based learning and receptive learning behaviour among medical undergraduate students in provincial colleges were higher than the national norm score for medical subjects, indicating a positive trend. However, the average scores for other indicators were lower than the national norm score. The utilization of learning strategies and the development of higher-order learning behaviours among students were affected by various factors such as grade and gender. The study suggests that the preference for certain learning strategies, such as enquiry-based, receptive, integrative and collaborative, can have a significant impact on the emergence of higher-order learning behaviours. CONCLUSIONS: The study has demonstrated a positive correlation between the utilization of learning strategies and the development of higher-order learning behaviours. This relationship has been observed in medical students attending provincial undergraduate colleges, where the adoption of enquiry-based, receptive, integrative and collaborative learning strategies has been found to significantly influence the emergence of higher-order learning behaviours.KEY MESSAGESThe implementation of learning strategies among medical students in provincial undergraduate colleges in China has a significant impact on high-level learning behaviours.The impact of high-level learning behaviours is reliant on comprehensive support from four distinct learning strategies: receptive learning, inquiry-based learning, comprehensive learning and collaborative learning.One of the most impactful learning strategies is receptive learning, particularly on high-order learning behaviours. On the other hand, reflective learning does not seem to have a significant effect.Changes in grades can significantly impact higher-order learning behaviours and affect the propensity for reflective and collaborative learning strategies.Females generally exhibit a greater preference for receptive learning strategies, while males tend to exhibit a greater preference for inquiry-based learning strategies.

Preclinical and pilot clinical evaluation of a small-molecule carbonic anhydrase IX targeting PET tracer in clear cell renal cell carcinoma.

PURPOSE: Clear cell renal cell carcinoma (ccRCC) highly expresses carbonic anhydrase IX (CAIX). The purpose of this study was to evaluate 68Ga-NY104, a small-molecule CAIX-targeting PET agent, in tumor models of ccRCC and patients diagnosed with confirmed, or suspicious, ccRCC. METHODS: The in vivo and ex vivo biodistribution of 68Ga-NY104 was investigated in CAIX-positive OS-RC-2 xenograft-bearing models. The binding of the tracer was further validated using autoradiography for human ccRCC samples. In addition, three patients with confirmed or suspicious ccRCC were studied. RESULTS: NY104 can be labeled with high radiochemical yield and purity. It quickly cleared through kidney with α-half-life of 0.15 h. Discernible uptake is noted in the heart, lung, liver, stomach, and kidney. The OS-RC-2 xenograft demonstrated intense uptake 5 min after injection and gradually increased until 3 h after injection with ID%/g of 29.29 ± 6.82. Significant binding was detected using autoradiography on sections of human ccRCC tumor. In the three patients studied, 68Ga-NY104 was well-tolerated and no adverse events were reported. Substantial accumulation was observed in both primary and metastatic lesions in patient 1 and 2 with SUVmax of 42.3. Uptake in the stomach, pancreas, intestine, and choroid plexus was noted. The lesion in third patient was correctly diagnosed as non-metastatic for negative 68Ga-NY104 uptake. CONCLUSION: 68Ga-NY104 can efficiently and specifically bind to CAIX. Given the pilot nature of our study, future clinical studies are warranted to evaluate 68Ga-NY104 for detection of CAIX-positive lesions in patients with ccRCC. TRIAL REGISTRATION: The clinical evaluation part of this study was retrospectively registered at ClinicalTrial.gov (NCT05728515) as NYPILOT on 6 Feb, 2023.

A synonymous codon variant altering splicing of RBCK1 expands the phenotype and genotype spectra of polyglucosan body myopathy 1.

Polyglucosan body myopathy type 1 (PGBM1, OMIM #615895.) is a rare autosomal recessive disorder caused by RBCK1 mutations. The patients displayed polyglucosan accumulation in skeletal and cardiac muscles, giving rise to loss of ambulation and heart failure with or without immune system dysregulation. So far, only 24 patients have been reported, all of whom exhibited symptoms before adulthood. Here, we reported the first case of an adult-onset PGBM1 patient with a novel compound heterozygous RBCK1 gene mutation consisting of a nonsense and synonymous variant affecting splicing.

Changes in brain gray matter volume in nasopharyngeal carcinoma patients after radiotherapy in long-term follow-up.

OBJECTIVES: The aim of this study was to examine the changes in gray matter in nasopharyngeal carcinoma patients with normal hearing (Group 1) and nasopharyngeal carcinoma patients with hearing loss (Group 2) after radiotherapy using voxel-based morphological analysis and to analyze the relationship with the radiation doses of the temporal lobe. METHODS: 21 patients in Group 1, 14 patients in Group 2, and 21 healthy volunteers were selected. All participants underwent an otologic examination and three-dimensional magnetization preparatory rapid acquisition gradient echo sequence scan. The correlation between the variation of whole brain gray matter volume and the doses of the temporal lobe was analyzed by Data Processing & Analysis for Brain Imaging software. RESULTS: Compared with the normal control group, the brain areas with reduced gray matter volume in nasopharyngeal carcinoma patients after radiotherapy were mainly in the left posterior cerebellar lobe (T = -8.797), left insular lobe (T = -7.96), and the right insular lobe (T = -6.632). Compared to Group 1, the brain areas of Group 2 patients with reduced gray matter volume were mainly in the left superior temporal gyrus (T = -2.366), left olfactory bulb (T = -2.52), left Rolandic operculum (T = -2.431), and right olfactory bulb (T = -3.100). Compared with Group 1, the brain areas of Group 2 patients with increased gray matter volume were mainly in the left calcarine sulcus (T=3.425) and right calcarine sulcus (T=3.169). There were no correlations between the changes of brain gray matter volume and the radiation doses of the temporal lobe in both Group 1 and Group 2. CONCLUSIONS: The radiotherapy may cause the changes of brain areas associated with cognitive function in nasopharyngeal carcinoma in a long-term follow-up. At the same time, nasopharyngeal carcinoma patients with the radiation-induced hearing loss had abnormal gray matter volumes in the auditory center and other sensory centers. Our findings might provide new understanding into the pathogenesis of radiation-induced brain damage in normal-appearing brain tissue. Yet this exploratory study should be taken with caution.

Comparative analysis of allergenicity and predicted linear epitopes in α and ß parvalbumin from turbot (Scophthalmus maximus).

BACKGROUND: Parvalbumin (PV) can be subdivided into two phylogenetic lineages, αPV and ßPV. The bony fish ßPV is considered a major fish allergen. However, there is no available report on the immunological property and epitope mapping of bony fish αPV. RESULTS: To characterize the allergenic property of bony fish αPV and investigate the difference in allergenic property of bony fish αPV and ßPV, turbot (Scophthalmus maximus) αPV and ßPV were identified by mass spectrometry and were expressed in Escherichia coli system in this study. Spectra analysis and three-dimensional (3D) modeling showed the similar structure between αPV and ßPV. However, αPV exhibited lower immunoglobulin E/immunoglobulin G (IgE/IgG) binding capacity than ßPV. Three identified ßPV epitopes possessed higher IgE reactivity and more hydrophobic residues than three identified αPV epitopes. In addition, less similarity in sequence homology of αPV epitopes was observed with allergen sequences in database. CONCLUSION: These finding expanded information on fish PV epitopes and substantiated the difference in allergenicity and epitope mapping between fish αPV and ßPV, which will improve the epitope-based detection tools of PV and diagnostic of PV induced fish allergy. © 2023 Society of Chemical Industry.

Dynamic PET/CT scan of 68Ga-FAPI-04 for the optimal acquisition time in suspected malignant hepatic cancer patients.

PURPOSE: Dynamic PET/CT scan of 68Ga-FAPI-04 in patients with suspected malignant hepatic lesions were retrospectively analyzed to find the optimal acquisition time with better lesion detection rate. METHODS: Twenty-two patients with lesions confirmed by CT or MRI were performed with dynamic 68Ga-FAPI-04 PET/CT scan. Tracer uptake of lesions and normal organs at different time points were analyzed. Standardized uptake value (SUV) and tumor-to-background (TBR) were calculated based on the quantification of images. RESULTS: SUV of normal organs decreased rapidly from 10 to 30 min and decreased gradually from 30 to 60 min. Besides, the uterus showed a particularly high uptake in all patients (12.62 ± 4.58 at 10 min p.i., 12.04 ± 3.99 at 30 min p.i., 10.92 ± 2.38 at 60 min p.i.). SUV of lesions decreased gradually, while TBR increased from 10- to 60-min post-injection. Visual analysis verified a comparable lesion detectability of 30 min and 60 min with images of 10 min showing a decreased lesion detection number. CONCLUSION: This study revealed that similar detection rates were achieved at both 30 and 60 min, suggesting a static scan at 30 min to be appropriate in the clinic. Besides, although with high lesion uptake, early 68Ga-FAPI-04 PET imaging at 10 min after tracer injection could cause missed lesion detection.

Alpinia officinarum mediated copper oxide nanoparticles: synthesis and its antifungal activity against Colletotrichum gloeosporioides.

Green synthesis offers an environmentally friendly and cost-effective alternative for the synthesis of copper oxide nanoparticles (CuO NPs). In this study, the synthesis of CuO NPs was optimized by using copper sulfate (CuSO4) and the aqueous extract of Alpinia officinarum and its antifungal activity were investigated. The synthesized CuO NPs were characterized by UV-visible spectroscopy (UV-vis), X-ray diffraction (XRD), Fourier-transform infrared radiation spectroscopy (FT-IR), scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), dynamic light scattering (DLS), and transmission electron microscopy (TEM). The results showed that the optimized conditions for the synthesis of CuO NPs were 1:2 ratio of extract and CuSO4 solution, pH 7, and 30 °C. The characteristic UV-vis peak of A. officinarum synthesized CuO NPs was at 264 nm. The synthesized CuO NPs had high crystallinity and purity and were spherical in morphology with the mean size of 46.40 nm. The synthesized CuO NPs reduced the fungal growth of Colletotrichum gloeosporioides in a dose-dependent manner. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of the CuO NPs were 125 µg·mL-1 and 500 µg·mL-1, respectively. The antifungal activity of CuO NPs may be attributed to its ability to deform the structure of fungal hyphae, induce excessive reactive oxygen species accumulation and lipid peroxidation in fungi, disrupt the mycelium cell membrane, and result cellular leakage.

ß-hydroxybutyrate inhibits ferroptosis-mediated pancreatic damage in acute liver failure through the increase of H3K9bhb.

Acute pancreatitis and hyperamylasemia are often seen in patients with acute liver failure (ALF). However, the underlying mechanisms remain elusive. This study describes pancreatic tissue damage and exocrine dysfunction in a mouse model of major-liver-resection-induced ALF. The analysis of 1,264 clinical cases of liver failure (LF) showed that the incidence of hyperamylasemia and hyperlipasemia in patients with LF is 5.5% and 20%, respectively. Metabolomic studies indicate that glutathione (GSH)-deficiency-caused ferroptosis contributes to pancreatic damage in mouse ALF. ß-hydroxybutyrate (ß-HB) is the only metabolite downregulated in the liver, serum, and pancreas. Our data suggest that ß-HB protects pancreatic cells and tissues from GSH-deficiency-caused ferroptosis. ß-HB administration in ALF mice restores the expression of ferroptosis-suppressor genes through histone H3 lysine 9 ß-hydroxybutyrylation (H3K9bhb)-mediated chromatin opening. Our findings highlight ß-HB as an endogenous metabolite regulating ferroptosis in the pancreas and extend our understanding of the pathophysiology of ALF-induced pancreatitis.

Activation of Pancreatic Acinar FXR Protects against Pancreatitis via Osgin1-Mediated Restoration of Efficient Autophagy.

Pancreatitis is the leading cause of hospitalization in gastroenterology, and no medications are available for treating this disease in current clinical practice. FXR plays an anti-inflammatory role in diverse inflammatory diseases, while its function in pancreatitis remains unknown. In this study, we initially observed a marked increase of nuclear FXR in pancreatic tissues of human patients with pancreatitis. Deleting the FXR in pancreatic acinar cells (FXRacinarΔ/Δ ) led to more severe pancreatitis in mouse models of caerulein-induced acute and chronic pancreatitis, while the FXR agonist GW4064 significantly attenuated pancreatitis in caerulein or arginine-induced acute pancreatitis and caerulein-induced chronic pancreatitis. FXR deletion impaired the viability and stress responses of pancreatic exocrine organoids (PEOs) in vitro. Utilizing RNA-seq and ChIP-seq of PEOs, we identified Osgin1 as a direct target of FXR in the exocrine pancreas, which was also increasingly expressed in human pancreatitis tissues compared to normal pancreatic tissues. Pancreatic knockdown of Osgin1 by AAV-pan abolished the therapeutic effects of FXR activation on pancreatitis, whereas pancreatic overexpression of Osgin1 effectively alleviated caerulein-induced pancreatitis. Mechanistically, we found that the FXR-OSGIN1 axis stimulated autophagic flux in the pancreatic tissues and cell lines, which was considered as the intrinsic mechanisms through which FXR-OSGIN1 protecting against pancreatitis. Our results highlight the protective role of the FXR-OSGIN1 axis in pancreatitis and provided a new target for the treatment of this disease.