Protocatechuic aldehyde increases pericyte coverage and mitigates pericyte damage to enhance the atherosclerotic plaque stability.

Pericyte dysfunction and loss contribute substantially to the destabilization and rupture of atherosclerotic plaques. Protocatechuic aldehyde (PCAD), a natural polyphenol, exerts anti-atherosclerotic effects. However, the effects and mechanisms of this polyphenol on pericyte recruitment, coverage, and pericyte function remain unknown. We here treated apolipoprotein E-deficient mice having high-fat diet-induced atherosclerosis with PCAD. PCAD achieved therapeutic effects similar to rosuvastatin in lowering lipid levels and thus preventing atherosclerosis progression. With PCAD administration, plaque phenotype exhibited higher stability with markedly reduced lesion vulnerability, which is characterized by reduced lipid content and macrophage accumulation, and a consequent increase in collagen deposition. PCAD therapy increased pericyte coverage in the plaques, reduced VEGF-A production, and inhibited intraplaque neovascularization. PCAD promoted pericyte proliferation, adhesion, and migration to mitigate ox-LDL-induced pericyte dysfunction, which thus maintained the capillary network structure and stability. Furthermore, TGFBR1 silencing partially reversed the protective effect exerted by PCAD on human microvascular pericytes. PCAD increased pericyte coverage and impeded ox-LDL-induced damages through TGF-ß1/TGFBR1/Smad2/3 signaling. All these novel findings indicated that PCAD increases pericyte coverage and alleviates pericyte damage to improve the stability of atherosclerotic plaques, which is accomplished by regulating TGF-ß1/TGFBR1/Smad2/3 signaling in pericytes.

Kinesin family member 11 promotes progression of hepatocellular carcinoma via the OCT4 pathway.

Hepatocellular carcinoma (HCC) is the tumor with the second highest mortality rate worldwide. Recent research data show that KIF11, a member of the kinesin family (KIF), plays an important role in the progression of various tumors. However, its expression and molecular mechanism in HCC remain elusive. Here, we evaluated the potential role of KIF11 in HCC. The effect of KIF11 was evaluated using the hepatocellular carcinoma cell lines, LM3 and Huh7, after genetic or pharmacological treatment. Evaluating the role of KIF11 in the xenograft animal models using its specific inhibitor. The role of KIF11 was systematically evaluated using specimens obtained from the aforementioned animal and cell models after various in vivo and in vitro experiments. The clinicopathological analysis showed that KIF11 was expressed at high levels in patients with hepatocellular carcinoma. Cell experiments in vitro showed that KIF11 deficiency significantly slowed the proliferation of liver tumor cells. And in the experiment using liver cancer cells overexpressing OCT4, overexpression of OCT4 substantially increased the proliferation of tumor cells compared with tumor cells with KIF11 knockdown alone. Both in vitro cell experiment and in vivo xenotransplantation tumor experiment showed that monastrol, an inhibitor of KIF11, could effectively delay the proliferation and migration of tumor cells. Based on these results, KIF11 is expressed at high levels in hepatocellular carcinoma and promotes tumor proliferation in an OCT4-dependent manner. KIF11 may become a therapeutic target for hepatocellular carcinoma, and its inhibitor monastrol may become a clinical antitumor drug.

The role of the ERK signaling pathway in promoting angiogenesis for treating ischemic diseases.

The main treatment strategy for ischemic diseases caused by conditions such as poor blood vessel formation or abnormal blood vessels involves repairing vascular damage and encouraging angiogenesis. One of the mitogen-activated protein kinase (MAPK) signaling pathways, the extracellular signal-regulated kinase (ERK) pathway, is followed by a tertiary enzymatic cascade of MAPKs that promotes angiogenesis, cell growth, and proliferation through a phosphorylation response. The mechanism by which ERK alleviates the ischemic state is not fully understood. Significant evidence suggests that the ERK signaling pathway plays a critical role in the occurrence and development of ischemic diseases. This review briefly describes the mechanisms underlying ERK-mediated angiogenesis in the treatment of ischemic diseases. Studies have shown that many drugs treat ischemic diseases by regulating the ERK signaling pathway to promote angiogenesis. The prospect of regulating the ERK signaling pathway in ischemic disorders is promising, and the development of drugs that specifically act on the ERK pathway may be a key target for promoting angiogenesis in the treatment of ischemic diseases.

Integrative proteomics, phosphoproteomics and acetylation proteomics analyses of acute pancreatitis in rats.

Acute pancreatitis (AP) is a common acute abdominalgia of the digestive tract. When the disease progresses to severe acute pancreatitis (SAP), the complications and mortality rate greatly increase. Determining the key factors and pathways underlying AP and SAP will help elucidate the pathological processes involved in disease progression and will be beneficial for identifying potential therapeutic targets. We conducted an integrative proteomics, phosphoproteomics and acetylation proteomics analysis of pancreas samples collected from normal, AP and SAP rat models. We identified 9582 proteins, 3130 phosphorylated modified proteins, and 1677 acetylated modified proteins across all samples. The differentiated expression proteins and KEGG pathway analysis suggested the pronounced enrichment of key pathways based on the following group comparisons: AP versus normal, SAP versus normal, and SAP versus AP. Integrative proteomics and phosphoproteomics analyses revealed 985 jointly detected proteins in the comparison of AP and normal samples, 911 proteins in the comparison of SAP and normal samples, and 910 proteins in the comparison of SAP and AP samples. Based on proteomics and acetylation proteomics analyses, we found that 984 proteins were jointly detected in the comparison of AP and normal samples, 990 proteins in SAP and normal samples, and 728 proteins in SAP and AP samples. Thus, our study offers a valuable resource to understand the proteomic and protein modification atlas in AP.

Identification and validation of core genes in tumor-educated platelets for human gastrointestinal tumor diagnosis using network-based transcriptomic analysis.

Gastrointestinal (GI) tumors have increasing incidence worldwide with their underlying mechanisms still not being fully understood. The use of tumor-educated platelets (TEPs) in liquid biopsy is a newly-emerged blood-based cancer diagnostic method. Herein, we aimed to investigate the genomic changes of TEPs in GI tumor development and their potential functions using network-based meta-analysis combined with bioinformatic methods. We used a total of three eligible RNA-seq datasets, which were integrated using multiple meta-analysis methods on the NetworkAnalyst website, and identified 775 DEGs (differentially expressed genes; 51 up-regulated and 724 down-regulated genes) in GI tumor relative to healthy control (HC) samples. These TEP DEGs were mostly enriched in bone marrow-derived cell types and associated with gene ontology (GO) of "carcinoma" and could affect pathways of "Integrated Cancer Pathway" and "Generic transcription pathway" respectively for highly and lowly expressed DEGs. Combined network-based meta-analysis and protein-protein interaction (PPI) analysis identified cyclin dependent kinase 1 (CDK1) and heat shock protein family A (Hsp70) member 5 (HSPA5) to be the hub genes with the highest degree centrality (DC), being up-regulated and down-regulated in TEPs, respectively. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that the hub genes were primarily related to cell cycle and division, nucleobase-containing compound and carbohydrate transport, and endoplasmic reticulum unfolded protein response. Additionally, the nomogram model suggested that the two-gene signature owns extraordinary predictive power for GI tumor diagnosis. Further, the two-gene signature was demonstrated to have potential value for metastatic GI tumor diagnosis. The expression levels of CDK1 and HSPA5 in clinical platelet samples were verified to be consistent with the results from bioinformatic analysis. This study identified a two-gene signature encompassing CDK1 and HSPA5 that can be used as a biomarker for GI tumor diagnosis and maybe even cancer-associated thrombosis (CAT)-related prognosis.

What is the context? Gastrointestinal (GI) tumors are now responsible for the majority of cancer-related mortalities worldwide.In the majority of cases of cancer, curative treatments are not recommended at the time of diagnosis. In this case, early screening and diagnosis is very important for overall tumor prognosis. Liquid biopsy emerged as a newly introduced minimally invasive approach for cancer diagnosis by detecting blood analytes as tumor-educated platelets (TEPs). Compared to tissue-based biopsies, liquid biopsies are less invasive, easy to access, convenient for serial tracking and better in eliminating intratumoral spatial heterogeneity. In recent years, specific gene signatures have been identified for cancer diagnosis, prognosis and prediction based on gene profiling data of TEPs. However, most of these studies were performed on the independent platelet profile datasets published on the Gene Expression Omnibus (GEO) database, which may harbor enormous heterogeneity. Additionally, few study revealed TEP mRNA functions and roles in GI tumors. Therefore, there's the need of using an integrated method to re-analyze these data, so we can gain new insights for GI tumor diagnosis.What is new? Herein, through network-based RNA-seq meta-analysis, we identified the CDK1-HSPA5 signature in TEPs that has the potential as a biomarker for diagnosing GI tumors. This is the first time, to our knowledge, that a shared transcriptional signature of tumor-educated platelets has been identified in human GI tumor patients based on meta-analysis. Additionally, we found the two-gene signature has potential value for metastatic GI tumor diagnosis. We also demonstrated that HSPA5 may have different roles in blood and tumor cells, so its expression deregulation in distinct types of tissue may have opposing diagnostic and prognostic values.What is the impact? Our work provides a novel biomarker for platelet-based GI tumor prediction and diagnosis, which may also be used as novel targets for thrombosis prevention during cancer development in the future.

RRP Regulates Autophagy through the AMPK Pathway to Alleviate the Effect of Cell Senescence on Atherosclerosis.

Autophagy is closely associated with atherosclerosis and other cardiovascular diseases (CVD). Compound Danshen prescription is widely used as a clinical antiatherosclerotic drug. In our previous studies, we have shown that the combined active component, ginsenoside Rg1-notoginsenoside R1-protocatechualdehyde (RRP), can effectively alleviate endothelial dysfunction and reduce atherosclerotic plaques. However, the association between cellular senescence, caused by reduced autophagy, and atherosclerosis remains unclear. In this study, we investigated whether RRP can enhance autophagy and alleviate cell senescence through the AMPK pathway. Our results showed that RRP reduced the secretion of inflammatory factors in the serum of atherosclerotic mice, enhanced autophagy, and alleviated aortic aging in mice, thus reducing atherosclerotic plaques. In human aortic endothelial cells (HAECs), RRP effectively enhanced autophagy and inhibited senescence by activating the AMPK pathway. When AMPKα was silenced, the effect of RRP was inhibited, thus reversing its antiaging effect. Overall, our results show that RRP regulates autophagy through the AMPK pathway, thereby inhibiting cell senescence and alleviating the progression of atherosclerosis, suggesting that RRP may be a potential candidate drug for the treatment of atherosclerosis.

Advances in relationship between cell senescence and atherosclerosis.

Cellular senescence is a biological process associated with the degeneration of cell structure and function, which contribute to age-related diseases. Atherosclerosis is a chronic inflammatory disease that can cause a variety of cardiovascular disorders. In this article, we review the effects of cellular senescence on the development of atherosclerosis through diverse physiopathological changes, focusing on the alterations in senescent organelles and the increased senescence-associated secretory phenotype (SASP), and exploring the relevant therapeutic strategies for atherosclerosis by clearing senescent cells and reducing SASP, to provide new insights for the treatment of atherosclerosis.

TCM Regulates PI3K/Akt Signal Pathway to Intervene Atherosclerotic Cardiovascular Disease.

Vascular endothelial injury is the initial stage of atherosclerosis (AS). Stimulating and activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway can regulate the expression of vascular endothelial cytokines, thus affecting the occurrence and development of AS. In addition, the PI3K/Akt signaling pathway can regulate the polarization and survival of macrophages and the expression of inflammatory factors and platelet function, thus influencing the progression of AS. In recent years, traditional Chinese medicine (TCM) has been widely recognized for its advantages of fewer side effects, multiple pathways, and multiple targets. Also, the research of TCM regulation of AS via the PI3K/Akt signaling pathway has achieved certain results. This study aimed to analyze the characteristics of the PI3K/Akt signaling pathway and its role in the pathogenesis of AS, as well as the role of Chinese medicine in regulating the PI3K/Akt signaling pathway. The findings are expected to provide a theoretical basis for the clinical treatment and pathological mechanism research of AS.

Maribacter luteus sp. nov., a marine bacterium isolated from intertidal sand of the Yellow Sea.

A novel rod-shaped and Gram-stain-negative bacterium, designated strain RZ05T, was isolated from a sand sample collected from the intertidal zone of the Yellow Sea, PR China. Results of phylogenetic analysis based on 16S rRNA gene sequences revealed that strain RZ05T clusters within the genus Maribacter, a member of the family Flavobacteriaceae, and has the highest sequence similarity to Maribacter polysiphoniae KCTC 22021T (97.8 %), followed by Maribacter arenosus KCTC 52191T (97.2 %). Cells of this strain were observed to be aerobic, oxidase- and catalase-positive, motile by gliding and formed yellow colonies. Growth occurred at 7-40 °C (optimum, 30 °C), at pH 6.5-9.5 (optimum, pH 7.0) and with 0.5-6 % (optimum, 2 %) NaCl. Its polar lipid profile included phosphatidylethanolamine, two unidentified glycolipids, one unidentified aminolipid and four unidentified lipids. The major cellular fatty acids were iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3-OH, iso-C16 : 0 3-OH, iso-C15 : 0 3-OH, summed feature 9 (10-methyl C16 : 0/iso-C17 : 1 ω9c) and summed feature 3 (iso-C15 : 0 2-OH/C16 : 1 ω7c/C16 : 1 ω6c). The only respiratory quinone was menaquinone 6 (MK-6). The genome of strain RZ05T was 4.65 Mbp with a G+C content of 38.9 mol%. The average nucleotide identity and in silico DNA-DNA hybridization values between strain RZ05T and its most closely related type strain M. polysiphoniae KCTC 22021T were 80.3 and 26.3  %, respectively. The results of phylogenetic, phenotypic and chemotaxonomic analyses indicated that strain RZ05T represents a novel species of the genus Maribacter, for which the name Maribacter luteus sp. nov. is proposed. The type strain is RZ05T (=KCTC 62834T=MCCC 1K03617T).

Separate As(V) from solution by mesoporous Y-Al binary oxide: batch experiments.

Contaminant arsenic(V) has been regarded as one of the top-priority pollutants to remove from water. In this contribution, different mesoporous Y-Al binary oxides were prepared by the wet impregnation method via varying the molar ratio of Y/Al in the range of 0.029 to 0.116. The manufactured materials were employed as adsorbent to separate arsenic(V) from water. The adsorbent was characterized by N2 adsorption-desorption isotherm, point of zero charge (PZC) and Fourier transform infrared (FT-IR). Furthermore, the effect of experimental parameters on adsorption performance was evaluated by batch experiments, including the molar ratio of Y/Al, adsorbent dosages and contact time, initial concentration, initial pH and temperature. The results indicated that the adsorbent presented an optimal adsorption performance for As(V) uptake when the molar ratio of Y/Al was 0.058. The obtained experimental data were best fitted by Langmuir isotherm and the maximum adsorption capacity was 60.93 mg/g at pH 6.6 ± 0.1. Additionally, according to the results of adsorption kinetics, it was pronounced that adsorption process was complied with pseudo-second-order model. The adsorption thermodynamic suggested that the adsorption of As(V) is endothermic and spontaneous natural. Moreover, based on the results of FT-IR, PZC and initial pH, it is demonstrated that ion-exchange and electrostatic interaction were the dominating adsorption mechanism.

Flexible TWDM PON system with pluggable optical transceiver modules.

A flexible TWDM PON system is proposed which allows pay-as-you-grow in capacity, supports load balancing among different ODNs, and achieves significant power saving at OLT. Integrated OLT transceiver in enhanced CFP module and low-cost tunable ONU transceiver in SFP+ module are developed, for the first time, for cost effective deployment of TWDM PONs. System experiments demonstrate error free performance with 36 dB power budget in a flexible TWDM PON test bed.

System evaluation of economic 16/32chs 1.25Gbps WDM-PON with self-seeded RSOA.

We investigate a novel WDM-PON system by using self-seeded Reflective Semiconductor Optical Amplifier (RSOA) both in downstream and upstream. The transmission performance is evaluated and reported for the first time and meets carrier level requirements.

Travelling wave analysis on high-speed performance of Q-modulated distributed feedback laser.

The structure of a Q-modulated distributed feedback laser is designed and simulated. A large reflectivity modulation of the rear reflector is achieved by using an anti-resonant cavity formed by two deep trenches with the one between the modulator and phase section filled by a high index dielectric material. The travelling wave model is presented to analyze the high speed performance of the laser. Due to the effect of the wave propagation in the structure, the modulation extinction ratio decreases with increasing cavity length. It is shown that 40 Gb/s RZ signal modulation can be achieved with an extinction ratio of 7 dB and 10 dB, respectively, for a cavity length of 500 µm and 300 µm.

Design and analysis of 2 x 2 half-wave waveguide couplers.

Conventional couplers including the 2 x 2 directional coupler and the self-imaging multimode interference coupler always produce a 90 degrees coupling phase to yield complementary power transfer functions when the relative phase of the two input fields changes. For applications in coupled-cavity lasers, a 2 x 2 half-wave optical coupler with a 180 degrees coupling phase is required in order to produce synchronous output power for achieving high single-mode selectivity. We present the designs and optimization of 2 x 2 half-wave couplers, including a three-waveguide directional coupler and a nonimaging multimode interference coupler.

Wavelength switchable semiconductor laser using half-wave V-coupled cavities.

A new semiconductor laser structure with digitally switchable wavelength is proposed. The device comprises two coupled cavities with different optical path lengths, which form V-shaped branches with a reflective 2x2 half-wave optical coupler at the closed end. The reflective 2x2 coupler is designed to have a pi-phase difference between cross-coupling and self-coupling so as to produce synchronous power transfer functions. High single-mode selectivity is achieved by optimizing the coupling coefficient. The switchable wavelength range is greatly increased by using Vernier effect. Using deep-etched trenches as partial reflectors, additional waveguide branch structures are used outside the laser cavities to form a complete Mach-Zehnder interferometer, allowing space switching, variable attenuation, or high speed modulation to be realized simultaneously. Detailed design principle and numerical results are presented.