Integrative bioinformatics analysis to screen key genes and signalling pathways related to ferroptosis in obesity.

Ferroptosis is closely associated with the development of disease in the body. However, there are few studies on ferroptosis-related genes (FRGs) in obesity. Therefore, key genes and signalling pathways related to ferroptosis in obesity were screened. Briefly, the RNA sequencing data of obesity and the non-obesity human samples and 259 FRGs were downloaded from GEO database and FerrDb database, respectively. The obesity-related module genes were firstly screened by weighted gene co-expression network analysis (WGCNA) and crossed with differentially expressed genes (DEGs) of obesity/normal samples and FRGs to obtain obesity-ferroptosis related (OFR) DEGs. Then, key genes were screened by PPI network. Next, the correlation of key genes and differential immune cells between obesity and normal samples were further explored by immune infiltration analysis. Finally, microRNA (miRNA)-messenger RNA (mRNA), transcription factor (TF)-mRNA networks and drug-gene interaction networks were constructed. As a result, 17 OFR DEGs were obtained, which mainly participated in processes such as lipid metabolism or adipocyte differentiation. The 4 key genes, STAT3, IL-6, PTGS2, and VEGFA, constituted the network. M2 macrophages, T cells CD8, mast cells activated, and T cells CD4 memory resting had significant differences between obesity and normal samples. Moreover, 51 miRNAs and 164 drugs were predicted for 4 key genes. All in all, this study has screened 4 FRGs, including IL-6, VEGFA, STAT3, and PTGS2, in obesity patients.

Advanced hormone receptor-positive/human epidermal growth factor receptor 2-positive invasive ductal carcinoma with cecal metastasis: A case report.

The incidence of gastrointestinal metastases from breast cancer (BC) is low. We report a special case of Luminal B (Hormone Receptor positive [HR+]/Human Epidermal Growth Factor receptor 2-positive [HER-2+]) BC. The patient presented with asymptomatic brain metastases two years after radical surgery for modified breast cancer and developed right lower abdominal pain during relief therapy. Electronic gastroenteroscopy revealed inflammatory changes in the cecal mucosa. These changes were confirmed on pathology to be cecal metastasis from BC. The patient's condition was stabilised after treatment with an antibody-drug conjugate (ADC). For patients with BC who develop appendicitis-like symptoms after treatment for invasive ductal carcinoma of the breast, clinicians should be fully aware that the possibility of cecal metastasis needs to be considered, despite the very low probability of occurrence.

Use of Contezolid for the Treatment of Refractory Infective Endocarditis in a Patient with Chronic Renal Failure: Case Report.

Infective endocarditis (IE) caused by methicillin-resistant Staphylococcus aureus (MRSA) is usually life threatening and difficult to treat. Contezolid is a newly approved oxazolidinone antimicrobial agent showing potent activity against MRSA. We successfully treated a case of refractory IE caused by MRSA with contezolid in a 41-year-old male patient. The patient was admitted due to recurrent fever and chills for more than 10 days. He had chronic renal failure for more than 10 years and under ongoing hemodialysis. The diagnosis of IE was confirmed by echocardiography and positive blood culture of MRSA. Antimicrobial therapy with vancomycin combined with moxifloxacin, and daptomycin combined with cefoperazone-sulbactam failed in the first 27 days. Moreover, the patient had to take oral anticoagulant after removal of tricuspid valve vegetation and tricuspid valve replacement. Contezolid 800 mg was added orally every 12 hours, to replace vancomycin, for its anti-MRSA activity and good safety profile. Temperature normalized after the contezolid add-on treatment for 15 days. No relapse of infection or drug-related adverse reaction was reported at 3-month follow-up since the diagnosis of IE. This successful experience serves as motivation for a well-designed clinical trial to confirm the utility of contezolid in managing IE.

Multi-trait analysis reveals large interspecific differences for phytoplankton in response to thermal change.

Understanding the responses of multiple traits in phytoplankton, and identifying interspecific variabilities to thermal changes is crucial for predicting the impacts of ocean warming on phytoplankton distributions and community structures in future scenarios. Here, we applied a trait-based approach by examining the patterns in multi-traits variations (eight traits) and interspecific variabilities in five phytoplankton species (two diatoms, three dinoflagellates) in response to a wide range of ecologically relevant temperatures (14-30 °C). Our results show large inter-traits and interspecific variabilities of thermal reaction norms in all of the tested traits. We also found that the interspecific variability exceeded the variations induced by thermal changes. Constrained variations and trade-offs between traits both revealed substantial interspecific differences and shifted as the temperature changed. Our study helps to understand the species-specific response patterns of multiple traits to ocean warming and to investigate the implications of these responses in the context of global change.

Attach importance to the individualized treatment of adult portal hypertension based on etiology and pathogenesis: A review.

There are many factors that can cause portal hypertension and secondary symptoms such as ascites, splenomegaly, and variceal hemorrhage, can seriously affect patients' quality of life and even threaten their lives. In this paper, we summarize various causes of portal hypertension based on etiology and pathogenesis and give individualized treatment strategies in order to remind clinicians to pay attention to the identification of different causes and select corresponding treatment, so that patients are provided with the optimal treatment strategies and benefit from them.

Long-term adaptation to elevated temperature but not CO2 alleviates the negative effects of ultraviolet-B radiation in a marine diatom.

Multifaceted changes in marine environments as a result of anthropogenic activities are likely to have a compounding impact on the physiology of marine phytoplankton. Most studies on the combined effects of rising pCO2, sea surface temperature, and UVB radiation on marine phytoplankton were only conducted in the short-term, which does not allow to test the adaptive capacity of phytoplankton and associated potential trade-offs. Here, we investigated populations of the diatom Phaeodactylum tricornutum that were long-term (∼3.5 years, ∼3000 generations) adapted to elevated CO2 and/or elevated temperatures, and their physiological responses to short-term (∼2 weeks) exposure of two levels of ultraviolet-B (UVB) radiation. Our results showed that while elevated UVB radiation showed predominantly negative effects on the physiological performance of P. tricornutum regardless of adaptation regimes. Elevated temperature alleviated these effects on most of the measured physiological parameters (e.g., photosynthesis). We also found that elevated CO2 can modulate these antagonistic interactions, and conclude that long-term adaptation to sea surface warming and rising CO2 may alter this diatom's sensitivity to elevated UVB radiation in the environment. Our study provides new insights into marine phytoplankton's long-term responses to the interplay of multiple environmental changes driven by climate change.

Investigation of Asian Dyes and Pigments from the Artifact of "Murongzhi" and the Silk Road in China.

In this paper, a series of modern analysis methods, including Raman spectroscopy, X-ray diffraction, UV-vis spectrophotometry, and ultra-high-pressure liquid chromatography coupled with a thermoelectric LTQ-Orbitrap XL ETD mass spectrometer (UHPLC-MS/MS), were applied to analyze and accurately identify the chemical composition of plant dyes and the mineral pigment from the samples collected from grave goods. As a result, the textiles were dyed by the madder, Kermes, Phellodendron chinense, indigo, Lithospermum L., and so forth. In addition, the mineral pigment, charcoal, hematite, minium, cinnabar, azurite, and malachite were used to paint the exquisite artifacts in the tomb of Murongzhi. This research demonstrates the profound impact on cultural transmission and fusion in the "Tuyuhong" dynasty and explores the Silk Road in Tang dynasty.

The association between preoperative blood calcium and postoperative blood loss in patients undergoing heart valve replacement surgery.

INTRODUCTION: Bleeding after heart valve surgery is a serious clinical challenge. Hypocalcemia has been associated with the extent of bleeding in patients with spontaneous intracerebral hemorrhage. However, the association between blood calcium levels and bleeding extent in heart valve replacement patients has not been clearly established. This study aimed at determining the association between blood calcium levels and perioperative hemorrhage after heart valve replacement therapy. METHODS: Based on preoperative blood calcium levels, patients were grouped into the hypocalcemia group and normocalcemia group. Postoperative bleeding, blood product use, and complications were monitored during hospitalization. The association between blood calcium levels and major bleeding was determined by multivariable logistic regression models. RESULTS: In the first 12 h after surgery, bleeding in hypocalcemia group was significantly larger than that of the normocalcemia group (338 ± 234 mL vs 232 ± 96 mL; p = .024). The outcome was the same when the overall chest tube output was considered (950 ± 447 mL vs 738 ± 220 mL; p = .038). The incidence of major bleeding was 65.91% in the hypocalcemia group and 18.97% in the normocalcemia group (p = .001). Postoperative complications in the two groups were similar. After adjusting for multiple covariates, the adjusted odds ratios (OR) for participants in hypocalcemia group was 10.01 (95% CI 3.35-34.82), compared with that in normocalcemia group (p < .001). CONCLUSION: In patients undergoing heart valve surgery, preoperative blood concentrations of calcium are associated with postoperative blood loss. Hypocalcemia before operation may increase the risk of postoperative bleeding. When patients with valvular heart disease present with hypocalcemia before surgery, prompt intervention may lead to better control of postoperative bleeding.

Directional Migration and Distribution of Magnetic Microparticles in Polypropylene-Matrix Magnetic Composites Molded by an Injection Molding Assisted by External Magnetic Field.

Surface-functionalized polymer composites with spherical particles as fillers offer great qualities and have been widely employed in applications of sensors, pharmaceutical industries, anti-icing, and flexible electromagnetic interference shielding. The directional migration and dispersion theory of magnetic microparticles in polypropylene (PP)-matrix magnetic composites must be studied to better acquire the functional surface with remarkable features. In this work, a novel simulation model based on multi-physical field coupling was suggested to analyze the directed migration and distribution of magnetic ferroferric oxide (Fe3O4) particles in injection molding assisted by an external magnetic field using COMSOL Multiphysics® software. To accurately introduce rheological phenomena of polymer melt into the simulation model, the Carreau model was used. Particle size, magnetic field intensity, melt viscosity, and other parameters impacting particle directional motion were discussed in depth. The directional distribution of particles in the simulation model was properly assessed and confirmed by experiment results. This model provides theoretical support for the control, optimization, and investigation of the injection-molding process control of surface-functionalized polymer composites.

Combined Approach of Compression Molding and Magnetic Attraction to Micropatterning of Magnetic Polydimethylsiloxane Composite Surfaces with Excellent Anti-Icing/Deicing Performance.

The accumulation of ice and contaminants on the surface of composite insulators will cause high energy consumption or even major hazards to power systems. In this work, the polydimethylsiloxane (PDMS) silicone rubber was modified by surface micropatterning and material compositing. Highly crosslinked poly(cyclotriphosphazene-co-4,4'-sulfonyldiphenol) (PZS) was used to directly coat ferroferric oxide (Fe3O4) nanoparticles. The obtained core-shell Fe3O4@PZS microspheres were loaded with carbon nanotubes (CNTs) to get CNTs/Fe3O4@PZS as the photothermal magnetic filler. The PDMS/CNTs/Fe3O4@PZS surfaces with micronscale truncated cones were prepared via a combined method of compression molding and magnetic attraction. The 1H,1H,2H,2H-perfluorodecyltrichlorosilane-coated template and magnetic field can increase the height of the microstructure to ∼76 µm and maintain the contact angle of microstructured PDMS/CNTs/Fe3O4@PZS surfaces at a high level (∼152°). Compared with the flat PDMS surface, the micronscale truncated cones extend the freezing time from 4.5 to 11.5 min and also undermine the ice adhesion strength from ∼25 to ∼17 kPa for the microstructured PDMS/CNTs/Fe3O4@PZS surface. The temperature of the PDMS/CNTs/Fe3O4@PZS surface molded with magnetic attraction increases linearly with time and the internal magnetic fillers and achieves 280 °C in 10 s. The efficiency of temperature rise is increased by ∼46%, and hence the entire frozen water droplet can melt within 20 s. The strategy combining active deicing with passive anti-icing undoubtedly promotes the development of high efficiency anti-icing materials and can be applied on insulators to prevent icing flashover.

Metformin Alleviates Hepatic Steatosis and Insulin Resistance in a Mouse Model of High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease by Promoting Transcription Factor EB-Dependent Autophagy.

Nonalcoholic fatty liver disease (NAFLD) results from an abnormal accumulation of lipids within hepatocytes, and is commonly associated with obesity, insulin resistance, and hyperlipidemia. Metformin is commonly used to treat type 2 diabetes mellitus and, in recent years, it was found to play a potential role in the amelioration of NAFLD. However, the mechanisms underlying the protective effect of metformin against NAFLD remain largely unknown. Transcription factor EB (TFEB) is a master transcriptional regulator of lysosomal biogenesis and autophagy and, when activated, is effective against disorders of lipid metabolism. However, the role of TFEB in hepatic steatosis is not well understood. In this report, we demonstrate that the activity of TFEB is reduced in the liver of mice fed a high-fat diet. Metformin treatment significantly reverses the activity of TFEB, and the protective effect of metformin against hepatic steatosis and insulin resistance is dependent on TFEB. We show that metformin-induced autophagy is regulated by TFEB, and our findings reveal that TFEB acts as a mediator, linking metformin with autophagy to reverse NAFLD, and highlight that TFEB may be a promising molecular target for the treatment of NAFLD.

Autophagy induced by H. pylori VacA regulated the survival mechanism of the SGC7901 human gastric cancer cell line.

BACKGROUND: Vacuolating cytotoxin (VacA) is an important virulence factor of Helicobacter pylori (H. pylori). It was previously believed that VacA can trigger the cascade of apoptosis on mitochondria to lead to cell apoptosis. Recently, it was found that VacA can induce autophagy. However, the molecular mechanism by which VacA induces autophagy is largely unknown. OBJECTIVE: We aimed to explore the molecular mechanism of autophagy induced by H. pylori in gastric cancer cells and the effect of autophagy on the survival of gastric cancer cells. METHODS: The autophagy of human gastric cancer cell line SGC7901 was detected by Western blot and RT-PCR in the treatment of VacA protein of H. pylori. The relationship between autophagy and reactive oxygen species (ROS) in the proliferation of gastric cancer cells were studied by gene expression silences (siRNA) and CM-H2DCFDA (DCF) staining. RESULTS: The results showed that VacA protein secreted by H. pylori in the supernatant stimulated autophagy in SGC7901 cells. After VacA protein treatment, the mRNA expressions of BECN1, ATG7 and PIK3C3, were up-regulated. ATG7 silencing by siRNA inhibited VacA-induced autophagy. Furthermore, our data demonstrated that VacA protein increased ROS levels. Addition of the antioxidant N-acetyl-L-cysteine (NAC) suppressed the levels of ROS, leading to inhibition of autophagy. CONCLUSIONS: H. pylori VacA is a key toxin that induces autophagy by increased ROS levels. And our findings demonstrated that VacA significantly inhibited proliferation in SGC7901 cells.

Long-Lived T-Shaped Micropillars with Submicron-Villi on PP/POE Surfaces with Grinding-Enhanced Water Repellency Fabricated via Hot Compression Molding.

Superhydrophobic properties are derived from the roughness of the surface of micro/nanostructures and low-surface-energy materials. However, they are both easy to damage on superhydrophobic surfaces after mechanical abrasion in practical applications, resulting in the transition from the Cassie-Baxter state to the Wenzel state and even the loss of water repellency. In this work, the mechanical properties of polypropylene (PP) toughened with poly(ethylene-co-octene) (POE) were improved for the fabrication of long-lived T-shaped micropillars with submicron-villi on top by a combined method of compression molding and grinding. A universal testing machine was modified as equipment for the precise control of the traveling distance of specimens on sandpaper in precise. The PP/POE blend possessed high tensile strength of up to ∼23.84 MPa as well as elongation at break of ∼533.60%. The abrasive grains on sandpaper reshaped their surface morphologies from micropillars to T-shaped microstructures, on which the submicron-villi as secondary structures formed. The abraded microstructured PP/POE surface exhibited the highest contact angle of 154.4° and the most stable wetting state with a bouncing height of 7.68 mm (3.2 times the diameter of the 7-µL droplet) after a traveling distance of 1000 mm on 3000-grit sandpaper among the abraded and unabraded PP/POE surfaces.

Fenofibrate Improves Insulin Resistance and Hepatic Steatosis and Regulates the Let-7/SERCA2b Axis in High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Mice.

Fenofibrate is widely used in clinical therapy to effectively ameliorate the development of non-alcoholic fatty liver disease (NAFLD); however, its specific molecular mechanism of action remains largely unknown. MicroRNAs (miRNAs) are key mediators in regulating endoplasmic reticulum (ER) stress during NAFLD, and the deregulation of miRNAs has been demonstrated in NAFLD pathophysiology. The present study aimed to identify whether fenofibrate could influence miRNA expression in NAFLD and investigate the specific mechanism of action of fenofibrate in lipid metabolism disorder-associated diseases. We found that fenofibrate alleviated ER stress and increased the levels of SERCA2b, which serves as a regulator of ER stress. Additionally, the levels of let-7 miRNA were regulated by fenofibrate; let-7 was found to target the 3' untranslated region of SERCA2b. The present data suggest that the protective effects of fenofibrate against insulin resistance and its suppressive activity against excessive hepatic lipid accumulation may be related to the alteration of the let-7/SERCA2b axis and alleviation of ER stress.

Constructing a Green Light Photodetector on Inorganic/Organic Semiconductor Homogeneous Hybrid Nanowire Arrays with Remarkably Enhanced Photoelectric Response.

We demonstrate that a novel photodetector is constructed by CdS/poly( p-phenylene vinylene) (PPV) homogeneous hybrid nanowire arrays via a simple template-assisted electrochemical codeposition approach. Owing to the well-matched energy levels between CdS and PPV, the recombination of photogenerated electrons and holes in CdS/PPV hybrid nanowire arrays is greatly inhibited. It is found that the homogeneous hybrid nanowire arrays exhibit remarkably enhanced photoelectric response and the ON/OFF ratio by 17 times compared to the individual CdS component. More importantly, the CdS/PPV hybrid nanowire arrays are observed with significant spectral selectivity especially for green light under 545 nm. In addition, a straight linear relationship is obtained between the ON/OFF ratios and the illumination intensities, implying that the quantitative detection of illumination intensity can be achieved. The new as-prepared homogeneous hybrid organic/inorganic semiconductor nanowire arrays have a bright prospect for applications in high-sensitivity and high-speed green photodetectors.

Total endoscopic repair of atrial septal defect under on-pump beating heart.

BACKGROUND: We previously reported the techniques for total endoscopic atrial septal defect (ASD) repair on hearts arrested with cardioplegia through three small incisions in the chest wall without aid of a surgical robotic system. The optimal results motivated us to use total thoracoscopic technology for ASD on perfused beating hearts. METHODS: From 2010 to 2017, 161 patients with a mean age of 28.31±12.34 years who underwent non-robotically assisted total thoracoscopic closure for ASD were included in this study, and those patients were also divided into two groups, including group A and group B. In group A, 115 patients underwent the procedure on beating hearts without aorta cross-clamped; in group B, 46 patients underwent the procedure on hearts arrested with cardioplegia with aorta cross-clamped. Cardiopulmonary bypass (CPB) was peripherally achieved as well. RESULTS: Total thoracoscopic ASD closures were successfully performed without in-hospital mortality or other serious complications in all patients of both groups. Dacron or bovine patches were used in 81 and 32 patients in the two groups, respectively. Duration of operation, duration of CPB, aorta cross-clamped time, duration of mechanical ventilation, the length of intensive care unit (ICU) and post-operative hospital stay in group A, were all shorter than those in group B (P<0.05). There was no statistically significant difference in blood transfusion during operation or post-operation thoracic drainage. During follow-up, echocardiograms at 3, 30, 90 and 365, showed no residual shunt or tricuspid regurgitation. CONCLUSIONS: Total thoracoscopic closure of ASD without assistance of a surgical robotic system on beating heart is safe and feasible and can be used as a therapeutic option for ASD, and by using the mentioned technique, less injuries are applied to patients.