Placement of a Catheter into the Transverse Sinus in Monitoring Intracranial Lesions: A Technical Note.

High intracranial pressure (ICP) can be induced by stroke, brain trauma, and brain tumor, and lead to cerebral injury. Monitoring the blood flow of a damaged brain is important for detecting intracranial lesions. Blood sampling is a better way to monitor changes in brain oxygen and blood flow than computed tomography perfusion and magnetic resonance imaging. This article describes how to take blood samples from the transverse sinus in a high ICP rat model. Also, it compares the blood samples from the transverse sinus and femoral artery/vein through blood gas analysis and neuronal cell staining. The findings may be of significance to the monitoring of the oxygen and blood flow of intracranial lesions.

Corrigendum: Inhibition of O-GlcNAc transferase sensitizes prostate cancer cells to docetaxel.

[This corrects the article DOI: 10.3389/fonc.2022.993243.].

[Corrigendum] METTL3 antagonizes 5­FU chemotherapy and confers drug resistance in colorectal carcinoma.

Subsequently to the publication of the above article, the authors alerted us to the fact that the data shown in Fig. 8I (for the 'Sh­CN / 0' panel) on p. 11 were mistakenly selected from those data belonging to the experiments shown in Fig. 7H (the 'Sh­CN / 0' panel) of this paper during the final assembly of the figures for review. Note that this error did not affect the conclusions reported in this paper, as both Fig. 7H ('Sh­CN / 0') and Fig. 8I ('Sh­CN / 0') show negative controls of the Comet assay, with no obvious trailing. The revised version of Fig. 8, showing the correct data for the 'Sh­CN / 0' panel in Fig. 8I, is shown on the next page. The authors are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a Corrigendum, and all the authors agree with its publication. Furthermore, the authors apologize to the readership for any inconvenience caused. [International Journal of Oncology 61: 106, 2022; DOI: 10.3892/ijo.2022.5396].

1H NMR-based metabolomics combined with chemometrics to detect edible oil adulteration in huajiao (Zanthoxylum bungeanum Maxim.).

Huajiao is a highly valued spice that is susceptible to fraudulent adulteration, particularly the addition of edible oils to increase weight and improve color. Nuclear magnetic resonance (1H NMR) and chemometrics were used to analyze 120 huajiao samples adulterated with different types and levels of edible oils. Using untargeted data and partial least squares-discriminant analysis (PLS-DA), the discrimination rate between types of adulteration reached 100% accuracy, and the R2 value of the prediction set for the level of adulteration using the targeted analysis dataset combined with PLS-regression methods reached 0.99. Triacylglycerols, major components of edible oils, were identified as a marker of adulteration through the variable importance in projection of the PLS-regression. A quantitative method based on the sn-3 triacylglycerol signal was developed that can achieve a detection limit of 0.11%. Testing of 28 market samples showed adulteration with various edible oils, with adulteration rates ranging from 0.96% to 4.41%.

Rabies virus glycoprotein 29 (RVG29) promotes CAR-T immunotherapy for glioma.

Chimeric antigen receptor T cell (CAR-T) therapy has limited efficacy for treating glioma because of the infiltrative nature of the blood-brain barrier (BBB) and T cell exhaustion. Conjugation with rabies virus glycoprotein (RVG) 29 enhances the brain-related efficacy of various agents. Here we assess whether RVG enhances the ability of CAR-T cells to cross the BBB and improves their immunotherapy. We generated 70R CAR-T cells (anti-CD70 CAR-T modified with RVG29) and validated their tumor-killing efficacy in vitro and in vivo. We validated their effects on tumor regression in a human glioma mouse orthotopic xenograft model as well as in patient-derived orthotopic xenograft (PDOX) models. The signaling pathways activated in 70R CAR-T cells were revealed by RNA sequencing. The 70R CAR-T cells we generated showed effective antitumor function against CD70+ glioma cells both in vitro and in vivo. 70R CAR-T cells were better able to cross the BBB into the brain than CD70 CAR-T cells under the same treatment conditions. Moreover, 70R CAR-T cells significantly promote the regression of glioma xenografts and improve the physical characteristics of mice without causing overt adverse effects. RVG modification enables CAR-T cells to cross the BBB, and stimulation with glioma cells induces 70R CAR-T cells to expand in a resting state. The modification of RVG29 has a positive impact on CAR-T therapy for brain tumors and may have potential in CAR-T therapy for glioma.

Identification of the Origin for Reconstructed Active Sites on Oxyhydroxide for Oxygen Evolution Reaction.

The regulation of atomic and electronic structures of active sites plays an important role in the rational design of oxygen evolution reaction (OER) catalysts toward electrocatalytic hydrogen generation. However, the precise identification of the active sites for surface reconstruction behavior during OER remains elusive for water-alkali electrolysis. Herein, irreversible reconstruction behavior accompanied by copper dynamic evolution for cobalt iron layered double hydroxide (CoFe LDH) precatalyst to form CoFeCuOOH active species with high-valent Co species is reported, identifying the origin of reconstructed active sites through operando UV-Visible (UV-vis), in situ Raman, and X-ray absorption fine-structure (XAFS) spectroscopies. Density functional theory analysis rationalizes this typical electronic structure evolution causing the transfer of intramolecular electrons to form ligand holes, promoting the reconstruction of active sites. Specifically, unambiguous identification of active sites for CoFeCuOOH is explored by in situ 18 O isotope-labeling differential electrochemical mass spectrometry (DEMS) and supported by theoretical calculation, confirming mechanism switch to oxygen-vacancy-site mechanism (OVSM) pathway on lattice oxygen. This work enables to elucidate the vital role of dynamic active-site generation and the representative contribution of OVSM pathway for efficient OER performance.

Analysis of N 6 -methyladenosine RNA Modification Levels by Dot Blotting.

N 6 -methyladenosine (m 6 A) is the most prevalent internal modification of eukaryotic messenger RNAs (mRNAs), affecting their fold, stability, degradation, and cellular interaction(s) and implicating them in processes such as splicing, translation, export, and decay. The m 6 A modification is also extensively present in non-coding RNAs, including microRNAs (miRNAs), ribosomal RNAs (rRNAs), and transfer RNAs (tRNAs). Common m 6 A methylation detection techniques play an important role in understanding the biological function and potential mechanism of m 6 A, mainly including the quantification and specific localization of m 6 A modification sites. Here, we describe in detail the dot blotting method for detecting m 6 A levels in RNA (mRNA as an example), including total RNA extraction, mRNA purification, dot blotting, and data analysis. This protocol can also be used to enrich specific RNAs (such as tRNA, rRNA, or miRNA) by isolation technology to detect the m 6 A level of single RNA species, so as to facilitate further studies of the role of m 6 A in biological processes. This protocol was validated in: eLife (2022), DOI: 10.7554/eLife.75231.

Inhibition of O-GlcNAc transferase sensitizes prostate cancer cells to docetaxel.

The expression of O-GlcNAc transferase (OGT) and its catalytic product, O-GlcNAcylation (O-GlcNAc), are elevated in many types of cancers, including prostate cancer (PC). Inhibition of OGT serves as a potential strategy for PC treatment alone or combinational therapy. PC is the second common cancer type in male worldwide, for which chemotherapy is still the first-line treatment. However, the function of inhibition of OGT on chemotherapeutic response in PC cells is still unknown. In this study, we show that inhibition of OGT by genetic knockdown using shRNA or by chemical inhibition using OGT inhibitors sensitize PC cells to docetaxel, which is the most common chemotherapeutic agent in PC chemotherapy. Furthermore, we identified that microRNA-140 (miR-140) directly binds to OGT mRNA 3' untranslated region and inhibits OGT expression. Moreover, docetaxel treatment stimulates miR-140 expression, whereas represses OGT expression in PC cells. Overexpression of miR-140 enhanced the drug sensitivity of PC cells to docetaxel, which could be reversed by overexpression of OGT. Overall, this study demonstrates miR-140/OGT axis as therapeutic target in PC treatment and provides a promising adjuvant therapeutic strategy for PC therapy.

Machine learning and bioinformatics to identify 8 autophagy-related biomarkers and construct gene regulatory networks in dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a condition of impaired ventricular remodeling and systolic diastole that is often complicated by arrhythmias and heart failure with a poor prognosis. This study attempted to identify autophagy-related genes (ARGs) with diagnostic biomarkers of DCM using machine learning and bioinformatics approaches. Differential analysis of whole gene microarray data of DCM from the Gene Expression Omnibus (GEO) database was performed using the NetworkAnalyst 3.0 platform. Differentially expressed genes (DEGs) matching (|log2FoldChange ≥ 0.8, p value < 0.05|) were obtained in the GSE4172 dataset by merging ARGs from the autophagy gene libraries, HADb and HAMdb, to obtain autophagy-related differentially expressed genes (AR-DEGs) in DCM. The correlation analysis of AR-DEGs and their visualization were performed using R language. Gene Ontology (GO) enrichment analysis and combined multi-database pathway analysis were served by the Enrichr online enrichment analysis platform. We used machine learning to screen the diagnostic biomarkers of DCM. The transcription factors gene regulatory network was constructed by the JASPAR database of the NetworkAnalyst 3.0 platform. We also used the drug Signatures database (DSigDB) drug database of the Enrichr platform to screen the gene target drugs for DCM. Finally, we used the DisGeNET database to analyze the comorbidities associated with DCM. In the present study, we identified 23 AR-DEGs of DCM. Eight (PLEKHF1, HSPG2, HSF1, TRIM65, DICER1, VDAC1, BAD, TFEB) molecular markers of DCM were obtained by two machine learning algorithms. Transcription factors gene regulatory network was established. Finally, 10 gene-targeted drugs and complications for DCM were identified.

METTL3 antagonizes 5­FU chemotherapy and confers drug resistance in colorectal carcinoma.

Colorectal cancer (CRC) is one of top five leading causes of cancer­associated mortalities worldwide. 5­Fluorouracil (5­FU) is the first­line chemotherapeutic drug in the treatment of CRC; however, its antineoplastic efficiency is limited due to acquired drug resistance. The regulatory mechanism underlying 5­FU chemotherapeutic response and drug resistance in CRC remains largely unknown. The present study identified that silencing of methyltransferase­like 3 (METTL3) suppressed the proliferation and migration of CRC HCT­8 cells. Using cell survival assays, flow cytometric and colony formation analyses, it was revealed that inhibition of METTL3 sensitized HCT­8 cells to 5­FU by enhancing DNA damage and inducing apoptosis in HCT­8 cells under 5­FU treatment. Furthermore, the expression of METTL3 was upregulated in 5­FU­resistant CRC cells (HCT­8R), which contributed to drug resistance through regulation of RAD51 associated Protein 1 (RAD51AP1) expression. Western blotting, immunofluorescence staining and drug sensitivity assays demonstrated that knockdown of METTL3 augmented 5­FU­induced DNA damage and overcame 5­FU­resistance in HCT­8R cells, which could be mimicked by inhibition of RAD51AP1. The present study revealed that the METTL3/RAD51AP1 axis plays an important role in the acquisition of 5­FU resistance in CRC, and targeting METTL3/RAD51AP1 may be a promising adjuvant therapeutic strategy for patients with CRC, particularly for those with 5­FU­resistant CRC.

Evidence Quality Assessment of Tai Chi Exercise Intervention in Cognitive Impairment: An Overview of Systematic Review and Meta-Analysis.

Background: Tai Chi (TC) exercise has recently received wide attention for its efficacy in the management of cognitive impairment. The purpose of this overview is to summarize the available evidence on TC treatment of cognitive impairment and assess its quality. Methods: We retrieved relevant systematic reviews/meta-analyses (SRs/MAs) from 7 databases from the time they were established to January 2, 2022. Two reviewers independently evaluated the methodological quality, risk of bias, report quality, and evidence quality of the included SRs/MAs on randomized controlled trials (RCTs). The tools used are Assessment System for Evaluating Methodological Quality 2 (AMSTAR-2), the Risk of Bias In Systematic (ROBIS) scale, the list of Preferred Reporting Items for Systematic Reviews And Meta-Analysis (PRISMA), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results: This overview finally included 8 SRs/MAs. According to the results of AMSTAR-2, all included SRs/MAs were rated as very low quality. Based on the ROBIS tool, none of the SR/MA had a low risk of bias. In light of PRISMA, all SRs/MAs had reporting deficiencies. According to the GRADE system, there was only 1 high-quality piece of evidence. Conclusion: TC is a promising complementary and alternative therapy for cognitive impairment with high safety profile. However, in view of the low quality of the included SRs/MAs supporting this conclusion, high-quality evidence with a more rigorous study design and a larger sample size is needed before making a recommendation for guidance.

METTL3 promotes homologous recombination repair and modulates chemotherapeutic response in breast cancer by regulating the EGF/RAD51 axis.

Methyltransferase-like 3 (METTL3) and N6-methyladenosine (m6A) are involved in many types of biological and pathological processes, including DNA repair. However, the function and mechanism of METTL3 in DNA repair and chemotherapeutic response remain largely unknown. In present study, we identified that METTL3 participates in the regulation of homologous recombination repair (HR), which further influences chemotherapeutic response in both MCF-7 and MDA-MB-231 breast cancer (BC) cells. Knockdown of METTL3 sensitized these BC cells to Adriamycin (ADR; also named as doxorubicin) treatment and increased accumulation of DNA damage. Mechanically, we demonstrated that inhibition of METTL3 impaired HR efficiency and increased ADR-induced DNA damage by regulating m6A modification of EGF/RAD51 axis. METTL3 promoted EGF expression through m6A modification, which further upregulated RAD51 expression, resulting in enhanced HR activity. We further demonstrated that the m6A 'reader,' YTHDC1, bound to the m6A modified EGF transcript and promoted EGF synthesis, which enhanced HR and cell survival during ADR treatment in BC. Our findings reveal a pivotal mechanism of METTL3-mediated HR and chemotherapeutic drug response, which may contribute to cancer therapy.

Engineering Lattice Oxygen Activation of Iridium Clusters Stabilized on Amorphous Bimetal Borides Array for Oxygen Evolution Reaction.

Developing robust oxygen evolution reaction (OER) catalysts requires significant advances in material design and in-depth understanding for water electrolysis. Herein, we report iridium clusters stabilized surface reconstructed oxyhydroxides on amorphous metal borides array, achieving an ultralow overpotential of 178 mV at 10 mA cm-2 for OER in alkaline medium. The coupling of iridium clusters induced the formation of high valence cobalt species and Ir-O-Co bridge between iridium and oxyhydroxides at the atomic scale, engineering lattice oxygen activation and non-concerted proton-electron transfer to trigger multiple active sites for intrinsic pH-dependent OER activity. The lattice oxygen oxidation mechanism (LOM) was confirmed by in situ 18 O isotope labeling mass spectrometry and chemical recognition of negative peroxo-like species. Theoretical simulations reveal that the OER performance on this catalyst is intrinsically dominated by LOM pathway, facilitating the reaction kinetics. This work not only paves an avenue for the rational design of electrocatalysts, but also serves the fundamental insights into the lattice oxygen participation for promising OER application.

Targeting the DNA damage response enhances CD70 CAR-T cell therapy for renal carcinoma by activating the cGAS-STING pathway.

Chimeric antigen receptor T-cell (CAR-T) therapy has shown tremendous success in eradicating hematologic malignancies. However, this success has not yet been extrapolated to solid tumors due to the limited infiltration and persistence of CAR-T cells in the tumor microenvironment (TME). In this study, we screened a novel anti-CD70 scFv and generated CD70 CAR-T cells that showed effective antitumor functions against CD70+ renal carcinoma cells (RCCs) both in vitro and in vivo. We further evaluated the effect and explored the molecular mechanism of a PARP inhibitor (PARPi) in CAR-T cell immunotherapy by administering the PARPi to mouse xenografts model derived from human RCC cells. Treatment with the PARPi promoted CAR-T cell infiltration by stimulating a chemokine milieu that promoted CAR-T cell recruitment and the modulation of immunosuppression in the TME. Moreover, our data demonstrate that PARPi modulates the TME by activating the cGAS-STING pathway, thereby altering the balance of immunostimulatory signaling and enabling low-dose CAR-T cell treatment to induce effective tumor regression. These data demonstrate the application of CD70 CAR-T cell therapeutic strategies for RCC and the cross-talk between targeting DNA damage responses and antitumor CAR-T cell therapy. These findings provide insight into the mechanisms of PARPis in CAR-T cell therapy for RCC and suggest a promising adjuvant therapeutic strategy for CAR-T cell therapy in solid tumors.

Engineering single-atomic ruthenium catalytic sites on defective nickel-iron layered double hydroxide for overall water splitting.

Rational design of single atom catalyst is critical for efficient sustainable energy conversion. However, the atomic-level control of active sites is essential for electrocatalytic materials in alkaline electrolyte. Moreover, well-defined surface structures lead to in-depth understanding of catalytic mechanisms. Herein, we report a single-atomic-site ruthenium stabilized on defective nickel-iron layered double hydroxide nanosheets (Ru1/D-NiFe LDH). Under precise regulation of local coordination environments of catalytically active sites and the existence of the defects, Ru1/D-NiFe LDH delivers an ultralow overpotential of 18 mV at 10 mA cm-2 for hydrogen evolution reaction, surpassing the commercial Pt/C catalyst. Density functional theory calculations reveal that Ru1/D-NiFe LDH optimizes the adsorption energies of intermediates for hydrogen evolution reaction and promotes the O-O coupling at a Ru-O active site for oxygen evolution reaction. The Ru1/D-NiFe LDH as an ideal model reveals superior water splitting performance with potential for the development of promising water-alkali electrocatalysts.

The Role of PARP Inhibitors in the Treatment of Prostate Cancer: Recent Advances in Clinical Trials.

Poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis) belong to a class of targeted drugs developed for the treatment of homologous recombination repair (HRR)-defective tumors. Preclinical and limited clinical data suggest that PARP inhibition is effective against prostate cancer (PC) in patients with HRR-deficient tumors and that PARPis can improve the mortality rate of PC in patients with BRCA1/2 mutations through a synthetic lethality. Olaparib has been approved by the FDA for advanced ovarian and breast cancer with BRCA mutations, and as a maintenance therapy for ovarian cancer after platinum chemotherapy. PARPis are also a new and emerging clinical treatment for metastatic castration-resistant prostate cancer (mCRPC). Although PARPis have shown great efficacy, their widespread use is restricted by various factors, including drug resistance and the limited population who benefit from treatment. It is necessary to study the combination of PARPis and other therapeutic agents such as anti-hormone drugs, USP7 inhibitors, BET inhibitors, and immunotherapy. This article reviews the mechanism of PARP inhibition in the treatment of PC, the progress of clinical research, the mechanisms of drug resistance, and the strategies of combination treatments.

Robust charge spatial separation and linearly tunable band gap of low-energy tube-edge phosphorene nanoribbon.

Versatile applications have been proposed for phosphorene nanoribbons (PNRs), whose properties depend strongly on the edge structures. Recently, a unique tube-reconstruction at the zigzag edge (ZZ[Tube]) of PNRs was discovered to be the lowest configuration. Therefore, studies on PNRs should be reconsidered. In this paper, we systemically explore the width and strain effects on zigzag PNRs with different edge structures, including ZZ[Tube], ZZ and ZZ[ad] edges. ZZ PNRs always have small band gaps which are nearly independent of both width and strain. A remarkable band gap exists in ZZ[ad] PNRs which increases with a decrease in the ribbon width but is not sensitive to strain. In contrast, the band gaps of ZZ[Tube] PNRs change from 1.08 to 0.70 eV as the width increases from 12 to 65 Å. In addition, the band gaps of ZZ[Tube] PNRs show a linear response under a certain range of strain. In addition, the carrier effective masses (0.50 m 0 for electrons and 0.94 m 0 for holes) of ZZ[Tube] PNRs are much lower than for ZZ[ad], and the VBM and CBM charges are robustly spatially separated even under strains ranging from -5% to 5%. Their ease of formation, lowest energy, light effective mass, linear band gap response to strain and robust charge spatial separation provide ZZ[Tube] PNRs with potentially excellent performance in microelectronic and opto-electric applications.

Anti-inflammatory and anxiolytic activities of Euphorbia hirta extract in neonatal asthmatic rats.

The current study evaluated the anti-inflammatory and anxiolytic activities of Euphorbia hirta extract in neonatal asthmatic rats. Rats were assigned to the following groups: group I, sham (normal rats); group II, control (asthmatic rats); group III, E. hirta extract (100 µg/100 µl) and group IV, E. hirta extract (200 µg/100 µl). We performed a phytoscreening analysis of E. hirta extract. Inflammatory cell counts in the bronchoalveolar lavage fluid, levels of anti-inflammatory and antioxidant markers, apoptosis, and a histopathological analysis were carried out. An open field test determined anxiolytic activity, an elevated plus maze, a hole board test, and a cross test. The presence of 9,12,15-octadecatrien-1-ol, pentadecylic acid, ethyl linoleate, 1,2,3-trihydroxy benzene, gamma-tocopherol, 5-hydroxymethyl-2-furancarboxaldehyde, myristic acid, 7,10-octadecadienoic acid methyl ester, phytol, ethyl palmitate, and squalene in E. hirta extract was noted. Following treatment with E. hirta extract, total leukocytes, eosinophils, tumor necrosis factor-α (TNF-α), interleukin (IL-6), and lipid peroxidation were reduced, whereas antioxidant levels were increased. The mRNA expression levels of TNF-α, inducible nitric oxide synthase, IL-6, cyclooxygenase-2, caspase-3, p53, nerve growth factor precursor, and Bax were reduced, whereas that of Bcl-2 was increased. Apoptosis and caspase-3 protein expression were significantly reduced. Treatment of rats with E. hirta extract significantly reduced inflammation and eosinophil infiltration in the lungs. Taken together, these results led us to conclude that E. hirta extract has anti-inflammatory and anxiolytic effects on neonatal asthmatic rats with inflammation.

Fisetin-treatment alleviates airway inflammation through inhbition of MyD88/NF-κB signaling pathway.

Asthma is a common chronic airway inflammation disease and is considered as a major public health problem. Fisetin (3,3',4',7-tetrahydroxyflavone) is a naturally occurring flavonoid abundantly found in different vegetables and fruits. Fisetin has been reported to exhibit various positive biological effects, including anti-proliferative, anticancer, anti-oxidative and neuroprotective effects. We evaluated the effects of fisetin on allergic asthma regulation in mice. Mice were first sensitized, then airway-challenged with ovalbumin (OVA). Whether fisetin treatment attenuated OVA-induced airway inflammation was examined via inflammation inhibition through MyD88-related NF-κB (p65) signaling pathway. Mice were divided into the control (Con), OVA-induced asthma (Mod), 40 (FL) and 50 (FH) mg/kg fisetin-treated OVA-induced asthma groups. Our results found that OVA-induced airway inflammation in mice caused a significant inflammatory response via the activation of MyD88 and NF-κB signaling pathways, leading to release of pro-inflammatory cytokines. In contrast, fisetin-treated mice after OVA induction inhibited activation of MyD88 and NF-κB signaling pathways, resulting in downregulation of pro-inflammatory cytokine secretion. Further, fisetin significantly ameliorated the airway hyperresponsiveness (AHR) towards methacholine (Mch). In addition, fisetin reduced the number of eosinophil, monocyte, neutrophil and total white blood cell in the bronchoalveolar lavage fluid (BALF) of OVA-induced mice. The serum and BALF samples obtained from the OVA-induced mice with fisetin showed lower levels of pro-inflammatory cytokines. The results of our study illustrated that fisetin may be a new promising candidate to inhibit airway inflammation response induced by OVA.