Pediatric diffuse intrinsic pontine glioma radiotherapy response prediction: MRI morphology and T2 intensity-based quantitative analyses.

OBJECTIVES: An easy-to-implement MRI model for predicting partial response (PR) postradiotherapy for diffuse intrinsic pontine glioma (DIPG) is lacking. Utilizing quantitative T2 signal intensity and introducing a visual evaluation method based on T2 signal intensity heterogeneity, and compared MRI radiomic models for predicting radiotherapy response in pediatric patients with DIPG. METHODS: We retrospectively included patients with brainstem gliomas aged ≤ 18 years admitted between July 2011 and March 2023. Applying Response Assessment in Pediatric Neuro-Oncology criteria, we categorized patients into PR and non-PR groups. For qualitative analysis, tumor heterogeneity vision was classified into four grades based on T2-weighted images. Quantitative analysis included the relative T2 signal intensity ratio (rT2SR), extra pons volume ratio, and tumor ring-enhancement volume. Radiomic features were extracted from T2-weighted and T1-enhanced images of volumes of interest. Univariate analysis was used to identify independent variables related to PR. Multivariate logistic regression was performed using significant variables (p < 0.05) from univariate analysis. RESULTS: Of 140 patients (training n = 109, and test n = 31), 64 (45.7%) achieved PR. The AUC of the predictive model with extrapontine volume ratio, rT2SRmax-min (rT2SRdif), and grade was 0.89. The AUCs of the T2-weighted and T1WI-enhanced models with radiomic signatures were 0.84 and 0.81, respectively. For the 31 DIPG test sets, the AUCs were 0.91, 0.83, and 0.81, for the models incorporating the quantitative features, radiomic model (T2-weighted images, and T1W1-enhanced images), respectively. CONCLUSION: Combining T2-weighted quantification with qualitative and extrapontine volume ratios reliably predicted pediatric DIPG radiotherapy response. CLINICAL RELEVANCE STATEMENT: Combining T2-weighted quantification with qualitative and extrapontine volume ratios can accurately predict diffuse intrinsic pontine glioma (DIPG) radiotherapy response, which may facilitate personalized treatment and prognostic assessment for patients with DIPG. KEY POINTS: Early identification is crucial for radiotherapy response and risk stratification in diffuse intrinsic pontine glioma. The model using tumor heterogeneity and quantitative T2 signal metrics achieved an AUC of 0.91. Using a combination of parameters can effectively predict radiotherapy response in this population.

Insights into the discovery and intervention of metalloproteinase in marine hazardous jellyfish.

The proliferation of toxic organisms caused by changes in the marine environment, coupled with the rising human activities along the coastal lines, has resulted in an increasing number of stinging incidents, posing a serious threat to public health. Here, we evaluated the systemic toxicity of the venom in jellyfish Chrysaora quinquecirrha at both cellular and animal levels, and found that jellyfish tentacle extract (TE) has strong lethality accompanied by abnormal elevation of blood biochemical indicators and pathological changes. Joint analysis of transcriptome and proteome indicated that metalloproteinases are the predominant toxins in jellyfish. Specially, two key metalloproteinases DN6695_c0_g3 and DN8184_c0_g7 were identified by mass spectrometry of the red blood cell membrane and tetracycline hydrochloride (Tch) inhibition models. Structurally, molecular docking and kinetic analysis are employed and observed that Tch could inhibit the enzyme activity by binding to the hydrophobic pocket of the catalytic center. In this study, we demonstrated that Tch impedes the metalloproteinase activity thereby reducing the lethal effect of jellyfish, which suggests a potential strategy for combating the health threat of marine toxic jellyfish.

Development and validation of a nomogram to predict leptomeningeal metastases in lung adenocarcinoma: Cervical lymph node metastasis is an important association factor.

BACKGROUND: The goal of this study was to create a nomogram using routine parameters to predict leptomeningeal metastases (LMs) in advanced lung adenocarcinoma (LAC) patients to prevent needless exams or lumbar punctures and to assist in accurately diagnosing LMs. METHODS: Two hundred and seventy-three patients with LMs and brain metastases were retrospectively reviewed and divided into derivation (n = 191) and validation (n = 82) cohorts using a 3:7 random allocation. All LAC patients with LMs had positive cerebrospinal fluid cytology results and brain metastases confirmed by magnetic resonance imaging. Binary logistic regression with backward stepwise selection was used to identify significant characteristics. A predictive nomogram based on the logistic model was assessed through receiver operating characteristic curves. The validation cohort and Hosmer-Lemeshow test were used for internal validation of the nomogram. RESULTS: Five clinicopathological parameters, namely, gene mutations, surgery at the primary lung cancer site, clinical symptoms of the head, N stage, and therapeutic strategy, were used as predictors of LMs. The area under the curve was 0.946 (95% CI 0.912-0.979) for the training cohort and 0.861 (95% CI 0.761-0.961) for the internal validation cohort. There was no significant difference in performance between the two cohorts (p = 0.116). In the internal validation, calibration plots revealed that the nomogram predictions were well suited to the actual outcomes. CONCLUSIONS: We created a user-friendly nomogram to predict LMs in advanced lung cancer patients, which could help guide treatment decisions and reduce unnecessary lumbar punctures.

Comparison of the structure-function of five newly members of the calcin family.

Calcins are a group of scorpion toxin peptides specifically binding to ryanodine receptors (RyRs) with high affinity, and have the ability to activate and stabilize RyR in a long-lasting subconductance state. Five newly calcins synthesized compounds exhibit typical structural characteristics of a specific family through chemical synthesis and virtual analysis. As the calcins from the same species, Petersiicalcin1 and Petersiicalcin2, Jendekicalcin2 and Jendekicalcin3, have only one residue difference. Both Petersiicalcin1 and Petersiicalcin2 exhibited different affinities in stimulating [3H]ryanodine binding, but the residue mutation resulted in a 2.7 folds difference. Other calcins also exhibited a stimulatory effect on [3H]ryanodine binding to RyR1, however, their affinities were significantly lower than that of Petersiiicalcin1 and Petersiiicalcin2. The channel domain of RyR1 was found to be capable of binding with the basic residues of these calcins, which also exhibited interactions with the S6 helices on RyR1. Dynamic simulations were conducted for Petersiicalcin1 and Petersiicalcin2, which demonstrated their ability to form a highly stable conformation and resulting in an asymmetric tetramer structure of RyR1. The discovery of five newly calcins further enriches the diversity of the natural calcin family, which provides more native peptides for the structure-function analysis between calcin and RyRs.

The Effect of Acidic Residues on the Binding between Opicalcin1 and Ryanodine Receptor from the Structure-Functional Analysis.

Calcin is a group ligand with high affinity and specificity for the ryanodine receptors (RyRs). Little is known about the effect of its acidic residues on the spacial structure as well as the interaction with RyRs. We screened the opicalcin1 acidic mutants and investigated the effect of mutation on activity. The results indicated that all acidic mutants maintained the structural features, but their surface charge distribution underwent significant changes. Molecular docking and dynamics simulations were used to analyze the interaction between opicalcin1 mutants and RyRs, which demonstrated that all opicalcin1 mutants effectively bound to the channel domain of RyR1. This stable binding induced a pronounced asymmetry in the structure of the RyR tetramer, exhibiting a high degree of structural dissimilarity. [3H]Ryanodine binding to RyR1 was enhanced in D2A and D15A, which was similar to opicalcin1, but that effect was suppressed in E12A and E29A and reversed for the DE-4A, thereby inhibiting ryanodine binding. Opicalcin1 and DE-4A also exhibited the ability to form stable docking structures with RyR2. Acidic residues play a crucial role in the structure of calcin and its functional interaction with RyRs that is beneficial for the calcin optimization to develop more active peptide lead compounds for RyR-related diseases.