The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty ...of the virus, there are currently no SARS-CoV-2-specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here, we developed a pilot-scale production of PiCoVacc, a purified inactivated SARS-CoV-2 virus vaccine candidate, which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats, and nonhuman primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against other strains. Three immunizations using two different doses, 3 or 6 micrograms per dose, provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support the clinical development and testing of PiCoVacc for use in humans.
Background
We conducted this study to explore clinicopathological profiles of brain metastases (BM) and establish a clinical prediction model that predicts the presence of BM in colorectal cancer ...(CRC) patients.
Methods
Patients with initially diagnosed CRC were reviewed between the year 2010 and 2015. Multiple imputations are used for handling missing values. Prognostic factors were identified by the univariate and multivariate Cox regression model. Univariate and multivariate logistic regression was used to identify the predictive factors for the presence of BM. A nomogram was constructed based on statistically significant risk factors of the presence of BM. The decision curve analysis (DCA) was used to assess the clinical usefulness and net benefits of the nomogram for the presence of BM.
Results
Four hundred ninety-five patients with brain metastasis at the initial diagnosis were identified, representing 0.24% of the whole cohort and 0.91% of the metastatic cohort. Multivariable logistic regression demonstrated that young age, positive CEA, adenocarcinoma, lower differentiated grade, presence of liver metastases, presence of lung metastases, and presence of bone metastases were significantly associated with higher risk of developing BM. The decision curve analysis inform clinical decisions were better than a scenario in which all patients or no patients are screened across a wide range of threshold at ≥ 0.027%.
Conclusions
The risk estimates provided by the nomogram can be extremely useful for earlier diagnosis, especially when discussing screening strategy among high-risk patients.
The devastating coronavirus disease of 2019 (COVID-2019) epidemic has been declared a public health emergency, resulting in a worldwide pandemic. The omicron variety is the most common epidemic ...mutant strain in the globe. Serum beta-2 microglobulin (β2-MG) is associated with endothelial cell injury and has value in monitoring the progression of inflammation in infected individuals. Nonetheless, the potential functions of β2-MG in omicron remain elusive.
To investigate the prognostic value of serum β2-MG levels at diagnosis, we retrospectively analyzed a cohort of 240 people with omicron. Over the course of 65 days, all patients were monitored, and death was the primary outcome. Patients were allocated to two groups: those with high and low β2-MG levels. The Kaplan-Meier method was used to examine OS, and the log-rank test was used to compare them. Univariate and multivariate Cox hazard models were used to determine the prognostic significance.
Our results revealed that β2-MG was significantly elevated in omicron. β2-MG levels in severe patients were higher than in mild-to-moderate patients, and the difference was statistically significant. Timely, interleukin-6 (IL-6) and interleukin-10 (IL-10) were observed to be significantly increased in individuals exhibiting elevated levels of β2-MG. In addition, patients exhibiting elevated levels of β2-MG demonstrated a statistically significant decrease in overall survival (OS,
< 0.0001). An elevated β2-MG level (≥4.72 mg/l) was found to be an independent, adverse prognostic factor for OS in omicron patients, according to multivariate Cox proportional hazards regression analysis (
= 0.001).
Serum β2-MG level at initial diagnosis was significantly correlated with omicron severity and prognosis. Thus, we propose that β2-MG may be an independent poor additional prognostic factor in patients with omicron.
Background. The current guideline for the management of adrenocortical carcinoma (ACC) is insufficient for accurate risk prediction to guide adjuvant therapy. Given frequent and severe therapeutic ...side effects, a better estimate of survival is warranted for risk-specific assignment to adjuvant treatment. We attempted to construct an integrated model based on a prognostic gene signature and clinicopathological features to improve risk stratification and survival prediction in ACC. Methods. Using a series of bioinformatic and statistical approaches, a gene-expression signature was established and validated in two independent cohorts. By combining the signature with clinicopathological features, a decision tree was generated to improve risk stratification, and a nomogram was constructed to personalize risk prediction. Time-dependent receiver operating characteristic (tROC) and calibration analysis were performed to evaluate the predictive power and accuracy. Results. A three-gene signature could discriminate high-risk patients well in both training and validation cohorts. Multivariate regression analysis demonstrated the signature to be an independent predictor of overall survival. The decision tree could identify risk subgroups powerfully, and the nomogram showed high accuracy of survival prediction. Particularly, expression of a gene hitherto unknown to be dysregulated in ACC, TIGD1, was shown to be prognostically relevant. Conclusion. We propose a novel gene signature to guide decision-making about adjuvant therapy in ACC. The score shows unprecedented survival prediction and hence constitutes a huge step towards personalized management. As a secondary important finding, we report the discovery and validation of a new oncogene, TIGD1, which was consistently overexpressed in ACC. TIGD1 might shed further light on the biology of ACC and might give rise to targeted therapies that not only apply to ACC but potentially also to other malignancies.
The continuous evolution and mutation of SARS-CoV-2 have highlighted the need for more effective vaccines. In this study, CpG, MF59-like, and Alum adjuvant Delta strain inactivated SARS-CoV-2 ...vaccines were prepared, and the immunogenicity of these vaccines in mice was evaluated. The Delta + MF59-like vaccine group produced the highest levels of S- and RBD-binding antibodies and live Delta virus neutralization levels after one shot of immunization, while mice in the Delta + Alum vaccine group had the highest levels of these antibodies after two doses, and the Delta + MF59-like and Delta + Alum vaccine groups produced high levels of cross-neutralization antibodies against prototype, Beta, and Gamma strain SARS-CoV-2 viruses. There was no significant decrease in neutralizing antibody levels in any vaccine group during the observation period. CpG, MF59-like, and Alum adjuvant Delta strain inactivated SARS-CoV-2 vaccines excited different antibody subtypes compared with unadjuvanted vaccines; the Delta + CpG vaccine group had a higher proportion of IgG2b antibodies, indicating bias towards Th1 immunity. The proportions of IgG1 and IgG2b in the Delta + MF59-like vaccine group were similar to those of the unadjuvanted vaccine. However, the Delta + Alum vaccine group had a higher proportion of IgG1 antibodies, indicating bias towards Th2 immunity. Antigen-specific cytokine secretion CD4/8
T cells were analyzed. In conclusion, the results of this study show differences in the immune efficacy of CpG, MF59-like, and Alum adjuvant Delta strain inactivated SARS-CoV-2 vaccines in mice, which have significant implications for the selection strategy for vaccine adjuvants.
Background
Hypoxic microenvironment is immunosuppressive and protumorigenic, and elevated lactate is an intermediary in the modulation of immune responses. However, as critical lactate transporters, ...the role of SLC16A1 and SLC16A3 in immune infiltration and evasion of glioma is not fully elucidated.
Methods
Gene expression in low‐ and high‐grade glioma (LGG and GBM) was evaluated with TCGA database. The TISIDB, TIMER and CIBERSORT databases were utilized for the analysis of the correlation between SLC16A1 or SLC16A3 and immunocyte infiltration as well as immune checkpoints.
Results
Compared with normal tissues, a significant increase of both SLC16A1 and SLC16A3 was found in LGG and GBM, and closely related to the poor prognosis only in LGG. Cancer SEA indicated that SLC16A1 was involved in hypoxia while SLC16A3 contributed to metastasis and inflammation in glioma. The SLC16A3 expression was significantly correlated with neutrophil activation by GO analysis. TISCH showed the distribution of SLC16A1 on glioma cells and SLC16A3 on immune cells, which was correlated to tumor‐associated macrophages and neutrophils that are immunosuppressive. SLC16A1 and SLC16A3 were identified to tightly interacted with diverse immune checkpoints (especially PD1, PD‐L1, PD‐L2, Tim‐3) and immunosuppressive factors (TGF‐β and IL‐10) in glioma. Furthermore, SLC16A3 had a positive correlation to activation markers of tumor‐associated neutrophils and chemokines such as CCL2, CCL22, CXCR2, CXCR4 in LGG and CCL7, CCL20 CXCL8 in GBM, which could enhance infiltration of immunosuppressive cells to the tumor microenvironment.
Conclusion
In general, our results suggest that SLC16A1 and SLC16A3 act as a bridge between tumor metabolism and immunity by promoting immunosuppressive cell infiltration, which contributes to immune evasion and a worse prognosis in glioma. Targeting SLC16A1 and SLC16A3 may provide novel therapeutic strategy for immunotherapy in glioma.
Both SLC16A1 and SLC16A3 expression were increased in LGG and GBM. GO analysis indicated that SLC16A1 was related to Herpes simplex virus 1 infection while SLC16A3 was involved in neutrophil activation. SLC16A3 as well as SLC16A1 were closely related to immune infiltration and checkpoints LGG and GBM.
Modification of vacuum chamber surface properties by introducing a layer of material with low secondary electron yield (SEY) is one of the most useful solutions to suppress the electron-cloud in ...high-energy particle accelerators. In the present work, amorphous carbon thin films have been produced by DC magnetron sputtering with Neon and Argon sputtering gases. Microstructures of the thin films have been characterized by using scanning electron microscopy (SEM) and atomic force microscopy (AFM). The sp2 and sp3 hybridized carbon atoms are evaluated using X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy. The amorphous carbon coatings comprise tiny granularities of tens of nanometers. The amorphous carbon films show more graphite-like properties as revealed by XPS and Raman spectroscopy. The secondary electron emission measurement results indicate that amorphous carbon coatings present SEY of <1.2. The thin film deposited by Ne exhibits a higher sp2 hybridization content, leading to a slightly lower SEY compared with the film produced with Ar.
Background
Approximately 30% of stage II and 50–60% of stage III colorectal cancer (CRC) patients who have undergone surgery will develop recurrence within 5 years. Thus, more reliable prognostic ...biomarkers are urgently needed to identify the high-risk subset of patients who will benefit from postoperative adjuvant therapy.
Methods
We retrospectively analyzed 911 stage II/III CRC patients in multiple cohorts. Using a series of bioinformatic and statistical approaches, an individualized prognostic signature was established in the training cohort and validated in four other independent cohorts. An integrated decision tree was generated to improve risk stratification, and a nomogram was built to quantify risk assessment for individual patients.
Results
Epithelial-mesenchymal transition (EMT) was identified as a dominant risk factor for recurrence-free survival (RFS) in stage II/III CRC patients. The EMT-related gene signature could discriminate high-risk subsets in a training cohort and four independent validation cohorts (with 473, 89, 130, 74 and 145 patients, respectively). Survival analyses demonstrated that the EMT-related gene signature served as an independent risk factor for RFS in different subgroups. The decision tree could optimize the risk stratification, and the nomogram could predict the 5-year RFS probability accurately.
Conclusion
The proposed EMT-related prognostic signature is a useful biomarker to predict RFS and identify the high-risk subset in stage II/III CRC patients.
The SARS‐CoV‐2 virus is responsible for the human disease known as COVID‐19. This virus is capable of generating a spectrum of infections ranging from moderate to severe. Serum apolipoprotein E ...(ApoE) inhibits inflammation by preserving immune regulatory function. Nonetheless, the relationship between serum ApoE and clinical prognosis in omicron remains elusive. A cohort of 231 patients was observed for 65 days, with death as the primary outcome. Based on their ApoE levels, the patients were categorized into patients with elevated ApoE levels and those with lower ApoE levels. To do statistical comparisons, the log‐rank test was utilized, and the Kaplan‐Meier method was utilized to estimate survival rates. Cox hazard models, both univariate and multivariate, were employed to examine the prognostic relevance. According to our research, omicron had significantly greater ApoE levels. In mild‐to‐moderate and severe cases, the study identified a statistically significant variation in ApoE levels. Additionally, there was a drop in overall survival that is statistically significant (OS, p < 0.0001) for patients with greater ApoE levels. Multiple Cox proportional hazards regression analysis indicates that an elevated ApoE level was determined to be an adverse and independent prognostic factor of OS in patients with omicron. Taken together, our study found that the level of serum ApoE at the time of initial diagnosis was substantially connected to the severity and prognosis of omicron. Consequently, we propose that ApoE might be a poor prognostic factor in individuals afflicted with the omicron variant.
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