Identification of a fatty acid metabolism-related gene signature to predict prognosis in stomach adenocarcinoma.

BACKGROUND: Fatty acid metabolism (FAM) contributes to tumorigenesis and tumor development, but the role of FAM in the progression of stomach adenocarcinoma (STAD) has not been comprehensively clarified. METHODS: The expression data and clinical follow-up information were obtained from The Cancer Genome Atlas (TCGA). FAM pathway was analyzed by gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA) methods. Univariate Cox regression analysis was conducted to select prognosis genes. Molecular subtypes were classified by consensus clustering analysis. Furthermore, least absolute shrinkage and selection operator (Lasso) analysis was employed to develop a risk model. ESTIMATE and tumour immune dysfunction and exclusion (TIDE) algorithm were used to assess immunity. pRRophetic package was conducted to predict drug sensitivity. RESULTS: Based on 14 FAM related prognosis genes (FAMRG), 2 clusters were determined. Patients in C2 showed a worse overall survival (OS). Furthermore, a 7-FAMRG risk model was established as an independent predictor for STAD, with a higher riskscore indicating an unfavorable OS. High riskscore patients had higher TIDE score and these patients were more sensitive to anticancer drugs such as Bortezomib, Dasatinib and Pazopanib. A nomogram based on riskscore was an effective prediction tool applicable to clinical settings. The results from pan-cancer analysis supported a prominent application value of riskscore model in other cancer types. CONCLUSION: The FAMRGs model established in this study could help predict STAD prognosis and offer new directions for future studies on dysfunctional FAM-induced damage and anti-tumor drugs in STAD disease.

Triglyceride levels and risk of cardiovascular disease and all-cause mortality in Chinese adults younger than 40 years old: a prospective cohort study.

Background: Data on the associations of triglyceride (TG) levels with cardiovascular disease (CVD) and all-cause mortality mainly focused on the middle-aged or elderly population, with limited information available for younger adults. This study aimed to identify such associations among Chinese young adults. Methods: This study included Chinese adults younger than 40 years free of CVD, cancer, and lipid-lowering agents at baseline in the Kailuan study who were enrolled during 2006 through 2016. All participants were biennially followed up till December 2020. The enzymatic colorimetric method was used to measure baseline fasting TG. Participants were categorized into four groups by quartiles of TG, with the lowest quartile (Q1) as the reference group. The primary outcomes were CVD [composite of myocardial infarction (MI) and ischemic stroke] and all-cause mortality. CVD and mortality risks were estimated with Cox regression models. Results: A total of 43,882 participants were included. Their mean age was 30.6±5.56 years, and 80.2% were males. During a median follow-up of 11.2 years, 298 CVD events and 345 deaths occurred. The incidences of CVD and all-cause mortality were 0.67 and 0.76 per 1,000 person-years, respectively. Compared with individuals in the lowest quartile (Q1), participants in the highest quartile (Q4) showed a 126% higher risk of developing CVD [adjusted hazard ratio (HR) 2.26; 95% confidence interval (CI): 1.56 to 3.29; P=0.001] and a 61% higher risk of all-cause mortality (adjusted HR 1.61; 95% CI: 1.14 to 2.28; P=0.007). In addition, analyses of CVD subtypes showed that adjusted HRs (Q4 vs. Q1) were 3.25 (95% CI: 1.33 to 7.97; P=0.01) for MI, and 1.88 (95% CI: 1.16 to 3.04; P=0.01) for ischemic stroke. Conclusions: Among Chinese young adults, elevated fasting TG levels were associated with increased CVD and all-cause mortality risks.

Loop PDE of viral capsid protein is involved in immune escape of the emerging novel variant infectious bursal disease virus.

Infectious bursa disease (IBD) is an acute, highly contactable, lethal, immunosuppressive infectious disease caused by the Infectious bursa disease virus (IBDV). Currently, the emerged novel variant IBDV (nVarIBDV) and the sustainedly prevalent very virulent IBDV (vvIBDV) are the two most prevalent strains of IBDV in China. The antigenic properties of the two prevalent strains differed significantly, which led to the escape of nVarIBDV from the immune protection provided by the existing vvIBDV vaccine. However, the molecular basis of the nVarIBDV immune escape remains unclear. In this study, we demonstrated, for the first time, that residues 252, 254, and 256 in the PDE of VP2 are involved in the immune escape of the emerging nVarIBDV. Firstly, the IFA-mediated antigen-antibody affinity assay showed that PBC and PDE of VP2 could affect the affinity of vvIBDV antiserum to VP2, of which PDE was more significant. The key amino acids of PDE influencing the antigen-antibody affinity were also identified, with G254N being the most significant, followed by V252I and I256V. Then the mutated virus with point or combined mutations was rescued by reverse genetics. it was further demonstrated that mutations of V252I, G254N, and I256V in PDE could individually or collaboratively reduce antigen-antibody affinity and interfere with antiserum neutralization, with G254N being the most significant. This study revealed the reasons for the widespread prevalence of nVarIBDV in immunized chicken flocks and provided innovative ideas for designing novel vaccines that match the antigen of the epidemic strain.

H8-BINOL-Derived Chiral η6-Benzene Ligands: New Opportunities for the Ruthenium-Catalyzed Asymmetric C-H Activation.

Given the tremendous success of (p-cymene)RuII-catalyzed C-H activation over the past 20 years, the community has long been aware that the development of chiral η6-benzene (Ben) ligands should be a potent strategy for achieving the attractive but incredibly underdeveloped ruthenium(II)-catalyzed asymmetric C-H activation. However, it has rarely been achieved due to the severe difficulty in developing proper chiral Ben ligands. In particular, designing chiral Ben ligands by connecting a benzene fragment to a chiral framework including benzene rings remained an unsolved challenge until this effort. Here we present a novel class of axially chiral Ben ligands derived from readily available (S)-5,5',6,6',7,7',8,8'-octahydro-1,1'-bi-2-naphthol ((S)-H8-BINOL) in 4-8 steps. Notably, when coordinated with ruthenium, such chiral Ben ligand containing three benzene rings only forms one of the three possible isomeric BenRuII complexes. The related chiral BenRuII catalysts could effectively catalyze the asymmetric C-H activation of N-sulfonyl ketimines with alkynes, affording a range of chiral spirocyclic sultams in up to 99% yield with up to >99% ee. These catalysts are expected to find broad applications in future.

Spinopelvic morphology impacts on postoperative proximal junctional kyphosis in congenital scoliosis with thoracolumbar hemivertebrae.

PURPOSE: It aims to investigate the lumbar and pelvic morphology in congenital scoliosis with thoracolumbar hemivertebrae and its impact on proximal junctional kyphosis (PJK) incidence after hemivertebra resection and short fusion. METHODS: 23 congenital scoliosis patients with thoracolumbar hemivertebra aged between 10 and 18 years were enrolled in the retrospective study. Spinopelvic sagittal parameters were analyzed on whole-spine standing lateral radiographs preoperatively, one-week postoperatively and at the final follow-up. Pearson correlations were calculated for local kyphosis (LK), lumbar and pelvic morphology parameters. Binary logistic regression and receiver operating characteristics (ROC) curve analysis were performed to identify the risk factors for PJK. RESULTS: Thoracolumbar hemivertebra caused LK of 29.2° ± 17.3°, an increased lumbar lordosis (LL) (-64.7° ± 16.3°), lower LL apex (52.2% at L5), and small pelvic incidence (PI) (36.8° ± 6.6°). LK was correlated with lumbar morphology parameters, including LL (r = - 0.837), upper arc of LL (LLUA) (r = - 0.879), thoracolumbar kyphosis (TLK) (r = 0.933), thoracic kyphosis (TK) (r = 0.762) and TK apex (TKA) (r = - 0.749). Surgical treatment improved the lumbar morphology, but not pelvic morphology. At the final follow-up, LL had returned to its preoperative value (p = 0.158). PJK occurred in 30.4% of cases as a compensatory mechanism. Preoperatively, significant differences of parameters between non-PJK and PJK groups were observed in LK and TLK. Binary logistic regression identified three independent risk factors for PJK: preoperative LLA (OR = 0.005, 95%CI = 0.000-0.287, p = 0.011), preoperative TLK (OR = 1.134, 95%CI = 1.001-1.286, p = 0.048), and preoperative lumbar lordosis morphology type (OR = 5.507, 95%CI = 1.202-25.227, p = 0.028). However, residual LK after surgery was not correlated with PJK incidence. ROC curve analysis verified that preoperative TLK > 22.59° was associated with increased PJK incidence after surgery. CONCLUSIONS: Lumbar morphology changes as a compensatory mechanism beneath the thoracolumbar hemivertebra. However, a stable pelvis tends to allow the LL to return to its preoperative value. PJK occurred as a cranial compensatory mechanism for increasing LL and corrected TLK. A larger TLK (> 22.59°) was an independent risk factor for PJK incidence in patients with type 2 and 3A lumbar lordosis morphology.

Transcriptomic and intervention evidence reveals domestic dogs as a promising model for anti-inflammatory investigation.

Domestic dogs have great potential to expand our understanding of the determinants of aging. To understand the aging pattern of domestic dogs and evaluate whether they can be used as an aging model, we performed RNA sequencing on white blood cells from domestic dogs aged 1-9 years and treated aged dogs with classical antiaging approaches. We obtained 30 RNA sequencing libraries and identified 61 age-associated genes with dynamic changes, the majority of which were related to metabolism and immune function, which may be predominant biomarkers for aging in dogs. We next treated aged dogs with canine mesenchymal stem cells (cMSCs), nicotinamide mononucleotide, and rapamycin to determine whether and how they responded to the antiaging interventions. The results showed that these treatments can significantly reduce the level of inflammatory factors (IL-6 and TNF-α). MSCs effectively improved the heart functions of aged dogs. Three key potential age-related genes (PYCR1, CCRL2, and TOX) were reversed by MSC treatment, two of which (CCRL2 and TOX) are implicated in immunity. Overall, we profiled the transcriptomic pattern of domestic dogs and revealed that they may be a good model of aging, especially in anti-inflammatory investigations.

Erector Spinae Atrophy Correlates with Global Sagittal Imbalance and Postoperative Proximal Junctional Kyphosis Incidence in Lumbar Degenerative Kyphosis.

STUDY DESIGN: Retrospective cohort study. PURPOSE: This study aimed to investigate the relationship between lumbar erector muscle atrophy and global sagittal imbalance in lumbar degenerative kyphosis (LDK) and with postoperative proximal junctional kyphosis. OVERVIEW OF LITERATURE: Lumbar erector muscle atrophy has been studied in LDK. However, its role in the compensatory mechanism is still under intense discussion, and the role of erector spinae (ES) muscle is always overlooked. METHODS: This study enrolled 51 patients with LDK out of 382 patients with adult degenerative spinal deformity. Baseline information was reviewed including demographic data and complications. Sagittal spinopelvic alignments and global imbalance parameters were assessed on full-length X-ray images of the spine. Muscularity and the fatty infiltration area of the ES and multifidus (MF) were measured at the L4/5 level on preoperative magnetic resonance image to evaluate the lumbar erector muscle atrophy. Stratification by sagittal vertical axis (SVA) was performed: group 1 with SVA <100 mm and group 2 with SVA >100 mm, and these groups were compared. Spearman correlation and multivariable logistic regression analyses were performed to analyze and define risk factors of postoperative proximal junctional kyphosis (PJK). RESULTS: Group 2 had lower ES and MF muscularity than group 1. ES muscularity correlated with SVA (r=-0.510, p<0.003), lumbar lordosis (r=-0.415, p<0.018), and postoperative PJK (r=-0.508, p<0.022). MF muscularity did not correlate with the above parameters. Multivariable logistic regression analysis verified ES muscularity (odds ratio [OR], 0.001; p<0.039) and SVA (OR, 1.034; p<0.048) as the risk factors for postoperative PJK. CONCLUSIONS: ES atrophy, besides the MF, is an important predictor in distinguishing decompensated LDK from well-compensated ones. It plays an important role in compensatory mechanism, not only correlates with global sagittal imbalance but also ties to PJK after deformity corrective surgery.

Establishment of nonobstructive coronary microcirculatory disorders in rabbits using three established methods and a comparative study.

To compare the merits and drawbacks of three approaches for establishing a rabbit model of nonobstructive coronary microcirculatory disease, namely, open thoracic subtotal ligation of coronary arteries, ultrasound-guided cardiac microsphere injection, and sodium laurate injection. New Zealand rabbits were allocated to four groups: a normal group (Blank group), an Open-chest group (Open-chest), a microsphere group (Echo-M), and a sodium laurate group (Echo-SL), each comprising 10 rabbits. The rabbits were sacrificed 24 h after the procedures, and their echocardiography, stress myocardial contrast echocardiography, pathology, and surgical times were compared. The results demonstrated varying degrees of reduced cardiac function in all three experimental groups, the Open-chest group exhibiting the most significant decline. The myocardial filling in the affected areas was visually analyzed by myocardial contrast echocardiography, revealing sparse filling at rest but more after stress. Quantitative analysis of perfusion parameters (ß, A, MBF) in the affected myocardium showed reduced values, the Open-chest group having the most severe reductions. No differences were observed in stress myocardial acoustic imaging parameters between the Echo-M and Echo-SL groups. Among the pathological presentations, the Open-chest model predominantly exhibited localized ischemia, while the Echo-M model was characterized by mechanical physical embolism, and the Echo-SL model displayed in situ thrombosis as the primary pathological feature. Inflammatory responses and collagen deposition were observed in all groups, with the severity ranking of Open-chest > Echo-SL > Echo-M. The ultrasound-guided intracardiac injection method used in this experiment outperformed open-chest surgery in terms of procedural efficiency, invasiveness, and maneuverability. This study not only optimizes established cardiac injection techniques but also offers valuable evidence to support clinical investigations through a comparison of various modeling methods.

TGF-ß1-Induced SOX18 Elevation Promotes Hepatocellular Carcinoma Progression and Metastasis Through Transcriptionally Upregulating PD-L1 and CXCL12.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is characterized by an immune-suppressive microenvironment, which contributes to tumor progression, metastasis, and immunotherapy resistance. Identification of HCC-intrinsic factors regulating the immunosuppressive microenvironment is urgently needed. Here, we aimed to elucidate the role of SYR-Related High-Mobility Group Box 18 (SOX18) in inducing immunosuppression and to validate novel combination strategies for SOX18-mediated HCC progression and metastasis. METHODS: The role of SOX18 in HCC was investigated in orthotopic allografts and diethylinitrosamine/carbon tetrachloride-induced spontaneous models by using murine cell lines, adeno-associated virus 8, and hepatocyte-specific knockin and knockout mice. The immune cellular composition in the HCC microenvironment was evaluated by flow cytometry and immunofluorescence. RESULTS: SOX18 overexpression promoted the infiltration of tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) while diminishing cytotoxic T cells to facilitate HCC progression and metastasis in cell-derived allografts and chemically induced HCC models. Mechanistically, transforming growth factor-beta 1 (TGF-ß1) upregulated SOX18 expression by activating the Smad2/3 complex. SOX18 transactivated chemokine (C-X-C motif) ligand 12 (CXCL12) and programmed death ligand 1 (PD-L1) to induce the immunosuppressive microenvironment. CXCL12 knockdown significantly attenuated SOX18-induced TAMs and Tregs accumulation and HCC dissemination. Antagonism of chemokine receptor 4 (CXCR4), the cognate receptor of CXCL12, or selective knockout of CXCR4 in TAMs or Tregs likewise abolished SOX18-mediated effects. TGFßR1 inhibitor Vactosertib or CXCR4 inhibitor AMD3100 in combination with anti-PD-L1 dramatically inhibited SOX18-mediated HCC progression and metastasis. CONCLUSIONS: SOX18 promoted the accumulation of immunosuppressive TAMs and Tregs in the microenvironment by transactivating CXCL12 and PD-L1. CXCR4 inhibitor or TGFßR1 inhibitor in synergy with anti-PD-L1 represented a promising combination strategy to suppress HCC progression and metastasis.

[O-arm navigation versus C-arm navigation for guiding percutaneous long sacroiliac screws placement in treatment of Denis type â ¡ sacral fractures].

Objective: To compare the effectiveness of O-arm navigation and C-arm navigation for guiding percutaneous long sacroiliac screws in treatment of Denis type Ⅱ sacral fractures. Methods: A retrospective study was conducted on clinical data of the 46 patients with Denis type Ⅱ sacral fractures between April 2021 and October 2022. Among them, 19 patients underwent O-arm navigation assisted percutaneous long sacroiliac screw fixation (O-arm navigation group), and 27 patients underwent C-arm navigation assisted percutaneous long sacroiliac screw fixation (C-arm navigation group). There was no significant difference in gender, age, causes of injuries, Tile classification of pelvic fractures, combined injury, the interval from injury to operation between the two groups ( P>0.05). The intraoperative preparation time, the placement time of each screw, the fluoroscopy time of each screw during placement, screw position accuracy, the quality of fracture reduction, and fracture healing time were recorded and compared, postoperative complications were observed. Pelvic function was evaluated by Majeed score at last follow-up. Results: All operations were completed successfully, and all incisions healed by first intention. Compared to the C-arm navigation group, the O-arm navigation group had shorter intraoperative preparation time, placement time of each screw, and fluoroscopy time, with significant differences ( P<0.05). There was no significant difference in screw position accuracy and the quality of fracture reduction ( P>0.05). There was no nerve or vascular injury during screw placed in the two groups. All patients in both groups were followed up, with the follow-up time of 6-21 months (mean, 12.0 months). Imaging re-examination showed that both groups achieved bony healing, and there was no significant difference in fracture healing time between the two groups ( P>0.05). During follow-up, there was no postoperative complications, such as screw loosening and breaking or loss of fracture reduction. At last follow-up, there was no significant difference in pelvic function between the two groups ( P>0.05). Conclusion: Compared with the C-arm navigation, the O-arm navigation assisted percutaneous long sacroiliac screws for the treatment of Denis typeⅡsacral fractures can significantly shorten the intraoperative preparation time, screw placement time, and fluoroscopy time, improve the accuracy of screw placement, and obtain clearer navigation images.

Advances in Metabolic Regulation of Macrophage Polarization State.

Macrophages are significant immune-related cells that are essential for tissue growth, homeostasis maintenance, pathogen resistance, and damage healing. The studies on the metabolic control of macrophage polarization state in recent years and the influence of polarization status on the development and incidence of associated disorders are expounded upon in this article. Firstly, we reviewed the origin and classification of macrophages, with particular attention paid to how the tricarboxylic acid cycle and the three primary metabolites affect macrophage polarization. The primary metabolic hub that controls macrophage polarization is the tricarboxylic acid cycle. Finally, we reviewed the polarization state of macrophages influences the onset and progression of cancers, inflammatory disorders, and other illnesses.

Metformin improves nonalcoholic fatty liver disease in db/db mice by inhibiting ferroptosis.

Nonalcoholic fatty liver disease (NAFLD) is the primary complication of type 2 diabetes (T2DM)-related liver disease, lacking effective treatment options. Metformin (Met), a widely prescribed anti-hyperglycemic medication, has been found to protect against NAFLD. Ferroptosis, a newly discovered form of cell death, is associated with the development of NAFLD. Despite this association, the extent of Met's protective effects on NAFLD through the modulation of ferroptosis has yet to be thoroughly investigated. In the present study, the administration of erastin or Ras-selective lethal 3 (RSL3), both known ferroptosis inducers, resulted in elevated cell mortality and reduced cell viability in AML12 hepatocytes. Notably, Met treatment demonstrated the capacity to mitigate these effects. Furthermore, we observed increased ferroptosis levels in both AML12 hepatocytes treated with palmitate and oleate (PA/OA) and in the liver tissue of db/db mice. Met treatment demonstrated significant reductions in iron accumulation and lipid-related reactive oxygen species production, simultaneously elevating the glutathione/glutathione disulfide ratio in both PA/OA-treated AML12 hepatocytes and the liver tissue of db/db mice. Interestingly, the anti-ferroptosis effects of Met were significantly reversed with the administration of RSL3, both in vitro and in vivo. Mechanistically, Met treatment regulated the glutathione peroxidase 4/solute carrier family 7 member 11/acyl-CoA synthetase long-chain family member 4 axis to alleviate ferroptosis in NAFLD hepatocytes. Overall, our findings highlight the crucial role of ferroptosis in the development of T2DM-related NAFLD and underscore the potential of Met in modulating key factors associated with ferroptosis in the context of NAFLD.

Over-expression of microRNA-145 Elevating Autophagy Activities via Downregulating FRS2 Expression.

OBJECTIVES: Osteoarthritis (OA) is one of the most common chronic and progressive joint diseases characterized by cartilage degeneration and chondrocyte death. In this study, we aimed to identify the modulation effect of miR-145 on chondrocytes' autophagy during the development of OA. BACKGROUND: Osteoarthritis (OA) is one of the most prevalent types of chronic and progressive joint disorder with the symptoms of joint pain and stiffness, and it leads to disability at the end stage. In recent years, microRNA-145 (miR-145) has been found to activate autophagy in various cell types, including mesenchymal stem cells, cardiomyocytes, and osteosarcoma cells. However, it is unknown whether miR-145 regulates the progression of OA by influencing chondrocyte autophagy. METHODS: Before investigating the regulatory effect of miR-145 on the autophagic activity of chondrocytes, the expression of miR-145 in human joint samples was analyzed. The targeting relationship between miR-145 and FRS2 was detected by dual luciferase assay. The effect of FRS2 and miR-145 on the autophagic activity of chondrocytes was observed by bidirectional expression of FRS2 and miR-145. RESULTS: The miR-145 expression and LC3-II/LC3-I ratio were significantly decreased and the SQSTM1 expression was increased in OA patients. The miR-145 overexpression in C20A4 cells increased LC3-II/LC3-I ratio, decreased SQSTM1 expression, and was positively correlated with autophagic activity. Under oxidative stress, miR-145 overexpression significantly improved chondrocyte viability through autophagy stimulation. FRS2 is a potential target of miR-145 via a binding sequence within its 3' UTR. FRS2 acts as the downstream mediator of miR-145 to suppress autophagy through activating PI3K/Akt/mTOR pathways. CONCLUSION: The miR-145 acts as a protective factor against chondrocytes by regulating miRFRS2- autophagy axis. The decrease of miR-145 in articular synovial fluid may turn out to be an important marker for early diagnosis of OA, and modulation of miR-145 may represent a promising therapeutic strategy for OA.

Relationship between Fusion Mass Shift and Postoperative Distal Adding-on in Lenke 1 Adolescent Idiopathic Scoliosis after Selective Thoracic Fusion.

STUDY DESIGN: This is a retrospective cohort study. PURPOSE: This study aims to investigate the risk factors for postoperative distal adding-on in Lenke 1 adolescent idiopathic scoliosis (AIS) and validate the relationship between fusion mass shift (FMS) and postoperative distal adding-on. OVERVIEW OF LITERATURE: Postoperative distal curve adding-on is one of the complications in AIS. FMS has been proposed to prevent postoperative distal adding-on, which requires further validation from different institutions. METHODS: This study included 60 patients with Lenke 1 AIS who underwent selective thoracic fusion surgery. Coronal spinal alignment parameters were analyzed preoperatively, postoperatively, and at the final follow-up. The postoperative FMS was divided into two groups: the balanced group (FMS ≤20 mm) and the unbalanced group (FMS >20 mm). An independent t-test was used to compare quantitative data between groups, and a chi-square test was used for qualitative data. Furthermore, binary logistic regression and receiver operating characteristics curve analyses were used to identify the risk factors for postoperative distal adding-on in AIS. RESULTS: At 2-year follow-up, the unbalanced group was more likely to have adding-on (17 of 24 patients) than the balanced group (six of 36 patients; p<0.001). Twenty-three patients with distal adding-on had significantly greater preoperative and postoperative lower instrumented vertebrae (LIV) rotation, FMS, and FMS angle (FMSA) than those without postoperative distal adding-on. Binary logistic regression analysis selected three independent risk factors for adding-on incidence after surgery: FMS (odds ratio [OR], 1.115; 95% confidence interval [CI], 1.049-1.185; p<0.001), FMSA (OR, 1.590; 95% CI, 1.225-2.064; p<0.001), and postoperative LIV rotation (OR, 6.581; 95% CI, 2.280-19.000; p<0.001). CONCLUSIONS: Achieving a balanced fusion mass intraoperatively is important to avoid postoperative distal adding-on, with FMS of <20 mm and FMS angle of <4.5°. Furthermore, correcting LIV rotation helps to decrease the incidence of postoperative distal addingon.

Polycarbosilane/Divinylbenzene-Modified Magnesium Hydroxide to Enhance the Flame Retardancy of Ethylene-Vinyl Acetate Copolymer.

The thermal decomposition product of magnesium hydroxide (MH) is magnesium oxide (MgO), which serves as the foundational material for fireproof layer construction in the condensed phase. However, the weak interaction force between particles of MgO generated by thermal decomposition leads to the insufficient strength and poor adhesion ability of the fireproof layer. The fireproof layer was easily damaged and detached in this study, resulting in the low flame-retardant efficiency of MH. In this work, polycarbosilane (PCS) and divinyl benzene (DVB) were used to modify MH, and EVA/MH/PCS/DVB composites were made via melt blending. The flame-retardant properties of EVA/MH/PCS/DVB were evaluated using the limiting oxygen index (LOI), vertical combustion (UL-94), and a cone calorimeter (CONE). The thermal stability of the composites and flame retardants was analyzed using a thermogravimetric analyzer. The char layer structure was observed and analyzed using scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), respectively. The results indicate that the LOI of the EVA/MH/PCS/DVB with 50 wt.% flame retardants in total was as high as 65.1, which increased by 160% in comparison with EVA/MH. Furthermore, the total smoke production (TSP) of the EVA/MH/PCS/DVB composite decreased by 22.7% compared to EVA/MH/PCS; the thermal stability of the MH/PCS/DVB and EVA/MH/PCS/DVB improved to some extent; and the compact residual char after the combustion of EVA/MH/PCS/DVB had fewer cracks due to the adhesive effect induced by PCS/DVB.

Association between the Khorana risk score and all-cause mortality in Japanese patients with gastric and colorectal cancer: A retrospective cohort study.

BACKGROUND: The Khorana risk score (KRS) has poor predictive value for cancer-associated thrombosis in a single tumor type but is associated with early all-cause mortality from cancer. Evidence for the association between KRS and all-cause mortality in Japanese patients with gastric and colorectal cancer is limited. AIM: To investigate whether KRS was independently related to all-cause mortality in Japanese patients with gastric and colorectal cancer after adjusting for other covariates and to shed light on its temporal validity. METHODS: Data from Dryad database were used in this study. Patients in the Gastroenterology Department of Sapporo General Hospital, Sapporo, Japan, were enrolled. The starting and ending dates of the enrollment were January 1, 2008 and January 5, 2015, respectively. The cutoff date for follow-up was May 31, 2016. The independent and dependent (target) variables were the baseline measured using the KRS and final all-cause mortality, respectively. The KRS was categorized into three groups: Low-risk group (= 0 score), intermediate-risk group (1-2 score), and high-risk group (≥ 3 score). RESULTS: Men and patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 2 displayed a higher 2-year risk of death than women and those with ECOG PS 0-1 in the intermediate/high risk group for KRS. The higher the score, the higher the risk of early death; however, the relevance of this independent prediction decreased with longer survival. The overall survival of each patient was recorded via real-world follow-up and retrospective observations, and this study yielded the overall relationship between KRS and all-cause mortality. CONCLUSION: The prechemotherapy baseline of KRS was independently associated with all-cause mortality within 2 years; however, this independent predictive relationship weakened as survival time increased.

miR­149­3p suppresses the proliferation and metastasis of glioma cells by targeting the CBX2/Wnt/ß­catenin pathway.

The present study aimed to investigate the role of miR-149-3p/chromobox 2 (CBX2)/Wnt/ß-catenin pathway in the proliferation and metastasis of glioma cells. The expression and clinical significance of miR-149-3p and CBX2 were analyzed using data from public databases. Cell Counting Kit-8 and colony formation assays were performed to measure cell proliferation. Transwell assays were used to assess cell invasion. The results showed that miR-149-3p was downregulated and CBX2 was upregulated in glioma, and that the downregulated expression of miR-149-3p promoted the proliferation and invasion of glioma cells. In addition, downregulated expression of CBX2 suppressed the proliferation and invasion of glioma cells. Dual-luciferase assay indicated that CBX2 is a target gene of miR149-3p. The possible molecular mechanism of CBX2 was probed by western blotting, which showed that it may further affect the Wnt/ß-catenin pathway. These present findings demonstrated that miR-149-3p may function as a tumor suppressor miRNA by directly regulating CBX2 and serve important roles in the malignancy of glioma.

Triggering endogenous Z-RNA sensing for anti-tumor therapy through ZBP1-dependent necroptosis.

ZBP1 senses viral Z-RNAs to induce necroptotic cell death to restrain viral infection. ZBP1 is also thought to recognize host cell-derived Z-RNAs to regulate organ development and tissue inflammation in mice. However, it remains unknown how the host-derived Z-RNAs are formed and how these endogenous Z-RNAs are sensed by ZBP1. Here, we report that oxidative stress strongly induces host cell endogenous Z-RNAs, and the Z-RNAs then localize to stress granules for direct sensing by ZBP1 to trigger necroptosis. Oxidative stress triggers dramatically increase Z-RNA levels in tumor cells, and the Z-RNAs then directly trigger tumor cell necroptosis through ZBP1. Localization of the induced Z-RNAs to stress granules is essential for ZBP1 sensing. Oxidative stress-induced Z-RNAs significantly promote tumor chemotherapy via ZBP1-driven necroptosis. Thus, our study identifies oxidative stress as a critical trigger for Z-RNA formation and demonstrates how Z-RNAs are directly sensed by ZBP1 to trigger anti-tumor necroptotic cell death.

[Finite element analysis of five internal fixation modes in treatment of Day type â ¡crescent fracture dislocation of pelvis].

Objective: To compare the biomechanical differences among the five internal fixation modes in treatment of Day type Ⅱ crescent fracture dislocation of pelvis (CFDP), and find an internal fixation mode which was the most consistent with mechanical principles. Methods: Based on the pelvic CT data of a healthy adult male volunteer, a Day type Ⅱ CFDP finite element model was established by using Mimics 17.0, ANSYS 12.0-ICEM, Abaqus 2020, and SolidWorks 2012 softwares. After verifying the validity of the finite element model by comparing the anatomical parameters with the three-dimensional reconstruction model and the mechanical validity verification, the fracture and dislocated joint of models were fixed with S 1 sacroiliac screw combined with 1 LC-Ⅱ screw (S 1+LC-Ⅱ group), S 1 sacroiliac screw combined with 2 LC-Ⅱ screws (S 1+2LC-Ⅱ group), S 1 sacroiliac screw combined with 2 posterior iliac screws (S 1+2PIS group), S 1 and S 2 sacroiliac screws combined with 1 LC-Ⅱ screw (S 1+S 2+LC-Ⅱ group), S 2-alar-iliac (S 2AI) screw combined with 1 LC-Ⅱ screw (S 2AI+LC-Ⅱ group), respectively. After each internal fixation model was loaded with a force of 600 N in the standing position, the maximum displacement of the crescent fracture fragments, the maximum stress of the internal fixation (the maximum stress of the screw at the ilium fracture and the maximum stress of the screw at the sacroiliac joint), sacroiliac joint displacement, and bone stress distribution around internal fixation were observed in 5 groups. Results: The finite element model in this study has been verified to be effective. After loading 600 N stress, there was a certain displacement of the crescent fracture of pelvis in each internal fixation model, among which the S 1+LC-Ⅱ group was the largest, the S 1+2LC-Ⅱ group and the S 1+2PIS group were the smallest. The maximum stress of the internal fixation mainly concentrated at the sacroiliac joint and the fracture line of crescent fracture. The maximum stress of the screw at the sacroiliac joint was the largest in the S 1+LC-Ⅱ group and the smallest in the S 2AI+LC-Ⅱ group. The maximum stress of the screw at the ilium fracture was the largest in the S 1+2PIS group and the smallest in the S 1+2LC-Ⅱ group. The displacement of the sacroiliac joint was the largest in the S 1+LC-Ⅱ group and the smallest in the S 1+S 2+LC-Ⅱ group. In each internal fixation model, the maximum stress around the sacroiliac screws concentrated on the contact surface between the screw and the cortical bone, the maximum stress around the screws at the iliac bone concentrated on the cancellous bone of the fracture line, and the maximum stress around the S 2AI screw concentrated on the cancellous bone on the iliac side. The maximum bone stress around the screws at the sacroiliac joint was the largest in the S 1+LC-Ⅱ group and the smallest in the S 2AI+LC-Ⅱ group. The maximum bone stress around the screws at the ilium was the largest in the S 1+2PIS group and the smallest in the S 1+LC-Ⅱ group. Conclusion: For the treatment of Day type Ⅱ CFDP, it is recommended to choose S 1 sacroiliac screw combined with 1 LC-Ⅱ screw for internal fixation, which can achieve a firm fixation effect without increasing the number of screws.

Effects of V-N Microalloying on Low-Cycle Fatigue Property in the Welded Joints of Constructional Steel.

Low-cycle fatigue testing was carried out for the welded joints of constructional steels containing 0% V + 0.0021% N and 0.10% V + 0.0078% N, and the effects of V-N microalloying on the low-cycle fatigue property of the welded joints were investigated. The results showed that when the total strain amplitudes were 1.2%, 1.4% and 1.6%, the mean low-cycle fatigue lives of the welded joints of steel containing 0.10% V + 0.0078% N were 5050, 2372 and 1535 cycles, respectively, which were significantly higher than those of the welded joints of steel containing 0% V + 0.0021% N; however, when the total strain amplitudes increased to 1.8% and 2.0%, the mean low-cycle fatigue lives of the welded joints of steel containing 0.10% V + 0.0078% N were 575 and 367 cycles, respectively, which were gradually lower than those of the welded joints of steel containing 0% V + 0.0021% N. The reasons causing the difference of low-cycle fatigue life were explained by the dislocation structure and precipitates in the welding heat-affected zone, plastic strain energy density of the welded joints, and fatigue fracture morphology. When the low-cycle fatigue life is between 100 and 200 cycles, the cyclic toughness of the welded joint of steel containing 0.10% V + 0.0078% N is between 57.48 and 78.22 J/cm3, which is higher than that of the welded joint of steel containing 0% V + 0.0021% N, indicating that the welded joint of steel containing 0.10% V + 0.0078% N is able to absorb more energy in a seismic condition, therefore possessing better seismic resistance.