The CEBPB+ glioblastoma subcluster specifically drives the formation of M2 tumor-associated macrophages to promote malignancy growth.

Rationale: The heterogeneity of tumor cells within the glioblastoma (GBM) microenvironment presents a complex challenge in curbing GBM progression. Understanding the specific mechanisms of interaction between different GBM cell subclusters and non-tumor cells is crucial. Methods: In this study, we utilized a comprehensive approach integrating glioma single-cell and spatial transcriptomics. This allowed us to examine the molecular interactions and spatial localization within GBM, focusing on a specific tumor cell subcluster, GBM subcluster 6, and M2-type tumor-associated macrophages (M2 TAMs). Results: Our analysis revealed a significant correlation between a specific tumor cell subcluster, GBM cluster 6, and M2-type TAMs. Further in vitro and in vivo experiments demonstrated the specific regulatory role of the CEBPB transcriptional network in GBM subcluster 6, which governs its tumorigenicity, recruitment of M2 TAMs, and polarization. This regulation involves molecules such as MCP1 for macrophage recruitment and the SPP1-Integrin αvß1-Akt signaling pathway for M2 polarization. Conclusion: Our findings not only deepen our understanding of the formation of M2 TAMs, particularly highlighting the differential roles played by heterogeneous cells within GBM in this process, but also provided new insights for effectively controlling the malignant progression of GBM.

Dry Lithography Patterning of Monolayer Flexible Field Effect Transistors by 2D Mica Stamping.

Organic field-effect transistors (OFETs) based on 2D monolayer organic semiconductors (OSC) have demonstrated promising potentials for various applications, such as light emitting diode (LED) display drivers, logic circuits, and wearable electrocardiography (ECG) sensors. To date, the fabrications of this class of highly crystallized 2D organic semiconductors (OSC) are dominated by solution shearing. As these organic active layers are only a few molecular layers thick, their compatibilities with conventional thermal evaporated top electrodes or sophisticated photolithography patterning are very limited, which also restricts their device density. Here, an electrode transfer stamp and a semiconductor patterning stamp are developed to fabricate OFETs with channel lengths down to 3 µm over a large area without using any chemicals or causing any damage to the active layer. 2D 2,9-didecyldinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene (C10 -DNTT) monolayer OFETs developed by this new approach shows decent performance properties with a low threshold voltage (VTH ) less than 0.5 V, intrinsic mobility higher than 10 cm2 V-1 s-1 and a subthreshold swing (SS) less than 100 mV dec-1 . The proposed patterning approach is completely comparable with ultraflexible parylene substrate less than 2 µm thick. By further reducing the channel length down to 2 µm and using the monolayer OFET in an AC/DC rectifying circuit, the measured cutoff frequency is up to 17.3 MHz with an input voltage of 4 V. The newly proposed electrode transfer and patterning stamps have addressed the long-lasting compatibility problem of depositing electrodes onto 2D organic monolayer and the semiconductor patterning. It opens a new path to reduce the fabrication cost and simplify the manufacturing process of high-density OFETs for more advanced electronic or biomedical applications.

LSM12 facilitates the progression of colorectal cancer by activating the WNT/CTNNB1 signaling pathway.

Aberrant activation of the WNT signaling pathway is a joint event in colorectal cancer (CRC), but the molecular mechanism is still unclear. Recently, RNA-splicing factor LSM12 (like-Sm protein 12) is highly expressed in CRC tissues. This study aimed to verify whether LSM12 is involved in regulating CRC progression via regulating the WNT signaling pathway. Here, we found that LSM12 is highly expressed in CRC patient-derived tissues and cells. LSM12 is involved in the proliferation, invasion, and apoptosis of CRC cells, similar to the function of WNT signaling in CRC. Furthermore, protein interaction simulation and biochemical experiments proved that LSM12 directly binds to CTNNB1 (also known as ß-Catenin) and regulates its protein stability to affect the CTTNB1-LEF1-TCF1 transcriptional complex formation and the associated WNT downstream signaling pathway. LSM12 depletion in CRC cells decreased the in vivo tumor growth through repression of cancer cell growth and acceleration of cancer cell apoptosis. Taken together, we suggest that the high expression of LSM12 is a novel factor leading to aberrant WNT signaling activation, and that strategies targeting this molecular mechanism may contribute to developing a new therapeutic method for CRC.

Lumboperitoneal shunt for the treatment of leptomeningeal metastasis.

Leptomeningeal metastasis (LM) is thought to be a devastating and increasingly frequent neurological complication of cancer characterized by infiltration of malignant cells into the leptomeninges and the subarachnoid space. Intracranial hypertension and hydrocephalus are observed in about half of patients with LM. They are responsible for rapidly declining neurological status and eventual poor outcome in many patients with LM. Impediment of CSF circulation is considered the pathophysiological basis of increased intracranial pressure and hydrocephalus related to LM, which makes ventriculoperitoneal shunt (VP shunt) an acceptable palliative approach for LM now. It is noteworthy that LM generally causes communicating hydrocephalus. Lumboperitoneal shunt (LP shunt) has been demonstrated to be effective in the treatment of communicating hydrocephalus secondary to hemorrhage or infection, idiopathic intracranial hypertension and normal pressure hydrocephalus. And LP shunt has several advantages over VP shunt. Therefore we hypothesize that LP shunt can be used in the treatment of intracranial hypertension and hydrocephalus related to LM and should be given greater priority over VP shunt.

The concentration of CYFRA 21-1, NSE and CEA in cerebro-spinal fluid can be useful indicators for diagnosis of meningeal carcinomatosis of lung cancer.

PURPOSES: We aimed to investigate the concentration of CYFRA 21-1, NSE and CEA in cerebro-spinal fluid (CSF) and to explore their clinical value in the meningeal carcinomatosis (MC) of lung cancer. So that, sensitive and specificity of CSF examination can be improved in the initial diagnosis of MC. METHOD: A total of 35 lung cancer patients and 35 patients with benign brain tumor in the same period enrolled in this study. The concentrations of tumor markers CEA, CYFRA 21-1 and NSE in CSF and peripheral blood were examined. RESULT: The concentrations of three tumor markers of CYFRA 21-1, NSE and CEA in blood serum and CSF were obviously higher than that of benign disease group. In MC patients, the concentrations of three tumor markers of CYFRA 21-1, NSE and CEA in blood serum were significant lower than that in CSF. The maximum of Youden's index was identified as the cutoff value of indicator of MC in three tumor markers in CSF which were CEA > 4.7 µg/L, NSE > 14.6 µg/L and CYFRA21-1 > 5.5 µg/L respectively. Based on the cutoff values, the CEA had the highest sensitivity while the CYFRA21-1 had the highest specificitiy. Three tumor markers in the CSF had higher positive rate than those in blood serum. We combined the levels of CEA, NSE and CYFRA21-1 in CSF to diagnosis of MC. Positive of CEA or CYFRA21-1 had the greatest sensitivity of 100% while the specificity of 91.4%; the positive of both CEA and CYFRA21-1 had the highest specificity of 100% while the sensitivity of 74.3%. Both positive predictive value and negative predictive value were 100% when combination positive were confirmed when the all three markers were positive. CONCLUSION: The combination of CEA and CYFRA21-1 can be recommended in early screening of meningeal carcinoma. Especially, for the patient who was difficult to be diagnosed by CSF histology and MRI, it will be a useful auxiliary marker in diagnosis of MC. The combination of CEA, NSE and CYFRA21-1 can be an effective clinically confirmation and exclusively diagnose indictor of MC.

[The clinical analysis of primary central nervous system lymphoma in 23 patients].

OBJECTIVE: To explore the clinical characteristics and the relationship between rational therapy and prognosis in primary central nervous system lymphoma (PCNSL). METHODS: Clinical data of 23 patients pathologically confirmed as PCNSL and treated in our hospital from January 2005 to December 2007 were collected and analyzed retrospectively. SPSS 13.0 statistical analysis software was used to analyze the correlation between therapy, clinical characteristics and prognosis. Among the 23 patient, 10 were male and 13 were female, with a median age of 50 (2 - 75) years old. Eighteen patients were undertaken lumbar puncture, and tumor cells in cerebral spinal fluid (CSF) was found in 4 patients. Tumorectomy was performed in 8 patient, while 15 patients biopsy. Among them, 4 accepted whole brain irradiation, 6 accepted associated chemotherapy based on a high-dose of methotrexate (MTX) and 13 accepted radiotherapy combined with chemotherapy. RESULTS: Kaplan-Meier analysis showed that in this serial patients, the median survival time was 45.0 months and the 3-year survival rate was 56.5%. Log-Rank test revealed that the whole survival time and the non-progression survival time of radiotherapy combined with chemotherapy (43.8 and 30.0 months, respectively) and high-dose MTX chemotherapy (39.7 and 29.7 months, respectively) were much longer than those of radiotherapy alone (25.7 and 19.8 months, respectively, all P < 0.05). Log-Rank test showed no significant difference between high-dose MTX chemotherapy alone and radiotherapy combined with chemotherapy (P > 0.05), but the whole survival time was much shorter in high-dose MTX chemotherapy (P < 0.05). CONCLUSIONS: The detection of tumor cells in CSF can confirm the diagnosis, but pathological biopsy is the gold standard. The efficacy of associated chemotherapy based on a high-dose of MTX combined with radiotherapy is much better than radiotherapy or chemotherapy alone.