Impaired arginine/ornithine metabolism drives severe HFMD by promoting cytokine storm.

Introduction: The Hand, Foot and Mouth Disease (HFMD), caused by enterovirus 71 infection, is a global public health emergency. Severe HFMD poses a significant threat to the life and well-being of children. Numerous studies have indicated that the occurrence of severe HFMD is associated with cytokine storm. However, the precise molecular mechanism underlying cytokine storm development remains elusive, and there are currently no safe and effective treatments available for severe HFMD in children. Methods: In this study, we established a mouse model of severe HFMD to investigate the molecular mechanisms driving cytokine storm. We specifically analyzed metabolic disturbances, focusing on arginine/ornithine metabolism, and assessed the potential therapeutic effects of spermine, an ornithine metabolite. Results: Our results identified disturbances in arginine/ornithine metabolism as a pivotal factor driving cytokine storm onset in severe HFMD cases. Additionally, we discovered that spermine effectively mitigated the inflammatory injury phenotype observed in mice with severe HFMD. Discussion: In conclusion, our findings provide novel insights into the molecular mechanisms underlying severe HFMD from a metabolic perspective while offering a promising new strategy for its safe and effective treatment.

Comparison of endovascular interventional embolization and microsurgical clipping for ruptured cerebral aneurysms: impact on patient outcomes.

OBJECTIVE: To compare the therapeutic efficacy of endovascular interventional embolization and microsurgical clipping in patients with ruptured cerebral aneurysms and investigate their subsequent influence on inflammatory indices, neurological function, prognosis, and recovery. METHODS: The two groups were compared in terms of surgery duration, hospital stay, Hunt-Hess classification, and inflammatory indices before and after the surgery, as well as National Institutes of Health Stroke Scale (NIHSS), Baethel Index (BI), and one-year prognosis of patients affected. RESULTS: The surgery duration and hospital stay of the intervention group were (116.27 ± 12.32) min and (19.82 ± 2.26) d, respectively, and those of the clipping group was (173.87 ± 10.39) min and (24.11 ± 2.33) d, respectively (both p < 0.05). Neither the intervention nor the microscopic approach had a significant impact on the severity of the patients' conditions in terms of Hunt-Hess classification (p > 0.05). In the intervention group, CRP was changed to (5.31 ± 1.22) mg/L and PCT decreased to (1.17 ± 0.39) µg/L after the surgery, while the corresponding values in clipping group were (9.78 ± 2.35) mg/L and (2.75 ± 0.81) µg/L (p > 0.05). After surgery, both groups' NIHSS scores declined dramatically, with the intervention group scoring lower than the microscopy group (6.81 ± 1.22 vs 8.72 ± 1.27) (p < 0.05). CONCLUSION: The findings of this study support the potential advantages of endovascular interventional embolization (coiling) over microsurgical clipping for the management of ruptured cerebral aneurysms. These advantages include shorter surgical duration, reduced hospital stay, lower inflammatory response, improved neurological and functional outcomes, and better long-term prognosis.

Robust evidence reveals the reliable rate of normal/balanced embryos for identifying reciprocal translocation and Robertsonian translocation carriers.

We aimed to evaluate the reliable rate of normal/balanced embryos for reciprocal translocation and Robertsonian translocation carriers and to provide convincing evidence for clinical staff to conduct genetic counselling regarding common structural rearrangements to alleviate patient anxiety. The characteristics of 39,459 embryos that were sourced from unpublished data and literature were analyzed. The samples consisted of 17,536 embryo karyotypes that were not published and 21,923 embryo karyotypes obtained from the literature. Using the PubMed, Cochrane Library, Web of Science, and Embase databases, specific keywords were used to screen the literature for reciprocal translocation and Robertsonian translocation. The ratio of normal/balanced embryos in the overall data was calculated and analyzed, and we grouped the results according to gender to confirm if there were gender differences. We also divided the data into the cleavage stage and blastocyst stage according to the biopsy period to verify if there was a difference in the ratio of normal/balanced embryos. By combining the unpublished data and data derived from the literature, the average rates of normal/balanced embryos for reciprocal translocation and Robertsonian translocation carriers were observed to be 26.96% (7953/29,495) and 41.59% (4144/9964), respectively. Reciprocal translocation and Robertson translocation exhibited higher rates in male carriers than they did in female carriers (49.60% vs. 37.44%; 29.84% vs. 27.67%). Additionally, the data for both translocations exhibited differences in the normal/balanced embryo ratios between the cleavage and blastocyst stages of carriers for both Robertsonian translocation and reciprocal translocation (36.07% vs 43.43%; 24.88% vs 27.67%). The differences between the two location types were statistically significant (P < 0.05). The normal/balanced ratio of embryos in carriers of reciprocal and RobT was higher than the theoretical ratio, and the values ranged from 26.96% to 41.59%. Moreover, the male carriers possessed a higher number of embryos that were normal or balanced. The ratio of normal/balanced embryos in the blastocyst stage was higher than that in the cleavage stage. The results of this study provide a reliable suggestion for future clinic genetic consulting regarding the rate of normal/balanced embryos of reciprocal translocation and Robertsonian translocation carriers.

Robust and Flame-Retardant Zylon Aerogel Fibers for Wearable Thermal Insulation and Sensing in Harsh Environment.

The exceptional lightweight, highly porous, and insulating properties of aerogel fibers make them ideal for thermal insulation. However, current aerogel fibers face limitations due to their low resistance to harsh environments and a lack of intelligent responses. Herein, a universal strategy for creating polymer aerogel fibers using crosslinked nanofiber building blocks is proposed. This approach combines controlled proton absorption gelation spinning with a heat-induced crosslinking process. As a proof-of-concept, Zylon aerogel fibers that exhibited robust thermal stability (up to 650 °C), high flame retardancy (limiting oxygen index of 54.2%), and extreme chemical resistance are designed and synthesized. These fibers possess high porosity (98.6%), high breaking strength (8.6 MPa), and low thermal conductivity (0.036 W m-1 K-1 ). These aerogel fibers can be knotted or woven into textiles, utilized in harsh environments (-196-400 °C), and demonstrate sensitive self-powered sensing capabilities. This method of developing aerogel fibers expands the applications of high-performance polymer fibers and holds great potential for future applications in wearable smart protective fabrics.

Combination of a bronchogenic cyst in the thoracic spinal canal with chronic myelocytic leukemia.

The presented case report describes an incredibly rare instance of an intramedullary bronchial cyst located in the thoracic spinal canal on the dorsal side of the spinal cord, which was observed in a patient with chronic myelogenous leukemia. A 29-year-old man presented with back pain for half a month, along with numbness and pain below the chest and ribs for 1 week. Hypersensitivity was present in the inferior plane of the long xiphoid process in the nervous system. Magnetic resonance imaging (MRI) showed intramedullary cystic lesions in the vertebral body plane of the third to the fourth thoracic vertebra. There was no recurrence during the 6-month postoperative follow-up period. The histopathological findings were consistent with bronchogenic cysts. Cystic lesions were eliminated through the posterior median approach. After the cyst ruptured during surgery, gel liquid was seen, and the majority of the cyst walls were removed. One week after the surgery, the hypersensitivity fully subsided. Six months following surgery, an updated MRI revealed no recurrence. Intramedullary bronchogenic cysts on the dorsal side of the thoracic spine are extremely uncommon. Diagnosis requires histopathological evidence, and it is challenging to diagnose before surgery. Prompt surgical resection is recommended in case of positive diagnosis.

Multifunctional MXene/C Aerogels for Enhanced Microwave Absorption and Thermal Insulation.

Two-dimensional transition metal carbides and nitrides (MXene) have emerged as promising candidates for microwave absorption (MA) materials. However, they also have some drawbacks, such as poor impedance matching, high self-stacking tendency, and high density. To tackle these challenges, MXene nanosheets were incorporated into polyacrylonitrile (PAN) nanofibers and subsequently assembled into a three-dimensional (3D) network structure through PAN carbonization, yielding MXene/C aerogels. The 3D network effectively extends the path of microcurrent transmission, leading to enhanced conductive loss of electromagnetic (EM) waves. Moreover, the aerogel's rich pore structure significantly improves the impedance matching while effectively reducing the density of the MXene-based absorbers. EM parameter analysis shows that the MXene/C aerogels exhibit a minimum reflection loss (RLmin) value of - 53.02 dB (f = 4.44 GHz, t = 3.8 mm), and an effective absorption bandwidth (EAB) of 5.3 GHz (t = 2.4 mm, 7.44-12.72 GHz). Radar cross-sectional (RCS) simulations were employed to assess the radar stealth effect of the aerogels, revealing that the maximum RCS reduction value of the perfect electric conductor covered by the MXene/C aerogel reaches 12.02 dB m2. In addition to the MA performance, the MXene/C aerogel also demonstrates good thermal insulation performance, and a 5-mm-thick aerogel can generate a temperature gradient of over 30 °C at 82 °C. This study provides a feasible design approach for creating lightweight, efficient, and multifunctional MXene-based MA materials.

HDGF promotes gefitinib resistance by activating the PI3K/AKT and MEK/ERK signaling pathways in non-small cell lung cancer.

Hepatoma-derived growth factor (HDGF) expression is associated with poor prognosis in non-small cell lung cancer (NSCLC); however, whether HDGF affects gefitinib resistance in NSCLC remains unknown. This study aimed to explore the role of HDGF in gefitinib resistance in NSCLC and to discover the underlying mechanisms. Stable HDGF knockout or overexpression cell lines were generated to perform experiments in vitro and in vivo. HDGF concentrations were determined using an ELISA kit. HDGF overexpression exacerbated the malignant phenotype of NSCLC cells, while HDGF knockdown exerted the opposite effects. Furthermore, PC-9 cells, which were initially gefitinib-sensitive, became resistant to gefitinib treatment after HDGF overexpression, whereas HDGF knockdown enhanced gefitinib sensitivity in H1975 cells, which were initially gefitinib-resistant. Higher levels of HDGF in plasma or tumor tissue also indicated gefitinib resistance. The effects of HDGF on promoting the gefitinib resistance were largely attenuated by MK2206 (Akt inhibitor) or U0126 (ERK inhibitor). Mechanistically, gefitinib treatment provoked HDGF expression and activated the Akt and ERK pathways, which were independent of EGFR phosphorylation. In summary, HDGF contributes to gefitinib resistance by activating the Akt and ERK signaling pathways. The higher HDGF levels may predict poor efficacy for TKI treatment, thus it has the potential to serve as a new target for overcoming tyrosine kinase inhibitor resistance in combating NSCLC.

In-Situ Growth of ZnO Whiskers on Ti2ZnC MAX Phases.

ZnO whiskers have many applications, such as in medical and photocatalysis fields. In this study, an unconventional preparation approach is reported, realizing the in-situ growth of ZnO whiskers on Ti2ZnC. The weak bonding between the layer of Ti6C-octahedron and the Zn-atom layers leads to the easy extraction of Zn atoms from Ti2ZnC lattice points, resulting in the formation of ZnO whiskers on the Ti2ZnC surface. This is the first time that ZnO whiskers have been found to grow in-situ on Ti2ZnC substrate. Further, this phenomenon is amplified when the size of the Ti2ZnC grains is mechanically reduced by ball-milling, which bodes a promising route to prepare ZnO in-situ on a large scale. Additionally, this finding can also help us better understand the stability of Ti2ZnC and the whiskering mechanism of MAX phases.

Lithium storage performance and mechanism of nano-sized Ti2InC MAX phase.

Fine powders of MAX phases (a family of layered carbides/nitrides) have been showing great promise in energy storage applications. A feasible method of obtaining nano-sized MAX phase particles is critical to realizing the practical application of the vast MAX phase family in more technologically important fields. Herein, ball milling, a commercial and feasible method, is employed to prepare nano-sized Ti2InC, which delivers a high specific capacity of 590 mA h g-1 after 500 cycles and maintains 574.4 mA h g-1 after 600 cycles at 0.1 A g-1 when used as a lithium storage anode. Compared with other methods (e.g., partial etching), decreasing the size of Ti2InC particles by ball milling can preserve the exfoliated indium (In) atoms, which have great volumetric and gravimetric capacities. In situ XRD analysis indicates that the capacity of the nano-sized Ti2InC primarily comes from the lithiation of elemental In exfoliated from Ti2InC, and in particular, the exfoliated In atoms by ball milling can increase the initial capacity. The lithiation/delithiation cycle can effectively activate and even exfoliate the Ti2InC grains, which accounts for the increasing capacity upon cycling.

Digital economy and industrial energy efficiency performance: evidence from the city of the Yangtze River Delta in China.

Industry dominates energy consumption and carbon emissions in China, and industrial energy efficiency is critical for the achievement of energy transformation and carbon emission reduction. With the rapid development of the digital economy, its impact on energy efficiency is gradually emerging, and it is necessary to clarify the influencing mechanism on industrial energy efficiency. Based on the panel data of industrial sectors in 41 cities in the Yangtze River Delta from 2011 to 2019, the main objectives of this study are to more accurately measure the industrial total factor energy efficiency in each city by using the Super-Dynamic-SBM model. It analyses the influence mechanism of the digital economy and other influencing factors on industrial total factor energy efficiency with different methods. The research results indicate that, first, the total factor energy efficiency of the industrial sector in the Yangtze River Delta urban agglomeration generally showed a steady upward trend. Second, the digital economy and environmental regulation play a significant role in promoting total factor energy efficiency. In addition, industrial energy efficiency and the digital economy show an inverted "U" shaped relationship. With the improvement of the digital economy, its marginal contribution to total factor energy efficiency gradually weakens. Finally, technological progress is an important transmission channel for the impact of the digital economy on total factor energy efficiency.

Lightweight and flexible PAN@PPy/MXene films with outstanding electromagnetic interference shielding and Joule heating performance.

Lightweight and flexible multifunctional materials with excellent electromagnetic interference (EMI) shielding and Joule heating performances are highly demanded for smart and wearable electronics. In this work, polyacrylonitrile (PAN) nanofiber films are prepared by electrospinning and then coated with polypyrrole (PPy) via vapor deposition, yielding a continuous three-dimensional (3D) conductive network of PAN@PPy. Ti3C2Tx MXene nanosheets with high electrical conductivity are sprayed on the PAN@PPy film to enhance its EMI shielding performance. The as-prepared PAN@PPy/MXene films (55 µm thick) exhibit a high EMI shielding effectiveness (SE) of 32 dB, achieving an extraordinarily high normalized surface-specific SE (SSE/t) of up to 17 534.5 dB cm2 g-1 from 8.2 to 12.4 GHz; simultaneously, the temperatures of PAN@PPy/MXene films can be driven up to 170.5 °C at an input voltage of 4 V, and exhibit fast-response, stable, and long-term Joule heating performance. The high SSE/t and efficient Joule heating ability of the films bode potential applications in smart and wearable devices.

Dye-Sensitized Solar Cell Based on TiO2 Anode Thin Film with Three-Dimensional Web-like Structure.

TiO2 films with a three-dimensional web-like porous structure were prepared using the photo polymerization-induced phase separation method integrated with the pulling coating process. By adjusting the ratio of the substance in the precursor sol and the coating times, the relationships between the sol ratio, the coating times, the film structure, and the performance of the DSC were studied. The optimal film structure was found and a detailed description is given. The performance of the DSC was further improved by introducing the barrier layer and the surface-modified layer of the TiO2 coating. This promoted the short-circuit current density and the photoelectric conversion efficiency of the DSC, the mechanism of which was also investigated. Ultimately, the photoelectric conversion efficiency of the DSC based on the TiO2 anode films with a three-dimensional web-like structure was stabilized at a higher level as a result of the structural improvement.

Blockade of STAT3/IL-4 overcomes EGFR T790M-cis-L792F-induced resistance to osimertinib via suppressing M2 macrophages polarization.

BACKGROUND: The mechanism of missense alteration at EGFR L792F in patients with non-small cell lung cancer resistant to osimertinib has not been sufficiently clarified. We aimed to explore the critical molecular events and coping strategies in osimertinib resistance due to acquired L792F mutation. METHODS: Circulating tumor DNA-based sequencing data of 1153 patients with osimertinib resistance were collected to illustrate the prevalence of EGFR L792F mutation. Sensitivity to osimertinib was tested with constructed EGFR 19Del/T790M-cis-L792F cell lines in vitro and in vivo. The correlation and linked pathways between M2 macrophage polarization and EGFR L792Fcis-induced osimertinib resistance were investigated. Possible interventions to suppress osimertinib resistance by targeting IL-4 or STAT3 were explored. FINDINGS: The concomitant EGFR L792F was identified as an independent mutation following the acquisition of T790M after osimertinib resistance, in that 5 of the 946 patients with osimertinib resistance harbored EGFR T790M-cis-L792F mutation. Transfected EGFR 19Del/T790M-cis-L792F in cell lines had decreased sensitivity to osimertinib and enhanced infiltrating macrophage with M2 polarization. Silico analyses confirmed the role of M2 polarization in osimertinib resistance induced by EGFR T790M-cis-L792F mutation. EGFR T790M-cis-L792F mutation upregulated phosphorylation of STAT3 Tyr705 and promoted its specific binding to IL4 promoter, enhancing IL-4 expression and secretion and inducing macrophage M2 polarization. Furthermore, blockade of STAT3/IL-4 (SH-4-54 or dupilumab) suppressed macrophage M2 polarization and regressed tumor sensitivity to osimertinib. INTERPRETATION: Our results proved that targeting EGFR T790M-cis-L792F/STAT3 Tyr705/IL-4 pathway could be a potential strategy to suppress osimertinib resistance in NSCLC. FUNDING: This work was supported by the National Natural Science Foundation of China (81871889, 82072586, 81902910), Beijing Natural Science Foundation (7212084, 7214249), the China National Natural Science Foundation Key Program (81630071), the National Key Research and Development Project (2019YFC1315704), CAMS Innovation Fund for Medical Sciences (CIFMS 2021-1-I2M-012), Aiyou Foundation (KY201701) and CAMS Key Laboratory of translational research on lung cancer (2018PT31035).

A Retrospective Trail Investigating Temozolomide Neoadjuvant Chemotherapy Combined with Radiotherapy in Low-Grade Pituitary Tumors.

Objective: To study and analyze the clinical application of temozolomide (TMZ) combined with radiotherapy in the treatment of low-grade pituitary tumors. Methods: A retrospective trail was conducted among 67 patients with low-grade pituitary tumors who were treated in our hospital from March 2018 to June 2020. According to different treatment methods, they were assigned into a combined group (37 cases, temozolomide capsules and radiotherapy) and a control group (30 cases, radiotherapy). The changes of serum prolactin (PRL), insulin-like growth factor-1 (IGF-1), GH levels, thyroid-stimulating hormone (TSH), serum free thyroxine (FT4), and adrenocorticotropic hormone (ACTH) were compared. Results: The chi-square test reports a significantly higher total effective rate in the combined group vs. control group (91.89% vs. 70.00%). Significant reductions in serum levels of PRL, IGF-1, and GH were observed in both groups after treatment, whereas the combined group treated with radiotherapy and TMZ resulted in significantly lower levels compared with the control group (p < 0.05). After treatment, TSH decreased, and FT4 and ACTH increased in both groups, and the treatment with radiotherapy and TMZ in the combined group led to a significantly greater amplitude of variation (p < 0.05). Conclusion: The combination of temozolomide and radiotherapy might be a promising technique for the treatment of pituitary tumors, thereby meriting promotion.

Does the environmental inequality matter? A literature review.

The environmental inequality theory reveals that the risk of environmental pollution exposure varies among regions and groups and that particular groups face a higher threat of environmental pollution. In recent years, studies on the environmental inequality issue in developed countries have been increasing, while related literature on developing countries is very scarce. It has been found that some factors, such as race and economic status, have a close relationship with the risk of environmental pollution exposure faced by individuals. For the first time, this paper provides an extensive review of existing theoretical and empirical studies on environmental inequality. We review, in detail, the evolution of the environmental inequality theory, including the definition and measurement of environmental inequality. Further, we provide a systematic refresher on the main performance of environmental inequality, including health, education, labor productivity, and real estate prices. We also identify several causes of environmental inequality, such as ethnic differences, economic status, human capital, and household registration systems. Finally, we discuss prospects for the future research on this issue.

Inhibiting CBX4 efficiently protects hepatocellular carcinoma cells against sorafenib resistance.

BACKGROUND: This study aimed to investigate the possible role of inhibiting chromobox protein homologue 4 (CBX4) to deregulate of cancer stem cells (CSCs) and to evaluate the contribution of these molecules to sorafenib resistance in advanced hepatocellular carcinoma (HCC). METHODS: HCC cell lines and a xenograft mouse model with resistance to sorafenib were employed to analyse the effects of miR424 on CSC characteristics. RNA expression was analysed by RT-PCR and next-generation sequencing in a cohort of HCC cancer patients and sorafenib-resistant (SR) cell lines, respectively, to validate the key microRNAs and targets in the network. RESULTS: MicroRNA and mRNA profiles of SR cell lines identified miR424 and its direct target CBX4 as significantly associated with stem-cell-like properties, poor survival, and clinical characteristics. Functional experiments demonstrated that miR424 suppressed CBX4 and CBX4 induced nuclear translocation of YAP1 protein but was not associated with protein production. When YAP1 and CBX4 were modulated with CA3 and UNC3866, tumorigenicity and stem-like properties were extremely inhibited, thus indicating that these compounds exerted a strong anti-tumour effect in vivo against SR HCC cells. CONCLUSIONS: Our results revealed that blocking CBX4 expression is critical in response to sorafenib resistance with advanced HCC.

Assessing the total factor performance of wastewater treatment in China: A city-level analysis.

China is currently facing huge challenges in mitigating water shortages and protecting water bodies. The inferior wastewater treatment of the country has become the main barrier impeding regional water pollution control and sustainable economic development. Therefore, creating an overview of the current performance and weaknesses of city-level wastewater treatment is crucial and beneficial for exploring the driving factors for improvement. This study employed the slack-based measure and improved Luenberger productivity indicator decomposition method to investigate wastewater treatment performance in Chinese cities from static and dynamic perspectives. Results showed that pollutants were the main factors leading to wastewater treatment inefficiency. The total factor productivity of wastewater treatment (WTFP) of Chinese cities demonstrated an increasing trend from a temporal perspective and distinct spatial heterogeneity. An in-depth decomposition revealed that the most influential factor leading to WTFP growth was efficiency improvement rather than technical progress, pollutants discharge reduction rather than intensification of inputs. Given the varied types of cities, corresponding optimal and differentiated strategies, including source-oriented controls and end-of-pipe-led regulations, were provided to improve the overall performance of wastewater treatment. The findings of this study can help decision makers design specific policies for wastewater governance, which would be beneficial for achieving the green and high-quality development targets.

The combination of circRNA-UMAD1 and Galectin-3 in peripheral circulation is a co-biomarker for predicting lymph node metastasis of thyroid carcinoma.

The diagnosis of lymph node metastasis (LNM) by liquid biopsy is a novel concept prompted by the necessity to develop a more convenient and accurate method to guide the clinical management of early LNM in papillary thyroid carcinoma (PTC). However, the sensitivity and specificity of many biomarkers are not high enough. We aimed to detect circRNAs from peripheral circulation that may be better associated with the prognosis of LNM in PTC. First, Galectin-3 (Gal3) in blood was determined to be highly expressed in LNM patients. Second, based on a bioinformatics analysis and miRNA sequencing analysis from 2 paired primary and LNM tumors, miR-873 was identified to directly target Gal3, which was significantly associated with clinical parameters including LNM. Third, from additional circRNA sequencing, circRNA-UMAD1 was selected as a specific sponge for miR-873 and was correlated with Gal3 levels in peripheral circulation. Fourth, circRNA-UMAD1 and Gal3 were identified to have stronger co-biomarker potential with relatively high expression in the serum of LNM patients compared with primary tumor patients, as demonstrated by the RNA expression levels in the serum of 50 PTC patients with or without LNM by quantitative real-time PCR. Overall, the combination of circRNA-UMAD1 and Gal3 is a useful and effective co-biomarker for the prognosis of LNM in PTC patients. This new molecular typing method for LNM in PTC is more precise.

Targeting DGAT1 Ameliorates Glioblastoma by Increasing Fat Catabolism and Oxidative Stress.

Glioblastoma (GBM), a mostly lethal brain tumor, acquires large amounts of free fatty acids (FAs) to promote cell growth. But how the cancer avoids lipotoxicity is unknown. Here, we identify that GBM upregulates diacylglycerol-acyltransferase 1 (DGAT1) to store excess FAs into triglycerides and lipid droplets. Inhibiting DGAT1 disrupted lipid homeostasis and resulted in excessive FAs moving into mitochondria for oxidation, leading to the generation of high levels of reactive oxygen species (ROS), mitochondrial damage, cytochrome c release, and apoptosis. Adding N-acetyl-cysteine or inhibiting FA shuttling into mitochondria decreased ROS and cell death induced by DGAT1 inhibition. We show in xenograft models that targeting DGAT1 blocked lipid droplet formation, induced tumor cell apoptosis, and markedly suppressed GBM growth. Together, our study demonstrates that DGAT1 upregulation protects GBM from oxidative damage and maintains lipid homeostasis by facilitating storage of excess FAs. Targeting DGAT1 could be a promising therapeutic approach for GBM.

The cysteine protease ATG4B of Trichinella spiralis promotes larval invasion into the intestine of the host.

The cysteine proteases of parasites are vital contributors that induce parasite migration to and invasion of host tissue. In this study, we analysed the cysteine protease ATG4B of Trichinella spiralis (TsATG4B) isolated from the soluble proteins of Trichinella spiralis (T. spiralis) adult worms to ascertain its biochemical properties and functions during invasion into the intestine of the host. The 43 kDa recombinant cysteine protease ATG4B protein (rTsATG4B) consists of a conserved peptidase_C54 domain and was expressed in Escherichia coli. Gelatine zymography showed that rTsATG4B could hydrolyse gelatine and that the hydrolytic activity was prevented by the cysteine protease inhibitor E-64 (pH 5.2). Immunofluorescence assays showed that TsATG4B is expressed at different stages and is localized at the cuticles and stichosomes of worms. Far-Western blotting and confocal microscopy revealed that rTsATG4B interacts with intestinal epithelial cells (IECs) and that it was subcellularly localized to the membrane and cytoplasm in IECs. Real­time quantitative PCR (qPCR) results indicated that the transcription level of the TsATG4B gene was the higher in 6-day-old adult worms (6 days AW) than in any other stage. An in vitro larval invasion assay verified that rTsATG4B promoted larval invasion and that invasion was inhibited when rTsATG4B was pre-incubated with E-64, whereas anti-rTsATG4B serum inhibited larval invasion in a dose-dependent manner. Collectively, these results suggested that the enzymatic activity of TsATG4B significantly influences the hydrolysis process, which is necessary for larval invasion of the host intestinal epithelium.