Dosimetric feasibility of stereotactic ablative radiotherapy in pulmonary vein isolation for atrial fibrillation using intensity-modulated proton therapy.

PURPOSE: To evaluate dosimetric properties of intensity-modulated proton therapy (IMPT) for simulated treatment planning in patients with atrial fibrillation (AF) targeting left atrial-pulmonary vein junction (LA-PVJ), in comparison with volumetric-modulated arc therapy (VMAT) and helical tomotherapy (TOMO). METHODS: Ten thoracic 4D-CT scans with respiratory motion and one with cardiac motion were used for the study. Ten respiratory 4D-CTs were planned with VMAT, TOMO, and IMPT for simulated AF. Targets at the LA-PVJ were defined as wide-area circumferential ablation line. A single fraction of 25 Gy was prescribed to all plans. The interplay effects from cardiac motion were evaluated based on the cardiac 4D-CT scan. Dose-volume histograms (DVHs) of the ITV and normal tissues were compared. Statistical analysis was evaluated via one-way Repeated-Measures ANOVA and Friedman's test with Bonferroni's multiple comparisons test. RESULTS: The median volume of ITV was 8.72cc. All plans had adequate target coverage (V23.75Gy  ≥ 99%). Compared with VMAT and TOMO, IMPT resulted in significantly lower dose of most normal tissues. For VMAT, TOMO, and IMPT plans, Dmean of the whole heart was 5.52 ± 0.90 Gy, 5.89 ± 0.78 Gy, and 3.01 ± 0.57 Gy (P < 0.001), mean dose of pericardium was 4.74 ± 0.76 Gy, 4.98 ± 0.62 Gy, and 2.59 ± 0.44 Gy (P < 0.001), and D0.03cc of left circumflex artery (LCX) was 13.96 ± 5.45 Gy, 14.34 ± 5.91 Gy, and 8.43 ± 7.24 Gy (P < 0.001), respectively. However, no significant advantage for one technique over the others was observed when examining the D0.03cc of esophagus and main bronchi. CONCLUSIONS: IMPT targeting LA-PVJ for patients with AF has high potential to reduce dose to surrounding tissues compared to VMAT or TOMO. Motion mitigation techniques are critical for a particle-therapy approach.

LncRNA AK148321 alleviates neuroinflammation in LPS-stimulated BV2 microglial cell through regulating microRNA-1199-5p/HSPA5 axis.

AIMS: Dysregulated long non-coding RNA (lncRNA) expression is closely related to neuroinflammation, leading to multiple neurodegenerative diseases. In this study, we investigated the function and regulation of lncRNA AK148321 in neuroinflammation using an in vitro lipopolysaccharide (LPS)-stimulated BV2 microglial cell system. METHODS: Expression of AK148321 was analyzed by qPCR. Inflammatory cytokine expression levels were determined by ELISA assay. The interaction between AK148321, microRNA (miRNA), and its target gene was validated by luciferase reporter assay and RNA immunoprecipitation (RIP). Cell apoptosis was analyzed by Annexin V/PI staining. RESULTS: LPS treatment suppressed AK148321 expression in BV2 cells. Overexpression of AK148321 inhibited LPS-induced BV2 microglial cell activation and decreased the expression of inflammatory cytokine TNF-α and IL-1ß. AK148321 function as a competing endogenous RNA (ceRNA) by sponging microRNA-1199-5p (MiR-1199-5p). In LPS-stimulated BV2 cells, AK148321 exerted its inhibitory function via negatively modulating miR-1199-5p expression. Moreover, we identified that Heat Shock Protein Family A Member 5 (HSPA5) was a direct target of miR-1199-5p. RIP assay using the anti-Ago2 antibody further validated the relationship among AK148321, miR-1199-5p and HSPA5. The AK148321/miR-1199-5p/HSPA5 axis regulated the neuroinflammation in LPS-induced BV2 microglial cells. Microglial cell culture supernatant from LPS-stimulated, AK148321-overexpressing BV2 cells suppressed the cell apoptosis of mouse hippocampal neuronal cell HT22, while HSPA5 knockdown abrogated the suppression effect. CONCLUSION: Our findings suggest that AK148321 alleviates neuroinflammation in LPS-stimulated BV2 microglial cells through miR-1199-5p/HSPA5 axis.

Parafoveal retinal massage combined with autologous blood cover in the management of giant, persistent or recurrent macular holes.

AIM: To assess the efficacy and safety of parafoveal retinal massage combined with autologous whole blood cover in the treatment of refractory macular holes (MHs) and present the surgical procedure. METHODS: Patients with giant (minimum diameter ≥800 µm), recurrent or persistent MHs who underwent PPV combined with parafoveal retinal massage and autologous whole blood cover using C3F8 as tamponade agent from February 2018 to May 2019 were enrolled in this retrospective study. After surgery, all patients were informed to maintain a prone position for at least 7d. Preoperative and postoperative best-corrected visual acuities (BCVAs) were compared and MH closure rate was measured as the main outcome. RESULTS: A total of 13 MH patients consisted of 6 giant MHs, 4 persistent holes and 3 recurrent holes (5 men and 8 women; average age was 56.40±11.72y) were enrolled in this study. MH closure was achieved in 11 eyes by this modified surgical technique while 2 eyes failed. Revitrectomy with autologous neurosensory retinal patch transplantations was applied for those 2 patients and then both holes were closed. No intraoperative complications were observed. BCVA improved from 1.73 logMAR to 0.74 logMAR at 6mo postoperation. There was significant difference in BCVA before versus after the surgery (P<0.05). There were no adverse events occurred during the follow-up period. CONCLUSION: With easier surgical procedure, parafoveal retinal massage combined with autologous whole blood cover is an effective addition to the surgical options for the management of refractory MHs.

Synthesis of Tetrahydroindolizino[8,7-b]indole Derivatives in the Presence of Fe(OTf)3 or CF3SO3H through Intramolecular Dearomatization of Indole.

We have developed a convenient synthesis of tetrahydroindolizino[8,7-b]indole derivatives via intramolecular dearomatization of indole. Highly functionalized tetrahydroindolizinoindoles can be prepared in the presence of trifluoromethanesulfonic acid in good to excellent yields (up to >99% yield) with novel designed pyrrole-tethered indoles. The same products can also be synthesized through a mild Fe(OTf)3-catalyzed process in acceptable to good yields (up to 75% yield).

Three Cases of Leber's Hereditary Optic Neuropathy with Rapid Increase in Visual Acuity After Gene Therapy.

BACKGROUND: During the first few trials of gene therapy for Leber's hereditary optic neuropathy performed by our group, the visual acuity of the patients increased gradually over several months, or even years. However, in the current round of gene therapy for Leber's hereditary optic neuropathy, we noted that the visual acuity of three patients increased rapidly, within a few days after treatment. CASE PRESENTATION: Three patients who were diagnosed with mitochondrial gene 11778 mutation (associated with a G-to-A transition at Mt-11778 in the ND4 subunit gene of complex I of mitochondrial DNA that changes an arginine to histidine at amino acid 340) by genetic diagnosis were followed up three times before gene therapy, which lasted for 1 year, without spontaneous improvement of vision. Visual acuity in one or both eyes of each of the three patients increased rapidly after the initial gene therapy treatment. CONCLUSION: We suspect that in some patients with Leber's hereditary optic neuropathy, a portion of the retinal ganglion cells might remain in a "dormant" state for a certain period of time; these may be activated, within an optimal timeframe, during gene therapy for Leber's hereditary optic neuropathy.

Synthesis of Benzoindolizines through 1,5-Electrocyclization/Oxidation Cascades.

This study presents a convenient synthesis of pyrrolo[1,2- a]quinolines and pyrrolo[2,1- a]isoquinolines with simple quinolines or isoquinolines and Morita-Baylis-Hillman carbonates in the presence of copper acetate. A range of functionalized benzoindolizines could be assembled through an SN2'/deprotonation/1,5-electrocyclization/oxidation cascade pathway in a one-step process.

Catalyst-free [3 + 2] cyclization of dihydroisoquinoline imines and isatin-derived Morita-Baylis-Hillman carbonates via 1,5-electrocyclization: synthesis of tetrahydroisoquinoline-fused spirooxindoles.

We have developed a mild and scalable catalyst-free [3 + 2] cyclization of dihydroisoquinolines and isatin-derived Morita-Baylis-Hillman carbonates. The incorporation of tetrahydroisoquinoline and spirooxindole frameworks could be realized affording highly functionalized heterocycles in moderate to excellent yields with good diastereocontrols (up to 92% yields, >20 : 1 dr). The extension of this method to dihydro-ß-carbolines has also been achieved. A gram-scale reaction could be performed successfully enabling the potential application for further biomedical research.

5,5'-Diazaisoindigo: an Electron-Deficient Building Block for Donor-Acceptor Conjugated Polymers.

A novel electron-deficient building block, 5,5'-diazaisoindigo (5DNIID), was synthesized through a facile method in good yield. As a derivative of isoindigo, 5DNIID shows an ultra-low LUMO level of -3.92 eV after incorporation of two electron-deficient nitrogen atoms into the para-position of the amine groups in the isoindigo π skeleton. Modified polymerization conditions were applied to efficiently afford the donor-acceptor (D-A) conjugated polymer 5DNIID-2T, which exhibited a p-type charge transport property.

[Study on the Micro-FTIR Spectra of the Euhedral Faceted Polycrystalline Diamonds (EFPCDs) from Western Yangtze Craton and Its Geological Significance].

The results of Micro-FTIR spectra analysis of the euhedral faceted polycrystalline diamonds (EFPCDs) from the Western Yangtze Craton show that the EFPCDs are mostly IaAB type, the concentration of nitrogen.varies greatly from 25. 70- 358.35 µg x g(-1). Different nitrogen content distributes in different diamond grains or position in same sample. The C Center was not found in the samples and the conversion from A center to B center is incomplete, in the meanwhile, B% value concentrated in 40%. Thus, polycrystalline diamonds are not formed in the stage of nucleation but gathered together after formation of the individual diamond grains during the residence time in the mantle. And its formation environment is. more complex than the euhedral faceted polycrystalline diamonds from Mengyin kimberlite, the Eastern of North China Craton. The diamonds extremely possibly originated in the deep mantle from 160 to 180 km, reaching the depth of the core of the Yangtze Craton, at the same time it is close to the bottom of the lithosphere. The C-H bond of sp2 hybridization are conducive to the formation of platelets in diamonds. Meanwhile, its concentrations are generally higher than the C-H bond of sp3 hybridization in the samples.

A new piezochromic fluorescence and aggregation-induced emission compound containing tetraphenylethylene and triphenylamine moieties with morphology-alterable property.

A novel piezochromic fluorescent (PCF) compound with aggregation-induced emission (AIE) effect and morphology-alterable emission property was developed. The amorphous and crystalline aggregates were obtained, and their spectroscopic properties and morphological structures were reversibly and repeatedly exhibited upon pressing (fuming) or annealing. The piezochromic fluorescent nature was generated through crystalline-amorphous phase transformation. It was proposed that AIE compounds existing a twisted propeller-shaped conformation will exhibit PCF activity. The common relationship betweeen AIE and PCF established will guide researchers in identifying and synthesizing more piezochromic fluorescent materials.

Synthesis and characterization of triphenylethylene derivatives with aggregation-induced emission characteristics.

New aggregation-induced emission (AIE) compounds derived from triphenylethylene were synthesized. The thermal, photophysical, electrochemical and aggregation-induced emissive properties were investigated. All the compounds had strong blue light emission capability and good thermal stability. Their maximum fluorescence emission wavelengths were between 443 to 461 nm in solid states, while their glass transition temperatures ranged from 86 to 129 °C. The decomposition temperatures of the synthesized compounds were in the range of 432-534 °C. The synthesized compounds possessed aggregation-induced emission properties, namely exhibited enhanced fluorescence emission in aggregated states. The highest occupied molecular orbital (HOMO) energy levels estimated from the oxidation potentials were between 5.61 and 5.66 eV and the lowest unoccupied molecular orbital/highest occupied molecular orbital (LUMO/HOMO) energy gap values were found to be in the range of 3.18-3.22 eV. The compounds 4-(4-(2,2-bis(4-(naphthalen-1-yl)phenyl)vinyl)phenyl) dibenzothiophene [(BN)(2)Bt] and 4-(4-(2,2-di(biphenyl-4-yl)vinyl)phenyl) dibenzothiophene [(BB)(2)Bt] exhibited vibronic fine-structure photoluminescence spectra when the water fraction was less than 70%.

Comparison of responsive behaviors of two cinnamic acid derivatives containing carbazolyl triphenylethylene.

Two cinnamic acid derivatives (CPA and CPC) containing carbazolyl triphenylethylene moiety have been synthesized and characterized. The two derivatives possessed aggregation-induced emission property. They exhibited different and interesting responsive behaviors to solvents, water and metal ions. Considering the structural differences between the two derivatives resulting in different interactions between their molecules and the various media was proposed as a possible explanation for these observations. The intermolecular interactions of CPC were much stronger than those of CPA, which promoted molecular association through intermolecular hydrogen bonding to form multimers. It was found that CPC and CPA exhibited high sensitivity to K(+) and Mn(2+), respectively. It is suggested that the derivatives have potential technological applications in chemosensor fields.

Synthesis and properties of diphenylcarbazole triphenylethylene derivatives with aggregation-induced emission, blue light emission and high thermal stability.

New aggregation-induced emission materials derived from diphenylcarbazole triphenylethylene were prepared. The thermal, photophysical, electrochemical and aggregation-induced emissive properties were investigated. All the compounds had strong blue light emission capability and excellent thermal stability. Their maximum fluorescence emission wavelengths were between 450 to 460 nm in TLC plates, while their glass transition temperatures ranged from 162.2 to 182.4 °C. The decomposition temperatures of the synthesized compounds were all well over 500 °C. The synthesized compounds possessed aggregation-induced emission (AIE) properties, which exhibited enhanced fluorescence emissions in aggregation states or in solid states. The HOMO energy levels estimated from the oxidation potentials were found in the range from 5.49 to5.52 eV. The lowest unoccupied molecular orbital/highest occupied molecular orbital (LUMO/HOMO) energy gaps (ΔEg) for the compounds were estimated from the onset absorption wavelengths of UV absorption spectra and ranged from 3.04 to 3.20 eV.

Assessment criteria for rotated stereociliary bundles in the guinea pig cochlea.

OBJECTIVE: Our study examined the relationship between variant stereociliary bundles of cochlear outer hair cells (OHCs) and auditory function to analyze assessment criteria for rotated stereociliary bundles in the guinea pig cochlea. METHODS: Auditory brainstem response and distortion product otoacoustic emission (DPOAE) were recorded on 100 guinea pigs. Variant hair cells were identified and counted by scanning electron and light microscopy. RESULTS: The most common variation observed was rotation of stereociliary bundles in the first-row OHCs (OHC1), with most 13.3% variant OHC1 rotated 90 degrees and a few 2.5% rotated 180 degrees. Occasionally, the length and angle of the 2 arms of an OHC deviated from the norm. The auditory brainstem response threshold of affected animals increased only slightly, 20- to 30-dB sound pressure level. More importantly, amplitude of DPOAE increased significantly (40.5 dB sound pressure level). CONCLUSION: Our study suggests that rotation of stereociliary bundles in the cochlear OHC was found to be prevalent in 28% of the animals. We established the assessment criteria for rotated stereociliary bundles that were more than 10% OHC1 rotated. This hair bundle seemed to be rotated by 90 degrees from the normal orientation and was accompanied with changes of auditory function. Increased amplitude of DPOAE is associated with the variation of rotated OHC that might result in hearing loss.