Aging and comprehensive molecular profiling in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.

Tailoring the Molecular Planarity of Perylene Diimide-Based Third Component toward Efficient Ternary Organic Solar Cells.

Incorporating a third component into binary organic solar cells (b-OSCs) has provided a potential platform to boost power conversion efficiency (PCEs). However, gaining control over the non-equilibrium blend morphology via the molecular design of the perylene diimide (PDI)-based third component toward efficient ternary organic solar cells (t-OSCs) still remains challenging. Herein, two novel PDI derivatives are developed with tailored molecular planarity, namely ufBTz-2PDI and fBTz-2PDI, as the third component for t-OSCs. Notably, after performing a cyclization reaction, the twisted ufBTz-2PDI with an amorphous character transferred to the highly planar fBTz-2PDI followed by a semi-crystalline character. When incorporating the semi-crystalline fBTz-2PDI into the D18:L8-BO system, the resultant t-OSC achieved an impressive PCE of 18.56%, surpassing the 17.88% attained in b-OSCs. In comparison, the addition of amorphous ufBTz-2PDI into the binary system facilitates additional charge trap sites and results in a deteriorative PCE of 14.37%. Additionally, The third component fBTz-2PDI possesses a good generality in optimizing the PCEs of several b-OSCs systems are demonstrated. The results not only provided a novel A-DA'D-A motif for further designing efficient third component but also demonstrated the crucial role of modulated crystallinity of the PDI-based third component in optimizing PCEs of t-OSCs.

Global trends and partial forecast of adverse effects of medical treatment from 1990 to 2019: an epidemiological analysis based on the global burden of disease study 2019.

BACKGROUND: The possibility of adverse effects of medical treatment (AEMT) is increasing worldwide, but little is known about AEMT in China. This study analyzed the health burden of AEMT in China in recent years through the Global Burden of Disease Study (GBD) 2019 and compared it with the worldwide average level and those in different sociodemographic index (SDI) regions. METHODS: We calculated the age-standardized rate (ASR) of deaths, disability-adjusted life years (DALYs), years of life lost (YLLs), years lived with disability (YLDs), incidence and prevalence attributed to AEMT in China, worldwide and countries with different sociodemographic indices during 1990-2019 using the latest data and methods from the GBD 2019. RESULTS: From 1990 to 2019, the global age-standardized death rate (ASDR), DALYs, and YLLs for AEMT showed a significant downward trend and were negatively associated with the SDI. By 2040, the ASDR is expected to reach approximately 1.58 (95% UI: 1.33-1.80). From 1990 to 2019, there was no significant change in the global incidence of AEMT. The occurrence of AEMT was related to sex, and the incidence of AEMT was greater among females. In addition, the incidence of AEMT-related injuries and burdens, such as ASR of DALYs, ASR of YLLs and ASR of YLDs, was greater among women than among men. Very old and very young people were more likely to be exposed to AEMT. CONCLUSIONS: From 1990 to 2019, progress was made worldwide in reducing the harm caused by AEMT. However, the incidence and prevalence of AEMT did not change significantly overall during this period. Therefore, the health sector should pay more attention to AEMT and take effective measures to reduce AEMT.

A Principal Component Regression-Based Electrophysiological Study of Patients with Severe Infections.

Objective: Severe infections can lead to neuromyopathy in critically ill patients, resulting in limb weakness and difficulty in weaning from a ventilator. This study aims to assess the electrophysiological test results in patients with severe infection and their correlation with severity scores (APACHE II and SOFA). Methods: Thirty-one patients with severe infection in the EICU were prospectively studied. Factor analysis and principal component regression were applied to develop linear models of electrophysiological diagnostic outcomes with APACHE II and SOFA scores for the entire patient cohort, the younger group (age<55) cohort, and the older group (age>55) cohort of patients with severe infections, respectively. Results: Among patients with a severe infection in the EICU, the proportion of patients without critical neuromyopathy with more than 50% F-wave presence in the median, ulnar, and tibial nerves (64.9%, 56.8%, 48.6%, respectively) was significantly higher than in the group with critical neuromyopathy (52.1%, 35.4%, 29.2%, respectively.), and the proportion of patients with critical neuromyopathy who did not elicit the three types of F wave was significantly higher in the cohort of patients with critical neuromyopathy (40.5%, 32.4%, 35.1%, respectively.) were significantly higher than in the cohort of patients without critical illness (18.8%, 12.5%, 20.8%, respectively). In addition, on average, patients with critical neuromyopathy had a much lower CMAP for the median nerve (wrist, elbow) (2.4, 1.88, respectively) (4.3, 3.9, respectively in undiagnosed cohort), ulnar nerve (wrist, elbow) (2.4, 1.88, respectively) (5.65, 5.4, respectively in undiagnosed cohort), and tibial nerve(ankle, popliteal fossa) (2.7, 1.57, respectively)(6.55, 5.3, respectively in undiagnosed cohort) nerves than patients without critical neuromyopathy, and showed more non-elicitation, which was not seen in the cohort of patients without critical neuromyopathy. The CMAP returned to normal in the cohort of patients without critical neuromyopathy. Therefore, with respect to our selected electrophysiological parameters, the two patient groups showed significant differences in terms of the specific values and statistical analysis (Table 1). Through factor analysis and principal component regression, we found that CMAP and F-wave were highly correlated with APACHE II and SOFA scores, and the correlation between the electrophysiological wave spectrum and the two scores was further quantified by principal component regression. Conclusion: Electrophysiological spectroscopy can serve as an early warning for the development of neuromuscular disease in EICU patients. Abnormal electrophysiological diagnosis prior to actual neuromuscular abnormalities and its subsequent return to normal can help identify high-risk patients and implement early interventions.

Geometric-phase-based axicon lens for computational achromatic imaging.

Conventional optical imaging systems usually utilize several lenses within a precise assembly to eliminate chromatic aberration, which increases the difficulty of system integration. In recent years, with the rapid development of metasurfaces and liquid crystals (LCs), planar optical elements provide feasible solutions to realize flexible light manipulation and lightweight systems. However, there also exists chromatic aberration, which can be corrected but at the cost of a complex device design. Here, a geometric-phase-based axicon lens is utilized to correct chromatic aberration across a broadband wavelength with the assistance of a post-process algorithm. The axicon lens is fabricated through arranging orientations of liquid-crystal molecules with a standard photoalignment technique, and it produces an approximately invariant point spread function (PSF) at several discrete wavelengths, which is used as the prior information to extract the object in the blurred image. In the experiment, the reconstruction quality is significantly improved after the post-process algorithm. We expect our work to provide further development to reduce the dispersion with both the device design and the computational image technique.

Impact of cigarette smoking on rheumatoid arthritis-associated lung diseases: a retrospective case control study on clinical and radiological features and prognosis.

Our study aimed to investigate the clinical and radiological features and prognosis of male smoker patients with rheumatoid arthritis (RA). We consecutively enrolled male inpatients with RA who received chest HRCT during hospitalization in Peking University Third Hospital from Jan 1st, 2012 to August 1st, 2021. 154 male patients with RA were eligible for analysis, of whom 76.6% (n = 118) were current smokers or had a history of cigarette smoking. Compared to never-smokers, smoker patients had more respiratory symptoms, including cough (31.4% vs 5.6%, p = 0.002) and sputum production (26.3% vs 2.8%, p = 0.002), and a higher positive rate of rheumatoid factor (RF) (77.6% vs 58.8%, p = 0.030). A higher percentage of smoker patients showed emphysema (45.8% vs 16.7%, p = 0.002) and signs of lung fibrosis (51/54, 94.4% vs 7/13, 53.8%, p < 0.001) in those with interstitial lung disease (ILD, n = 67) on chest HRCT. The overall survival rate was different between smoker and never-smoker patients (p = 0.031), but instead of cigarette smoking, lung fibrosis on HRCT was the risk factor for survival of our patients. In conclusion, male patients with RA who were current smokers or had a history of cigarette smoking presented more respiratory symptoms and a higher positive rate of RF. They also showed more emphysema and signs of lung fibrosis on chest HRCT. Cigarette smoking impacted on the overall survival as a confounding factor in this cohort of male patients with RA.

Association of blood total immunoglobulin E and eosinophils with radiological features of bronchiectasis.

BACKGROUND: Our study aimed to investigate whether serum total IgE and blood eosinophils were associated with radiological features of bronchiectasis in a Chinese cohort. METHODS: We retrospectively enrolled bronchiectasis patients who visited Peking University Third Hospital from Jan 1st, 2012 to Oct 7th, 2021. The clinical, laboratory and chest CT characteristics were analyzed in association with serum total IgE level and blood eosinophil count. RESULTS: A total of 125 bronchiectasis patients were enrolled, with 50.4% (63/125) female, and a mean age of 62.4 ± 14.1 years. The median serum total IgE level and blood eosinophil count were 47.7 (19.8, 123.0) KU/L and 140 (90, 230) cells/µl, respectively. In patients with a higher than normal (normal range, 0-60 KU/L) total IgE (43.2%, n = 54), more lobes were involved [4 (3, 5) vs. 3 (2, 4), p = 0.008], and mucus plugs were more common (25.9% vs. 9.9%, p =0.017) on HRCT, as compared to those with a normal level of total IgE. The higher IgE group was more likely to have bilateral involvement (p = 0.059), and had numerically higher Smith and Bhalla scores, but the differences were not statistically significant. In patients with an eosinophil count ≥ 150 cells/µl (49.6%, n = 62), the number of lobes involved was greater [4 (3, 5) vs. 3 (2, 4), p = 0.015], and the Smith and Bhalla scores were higher [9 (5, 12) vs. 6 (3, 9), p = 0.009, 7 (5, 11) vs. 5 (3, 9), p = 0.036]. The Smith score was correlated positively with the eosinophil count (r = 0.207, p = 0.020). Fractional exhaled nitric oxide (FeNO) was correlated with total IgE (r = 0.404, p = 0.001) and eosinophil count (r = 0.310, p = 0.014). CONCLUSIONS: Our study demonstrated that serum total IgE and the blood eosinophil count were associated with the radiological extent and severity of bronchiectasis, necessitating further investigation on the role of T2 inflammation in structural abnormalities of this heterogeneous disease.

Naringin against doxorubicin-induced hepatotoxicity in mice through reducing oxidative stress, inflammation, and apoptosis via the up-regulation of SIRT1.

Clinical application of doxorubicin is limited because of its potential side effects. The present study examined whether naringin had protective actions on doxorubicin-induced liver injury. Male BALB/c mice and alpha mouse liver 12 (AML-12) cells were used in this paper. The results showed that AML-12 cells treated with naringin significantly reduced cell injury, reactive oxygen species release and apoptosis level; Moreover, naringin notably alleviated liver injury by decreasing aspartate transaminase, alanine transaminase and malondialdehyde, and increasing superoxide dismutase, glutathione and catalase levels. Mechanism researches indicated that naringin increased the expression levels of sirtuin 1 (SIRT1), and inhibited the downstream inflammatory, apoptotic and oxidative stress signaling pathways. Further validation was obtained by knocking down SIRT1 in vitro, which proved the effects of naringin on doxorubicin-induced liver injury. Therefore, naringin is a valuable lead compound for preventing doxorubicin-induced liver damage by reducing oxidative stress, inflammation, and apoptosis via up-regulation of SIRT1.

Modelling and Research on Intuitionistic Fuzzy Goal-Based Attack and Defence Game for Infrastructure Networks.

Network attack and defence games are gradually becoming a new approach through which to study the protection of infrastructure networks such as power grids and transportation networks. Uncertainty factors, such as the subjective decision preferences of attackers and defenders, are not considered in existing attack and defence game studies for infrastructure networks. In this paper, we introduce, respectively, the attacker's and defender's expectation value, rejection value, and hesitation degree of the target, as well as construct an intuitionistic fuzzy goal-based attack and defence game model for infrastructure networks that are based on the maximum connectivity slice size, which is a network performance index. The intuitionistic fuzzy two-player, zero-sum game model is converted into a linear programming problem for solving, and the results are analysed to verify the applicability and feasibility of the model proposed in this paper. Furthermore, different situations, such as single-round games and multi-round repeated games, are also considered. The experimental results show that, when attacking the network, the attacker rarely attacks the nodes with higher importance in the network, but instead pays more attention to the nodes that are not prominent in the network neutrality and median; meanwhile, the defender is more inclined to protect the more important nodes in the network to ensure the normal performance of the network.

Macrophages: A rising star in immunotherapy for chronic pancreatitis.

Chronic pancreatitis (CP) is a chronic wasting disease with an increasing incidence. As an important factor in the pathogenesis of CP, macrophages play a considerable role in the most typical pathological agents throughout the early to late stages of CP. Macrophage-associated cytokines are biomarkers that bring new possibilities for the early diagnosis of CP and differential diagnosis with pancreatic cancer and pancreatic diseases. In addition, in established CP, macrophage interactions with T lymphocytes leads to immune dysregulation, and macrophage secretion of proinflammatory cytokines is considered a potent driver of acinar-to-ductal metaplasia (ADM). In advanced CP, macrophages interact with pancreatic stellate cells (PSCs) and islet cells in an autocrine or paracrine manner to promote the development of pancreatic fibrosis and islet dysfunction. Here, we review the crosstalk of macrophages with pancreatic acinar cells, PSCs, other immune cells and islet cells at different stages of CP progression, as well as current CP immunotherapies targeting macrophages, which will help explain the decisive role of macrophages in CP and their potential as targets of CP immunotherapy. Furthermore, macrophage-targeted immunotherapy can be advanced, not only in terms of physiology and pathology but also in terms of further optimization of dose, forms and delivery. All these efforts are beneficial to enhancing the targeting of macrophages in the treatment of CP.

Molecularly Engineered Covalent Organic Frameworks for Hydrogen Peroxide Photosynthesis.

Synthesizing H2 O2 from water and air via a photocatalytic approach is ideal for efficient production of this chemical at small-scale. However, the poor activity and selectivity of the 2 e- water oxidation reaction (WOR) greatly restricts the efficiency of photocatalytic H2 O2 production. Herein we prepare a bipyridine-based covalent organic framework photocatalyst (denoted as COF-TfpBpy) for H2 O2 production from water and air. The solar-to-chemical conversion (SCC) efficiency at 298 K and 333 K is 0.57 % and 1.08 %, respectively, which are higher than the current reported highest value. The resulting H2 O2 solution is capable of degrading pollutants. A mechanistic study revealed that the excellent photocatalytic activity of COF-TfpBpy is due to the protonation of bipyridine monomer, which promotes the rate-determining reaction (2 e- WOR) and then enhances Yeager-type oxygen adsorption to accelerate 2 e- one-step oxygen reduction. This work demonstrates, for the first time, the COF-catalyzed photosynthesis of H2 O2 from water and air; and paves the way for wastewater treatment using photocatalytic H2 O2 solution.

Impact of maternal late gestation undernutrition on surfactant maturation, pulmonary blood flow and oxygen delivery measured by magnetic resonance imaging in the sheep fetus.

Restriction of fetal substrate supply has an adverse effect on surfactant maturation in the lung and thus affects the transition from in utero placental oxygenation to pulmonary ventilation ex utero. The effects on surfactant maturation are mediated by alteration in mechanisms regulating surfactant protein and phospholipid synthesis. This study aimed to determine the effects of late gestation maternal undernutrition (LGUN) and LGUN plus fetal glucose infusion (LGUN+G) compared to Control on surfactant maturation and lung development, and the relationship with pulmonary blood flow and oxygen delivery ( DO2 ) measured by magnetic resonance imaging (MRI) with molecules that regulate lung development. LGUN from 115 to 140 days' gestation significantly decreased fetal body weight, which was normalized by glucose infusion. LGUN and LGUN+G resulted in decreased fetal plasma glucose concentration, with no change in fetal arterial PO2 compared to control. There was no effect of LGUN and LGUN+G on the mRNA expression of surfactant proteins (SFTP) and genes regulating surfactant maturation in the fetal lung. However, blood flow in the main pulmonary artery was significantly increased in LGUN, despite no change in blood flow in the left or right pulmonary artery and DO2 to the fetal lung. There was a negative relationship between left pulmonary artery flow and DO2 to the left lung with SFTP-B and GLUT1 mRNA expression, while their relationship with VEGFR2 was positive. These results suggest that increased pulmonary blood flow measured by MRI may have an adverse effect on surfactant maturation during fetal lung development. KEY POINTS: Maternal undernutrition during gestation alters fetal lung development by impacting surfactant maturation. However, the direction of change remains controversial. We examined the effects of maternal late gestation maternal undernutrition (LGUN) on maternal and fetal outcomes, signalling pathways involved in fetal lung development, pulmonary haemodynamics and oxygen delivery in sheep using a combination of molecular and magnetic resonance imaging (MRI) techniques. LGUN decreased fetal plasma glucose concentration without affecting arterial PO2 . Surfactant maturation was not affected; however, main pulmonary artery blood flow was significantly increased in the LGUN fetuses. This is the first study to explore the relationship between in utero MRI measures of pulmonary haemodynamics and lung development. Across all treatment groups, left pulmonary artery blood flow and oxygen delivery were negatively correlated with surfactant protein B mRNA and protein expression in late gestation.

Network-Based Driving Force of National Economic Development: A Social Capital Perspective.

Network science has been widely applied in theoretical and empirical studies of global value chain (GVC), and many related articles have emerged, forming many more mature and complete analytical frameworks. Among them, the GVC accounting method based on complex network theory is different from the mainstream economics in both research angle and content. In this paper, we build up global industrial value chain network (GIVCN) models based on World Input-Output Database, introduce the theoretical framework of Social Capital, and define the network-based indicators with economic meanings. Second, we follow the econometric framework to analyze the hypothesis and test whether it is true. Finally, we study how the three types of capital constituted by these indicators interact with each other, and discuss their impact on the social capital (economic development level, i.e., GDP). The results prove that the structural capital (industrial status) has a positive impact on the social capital; the relational capital (industrial correlation) has a positive impact on both social capital and structural capital; the cognitive capital (industrial structure) has a small impact on the social capital, structural capital, and relational capital.

Nestedness-Based Measurement of Evolutionarily Stable Equilibrium of Global Production System.

A nested structure is a structural feature that is conducive to system stability formed by the coevolution of biological species in mutualistic ecosystems The coopetition relationship and value flow between industrial sectors in the global value chain are similar to the mutualistic ecosystem in nature. That is, the global economic system is always changing to form one dynamic equilibrium after another. In this paper, a nestedness-based analytical framework is used to define the generalist and specialist sectors for the purpose of analyzing the changes in the global supply pattern. We study why the global economic system can reach a stable equilibrium, what the role of different sectors play in the steady status, and how to enhance the stability of the global economic system. In detail, the domestic trade network, export trade network and import trade network of each country are extracted. Then, an econometric model is designed to analyze how the microstructure of the production system affects a country's macroeconomic performance.

Correction to: Systemic vasculitis involving the breast: a case report and literature review.

The article "Systemic vasculitis involving the breast: a case report and literature review" written by Jinxia Zhao, was originally published electronically on the publisher's internet portal (currently SpringerLink) on March 14, 2019 with open access. With the author(s) decision to step back from Open Choice, the copyright of the article changed to ©Springer-Verlag GmbH Germany, part of Springer Nature 2019 and the article is forthwith distributed under the terms of copyright.The original article has been corrected.

Systemic vasculitis involving the breast: a case report and literature review.

Systemic vasculitis involving the breast is a rare clinical condition and may mimic breast cancer or mastitis clinically or radiographically. Here, we report a case of polyarteritis nodosa (PAN) with breast involvement and perform a literature review of published cases of systemic vasculitis affecting the breast to better understand this disorder. We report a case of PAN affecting the right breast in a young woman. A retrospective review was performed by searching Medline, Embase, Web of Science, the Cochrane Library, and Scopus for cases of systemic vasculitis involving the breast written in English up to June 1st, 2018. A 27-year-old woman presented with a painful mass in the right breast was diagnosed as PAN by the biopsy. She was treated with prednisone and methotrexate for 6 months, at which time her condition had stabilized and inflammatory markers had normalized. A total of 66 cases were identified, with granulomatosis with polyangiitis (GPA), giant cell arteritis (GCA), and PAN as the main types. The typical manifestation was mass (79.2%, 53/67) in the breast, and all diagnoses were made by the pathology of the breast biopsy. Glucocorticoid and immunosuppressant were the main therapies, and 74.6% (50/67) patients achieved remission during follow-up. Our case and a literature review of 66 cases of systemic vasculitis involving the breast reveal the importance of tissue biopsy to obtain a definitive diagnosis, because the vasculitis subtype strongly influences prognosis.

Elevated CD4+ T Cell Senescence Associates with Impaired Immune Responsiveness in Severe COVID-19.

Aging is a critical risk factor for unfavorable clinical outcomes among COVID-19 patients and may impact vaccine efficacy. However, whether the senescence of T cells is associated with severe COVID-19 outcome in elderly individuals is unclear. Using flow cytometry, we analyzed the frequency of senescent T cells (Tsens) in peripheral blood from 100 hospitalized elderly COVID-19 patients and compared differences between those with mild/moderate and severe/critical illness. We also assessed correlations between the percentage of Tsens and the quantity and quality of spike-specific antibodies by ELISA, neutralizing antibody test kit, and ELISPOT assay respectively, the cytokine production profile of COVID-19 reactive T cells, and plasma soluble factors by cytometric bead array (CBA). Our study found a significantly elevated level of CD4+ Tsens in patients with severe/critical disease compared to those with mild/moderate illness. Patients with a higher level of CD4+ Tsens (>19.78%) showed a decreased survival rate compared to those with a lower level (≤19.78%). This is more pronounced among patients with breakthrough infections. The percentage of CD4+ Tsens was negatively correlated with spike-specific antibody titers, neutralization ability, and COVID-19 reactive IL-2+CD4+ T cells. In addition, spike-specific antibody levels were positively correlated with IL-2 producing T cells and plasma IL-2 amount. Mechanistically, with defective CD40L, T cells from patients with CD4+ Tsens >19.78% were unable to support B cell proliferation and differentiation. Our data demonstrate that the percentage of CD4+ Tsens in peripheral blood may serve as a reliable biomarker for the prognosis of severe COVID-19 patients, especially in breakthrough infections. Therefore, restoring the immune response of CD4+ Tsens may be key to preventing severe illness and improving vaccine efficacy in older adults.

Dl-3-n-butylphthalide exerts neuroprotective effects by modulating hypoxia-inducible factor 1-alpha ubiquitination to attenuate oxidative stress-induced apoptosis.

Dl-3-n-butylphthalide is used to treat mild and moderate acute ischemic stroke. However, the precise underlying mechanism requires further investigation. In this study, we investigated the molecular mechanism of Dl-3-n-butylphthalide action by various means. We used hydrogen peroxide to induce injury to PC12 cells and RAW264.7 cells to mimic neuronal oxidative stress injury in stroke in vitro and examined the effects of Dl-3-n-butylphthalide. We found that Dl-3-n-butylphthalide pretreatment markedly inhibited the reduction in viability and reactive oxygen species production in PC12 cells caused by hydrogen peroxide and inhibited cell apoptosis. Furthermore, Dl-3-n-butylphthalide pretreatment inhibited the expression of the pro-apoptotic genes Bax and Bnip3. Dl-3-n-butylphthalide also promoted ubiquitination and degradation of hypoxia inducible factor 1α, the key transcription factor that regulates Bax and Bnip3 genes. These findings suggest that Dl-3-n-butylphthalide exhibits a neuroprotective effect on stroke by promoting hypoxia inducible factor-1α ubiquitination and degradation and inhibiting cell apoptosis.

Identification of PPT1 as a lysosomal core gene with prognostic value in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most frequent cancer worldwide with a poor prognosis. Unfortunately, there are few reports on effective biomarkers for HCC, identification of novel cancer targets is urgently needed. Lysosomes are central organelles for degradation and recycling processes in cells, and how lysosome-related genes are involved in the progression of hepatocellular carcinoma remains unclear. The aim of the present study was to identify key lysosome-related genes affecting HCC. In the present study, lysosome-related genes involved in HCC progression were screened based on the TCGA (The Cancer Genome Atlas) dataset. Differentially expressed genes (DEGs) were screened, and core lysosomal genes were obtained in combination with prognostic analysis and protein interaction networks. Two genes were associated with survival, and their prognostic value was validated by prognostic profiling. After mRNA expression validation and IHC, the palmitoyl protein thioesterase 1 (PPT1) gene was identified as an important lysosomal-related gene. We demonstrated that PPT1 promotes the proliferation of HCC cells in vitro. In addition, quantitative proteomics and bioinformatics analysis confirmed that PPT1 acts by affecting the metabolism, localization, and function of various macromolecular proteins. The present study reveals that PPT1 could be a promising therapeutic target for the treatment of HCC. These findings provided new insights into HCC and identified candidate gene prognosis signatures for HCC.

Improved Interlaminar Properties of Glass Fiber/Epoxy Laminates by the Synergic Modification of Soft and Rigid Particles.

Poor interlaminar fracture toughness has been a major issue in glass fiber-reinforced epoxy resin (GF/EP) laminate composites. In this paper, soft carboxy-terminated nitrile (CTBN) rubber particles and rigid nano-SiO2 are used to toughen the epoxy resin (EP) matrix to improve the interlayer properties of GF/EP laminate composites. The effects of adding two toughening agents on the mechanical and interlayer properties of GF/EP laminates were studied. The results showed that adding the two kinds of particles improved the mechanical properties of the epoxy matrix. When the additional amount of flexible CTBN rubber particles was 8 wt%, and the rigid nano-SiO2 was 0.5 wt%, the fracture toughness of the matrix resin was increased by 215.8%, and the tensile strength was only decreased by 2.3% compared with the pure epoxy resin. On this basis, the effects of two kinds of particles on the interlayer properties of GF/EP composites were studied. Compared with the unmodified GF/EP laminates, the interlayer shear strength and mode I interlayer fracture toughness is significantly improved by a toughening agent, and the energy release rate GIC of interlayer shear strength and interlayer fracture toughness is increased by 109.2%, and 86.8%, respectively. The flexible CTBN rubber particles and rigid nano-SiO2 improve the interfacial adhesion between GF and EP. The cavitation of the two particles and the plastic deformation of the matrix is the toughening mechanism of the interlayer properties of the composite. Such excellent interlaminar mechanical properties make it possible for GF/EP laminates to be widely used as engineering materials in various industries (e.g., aerospace, hydrogen energy, marine).