Sevoflurane postconditioning ameliorates cerebral hypoxia/reoxygenation injury in zebrafish involving the Akt/GSK-3ß pathway activation and the microtubule-associated protein 2 promotion.

Sevoflurane postconditioning has been shown to provide neuroprotection against cerebral hypoxia-ischemia injury, but the mechanisms remain elusive. Microtubule-associated protein 2 (MAP2) is implicated in early neuronal hypoxia-ischemia injury. This study aimed to investigate whether the neuroprotective effects of sevoflurane postconditioning are related to the Akt/GSK-3ß pathway and its downstream target MAP2 in zebrafish hypoxia/reoxygenation (H/R) model. Sevoflurane postconditioning or GSK-3ß inhibitor TDZD-8 were used to treat H/R zebrafish. The cerebral infarction, neuronal apoptosis, and mitochondrial changes were evaluated using TTC staining, TUNEL staining, and transmission electron microscopy, respectively. The distribution of MAP2 in the brain was determined by immunofluorescence imaging. The levels of Akt, p-Akt, GSK-3ß, p-GSK-3ß, and MAP2 proteins were evaluated by Western blotting. The neurobehavioral recovery of zebrafish was assessed based on optokinetic response behavior. Our results indicated that sevoflurane postconditioning and TDZD-8 significantly reduced the cerebral infarction area, suppressed cell apoptosis, and improved mitochondrial integrity in zebrafish subjected to H/R. Furthermore, sevoflurane postconditioning and TDZD-8 elevated the ratios of p-Akt/Akt and p-GSK-3ß/GSK-3ß. However, the neuroprotective effect of sevoflurane postconditioning was effectively abolished upon suppression of MAP2 expression. In conclusion, sevoflurane postconditioning ameliorated cerebral H/R injury and facilitated the restoration of neurobehavioral function through the activation of Akt/GSK-3ß pathway and promotion of MAP2 expression.

Transformation of a Viral Capsid from Nanocages to Nanotubes and Then to Hydrogels: Redirected Self-Assembly and Effects on Immunogenicity.

The ability to manipulate the self-assembly of proteins is essential to understanding the mechanisms of life and beneficial to fabricating advanced nanomaterials. Here, we report the transformation of the MS2 phage capsid from nanocages to nanotubes and then to nanotube hydrogels through simple point mutations guided by interfacial interaction redesign. We demonstrate that site 70, which lies in the flexible FG loop of the capsid protein (CP), is a "magic" site that can largely dictate the final morphology of assemblies. By varying the amino acid at site 70, with the aid of a cysteine-to-alanine mutation at site 46, we achieved the assembly of double-helical or single-helical nanotubes in addition to nanocages. Furthermore, an additional cysteine substitution on the surface of nanotubes mediated their cross-linking to form hydrogels with reducing agent responsiveness. The hierarchical self-assembly system allowed for the investigation of morphology-related immunogenicity of MS2 CPs, which revealed dramatic differences among nanocages, nanotubes, and nanotube hydrogels in terms of immune response types, antibody levels and T cell functions. This study provides insights into the assembly manipulation of protein nanomaterials and the customized design of nanovaccines and drug delivery systems.

The relationship between school bullying victimization and mental health among high school sexual minority students in China: A cross-sectional study.

BACKGROUND: School bullying has become a matter of global concern for the general public. Sexual minority youth (SMY) may experience minority stress and victimization which are known to adversely affect mental health and happiness. However, a few scholars explored and linked sexual orientation with campus bullying, depression, and anxiety symptoms under the specific cultural background of China. OBJECTIVE: This study was to examine the effect of traditional and cyber bullying victimization on depression and anxiety among Chinese sexual minority adolescents. METHODS: This is a cross-sectional survey with a total of 3841 subjects among senior high school students in Hunan Province, China. Related information was collected through a series of self-reported questionnaires. The association between variables was examined via a set of logistic regressions. RESULTS: Homosexuality (OR: 6.398; 95 % CI: 3.321 to 12.325), bisexuality (OR: 3.146; 95 % CI: 1.499 to 6.603) and uncertainty of sexual orientation (OR: 2.341; 95 % CI: 1.516 to 3.615) were significantly associated with a combination of traditional and cyber bullying victimization. Compared to the heterosexual group, the sexual minority students, especially the bisexual students has a higher risk of depressive mood (OR: 2.349; 95 % CI: 1.664 to 3.316) and anxiety mood (OR: 3.049; 95 % CI: 2.150 to 4.324). Further multivariate binary hierarchical regression showed that the effects of sexual orientation and mental health were statistically significant only among those who are not involved in bullying victimization, OR values are from 1.929 (95 % CI: 1.061 to 3.507) to 3.209 (95 % CI: 2.090 to 4.927). CONCLUSIONS: Homosexuals are most likely to be victims of a combination of traditional and cyber bullying victims. Bisexuals are most at risk for emotional problems. Sexual minorities in particular, showed differences in mental health risks between bullied and non-bullied groups. More attention needs to be paid to bullying and mental health among sexual minority students in China.

Association of CHA2DS2-VASC Score with in-Hospital Cardiovascular Adverse Events in Patients with Acute ST-Segment Elevation Myocardial Infarction.

Background: Acute ST-elevation myocardial infarction (STEMI) is a common clinical critical illness, and accurate, reliable, simple, and easy-to-remember tools are needed in clinical practice to quickly identify the risk of this condition in STEMI patients. This study investigates the predictive value of the admission CHA2DS2-VASc score for in-hospital MACE in STEMI patients. Methods: A total of 210 STEMI patients who visited the Chest Pain Center of the Second People's Hospital of Hefei from December 2019 to December 2021 were retrospectively analyzed. They were divided into MACE and non-MACE groups. The receiver operating characteristic curve (ROC) was used to assess the predictive value of the CHA2DS2-VASc score for MACE events during hospitalization. Results: The CHA2DS2-VASc score was higher in the MACE group than in the non-MACE group (P < 0.05), and multivariate logistic regression analysis showed that the CHA2DS2-VASc score was an independent risk factor for MACE events during hospitalization in STEMI patients (OR = 1.391, 95%CI 1.044-1.853, P=0.024); ROC curve analysis showed that the area under the curve (AUC) of the CHA2DS2-VASc score was 0.744, the sensitivity was 0.64, the specificity was 0.694, and the optimal cutoff value was 3.5 in predicting the risk of MACE events during hospitalization in STEMI patients. There were no significant differences between the GRACE score (0.744 VS.0.827) and TIMI score (0.744VS.0.745) (P > 0.05). Conclusion: The CHA2DS2-VASc score can successfully predict the occurrence of in-hospital MACE events in STEMI patients.

The Value of Serum YKL-40 and TNF-α in the Diagnosis of Acute ST-Segment Elevation Myocardial Infarction.

Background: Acute ST-segment elevation myocardial infarction (STEMI) is a serious cardiovascular disease that poses a great threat to the life and health of patients. Therefore, early diagnosis is important for STEMI patient treatment and prognosis. The purpose of this study was to investigate the value of serum YKL-40 and TNF-α in the diagnosis of STEMI. Methods: From October 2020 to February 2022, 120 patients with STEMI were admitted to the Chest Pain Center of the Second People's Hospital of Hefei, and 81 patients with negative coronary angiography were selected as the control group. Serum YKL-40 and TNF-α concentrations were measured by sandwich ELISA. Pearson correlation was used to analyze the correlation between serum YKL-40, TNF-α, and serum troponin I (cTnI) in STEMI patients; multivariate logistic regression analysis was used to screen independent risk factors for STEMI. Three diagnostic models were constructed: cTnI univariate model (model A), combined serum YKL-40 and TNF-α model other than cTnI (model B), and combined cTnI and serum YKL-40 and TNF-α model (model C). We assessed the clinical usefulness of the diagnostic model by comparing AUC with decision curve analysis (DCA). Results: Serum YKL-40 and TNF-α in the STEMI group were significantly higher than those in the control group (P < 0.001). On Pearson correlation analysis, there was a significant positive correlation between serum YKL-40, TNF-α, and cTnI levels in STEMI patients. Multivariate logistic regression analysis showed that serum YKL-40 and TNF-α were independent risk factors for the development of STEMI. The results of ROC analysis showed that the area under the curve (AUC) of serum YKL-40 for predicting the occurrence of STEMI was 0.704. The AUC of serum TNF-α for predicting the occurrence of STEMI was 0.852. The AUC of cTnI as a traditional model, model A, for predicting the occurrence of STEMI was 0.875. Model B predicted STEMI with an AUC of 0.851. The addition of serum YKL-40 and serum TNF-α to the traditional diagnostic model composed of cTnI constituted a new diagnostic model; that is, the AUC of model C for predicting the occurrence of STEMI was 0.930. Model C had a better net benefit between a threshold probability of 70-95% for DCA. Conclusion: In this study, we demonstrate the utility of serum YKL-40 and TNF-α as diagnostic markers for STEMI and the clinical utility of diagnostic models by combining serum YKL-40 and TNF-α with cTnI.

Elucidating the anatomy of the quadrivial pattern of the right upper lobe bronchus using 3D-CT images.

Background: A preoperative understanding of the thoracic anatomy of the patients with the quadrivial pattern of branching of the right upper lobe is key to successful surgery. We analyzed the quadrivial pattern of division of the right upper lobe bronchus of patients using three-dimensional (3D) computed tomography (CT) angiography and bronchography. Methods: A total of 212 consecutive adult patients who had undergone thoracic CT scans before surgery at the Zhujiang Hospital of the Southern Medical University from August 2020 to August 2021 was used for retrospective study. The 3D-CT images were taken using Mimics software. Radiology technicians processed all the 3D images, and thoracic surgeons confirmed the validity of all the reconstructions. Results: Six (2.83%) were identified as having a quadrivial pattern of division of the right upper lobe bronchus with 1 female, and 5 males. Based on the number of pulmonary artery branches, 5 (83.3%) and 1 (16.7%) were classified as "trunk superior (Tr.sup) + ascending artery (A.asc) and Tr.sup + trunk inferior (Tr.inf) + ascending artery (A.asc) (1/6, 16.7%). Based on the number of ascending artery branches, the patients were also divided into type A (3/6, 50%) and type B (3/6, 50%). The patients were also divided into 1 of the following three types based on the origins of the A2: (I) A2 originates from A6 (1/6, 16.7%); (II) A2 originates from the pulmonary trunk (4/6, 66.7%); and (III) A2a originates from A3, and A2b originates from the pulmonary artery stem (1/6, 16.7%). According to the number of A1b branches, patients were divided into two types: (I) 1 branch (4/6, 66.7 %); and (II) 2 branches (2/6, 33.3 %). In the present study, anterior + central type was observed which classified into two types: (I) type Iab, the anterior vein ran from V1a to V1b (4/6, 66.7%); and (II) type Ib, the anterior vein ran from V1b only (2/6, 33.3%). Conclusions: 3D-CT was successfully used for analyzing the quadrivial bronchovascular patterns of the right upper lobe bronchus. Our study provides certain references to perform anatomical pulmonary segmentectomy, which should improve the success rate of operations.

Cross-talk between cuproptosis and ferroptosis regulators defines the tumor microenvironment for the prediction of prognosis and therapies in lung adenocarcinoma.

Cuproptosis, a newly identified form of programmed cell death, plays vital roles in tumorigenesis. However, the interconnectivity of cuproptosis and ferroptosis is poorly understood. In our study, we explored genomic alterations in 1162 lung adenocarcinoma (LUAD) samples from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) cohort to comprehensively evaluate the cuproptosis regulators. We systematically performed a pancancer genomic analysis by depicting the molecular correlations between the cuproptosis and ferroptosis regulators in 33 cancer types, indicating cross-talk between cuproptosis and ferroptosis regulators at the multiomic level. We successfully identified three distinct clusters based on cuproptosis and ferroptosis regulators, termed CuFeclusters, as well as the three distinct cuproptosis/ferroptosis gene subsets. The tumor microenvironment cell-infiltrating characteristics of three CuFeclusters were highly consistent with the three immune phenotypes of tumors. Furthermore, a CuFescore was constructed and validated to predict the cuproptosis/ferroptosis pathways in individuals and the response to chemotherapeutic drugs and immunotherapy. The CuFescore was significantly associated with the expression of miRNA and the regulation of post-transcription. Thus, our research established an applied scoring scheme, based on the regulators of cuproptosis/ferroptosis to identify LUAD patients who are candidates for immunotherapy and to predict patient sensitivity to chemotherapeutic drugs.

Construction and evaluation of nomogram model for individualized prediction of risk of major adverse cardiovascular events during hospitalization after percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction.

Background: Emergency percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI) helps to reduce the occurrence of major adverse cardiovascular events (MACEs) such as death, cardiogenic shock, and malignant arrhythmia, but in-hospital MACEs may still occur after emergency PCI, and their mortality is significantly increased once they occur. The aim of this study was to investigate the risk factors associated with MACE during hospitalization after PCI in STEMI patients, construct a nomogram prediction model and evaluate its effectiveness. Methods: A retrospective analysis of 466 STEMI patients admitted to our hospital from January 2018 to June 2022. According to the occurrence of MACE during hospitalization, they were divided into MACE group (n = 127) and non-MACE group (n = 339), and the clinical data of the two groups were compared; least absolute shrinkage and selection operator (LASSO) regression was used to screen out the predictors with non-zero coefficients, and multivariate Logistic regression was used to analyze STEMI Independent risk factors for in-hospital MACE in patients after emergency PCI; a nomogram model for predicting the risk of in-hospital MACE in STEMI patients after PCI was constructed based on predictive factors, and the C-index was used to evaluate the predictive performance of the prediction model; the Bootstrap method was used to repeat sampling 1,000 Internal validation was carried out for the second time, the Hosmer-Lemeshow test was used to evaluate the model fit, and the calibration curve was drawn to evaluate the calibration degree of the model. Receiver operating characteristic (ROC) curves were drawn to evaluate the efficacy of the nomogram model and thrombolysis in myocardial infarction (TIMI) score in predicting in-hospital MACE in STEMI patients after acute PCI. Results: The results of LASSO regression showed that systolic blood pressure, diastolic blood pressure, Killip grade II-IV, urea nitrogen and left ventricular ejection fraction (LVEF), IABP, NT-ProBNP were important predictors with non-zero coefficients, and multivariate logistic regression analysis was performed to analyze that Killip grade II-IV, urea nitrogen, LVEF, and NT-ProBNP were independent factors for in-hospital MACE after PCI in STEMI patients; a nomogram model for predicting the risk of in-hospital MACE after PCI in STEMI patients was constructed with the above independent predictors, with a C-index of 0.826 (95% CI: 0.785-0.868) having a good predictive power; the results of H-L goodness of fit test showed χ2 = 1.3328, P = 0.25, the model calibration curve was close to the ideal model, and the internal validation C-index was 0.818; clinical decision analysis also showed that the nomogram model had a good clinical efficacy, especially when the threshold probability was 0.1-0.99, the nomogram model could bring clinical net benefits to patients. The nomogram model predicted a greater AUC (0.826) than the TIMI score (0.696) for in-hospital MACE after PCI in STEMI patients. Conclusion: Urea nitrogen, Killip class II-IV, LVEF, and NT-ProBNP are independent factors for in-hospital MACE after PCI in STEMI patients, and nomogram models constructed based on the above factors have high predictive efficacy and feasibility.

An Ultrastable Virus-Like Particle with a Carbon Dot Core and Expanded Sequence Plasticity.

Ordered bio-inorganic hybridization has evolved for the generation of high-performance materials in living organisms and inspires novel strategies to design artificial hybrid materials. Virus-like particles (VLPs) are attracting extensive interest as self-assembling systems and platforms in the fields of biotechnology and nanotechnology. However, as soft nanomaterials, their structural stability remains a general and fundamental problem in various applications. Here, an ultrastable VLP assembled from the major capsid protein (VP1) of simian virus 40 is reported, which contains a carbon dot (C-dot) core. Co-assembly of VP1 with C-dots led to homogeneous T = 1 VLPs with a fourfold increase in VLP yields. The resultant hybrid VLPs showed markedly enhanced structural stability and sequence plasticity. C-dots and a polyhistidine tag fused to the inner-protruding N-terminus of VP1 contributed synergistically to these enhancements, where extensive and strong noncovalent interactions on the C-dot/VP1 interfaces are responsible according to cryo-EM 3D reconstruction, molecular simulation, and affinity measurements. C-dot-enhanced ultrastable VLPs can serve as a new platform, enabling the fabrication of new architectures for bioimaging, theranostics, nanovaccines, etc. The hybridization strategy is simple and can easily be extended to other VLPs and protein nanoparticle systems.

Passive cancer targeting with a viral nanoparticle depends on the stage of tumorigenesis.

Tumor targeting with nanoparticles is a promising strategy for cancer diagnosis and treatment, especially for drug delivery to solid tumors. Previous studies mainly focused on nanoparticle design to improve their targeting efficiency, but few have investigated the impact of tumor progression stages on the targeting efficiency. Here, we used PEGylated viral nanoparticles (VNPs) of bacteriophage P22 to explore the relationship between targeting efficiency and tumor progression stages using a colorectal cancer model. We found an 8.1-fold increase in the accumulation of P22 VNPs systematically injected 7 days after tumor inoculation compared with those injected 21 days after tumor inoculation. Most tumor-targeted P22 VNPs were concentrated in tumor-associated macrophages in the tumor blood vessels, the density of which decreased with the progression of tumors. These results reveal that the tumor targeting efficiency of P22 VNPs decreased with tumor progression. These findings provide valuable information for not only the understanding of controversial observations regarding targeted cancer therapy in experimental and clinical studies but also the design of nanoparticle-based tumor targeting probes or therapeutics.