Sperm methylation profiles reveal features of epigenetic inheritance and evolution in primates.

During germ cell and preimplantation development, mammalian cells undergo nearly complete reprogramming of DNA methylation patterns. We profiled the methylomes of human and chimp sperm as a basis for comparison to methylation patterns of ESCs. Although the majority of promoters escape methylation in both ESCs and sperm, the corresponding hypomethylated regions show substantial structural differences. Repeat elements are heavily methylated in both germ and somatic cells; however, retrotransposons from several subfamilies evade methylation more effectively during male germ cell development, whereas other subfamilies show the opposite trend. Comparing methylomes of human and chimp sperm revealed a subset of differentially methylated promoters and strikingly divergent methylation in retrotransposon subfamilies, with an evolutionary impact that is apparent in the underlying genomic sequence. Thus, the features that determine DNA methylation patterns differ between male germ cells and somatic cells, and elements of these features have diverged between humans and chimpanzees.

Long-Chain Hydrocarbons from Nonthermal Plasma-Driven Biogas Upcycling.

The burgeoning necessity to discover new methodologies for the synthesis of long-chain hydrocarbons and oxygenates, independent of traditional reliance on high-temperature, high-pressure, and fossil fuel-based carbon, is increasingly urgent. In this context, we introduce a nonthermal plasma-based strategy for the initiation and propagation of long-chain carbon growth from biogas constituents (CO2 and CH4). Utilizing a plasma reactor operating at atmospheric room temperature, our approach facilitates hydrocarbon chain growth up to C40 in the solid state (including oxygenated products), predominantly when CH4 exceeds CO2 in the feedstock. This synthesis is driven by the hydrogenation of CO2 and/or amalgamation of CHx radicals. Global plasma chemistry modeling underscores the pivotal role of electron temperature and CHx radical genesis, contingent upon varying CO2/CH4 ratios in the plasma system. Concomitant with long-chain hydrocarbon production, the system also yields gaseous products, primarily syngas (H2 and CO), as well as liquid-phase alcohols and acids. Our finding demonstrates the feasibility of atmospheric room-temperature synthesis of long-chain hydrocarbons, with the potential for tuning the chain length based on the feed gas composition.

Flotation Separation of Fluorite from Calcite using an Efficient Depressant Nitrilotriacetic Acid in the NaOL System.

Fluorite and calcite were separated with nitrilotriacetic acid (NTA) as a depressant. The single mineral flotation experiment confirmed that with 40 mg/L NaOL and 80 mg/L NTA, the fluorite recovery and calcite recovery were 24.37 and 94.13%, respectively, at pH 9. Meanwhile, in the fluorite-calcite binary mixed ore flotation experiment, the calcite recovery and fluorite recovery were 75.50 and 26.84%, respectively, and the CaCO3 and CaF2 grade in concentrate was 74.32 and 25.61%, respectively. The results confirmed that NTA could be used as a depressant to selectively inhibit fluorite flotation. The mechanism study illustrated that NTA was selectively reacted with fluorite by chemical interaction between O of NTA and Ca of fluorite. The adsorption of NTA on fluorite will impede the interaction between fluorite and NaOL. NTA could adsorb on fluorite in three ways, while the dominant two ways were the complex between double O of NTA and Ca of fluorite in a vertical model and the complex between double O of NTA and Ca of fluorite in a horizontal model.

Expression of Concern: Conjugation of substituted naphthalimides to polyamines as cytotoxic agents targeting the Akt/mTOR signal pathway.

Expression of Concern for 'Conjugation of substituted naphthalimides to polyamines as cytotoxic agents targeting the Akt/mTOR signal pathway' by Zhi-Yong Tian et al., Org. Biomol. Chem., 2009, 7, 4651-4660, https://doi.org/10.1039/B912685F.

Association Study between SNPs in MST1 and MST2 and H. pylori Infection as well as Noncardia Gastric Carcinogenesis.

INTRODUCTION: Gastric cancer (GC) remains a global health challenge, and H. pylori infection is a main risk factor for noncardia GC. The present study aimed to investigate the association between single nucleotide polymorphisms (SNPs) in mammalian sterile 20-like kinase 1 (MST1) and MST2, H. pylori (H. pylori) infection, and the risk of noncardia gastric cancer (GC). METHODS: A case-control study was conducted using enzyme-linked immunosorbent assay (ELISA) and TaqMan method to detect the titer of anti-H. pylori antibody in normal human serum and genotype 9 SNPs of MST1 and MST2 genes among 808 samples. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between SNPs and H. pylori infection, as well as the risk of noncardia gastric cancer in codominant, dominant, overdominant, recessive, and log-additive genetic models. Haplotypes were constructed using the Haploview 4.2 software. RESULTS: The CC genotype of MST2 SNP rs10955176 was associated with a reduced risk of H. pylori infection compared to the TT + CT genotype. None of other SNPs were associated with H. pylori infection. The TT genotype of MST2 SNP rs7827435 was associated with a reduced risk of noncardia gastric cancer compared to the AA + AT genotype. None of the SNPs were associated with noncardia gastric cancer. There were no associations between haplotypes and H. pylori infection or the risk of noncardia gastric cancer. CONCLUSIONS: The CC genotype of rs10955176 and the TT genotype of rs7827435 may serve as protective factors against H. pylori infection and noncardia gastric cancer risk, respectively.

Activation Mechanism of Fe2+ in Pyrrhotite Flotation: Microflotation and DFT Calculations.

In industrial manufacturing, pyrrhotite(Fe1-xS), once depressed, is commonly activated for flotation. However, the replacement of CuSO4 is necessary due to the need for exact control over the dosage during the activation of pyrrhotite, which can pose challenges in industrial settings. This research introduces the use of FeSO4 for the first time to efficiently activate pyrrhotite. The impact of two different activators on pyrrhotite was examined through microflotation experiments and density functional theory (DFT) calculations. Microflotation experiments confirmed that as the CuSO4 dosage increased from 0 to 8 × 10-4 mol/L, the recovery of pyrrhotite initially increased slightly from 71.27% to 87.65% but then sharply decreased to 16.47%. Conversely, when the FeSO4 dosage was increased from 0 to 8 × 10-4 mol/L, pyrrhotite's recovery rose from 71.27% to 82.37%. These results indicate a higher sensitivity of CuSO4 to dosage variations, suggesting that minor alterations in dosage can significantly impact its efficacy under certain experimental conditions. In contrast, FeSO4 might demonstrate reduced sensitivity to changes in dosage, leading to more consistent performance. Fe ions can chemically adsorb onto the surface of pyrrhotite (001), creating a stable chemical bond, thereby markedly activating pyrrhotite. The addition of butyl xanthate (BX), coupled with the action of Fe2+ on activated pyrrhotite, results in the formation of four Fe-S bonds on Fe2+. The proximity of their atomic distances contributes to the development of a stable double-chelate structure. The S 3p orbital on BX hybridizes with the Fe 3d orbital on pyrrhotite, but the hybrid effect of Fe2+ activation is stronger than that of nonactivation. In addition, the Fe-S bond formed by the addition of activated Fe2+ has a higher Mulliken population, more charge overlap, and stronger covalent bonds. Therefore, Fe2+ is an excellent, efficient, and stable pyrrhotite activator.

Catalyst-Free Carbon Dioxide Conversion in Water Facilitated by Pulse Discharges.

By inducing CO2-pulsed discharges within microchannel bubbles and regulating thus-forming plasma microbubbles, we observe high-performance, catalyst-free coformation of hydrogen peroxide (H2O2) and oxalate directly from CO2 and water. With isotope-labeled C18O2 as the feedstock, peaks of H218O16O and H216O2 observed by ex situ surface-enhanced Raman spectra indicate that single-atom oxygen (O) from CO2 dissociations and H2O-derived OH radicals both contribute to H2O2 formation. The global plasma chemistry modeling suggests that high-density, energy-intense electron supply enables high-density CO2- (aq) and HCO2- (aq) formation and their subsequent coupling to produce oxalate. The enhanced solvation of CO2, facilitated by the efficient transport of CxOy ionic species and CO, is demonstrated as a crucial benefit of spark discharges interacting with water at the bubble interface. We expect this plasma microbubble approach to provide a novel power-to-chemical avenue to convert CO2 into valuable H2O2 and oxalic acid platform chemicals, thus leveraging renewable energy resources.

Impaired tectorial membrane and ribbon synapse maturation in the cochlea of mice with congenital hypothyroidism.

Thyroid hormone deficiency can lead to abnormal auditory development of varying severity. Retardation of morphological development, including delays in degeneration of Kölliker's organ and subsequent delayed formation of the inner sulcus, along with delayed opening of the tunnel of Corti and malformation of the tectorial membrane, was consistently observed in an antithyroid drug-induced congenital hypothyroidism rodent model. Abnormal morphological development could partly explain impaired adult auditory function. However, whether the development of inner hair cell ribbon synapses is influenced by hypothyroidism remains unclear. In the present study, we characterize the normal degeneration pattern of Kölliker's organ along the basal-to-apical axis. Then, we verified the retardation of morphological development in congenital hypothyroid mice. Using this model, we found that twisted collagen is present in the major tectorial membrane and delayed separation from supporting cells affects the minor tectorial membrane. Finally, we found that the number of synaptic ribbons was not significantly altered but the ribbon synapse maturation process was significantly impaired in congenital hypothyroid mice. We conclude that thyroid hormone is involved in structural development of the tectorial membrane and the ribbon synapse maturation process.

Super multi-view near-eye virtual reality with directional backlights from wave-guides.

Directional backlights have often been employed for generating multiple view-zones in three-dimensional (3D) display, with each backlight converging into a corresponding view-zone. By designing the view-zone interval for each pupil smaller than the pupil's diameter, super multi-view (SMV) can get implemented for a VAC-free 3D display. However, expanding the backlight from a light-source to cover the corresponding display panel often needs an extra thickness, which results in a thicker structure and is unwanted by a near-eye display. In this paper, two wave-guides are introduced into a near-eye virtual reality (NEVR) system, for sequentially guiding more than one directional backlight to each display panel for SMV display without bringing obvious extra thickness. A prototype SMV NEVR gets demonstrated, with two backlights from each wave-guide converging into two view-zones for a corresponding pupil. Although the additional configured light-sources are positioned far from the corresponding wave-guide in our proof-of-concept prototype, multiple light-sources can be attached to the corresponding wave-guide compactly if necessary. As proof, a 3D scene with defocus-blur effects gets displayed. The design range of the backlights' total reflection angles in the wave-guide is also discussed.

Epidemiology and Association Rules Analysis for Pulmonary Tuberculosis Cases with Extrapulmonary Tuberculosis from Age and Gender Perspective: A Large-Scale Retrospective Multicenter Observational Study in China.

Background: Tuberculosis (TB), a multisystemic disease with protean presentation, remains a major global health problem. Although concurrent pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) cases are commonly observed clinically, knowledge regarding concurrent PTB-EPTB is limited. Here, a large-scale multicenter observational study conducted in China aimed to study the epidemiology of concurrent PTB-EPTB cases by diagnostically defining TB types and then implementing association rules analysis. Methods: The retrospective study was conducted at 21 hospitals in 15 provinces in China and included all inpatients with confirmed TB diagnoses admitted from Jan 2011 to Dec 2017. Association rules analysis was conducted for cases with concurrent PTB and various types of EPTB using the Apriori algorithm. Results: Evaluation of 438,979TB inpatients indicated PTB was the most commonly diagnosed (82.05%) followed by tuberculous pleurisy (23.62%). Concurrent PTB-EPTB was found in 129,422 cases (29.48%) of which tuberculous pleurisy was the most common concurrent EPTB type observed. The multivariable logistic regression models demonstrated that odds ratios of concurrent PTB-EPTB cases varied by gender and age group. For PTB cases with concurrent EPTB, the strongest association was found between PTB and concurrent bronchial tuberculosis (lift = 1.09). For EPTB cases with concurrent PTB, the strongest association was found between pharyngeal/laryngeal tuberculosis and concurrent PTB (lift = 1.11). Confidence and lift values of concurrent PTB-EPTB cases varied with gender and age. Conclusions: Numerous concurrent PTB-EPTB case types were observed, with confidence and lift values varying with gender and age. Clinicians should screen for concurrent PTB-EPTB in order to improve treatment outcomes.

On Model-Based Transfer Learning Method for the Detection of Inter-Turn Short Circuit Faults in PMSM.

The early detection of an inter-turn short circuit (ITSC) fault is extremely critical for permanent magnet synchronous motors (PMSMs) because it can lead to catastrophic consequences. In this study, a model-based transfer learning method is developed for ITSC fault detection. The contribution can be summarized as two points. First of all, a Bayesian-optimized residual dilated CNN model was proposed for the pre-training of the method. The dilated convolution is utilized to extend the receptive domain of the model, the residual architecture is employed to surmount the degradation problems, and the Bayesian optimization method is launched to address the hyperparameters tuning issues. Secondly, a transfer learning framework and strategy are presented to settle the new target domain datasets after the pre-training of the proposed model. Furthermore, motor fault experiments are carried out to validate the effectiveness of the proposed method. Comparison with seven other methods indicates the performance and advantage of the proposed method.

[Mechanism study on the effect of androgen antagonism in prostate cancer].

OBJECTIVE: To explore the mechanism of tetrahydroxynonene (4-HNE) in the androgen antagonistic effect of prostate cancer through the androgen receptor (AR) - mitogen activated protein kinase (MAPK) signaling pathway. METHOD: Prostate cancer LNCaP cells were divided into wild-type group (NC, control group) and transfection group. The transfection group was further divided into empty vector transfection group (NC-L7 group) and GSTA4 gene transfection group (A0718, GSTA4-OE group). The GSTA4-OE group received LNCaP cell culture and GSTA4 plasmid transfection to construct LNCaP stable 4-HNE cell lines, while the control group received LNCaP cell culture without GSTA4 plasmid transfection. Stimulating prostate cancer cells with different concentrations of 4-HNE (0, 40, 80, 120µmol/L) to activate the AR signaling pathway, Western blot was used to detect the expression of AR, MAKp, AKT, and PKCα proteins. Sixty cases of prostate cancer tissues and sixty cases of benign prostatic hyperplasia tissues were selected. Immunohistochemical staining was used to determine the positive expression rate of 4-HNE in the aforementioned tissues. The correlation between the positive expression of 4-HNE and tumor Gleason grade, as well as the progression of prostate cancer to CRPC, was analyzed. RESULT: The level of 4-HNE in the GSTA4-OE group cells was inhibited. Western blot analysis showed that compared with the control group, the GSTA4-OE group had PKC in cells α The protein expression level significantly decreased (P<0.05), while the expression levels of AR and AKT proteins significantly increased (P<0.05). After treating prostate cancer cells with 40, 80, and 120µmol/L 4-HNE, compared with the control group, the expression level of AKT in the treatment group was significantly reduced (P<0.01), while the expression levels of MAKP (P<0.01), PKC (P<0.01), and AR (P<0.01) were significantly increased. The immunohistochemical results showed that the positive rate of 4-HNE was 5.0% in 60 cases of benign prostatic hyperplasia tissue and 63.3% in 60 cases of prostate cancer tissue, with a statistically significant difference (P<0.01). The positive rates of 4-HNE in Gleason grades 1-5 were 41.2%, 50.0%, 63.6%, 81.8%, and 100.0%, respectively. The higher the Gleason grade, the higher the positive rate of 4-HNE, and the difference was statistically significant (P<0.05). During a follow-up period of 10-35 months, 33 patients advanced to CRCP, while 27 patients did not. The positive expression rate of 4-HNE in the two groups showed a statistically significant difference (P<0.01). CONCLUSION: Under the action of 4-HNE, the expression of AR-MAPK pathway related proteins increase. 4-HNE may promote the progression of prostate cancer through the AR-MAPK pathway, and 4-HNE is expected to become a new therapeutic target for CRPC.

[Correlation of the expressions of 4-HNE and GPC5 with the progression of prostate cancer].

OBJECTIVE: To investigate the expressions of phosphatidylinositol proteoglycan 5 (GPC5) and tetrahydroxynonene (4-HNE) in the PCa tissue and their impact on tumor progression. METHODS: Using immunohistochemistry, we determined the expression rates of GPC5 and 4-HNE in 50 PCa and 50 BPH tissue samples, followed by comparative analysis of the correlation between their expressions and Gleason grading. RESULTS: The positive expression rate of GPC5 was 94.0% in the BPH tissue, remarkably higher than 86.7%, 66.7%, 75.0%, 55.6% and 33.3% in the PCa tissues of Gleason grades 1, 2, 3, 4 and 5 (P = 0.001), with a negative correlation between the positive expression rate of GPC5 and the Gleason grade of tumors (P = 0.021). In contrast, the positive expression rate of 4-HNE was 4.0% in the BPH tissue, dramatically lower than 55.6%, 66.7%, 75.0%, 77.8% and 88.9% in the PCa tissues of Gleason grades 1, 2, 3, 4 and 5 (P = 0.001), with a positive correlation between the expression rate of GPC5 and the Gleason grade of tumors (P = 0.001). After a follow-up of 10－30 months, the expression rates of GPC5 and 4-HNE in the tissues converted to castration-resistant PCa (CRPC) showed a statistically significant difference from those remaining unconverted (P = 0.001, P = 0.048). There was a negative correlation between the positive expression rate of 4-HNE and that of GPC5 in the PCa tissue (R = －0.983, P = 0.003). CONCLUSION: The low expression of GPC5 and high expression of 4-HNE are closely related to the pathological grade of PCa and its conversion to CRP, which may serve as new biological markers in assessing the malignancy and prognosis of tumors.

Bladder cancer-derived exosomal KRT6B promotes invasion and metastasis by inducing EMT and regulating the immune microenvironment.

BACKGROUND: Tumour-derived exosomes have recently been shown to participate in the formation and progression of different cancer processes, including tumour microenvironment remodelling, angiogenesis, invasion, metastasis, and drug resistance. However, the function and mechanism of exosome-encapsulated nucleic acids and proteins in bladder cancer remain unclear. This study aimed to investigate the effects of tumour-derived exosomes on the tumorigenesis and development of bladder cancer. METHODS: In this study, gene expression profiles and clinical information were collected from The Cancer Genome Atlas (TCGA) database and two independent Gene Expression Omnibus (GEO) datasets. The nucleic acids and proteins encapsulated in bladder cancer-derived exosomes were obtained from the ExoCarta database. Based on these databases, the expression patterns of exosomal mRNAs and proteins and the matched clinicopathological characteristics were analysed. Furthermore, we carried out a series of experiments to verify the relevant findings. RESULTS: A total of 7280 differentially expressed mRNAs were found in TCGA data, of which 52 mRNAs were shown to be encapsulated in bladder cancer-derived exosomes. Survival analysis based on the UALCAN database showed that among the top 10 upregulated and the top 10 downregulated exosomal genes, only the expression of KRT6B had a statistically significant effect on the survival of bladder cancer patients. Additionally, clinical correlation analysis showed that the elevated level of KRT6B was highly associated with bladder cancer stage, grade, and metastasis status. GSEA revealed that KRT6B was involved not only in epithelial-mesenchymal transition-related pathways but also in the immune response in bladder cancer. Ultimately, our experimental results were also consistent with the bioinformatic analysis. CONCLUSION: KRT6B, which can be detected in bladder cancer-derived exosomes, plays an important role in the epithelial-mesenchymal transition and immune responses in bladder cancer. Further research will enable its potentially prognostic marker and therapeutic target for bladder cancer.

N6-methyladenosine-related single-nucleotide polymorphism analyses identify oncogene RNFT2 in bladder cancer.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in N6-methyladenosine (m6A) related genetic locus play significant roles in tumorigenesis and development. The expression level of many oncogenes and tumour suppressor genes changed because of m6A-associated SNPs. In addition, the relationship between m6A-SNP and bladder cancer (BCa) has not been well studied. METHODS: We screened m6A-SNPs in BCa by combining m6A-SNPs data and GWAS-SNPs data. Expression quantitative trait loci (eQTL) and differential expression gene (DEGs) analyses were performed. In ring finger protein, transmembrane 2 (RNFT2), rs3088107 (C > G) was found to have significant eQTL signals and make RNFT2 gene differentially-regulated mostly in BCa. We validated the expression level of RNFT2 in 32 pairs of BCa tissues and eight BCa cell lines by quantitative real-time PCR (qRT-PCR). Functional assays were performed to investigate the role of rs3088107 and RNFT2 in BCa in vitro. RESULTS: We identified 673 m6A-SNPs, which were associated with BCa. Of these m6A-SNPs, 221 showed eQTL signals, amongst which, rs3088107 in RNFT2 showed significant eQTL signals. Results of bioinformatic analyses showed that 11 genes with m6A-SNPs had a differential expression level in BCa. RNFT2 was predicted to be significantly up-regulated in BCa. The qRT-PCR results validated that RNFT2 was highly expressed in our own BCa tissues and cell lines. High expression of RNFT2 also indicated a worse overall survival. We also revealed that rs3088107 (C > G) could inhibit the expression and m6A modification of RNFT2 by qRT-PCR, western-blot and m6A-RIP assays. Moreover, the results of functional assays indicated that RNFT2 promoted BCa cell proliferation and migration. CONCLUSION: This research found that m6A-SNPs were associated with oncogene RNFT2 in BCa. Furthermore, m6A-SNPs showed great application potential as a new BCa diagnostic biomarker and prognostic indicator.

Optimization of a laparoscopic procedure for advanced intrahepatic cholangiocarcinoma based on the concept of "waiting time": a preliminary report.

INTRODUCTION: Clinicians increasingly perform laparoscopic surgery for intrahepatic cholangiocarcinoma (ICC). However, this surgery can be difficult in patients with advanced-stage ICC because of the complicated procedures and difficulty in achieving high-quality results. We compared the effects of a three-step optimized procedure with a traditional procedure for patients with advanced-stage ICC. METHODS: Forty-two patients with advanced-stage ICC who received optimized laparoscopic hemihepatectomy with lymph node dissection (LND, optimized group) and 84 propensity score-matched patients who received traditional laparoscopic hemihepatectomy plus LND (traditional group) were analyzed. Surgical quality, disease-free survival (DFS), and overall survival (OS) were compared. RESULTS: The optimized group had a lower surgical bleeding score (P = 0.038) and a higher surgeon satisfaction score (P = 0.001). Blood loss during hepatectomy was less in the optimized group (190 vs. 295 mL, P < 0.001). The optimized group had more harvested LNs (12.0 vs. 8.0, P < 0.001) and more positive LNs (8.0 vs. 5.0, P < 0.001), and a similar rate of adequate LND (88.1% vs. 77.4%, P = 0.149). The optimized group had longer median DFS (9.0 vs. 7.0 months, P = 0.018) and median OS (15.0 vs. 13.0 months, P = 0.046). In addition, the optimized group also had a shorter total operation time (P = 0.001), shorter liver resection time (P = 0.001), shorter LND time (P < 0.001), shorter hospital stay (P < 0.001), and lower incidence of total morbidities (14.3% vs. 36.9%, P = 0.009). CONCLUSIONS: Our optimization of a three-step laparoscopic procedure for advanced ICC was feasible, improved the quality of liver resection and LND, prolonged survival, and led to better intraoperative and postoperative outcomes.

Elevation of spermine remodels immunosuppressive microenvironment through driving the modification of PD-L1 in hepatocellular carcinoma.

BACKGROUND: Spermine is frequently elevated in tumor tissues and body fluids of cancer patients and is critical for cancer cell proliferation, migration and invasion. However, the immune functions of spermine in hepatocellular carcinoma progression remains unknown. In the present study, we aimed to elucidate immunosuppressive role of spermine in hepatocellular carcinoma and to explore the underlying mechanism. METHODS: Whole-blood spermine concentration was measured using HPLC. Human primary HCC tissues were collected to examine the expression of CaSR, p-Akt, ß-catenin, STT3A, PD-L1, and CD8. Mouse model of tumorigenesis and lung metastasis were established to evaluate the effects of spermine on hepatocellular carcinoma. Western blotting, immunofluorescence, real time PCR, digital Ca2+ imaging, and chromatin immunoprecipitation assay were used to investigate the underlying mechanisms by which spermine regulates PD-L1 expression and glycosylation in hepatocellular carcinoma cells. RESULTS: Blood spermine concentration in the HCC patient group was significantly higher than that in the normal population group. Spermine could facilitate tumor progression through inducing PD-L1 expression and decreasing the CD8+ T cell infiltration in HCC. Mechanistically, spermine activates calcium-sensing receptor (CaSR) to trigger Ca2+ entry and thereby promote Akt-dependent ß-catenin stabilization and nuclear translocation. Nuclear ß-catenin induced by spermine then activates transcriptional expression of PD-L1 and N-glycosyltransferase STT3A, while STT3A in turn increases the stability of PD-L1 through inducing PD-L1 protein N-glycosylation in HCC cells. CONCLUSIONS: This study reveals the crucial function of spermine in establishing immune privilege by increasing the expression and N-glycosylation of PD-L1, providing a potential strategy for the treatment of hepatocellular carcinoma. Video Abstract.

Formation of Liquid Film in Heterogeneous Condensation of Water Vapor: Effects of Solid-Fluid Interaction and Sulfuric Acid Component.

Understanding the phenomenon of filmwise condensation on solid surfaces is vital for industrial processes such as air pollutant control and desalination. In this work, we study the formation of condensed liquid films via molecular dynamics simulations, and the effects of solid-fluid interactions and the sulfuric acid component are given major attention. Water is chosen as the fluid, while the solid-fluid interaction is modified to characterize different solid surfaces. The results show that as the solid-fluid interaction decreases, the solid surface transforms from a completely wetting surface to a partially wetting surface, and the film formation process shows significant differences. The condensed liquid on the completely wetting surface forms small liquid films, which merge to form a complete film covering the surface. With the enhancement of solid-fluid interaction, the condensation rate increases first and then remains virtually invariant, resulting in a film formation time that decreases first and then maintains constant. The condensed liquid on the partially wetting surfaces appears as nanodroplets, and the coalescence between nanodroplets leads to the formation of the liquid film. It is found that the stronger the solid-fluid interaction, the more the coalesced droplets tend to be pinned at nucleation sites, the easier it is to form a liquid film, and the shorter the time required for droplet merging. The sulfuric acid component accelerates liquid film formation on both completely wetting and partially wetting surfaces, but the effect of sulfuric acid is more significant on partially wetting surfaces. The 5% molar fraction of sulfuric acid reduces the nucleation time by 72% and increases the condensation rate by 137% under partial wetting, while the same amount of sulfuric acid only increases the nucleation rate by 6% on the completely wetting surface.

Safety and Efficacy of Drug-Coated Balloon in the Treatment of Below-the-Knee Artery: A Meta-analysis.

INTRODUCTION: Chronic limb threat ischemia is associated with cardiovascular events, resulting in high amputation, morbidity and mortality rates. This study aims to accomplish a comprehensive summary of randomized controlled trials and single-center trials related to drug-coated balloons (DCBs) in the treatment of below-the-knee (BTK) artery disease, and to provide a recommendation for the application of DCBs in BTK artery disease. METHODS: Five electronic databases were used to retrieve relevant articles on the safety and effectiveness of DCBs in the treatment of BTK artery disease. A random-effects model was applied to calculate the standard mean deviation, odds ratio (OR) and their 95% of confidence interval (CI). RESULTS: As of April 8, 2021, a total of 241 articles were retrieved, but only 13 articles were finally included for meta-analysis. The 12 mo follow-up study found that major adverse events , all-cause mortality, major amputation ,and target lesion revascularization had no statistically significant difference between the DCBs group and the control group (target lesion revascularization: OR = 0.68, 95% CI: 0.36, 1.31; all-cause mortality: OR = 1.30, 95% CI: 0.69, 2.46; major amputation: OR = 1.34, 95% CI: 0.64, 2.79; target lesion revascularization: OR = 0.72, 95% CI: 0.35, 1.45). CONCLUSIONS: The meta-analysis results of randomized controlled trials focusing on comparing DCBs and other treatments suggest that DCBs do not have significant advantages in the treatment of BTK artery disease when compare with percutaneous transluminal angioplasty (PTA), but better than control intervention except PTA in both safety and efficacy end points. However, the results of meta-analysis of single-arm trial reported DCBs in treating BTK artery lesions are significantly improved compared with the meta-analysis concentrating on PTA.

WWP2 ameliorates oxidative stress and inflammation in atherosclerotic mice through regulation of PDCD4/HO-1 pathway.

WWP2 is a HECT-type E3 ubiquitin ligase that regulates various physiological and pathological activities by binding to different substrates, but its role in atherosclerosis (AS) remains largely unknown. The objective of the present study is to investigate the role and underlying molecular mechanisms of WWP2 in endothelial injury. We found that WWP2 expression is significantly decreased in Apolipoprotein E (ApoE) -/- mice. Overexpression of WWP2 attenuates oxidative stress and inflammation in AS mice, while knockdown of WWP2 has opposite effects. WWP2 overexpression alleviates oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cell (HUVEC) injury, evidenced by the decreased oxidative stress levels and the secretion of inflammatory cytokines. Programmed cell death 4 (PDCD4) is identified as a potential substrate of WWP2. Co-immunoprecipitation (Co-IP) further demonstrates that WWP2 interacts with PDCD4, which is enhanced by ox-LDL treatment. Furthermore, the level of PDCD4 ubiquitination is significantly increased by WWP2 overexpression under the condition of MG132 treatment, while WWP2 knockdown shows opposite results. Subsequently, rescue experiments demonstrate that WWP2 knockdown further aggravates oxidative stress and inflammation in ox-LDL-treated HUVECs, while knockdown of PDCD4 alleviates this effect. Moreover, the use of sn-protoporphyrin (SnPP), an inhibitor of HO-1 pathway, confirms that PDCD4 enhances endothelial injury induced by ox-LDL through inhibiting HO-1 pathway. In conclusion, our results suggest that WWP2 protects against atherosclerosis progression via the PDCD4/HO-1 pathway, which may provide a novel treatment strategy for atherosclerosis.