Effectiveness of the six-step approach guided online training program to improve knowledge of Mycoplasma pneumoniae pneumonia among pediatricians: a pretest-posttest study.

Background: In 2023, China witnessed an earlier and more widespread outbreak of Mycoplasma pneumoniae pneumonia (MPP). To address this situation, an online training program was designed to enhance the knowledge of MPP among pediatricians in Shanghai, China. Methods: An online training program on the diagnosis and treatment of MPP, guided by Kern's six-step approach, was developed by the Shanghai Pediatric Clinical Quality Control Center. A pre- and post-training survey was conducted using a 20-item self-administered questionnaire to investigate the pediatricians' knowledge of MPP. A linkage mechanism was established to match pretest/posttest questionnaires using personal identifiers. Paired t-tests and McNemar tests were performed to measure the differences, as appropriate, between pre- and post-training groups. A higher survey score indicated better knowledge. Results: There were 289 participants performed pre- and post-tests. The average age of the respondents was 38.7 years (standard deviation: 8.9). Over 80% of the participants were primary (32.5%) and intermediate (47.8%) pediatricians. Those from specialized hospitals accounted for the highest proportion (41.5%). The post-training group achieved significantly higher total scores than the pre-training group (91.3 vs. 67.7, t=22.48, P<0.001), regardless of the professional titles or hospital levels (all P<0.001). The accuracy rates of each question increased significantly in the post-training group (all P<0.001). Conclusions: The online training program effectively enhanced pediatricians' understanding of diagnosing and treating MPP. It is recommended to maintain continuous education and training targeting all healthcare providers.

Advances in gross tumor target volume determination in radiotherapy for patients with hepatocellular carcinoma.

Hepatocellular Carcinoma (HCC) is one of the most common malignant neoplasms. With the advancement of technology, the precision of radiotherapy (RT) for HCC has considerably increased, and it is an indispensable modality in the comprehensive management of HCC. Some RT techniques increase the radiation dose to HCC, which decreases the radiation dose delivered to the surrounding normal liver tissue. This approach significantly improves the efficacy of HCC treatment and reduces the incidence of Radiation-induced Liver Disease (RILD). Clear imaging and precise determination of the Gross Target Volume (GTV) are prerequisites of precise RT of HCC. The main hindrances in determining the HCC GTV include indistinct tumor boundaries on imaging and the impact on respiratory motion. The integration of multimodal imaging, four-dimensional imaging, and artificial intelligence (AI) techniques can help overcome challenges for HCC GTV. In this article, the advancements in medical imaging and precise determination for HCC GTV have been reviewed, providing a framework for the precise RT of HCC.

The correlation between selenium intake and lung function in asthmatic people: a cross-sectional study.

Objective: This study aimed to examine the correlation between selenium intake and lung function in asthmatic people. Methods: A total of 4,541 individuals in the US National Health and Nutrition Examination Survey (NHANES) were included in this study. Multivariate linear regression, variance inflation factor, restricted cubic splines and quantile regression were used to analyze the relationship between Se intake and lung function. We divided selenium intake into four levels based on quartiles: Q1: Se ≤ 76.75 mcg/d; Q2: 76.75-105.1 mcg/d; Q3: 105.1-137.65 mcg/d; and Q4: Se ≥137.65 mcg/d. Results: Asthma was negatively associated with the Ratio of Forced Expiratory Volume 1st Second to Forced Vital Capacity (FEV1/FVC) (ß = -0.04, 95% CI: -0.06 to -0.02) and FEV1 (ß = -215, 95% CI: -340 to -90). Se intake was positively associated with Forced Expiratory Volume 1st Second (FEV1) (ß =3.30 95% CI: 2.60 to 4.00) and Forced Vital Capacity (FVC) (ß =4.30, 95% CI: 3.50 to 5.10). In asthmatic individuals, the positive effects of Se intake on FVC were enhanced with increasing Se intake, while the positive effects of Se intake on FEV1 varied less dramatically. High Se intake (Q4 level, above 137.65 mcg/d) improved FVC (ß = 353, 95% CI: 80 to 626) and FEV1 (ß = 543, 95% CI: 118 to 969) in asthmatic patients compared to low Se intake (Q1 level, below 76.75 mcg/d). At the Q2 level (76.75-105.1 mcg/d) and Q4 level (Se ≥137.65 mcg/d) of Se intake, the correlation between FEV1 and asthma disappeared. Conclusion: Our research has revealed a positive correlation between selenium intake and lung function in asthma patients and the strength of this positive correlation is related to the amount of selenium intake. We recommend that asthma patients consume 137.65 mcg to 200 mcg of selenium daily to improve pulmonary function while avoiding the adverse effects of selenium on the human body.

Nano-enzyme hydrogels for cartilage repair effectiveness based on ternary strategy therapy.

Designing artificial nano-enzymes for scavenging reactive oxygen species (ROS) in chondrocytes (CHOs) is considered the most feasible pathway for the treatment of osteoarthritis (OA). However, the accumulation of ROS due to the amount of nano-enzymatic catalytic site exposure and insufficient oxygen supply seriously threatens the clinical application of this therapy. Although metal-organic framework (MOF) immobilization of artificial nano-enzymes to enhance active site exposure has been extensively studied, artificial nano-enzymes/MOFs for ROS scavenging in OA treatment are still lacking. In this study, a biocompatible lubricating hydrogel-loaded iron-doped zeolitic imidazolate framework-8 (Fe/ZIF-8/Gel) centrase was engineered to scavenge endogenous overexpressed ROS synergistically generating dissolved oxygen and enhancing sustained lubrication for CHOs as a ternary artificial nano-enzyme. This property enabled the nano-enzymatic hydrogels to mitigate OA hypoxia and inhibit oxidative stress damage successfully. Ternary strategy-based therapies show excellent cartilage repair in vivo. The experimental results suggest that nano-enzyme-enhanced lubricating hydrogels are a potentially effective OA treatment and a novel strategy.

Revealing core functional microorganisms in the fermentation process of Qicaipaojiao (Capsicum annuum L.) based on microbial metabolic network.

Paojiao, a typical Chinese traditional fermented pepper, is favored by consumers for its unique flavor profile. Microorganisms, organic acids, amino acids, and volatile compounds are the primary constituents influencing the development of paojiao's flavor. To elucidate the key flavor compounds and core microorganisms of Qicaipaojiao (QCJ), this study conducted a comprehensive analysis of the changes in taste substances (organic acids and amino acids) and volatile flavor compounds during QCJ fermentation. Key flavor substances in QCJ were identified using threshold aroma value and odor activity value and the core microorganisms of QCJ were determined based on the correlation between dominant microorganisms and the key flavor substances. During QCJ fermentation, 16 key taste substances (12 free amino acids and 4 organic acids) and 12 key aroma substances were identified. The fermentation process involved 10 bacteria and 7 fungal genera, including Lactiplantibacillus, Leuconostoc, Klebsiella, Pichia, Wickerhamomyces, and Candida. Correlation analysis revealed that the core functional microorganisms encompassed representatives from 8 genera, including 5 bacterial genera (Lactiplantibacillus, Weissella, Leuconostoc, Klebsiella, and Kluyvera) and 3 fungal genera (Rhodotorula, Phallus, and Pichia). These core functional microorganisms exhibited significant correlations with approximately 70 % of the key flavor substances (P < 0.05). This study contributes to an enhanced understanding of flavor formation mechanisms and offers valuable insight into flavor quality control in food fermentation processes.

Impact of different respiratory gating methods on target delineation and a radiotherapy plan for solitary pulmonary tumors.

BACKGROUND AND PURPOSE: Respiratory movement has an important impact on the radiotherapy for lung tumor. Respiratory gating technology is helpful to improve the accuracy of target delineation. This study investigated the value of prospective and retrospective respiratory gating simulations in target delineation and radiotherapy plan design for solitary pulmonary tumors (SPTs) in radiotherapy. METHODS: The enrolled patients underwent CT simulation with three-dimensional (3D) CT non gating, prospective respiratory gating, and retrospective respiratory gating simulation. The target volumes were delineated on three sets of CT images, and radiotherapy plans were prepared accordingly. Tumor displacements and movement information obtained using the two respiratory gating approaches, as well as the target volumes and dosimetry parameters in the radiotherapy plan were compared. RESULTS: No significant difference was observed in tumor displacement measured using the two gating methods (p > 0.05). However, the internal gross tumor volumes (IGTVs), internal target volumes (ITVs), and planning target volumes (PTVs) based on the retrospective respiratory gating simulation were larger than those obtained using prospective gating (group A: pIGTV = 0.041, pITV = 0.003, pPTV = 0.008; group B: pIGTV = 0.025, pITV = 0.039, pPTV = 0.004). The two-gating PTVs were both smaller than those delineated on 3D non gating images (p < 0.001). V5Gy, V10Gy, V20Gy, V30Gy, and mean lung dose in the two gated radiotherapy plans were lower than those in the 3D non gating plan (p < 0.001); however, no significant difference was observed between the two gating plans (p > 0.05). CONCLUSIONS: The application of respiratory gating could reduce the target volume and the radiation dose that the normal lung tissue received. Compared to prospective respiratory gating, the retrospective gating provides more information about tumor movement in PTV.

The effect of time-delayed contrast-enhanced scanning in determining the gross tumor target volume of large-volume brain metastases.

BACKGROUND AND PURPOSE: To assess the variation of large-volume brain metastases (BMs) boundaries and shapes using enhanced magnetic resonance (MR) scanning with different delay times and to provide a basis for determining the gross tumor target volume (GTV) for radiotherapy of BMs. MATERIALS AND METHODS: We prospectively enrolled 155 patients initially diagnosed with BMs (561 lesions > 1 cm). Contrast-enhanced (CE) T1-weighted imaging scans were performed 1, 3, 5, 10, 18, and 20 min after gadolinium-based contrast agent injection and GTVs were determined as GTV-1min, GTV-3min, GTV-5min, GTV-10min, GTV-18min, and GTV-20min, respectively, which were subsequently fused in different phases. Fusion of the six GTVs was defined as GTV-total, which was set as the reference GTV. The volume, shape, and signal intensity of the GTVs and brain white matter (BWM) were compared at different delay times. RESULTS: GTV-3min, GTV-5min, GTV-10min, GTV-18min, and GTV-20min volumes increased by 2.2 %, 3.8 %, 6.5 %, 9.5 %, and 10.6 %, respectively (P < 0.05) compared with GTV-1min. Compared with GTV-total, GTV-1min, GTV-3min, GTV-5min, GTV-10min, GTV-18min, and GTV-20min volumes reduced by 25.4 %, 22.1 %, 18.7 %, 15.0 %, 11.2 %, and 10.3 %, respectively (P < 0.05). Compared with GTV-total, 29 (51.8 %) fused GTVs had a volume reduction rate < 5 %, 45 (80.4 %) had a Dice similarity coefficient > 0.95, and all contained GTV-10min, GTV-18min or GTV-20min. The signal intensity ratio between the GTV and BWM peaked at 5 min (0.351 ± 0.24). CONCLUSION: Enhanced MR scans with different delay times show significant differences in the boundaries and shapes of large-volume BMs, and time-delayed multi-phase CE scanning should be used in GTV determination, with time phases ≥ 10 min being mandatory.

Advances in determining the gross tumor target volume for radiotherapy of brain metastases.

Brain metastases (BMs) are the most prevalent intracranial malignant tumors in adults and are the leading cause of mortality attributed to malignant brain diseases. Radiotherapy (RT) plays a critical role in the treatment of BMs, with local RT techniques such as stereotactic radiosurgery (SRS)/stereotactic body radiotherapy (SBRT) showing remarkable therapeutic effectiveness. The precise determination of gross tumor target volume (GTV) is crucial for ensuring the effectiveness of SRS/SBRT. Multimodal imaging techniques such as CT, MRI, and PET are extensively used for the diagnosis of BMs and GTV determination. With the development of functional imaging and artificial intelligence (AI) technology, there are more innovative ways to determine GTV for BMs, which significantly improve the accuracy and efficiency of the determination. This article provides an overview of the progress in GTV determination for RT in BMs.

Machine learning for differentiating lung squamous cell cancer from adenocarcinoma using Clinical-Metabolic characteristics and 18F-FDG PET/CT radiomics.

Noninvasive differentiation between the squamous cell carcinoma (SCC) and adenocarcinoma (ADC) subtypes of non-small cell lung cancer (NSCLC) could benefit patients who are unsuitable for invasive diagnostic procedures. Therefore, this study evaluates the predictive performance of a PET/CT-based radiomics model. It aims to distinguish between the histological subtypes of lung adenocarcinoma and squamous cell carcinoma, employing four different machine learning techniques. A total of 255 Non-Small Cell Lung Cancer (NSCLC) patients were retrospectively analyzed and randomly divided into the training (n = 177) and validation (n = 78) sets, respectively. Radiomics features were extracted, and the Least Absolute Shrinkage and Selection Operator (LASSO) method was employed for feature selection. Subsequently, models were constructed using four distinct machine learning techniques, with the top-performing algorithm determined by evaluating metrics such as accuracy, sensitivity, specificity, and the area under the curve (AUC). The efficacy of the various models was appraised and compared using the DeLong test. A nomogram was developed based on the model with the best predictive efficiency and clinical utility, and it was validated using calibration curves. Results indicated that the logistic regression classifier had better predictive power in the validation cohort of the radiomic model. The combined model (AUC 0.870) exhibited superior predictive power compared to the clinical model (AUC 0.848) and the radiomics model (AUC 0.774). In this study, we discovered that the combined model, refined by the logistic regression classifier, exhibited the most effective performance in classifying the histological subtypes of NSCLC.

Simplified S1 vertebral bone quality score independently predicts proximal junctional kyphosis after surgery for degenerative lumbar scoliosis.

OBJECTIVE: Our study aimed to assess the effectiveness of the simplified S1 vertebral bone quality (VBQ) score in predicting the incidence of proximal junctional kyphosis (PJK) after surgery for degenerative lumbar scoliosis (DLS). METHODS: We reviewed 122 patients with DLS who underwent posterior lumbar decompression and long-segment fusion surgery in our hospital from January 2016 to December 2020. The patients were classified into PJK group and non-PJK group. S1 VBQ scores are determined by signal intensity measurements taken from the mid-sagittal plane of T1-weighted non-contrast MRI. Logistic regression analysis was used to identify factors associated with PJK. Receiver-operating characteristic curve (ROC) analysis was used to evaluate the value of S1 VBQ score in predicting pedicle PJK after DLS. RESULTS: 122 DLS patients (90 females and 32 males) met the inclusion criteria. In addition, 27 patients (22.13%) had PJK at the time of last follow-up. VBQ was higher in PJK patients than non-PJK patients (3.58 ± 0.67 vs. 3.08 ± 0.54, p < 0.001). Preoperatively, patients in the PJK group had a greater TLK than those in the non-PJK group (20.00 ± 6.22 vs. 16.86 ± 5.38, p = 0.011). After surgery, patients in the PJK group had greater TLK (p < 0.001) and PJA (p < 0.001) compared with the non-PJK group. At final FU, patients in the PJK group had greater TK (p = 0.002), TLK (p < 0.001), SVA (p < 0.001), and PJA (p < 0.001) than patients in the non-PJK group (Table 4). In multivariate logistic regression analysis, higher VBQ score (OR 4.565, 95% CI 1.43-14.568, p = 0.010), advanced age (OR 1.119, 95% CI 1.021-1.227, p = 0.016), and larger TLK (OR 1.191, 95% CI 1.041-1.362, p = 0.011) were significant predictors of postoperative PJK in patients with DLS (Table 6). A statistically significant positive correlation existed between VBQ score and PJA change (r = 0.370, p < 0.001). We created ROC curves for VBQ scores as predictors of PJK with a diagnostic accuracy of 72.1% (95% CI 60.15-82.9%.The ideal limit for the VBQ score was 3.205 (sensitivity: 77.8%, specificity: 81.4%). CONCLUSION: To the best of our knowledge, this is the first study to evaluate the effectiveness of the S1 VBQ score in predicting postoperative PJK in DLS. Our study included major risk factors and found that S1 VBQ score was a significant predictor of PJK in patients undergoing DLS surgery. The higher the S1 VBQ score, the higher the probability of PJK.

Challenges in the treatment of pediatric Mycoplasma pneumoniae pneumonia.

Mycoplasma pneumoniae (MP) is an important cause of community-acquired pneumonia in children and young adolescents. Despite macrolide antibiotics effectiveness as a first-line therapy, persistence of fever and/or clinical deterioration sometimes may complicate treatment and may even lead to severe systemic disease. To date, there is no consensus on alternative treatment options, optimal dosage, and duration for treating severe, progressive, and systemic MP pneumonia after macrolide treatment failure. Macrolide-resistant MP pneumonia and refractory MP pneumonia are the two major complex conditions that are clinically encountered. Currently, the vast majority of MP isolates are resistant to macrolides in East Asia, especially China, whereas in Europe and North America, whereas in Europe and North America prevalence is substantially lower than in Asia, varying across countries. The severity of pneumonia and extrapulmonary presentations may reflect the intensity of the host's immune reaction or the dissemination of bacterial infection. Children infected with macrolide-resistant MP strains who receive macrolide treatment experience persistent fever with extended antibiotic therapy and minimal decrease in MP-DNA load. Alternative second-line agents such as tetracyclines (doxycycline or minocycline) and fluoroquinolones (ciprofloxacin or levofloxacin) may lead to clinical improvement after macrolide treatment failure in children. Refractory MP pneumonia reflects a deterioration of clinical and radiological findings due to excessive immune response against the infection. Immunomodulators such as corticosteroids and intravenous immunoglobulin (IVIG) have shown promising results in treatment of refractory MP pneumonia, particularly when combined with appropriate antimicrobials. Corticosteroid-resistant hyperinflammatory MP pneumonia represents a persistent or recrudescent fever despite corticosteroid therapy with intravenous methylprednisolone at standard dosage. CONCLUSION:  This report summarizes the clinical significance of macrolide-resistant and refractory MP pneumonia and discusses the efficacy and safety of alternative drugs, with a stepwise approach to the management of MP pneumonia recommended from the viewpoint of clinical practice. WHAT IS KNOWN: • Although MP pneumonia is usually a benign self-limited infection with response macrolides as first line therapy, severe life-threatening cases may develop if additional treatment strategies are not effectively implemented. • Macrolide-resistant and refractory MP pneumonia are two conditions that may complicate the clinical course of MP pneumonia, increasing the risk for exacerbation and even death. WHAT IS NEW: • This report summarizes the clinical relevance of macrolide-resistant and refractory MP pneumonia and discusses the efficacy and safety of alternative drug therapies. • A practical stepwise approach to the management of MP pneumonia is developed based on a comprehensive analysis of existing evidence and expert opinion.

Plasma-assisted manipulation of vanadia nanoclusters for efficient selective catalytic reduction of NOx.

Supported nanoclusters (SNCs) with distinct geometric and electronic structures have garnered significant attention in the field of heterogeneous catalysis. However, their directed synthesis remains a challenge due to limited efficient approaches. This study presents a plasma-assisted treatment strategy to achieve supported metal oxide nanoclusters from a rapid transformation of monomeric dispersed metal oxides. As a case study, oligomeric vanadia-dominated surface sites were derived from the classic supported V2O5-WO3/TiO2 (VWT) catalyst and showed nearly an order of magnitude increase in turnover frequency (TOF) value via an H2-plasma treatment for selective catalytic reduction of NO with NH3. Such oligomeric surface VOx sites were not only successfully observed and firstly distinguished from WOx and TiO2 by advanced electron microscopy, but also facilitated the generation of surface amide and nitrates intermediates that enable barrier-less steps in the SCR reaction as observed by modulation excitation spectroscopy technologies and predicted DFT calculations.

Pretreatment multiparametric MRI radiomics-integrated clinical hematological biomarkers can predict early rapid metastasis in patients with nasopharyngeal carcinoma.

BACKGROUND: To establish and validate a predictive model combining pretreatment multiparametric MRI-based radiomic signatures and clinical characteristics for the risk evaluation of early rapid metastasis in nasopharyngeal carcinoma (NPC) patients. METHODS: The cutoff time was used to randomly assign 219 consecutive patients who underwent chemoradiation treatment to the training group (n = 154) or the validation group (n = 65). Pretreatment multiparametric magnetic resonance (MR) images of individuals with NPC were employed to extract 428 radiomic features. LASSO regression analysis was used to select radiomic features related to early rapid metastasis and develop the Rad-score. Blood indicators were collected within 1 week of pretreatment. To identify independent risk variables for early rapid metastasis, univariate and multivariate logistic regression analyses were employed. Finally, multivariate logistic regression analysis was applied to construct a radiomics and clinical prediction nomogram that integrated radiomic features and clinical and blood inflammatory predictors. RESULTS: The NLR, T classification and N classification were found to be independent risk indicators for early rapid metastasis by multivariate logistic regression analysis. Twelve features associated with early rapid metastasis were selected by LASSO regression analysis, and the Rad-score was calculated. The AUC of the Rad-score was 0.773. Finally, we constructed and validated a prediction model in combination with the NLR, T classification, N classification and Rad-score. The area under the curve (AUC) was 0.936 (95% confidence interval (95% CI): 0.901-0.971), and in the validation cohort, the AUC was 0.796 (95% CI: 0.686-0.905). CONCLUSIONS: A predictive model that integrates the NLR, T classification, N classification and MR-based radiomics for distinguishing early rapid metastasis may serve as a clinical risk stratification tool for effectively guiding individual management.

Design and biological evaluation of dual tubulin/HDAC inhibitors based on millepachine for treatment of prostate cancer.

In this work, a novel of dual tubulin/HDAC inhibitors were designed and synthesized based on the structure of natural product millepachine, which has been identified as a tubulin polymerization inhibitor. Biological evaluation revealed that compound 9n exhibited an impressive potency against PC-3 cells with the IC50 value of 16 nM and effectively inhibited both microtubule polymerization and HDAC activity. Furthermore, compound 9n not only induced cell cycle arrest at G2/M phase, but also induced PC- 3 cells apoptosis. Further study revealed that the induction of cell apoptosis by 9n was accompanied by a decrease in mitochondrial membrane potential and an elevation in reactive oxygen species levels in PC-3 cells. Additionally, 9n exhibited inhibitory effects on tumor cell migration and angiogenesis. In PC-3 xenograft model, 9n achieved a remarkable tumor inhibition rate of 90.07%@20 mg/kg, significantly surpassing to that of CA-4 (55.62%@20 mg/kg). Meanwhile, 9n exhibited the favorable drug metabolism characteristics in vivo. All the results indicate that 9n is a promising dual tubulin/HDAC inhibitor for chemotherapy of prostate cancer, deserving the further investigation.

Treadmill training impacts the skeletal muscle molecular clock after ischemia stroke in rats.

Objective: Stroke is frequently associated with muscle mass loss. Treadmill training is considered the most effective treatment for sarcopenia. Circadian rhythms are closely related to exercise and have been extensively studied. The skeletal muscle has its molecular clock genes. Exercise may regulate skeletal muscle clock genes. This study evaluated the effects of early treadmill training on the skeletal muscle molecular clock machinery in rats with stroke and determined the relationship of these changes with exercise-induced improvements in skeletal muscle health. Materials and methods: Overall, 168 Sprague-Dawley rats were included in this study. We established an ischemic stroke rat model of sarcopenia. Finally, 144 rats were randomly allocated to four groups (36 per group): normal, sham, middle cerebral artery occlusion, and training. Neurological scores, rotating rod test, body weight, muscle circumference, wet weight, and hematoxylin-eosin staining were assessed. Twenty-four rats were used for transcriptome sequencing. Gene and protein expressions of skeletal muscles, such as brain muscle arnt-like 1, period 1, and period 2, were measured by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assays. Results: Neurological function scores and rotating rod test results improved after treadmill training. Nine differentially expressed genes were identified by comparing the sham group with the hemiplegic side of the model group. Seventeen differentially expressed genes were identified between the hemiplegic and non-hemiplegic sides. BMAL1, PER1, and PER2 mRNA levels increased on both sides after treadmill training. BMAL1 expression increased, and PER1 expression decreased on both sides, whereas PER2 expression decreased on the hemiplegic side but increased on the non-hemiplegic side. Conclusion: Treadmill training can mitigate muscle loss and regulate skeletal muscle clock gene expression following ischemic stroke. Exercise affects the hemiplegic side and has a positive regulatory effect on the non-hemiplegic side.

Differential genetic mutations and immune cell infiltration in high- and low-risk STAD: Implications for prognosis and immunotherapy efficacy.

This study investigates genetic mutations and immune cell dynamics in stomach adenocarcinoma (STAD), focusing on identifying prognostic markers and therapeutic targets. Analysis of TCGA-STAD samples revealed C > A as the most common single nucleotide variant (SNV) in both high and low-risk groups. Key mutated driver genes included TTN, TP53 and MUC16, with frame-shift mutations more prevalent in the low-risk group and missense mutations in the high-risk group. Interaction analysis of hub genes such as C1QA and CD68 showed significant correlations, impacting immune cell infiltration patterns. Using ssGSEA, we found higher immune cell infiltration (B cells, CD4+ T cells, CD8+ T cells, DC cells, NK cells) in the high-risk group, correlated with increased risk scores. xCell algorithm results indicated distinct immune infiltration levels between the groups. The study's risk scoring model proved effective in prognosis prediction and immunotherapy efficacy assessment. Key molecules like CD28, CD27 and SLAMF7 correlated significantly with risk scores, suggesting potential targets for high-risk STAD patients. Drug sensitivity analysis showed a negative correlation between risk scores and sensitivity to certain treatments, indicating potential therapeutic options for high-risk STAD patients. We also validated the carcinogenic role of RPL14 in gastric cancer through phenotypic experiments, demonstrating its influence on cancer cell proliferation, invasion and migration. Overall, this research provides crucial insights into the genetic and immune aspects of STAD, highlighting the importance of a risk scoring model for personalized treatment strategies and clinical decision-making in gastric cancer management.

Design, synthesis and biological evaluation of CDC20 inhibitors for treatment of triple-negative breast cancer.

The involvement of CDC20 in promoting tumor growth in different types of human cancers and it disturbs the process of cell division and impedes tumor proliferation. In this work, a novel of Apcin derivatives targeting CDC20 were designed and synthesized to evaluate for their biological activities. The inhibitory effect on the proliferation of four human tumor cell lines (MCF-7, MDA-MB-231, MDA-MB-468 and A549) was observed. Among them, compound E1 exhibited the strongest inhibitory effect on the proliferation of MDA-MB-231 cells with an IC50 value of 1.43 µM, which was significantly superior to that of Apcin. Further biological studies demonstrated that compound E1 inhibited cancer cell migration and colony formation. Furthermore, compound E1 specifically targeted CDC20 and exhibited a higher binding affinity to CDC20 compared to that of Apcin, thereby inducing cell cycle arrest in the G2/M phase of cancer cells. Moreover, it has been observed that compound E1 induces autophagy in cancer cells. In 4T1 Xenograft Models compound E1 exhibited the potential antitumor activity without obvious toxicity. These findings suggest that E1 could be regarded as a CDC20 inhibitor deserved further investigation.

UV-A radiation increases biomass yield by enhancing energy flow and carbon assimilation in the edible cyanobacterium Nostoc sphaeroides.

Ultraviolet (UV) A radiation (315-400 nm) is the predominant component of solar UV radiation that reaches the Earth's surface. However, the underlying mechanisms of the positive effects of UV-A on photosynthetic organisms have not yet been elucidated. In this study, we investigated the effects of UV-A radiation on the growth, photosynthetic ability, and metabolome of the edible cyanobacterium Nostoc sphaeroides. Exposures to 5-15 W m-2 (15-46 µmol photons m-2 s-1) UV-A and 4.35 W m-2 (20 µmol photons m-2 s-1) visible light for 16 days significantly increased the growth rate and biomass production of N. sphaeroides cells by 18%-30% and 15%-56%, respectively, compared to the non-UV-A-acclimated cells. Additionally, the UV-A-acclimated cells exhibited a 1.8-fold increase in the cellular nicotinamide adenine dinucleotide phosphate (NADP) pool with an increase in photosynthetic capacity (58%), photosynthetic efficiency (24%), QA re-oxidation, photosystem I abundance, and cyclic electron flow (87%), which further led to an increase in light-induced NADPH generation (31%) and ATP content (83%). Moreover, the UV-A-acclimated cells showed a 2.3-fold increase in ribulose-1,5-bisphosphate carboxylase/oxygenase activity, indicating an increase in their carbon-fixing capacity. Gas chromatography-mass spectrometry-based metabolomics further revealed that UV-A radiation upregulated the energy-storing carbon metabolism, as evidenced by the enhanced accumulation of sugars, fatty acids, and citrate in the UV-A-acclimated cells. Therefore, our results demonstrate that UV-A radiation enhances energy flow and carbon assimilation in the cyanobacterium N. sphaeroides.IMPORTANCEUltraviolet (UV) radiation exerts harmful effects on photo-autotrophs; however, several studies demonstrated the positive effects of UV radiation, especially UV-A radiation (315-400 nm), on primary productivity. Therefore, understanding the underlying mechanisms associated with the promotive effects of UV-A radiation on primary productivity can facilitate the application of UV-A for CO2 sequestration and lead to the advancement of photobiological sciences. In this study, we used the cyanobacterium Nostoc sphaeroides, which has an over 1,700-year history of human use as food and medicine, to explore its photosynthetic acclimation response to UV-A radiation. As per our knowledge, this is the first study to demonstrate that UV-A radiation increases the biomass yield of N. sphaeroides by enhancing energy flow and carbon assimilation. Our findings provide novel insights into UV-A-mediated photosynthetic acclimation and provide a scientific basis for the application of UV-A radiation for optimizing light absorption capacity and enhancing CO2 sequestration in the frame of a future CO2 neutral, circular, and sustainable bioeconomy.

Quantitative analysis of the impact of respiratory state on the heartbeat-induced movements of the heart and its substructures.

PURPOSE: This study seeks to examine the influence of the heartbeat on the position, volume, and shape of the heart and its substructures during various breathing states. The findings of this study will serve as a valuable reference for dose-volume evaluation of the heart and its substructures in radiotherapy for treating thoracic tumors. METHODS: Twenty-three healthy volunteers were enrolled in this study, and cine four-dimensional magnetic resonance images were acquired during periods of end-inspiration breath holding (EIBH), end-expiration breath holding (EEBH), and deep end-inspiration breath holding (DIBH). The MR images were used to delineate the heart and its substructures, including the heart, pericardium, left ventricle (LV), left ventricular myocardium, right ventricle (RV), right ventricular myocardium (RVM), ventricular septum (VS), atrial septum (AS), proximal and middle portions of the left anterior descending branch (pmLAD), and proximal portion of the left circumflex coronary branch (pLCX). The changes in each structure with heartbeat were compared among different respiratory states. RESULTS: Compared with EIBH, EEBH increased the volume of the heart and its substructures by 0.25-3.66%, while the average Dice similarity coefficient (DSC) increased by - 0.25 to 8.7%; however, the differences were not statistically significant. Conversely, the VS decreased by 0.89 mm in the left-right (LR) direction, and the displacement of the RV in the anterior-posterior (AP) direction significantly decreased by 0.76 mm (p < 0.05). Compared with EIBH and EEBH, the average volume of the heart and its substructures decreased by 3.08-17.57% and 4.09-20.43%, respectively, during DIBH. Accordingly, statistically significant differences (p < 0.05) were observed in the volume of the heart, pericardium, LV, RV, RVM, and AS. The average DSC increased by 0-37.04% and - 2.6 to 32.14%, respectively, with statistically significant differences (p < 0.05) found in the right ventricular myocardium and interatrial septum. Furthermore, the displacements under DIBH decreased in the three directions (i.e.,- 1.73 to 3.47 mm and - 0.36 to 2.51 mm). In this regard, the AP displacement of the heart, LV, RV, RVM, LR direction, LV, RV, and AS showed statistically significant differences (p < 0.05). The Hausdorff distance (HD) of the heart and its substructures under the three breathing states are all greater than 11 mm. CONCLUSION: The variations in the displacement and shape alterations of the heart and its substructures during cardiac motion under various respiratory states are significant. When assessing the dose-volume index of the heart and its substructures during radiotherapy for thoracic tumors, it is essential to account for the combined impacts of cardiac motion and respiration.

Discovery of Novel Isoquinoline Analogues as Dual Tubulin Polymerization/V-ATPase Inhibitors with Immunogenic Cell Death Induction.

Cancer immunotherapy has revolutionized clinical advances in a variety of cancers. Due to the low immunogenicity of the tumor, only a few patients can benefit from it. Specific microtubule inhibitors can effectively induce immunogenic cell death and improve immunogenicity of the tumor. A series of isoquinoline derivatives based on the natural products podophyllotoxin and diphyllin were designed and synthesized. Among them, F10 showed robust antiproliferation activity against four human cancer cell lines, and it was verified that F10 exerted antiproliferative activity by inhibiting tubulin and V-ATPase. Further studies indicated that F10 is able to induce immunogenic cell death in addition to apoptosis. Meanwhile, F10 inhibited tumor growth in an RM-1 homograft model with enhanced T lymphocyte infiltration. These results suggest that F10 may be a promising lead compound for the development of a new generation of microtubule drugs.