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Abstract Abnormal lipid metabolism is an essential hallmark of glioblastoma. Hormone sensitive lipase (HSL), an important rate-limiting enzyme contributed to lipolysis, which was involved in aberrant lipolysis of glioblastoma, however, its definite roles and the relevant regulatory pathway have not been fully elucidated. Our investigations disclosed high expression of HSL in glioblastoma. Knock-down of HSL restrained proliferation, migration, and invasion of glioblastoma cells while adding to FAs could significantly rescue the inhibitory effect of si-HSL on tumor cells. Overexpression of HSL further promoted tumor cell proliferation and invasion. Bioinformatics analysis and dual-luciferase reporter assay were performed to predict and verify the regulatory role of ncRNAs on HSL. Mechanistically, hsa_circ_0021205 regulated HSL expression by sponging miR-195-5p, which further promoted lipolysis and drove the malignant progression of glioblastoma. Besides, hsa_circ_0021205/miR-195-5p/HSL axis activated the epithelial-mesenchymal transition (EMT) signaling pathway. These findings suggested that hsa_circ_0021205 promoted tumorigenesis of glioblastoma through regulation of HSL, and targeting hsa_circ_0021205/miR-195-5p/HSL axis can serve as a promising new strategy against glioblastoma.

Large-scale short carbon fibre-reinforced silicon carbide (Csf/SiC) ceramic matrix composites (CMCs) have important applications in the field of aerospace engineering. This study proposed the use of material extrusion based additive manufacturing to fabricate large-scale Csf/SiC CMC preforms. In this paper, we determined how the key material extrusion parameters, including solid loading, nozzle diameter and layer height impact the stability of the additively manufactured Csf/SiC CMCs. The solid loading significantly influenced the stability of the Csf/SiC CMCs, and the slurry with 50 vol.% solid loading was better for additive manufacturing. The layer height played a significant role in the void formation in CMCs. It was appropriate for structure retention to set the layer height as 60–75% of the nozzle diameter. The effect of angle from vertical on the stability of out-of-plane structure was also investigated. When the angle was over 40o, the out-of-plane structure additively manufactured without supports tended to collapse. Large-scale Csf/SiC CMC preforms with out-of-plane structures were finally successfully fabricated. This study is believed to provide some fundamental understanding for the fabrication of large-scale fibre-reinforced ceramic matrix composites.

Abstract Chemo-resistance hinders the therapeutic efficacy of temozolomide (TMZ) in treating glioblastoma multiforme (GBM). Recurrence of GBM even after combination of maximal tumor resection, concurrent radio-chemotherapy, and systemic TMZ applocation is inevitable and attributed to the high therapeutic resistance of glioma stem cells (GSCs), which can survive, evolve, and initiate tumor tissue remodeling, the underlying mechanisms of GSCs chemo-resistance, have not been fully elucidated up-to-now. Emerging evidence showed that METTL3-mediated N6-methyladenosine (m6A) modification contributed to the self-renew and radio-resistance in GSCs, however, its role on maintenance of TMZ resistance of GSCs has not been clarified and need further investigations. We found that the cell viability and half-maximal inhibitory concentration (IC50) of GSCs against TMZ significantly decreased after GSCs underwent serum-induced differentiation to adherent growth of tumor cells. Besides, METTL3 expression and total m6A modification declined dramatically in consistence with GSCs differentiation. Knockdown of METTL3 weakened self-renew, proliferation and TMZ IC50 of GSCs, whereas enhanced TMZ induced γH2AX level, indicating upregulation of double-strand DNA damage. We also found that mRNA stability of two critical DNA repair genes (MGMT and APNG) was regulated by METTL3-mediated m6A modification. In conclusion, we speculated that METTL3-mediated m6A modification of MGMT and APNG mRNAs played crucial roles on suppression of TMZ sensitivity of GSCs, which suggest a potential new therapeutic target of METTL3 against GBM.

Metabolism remodelling of macrophages in the glioblastoma microenvironment contributes to immunotherapeutic resistance. However, glioma stem cell (GSC)-initiated lipid metabolism remodelling of transformed macrophages (tMΦs) and its effect on the glioblastoma microenvironment have not been fully elucidated. Total cholesterol (TC) levels and lipid metabolism enzyme expression in macrophages in the GSC microenvironment were evaluated and found that the TC levels of tMΦs were increased, and the expression of the lipid metabolism enzymes calmodulin (CaM), apolipoprotein E (ApoE), and liver X receptor (LXR) was upregulated. Knockdown of HOXC-AS3 led to a decrease in the proliferation, colony formation, invasiveness, and tumorigenicity of tMΦs. Downregulation of CaM resulted in a decline in TC levels. HOXC-AS3 overexpression led to increases in both CaM expression levels and TC levels in tMΦs. RNA pull down and mass spectrometry experiments were conducted and heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) was screened as the HOXC-AS3 binding proteins related to lipid metabolism. RIP and RNA pull down assays verified that HOXC-AS3 can form a complex with hnRNPA1. Knockdown of hnRNPA1 downregulated CaM expression; however, downregulation of HOXC-AS3 did not affect hnRNPA1 expression.TMΦs underwent lipid metabolism remodelling induced by GSC via the HOXC-AS3/hnRNPA1/CaM pathway, which enhanced the protumor activities of tMΦs, and may serve as a potential metabolic intervening target to improve glioblastoma immunotherapy.

Summary: Generation of chimeric antigen receptor (CAR) T cells from pluripotent stem cells (PSCs) will enable advances in cancer immunotherapy. Understanding how CARs affect T cell differentiation from PSCs is important for this effort. The recently described artificial thymic organoid (ATO) system supports in vitro differentiation of PSCs to T cells. Unexpectedly, PSCs transduced with a CD19-targeted CAR resulted in diversion of T cell differentiation to the innate lymphoid cell 2 (ILC2) lineage in ATOs. T cells and ILC2s are closely related lymphoid lineages with shared developmental and transcriptional programs. Mechanistically, we show that antigen-independent CAR signaling during lymphoid development enriched for ILC2-primed precursors at the expense of T cell precursors. We applied this understanding to modulate CAR signaling strength through expression level, structure, and presentation of cognate antigen to demonstrate that the T cell-versus-ILC lineage decision can be rationally controlled in either direction, providing a framework for achieving CAR-T cell development from PSCs.

Background: Cinnamon is a spice used in cooking and in large quantities as a medical complement with hypoglycemic and lipid-lowering properties. The potential pharmacological mechanisms underlying cinnamon’s anti-diabetic properties and its active ingredients have not been adequately determined. The current meta-analysis aims to systematically review the potential pharmacological mechanisms underlying the hypoglycemic and hypolipidemic efficacy of cinnamon administration and summarize clinical recommendations of cinnamon and its active ingredients.Method: Relevant randomized clinical trials (RCTs) were identified through a literature search that spanned the years January 2005 to April 2022. Retrieve electronic databases including Web of Science, PubMed, Embase, Medline, and the Cochrane Library. To obtain standardized mean differences (SMDs), continuous outcomes were pooled and 95 percent confidence intervals (CIs) were provided. Categorical outcomes were aggregated to calculate relative risks (RRs) and were accompanied by 95% CIs. Heterogeneity was measured using the Cochrane Q-test and I2 statistics, with a p < 0.05 considered as substantial heterogeneity. If I2 was less than 50%, a fixed effect model was employed; otherwise, a random effect model was used. Subgroup analyses and sensitivity analyses were performed to identify the origins of heterogeneity. Publication bias was retrieved by means of a funnel-plot analysis and Egger’s test. The data were analyzed using revman (V.5.3) and stata (V.15) software packages.Results: These 16 RCTs included a total of 1,020 patients who were followed for a duration ranging from 40 days to 4 months. According to the current meta-analysis results, glycolipid levels in diabetic individuals who received cinnamon were significantly improved as compared to those who got placebo (All p < 0.05). An adverse effect was only detected in one patient.Conclusion: These findings imply that cinnamon has a significant influence on lipid and glucose metabolism regulation. An even more pronounced effect was observed in patients with HbA1c of 8%. The results of this study suggested that cinnamon may be utilized as hypoglycemic and lipid-lowering supplement in clinical settings with a guaranteed safety profile.Systematic Review Registration: [PROSPERO], identifier [CRD42022322735].

Purine nucleoside phosphorylase (PNP) enables the breakdown and recycling of guanine nucleosides. PNP insufficiency in humans is paradoxically associated with both immunodeficiency and autoimmunity, but the mechanistic basis for these outcomes is incompletely understood. Here, we identify two immune lineage-dependent consequences of PNP inactivation dictated by distinct gene interactions. During T cell development, PNP inactivation is synthetically lethal with downregulation of the dNTP triphosphohydrolase SAMHD1. This interaction requires deoxycytidine kinase activity and is antagonized by microenvironmental deoxycytidine. In B lymphocytes and macrophages, PNP regulates Toll-like receptor 7 signaling by controlling the levels of its (deoxy)guanosine nucleoside ligands. Overriding this regulatory mechanism promotes germinal center formation in the absence of exogenous antigen and accelerates disease in a mouse model of autoimmunity. This work reveals that one purine metabolism gene protects against immunodeficiency and autoimmunity via independent mechanisms operating in distinct immune lineages and identifies PNP as a potentially novel metabolic immune checkpoint.

Abstract Many studies have reported that circular RNAs play a vital role in the malignant progression of human cancers. However, the role and underlying mechanism of circRNAs in the development of gliomas have not been fully clarified. In this study, we found that circ_0001367 was downregulated in glioma tissues and showed a close correlation with glioma patient survival. Functional assays demonstrated that upregulation of circ_0001367 could suppress the proliferation, migration and invasion of glioma cells in vitro and inhibit glioma growth in vivo. Furthermore, bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation assay indicated that circ_0001367 can serve as a sponge for miR-431 and that miR-431 acts as an oncogene by regulating neurexin 3 (NRXN3). In addition, rescue experiments verified that circ_0001367 could regulate both the expression and function of NRXN3 in a miR-431-dependent manner. In conclusion, circ_0001367 functions as an suppressor in glioma by targeting the miR-431/NRXN3 axis and may be a promising therapeutic target against gliomas.

With the spread of the COVID-19 pandemic and the implementation of closure measures in 2020, population mobility and human activities have decreased, which has seriously impacted atmospheric quality. Huaibei City is an important coal and chemical production base in East China, which faces increasing environmental problems. The impact of anthropogenic activities on air quality in this area was investigated by comparing the COVID-19 lockdown in 2020 with the normal situation in 2021. Tropospheric NO2, HCHO and SO2 column densities were observed by ground-based multiple axis differential optical absorption spectroscopy (MAX-DOAS). In situ measurements for PM2.5, NO2, SO2 and O3 were also taken. The observation period was divided into four phases, the pre-lockdown period, phase 1 lockdown, phase 2 lockdown and the post-lockdown period. Ground-based MAX-DOAS results showed that tropospheric NO2, HCHO and SO2 column densities increased by 41, 14 and 14%, respectively, during phase 1 in 2021 vs. 2020. In situ results showed that NO2 and SO2 increased by 59 and 11%, respectively, during phase 1 in 2021 vs. 2020, but PM2.5 and O3 decreased by 15 and 17%, respectively. In the phase 2 period, due to the partial lifting of control measures, the concentration of pollutants did not significantly change. The weekly MAX-DOAS results showed that there was no obvious weekend effect of pollutants in the Huaibei area, and NO2, HCHO and SO2 had obvious diurnal variation characteristics. In addition, the relationship between the column densities and wind speed and direction in 2020 and 2021 was studied. The results showed that, in the absence of traffic control in 2021, elevated sources in the Eastern part of the city emitted large amounts of NO2. The observed ratios of HCHO to NO2 suggested that tropospheric ozone production involved NOX-limited scenarios. The correlation analysis between HCHO and different gases showed that HCHO mainly originated from primary emission sources related to SO2.

Direct-ink-writing (DIW)-based 3D-printing technology combined with the direct-foaming method provides a new strategy for the fabrication of porous materials. We herein report a novel method of preparing porous SiC ceramics using the DIW process and investigate their mechanical and wave absorption properties. We investigated the effects of nozzle diameter on the macroscopic shape and microstructure of the DIW SiC green bodies. Subsequently, the influences of the sintering temperature on the mechanical properties and electromagnetic (EM) wave absorption performance of the final porous SiC-sintered ceramics were also studied. The results showed that the nozzle diameter played an important role in maintaining the structure of the SiC green part. The printed products contained large amounts of closed pores with diameters of approximately 100–200 μm. As the sintering temperature increased, the porosity of porous SiC-sintered ceramics decreased while the compressive strength increased. The maximum open porosity and compressive strength were 65.4% and 7.9 MPa, respectively. The minimum reflection loss (RL) was −48.9 dB, and the maximum effective absorption bandwidth (EAB) value was 3.7 GHz. Notably, porous SiC ceramics after sintering at 1650 °C could meet the application requirements with a compressive strength of 7.9 MPa, a minimum RL of −27.1 dB, and an EAB value of 3.4 GHz. This study demonstrated the potential of direct foaming combined with DIW-based 3D printing to prepare porous SiC ceramics for high strength and excellent EM wave absorption applications.

Glioma is the most common primary intracranial malignant tumour in adults. It has a high incidence and poses a serious threat to human health. Circular RNA is a hotspot of cancer research. In this study, we aimed to explore the role of circ_0001367 in gliomagenesis and the underlying mechanism. First, qRT-PCR was conducted, which showed that circ_0001367 level was downregulated in glioma tissues and cells. Next, gain-of-function and loss-of-function assays were performed, which indicated that circ_0001367 inhibited the proliferation, migration and invasion of glioma cells. Subsequent bioinformatics analysis, dual-luciferase reporter assays, RNA immunoprecipitation assays and cell function assays demonstrated that circ_0001367 inhibited the proliferation, migration and invasion of glioma cells by absorbing miR-545-3p and thereby regulating the expression of leucine zipper protein (LUZP1). Finally, an in vivo experiment was conducted, which demonstrated that circ_0001367 inhibited glioma growth in vivo by modulating miR-545-3p and LUZP1. Taken together, the results of this study demonstrate that the circ_0001367/miR-545-3p/LUZP1 axis may be a novel target for glioma therapy.

Acquired chemoresistance is a major limiting factor in the clinical treatment of glioblastoma (GBM). However, the mechanism by which GBM acquires therapeutic resistance remains unclear. Here, we aimed to investigate whether METTL3-mediated N6-methyladenosine (m6A) modification contributes to the temozolomide (TMZ) resistance in GBM. We demonstrated that METTL3 METTL3-mediated m6A modification were significantly elevated in TMZ-resistant GBM cells. Functionally, METTL3 overexpression impaired the TMZ-sensitivity of GBM cells. In contrast, METTL3 silencing or DAA-mediated total methylation inhibition improved the sensitivity of TMZ-resistant GBM cells to TMZ in vitro and in vivo. Furthermore, we found that two critical DNA repair genes (MGMT and APNG) were m6A-modified by METTL3, whereas inhibited by METTL3 silencing or DAA-mediated total methylation inhibition, which is crucial for METTL3-improved TMZ resistance in GBM cells. Collectively, METTL3 acts as a critical promoter of TMZ resistance in glioma and extends the current understanding of m6A related signaling, thereby providing new insights into the field of glioma treatment.

Recent studies have reported that cancer associated fibroblasts (CAFs) and glioma stem-like cells (GSCs) played active roles in glioma progression in tumor microenvironment (TME). Long non-coding RNAs (lncRNAs) have been found to be closely associated with glioma development in recent years, however, their molecular regulatory mechanisms on CAFs in GSCs remodeled TME kept largely unelucidated. Our study found that GSCs could induce malignant transformation of fibroblasts (t-FBs) based on dual-color fluorescence tracing orthotopic model. Associated with poor prognosis, Lnc HOXA transcript antisense RNA, myeloid-specific 1 (HOTAIRM1) was highly expressed in high-grade gliomas and t-FBs. Depleting HOTAIRM1 inhibited the proliferation, invasion, migration, and even tumorigenicity of t-FB. Conversely, overexpression of HOTAIRM1 promoted malignancy phenotype of t-FB. Mechanistically, HOTAIRM1 directly bound with miR-133b-3p, and negatively regulated the latter. MiR-133b-3p partly decreased the promotion effect of HOTAIRM1 on t-FBs. Furthermore, transforming growth factor-β (TGFβ) was verified to be a direct target of miR-133b-3p. HOTAIRM1 can modulate TGFβ via competing with miR-133b-3p. Collectively, HOTAIRM1/miR-133b-3p/TGFβ axis was involved in modulating t-FBs malignancy in TME remodeled by GSCs, which had the potential to serve as a target against gliomas.

Summary: Various mesenchymal cell types have been identified as critical components of the hematopoietic stem/progenitor cell (HSPC) niche. Although several groups have described the generation of mesenchyme from human pluripotent stem cells (hPSCs), the capacity of such cells to support hematopoiesis has not been reported. Here, we demonstrate that distinct mesenchymal subpopulations co-emerge from mesoderm during hPSC differentiation. Despite co-expression of common mesenchymal markers (CD73, CD105, CD90, and PDGFRβ), a subset of cells defined as CD146hiCD73hi expressed genes associated with the HSPC niche and supported the maintenance of functional HSPCs ex vivo, while CD146loCD73lo cells supported differentiation. Stromal support of HSPCs was contact dependent and mediated in part through high JAG1 expression and low WNT signaling. Molecular profiling revealed significant transcriptional similarity between hPSC-derived CD146++ and primary human CD146++ perivascular cells. The derivation of functionally diverse types of mesenchyme from hPSCs opens potential avenues to model the HSPC niche and develop PSC-based therapies. : Crooks and colleagues demonstrated a previously underappreciated functional and molecular heterogeneity in mesenchyme generated from human pluripotent stem cells. Two mesenchymal subsets were distinguished by the reciprocal expression of CD146, CD73, and CD140a. CD146hiCD73hi mesenchyme supported self-renewing hematopoietic stem and progenitor cells (HSPCs), expressed markers of the HSPC niche, and shared a similar molecular signature with primary human adult pericytes. Keywords: pluripotent stem cell, mesenchyme, hematopoietic stem cell niche, pericyte biology, directed differentiation, mesoderm

Phase change memory (PCM) formed by Ge2Sb2Te5 (GST) on vertical carbon nanotube (CNT) filled contact plug is demonstrated in this paper. In order to achieve compatibility with the underlying process, the CNTs are synthesized using nickel catalyst at a low temperature. Reasonable contact characteristics between the CNTs and GST are achieved without material compatibility problem. Due to the small contact size of the CNT to the phase change material, a significant reduction in programming power is achieved compared to metal contact at the same via size. The temperature simulation result shows that the CNT filled via helps to reduce the programming area. The fabricated PCM on CNT filled via is able to endure more than 104 SET/RESET cycles without observable degradation.

Synthesis of the vertically aligned carbon nanotubes (CNTs) using complementary metal-oxide-semiconductor (CMOS)-compatible methods is essential to integrate the CNT contact and interconnect to nanoscale devices and ultra-dense integrated nanoelectronics. However, the synthesis of high-density CNT array at low-temperature remains a challenging task. The advances in the low-temperature synthesis of high-density vertical CNT structures using CMOS-compatible methods are reviewed. Primarily, recent works on theoretical simulations and experimental characterizations of CNT growth emphasized the critical roles of catalyst design in reducing synthesis temperature and increasing CNT density. In particular, the approach of using multilayer catalyst film to generate the alloyed catalyst nanoparticle was found competent to improve the active catalyst nanoparticle formation and reduce the CNT growth temperature. With the multilayer catalyst, CNT arrays were directly grown on metals, oxides, and 2D materials. Moreover, the relations among the catalyst film thickness, CNT diameter, and wall number were surveyed, which provided potential strategies to control the tube density and the wall density of synthesized CNT array.

From July 4 to 11, 2006 at Back Garden site (23°28’86”N; 113°02’91”E), nighttime nitrate radical (NO3) was measured with a long path differential optical absorption spectroscopy (DOAS) during an intensive field campaign in the Pearl River Delta of China. The NO3 concentration in polluted air masses varied from 3.6 to 82.5 ppt with an average level of 21.8 ± 1.8 ppt. NO3 at these levels can play a significant role in oxidation of volatile organic compounds (VOCs). The calculated production rate of nitrate radical ranged from 8 × 105 to 2.98 × 107 cm-3 s-1, while its lifetimes spanned from between just several seconds to 650 seconds, with an average of 89 seconds. N2O5 levels were calculated with the average of 620 ± 93 ppt during this campaign. The possible scavenging processes for the nitrate radical were obtained by using a statistical analysis of the correlation between NO3 and NO levels, NO3 concentration and its production rate, and the NO3 lifetime and NO2 levels, respectively. Results showed that the direct losses were of importance at Back Garden in summer Pearl River Delta, China.

CaF2: Eu3+ nanoparticles with different doping concentrations were prepared by a hydrothermal method. The surface of the prepared nanoparticles was modified by 1,2,4,5-benzenetetracarboxylic acid. The structure, morphology, photoluminescence properties, and fluorescence dynamics are studied systemically. The functionalized nanoparticles have a broad excitation band in UV-vis area and high asymmetry radio. The luminescence of Eu3+ ions in CaF2 nanoparticles is improved by 1,2,4,5-benzenetetracarboxylic acid bonded onto the surface of nanoparticles via the energy transfer process. The excited state lifetimes of functionalized nanoparticles are longer than those of un-functionalized nanoparticles. These kinds of materials have the potential to be applied in luminescent solar concentrators. [ABSTRACT FROM AUTHOR]

Colitis is an inflammatory intestinal disease that lasts for a long time, has an unknown cause, and occurs repeatedly. It is usually accompanied by symptoms such as intestinal cell damage, intestinal immunity, and abnormal intestinal flora. Numerous studies have shown that dietary fiber, as a prebiotic, its metabolites can selectively improve the composition of the intestinal flora, which in turn improves the level of intestinal short-chain fatty acids, reduces the expression of inflammatory factors, and enhances the function of the intestinal immune barrier, thereby improving the inflammatory response of the organism. This anti-inflammatory effect of dietary fiber through its metabolites provides new research ideas to assist in the treatment of colitis. This paper outlines the pathogenesis of colitis, and the mechanism of interaction between dietary fiber and its metabolites with intestinal flora, inflammatory factors and immune cells, aiming to provide theoretical basis for the alleviation of colitis by dietary fiber and the development of functional foods.

Background: Glioma is the most common malignant tumor of the central nervous system, with high heterogeneity, strong invasiveness, high therapeutic resistance, and poor prognosis, comprehending a serious challenge in neuro-oncology. Until now, the mechanisms underlying glioma progression have not been fully elucidated. Methods: The expression of DExH-box helicase 9 (DHX9) in tissues and cells was detected by qRT-PCR and western blot. EdU and transwell assays were conducted to assess the effect of DHX9 on proliferation, migration and invasion of glioma cells. Cocultured model was used to evaluate the role of DHX9 on macrophages recruitment and polarization. Animal study was performed to explore the role of DHX9 on macrophages recruitment and polarization in vivo. Bioinformatics analysis, dualluciferase reporter assay and chromatin immunoprecipitation (ChIP)-qPCR assay was used to explore the relation between DHX9 and TCF12/CSF1. Results: DHX9 was elevated in gliomas, especially in glioblastoma multiforme (GBM). Besides promoting the proliferation, migration, and invasion of glioma cells, DHX9 facilitated the infiltration of macrophages into glioma tissues and polarization to M2-like macrophages, known as tumor-associated macrophages (TAMs). DHX9 silencing decreased the expression of colony-stimulating factor 1 (CSF1), which partially restored the inhibitory effect on malignant progress of glioma and infiltration of TAMs caused by DHX9 knockdown by targeting the transcription factor 12 (TCF12). Moreover, TCF12 could directly bind to the promoter region of CSF1. Conclusion: DHX9/TCF12/CSF1 axis regulated the increases in the infiltration of TAMs to promote glioma progression and might be a novel potential target for future immune therapies against gliomas. [ABSTRACT FROM AUTHOR]