Comprehensive Analysis of Predictive Value and the potential therapeutic target of NLRP3 inflammasome in glioma based on tumor microenvironment.

BACKGROUND: Glioma exhibits high recurrence rates and poor prognosis. The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in inflammation. There is a lack of research exploring the NLRP3 in glioma. METHODS: We used several databases, networks, Western blotting, multiple immunofluorescence staining to analyze the role of NLRP3 in inflammatory tumor microenvironment (TME). RESULTS: NLRP3 is higher-expression in glioma with a low mutation load. NLRP3 expression is linked to the infiltration of immune cells, chemokines, immunomodulators, and the TME. Signaling pathways, co-expression genes and interacting proteins contribute to the up-regulation of NLRP3. Patients responding to immunotherapy positively tend to have lower NLRP3 expression relating to the overall survival based on nomogram. Sensitivity to molecular medicines is observed in relation to NLRP3. CONCLUSION: The NLRP3 inflammasome plays a pivotal role in TME which could serve as a higher predictive value biomarker and therapeutic target for glioma treatment.

Combined application of myo-inositol and corn steep liquor enhances seedling growth and cold tolerance in cucumber and tomato.

Low temperatures pose a common challenge in the production of cucumbers and tomatoes, hindering plant growth and, in severe cases, leading to plant death. In our investigation, we observed a substantial improvement in the growth of cucumber and tomato seedlings through the application of corn steep liquor (CSL), myo-inositol (MI), and their combinations. When subjected to low-temperature stress, these treatments resulted in heightened levels of photosynthetic pigments, thereby fostering enhanced photosynthesis in both tomato and cucumber plants. Furthermore, it contributed to a decrease in malondialdehyde (MDA) levels and electrolyte leakage (REP). The effectiveness of the treatment was further validated through the analysis of key gene expressions (CBF1, COR, MIOX4, and MIPS1) in cucumber. Particularly, noteworthy positive outcomes were noted in the treatment involving 0.6 mL L-1 CSL combined with 72 mg L-1 MI. This study provides valuable technical insights into leveraging the synergistic effects of inositol and maize leachate to promote early crop growth and bolster resistance to low temperatures.

A Patient With Giant Meningioma With Intracranial and Extracranial Communication.

Atypical meningiomas, classified as World Health Organization (WHO) grade-2 tumors, are characterized by varied and unpredictable clinical behavior. Here, we report the case of an 80-year-old woman with a large meningioma displaying communication both intracranially and extracranially. The histopathological diagnosis confirmed a WHO grade-2 atypical meningioma. After complete surgical resection, the patient experienced a significant improvement in symptoms, with no evidence of recurrence on follow-up imaging. This case highlights the significance of understanding giant intracranial and extracranial communication meningiomas, shedding light on the favorable prognosis associated with WHO grade-2 atypical meningiomas after complete surgical resection.

Review and prospects of targeted therapies for Spleen tyrosine kinase (SYK).

Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase. The dysregulation of SYK is closely related to the occurrence and development of allergic diseases, autoimmune diseases and cancer. SYK has become an attractive target for drug discovery due to its important biological functions. This article reviews the biological function of SYK, the relationship between SYK and disease, and therapies targeting SYK. In addition, inspired by new technologies such as proteolysis targeting chimeras (PROTACs) and phosphatase recruiting chimeras (PHORCs), we propose the development of new therapeutic approaches for targeting SYK, such as SYK PROTACs and SYK PHORCs, which may overcome deficiencies of existing methods.

Editorial for Special Issue: Machine Health Monitoring and Fault Diagnosis Techniques.

Machine health monitoring and fault diagnosis have played crucial roles in automatic and intelligent industrial plants [...].

Machinery Prognostics and High-Dimensional Data Feature Extraction Based on a Transformer Self-Attention Transfer Network.

Machinery degradation assessment can offer meaningful prognosis and health management information. Although numerous machine prediction models based on artificial intelligence have emerged in recent years, they still face a series of challenges: (1) Many models continue to rely on manual feature extraction. (2) Deep learning models still struggle with long sequence prediction tasks. (3) Health indicators are inefficient for remaining useful life (RUL) prediction with cross-operational environments when dealing with high-dimensional datasets as inputs. This research proposes a health indicator construction methodology based on a transformer self-attention transfer network (TSTN). This methodology can directly deal with the high-dimensional raw dataset and keep all the information without missing when the signals are taken as the input of the diagnosis and prognosis model. First, we design an encoder with a long-term and short-term self-attention mechanism to capture crucial time-varying information from a high-dimensional dataset. Second, we propose an estimator that can map the embedding from the encoder output to the estimated degradation trends. Then, we present a domain discriminator to extract invariant features from different machine operating conditions. Case studies were carried out using the FEMTO-ST bearing dataset, and the Monte Carlo method was employed for RUL prediction during the degradation process. When compared to other established techniques such as the RNN-based RUL prediction method, convolutional LSTM network, Bi-directional LSTM network with attention mechanism, and the traditional RUL prediction method based on vibration frequency anomaly detection and survival time ratio, our proposed TSTN method demonstrates superior RUL prediction accuracy with a notable SCORE of 0.4017. These results underscore the significant advantages and potential of the TSTN approach over other state-of-the-art techniques.

ß-Lactams modulate neutrophil extracellular traps formation mediated by mTOR signaling pathway.

BACKGROUND: Some biotics, like ß-Lactams, have shown immunomodulation effects during sepsis, but the detailed mechanism was still unclear. Here we postulated that neutrophils play an essential role and ß-Lactams exert immunomodulation effects through modulating neutrophil extracellular traps (NETs) formation. METHODS: NETs formation induced by two ß-Lactams, Meropenem (MEM) and ceftazidime/tazobactam (CAZ/TB) in neutrophils from healthy donors and HL-60 cells was performed. Reactive oxygen species (ROS) generation and the activity of nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase were examined. Additionally, the upstream signal pathway of NETs formation, including protein kinase C (PKC), protein kinase B (Akt) and mammalian target of rapamycin (mTOR), were detected. RESULTS: MEM and CAZ/TB modulate NETs formation in activated PMNs, not resting PMNs. Both reduced ROS generation in resting PMNs and increased in activated PMNs. To test the activity of NADPH oxidase, we detected NADPH in MEM and CAZ/TB pre-cultivated activated PMNs, which showed that MEM and CAZ/TB modulates NETs formation through activation of NADHP oxidase by affecting the subunits of key enzymes. However, MEM reduced levels of phosho-PKC-Akt-mTOR, with no changes in CAZ/TB. CONCLUSIONS: We firstly demonstrate that ß-Lactams showed the definitive immunomodulation effects through modulating NETs formation, which is depended on PKC-Akt-mTOR signal pathway.

Outcomes and clinical characteristics of transmural intestinal necrosis in acute mesenteric ischemia.

Background: Acute mesenteric ischemia (AMI) is a rare life-threatening condition, especially for the patients with transmural intestinal necrosis (TIN). However, the optimal time for surgical intervention is controversial. As a series study, this study aimed to identify the outcomes and clinical characteristic of patients with TIN. Methods: Clinical data of 158 patients with AMI from January 2010 to December 2017 were retrospectively analyzed in a national gastrointestinal referral center in China to confirm the outcomes and identify predictors for TIN. Results: According to the results of pathological assessment and follow-up, 62 patients were TIN and 96 were non-TIN. Patients with TIN have a higher mortality and incidence of severe complications. The significant independent predictors for TIN were arterial lactate level (OR: 4.76 [2.29 ∼ 9.89]), free intraperitoneal fluid (OR: 9.49 [2.56 ∼ 35.24]) and pneumatosis intestinalis (OR: 7.08 [1.68 ∼ 29.82]) in computed tomography (CT) scan imaging. The overall area under the receiver operating characteristics (ROC) curve of the model was 0.934 (95% confidence interval: 0.893 ∼ 0.974). Using ROC curve, the cutoff value of arterial lactate level predicting the onset of TIN was 2.65 mmol/L. Conclusions: Patients concomitant with TIN manifest a higher risk of poor prognosis. The three predictors for TIN were arterial lactate level >2.65 mmol/L, free intraperitoneal fluid and pneumatosis intestinalis. Close monitoring these predictors would help identify AMI patients developed TIN and in urgent need for bowel resection.

Association between EZH2 Genetic Variants and Hepatocellular Carcinoma in a Chinese Han Population.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Studies have shown that EZH2, as the member of the Polycomb groups (PcGs) family, plays an important biological role in the occurrence and development of HCC. The association between the genetic variants of EZH2 and HCC is not yet fully established. METHODS: In this study, we used 175 patients with HCC and 209 healthy volunteers' blood samples of Chinese Han population to further analyze the relationship between EZH2 variants and HCC susceptibility. RESULTS: The results showed significant differences in distribution of alleles rs2302427 and rs3757441 between patients and the controls (p < 0.05). The three SNPs of EZH2 investigated show significant association with the elevated risk of HCC (p < 0.05) in addition to the overdominant model of rs3757441 and recessive model of rs41277434 (p > 0.05). The haplotype analysis of the three EZH2 SNPs revealed that the CCA and GTA haplotypes were associated with a higher risk of HCC (p < 0.05). CONCLUSIONS: The results of these experiments indicated that the presence of EZH2 variants was significantly associated with HCC, and these variants could be useful genetic markers for predicting susceptibility to HCC in a Chinese Han population.

A panel of autoantibodies as potential early diagnostic serum biomarkers in patients with breast cancer.

BACKGROUND: Specific circulating autoantibodies are produced by host immune systems to respond to antigens that arise during tumorigenesis. To achieve auxiliary diagnosis, the present study was designed to test whether circulating autoantibodies against tumor-associated antigens (TAAs) were altered in early breast cancer. METHODS: A total of 102 breast cancer patients and 146 age-matched healthy volunteers were recruited to participate in this study. Autoantibody expression was tested using in-house developed enzyme-linked immunosorbent assay (ELISA) with linear peptide envelope antigens derived from TAAs. RESULTS: Student's t tests showed that expression of autoantibodies against the panel (p16, c-myc, TP53, and ANXA-1) was significantly higher in the breast cancer group, stage I and II breast cancer group, and stage III and IV breast cancer group than in the healthy control group (p < 0.001, p < 0.001, p < 0.001). The sensitivities of detection of the panel (90% specificity) in these groups were 33.3%, 31.7%, and 33.3%, respectively, significantly higher than that of any single autoantibody. CONCLUSION: The panel of autoantibodies is more sensitive than single TAA autoantibody detection and may be used as biomarkers for early diagnosis of breast cancer.

A panel of autoantibodies as potential early diagnostic serum biomarkers in patients with cervical cancer.

The study was designed to test whether circulating autoantibodies against associated antigens (TAAs) were altered in early cervical cancer and benign cervical tumors. A total of 111 cervical cancer patients, 137 cervical benign tumor patients, and 160 healthy volunteers matched in age were recruited in this study. The expression of autoantibodies was tested using in-house developed enzyme-linked immunosorbent assay (ELISA) with linear peptide envelope antigens derived from TAAs. One-way ANOVA test showed that there was no difference in the CD25 autoantibody expression among the cervical cancer group, benign tumor group, and healthy control group (P = 0.063; P = 0.191). The expression of autoantibodies against survivin and TP53 in the cervical cancer group was significantly higher than that in the benign tumor group (P < 0.001; P < 0.001). The levels of autoantibodies against cyclinB-1 and ANXA-1 were higher in the cervical cancer group than in the healthy control group (P = 0.010; P = 0.001), while autoantibodies in the cervical cancer group showed no difference in expression compared with that in the benign tumor group. The panel of five TAAs showed a sensitivity of 37.8 % and a specificity of 90 %, which was much higher than the sensitivity of the single-TAA testing group. The data from this study further support our previous hypothesis that the detection of autoantibodies for the diagnosis of a specific cancer type can be enhanced using a panel of several selected TAAs as target antigens.

Detecting of p16 Autoantibody as a Potential Early Diagnostic Serum Biomarker in Patients with Cervical Cancer.

BACKGROUND: Over-expression of tumor-associated antigens (TAAs) may trigger secretion of their auto-antibodies. The present work was designed to test whether circulating antibody to P16 protein-derived antigens was altered in cervical cancer. METHODS: 141 cases of cervical cancer patients, 133 cases of cervical benign tumor patients, and 153 healthy volunteers matched in age were recruited. The level of circulating P16 auto-antibody was tested using an ELISA developed in-house with linear peptide antigens derived from the P16 protein. RESULTS: The P16 auto-antibody in the malignant tumor group had a significantly higher level than the healthy control group and the benign tumor group (t = 4.016, p < 0.001; t = 3.879, p < 0.001). Patients with stage I cervical cancer have the highest level of P16 autoantibody and the sensitivity against > 90% specificity was 20.3%. CONCLUSIONS: The circulating auto-antibody to P16 may be one of a series of potential biomarkers with early prognostic values for cervical cancer.

Functional magnetic resonance imaging reveals abnormal brain connectivity in EGR3 gene transfected rat model of schizophrenia.

Schizophrenia is characterized by the disorder of "social brain". However, the alternation of connectivity density in brain areas of schizophrenia patients remains largely unknown. In this study, we successfully created a rat model of schizophrenia by the transfection of EGR3 gene into rat brain. We then investigated the connectivity density of schizophrenia susceptible regions in rat brain using functional magnetic resonance imaging (fMRI) in combination with multivariate Granger causality (GC) model. We found that the average signal strength in prefrontal lobe and hippocampus of schizophrenia model group was significantly higher than the control group. Bidirectional Granger causality connection was observed between hippocampus and thalamic in schizophrenia model group. Both connectivity density and Granger causality connection were changed in prefrontal lobe, hippocampus and thalamus after risperidone treatment. Our results indicated that fMRI in combination with GC connection analysis may be used as an important method in diagnosis of schizophrenia and evaluation the effect of antipsychotic treatment. These findings support the connectivity disorder hypothesis of schizophrenia and increase our understanding of the neural mechanisms of schizophrenia.

Investigation of circulating antibodies to ANXA1 in breast cancer.

Our recent work demonstrated that circulating levels of IgG antibody to linear peptide antigens derived from annexin A1 (ANXA1) were significantly increased in lung cancer. The present study was then undertaken to test whether circulating anti-ANXA1 antibodies were also altered in breast cancer. An enzyme-linked immunosorbent assay was developed in-house to determine circulating IgG against ANXA1-derived peptide antigens in 152 female patients with breast cancer and 160 female control subjects. Student's t test revealed that patients with breast cancer had significantly higher levels of anti-ANXA1 IgG than control subjects (t = 4.75, P < 0.0001). Receiver operating characteristic (ROC) analysis showed that the area under the ROC curve was 0.73 with 95% confidence interval (CI) 0.67-0.78, and the sensitivity of anti-ANXA1 IgG assay was 23.2% against the specificity of 90%. The levels of anti-ANXA1 IgG did not appear to be stage-dependent, and Pearson correlation analysis showed no correlation between the anti-ANXA1 IgG levels and the stages of breast cancer (r = -0.02, df = 149, P = 0.796). This work suggests that circulating IgG for ANXA1-derived peptide antigens may have both diagnostic and prognostic values for breast cancer although further screening is needed to identify more such peptide antigens derived from tumor-associated antigens.

FOXP3 autoantibody as a potential early prognostic serum biomarker in patients with cervical cancer.

BACKGROUND: Overexpression of tumor-associated antigens has been reported in many types of cancer and may trigger secretion of their autoantibodies. The present work was designed to test whether circulating antibody to FOXP3 protein-derived antigens was altered in early cervical cancer and cervical benign tumors. METHODS: A total of 141 patients with cervical cancer, 133 patients with cervical benign tumors and 148 healthy age-matched volunteers were recruited. The level of circulating anti-FOXP3 IgG antibody was tested using an enzyme-linked immunosorbent assay developed in-house with linear peptide antigens derived from FOXP3 protein. The linear peptide antigens were designed according to the computational prediction of HLA-II epitopes. RESULTS: Student's t test showed that anti-FOXP3 IgG in the malignant tumor group and the benign tumor group was significantly higher than in the control group (t = 6.127, p < 0.001; t = 2.704, p = 0.007). In addition, patients with stage I cervical cancer (t = 2.968, p = 0.003) had a significantly higher level of FOXP3 autoantibodies than patients with benign tumors. The sensitivity against >90 % specificity was 20.6 % with an interassay deviation of 11.7 % in the cervical cancer group. Based on a cut-off value determined by the 98th percentile of the control group IgG levels, the anti-FOXP3 IgG positivity was 2.1 % in patients with cervical cancer compared to 2.0 % in the health controls (chi-squared = 0.004, p = 0.952, OR = 1.051, 95 % CI 0.209-5.295). CONCLUSION: The circulating autoantibody to FOXP3 reflecting the continuous development of the cervical lesion, may be a potential biomarker with early prognostic values for cervical cancer.

[Roles of biochemical factors in lateral compartment wear from varus knee osteoarthritis].

OBJECTIVE: To explore the roles of type II collagen C-terminal telopeptide (CTX-II), matrix metalloproteinase-13 (MMP-13) and interleukin-6 (IL-6) in lateral compartment wear in varus knee osteoarthritis. METHODS: Prospective reviews were conducted for the clinical data of varus knee osteoarthritis patients with lateral compartment wear undergoing total knee arthropalsty from June 2013 to June 2014. The gross findings of lateral compartment articular cartilage were recorded intraoperatively. And the slices were evaluated histologically. Synovial fluid was obtained by arthrocentesis. An equal number of operative patients from varus knee osteoarthritis without lateral compartment wear during the same period were selected and matched with respects to age, varus, preoperative range of motion and radiological grade of knee arthrosis. Synovial fluid concentrations of CTX-II, MMP-13 and IL-6 were evaluated. RESULTS: Histologic examination showed microscopic cartilage degeneration in both groups. The concentrations of CTX-II, IL-6 and MMP-13 in synovial fluid from lateral compartment wear group were (111.8±55.7) ng/L, (2.5±1.0) ng/L and (134.4±33.1) µg/L respectively. And there were no differences with control group (91.7±57.1) ng/L, (2.1±0.5) ng/L, (122.7±28.3) µg/L respectively. CONCLUSION: The above biochemical factors may not play key roles in lateral compartment wear of varus knee osteoarthritis.

Detection of circulating antibodies to linear peptide antigens derived from ANXA1 and DDX53 in lung cancer.

The EarlyCDT®-Lung test was the first autoantibody-based diagnostic tool for lung cancer, which was developed with a panel of recombinant protein antigens. To confirm whether the antibody test developed with linear peptide antigens has a similar power to that developed with the whole protein molecules, the present work was then undertaken to develop an in-house enzyme-linked immunosorbent assay with linear peptide antigens derived from annexin A1 (ANXA1) and DEAD box protein 53 (DDX53), which have been used to develop the EarlyCDT®-Lung test. A total of 272 patients with non-small cell lung cancer (NSCLC) and 227 control subjects matched in age and smoking history were recruited. Student's t test showed that the levels of circulating IgG to ANXA1-derived peptide antigens were significantly higher in patients with NSCLC than control subjects (t = 5.66, P < 0.0001), in which the increased anti-ANXA1 IgG levels were observed only in patients at stages I, II, or III, but not in those at stage IV. However, the levels of circulating IgG to DDX53-derived peptide antigens were not significantly altered in NSCLC (t = 1.78, P = 0.076). Receiver operating characteristic analysis showed that the sensitivity against specificity of >90% was 23.7% for ANXA1 IgG assay and 13.8% for DDX53 IgG assay. This work suggests that the linear peptide antigen derived from ANXA1 may be suitable for the development of diagnostic tool for lung cancer although further screening is needed to identify more such peptide antigens derived from tumor-associated antigens.

Autoantibodies against p16 protein-derived peptides may be a potential biomarker for non-small cell lung cancer.

Overexpression of tumor-associated antigens (TAAs) has been reported in many types of cancer and may trigger secretion of their autoantibodies. The present work was thus designed to test whether circulating antibody to p16 protein-derived antigens was altered in lung cancer. Two hundred seventy-one patients with non-small cell lung cancer (NSCLC) and 226 control subjects matched in age, gender, and smoking history were recruited in this study. The levels of circulating anti-p16 IgA and IgG antibodies were tested using an enzyme-linked immunosorbent assay (ELISA) developed in-house with linear peptide antigens derived from p16 protein. Student's t test showed that patients with NSCLC had a significant higher level of anti-p16 IgG antibody than control subjects (t = 2.74, P = 0.0063) but did not have a significant increase in IgA antibody levels (t = 1.92, P = 0.056). The sensitivity against >90% specificity was 19.7% for the IgG assay with an inter-assay deviation of 11.6%, and 10.3% for the IgA assay with an inter-assay deviation of 14.7%. Based on a cut-off value determined by the 99th percentile of control IgG levels, the anti-p16 IgG positivity was 6.7% in patients with NSCLC compared to 0.88% in control subjects (χ (2) = 10.58, P = 0.001, OR = 7.97, 95% CI 1.84­34.85). Circulating anti-p16 IgG levels were increased with stages of NSCLC, and patients with stage IV NSCLC had the highest IgG level among all four stages (t = 2.42, P = 0.016, compared with the control group). Pearson correlation analysis showed a significant correlation between circulating levels of IgA and IgG in the patient group (r = −0.2, df = 236, P = 0.0021) but not in the control group (r = −0.1, df = 205, P = 0.146). Circulating IgG antibody to p16 protein may be a potential biomarker with prognostic values for lung cancer.

Meningioma of the Fourth Ventricle of the Brain: A Case Report.

Meningiomas constitute a significant proportion of primary intracranial tumors; however, their occurrence within the brain's ventricles is exceptionally uncommon. This report details the case of a 24-year-old man who presented with six months of diplopia. Diagnostic imaging revealed a mass in the fourth ventricle, causing obstructive hydrocephalus. The patient underwent a lateral ventricular puncture for drainage, followed by surgical removal of the tumor. Histopathological examination identified the mass as a fibrous World Health Organization grade 1 meningioma. Symptoms were significantly relieved after surgery, and follow-up imaging results after three months showed that the patient had recovered well from surgery, with no residual lesions and no recurrence of the tumor. Intraventricular meningiomas often pose diagnostic challenges because of their resemblance to more prevalent intracranial lesions on imaging studies such as choroid plexus papillomas. This case underscores the critical role of histopathological analysis in establishing a definitive diagnosis. Surgical excision is the primary treatment strategy for intraventricular meningiomas, generally resulting in positive outcomes.

Contrastive learning and dynamics embedding neural network for label-free interpretable machine fault diagnosis.

Industrial machinery often produces vibration signals that can serve as indicators of underlying faults. However, these signals often need to be labeled, presenting a challenge for accurate and interpretable fault diagnosis. While supervised learning methods, such as deep neural networks, have been applied for fault diagnosis, they need help in effectively distinguishing between different vibration-related faults. In response to this issue, our study introduces an innovative approach for automatic fault diagnosis through the application of the Bootstrap Your Own Latent and Dynamical Systems Model Discovery algorithm (BYOLDIS). This method not only addresses the challenge of unlabelled signals but also provides readily interpretable results. The proposed methodology consists of three fundamental steps. First, we derive a matrix of differential equations to capture the dynamic behavior of faulty bearings. Second, we employ a contrastive learning network alongside a time-delay embedding matrix to reconstruct the coordinates of the fault-dynamical system. Lastly, we construct a library of fault machine dynamic polynomial equations, incorporating prior constraints based on physical models. To assess the effectiveness and robustness of our proposed method, we conducted both simulations and experiments. The results of these case studies affirm that BYOLDIS can accurately diagnose bearing faults and offer dynamic explanations for the diagnostic outcomes. This suggests that BYOLDIS holds substantial promise as a diagnostic tool for processing unlabelled vibrational data.