Interferon signaling and ferroptosis in tumor immunology and therapy.

This study sought to elucidate the mechanisms underlying the impact of the interferon signaling pathway on Ferroptosis in tumor cells and its correlation with CD8 + T cell exhaustion. Using mouse models and single-cell sequencing, the researchers studied the interaction between CD8 + T cells and the interferon signaling pathway. Differential gene analysis revealed key genes involved in CD8 + T cell exhaustion, and their downstream factors were explored using bioinformatics tools. The expression levels of interferon-related genes associated with Ferroptosis were analyzed using data from the TCGA database, and their relevance to tumor tissue Ferroptosis and patients' prognosis was determined. In vitro experiments were conducted to measure the levels of IFN-γ, MDA, and LPO, as well as tumor cell viability and apoptosis. In vivo validation using a mouse tumor model confirmed the results obtained from the in vitro experiments, highlighting the potential of silencing HSPA6 or DNAJB1 in enhancing the efficacy of PD-1 therapy and inhibiting tumor growth and migration.

Evaluation of metagenomic and pathogen-targeted next-generation sequencing for diagnosis of meningitis and encephalitis in adults: A multicenter prospective observational cohort study in China.

BACKGROUND: Next-generation sequencing (NGS) might aid in the identification of causal pathogens. However, the optimal approaches applied to cerebrospinal fluid (CSF) for detection are unclear, and studies evaluating the application of different NGS workflows for the diagnosis of intracranial infections are limited. METHODS: In this multicenter, prospective observational cohort study, we described the diagnostic efficacy of pathogen-targeted NGS (ptNGS) and metagenomic NGS (mNGS) compared to that of composite microbiologic assays, for infectious meningitis/encephalitis (M/E). RESULTS: In total, 152 patients diagnosed with clinically suspected M/E at four tertiary hospitals were enrolled; ptNGS and mNGS were used in parallel for pathogen detection in CSF. Among the 89 patients who were diagnosed with definite infectious M/E, 57 and 39 patients had causal microbial detection via ptNGS and mNGS, respectively. The overall accuracy of ptNGS was 65.1%, with a positive percent agreement (PPA) of 64% and a negative percent agreement (NPA) of 66.7%; and the overall accuracy of mNGS was 47.4%, with a PPA of 43.8% and an NPA of 52.4% after discrepancy analysis. There was a significant difference in the detection efficiency between these two methods both for PPA (sensitivity) and overall accuracy for pathogen detection (P < 0.05). CONCLUSIONS: NGS tests have provided new information in addition to conventional microbiologic tests. ptNGS seems to have superior performance over mNGS for common causative pathogen detection in CSF for infectious M/E.

Fullerene-like Niobovanadate Cage Built from {(Nb)V5 } Pentagon.

The striking aesthetic appeal of fullerene-like clusters has captured the interest of researchers. Nevertheless, the assembly of fullerene-like polyoxovadanadate (POV) cages remains a significant challenge due to the scarcity of suitable pentagonal motif. Herein, we have successfully synthesized the first fullerene-like all-inorganic POV cage, {(V2 O)V30 Nb12 O102 (H2 O)12 } (V30 Nb12 ), by introducing Nb into the POVs. V30 Nb12 is assembled by 12 heterometallic {(Nb)V5 } pentagons through sharing V centers with Ih symmetry, reminiscent of C60 . To our knowledge, the fullerene-like V30 Nb12 not only represents the highest-nuclearity POV cage but also stands as the first niobovanadate cluster. Notably, V30 Nb12 exhibits excellent solution stability, as confirmed by ESI-MS, FT-IR and UV/Vis spectra. As there is no protection organic ligand on its outer surface, V30 Nb12 can be further modified with Cu-complexes to form a fullerene-like cluster based zigzag chain (Cu-V30 Nb12 ).

TIPE2 sensitizes breast cancer cells to paclitaxel by suppressing drug-induced autophagy and cancer stem cell properties.

Drug resistance is a great obstacle to the clinical application of paclitaxel (PTX) in breast cancer treatment. Chemoresistance can be either primary or acquired. Multifarious factors are related to drug resistance. Among these factors, drug-induced autophagy has been shown to contribute to acquired chemoresistance in cancer cells. Additionally, cancer stem cells (CSCs) drive primary chemoresistance. Recent advances regarding TIPE2 demonstrate that TIPE2 enhances osteosarcoma and non-small cell lung cancer cell sensitivity to cisplatin. However, the role of TIPE2 in PTX resistance in breast cancer cells has not been elucidated. Here, the in vitro and in vivo study demonstrated that TIPE2 sensitized breast cancer cells to PTX by suppressing drug-induced autophagy and CSC properties. Mechanistically, we found that TIPE2 activated the AKT/mTOR signalling pathway and inhibited the TAK1/MAPK signalling pathway to suppress drug-induced autophagy. Moreover, TIPE2 inhibited TAK1/NF-κB activation to reduce breast CSC properties. Collectively, our results first elucidated the inhibitory role of TIPE2 in breast cancer chemoresistance. Thus, TIPE2 may be a new target for breast cancer chemotherapy.

In reply to the letter to editor regarding "Fourth ventricle stent placement for treatment of type I Chiari malformation in children".

We made a reply to the letter to editor regarding "Fourth ventricle stent placement for treatment of type I Chiari malformation in children" by Prof. Afshari. He gave some comments on the primary cause of low-lying cerebellar tonsils and the risk of the fourth ventricle stent (FVS). We make further explanation of our opinion on Chiari malformation and the value of FVS.

Pediatric spinal cord diffuse midline glioma with H3 K27M-alteration with leptomeningeal dissemination: a rare case with intracranial hypertension onset and no spinal cord-related symptom.

PURPOSE: Spinal cord diffuse midline glioma (DMG) with H3 K27-alteration is a group of spinal cord high-grade glioma with poor outcome. We present a case with rare onset symptom pattern of pediatric spinal DMG, contributing to the understanding of the clinical presentations and natural history of pediatric spinal cord DMG. METHODS AND RESULTS: A 7-year-old boy was admitted due to symptoms of intracranial hypertension without obvious spinal cord-related symptoms. Head radiological examinations, blood and cerebral spinal fluid tests did not support intracranial lesion, infection, or autoimmune diseases. Spinal magnetic resonance imaging revealed intraspinal occupying lesion with leptomeningeal dissemination. Pathology of the lesion verified DMG with H3 K27M-alteration. CONCLUSION: Pediatric DMG with leptomeningeal dissemination could present with initial symptoms of intracranial hypertension without obvious spinal cord-related symptoms. Spinal cord examinations in cases of intracranial hypertension with negative head radiological examination results could be valuable in finding the etiology.

Preferential Enrichment of Enantiomer from Amino Acid Schiff Bases by Coordination Interaction and Crystallization.

In this paper, preferential enrichment (PE) is described for three pairs of novel amino acid Schiff base Cu(II)/Cu(I) complexes. Single crystal X-ray diffraction indicated that 1-S/R are one-dimensional coordination polymers (CPs) with helical structures, and 2-S/R and 3-S/R are one-dimensional CPs with auxiliary ligands. By tuning the pH, the solvent and second ligands, the 1-S/R, 3-S/R underwent polymorphic transitions, resulting in enantioselective liberation of excess enantiomers into solution, until the deposited crystals were slightly enriched with the opposite enantiomer, thereby successfully exhibiting PE. However, under the effects of Cu(II), the solvent and low pH, 2-S/R did not exhibit PE and resulted in enrichment of racemic compounds, which was attributed to amino acid Schiff base chiral complex mechanisms of PE. The three pairs of Cu complex structures were characterized by UV-vis, MS and X-ray photoelectron spectroscopy (XPS). All chiral properties were studied by circular dichroism (CD) in the solid and liquid.

Meningioma originating from the oculomotor nerve without dural attachment in a child.

Meningioma originating from the oculomotor nerve without dural attachment in children has been rarely reported. A 6-year-old patient presented ptosis of the right eye for 5 years. MRI indicated an occupying lesion in the right cavernous sinus. A tumor originating from the oculomotor nerve without dural attachment was found during subsequent surgery and confirmed as meningioma by pathology. Subsequently, the tumor was removed completely, and the oculomotor nerve was reconstructed using the sural nerve. The patient's symptoms were relieved partially after 3 months. The findings of this case suggested that the mechanisms underlying meningioma involve ectopic arachnoid cap cells within the nerve sheath. Thus, the tumor should be removed completely; also, nerve reconstruction is suggested.

Cl-amidine attenuates lipopolysaccharide-induced inflammation in human gingival fibroblasts via the JNK/MAPK, NF-κB, and Nrf2 signalling pathways.

Cl-amidine has been reported to have anti-inflammatory properties in a variety of diseases. However, the role of Cl-amidine in periodontal disease remains unclear. Here, the purpose of this study was to investigate the effect of Cl-amidine on lipopolysaccharide (LPS)-induced inflammation in human gingival fibroblasts (HGFs). The cytotoxic effect of Cl-amidine was measured with the Cell Counting Kit-8 (CCK-8) assay and Annexin V-FITC/PI staining. The protein levels of IL-6 and IL-8 in culture supernatants were measured with enzyme-linked immunosorbent assay (ELISA). The mRNA levels of inflammatory cytokines, TLR4 and MyD88 were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The expression patterns of IL-6, TNF-ɑ, and IL-1ß in HGFs were tested with western blot. The levels of NF-κB, MAPK, and Nrf2 pathway-related proteins were detected by western blot. Immunofluorescence (IF) staining was used to examine the nuclear translocation of NF-κB p65. Moreover, a rat gingivitis model was established to further clarify the role of Cl-amidine. Our results showed that Cl-amidine suppressed LPS-induced gingival inflammation both in vitro and in vivo. Mechanistically, Cl-amidine inhibited LPS-induced MyD88 expression, NF-κB activation, and JNK phosphorylation. Additionally, Cl-amidine upregulated Nrf2 and Ho-1 expression both with and without LPS stimulation but did not alter ROS levels or Keap1 expression. Overall, our data suggest that Cl-amidine acts as an inhibitor of LPS-induced gingival inflammation via the JNK/MAPK, NF-κB, and Nrf2 signalling pathways.

Hydration mechanism and environmental impacts of blended cements containing co-combustion ash of sewage sludge and rice husk: Compared with blended cements containing sewage sludge ash.

In this study, the hydration mechanism and environmental impacts of blended cements with the co-combustion ash of rice husk and sewage sludge (CCA) were investigated and compared to those of blended cements with sewage sludge ash (SSA). CCA possesses lower phosphate contents than SSA, leading to lower inhibition effects on early hydration of cement clinker. Moreover, the pozzolanic activity of CCA is higher than that of SSA. Thus, more hydration products from the pozzolanic reaction of CCA are generated in CCA-based blended cements. Compared to the matrix of SSA-based blended cements, that of their CCA-based counterpart is filled with more hydration products, which promotes porosity refinement and strength development of CCA-based blended cements at later ages. CCA-based blended cements exhibit greater environmental benefits than SSA-based blended cements because fossil consumption and toxic substance emissions during the co-combustion of rice husk and sewage sludge is lower than that during the mono-combustion of sewage sludge.

Fourth ventricle stent placement for treatment of type I Chiari malformation in children.

INTRODUCTION: Type I Chiari malformation (CM-I) is a common congenital malformation, often accompanied by syringomyelia. Obstruction of CSF circulation in the foramen magnum is the reason for the formation of the syringomyelia. Fourth ventricle stenting (FVS) could ensure the CSF flow from the fourth ventricle, which might represent an effective approach to achieve syringomyelia relief. METHODS: We have reviewed four cases of CM-I children who received FVS implantation from November 2021 to July 2022. Each of the patients underwent FMD. The ventricular catheter of an Ommaya reservoir (Medtronic, Inc.) was used as a stent. Duraplasty was performed with autologous fascia. Cervical MRI rechecks were routinely done 3 months later, and the clinical symptoms were followed up. RESULTS: Four children received FVS, including one boy and three girls, aged from 12 months to 10 years, with a mean age of 6.8 years. No major complication occurred. The syringomyelia or hydrocephalus in each patient were all attenuated, as observed on the reexamination MRI images. During the follow-up time with a mean of 10.8 months, no patient had new symptoms. CONCLUSION: FVS is an effective and safe method for operation of CM-1 in children. The indications of FVS include redo-FMD, difficulties to ensure post-FMD CSF circulation patency at the foramen magnum and with obstructive hydrocephalus. A long-term follow-up duration is necessary.

Analysis of the risk factors of post-operative seizure in pediatric patients with hydrocephalus undergoing endoscopic third ventriculostomy.

OBJECTIVE: The cause and mechanism of epilepsy after endoscopic third ventriculostomy (ETV) have still remained elusive. This single-center study aimed to explore and analyze the risk factors of post-operative seizure in pediatric patients with hydrocephalus undergoing ETV. METHODS: Data of pediatric patients with hydrocephalus who were treated with ETV from October 1, 2015, to November 31, 2021, were retrospectively analyzed. Basic demographic characteristics, etiology of hydrocephalus, surgical details, and laboratory measurements were collected. An early postoperative seizure was defined as the occurrence of at least one clinical seizure within 24 h of ETV. RESULTS: A total of 50 participants were included in the study, of whom 5 (10.00%) cases were in postoperative epilepsy group and 45 (90.00%) cases were in non-epilepsy group. Epilepsy patients were younger than those without epilepsy, while no statistically significant difference was found (P = 0.0836). In the age subgroup, children with epilepsy were younger than 2 years old. All patients with epilepsy received Ringer's solution intraoperatively. The mean postoperative serum calcium and potassium concentrations were significantly lower in patients with epilepsy than in those without epilepsy (Pcalcium = 0.0429; Ppotassium = 0.0250). Moreover, a faster decrease of serum potassium and calcium levels was found in children with epilepsy compared with those without epilepsy after ETV. CONCLUSION: The decrease of serum calcium and potassium levels, younger age, and using Ringer's solution as irrigation fluid were risk factors for epilepsy after ETV.

Pediatric Cerebral Meningioma: A Single-Center Study with 10 Children Not Associated with Neurofibromatosis Type 2 and Literature Review.

INTRODUCTION: Pediatric meningiomas (PMs) are rare tumors; they differ from their adult counterparts by their atypicality of location, higher rates of malignant change, male preponderance, recurrence, and sometimes, their association with neurofibromatosis. This case series analyzes the clinical behavior, pathological presentation, location, and its association with neurofibromatosis type 2 (NF2). METHODS: This case series consists of pediatric patients between the ages of 4 and 16 years who were hospitalized in the neurosurgical department of our hospital from 2012 to 2021 with different neurological symptoms and a literature review using the PubMed/MEDLINE database. RESULTS: Sixty percent of the patients were males, while 40% were females. The most common neurological manifestations were signs of increased intracranial pressure. NF2 was absent in all patients. The predominant histopathology subtypes are atypical and WHO grade II, representing 30% and 40%, respectively. CONCLUSION: This study supports the relationship between NF2 and pediatric cerebral meningioma but at a lower concomitant rate from 0 to 13%, taking into consideration our original data and the literature review, contrasting some reported cases, which suggest rates as high as 33%, 50%, and 100% in a very small number of patients. Gross total resection without postoperative radiation therapy for nonmalignant and non-NF2-associated PM proved to be a sufficient and a good treatment option.

Abscess of the cavernous sinus in a child: a case report.

BACKGROUND: The cavernous sinus, which has several important structures, can be affected by various lesions, including tumor, vascular, infection, and inflammation. CASE REPORT: We reported a rare case of abscess of the cavernous sinus in a child presenting with headache and abducens paralysis. Exploratory surgery was performed via the Dolenc approach, and the patient recovered from abducens paralysis 3 months later. CONCLUSION: Abscess of the cavernous sinus is rare.  Inspection of cavernous sinus can confirm the characteristics of the lesion and decompress the cavernous sinus, which may be beneficial for nerve function recovery.

Treatment of spontaneous spinal epidural hematoma in children: analysis of 25 cases.

INTRODUCTION: Spontaneous spinal epidural hematoma (SSEH) is a rare neurosurgical emergency, presenting as sudden onset of back pain and weakness of lower extremities. Many patients have no definite cause. Some cases of SSEH caused by vascular malformation have been reported. The treatment strategy remains controversial. This study aimed to analyze the causes of SSEH and proposed a treatment strategy according to clinical outcomes of patients at a single institution. METHODS: A total of 25 cases of SSEH under 18 years of age treated between March 2004 and July 2021 were retrospectively analyzed. RESULTS: The mean age of the first SSEH onset was 7.1 years. The most common location was cervicothorax. Nine patients suffered from multiple episodes. Twenty-three patients underwent spinal digital subtraction angiography (DSA), of which seven (30.4%) patients had positive findings: three cases had epidural artery venous fistula (AVF), two cases had epidural artery venous malformation (AVM), and two cases had abnormal concentration of contrast agent. Seventeen patients received surgery. Eleven patients (44%) were diagnosed as vascular malformation by either DSA or pathology. The follow-up rate was 80%, with 20 patients (80%) achieving satisfactory clinical outcome. Risk factors for poor clinical outcome included multiple episodes (p = 0.028) and higher Aminoff-Logue score (p = 0.005). CONCLUSION: Spinal epidural vascular malformation is a significant cause of SSEH. Spinal DSA is necessary. Surgery should be recommended for patients with multiple episodes, positive findings on DSA, or severe neurological deficits. Conservation therapy can be considered for other patients, but long-time follow-up is necessary.

Silencing lncRNA HOXA10-AS decreases cell proliferation of oral cancer and HOXA10-antisense RNA can serve as a novel prognostic predictor.

OBJECTIVE: Long noncoding (lnc)RNAs regulate multiple biological processes including cancer. Oral squamous cell carcinoma (OSCC) is a common malignancy with poor prognosis. We aimed to identify the function of lncRNA HOXA10 antisense RNA (HOXA10-AS) and its clinical significance. METHODS: We used differential expression analysis to identify aberrantly expressed lncRNAs associated with OSCC. We identified key genes related to HOXA10-AS and their biological functions using bioinformatics tools and functional enrichment analyses. We predicted the function of HOXA10-AS using gene set enrichment and variation analyses and analyzed proliferation markers at the mRNA and protein levels. Finally, we silenced HOXA10-AS using antisense oligonucleotide and assessed proliferation ability using a cell counting kit (CCK8) and clone formation assays. RESULTS: In total, 506 aberrantly expressed lncRNAs were identified. HOXA10-AS was identified as a risk factor for OSCC and its expression was positively associated with tumor grade. We identified hub genes involved in regulating proliferation and predicted that HOXA10-AS is associated with an active cell cycle and increased proliferation. Silencing HOXA10-AS decreased proliferation in OSCC cell lines. CONCLUSIONS: HOXA10-AS is involved in cell proliferation and silencing it decreases proliferation. Thus, HOXA10-AS could serve as prognostic biomarker and therapeutic target for OSCC.

TIPE1 Inhibits Breast Cancer Proliferation by Downregulating ERK Phosphorylation and Predicts a Favorable Prognosis.

TIPE1, which acts as a cell death regulator, has emerged as a tumor suppressor in the process of carcinogenesis. However, our recent research demonstrated that it serves as an oncogene in the pathogenesis of cervical cancer, indicating that the role of TIPE1 in carcinogenesis needs to be further evaluated. In this study, we show that TIPE1 is able to inhibit breast cancer cell growth both in vivo and in vitro. Functionally, TIPE1 inhibits cancer cell proliferation preferentially by downregulating ERK phosphorylation. Furthermore, the expression of TIPE1 is decreased in breast cancer tissues compared to matched adjacent tissues, and its expression is positively correlated with patients' lifespan. These data indicate that TIPE1 suppresses breast cancer proliferation by inhibiting the ERK signaling pathway. This study also suggests that TIPE1 could serve as a potential therapeutic target and a diagnostic biomarker for breast cancer.

Pediatric perimedullary arteriovenous fistula: clinical features and endovascular treatments.

OBJECTIVE: Pediatric spinal perimedullary arteriovenous fistula (PMAVF) is rare but may cause permanent disability. We aim to summarize the clinical features of pediatric PMAVFs and our clinical experience in their treatment and to evaluate the effect of endovascular treatment in a large cohort. METHODS: From 2008 to 2017, 51 PMAVFs in pediatric patients (<14 years' old) treated with endovascular techniques were retrospectively reviewed, including 24 type IVb (47.1%) and 27 type IVc (52.9%) lesions. Clinical features, radiological findings, treatment, and outcomes were evaluated. RESULTS: Thirty-eight boys and thirteen girls were included, and the mean age at presentation was 5.6±4.1 years. Acute neurological deterioration was identified in 33 patients, and 21 of those patients (63.6%) suffered from bleeding. The annual bleeding rate before treatment was 2.55%. After transarterial embolization with coils and glue, 46 PMAVFs (90.2%) were completely occluded, and five (9.8%) were obliterated by supplementary microsurgery. During a follow-up period of 6 to 119 months (mean 58.4±16.7 months), the patients' clinical states were improved in 42 cases (82.4%), stationary in nine cases (17.6%), and aggravated in none. Type IVc patients had a longer preoperative period, more chronic symptoms, a lower cure rate by embolization, and less improvement of symptoms than type IVb patients had (P<0.05). CONCLUSIONS: Pediatric PMAVF is a special subgroup of intradural arteriovenous shunt that should be treated early. Endovascular embolization is safe and effective in the treatment of pediatric PMAVFs.