The digestion and dietary carbohydrate pathway contains 100% gene mutations enrichment among 117 patients with major depressive disorder.

Introduction: Major depressive disorder (MDD) is partially inheritable while its mechanism is still uncertain. Methods: This cross-sectional study focused on gene pathways as a whole rather than polymorphisms of single genes. Deep sequencing and gene enrichment analysis based on pathways in Reactome database were obtained to reveal gene mutations. Results: A total of 117 patients with MDD and 78 healthy controls were enrolled. The Digestion and Dietary Carbohydrate pathway (Carbohydrate pathway) was determined to contain 100% mutations in patients with MDD and 0 mutation in matched healthy controls. Discussion: Findings revealed in the current study enable a better understanding of gene pathways mutations status in MDD patients, indicating a possible genetic mechanism of MDD development and a potential diagnostic or therapeutic target.

Mechanism of tartaric acid mediated dissipation and biotransformation of tetrabromobisphenol A and its derivatives in soil.

Biotransformation is a major dissipation process of tetrabromobisphenol A and its derivatives (TBBPAs) in soil. The biotransformation and ultimate environmental fate of TBBPAs have been widely studied, yet the effect of root exudates (especially low-molecular weight organic acids (LMWOAs)) on the fate of TBBPAs is poorly documented. Herein, the biotransformation behavior and mechanism of TBBPAs in bacteriome driven by LMWOAs were comprehensively investigated. Tartaric acid (TTA) was found to be the main component of LMWOAs in root exudates of Helianthus annus in the presence of TBBPAs, and was identified to play a key role in driving shaping bacteriome. TTA promoted shift of the dominant genus in soil bacteriome from Saccharibacteria_genera_incertae_sedis to Gemmatimonas, with a noteworthy increase of 24.90-34.65% in relative abundance of Gemmatimonas. A total of 28 conversion products were successfully identified, and ß-scission was the principal biotransformation pathway for TBBPAs. TTA facilitated the emergence of novel conversion products, including 2,4-dibromophenol, 3,5-dibromo-4-hydroxyacetophenone, para-hydroxyacetophenone, and tribromobisphenol A. These products were formed via oxidative skeletal cleavage and debromination pathways. Additionally, bisphenol A was observed during the conversion of derivatives. This study provides a comprehensive understanding about biotransformation of TBBPAs driven by TTA in soil bacteriome, offering new insights into LMWOAs-driven biotransformation mechanisms.

Characterization of a G2M checkpoint-related gene model and subtypes associated with immunotherapy response for clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) presents challenges in early diagnosis and effective treatment. In this study, we aimed to establish a prognostic model based on G2M checkpoint-related genes and identify associated clusters in ccRCC through clinical bioinformatic analysis and experimental validation. Utilizing a single-cell RNA dataset (GSE159115) and bulk-sequencing data from The Cancer Genome Atlas (TCGA) database, we analyzed the G2M checkpoint pathway in ccRCC. Differential expression analysis identified 45 genes associated with the G2M checkpoint, leading to the construction of a predictive model with four key genes (E2F2, GTSE1, RAD54L, and UBE2C). The model demonstrated reliable predictive ability for 1-, 3-, and 5-year overall survival, with AUC values of 0.794, 0.790, and 0.794, respectively. Patients in the high-risk group exhibited a worse prognosis, accompanied by significant differences in immune cell infiltration, immune function, TIDE and IPS scores, and drug sensitivities. Two clusters of ccRCC were identified using the "ConsensusClusterPlus" package, cluster 1 exhibited a worse survival rate and was resistant to chemotherapeutic drugs of Axitinib, Erlotinib, Pazopanib, Sunitinib, and Temsirolimus, but not Sorafenib. Targeted experiments on RAD54L, a gene involved in DNA repair processes, revealed its crucial role in inhibiting proliferation, invasion, and migration in 786-O cells. In conclusion, our study offers valuable insights into the molecular mechanisms underlying ccRCC, identifying potential prognostic genes and molecular subtypes associated with the G2M checkpoint. These findings hold promise for guiding personalized treatment strategies in the management of ccRCC.

MAPK14 as a key gene for regulating inflammatory response and macrophage M1 polarization induced by ferroptotic keratinocyte in psoriasis.

Psoriasis is a prevalent condition characterized by chronic inflammation, immune dysregulation, and genetic alterations, significantly impacting the well-being of affected individuals. Recently, a novel aspect of programmed cell death, ferroptosis, linked to iron metabolism, has come to light. This research endeavors to unveil novel diagnostic genes associated with ferroptosis in psoriasis, employing bioinformatic methods and experimental validation. Diverse analytical strategies, including "limma," Weighted Gene Co-expression Network Analysis (WGCNA), Least Absolute Shrinkage and Selection Operator (LASSO), Support Vector Machine Recursive Feature Elimination (SVM-RFE), and Random Forest (RF), were employed to pinpoint pivotal ferroptosis-related diagnostic genes (FRDGs) in the training datasets GSE30999, testing dataset GSE41662 and GSE14905. The discriminative potential of FRDGs in distinguishing between normal and psoriatic patients was gauged using Receiver Operating Characteristic (ROC) curves, while the functional pathways of FRDGs were scrutinized through Gene Set Enrichment Analysis (GSEA). Spearman correlation and ssGSEA analysis were applied to explore correlations between FRDGs and immune cell infiltration or oxidative stress-related pathways. The study identified six robust FRDGs - PPARD, MAPK14, PARP9, POR, CDCA3, and PDK4 - which collectively formed a model boasting an exceptional AUC value of 0.994. GSEA analysis uncovered their active involvement in psoriasis-related pathways, and substantial correlations with immune cells and oxidative stress were noted. In vivo, experiments confirmed the consistency of the six FRDGs in the psoriasis model with microarray results. In vitro, genetic knockdown or inhibition of MAPK14 using SW203580 in keratinocytes attenuated ferroptosis and reduced the expression of inflammatory cytokines. Furthermore, the study revealed that intercellular communication between keratinocytes and macrophages was augmented by ferroptotic keratinocytes, increased M1 polarization, and recruitment of macrophage was regulated by MAPK14. In summary, our findings unveil novel ferroptosis-related targets and enhance the understanding of inflammatory responses in psoriasis. Targeting MAPK14 signaling in keratinocytes emerges as a promising therapeutic approach for managing psoriasis.

CircNOP14 increases the radiosensitivity of hepatocellular carcinoma via inhibition of Ku70-dependent DNA damage repair.

Circular RNAs (circRNAs) are profoundly affected in hepatocellular carcinoma (HCC) through various pathways. However, the role of circRNAs in the radiosensitivity of HCC cells is yet to be explored. In this study, we identified a circRNA-hsa_circ_0006737 (circNOP14) involved in the radiosensitivity of HCC. We found that circNOP14 increased the radiosensitivity of HCC cells both in vitro and in vivo. Notably, using a circRNA pulldown assay and RNA-binding protein immunoprecipitation, we identified Ku70 as a novel and robust interacting protein of circNOP14. Mechanistically, circNOP14 interacts with Ku70 and prevents its nuclear translocation, thereby increasing irradiation-induced DNA damage. Therefore, our findings may provide a predictive indicator and intervention option for 125I brachytherapy or external radiotherapy in HCC.

Chemotherapy alone versus chemotherapy plus 125I brachytherapy for the second-line treatment of locally recurrent cervical cancer after/with radical treatment: A propensity score analysis.

Rationale and objectives: The primary aim of this study was to conduct a retrospective comparative analysis of the survival outcomes in patients with recurrent cervical cancer (CC). Specifically, we aimed to compare the efficacy of chemotherapy alone versus the combined approach of chemotherapy and 125I brachytherapy subsequent to the failure of initial chemotherapy treatment. Materials and methods: Patients diagnosed with recurrent CC subsequent to the failure of initial chemotherapy from January 2007 to December 2016 were enrolled from 2 hospitals. These patients were then divided into two groups: Group A, which underwent second-line chemotherapy alone, and Group B, which received both second-line chemotherapy and 125I brachytherapy. The assessment of overall survival (OS) and progression-free survival (PFS) was carried out through propensity score matching (PSM) (1:1), Kaplan-Meier curves, log-rank tests, and Cox proportional hazard regression for survival analysis. Results: A matched cohort comprising 88 patients each in Group A and Group B was included in the study. In Group A, the 1-, 2-, and 3-year cumulative PFS rates were 40.9 %, 15.9 %, and 5.7 % respectively, while in Group B, these rates were significantly higher at 79.5 %, 48.9 %, and 25.0 % (P = 0.003). Similarly, the 1-, 2-, and 3-year cumulative OS rates among Group A were 67.0 %, 27.3 %, and 5.7 % compared to 89.8 %, 63.6 %, and 30.7 % among Group B, suggesting a difference with statistical significance (P < 0.001) between the two groups. Moreover, the incidence of complications was similar between groups (P = 0.698). Conclusions: Our findings suggest that the combined approach of chemotherapy and 125I brachytherapy yields superior therapeutic effects but similar complication rates compared to chemotherapy alone in patients experiencing local recurrence of CC following failed initial chemotherapy.

Milk fat globule membrane promotes brain development in piglets by enhancing the connection of white matter fiber trace.

Introduction: Brain development during infancy is crucial for later health and development. Although Milk Fat Globule Membrane (MFGM) has been demonstrated to enhance brain development, further investigation is needed to determine the optimal dose. Methods: In this study, 80 piglets aged 2 days were randomly assigned to four groups: Control group, MFGM-L (1.74 g MFGM per 100 g diet), MFGM-M (4.64 g MFGM per 100 g diet), and MFGM-H (6.09 g MFGM per 100 g diet). Daily body weight and milk intake of the piglets were recorded until 31 days postnatal. Learning and memory abilities were evaluated using the spatial T-maze test on day 15. MRI analysis was conducted to assess functional and structural changes in brain tissues. Additionally, mRNA and protein expression of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NTF-3) in the hippocampus and prefrontal cortex were evaluated. Results: The results indicated that the MFGM supplemented diet significantly improved the accuracy of the piglets in the T-maze test, with the MFGM-L group exhibiting the best performance. MRI showed no volumetric differences in the gray and white matter between the groups. However, the fractional anisotropy in the left and right hippocampus of piglets in the MFGM-L group was significantly higher than in the other three groups. Furthermore, there was a strong correlation between the accuracy of the T-maze test and hippocampal fractional anisotropy. Discussion: The MFGM supplemented diet also increased the expression of BDNF in the cerebral cortex. However, the changes in BDNF were not consistent with the results of the T-maze test. In conclusion, adding 1.74 g MFGM per 100 g diet can significantly improve neonatal piglets' learning and memory abilities, potentially by enhancing the connection of white matter fiber bundles in the brain.

The bioaccumulation and biotransformation of tetrabromobisphenol A bis (allyl ether) in common carp (Cyprinus carpio).

Tetrabromobisphenol A bis (allyl ether) (TBBPA-BAE) is an extensively used brominated flame retardant, which has raised considerable concern because of its neurotoxic and endocrine disruption effects on aquatic organisms. However, previous studies mainly focused on the parent compound before modification, tetrabromobisphenol A (TBBPA), and little information is available about the bioconcentration and biotransformation of TBBPA derivatives in fish. In this study, we investigated the tissue-specific uptake, elimination kinetic, and biotransformation of TBBPA-BAE in common carp (Cyprinus carpio). The fish were exposed to TBBPA-BAE at environmentally relevant concentrations (20 µg·L-1) for 28 days, followed by 14 days of depuration. The results showed TBBPA-BAE could rapidly accumulate in common carp. Among the seven tissues studied, the highest concentrations of TBBPA-BAE were observed in the liver (6.00 µg·g-1 wet weight [ww]) on day 24, while the longest residence time was observed in the kidney (t1/2 values of 18.7 days). Biotransformation of TBBPA-BAE was documented in the in vivo experiments, and 14 different phase I and phase II metabolites were identified in the liver. These findings suggest the biotransformation products of TBBPA-BAE should be considered for a comprehensive risk evaluation.

A Functional Stent Encapsulating Radionuclide in Temperature-Memory Spiral Tubes for Malignant Stenosis of Esophageal Cancer.

Stent implantation is a commonly used palliative treatment for alleviating stenosis in advanced esophageal cancer. However, tissue proliferation induced by stent implantation and continuous tumor growth can easily lead to restenosis. Therefore, functional stents are required to relieve stenosis while inhibiting tissue proliferation and tumor growth, thereby extending the patency. Currently, no ideal functional stents are available. Here, iodine-125 (125 I) nuclides are encapsulated into a nickel-titanium alloy (NiTi) tube to develop a novel temperature-memory spiral radionuclide stent (TSRS). It has the characteristics of temperature-memory, no cold regions at the end of the stent, and a uniform spatial dose distribution. Cell-viability experiments reveal that the TSRS can reduce the proliferation of fibroblasts and tumor cells. TSRS implantation is feasible and safe, has no significant systemic radiotoxicity, and can inhibit in-stent and edge stenosis caused by stent-induced tissue proliferation in healthy rabbits. Moreover, TSRS can improve malignant stenosis and luminal patency resulting from continuous tumor growth in a VX2 esophageal cancer model. As a functional stent, the TSRS combines the excellent properties of NiTi with brachytherapy of the 125 I nuclide and will make significant contributions to the treatment of malignant esophageal stenosis.

Combination of Walnut Peptide and Casein Peptide alleviates anxiety and improves memory in anxiety mices.

Introduction: Anxiety disorders continue to prevail as the most prevalent cluster of mental disorders following the COVID-19 pandemic, exhibiting substantial detrimental effects on individuals' overall well-being and functioning. Even after a search spanning over a decade for novel anxiolytic compounds, none have been approved, resulting in the current anxiolytic medications being effective only for a specific subset of patients. Consequently, researchers are investigating everyday nutrients as potential alternatives to conventional medicines. Our prior study analyzed the antianxiety and memory-enhancing properties of the combination of Walnut Peptide (WP) and Casein Peptide (CP) in zebrafish. Methods and Results: Based on this work, our current research further validates their effects in mice models exhibiting elevated anxiety levels through a combination of gavage oral administration. Our results demonstrated that at 170 + 300 mg human dose, the WP + CP combination significantly improved performances in relevant behavioral assessments related to anxiety and memory. Furthermore, our analysis revealed that the combination restores neurotransmitter dysfunction observed while monitoring Serotonin, gamma-aminobutyric acid (GABA), dopamine (DA), and acetylcholine (ACh) levels. This supplementation also elevated the expression of brain-derived neurotrophic factor mRNA, indicating protective effects against the neurological stresses of anxiety. Additionally, there were strong correlations among behavioral indicators, BDNF (brain-derived neurotrophic factor), and numerous neurotransmitters. Conclusion: Hence, our findings propose that the WP + CP combination holds promise as a treatment for anxiety disorder. Besides, supplementary applications are feasible when produced as powdered dietary supplements or added to common foods like powder, yogurt, or milk.

Establishment and Characterization of Patient-Derived Xenograft Models of Anaplastic Thyroid Carcinoma and Head and Neck Squamous Cell Carcinoma.

Patient-derived xenograft (PDX) models faithfully preserve the histological and genetic characteristics of the primary tumor and maintain its heterogeneity. Pharmacodynamic results based on PDX models are highly correlated with clinical practice. Anaplastic thyroid carcinoma (ATC) is the most malignant subtype of thyroid cancer, with strong invasiveness, poor prognosis, and limited treatment. Although the incidence rate of ATC accounts for only 2%-5% of thyroid cancer, its mortality rate is as high as 15%-50%. Head and neck squamous cell carcinoma (HNSCC) is one of the most common head and neck malignancies, with over 600,000 new cases worldwide each year. Herein, detailed protocols are presented to establish PDX models of ATC and HNSCC. In this work, the key factors influencing the success rate of model construction were analyzed, and the histopathological features were compared between the PDX model and the primary tumor. Furthermore, the clinical relevance of the model was validated by evaluating the in vivo therapeutic efficacy of representative clinically used drugs in the successfully constructed PDX models.

CT-guided 125I brachytherapy for hepatocellular carcinoma in high-risk locations after transarterial chemoembolization combined with microwave ablation: a propensity score-matched study.

BACKGROUND: This study aimed to evaluate the safety and efficacy of 125I brachytherapy combined with transarterial chemoembolization (TACE) and microwave ablation (MWA) for unresectable hepatocellular carcinoma (HCC) in high-risk locations. PATIENTS AND METHODS: After 1:2 propensity score matching (PSM), this retrospectively study analyzed 49 patients who underwent TACE +MWA+125I brachytherapy (group A) and 98 patients who only received TACE +MWA (group B). The evaluated outcomes were progression-free survival (PFS), overall survival (OS), and treatment complications. Cox proportional hazards regression analysis survival was used to compare the two groups. RESULTS: The patients in group A showed a longer PFS than group B (7.9 vs. 3.3 months, P = 0.007). No significant differences were observed in median OS between the two groups (P = 0.928). The objective response rate (ORR), disease control rate of tumors in high-risk locations, and the ORR of intrahepatic tumors were 67.3%, 93.9%, and 51.0%, respectively, in group A, and 38.8%, 79.6% and 29.6%, respectively, in group B (P < 0.001, P = 0.025 and P = 0.011, respectively). TACE-MWA-125I (HR = 0.479, P < 0.001) was a significant favorable prognostic factor that affected PFS. The present of portal vein tumor thrombosis was an independent prognostic factor for PFS (HR = 1.625, P = 0.040). The Barcelona clinic liver cancer (BCLC) stage (BCLC C vs. B) was an independent factor affecting OS (HR = 1.941, P = 0.038). The incidence of complications was similar between the two groups, except that the incidence of abdominal pain was reduced in the group A (P = 0.007). CONCLUSIONS: TACE-MWA-125I resulted in longer PFS and better tumor control than did TACE-MWA in patients with unresectable hepatocellular carcinoma in high-risk locations.

A new method for preparing a rat intracerebral hemorrhage model by combining focused ultrasound and microbubbles.

BACKGROUND: We aimed to prepare a non-invasive, reproducible, and controllable rat model of intracerebral hemorrhage with focused ultrasound (FUS). METHODS: A rat intracerebral hemorrhage (ICH) model was established by combining FUS and microbubbles (µBs), and edaravone was used to verify whether the free radical scavenger had a protective effect on the model. The brain tissue of each group was sectioned to observe the gross histology, blood-brain barrier (BBB) permeability, cerebral infarction volume, and histopathological changes. RESULTS: Compared with the FUS group, the BBB permeability was significantly increased in the FUS + µBs (F&B) group (p = 0.0021). The second coronal slice in the F&B group had an obvious hemorrhage lesion, and the FUS + µBs + edaravone (F&B&E) group had smaller hemorrhage areas; however, ICH did not occur in the FUS group. The cerebral infarction volume in the F&B group was significantly larger than that in the FUS group (p = 0.0030) and F&B&E group (p = 0.0208). HE staining results showed that nerve fibrinolysis, neuronal necrosis, microglia production, and erythrocytes were found in both the F&B group and the F&B&E group, but the areas of the nerve fibrinolysis and neuronal necrosis in the F&B group were larger than the F&B&E group. CONCLUSIONS: A rat ICH model was successfully prepared using the µBs assisted FUS treatment, and edaravone had a therapeutic effect on this model. This model can be used to study the pathophysiological mechanism of ICH-related diseases and in preclinical research on related new drugs.

Clinical efficacy of CT-guided 125I brachytherapy in patients with local residual or recurrent hepatocellular carcinoma after thermal ablation.

OBJECTIVES: Treatment methods of local residual or recurrent hepatocellular carcinoma (HCC) after thermal ablation are limited. Therefore, our study aimed to explore the efficacy and prognostic factors of 125I brachytherapy for local residual or recurrent lesion after thermal ablation. METHODS: A total of 114 patients with 212 local residual or recurrent HCC tumors after thermal ablation underwent 125I brachytherapy. Local progression-free survival (LPFS) and prognostic factors were analyzed by Kaplan-Meier curves and the Cox model. RESULTS: After a 6-month follow-up, the percentage of patients who achieved complete response (CR), partial response (PR), and stable disease (SD) was 57%, 13.2%, and 5.2%, respectively. The 1-, 2-, and 3-year LPFS rates were 58.7%, 50.0%, and 41.2%, respectively. Portal vein tumor thrombus (PVTT) (p = 0.03), the number of intrahepatic tumors (p = 0.01), and AFP level (p = 0.02) were independent risk factors for local tumor progression (LTP). The median LPFS in patients without PVTT (22 months) was much longer compared to those with PVTT (10 months). The median LPFS in patients with less than three intrahepatic lesions improved from 17 to 24 months. The median LPFS was only 5 months in the high AFP group, but was prolonged with a decrease in AFP level (24 months). No severe complications were recorded. All complications were controllable and treatable. CONCLUSIONS: CT-guided 125I brachytherapy was a safe and effective treatment for patients with local residual or recurrent HCC after thermal ablation to improve local control rate.

Retrograde venous coil embolization prior to transarterial chemoembolization in hepatocellular carcinoma with arterio-hepatic venous shunts.

PURPOSE This study explored the clinical efficacy of transcatheter retrograde shunt occlusion with coils to prevent pulmonary oil or particle embolization prior to transarterial chemoembolization (TACE) in patients with artero-hepatic venous shunts (AHVS) secondary to hepatocellular carcinoma (HCC). METHODS From July 2017 to January 2021, 6 patients with advanced, unresectable HCC were found to have an AHVS by hepatic arteriography at the time of attempted TACE. The AHVS was embolized ret rogradely with metal coils through a transfemoral or transjugular venous approach. After venous embolization and confirmation of the absence of the AHVS, TACE was performed using an emul sion of iodized oil and doxorubicin or drug-eluting beads. Follow-up computed tomography (CT) was performed within 1 month after the first TACE to evaluate the results and complications. RESULTS Hepatic angiography after venous embolization showed that AHVS had utterly disappeared in all patients during the operation. The immediate technical success of the retrograde venous embo lization was 100%. The AHVS had disappeared entirely during the follow-up period through triple-phase enhancement CT scanning. According to the modified response evaluation criteria in solid tumors, TACE in all 6 patients had a disease control response rate of 100% (6/6) with complete response in 2 patients and partial response in 4 patients. One patient died during the 6-month follow-up, and the other 5 were still alive. No complications related to pulmonary embolism occurred. CONCLUSION Retrograde venous coil embolization of AHVS via the draining hepatic vein appears to be a safe, feasible, and effective treatment to allow TACE treatment without pulmonary embolic events. This approach appears to provide better tumor control and effectively decreases the occurrence of pulmonary embolism.

Construction and Verification of a Novel Pyroptosis-Related lncRNA Signature Associated with Immune Landscape in Gliomas.

Gliomas are the most common tumor in the central nervous system with limited prognostic markers making it difficult to research progression. Induction of cellular immunogenic death is a promising treatment for glioma. Pyroptosis is one of the recently discovered programmed immuogenic cell death modes which remains unclear in glioma. We obtained glioma datasets from the CGGA and TCGA websites. Pearson correlation analysis was used to find pyroptosis-related lncRNAs. Subsequently, the univariate, LASSO, and multivariate Cox regression were applied to construct a prognostic signature based on pyroptosis-related lncRNAs. Kaplan-Meier plots, ROC curves, and PCA were utilized for testing the prognostic performance of the signature. We conducted the univariate and multivariate Cox regressions to ascertain if the signature worked as an independent factor for predicting overall survival (OS) for individuals with glioma from other characteristics. For evaluating the immune landscape differences between the subgroups, ESTIMATE, CIBERTSORT, and ssGSEA were adopted. Additionally, biological functions and pathways of DEGs were identified by KEGG and GO. We also screened potential drugs and measured sensitivities of chemotherapeutics between the subgroups by CellMiner and pRRophetic package. Finally, shRNA was conducted to knockdown of COX10-AS1 in U87 cells to determine its relationship with pyroptosis. We successfully created an effective pyroptosis-related lncRNA signature that divided individuals into groups of low- and high-risk, and individuals in the high-risk group were with poor prognosis in comparison to the individuals in the other group. A nomogram including clinical factors and risk scores to predict the OS was built. Furthermore, the two groups appeared to have different immune landscapes; the high-risk group showed greater levels of ESTIMATE scores, immune cell infiltration, and immune checkpoints. Additionally, immune-related pathways and functions were shown to be enriched according to KEGG and GO findings. Knockdown of COX10-AS1 inhibited U87 cell growth, upregulated CASP1 and NLRP3, and released more IL1-ß and IL-18 than the negative control. In summary, our study developed an lncRNA signature related to pyroptosis for OS prediction of gliomas and demonstrated its relationship with immune infiltration and drug sensitivity.

Synthesis of cyclodextrin derivatives for enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylate.

Photochemical methods are increasingly being used in organic synthesis. They are especially useful for preparing many compounds that are not readily accessible through thermal or enzymatic reactions. The supramolecular strategy has proved highly promising in recent years for manipulating the stereochemical outcome of chiral photoreactions through relatively strong and long-lasting noncovalent interactions in both ground and excited states. Among the numerous chiral photochemical reactions, photocyclodimerization of 2-anthracenecarboxylate (AC) is the most comprehensively studied supramolecular chiral photoreaction and has essentially become a benchmark reaction for evaluating supramolecular photochirogenesis. Cyclodextrin (CD) derivatives were the earliest and are the most widely applied chiral host for mediating photoreactions. Herein, we use CD-mediated photocyclodimerization of AC as an example to introduce the operation process of supramolecular chiral photoreactions. The protocol includes the following contents: (i) the preparation, purification and characterization of ß-CD derivatives; (ii) methods for investigating the host-guest inclusion behavior between AC and ß-CD derivatives; (iii) the photochemical reaction operation flow under different solvent and temperature conditions; (iv) chiral high-performance liquid chromatography (HPLC) analyses of the product distribution and enantioselectivity. The protocol is introduced by using representative examples of the synthesis of ß-CD derivatives and the manipulation of environmental factors that give excellent regio- and enantioselectivities in the photocyclodimerization of AC. The synthesis and purification of ß-CD derivatives require 3-5 d of work. The photoirradiation of AC with ß-CD derivatives can be done within 1 h. The product analysis requires 5 h.

Peritumoral abnormalities on dynamic-enhanced CT after brachytherapy for hepatic malignancies: local progression or benign changes?

OBJECTIVES: To determine if dynamic CT can differentiate local progression from radioactive seed-induced peritumoral reaction (RSIPR) after brachytherapy with iodine-125 radioactive seeds (BIRS) for advanced hepatic malignancies. METHODS: Enhanced CT images of seed-implanted lesions between 2006 and 2018 were retrospectively evaluated. Hounsfield units of peritumoral parenchyma were measured and assessed quantitatively. The classification, conversion, consequences, and serological indicators during follow-up were recorded and quantified. Statistical differences were analyzed using a Pearson χ2 test. RESULTS: RSIPR was observed in 201 of 290 (69.3%) lesions (161 patients; median age, 55 years; range, 26-79 years), while local progression occurred in 53 lesions. The low density of local progression was much lower than that of RSIPR (p < 0.001), and the former did not exhibit iso-/high density in the portal or equilibrium phase. Ring-like enhancement in progressive lesions was also quite different from RSIPR. Local progression rate was lower for lesions with RSIPR than for those without RSIPR (14.9% vs 25.8%; p = 0.03), and their doses were different (397.2 Gy vs 120.3 Gy, p < 0.001). CONCLUSIONS: Radioactive seed-induced peritumoral reaction has characteristic manifestations on CT images, which is associated with a higher dose of lesions and lower local progression rate. Notably, the enhancement pattern of local progression was distinct from RSIPR and was clearly distinguishable on dynamic-enhanced CT. KEY POINTS: • Radioactive seed-induced peritumoral reaction after brachytherapy with 125I seeds for liver malignancies has characteristic manifestations on CT images, which is associated with a higher dose of lesions (397.2 Gy vs 120.3 Gy, p < 0.001), as a focal radiation injury. • Lesions with RSIPR were less likely to develop local progression, while those without RSIPR had a higher rate of local progression (14.9% vs 25.8%; p = 0.03). • The enhancement pattern of local progression after brachytherapy was distinct from radioactive seed-induced peritumoral reaction and was clearly distinguishable on dynamic-enhanced CT.

Human umbilical cord mesenchymal stem cell-derived exosomal miR-335-5p attenuates the inflammation and tubular epithelial-myofibroblast transdifferentiation of renal tubular epithelial cells by reducing ADAM19 protein levels.

BACKGROUND: Renal tubular epithelial-myofibroblast transdifferentiation (EMT) plays a key role in the regulation of renal fibrosis. Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) play a crucial role in alleviating renal fibrosis and injury. Additionally, hucMSC-derived exosomes contain numerous microRNAs (miRNAs). However, it is unclear whether mesenchymal stem cells can regulate the transforming growth factor (TGF)-ß1-induced EMT of human renal tubular epithelial cells (RTECs) through exosomal miRNAs. METHOD: HK-2, a human RTEC line, was co-treated with TGF-ß1 and hucMSC-derived exosomes. Additionally, TGF-ß1-treated HK-2 cells were transfected with a miR-335-5p mimic and disintegrin and metalloproteinase domain-containing protein 19 (ADAM19)-overexpression plasmid. miR-335-5p expression and ADAM19 protein and inflammation levels were measured via quantitative reverse transcription polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assays, respectively. RESULTS: TGF-ß1 treatment changed the shape of HK-2 cells from a cobblestone morphology to a long spindle shape, accompanied by an increase in interleukin (IL)-6, tumor necrosis factor-α, IL-1ß, collagen I, collagen III, α-smooth muscle actin, vimentin, and N-cadherin protein levels, whereas E-cadherin protein levels were reduced in these HK-2 cells, suggesting that TGF-ß1 treatment induced the inflammation and EMT of HK-2 cells. HucMSC-exosomes improved the inflammation and EMT phenotype of TGF-ß1-induced HK-2 cells by transferring miR-335-5p. miR-335-5p was found to bind the ADAM19 3'-untranslated region to reduce ADAM19 protein levels. Additionally, miR-335-5p improved the inflammation and EMT phenotype of HK-2 cells by reducing ADAM19 protein levels with TGF-ß1 induction. CONCLUSIONS: HucMSC-derived exosomal miR-335-5p attenuates the inflammation and EMT of HK-2 cells by reducing ADAM19 protein levels upon TGF-ß1 induction. This study provides a potential therapeutic strategy and identifies targets for clinically treating renal fibrosis.