Longitudinal change of serum AIM2 levels after aneurysmal subarachnoid hemorrhage and its prognostic significance: a two-center prospective cohort study.

Absent in melanoma 2 (AIM2) is implicated in neuroinflammation. Here, we explored the prognostic significance of serum AIM2 in human aneurysmal subarachnoid hemorrhage (aSAH). We conducted a consecutive enrollment of 127 patients, 56 of whom agreed with blood-drawings not only at admission but also at days 1, 2, 3, 5, 7 and 10 days after aSAH. Serum AIM2 levels of patients and 56 healthy controls were measured. Disease severity was assessed using the modified Fisher scale (mFisher) and World Federation of Neurological Surgeons Scale (WFNS). Neurological outcome at poststroke 90 days was evaluated via the modified Rankin Scale (mRS). Univariate analysis and multivariate analysis were sequentially done to ascertain relationship between serum AIM2 levels, severity, delayed cerebral ischemia (DCI) and 90-day poor prognosis (mRS scores of 3-6). Patients, in comparison to controls, had a significant elevation of serum AIM2 levels at admission and at days 1, 2, 3, 5, 7 and 10 days after aSAH, with the highest levels at days 1, 2, 3 and 5. AIM2 levels were independently correlated with WFNS scores and mFisher scores. Significantly higher serum AIM2 levels were detected in patients with a poor prognosis than in those with a good prognosis, as well as in patients with DCI than in those without DCI. Moreover, serum AIM2 levels independently predicted a poor prognosis and DCI, and were linearly correlated with their risks. Using subgroup analysis, there were no significant interactions between serum AIM2 levels and age, gender, hypertension and so on. There were substantially high predictive abilities of serum AIM2 for poor prognosis and DCI under the receiver operating characteristic curve. The combination models of DCI and poor prognosis, in which serum AIM2, WFNS scores and mFisher scores were incorporated, showed higher discriminatory efficiencies than anyone of the preceding three variables. Moreover, the models are delineated using the nomogram, and performed well under the calibration curve and decision curve. Serum AIM2 levels, with a substantial enhancement during early phase after aSAH, are closely related to bleeding severity, poor 90-day prognosis and DCI of patients, substantializing serum AIM2 as a potential prognostic biomarker of aSAH.

Correction: Facile preparation of a Ni-imidazole compound with high activity for ethylene dimerization.

Correction for 'Facile preparation of a Ni-imidazole compound with high activity for ethylene dimerization' by Zhaohui Liu et al., Chem. Commun., 2024, 60, 188-191, https://doi.org/10.1039/D3CC04794F.

Noninvasive Stereotactic Radiotherapy for PADN in an Acute Canine Model of Pulmonary Arterial Hypertension.

This study assesses the feasibility, safety, and effectiveness of noninvasive stereotactic body radiotherapy (SBRT) as an approach for pulmonary artery denervation in canine models. SBRT with CyberKnife resulted in reduced mean pulmonary artery pressure, pulmonary capillary wedge pressure, and pulmonary vascular resistance, and insignificantly increased cardiac output. In comparison to the control group, serum norepinephrine levels at 1 month and 6 months were significantly lower in the CyberKnife group. Computed tomography, pulmonary angiography, and histology analysis revealed that SBRT was associated with minimal collateral damage.

Facile preparation of a Ni-imidazole compound with high activity for ethylene dimerization.

A compound consisting of Ni and imidazole (Ni-imidazole) was synthesized in large quantities by a one-step co-precipitation method. The structure and stability of this Ni-imidazole were well studied by a series of characterization methods. The Ni-imidazole compound exhibited excellent catalytic properties for the dimerization of ethylene to 1-butene.

Four Ounces Can Move a Thousand Pounds: The Enormous Value of Nanomaterials in Tumor Immunotherapy.

The application of nanomaterials in healthcare has emerged as a promising strategy due to their unique structural diversity, surface properties, and compositional diversity. In particular, nanomaterials have found a significant role in improving drug delivery and inhibiting the growth and metastasis of tumor cells. Moreover, recent studies have highlighted their potential in modulating the tumor microenvironment (TME) and enhancing the activity of immune cells to improve tumor therapy efficacy. Various types of nanomaterials are currently utilized as drug carriers, immunosuppressants, immune activators, immunoassay reagents, and more for tumor immunotherapy. Necessarily, nanomaterials used for tumor immunotherapy can be grouped into two categories: organic and inorganic nanomaterials. Though both have shown the ability to achieve the purpose of tumor immunotherapy, their composition and structural properties result in differences in their mechanisms and modes of action. Organic nanomaterials can be further divided into organic polymers, cell membranes, nanoemulsion-modified, and hydrogel forms. At the same time, inorganic nanomaterials can be broadly classified as nonmetallic and metallic nanomaterials. The current work aims to explore the mechanisms of action of these different types of nanomaterials and their prospects for promoting tumor immunotherapy.

The role of ARL4C in predicting prognosis and immunotherapy drug susceptibility in pan-cancer analysis.

Background: ARLs, which are a class of small GTP-binding proteins, play a crucial role in facilitating tumor tumorigenesis and development. ARL4C, a vital member of the ARLs family, has been implicated in the progression of tumors, metastatic dissemination, and development of resistance to therapeutic drugs. Nevertheless, the precise functional mechanisms of ARL4C concerning tumor prognosis and immunotherapy drug susceptibility remain elusive. Methods: By combining the GTEx and TCGA databases, the presence of ARL4C was examined in 33 various types of cancer. Immunohistochemistry and immunofluorescence staining techniques were utilized to confirm the expression of ARL4C in particular tumor tissues. Furthermore, the ESTIMATE algorithm and TIMER2.0 database were utilized to analyze the tumor microenvironment and immune infiltration associated with ARL4C. The TISCH platform facilitated the utilization of single-cell RNA-seq datasets for further analysis. ARL4C-related immune escape was investigated using the TISMO tool. Lastly, drug sensitivity analysis was conducted to assess the sensitivity of different types of tumors to compounds based on the varying levels of ARL4C expression. Results: The study found that ARL4C was highly expressed in 23 different types of cancer. Moreover, the presence of high ARL4C expression was found to be associated with a poor prognosis in BLCA, COAD, KIRP, LGG, and UCEC. Notably, ARL4C was also expressed in immune cells, and its high expression was found to be correlated with cancer immune activation. Most importantly, the drug sensitivity analysis revealed a positive correlation between ARL4C expression and the heightened sensitivity of tumors to Staurosporine, Midostaurin, and Nelarabine. Conclusion: The findings from our study indicate that the expression level of ARL4C may exert an influence on cancer development, prognosis, and susceptibility to immunotherapy drugs. In addition, the involvement of ARL4C in the tumor immune microenvironment has expanded the concept of ARL4C-targeted immunotherapy.

Nanomaterials: small particles show huge possibilities for cancer immunotherapy.

With the economy's globalization and the population's aging, cancer has become the leading cause of death in most countries. While imposing a considerable burden on society, the high morbidity and mortality rates have continuously prompted researchers to develop new oncology treatment options. Anti-tumor regimens have evolved from early single surgical treatment to combined (or not) chemoradiotherapy and then to the current stage of tumor immunotherapy. Tumor immunotherapy has undoubtedly pulled some patients back from the death. However, this strategy of activating or boosting the body's immune system hardly benefits most patients. It is limited by low bioavailability, low response rate and severe side effects. Thankfully, the rapid development of nanotechnology has broken through the bottleneck problem of anti-tumor immunotherapy. Multifunctional nanomaterials can not only kill tumors by combining anti-tumor drugs but also can be designed to enhance the body's immunity and thus achieve a multi-treatment effect. It is worth noting that the variety of nanomaterials, their modifiability, and the diversity of combinations allow them to shine in antitumor immunotherapy. In this paper, several nanobiotics commonly used in tumor immunotherapy at this stage are discussed, and they activate or enhance the body's immunity with their unique advantages. In conclusion, we reviewed recent advances in tumor immunotherapy based on nanomaterials, such as biological cell membrane modification, self-assembly, mesoporous, metal and hydrogels, to explore new directions and strategies for tumor immunotherapy.

Nanomaterials: A powerful tool for tumor immunotherapy.

Cancer represents the leading global driver of death and is recognized as a critical obstacle to increasing life expectancy. In recent years, with the development of precision medicine, significant progress has been made in cancer treatment. Among them, various therapies developed with the help of the immune system have succeeded in clinical treatment, recognizing and killing cancer cells by stimulating or enhancing the body's intrinsic immune system. However, low response rates and serious adverse effects, among others, have limited the use of immunotherapy. It also poses problems such as drug resistance and hyper-progression. Fortunately, thanks to the rapid development of nanotechnology, engineered multifunctional nanomaterials and biomaterials have brought breakthroughs in cancer immunotherapy. Unlike conventional cancer immunotherapy, nanomaterials can be rationally designed to trigger specific tumor-killing effects. Simultaneously, improved infiltration of immune cells into metastatic lesions enhances the efficiency of antigen submission and induces a sustained immune reaction. Such a strategy directly reverses the immunological condition of the primary tumor, arrests metastasis and inhibits tumor recurrence through postoperative immunotherapy. This paper discusses several types of nanoscale biomaterials for cancer immunotherapy, and they activate the immune system through material-specific advantages to provide novel therapeutic strategies. In summary, this article will review the latest advances in tumor immunotherapy based on self-assembled, mesoporous, cell membrane modified, metallic, and hydrogel nanomaterials to explore diverse tumor therapies.

Ultrasound-assisted desalination of crude oil: The influence of mixing extent, crude oil species, chemical demulsifier and operation variables.

Coalescence of water droplets in crude oil has been effectively promoted by chemical demulsifiers integrated with ultrasound. Temporary images of water droplets in W/O emulsions were directly monitored using a metallurgical microscope. Water droplets achieved expansion of 118% at 40 min ultrasonic irradiation time under well mixing conditions. However, water droplets in heavy crude oil undergo less aggregation than those in light crude oil, due to resistance of mobility in highly viscous fluid. In the absence of chemical demulsifiers, water droplets enveloped by native surfactants appeared to aggregate arduously because of occurrence of interfacial tension gradients. Influential significance analyses have been executed by a factorial design method on operation variables, including acoustic power intensity, operation temperature, ultrasonic irradiation time and chemical demulsifier dosages. In this work, the outcomes indicate that the optimal operating conditions for desalination of crude oil assisted by ultrasound were as follows: acoustic power intensity = 300 W, operation temperature = 90℃, ultrasonic irradiation time = 75 min and chemical demulsifier dosages = 54 mg/L. Besides, it was found that the most influential importance of operation parameter was temperature, followed with acoustic power intensity, ultrasonic irradiation time and chemical demulsifier dosages.

A clinical study of a CD44v6-targeted fluorescent agent for the detection of non-muscle invasive bladder cancer.

BACKGROUND: Bladder cancer is the fifth most common malignancy in humans. Cystoscopy under white light imaging is the gold standard for bladder cancer diagnosis, but some tumors are difficult to visualize and can be overlooked, resulting in high recurrence rates. We previously developed a phage display-derived peptide-based near-infrared imaging probe, PLSWT7-DMI, which binds specifically to bladder cancer cells and is nontoxic to animals. Here, we report a clinical research of this probe for near-infrared fluorescence endoscopic detection of bladder cancer. RESULTS: The purity, efficacy, safety, and nontoxicity of PLSWT7-DMI were confirmed prior to its clinical application. Twenty-two patients diagnosed with suspected non-muscle invasive bladder cancer were enrolled in the present study. Following intravesical administration of the probe, the entire mucosa was imaged under white and near-infrared imaging using an in-house developed endoscope that could switch between these two modes. The illuminated lesions under near-infrared light were biopsied and sent for histopathological examination. We observed a 5.1-fold increase in the fluorescence intensity in the tumor samples compared to normal tissue, and the probe demonstrated a sensitivity and specificity of 91.2% and 90%, respectively. Common diagnostic challenges, such as small satellite tumors, carcinoma in situ, and benign suspicious mucosa, were visualized and could be distinguished from cancer. Furthermore, no adverse effects were observed in humans. These first-in-human results indicate that PLSWT7-DMI-based near-infrared fluorescence endoscopy is a safe and effective approach for the improved detection of bladder cancer, and may enable thorough resection to prevent recurrence.

Stereotactic body radiation therapy for non-small cell lung cancer using the non-coplanar radiation of Cyberknife and Varian linac.

PURPOSE: This study aims to evaluate the planned dose of stereotactic body radiation therapy (SBRT) for treating early peripheral non-small cell lung cancer (NSCLC) using the non-coplanar radiation from Cyberknife and Varian linac. Moreover, this study investigates whether Cyberknife and Varian linac are qualified for non-coplanar radiation SBRT for treating early peripheral NSCLC, and which one is better for protecting organs at risk (OARs). METHODS: Retrospective analysis was performed based on the Cyberknife radiation treatment plans (RTPs) and Varian Eclipse RTPs of 10 patients diagnosed with early peripheral NSCLC. The dose distributions in the target and OARs were compared between the RTPs of Cyberknife and Varian Eclipse using Mim medical imaging software. RESULTS: For PTV, no significant difference in D98 and D95 between the Cyberknife and Eclipse was observed (t = -0.35, -1.67, P > 0.05). The homogeneity indexes (HIs) of Cyberknife plans are higher (t = 71.86, P < 0.05) than those of Eclipse plans. The V10, V15, V20, V25, V30 and Dmean of the lung with NSCLC and the V20 of the whole lung for Cyberknife were less than those for Eclipse (t = -4.73, -5.62, -7.75, -6.38, -6.89, -3.14, -7.09, respectively, P < 0.05). Cyberknife plans have smaller spinal cord Dmax, trachea Dmax, heart Dmax, chest wall Dmax (t = -2.49, -2.57, -3.71, -3.56, respectively, P < 0.05) and esophagus Dmax (t = -1.95, P > 0.05) than Varian Eclipse plans. CONCLUSION: To fulfill SBRT by non-coplanar radiation, Cyberknife is recommended for the institutions equipped with Cyberknife, while Varian linac can be applied for the institutions that have not adopted Cyberknife in clinical radiotherapy yet.

Intravesical In Situ Immunostimulatory Gel for Triple Therapy of Bladder Cancer.

Bladder cancer displays multiple biological features aided in drug resistance; therefore, single therapy fails to induce complete tumor regression. To address this issue, various kinds of cell death of cancer cells as well as restoring tumor immune microenvironment need to be taken into consideration. Here, we introduce a gel system termed AuNRs&IONs@Gel, which target-delivers a combination of photothermal, ferroptotic, and immune therapy through intravesical instillation. AuNRs&IONs@Gel consists of a gel delivery platform, embedded gold nanorods (AuNRs), and iron oxide nanoparticles (IONs). The targeted delivery gel platform provides dextran aldehyde-selective adhesion with cancer collagen. In this condition, photothermal therapy can be performed by gold nanorods (AuNRs) under imaging-guided near-infrared radiation. Local high concentrations of IONs can be absorbed by cancer cell to induce ferroptosis. Moreover, tumor-associated macrophages which often display an immune-suppressive M2-like phenotype will be repolarized by IONs into the antitumor M1-like phenotype, exerting a direct antitumor effect and professional antigen presentation of dead cancer cells. This process triggers a potent immune response of innate and adapt immunities to protect tumor rechallenge in long terms. Our triple-therapy strategy employs FDA-approved nanoparticles to inhibit bladder cancer which may possess great potential for clinical translation.

Identification of a Set of Genes Improving Survival Prediction in Kidney Renal Clear Cell Carcinoma through Integrative Reanalysis of Transcriptomic Data.

BACKGROUND: With an enormous amount of research concerning kidney cancer being conducted, various treatments have been applied to its cure. However, high recurrence and metastasis rates continue to pose a threat to the survival of patients with kidney renal clear cell carcinoma (KIRC). METHODS: Data from The Cancer Genome Atlas were downloaded, and a series of analyses were performed, including differential analysis, Cox analysis, weighted gene coexpression network analysis, least absolute shrinkage and selection operator analysis, multivariate Cox analysis, survival analysis, and receiver operating characteristic curve and functional enrichment analysis. RESULTS: A total of 5,777 differentially expressed genes were identified from the differential analysis. The Cox analysis showed 1,853 significant genes (P < 0.01). Weighted gene coexpression network analysis revealed that 226 genes in the module were related to clinical parameters, including Tumor-Node-Metastasis (TNM) staging. Least absolute shrinkage and selection operator and multivariate Cox analyses suggested that four genes (CDKL2, LRFN1, STAT2, and SOWAHB) had a potential function in predicting the survival time of patients with KIRC. Survival analysis uncovered that a high risk of these four genes was associated with an unfavorable prognosis. Receiver operating characteristic curve analysis further confirmed the accuracy of the risk score model. The analysis of clinicopathological parameters of the four identified genes revealed that they were associated with the progression of KIRC. CONCLUSION: The gene expression model consisting of CDKL2, LRFN1, STAT2, and SOWAHB is a promising tool for predicting the prognosis of patients with KIRC. The results of this study may provide insights into the diagnosis and treatment of KIRC.

Comparative effectiveness of different consolidation chemotherapy regimens for pediatric acute lymphoblastic leukemia: A protocol for systematic review and network meta analysis.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is one of the most commonly seen cancers in children, which mainly relates with inherited genetic variations. Consolidation chemotherapy is usually given to the pediatric ALL patients, however there is no meta-analysis and network analysis conducting the efficacy of the chemotherapy. Therefore, we perform a protocol to assess the efficacy of chemotherapeutics for pediatric ALL. METHODS: A literature search for randomized controlled trials about some specific chemotherapy regimens for pediatric ALL will be carried out in 7 electronic databases from their establishment to June 2019: the Cochrane Library, Embase, MEDLINE, the Chinese National Knowledge Infrastructure (CNKI), the Sino Med, the Chinese Scientific Journal Database (VIP) and the Wanfang Database. Complete continuous remission will be measured as primary outcome. Stata 14.0 will be utilized to perform a standard pairwise meta-analysis and the NMA, as well as draw Network Plots of Network Meta. RESULTS: This network meta-analysis will evaluate the efficacy of different consolidation chemotherapy regimens. CONCLUSION: This study will furnish decision-making reference on optimum proposal of chemotherapy regimens for pediatric ALL. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019134518.

New model for explaining the over-response phenomenon in percentage of depth dose curve measured using inorganic scintillating materials for optical fiber radiation sensors.

Inorganic scintillating material used in optical fibre sensors (OFS) when used as dosimeters for measuring percentage depth dose (PDD) characteristics have exhibited significant differences when compared to those measured using an ionization chamber (IC), which is the clinical gold standard for quality assurance (QA) assessments. The percentage difference between the two measurements is as high as 16.5% for a 10 × 10 cm2 field at 10 cm depth below the surface. Two reasons have been suggested for this: the presence of an energy effect and Cerenkov radiation. These two factors are analysed in detail and evaluated quantitatively. It is established that the influence of the energy effect is only a maximum of 2.5% difference for a beam size 10 × 10 cm2 compared with the measured ionization chamber values. And the influence of the Cerenkov radiation is less than 0.14% in an inorganic scintillating material in the case of OFS when using Gd2O2S:Tb as the luminescent material. Therefore, there must be other mechanisms leading to over-response. The luminescence mechanism of inorganic scintillating material is theoretically analysed and a new model is proposed and validated that helps explain the over-response phenomenon.

Water-equivalent fiber radiation dosimeter with two scintillating materials.

An inorganic scintillating material plastic optical fiber (POF) dosimeter for measuring ionizing radiation during radiotherapy applications is reported. It is necessary that an ideal dosimeter exhibits many desirable qualities, including water equivalence, energy independence, reproducibility, dose linearity. There has been much recent research concerning inorganic dosimeters. However, little reference has been made to date of the depth-dose characteristics of dosimeter materials. In the case of inorganic scintillating materials, they are predominantly non water-equivalent, with their effective atomic weight (Zeff) being typically much greater than that of water. This has been a barrier in preventing inorganic scintillating material dosimeter from being used in actual clinical applications. In this paper, we propose a parallel-paired fiber light guide structure to solve this problem. Two different inorganic scintillating materials are embedded separately in the parallel-paired fiber. It is shown that the information of water depth and absorbed dose at the point of measurement can be extracted by utilizing their different depth-dose properties.