LncRNA PSMB8-AS1 Instigates Vascular Inflammation to Aggravate Atherosclerosis.

BACKGROUND: Increasing evidence suggests that long noncoding RNAs play significant roles in vascular biology and disease development. One such long noncoding RNA, PSMB8-AS1, has been implicated in the development of tumors. Nevertheless, the precise role of PSMB8-AS1 in cardiovascular diseases, particularly atherosclerosis, has not been thoroughly elucidated. Thus, the primary aim of this investigation is to assess the influence of PSMB8-AS1 on vascular inflammation and the initiation of atherosclerosis. METHODS: We generated PSMB8-AS1 knockin and Apoe (Apolipoprotein E) knockout mice (Apoe-/-PSMB8-AS1KI) and global Apoe and proteasome subunit-ß type-9 (Psmb9) double knockout mice (Apoe-/-Psmb9-/-). To explore the roles of PSMB8-AS1 and Psmb9 in atherosclerosis, we fed the mice with a Western diet for 12 weeks. RESULTS: Long noncoding RNA PSMB8-AS1 is significantly elevated in human atherosclerotic plaques. Strikingly, Apoe-/-PSMB8-AS1KI mice exhibited increased atherosclerosis development, plaque vulnerability, and vascular inflammation compared with Apoe-/- mice. Moreover, the levels of VCAM1 (vascular adhesion molecule 1) and ICAM1 (intracellular adhesion molecule 1) were significantly upregulated in atherosclerotic lesions and serum of Apoe-/-PSMB8-AS1KI mice. Consistently, in vitro gain- and loss-of-function studies demonstrated that PSMB8-AS1 induced monocyte/macrophage adhesion to endothelial cells and increased VCAM1 and ICAM1 levels in a PSMB9-dependent manner. Mechanistic studies revealed that PSMB8-AS1 induced PSMB9 transcription by recruiting the transcription factor NONO (non-POU domain-containing octamer-binding protein) and binding to the PSMB9 promoter. PSMB9 (proteasome subunit-ß type-9) elevated VCAM1 and ICAM1 expression via the upregulation of ZEB1 (zinc finger E-box-binding homeobox 1). Psmb9 deficiency decreased atherosclerotic lesion size, plaque vulnerability, and vascular inflammation in Apoe-/- mice in vivo. Importantly, endothelial overexpression of PSMB8-AS1-increased atherosclerosis and vascular inflammation were attenuated by Psmb9 knockout. CONCLUSIONS: PSMB8-AS1 promotes vascular inflammation and atherosclerosis via the NONO/PSMB9/ZEB1 axis. Our findings support the development of new long noncoding RNA-based strategies to counteract atherosclerotic cardiovascular disease.

Pd-Catalyzed Intramolecular Dearomative [4 + 2] Cycloaddition of Naphthalenes with Arylalkynes.

A Pd-catalyzed intramolecular dearomative [4 + 2] cycloaddition reaction of naphthalenes with arylalkynes is developed. The protocol provides a straightforward method to access a range of polycyclic dihydronaphthalenes containing two vicinal all-carbon stereocenters in moderate yields under mild conditions in an air atmosphere. The deuterium labeling experiment suggests a pathway involving electrophilic dearomatization followed by Friedel-Crafts cyclization. Several synthetic transformations of the product were conducted to demonstrate the utility of this reaction.

Laser Direct Writing of Sol-Gel-Derived Vacancy-Rich Functional Oxide Semiconductors.

Fabricating micro/nanostructures of oxide semiconductors with oxygen vacancies (OVs) is crucial for advancing miniaturized functional devices. However, traditional methods for the synthesis of semiconductor metal oxides (SMOs) with OVs usually involve thermal treatment, such as annealing or sintering, under anaerobic conditions. Herein, a multiphoton-induced femtosecond laser (fs) additive manufacturing method is reported for directly writing micropatterns with high resolution (∼1 µm) and abundant OVs in an atmospheric environment at room temperature (25 °C). The interdigitated functional devices fabricated by these micropatterns exhibit both photosensitivity and gas sensitivity. Additionally, this method can be applied to flexible and rigid substrates. The proposed method realizes the high-precision fabrication of SMOs with OVs, enabling the future heterogeneous integration of oxide semiconductors on various substrates, especially flexible substrates, for various device applications, such as soft and wearable electronics/optoelectronics.

Dearomatizing [2+2+1] Spiroannulation of Indoles with Alkynes.

A palladium-catalyzed dearomatizing [2+2+1] spiroannulation of indoles with two molecular internal alkynes is developed in the presence of Cu(OAc)2/O2 as the oxidant, in which a domino sequence including C-H activation of indole followed by consecutive Heck reactions is involved. A range of 3,3'-spiroindolines bearing tetrasubstituted cyclopentadiene moieties and exocyclic C═C bonds at C2 are obtained in moderate to excellent yields.

Palladium-Catalyzed Enantioselective Heteroarenyne Cycloisomerization Reaction.

The extensively developed ene-type enantioselective cycloisomerization of classical 1,n-enynes provides an efficient approach to chiral cyclic 1,4-dienes. In contrast, the catalytic asymmetric heteroarenyne (heteroarene-alkyne) cycloisomerization involving the dearomative transformation of endocyclic aromatic C=C bonds remains unknown. Herein, we communicate a PdH-catalyzed enantioselective heteroarenyne cycloisomerization reaction of alkyne-tethered indole substrates (formal 1,5- and 1,6-enynes). Based on this strategy, a variety of structurally diverse chiral spiro and fused indoline derivatives bearing quaternary stereocenters and exocyclic C=C bonds are afforded in moderate to excellent yields and excellent enantioselectivities (up to 98 % ee). The classical ene-type enantioselective 1,5-enyne cycloisomerization of N-vinylpropiolamides is also developed to afford chiral 2-pyrrolones in good to excellent ee values.

Host-guest fabrication of dual-responsive hyaluronic acid/mesoporous silica nanoparticle based drug delivery system for targeted cancer therapy.

In this paper, a targeting hyaluronic acid (HA)/mesoporous silica nanoparticle (MSN) based drug delivery system (DDS) with dual-responsiveness was prepared for cancer therapy. To avoid the side reaction between the anti-cancer drug doxorubicin hydrochloride (DOX) and HA, host-guest interaction was applied to fabricate the DDS named DOX@MSN-SS-N=C-HA. The "nanocontainer" MSN was modified with benzene ring via both pH-sensitive benzoic imine bond and redox-sensitive disulfide linkage. When DOX was loaded in the pores of MSN, the channels were then capped by the "gatekeeper" ß-CD grafted HA (HA-g-CD) through host-guest interaction between ß-CD and benzene. HA endowed the drug carriers with the targeting capability in CD44 over-expressed cancer cells. After cellular uptake, the carriers could rapidly release DOX for cell apoptosis due to both the hydrolysis of benzoic imine bond at low pH and the cleavage of disulfide bond at a high concentration of glutathione (GSH) intracellular. In vitro drug release studies and in vitro cytotoxicity studies were taken to investigate the dual-responsiveness of the carriers. And the CD44-receptor mediated cancer cell targeting capability was investigated as well. In conclusion, the targeted dual-responsive complex DDS fabricated through host-guest interaction has promising potential in cancer therapy.

A feedback circuit of miR-34a/MDM4/p53 regulates apoptosis in chronic lymphocytic leukemia cells.

BACKGROUND: Dysfunction of apoptosis is a significant characteristic in chronic lymphocytic leukemia (CLL). Murine double minute 4 (MDM4), miR-34a and TP53 are found to participate in modulating cellular apoptosis while the specific mechanism keeps unclear. This study was designed to investigate the potential feedback circuit among MDM4, miR-34a and TP53. METHODS: According to the bioinformatic approaches, there are 4 miR-34a candidate binding domains in MDM4. Use dual luciferase reporter gene to verify the regulation between miR-34a and MDM4. Flow cytometry was used to detect the change of apoptosis level in CLL cells before and after miR-34a mimics and shMDM4 were respectively transfected into primary CLL cells in vitro. Meanwhile, Real-time PCR was used to detect the change of RNA expression of MDM4, miR-34a and TP53. RESULTS: Up-regulated expression of miR-34a or down-regulated expression of MDM4 could increase apoptosis of CLL cells, inhibit expression of MDM4 and decrease expression of p53 in mRNA level compared to negative control (NC) or shNC (P<0.05). The luminescence of psiCHECK-2-MDM4 EXON 11 can be effectively inhibited by miR-34a (P<0.05). CONCLUSIONS: MiR-34a could modulate MDM4 by binding to MDM4 exon 11 instead of 3'UTR. This research thus highlights a forceful evidence for miR-34a/MDM4/p53 feedback circuit in CLL apoptosis.

Analysis of hazardous organic residues from sodium hydrosulfite industry and utilization as raw materials in a novel solid lubricant production.

The hazardous organic residual wastes produced by the sodium hydrosulfite industry are demonstrated to be convertible into a novel solid lubricant. Identification and isolation of the organic residues are achieved by Fourier transform infrared (FTIR) spectroscopy, gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR). FTIR and GC-MS provide important information about the residues and the two main components obtained by column chromatography are further analyzed by NMR. The main organic residues are found to be thiodiglycol and 2,2'-dithiodiethanol which have potential applications in petroleum drilling because of their S-S and/or C-S functional groups. The lubricity of the organic residues is subsequently studied and the influence of different adsorbents on the lubricity is investigated and discussed. This homemade lubricant is observed to have good lubricity and by increasing the concentration of the commercial solid lubricant M, the lubricity diminishes. The process is expected to not only have commercial impact but also help to reduce environmental pollution.

[Study on hyperuricemia with hyperlipaemia, high blood sugar and hypertension in 1320 elderly people].

OBJECTIVE: To investigate the prevalence of hyperuricemia with hyperlipaemia, high blood sugar and hypertension among elderly people. METHODS: Serum uric acid (SUA), cholesterol, triglycerides, blood sugar and blood pressure were detected in 1320 elderly people and 6107 people at young and middle age. RESULTS: The mean SUAs in elderly male and female groups were significantly higher than that in young and middle aged male groups respectively (P < 0.05). The prevalence rates of hyperuricemia in elderly male and female groups were significantly higher than in young and middle aged male groups respectively (P < 0.05). The prevalence rates of hyperlipaemia, high blood sugar and hypertension in the elderly people of hyperuricemia were significantly higher than that in the elderly people of normal serum uric acid (P < 0.05). The prevalence rates of hyperuricemia in the elderly people were complicated by hyperlipaemia, high blood sugar and hypertension which was significantly higher than that in young and middle aged people of hyperuricemia (P < 0.05). CONCLUSION: Hyperuricemia is a common disease in elderly people and more attention should be paid to the closer relations among hyperuricemia with hyperlipaemia, high blood sugar and hypertension among the elderly.