Ablation of PKM2 ameliorated ER stress-induced apoptosis and associated inflammation response in IL-1ß-treated chondrocytes via blocking Rspo2-mediated Wnt/ß-catenin signaling.

Endoplasmic reticulum (ER) stress and the related apoptosis and inflammation damage play key roles in osteoarthritis development. The aim of the present work was to investigate the exact role and potential underlying mechanism of pyruvate kinase M2 (PKM2) in rat chondrocytes exposed to interleukin-Iß (IL-1ß). We observed that IL-1ß stimulation resulted in an apparent enhancement in PKM2 expression. Additionally, loss of PKM2 evidently ascended cell viability in response to IL-1ß exposure. Simultaneously, elimination of PKM2 manifestly repressed IL-1ß-stimulated chondrocyte apoptosis, concomitant with attenuated in the proapoptotic protein markers Bax and cleaved caspase-3, and elevated the antiapoptotic protein Bcl-2. In the meanwhile, knockdown of PKM2 ameliorated ER stress in IL-1ß-treated chondrocytes, as evidenced by reduced expression of the ER stress-associated proteins GRP78, CHOP, and cleaved caspase-12. Furthermore, PKM2 silencing protected chondrocytes against IL-1ß-triggered inflammatory response, as reflected by the downregulated release of proinflammatory mediators, including tumor necrosis factor-α, IL-6, inducible nitric oxide synthase, cyclooxygenase-2, and prostaglandin E2, as well as decreased nitric oxide generation. More important, abrogating PKM2 expression caused a marked decline in Rspo2 expression, and subsequently blocked Wnt/ß-catenin signaling. Mechanistically, the Wnt/ß-catenin signaling activator Licl effectively impeded the beneficial effects of PKM2 ablation on IL-1ß-stimulated apoptosis and inflammatory response. These findings collectively implicated that PKM2 inhibition protected against ER stress-mediated cell apoptosis and inflammatory injury in rat chondrocytes stimulated with IL-1ß by inactivating Rspo2-mediated Wnt/ß-catenin pathway, and may represented a novel therapeutic target for osteoarthritis.

Controllable Synthesis of Organic Microcrystals with Tunable Emission Color and Morphology Based on Molecular Packing Mode.

Organic microcrystals are of essential importance for high fluorescence efficiency, ordered molecular packing mode, minimized defects, and smooth shapes, which are extensively applied in organic optoelectronics. The molecular packing mode significantly influences the optical/electrical properties of organic microcrystals, which makes the controllable preparation of organic microcrystals with desired molecular packing mode extremely important. In the study, yellow-emissive α phase organic microcrystals with rectangular morphology and green-emissive ß phase perylene microcrystals with rhombic morphology are separately prepared by simply controlling the solution concentration. The distinct molecular staking modes of the H/J-aggregate are found in these two types of perylene microcrystals, which contribute to the different emission color, morphology, and radiative decay rate. What is more interesting, the α-doped ß phase and the ß-doped α phase organic microcrystals can also be fabricated by modulating the evaporation rate from 100 to 10 µL min-1 . The findings can contribute to the future development of organic optoelectronics at the microscale.

White-Emissive Self-Assembled Organic Microcrystals.

Organic semiconductor micro-/nanocrystals with regular shapes have been demonstrated for many applications, such as organic field-effect transistors, organic waveguide devices, organic solid-state lasers, and therefore are inherently ideal building blocks for the key circuits in the next generation of miniaturized optoelectronics. In the study, blue-emissive organic molecules of 1,4-bis(2-methylstyryl)benzene (o-MSB) can assemble into rectangular microcrystals at a large scale via the room-temperature solution-exchange method. Because of the Förster resonance energy transfer, the energy of the absorbed photons by the host matrix organic molecules of o-MSB can directly transfer to the dopant organic molecules of tetracene or 1,2:8,9-dibenzopentacene (DBP), which then emit visible photons in different colors from blue to green, and to yellow. More impressively, by modulating the doping molar ratios of DBP to o-MSB, bright white-emissive organic microcrystals with well-preserved rectangular morphology can be successfully achieved with a low doping ratio of 1.5%. These self-assembled organic semiconductor microcrystals with multicolor emissions can be the white-light sources for the integrated optical circuits at micro-/nanoscale.

Surgical site infection after laparoscopic and open appendectomy: a multicenter large consecutive cohort study.

BACKGROUND: Laparoscopic appendectomy (LA) has been rapidly applied worldwide recently. The issue of surgical site infection (SSI) after appendectomy needs to be re-investigated and analyzed along with this trend. This study aimed to identify risk factors of SSI after appendectomy in recent years. METHODS: This retrospective study was conducted among patients with acute appendicitis who underwent either laparoscopic or open appendectomy (OA) at 7 general hospitals in China from 2010 to 2013. The incidence of SSI, classified as incisional SSI and organ/space SSI, was investigated. A multivariate logistic regression model was used to assess independent risk factors associated with overall, incisional, and organ/space SSI, respectively. RESULTS: Among 16,263 consecutive patients, 3,422 (21.0 %) and 12,841 (79.0 %) patients underwent LA and OA, respectively. The incidences of overall, incisional, and organ/space SSI were 6.2, 3.7, and 3.0 %, respectively. The proportion of LAs among both procedures increased yearly from 5.3 to 46.5 %, while the incidences of overall and incisional SSI after appendectomy simultaneously decreased yearly from 9.6 to 4.5 % and from 6.7 to 2.2 %, respectively. In comparison with OA, LA was associated with lower incidences of overall and incisional SSI (4.5 vs 6.7 %, P < 0.001; and 1.9 vs 4.2 %, P < 0.001), but a similar incidence of organ/space SSI (3.0 vs 3.0 %, P = 0.995). After multivariate logistic regression analyses were performed, LA was found to be independently associated with a decrease in development of overall SSI [odds ratio (95 % confidence interval) OR (95 % CI), 1.24 (1.03-1.70); P = 0.04] or incisional SSI [OR (95 % CI), 1.32 (1.10-1.68); P = 0.01]. CONCLUSION: With the increasing application trends of laparoscopic procedure, the incidence of SSI after appendectomy declined accordingly. Compared with OA, LA was independently associated with a significantly lower incidence of incisional SSI, but a similar incidence of organ/space SSI.

MiR-22 restrains proliferation of rheumatoid arthritis by targeting IL6R and may be concerned with the suppression of NF-κB pathway.

It has demonstrated that miR-22 overexpression can suppress the inflammation process of rheumatoid arthritis (RA) in synoviocytes. But, the underlying mechanism of miR-22 expression in regulating RA is still not well illustrated. In this study, we investigated the functional role and underlying mechanism of miR-22 in regulating RA. Human RA fibroblast-like synoviocyte (FLS) cell line MH7A cells was transfected by miR-22 mimic and its control. CCK8 was utilized to detect cell proliferation. Cell apoptosis was analyzed by flow cytometry. MH7A cells stimulating with interleukin-1ß (IL-1ß) were transfected with miR-22 mimic. Quantitative real time polymerase chain reaction (qRT-PCR) and western blot assays were utilized to detect mRNA and protein expression. miR-22 targets were predicted and validated by Targetscan and luciferase reporter assay. We revealed that miR-22 showed downregulated expression in MH7A after stimulation with IL-1ß. Additionally, miR-22 overexpression suppressed the proliferation and facilitated apoptosis in MH7A cells. IL6R was a target of miR-22. Besides, miR-22 overexpression inhibited the expression of IL6R and also suppressed inflammatory pathway NF-κB. These results indicated that miR-22 overexpression could restrain the activity of inflammation cells in RA by targeting IL6R and might be concerned with the inhibition of NF-κB pathway.

Low-Threshold Organic Lasers Based on Single-Crystalline Microribbons of Aggregation-Induced Emission Luminogens.

Solid-state lasers (SSLs) play an important role in developing optoelectronic devices, optical communication, and modern medicine fields. As compared with inorganic SSLs, the electrically pumped organic SSLs (OSSLs) still remain unrealized because of the high lasing threshold and low carrier mobility. Herein, we first demonstrate the laser action at ∼520 nm based on the self-assembled single-crystalline organic microribbons of the aggregation-induced emission (AIE) molecules of 1,4-bis(( E)-4-(1,2,2-triphenylvinyl)styryl)-2,5-dimethoxybenzene (TPDSB). Moreover, these as-prepared organic microribbons exhibit an effective optical waveguide with a low optical loss of 0.012 dB µm-1, indicating good light confinement for laser resonator feedback. Impressively, the multiple mode and the single mode lasing are both achieved from individual organic microribbons, whose lasing threshold is as low as 653 nJ cm-2. These "bottom-up" synthesized organic microribbons based on AIE-active molecules offer a new strategy for the realization of the ultralow threshold OSSLs, which would eventually contribute to the realization of electrically pumped OSSLs.

Controlled synthesis of organic single-crystalline nanowires via the synergy approach of the bottom-up/top-down processes.

The controlled fabrication of organic single-crystalline nanowires (OSCNWs) with a uniform diameter in the nanoscale via the bottom-up approach, which is just based on weak intermolecular interaction, is a great challenge. Herein, we utilize the synergy approach of the bottom-up and the top-down processes to fabricate OSCNWs with diameters of 120 ± 10 nm through stepwise evolution processes. Specifically, the evolution processes vary from the self-assembled organic micro-rods with a quadrangular pyramid-like end-structure bounded with {111}s and {11-1}s crystal planes to the "top-down" synthesized organic micro-rods with the flat cross-sectional {002}s plane, to the organic micro-tubes with a wall thickness of ∼115 nm, and finally to the organic nanowires. Notably, the anisotropic etching process caused by the protic solvent molecules (such as ethanol) is crucial for the evolution of the morphology throughout the whole top-down process. Therefore, our demonstration opens a new avenue for the controlled-fabrication of organic nanowires, and also contributes to the development of nanowire-based organic optoelectronics such as organic nanowire lasers.

Fluorescence/phosphorescence-conversion in self-assembled organic microcrystals.

Organic molecules of DIDB can inherently assemble into fluorescent green-emissive microwires with a low photoluminescence quantum efficiency (PLQY) of 1.0%. Impressively, by doping DIDB into the nonluminous 4-iodobenzonitrile crystal matrix with a molar ratio of 1 : 100, phosphorescent yellow-emissive microwires with a much higher PLQY of 50.5% are obtained.