The diagnostic efficiency of integration of 2HG MRS and IVIM versus individual parameters for predicting IDH mutation status in gliomas in clinical scenarios: A retrospective study.

PURPOSE: Currently, there remains a scarcity of established preoperative tests to accurately predict the isocitrate dehydrogenase (IDH) mutation status in clinical scenarios, with limited research has explored the potential synergistic diagnostic performance among metabolite, perfusion, and diffusion parameters. To address this issue, we aimed to develop an imaging protocol that integrated 2-hydroxyglutarate (2HG) magnetic resonance spectroscopy (MRS) and intravoxel incoherent motion (IVIM) by comprehensively assessing metabolic, cellular, and angiogenic changes caused by IDH mutations, and explored the diagnostic efficiency of this imaging protocol for predicting IDH mutation status in clinical scenarios. METHODS: Patients who met the inclusion criteria were categorized into two groups: IDH-wild type (IDH-WT) group and IDH-mutant (IDH-MT) group. Subsequently, we quantified the 2HG concentration, the relative apparent diffusion coefficient (rADC), the relative true diffusion coefficient value (rD), the relative pseudo-diffusion coefficient (rD*) and the relative perfusion fraction value (rf). Intergroup differences were estimated using t-test and Mann-Whitney U test. Finally, we performed receiver operating characteristic (ROC) curve and DeLong's test to evaluate and compare the diagnostic performance of individual parameters and their combinations. RESULTS: 64 patients (female, 21; male, 43; age, 47.0 ± 13.7 years) were enrolled. Compared with IDH-WT gliomas, IDH-MT gliomas had higher 2HG concentration, rADC and rD (P < 0.001), and lower rD* (P = 0.013). The ROC curve demonstrated that 2HG + rD + rD* exhibited the highest areas under curve (AUC) value (0.967, 95%CI 0.889-0.996) for discriminating IDH mutation status. Compared with each individual parameter, the predictive efficiency of 2HG + rADC + rD* and 2HG + rD + rD* shows a statistically significant enhancement (DeLong's test: P < 0.05). CONCLUSIONS: The integration of 2HG MRS and IVIM significantly improves the diagnostic efficiency for predicting IDH mutation status in clinical scenarios.

Construction of rBCG carrying the IL-2-BZLF1 fusion gene and its immunological function.

In this research, a recombinant Bacillus Calmette Guerin (rBCG) vector vaccine carrying a human IL-2 and EBV BZLF1 fusion gene (IL-2-BZLF1-rBCG) was constructed. The IL-2-BZLF1-rBCG construct was successfully generated and stably expressed the IL-2 and BZLF1 proteins. IL-2-BZLF1-rBCG activated the immune system and promoted the secretion of IFN-γ and TNF-α by CD4+ and CD8+ T cells. IL-2-BZLF1-rBCG activated lymphocytes to effectively kill EBV-positive NPC cells in vitro. Additionally, IL-2-BZLF1-rBCG stimulated the proliferation of NK cells and lymphocytes in vivo, activated related immune responses, and effectively treated EBV-positive NPC. The immune response to and pharmacological effect of IL-2-BZLF1-rBCG were explored in vitro and in vivo to provide a theoretical and experimental basis for the prevention and treatment of EBV-positive tumors with an rBCG vector vaccine. KEY POINTS: • rBCG with human IL-2 and BZLF1 of EB virus was constructed • The IL-2-BZLF1 fusion gene was stably expressed with rBCG • rBCG with IL-2-BZLF1 has an obvious immune response in vitro and in vivo.

Nursing care of patients with relapsed and refractory multiple myeloma treated with B-cell mature antigen-targeted universal chimeric antigen receptor T cells.

To investigate the efficacy of a nursing approach using B-cell maturation antigen (BCMA)-targeted universal chimeric antigen receptor T-cell (BCMA-UCART) immunotherapy in the treatment of 8 patients with relapsed refractory multiple myeloma (MM). In this study, 16 patients with relapsed and refractory MM who were treated with BCMA-targeted UCART in our department from May 2020 to November 2022 were selected, and were divided into a control group and an experimental group of 8 cases each according to the difference in the nursing methods, and the control group adopted the conventional universal nursing program. The experimental group used the nursing protocol that cooperated with the immunotherapy of this study, and the main points of nursing care included timely assessment of organ functional status, safe and accurate infusion of BCMA-UCART, identification and management of hyperthermia, hypotension, arrhythmia and central nervous system adverse reactions caused by cytokine release after BCMA-UCART infusion, as well as management of fluid imbalance, maintenance of stable blood pressure, and cooperation with physicians to effectively control of inflammatory factors. In addition, patients were provided with psychological and dietary support. The duration of hospitalization was compared between the two groups after the intervention. The discharge time of the experimental group was significantly shorter than that of the control group (P he.05), and the experimental group effectively controlled cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome and acute graft-versus-host disease. The nursing program with BCMA-UCART immunotherapy is effective in intervening MM patients and promotes their early recovery and discharge from the hospital.

"Salting out" in Hofmeister Effect Enhancing Mechanical and Electrochemical Performance of Amide-based Hydrogel Electrolytes for Flexible Zinc-Ion Battery.

With the development of flexible and wearable electronic devices, it is a new challenge for polymer hydrogel electrolytes to combine high mechanical flexibility and electrochemical performance into one membrane. In general, the high content of water in hydrogel electrolyte membranes always leads to poor mechanical strength, and limits their applications in flexible energy storage devices. In this work, based on the "salting out" phenomenon in Hofmeister effect, a kind of gelatin-based hydrogel electrolyte membrane is fabricated with high mechanical strength and ionic conductivity by soaking pre-gelated gelatin hydrogel in 2 m ZnSO4 aqueous. Among various gelatin-based electrolyte membranes, the gelatin-ZnSO4 electrolyte membrane delivers the "salting out" property of Hofmeister effect, which improves both the mechanical strength and electrochemical performance of gelatin-based electrolyte membranes. The breaking strength reaches 1.5 MPa. When applied to supercapacitors and zinc-ion batteries, it can sustain over 7500 and 9300 cycles for repeated charging and discharging processes. This study provides a very simple and universal method to prepare polymer hydrogel electrolytes with high strength, toughness, and stability, and its applications in flexible energy storage devices provide a new idea for the construction of secure and stable flexible and wearable electronic devices.

Electrolyte-Wettability Issues and Challenges of Electrode Materials in Electrochemical Energy Storage, Energy Conversion, and Beyond.

The electrolyte-wettability of electrode materials in liquid electrolytes plays a crucial role in electrochemical energy storage, conversion systems, and beyond relied on interface electrochemical process. However, most electrode materials do not have satisfactory electrolyte-wettability for possibly electrochemical reaction. In the last 30 years, there are a lot of literature have directed at exploiting methods to improve electrolyte-wettability of electrodes, understanding basic electrolyte-wettability mechanisms of electrode materials, exploring the effect of electrolyte-wettability on its electrochemical energy storage, conversion, and beyond performance. This review systematically and comprehensively evaluates the effect of electrolyte-wettability on electrochemical energy storage performance of the electrode materials used in supercapacitors, metal ion batteries, and metal-based batteries, electrochemical energy conversion performance of the electrode materials used in fuel cells and electrochemical water splitting systems, as well as capacitive deionization performance of the electrode materials used in capacitive deionization systems. Finally, the challenges in approaches for improving electrolyte-wettability of electrode materials, characterization techniques of electrolyte-wettability, as well as electrolyte-wettability of electrode materials applied in special environment and other electrochemical systems with electrodes and liquid electrolytes, which gives future possible directions for constructing interesting electrolyte-wettability to meet the demand of high electrochemical performance, are also discussed.

Pyruvate Kinase M2 Contributes to TLR-Mediated Inflammation and Autoimmunity by Promoting Pyk2 Activation.

Toll-like receptors (TLRs) play critical roles in regulating the abnormal activation of the immune cells resulting in the pathogenesis of inflammation and autoimmune diseases. Pyruvate kinase M2 (PKM2), which governs the last step of glycolysis, is involved in multiple cellular processes and pathological conditions. However, little is known about the involvement of PKM2 in regulating TLR-mediated inflammation and autoimmunity. Herein, we investigated the role of PKM2 in the activation of the TLR pathways and the pathogenesis of inflammation and autoimmune diseases. The activation of TLR4, TLR7 and TLR9 pathways was found to induce the up-regulation of PKM2 expression in macrophages, dendritic cells (DCs) and B cells. The over-expression of PKM2 promotes the activation of TLR4, TLR7 and TLR9 pathways while interference with the PKM2 expression or the addition of the PKM2 inhibitor (PKM-IN) markedly inhibited the activation of TLR4, TLR7 and TLR9 pathways. Mechanistically, PKM2 augmented the activation of TLR4, TLR7 and TLR9 pathways by promoting the activation of the proline-rich tyrosine kinase 2 (Pyk2). Intriguingly, the PKM2 inhibitor PKM2-IN significantly protected the mice from the endotoxic shock mediated by the TLR4-agonist LPS. Additionally, it alleviated the progression in the TLR7-agonist imiquimod-mediated lupus mice and spontaneous lupus MRL/lpr mice. Moreover, PKM2 expression was highly elevated in the monocytes, DCs and B cells from systemic lupus erythematous (SLE) patients compared with those from the healthy donors. Besides, the PKM2 expression level was positively correlated with the degree of activation of these immune cells. In summary, PKM2 contributed to TLR-mediated inflammation and autoimmunity and can be a valuable target to control inflammation and autoimmunity.

Chemically building interpenetrating polymeric networks of Bi-crosslinked hydrogel macromolecules for membrane supercapacitors.

Macromolecular polymer hydrogels used in flexible supercapacitors and batteries have attracted extensive attention in recent years. In this paper, we use a simple polymer interpenetrating technology involving covalent cross-linking and non-covalent cross-linking aspects based on polyvinyl alcohol and carboxylated chitosan to prepare a flexible polymer hydrogel membrane for supercapacitor. The obtained hydrogel membrane has good flexibility and high ionic conductivity of 2.561×10-2 s·cm-1. The hydrogel electrode membrane prepared by in-situ polymerization of aniline exhibits an area specific capacitance of 580 mF·cm-2 at a current density of 0.5 mA·cm-2. And the symmetric all-gel-state supercapacitor with hydrogel membrane as the gel electrolyte shows a high specific capacitance of 325 mF·cm-2 at 1.0 mA·cm-2. We believe that this hydrogel film has considerable application prospects in flexible wearable electronic devices.

Differential Diagnosis of Solitary Fibrous Tumor/Hemangiopericytoma and Angiomatous Meningioma Using Three-Dimensional Magnetic Resonance Imaging Texture Feature Model.

BACKGROUND: Intracranial solitary fibrous tumor(SFT)/hemangiopericytoma (HPC) is an aggressive malignant tumor originating from the intracranial vasculature. Angiomatous meningioma (AM) is a benign tumor with a good prognosis. The imaging manifestations of the two are very similar. Thus, novel noninvasive diagnostic method is urgently needed in clinical practice. Texture analysis and model building through machine learning may have good prospects. AIM: To evaluate whether a 3D-MRI texture feature model could be used to differentiate malignant intracranial SFT/HPC from AM. METHOD: A total of 97 patients with SFT/HPC and 95 with AM were included in this study. Patients from each group were randomly divided into the train (70%) and test (30%) sets. ROIs were drawn along the edge of the tumor on each section of T1WI, T2WI, and contrasted T1WI using ITK-SNAP software. The segmented image was imported into the AK software for texture feature extraction, and the 3D ROI signal intensity histograms of T1WI, T2WI, and contrasted T1WI were automatically obtained along with all the parameters. Modeling was performed using the language R. Confusion matrix was used to analyze the accuracy of the model. ROC curve was constructed to assess the grading ability of the logistic regression model. RESULTS: After Lasso dimension reduction, 5, 9, and 7 texture features were extracted from T1WI, T2WI, and contrasted T1WI, respectively; additional 8 texture features were extracted from the combined sequence for modeling. The ROC analyses on four models resulted in an area under the curve (AUC) of 0.885 (sensitivity 76.1%, specificity 87.9%) for T1WI model, 0.918 (73.1%, 95.5%) for T2WI model, 0.815 (55.2%, 93.9%) for contrasted T1WI model, and 0.959 (92.5%, 84.8%) for the combined sequence model and were enough to correctly distinguish the two groups in 71.2%, 81.4%, 69.5%, and 83.1% of cases in test set, respectively. CONCLUSIONS: The radiological model based on texture features could be used to differentiate SFT/HPC from AM.

Chromosome painting and its applications in cultivated and wild rice.

BACKGROUND: The chromosome-specific probe is a fundamental tool of chromosome painting and has been commonly applied in mammalian species. The technology, however, has not been widely applied in plants due to a lack of methodologies for probe development. Identification and labeling of a large number of oligonucleotides (oligos) specific to a single chromosome offers us an opportunity to establish chromosome-specific probes in plants. However, never before has whole chromosome painting been performed in rice. RESULTS: We developed a pooled chromosome 9-specific probe in rice, which contains 25,000 oligos based on the genome sequence of a japonica rice (Oryza sativa L., AA, 2n = 2× = 24). Chromosome 9 was easily identified in both japonica and indica rice using this chromosome 9-painting probe. The probe was also successfully used to identify and characterize chromosome 9 in additional lines of O. sativa, a translocation line, two new aneuploids associated with chromosome 9 and a wild rice (Oryza eichingeri A. Peter, CC, 2n = 2× = 24). CONCLUSION: The study reveals that a pool of oligos specific to a chromosome is a useful tool for chromosome painting in rice.

Rice RAD51 paralogs play essential roles in somatic homologous recombination for DNA repair.

Synthesis-dependent strand annealing (SDSA) and single-strand annealing (SSA) are the two main homologous recombination (HR) pathways in double-strand break (DSB) repair. The involvement of rice RAD51 paralogs in HR is well known in meiosis, although the molecular mechanism in somatic HR remains obscure. Loss-of-function mutants of rad51 paralogs show increased sensitivity to the DSB-inducer bleomycin, which results in greatly compromised somatic recombination efficiencies (xrcc3 in SDSA, rad51b and xrcc2 in SSA, rad51c and rad51d in both). Using immunostaining, we found that mutations in RAD51 paralogs (XRCC3, RAD51C, or RAD51D) lead to tremendous impairment in RAD51 focus formation at DSBs. Intriguingly, the RAD51C mutation has a strong effect on the protein loading of its partners (XRCC3 and RAD51B) at DSBs, which is similar to the phenomenon observed in the case of blocking PI3K-like kinases in wild-type plant. We conclude that the rice CDX3 complex acts in SDSA recombination while the BCDX2 complex acts in SSA recombination in somatic DSB repair. Importantly, RAD51C serves as a fulcrum for the local recruitment of its partners (XRCC3 for SDSA and RAD51B for SSA) and is positively modulated by PI3K-like kinases to facilitate both the SDSA and SSA pathways in RAD51 paralog-dependent somatic HR.

Transcriptional changes of rice in response to rice black-streaked dwarf virus.

Rice black-streaked dwarf virus (RBSDV), a member of the genus Fijivirus in the family Reoviridae, causes significant economic losses in rice production in China and many other Asian countries. Although a great deal of effort has been made to elucidate the interactions among the virus, insect vectors, host and environmental conditions, few RBSDV proteins involved in pathogenesis have been identified, and the biological basis of disease development in rice remains largely unknown. Transcriptomic information associated with the disease development in rice would be helpful to unravel the biological mechanism. To determine how the rice transcriptome changes in response to RBSDV infection, we carried out RNA-Seq to perform a genome-wide gene expression analysis of a susceptible rice cultivar KTWYJ3. The transcriptomes of RBSDV-infected samples were compared to those of RBSDV-free (healthy) at two time points (time points are represented by group I and II). The results derived from the differential expression analysis in RBSDV-infected libraries vs. healthy ones in group I revealed that 102 out of a total of 281 significant differentially expressed genes (DEGs) were up-regulated and 179 DEGs were down-regulated. Of the 2592 identified DEGs in group II, 1588 DEGs were up-regulated and 1004 DEGs were down-regulated. A total of 66 DEGs were commonly identified in both groups. Of these 66 DEGs, expression patterns for 36 DEGs were similar in both groups. Our analysis demonstrated that some genes related to disease defense and stress resistance were up-regulated while genes associated with chloroplast were down-regulated in response to RBSDV infection. In addition, some genes associated with plant-height were differentially expressed. This result indicates those genes might be involved in dwarf symptoms caused by RBSDV. Taken together, our results provide a genome-wide transcriptome analysis for rice plants in response to RBSDV infection which may contribute to the understanding of the regulatory mechanisms involved in rice-RBSDV interaction and the biological basis of rice black-streaked dwarf disease development in rice.

Systemic minor histocompatibility antigen expression in blood endothelial cells prevents T cell-mediated vascular immunopathology.

Attenuation of T cell-mediated damage of blood endothelial cells (BECs) in transplanted organs is important to prevent transplant vasculopathy (TV) and chronic rejection. Here, we assessed the importance of minor histocompatibility antigen (mHA) distribution and different coinhibitory molecules for T cell-BEC interaction. A transgenic mHA was directed specifically to BECs using the Tie2 promoter and cellular interactions were assessed in graft-versus-host disease-like and heterotopic heart transplantation settings. We found that cognate CD4(+) T-cell help was critical for the activation of BEC-specific CD8(+) T cells. However, systemic mHA expression on BECs efficiently attenuated adoptively transferred, BEC-specific CD4(+) and CD8(+) T cells and hence prevented tissue damage, whereas restriction of mHA expression to heart BECs precipitated the development of TV. Importantly, the lack of the coinhibitory molecules programmed death-1 (PD-1) and B and T lymphocyte attenuator fostered the initial activation of BEC-specific CD4(+) T cells, but did not affect development of TV. In contrast, TV was significantly augmented in the absence of PD-1 on BEC-specific CD8(+) T cells. Taken together, these results indicate that antigen distribution in the vascular bed determines the impact of coinhibition and, as a consequence, critically impinges on T cell-mediated vascular immunopathology.

Total cholesterol content of erythrocyte membranes levels are associated with the presence of acute coronary syndrome and high sensitivity C-reactive protein.

In this study we assessed whether total cholesterol content of erythrocyte membranes (CEM) was associated with the presence of acute coronary syndrome (ACS) and high sensitivity C-reactive protein (hs-CRP). Consecutive angina patients were assessed; 98 had ACS and 45 had stable angina pectoris (SAP). CEM in the ACS group was significantly higher compared with the SAP group (p< 0.05). Multiple logistic regression analyses revealed a significant independent relation between CEM and the presence of ACS (OR 24.990, p<0.001). CEM was positively correlated with serum hs-CRP levels (r=0.328, p<0.001). These findings suggest a potential role of CEM as a marker of vulnerable plaque.