Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04563936.

Ureteral- artificial iliac artery fistula: A case report.

BACKGROUND: Ureteral-iliac artery fistula is a rare disease resulting from the pathological connection between the ureter and iliac artery, with artificial iliac artery-ureteral fistula being rarer. Iliac artery ureteral fistula is challenging to diagnose, and the misdiagnosis and mortality rates are high. CASE SUMMARY: A case of artificial iliac artery ureteral fistula was reported in this paper. The patient was a 69-year-old male with paroxysmal painless hematuria. The artificial iliac artery ureteral fistula was diagnosed by angiography. The hematuria was stopped after intravascular embolization, and no bleeding occurred after 6 months of follow-up. CONCLUSION: Ureteral arterial fistula should be considered when inconspicuous hematuria with previous iliac vessels is encountered in addition to local ureteral surgery history. A rapid endovascular approach is recommended for fistula identification.

Several Key Factors for Efficient Electrocatalytic Water Splitting: Active Site Coordination Environment, Morphology Changes and Intermediates Identification.

Water-splitting has emerged as a promising alternative strategy to produce clean hydrogen fuel. However, current electrocatalytic water splitting suffers from sluggish kinetics, thus developing efficient electrocatalysts is crucial. Identifying reaction centers discloses the reaction mechanism and will undoubtedly facilitate the design and optimization of efficient water splitting electrocatalysts. This review summarizes several advances involving the identification of the actual active sites and intermediates capture on the catalytic surface. The morphology and valence states change on 2D materials are chose to illustrate how structural evolution affect catalytic activity. Specifically, in situ/ex situ electron microscopy techniques that used for the characterization of catalytic sites, and spectroscopy techniques that used to detect active intermediates at the molecular level are highlighted. In addition, several perspectives, such as the development of new in situ techniques and electrokinetic analysis methods, are emphasized to shed light on future research.

High-performance large-area quasi-2D perovskite light-emitting diodes.

Serious performance decline arose for perovskite light-emitting diodes (PeLEDs) once the active area was enlarged. Here we investigate the failure mechanism of the widespread active film fabrication method; and ascribe severe phase-segregation to be the reason. We thereby introduce L-Norvaline to construct a COO--coordinated intermediate phase with low formation enthalpy. The new intermediate phase changes the crystallization pathway, thereby suppressing the phase-segregation. Accordingly, high-quality large-area quasi-2D films with desirable properties are obtained. Based on this, we further rationally adjusted films' recombination kinetics. We reported a series of highly-efficient green quasi-2D PeLEDs with active areas of 9.0 cm2. The peak EQE of 16.4% is achieved in = 3, represent the most efficient large-area PeLEDs yet. Meanwhile, high brightness device with luminance up to 9.1 × 104 cd m-2 has achieved in = 10 film.

High-performance quasi-2D perovskite light-emitting diodes: from materials to devices.

Quasi-two-dimensional (quasi-2D) perovskites have attracted extraordinary attention due to their superior semiconducting properties and have emerged as one of the most promising materials for next-generation light-emitting diodes (LEDs). The outstanding optical properties originate from their structural characteristics. In particular, the inherent quantum-well structure endows them with a large exciton binding energy due to the strong dielectric- and quantum-confinement effects; the corresponding energy transfer among different n-value species thus results in high photoluminescence quantum yields (PLQYs), particularly at low excitation intensities. The review herein presents an overview of the inherent properties of quasi-2D perovskite materials, the corresponding energy transfer and spectral tunability methodologies for thin films, as well as their application in high-performance LEDs. We then summarize the challenges and potential research directions towards developing high-performance and stable quasi-2D PeLEDs. The review thus provides a systematic and timely summary for the community to deepen the understanding of quasi-2D perovskite materials and resulting LED devices.

Energy-Funneling Process in Quasi-2D Perovskite Light-Emitting Diodes.

Quasi-two-dimensional (quasi-2D) perovskites, demonstrating excellent radiative efficiency and facile processability, have been considered as next-generation materials for light-emitting applications. Quasi-2D perovskites with a unique energy-funneling process offer an approach to achieve not only high photoluminescence quantum yields at low excitation but also tunable emission induced by dielectric and quantum confinement. In this Perspective, we highlight the mechanism of the energy-funneling process and discuss the salient position of it in quasi-2D perovskite materials for light-emitting applications; we then present the significance of component and molecular engineering strategies for the energy-funneling process to meet the requirements of stable emission and display technologies. Considering present achievements, we also provide promising directions for future advancements of quasi-2D perovskite materials. We hope this Perspective can provide a new viewpoint for researchers to encourage the commercial progress of quasi-2D perovskites for light-emitting applications.

Reducing the impact of Auger recombination in quasi-2D perovskite light-emitting diodes.

Rapid Auger recombination represents an important challenge faced by quasi-2D perovskites, which induces resulting perovskite light-emitting diodes' (PeLEDs) efficiency roll-off. In principle, Auger recombination rate is proportional to materials' exciton binding energy (Eb). Thus, Auger recombination can be suppressed by reducing the corresponding materials' Eb. Here, a polar molecule, p-fluorophenethylammonium, is employed to generate quasi-2D perovskites with reduced Eb. Recombination kinetics reveal the Auger recombination rate does decrease to one-order-of magnitude lower compared to its PEA+ analogues. After effective passivation, nonradiative recombination is greatly suppressed, which enables resulting films to exhibit outstanding photoluminescence quantum yields in a broad range of excitation density. We herein demonstrate the very efficient PeLEDs with a peak external quantum efficiency of 20.36%. More importantly, devices exhibit a record luminance of 82,480 cd m-2 due to the suppressed efficiency roll-off, which represent one of the brightest visible PeLEDs yet.

Spectra stable blue perovskite light-emitting diodes.

Device performance and in particular device stability for blue perovskite light-emitting diodes (PeLEDs) remain considerable challenges for the whole community. In this manuscript, we conceive an approach by tuning the 'A-site' cation composition of perovskites to develop blue-emitters. We herein report a Rubidium-Cesium alloyed, quasi-two-dimensional perovskite and demonstrate its great potential for pure-blue PeLED applications. Composition engineering and in-situ passivation are conducted to further improve the material's emission property and stabilities. Consequently, we get a prominent film photoluminescence quantum yield of around 82% under low excitation density. Encouraged by these findings, we finally achieve a spectra-stable blue PeLED with the peak external quantum efficiency of 1.35% and a half-lifetime of 14.5 min, representing the most efficient and stable pure-blue PeLEDs reported so far. The strategy is also demonstrated to be able to generate efficient perovskite blue emitters and PeLEDs in the whole blue spectral region (from 454 to 492 nm).

Daphnetin protects hippocampal neurons from oxygen-glucose deprivation-induced injury.

Daphnetin, a coumarin derivative extracted from Daphne odora var., was reported to possess a neuroprotective effect. Recently, it has been demonstrated that daphnetin attenuates ischemia/reperfusion (I/R) injury. However, the role of daphnetin in cerebral I/R injury and the potential mechanism have not been fully understood. The present study aimed to explore the regulatory roles of daphnetin on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cell injury in a model of hippocampal neurons. Our results demonstrated that daphnetin improved cell viability and reduced the lactate dehydrogenase leakage in OGD/R-stimulated hippocampal neurons. In addition, daphnetin inhibited oxidative stress and cell apoptosis in hippocampal neurons after OGD/R stimulation. Furthermore, daphnetin significantly enhanced the nuclear translocation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression in hippocampal neurons exposed to OGD/R. Knockdown of Nrf2 blocked the protective effect of daphnetin on OGD/R-induced hippocampal neurons. In conclusion, these findings demonstrated that daphnetin attenuated oxidative stress and neuronal apoptosis after OGD/R injury through the activation of the Nrf2/HO-1 signaling pathway in hippocampal neurons. Thus, daphnetin may be a novel therapeutic agent for cerebral I/R injury.

Impact of environmental bacterial communities on fish health in marine recirculating aquaculture systems.

Marine cultured fish diseases caused by bacteria in recirculating aquaculture systems (RASs) greatly threaten fish aquaculture. To date, the dynamics of bacterial populations in RAS and their impacts to fish health remain largely unknown. In the present study, the bacterial communities in the water from two different marine RASs were analyzed using pyrosequencing technique. Fish disease syndromes and mortality had been reported from one RAS (RAS-d) while the fish in the other RAS remained healthy (RAS-h). The diversity of bacteria in each RAS and the abundance of each bacterium were identified based on sequencing the V4 hypervariable region of the 16S rRNA gene. A total number of 107,476 effective sequences were obtained from the pyrosequencing results. 640 and 844 operational taxonomic units (OTUs) were identified in RAS-d and RAS-h, respectively. In order level, tags annotation showed that Vibrionales and Flavobacteriales were the predominant strains in RAS-d with a relative abundance 50.5% and 36.5%, respectively. In contrast, the bacterial community in RAS-h contained 35.8% Vibrionales, 17.3% Alteromonadales, 10.7% Rhodobacterales, 7.43% Kordiimonadales, and 6.26% Oceanospirillales. In addition, the Vibrionaceae in the RAS-d represented 6.98% of the population which was significantly higher than that in RAS-h (0.40%). More potential pathogenic bacteria in fish, such as Vibrio harveyi, Vibrio rotiferianus were also found in the bacterial population in RAS-d. The results also showed that the bacteria community in RAS-h was more diverse and balanced than in RAS-d. These findings of this study suggested a potential correlation between fish diseases and environmental bacterial populations.

Molecular characterization and expression analysis of ATP-gated P2X7 receptor involved in Japanese flounder (Paralichthys olivaceus) innate immune response.

ATP-gated P2X7 receptor (P2RX7) channel is a key component for purinergic signaling and plays important roles in the innate immune response in mammals. However, the expression, molecular properties and immune significances of P2RX7 in lower vertebrates are still very limited. Here we identified and characterized a novel bony fish P2RX7 homologue cDNA, termed poP2RX7, in Japanese flounder (Paralichthys olivaceus). PoP2RX7 protein shares about 60-88% sequence similarity and 45-78% sequence identity with known vertebrate P2RX7 proteins. Phylogenetic analysis placed poP2RX7 and other P2RX7 proteins within their own cluster apart from other P2RX members. While the functional poP2RX7 channel shares structural features in common with known P2RX7 homologs, electrophysiological studies revealed that BzATP, the more potent agonist for known mammalian and fish P2RX7s, shows similar potency to ATP in poP2RX7 activation. poP2RX7 mRNA constitutively expressed in all examined tissues from unstimulated healthy Japanese flounder with dominant expression in hepatopancreas and the lowest expression in head kidney, trunk kidney, spleen and gill. poP2RX7 mRNA expression, however, was significantly induced in Japanese flounder head kidney primary cells by Poly(I:C) and bacterial endotoxin LPS stimulations. In vivo experiments further revealed that poP2RX7 gene expression was substantially up-regulated by immune challenge with infectious bacteria Edwardsiella tarda and Vibrio anguillarum. Moreover, activation of poP2RX7 results in an increased gene expression of multifunctional cytokines IL-1ß and IL-6 in the head kidney primary cells. Collectively, we identified and characterized a novel fish P2RX7 homolog which is engaged in Japanese flounder innate immune response probably through modulation of pro-inflammatory cytokines expression.

Identification and characterization of lipopolysaccharide-induced TNF-alpha factor gene from Japanese flounder Paralichthys olivaceus.

Lipopolysaccharide-induced TNF-α factor (LITAF) is an important transcription factor participating in innate immunity through regulating TNF-α and other inflammatory cytokines expression. However, the expression and biological relevance of LITAF in fish is still very limited. In this study, a full-length LITAF cDNA, termed PoLITAF, was identified from Japanese flounder Paralichthys olivaceus. PoLITAF contains a 67 bp 5'-untranslated sequence, a 435 bp open reading frame, and a 647 bp 3'-untranslated sequence. PoLITAF protein is comprised of 144 amino acids with a conserved C-terminal LITAF-like domain and shows 51-76% sequence similarity and 40-65% sequence identity with other LITAF homologues. Characterization of this new gene revealed that PoLITAF mRNA was detected in all examined tissues with the highest expression in gill. In head kidney primary culture, the expression of Japanese flounder PoLITAF and TNF-α was significantly up-regulated in response to Poly(I:C) and bacterial endotoxin LPS stimulation. Further in vivo experiments demonstrated that PoLITAF expression was up-regulated in head kidney, gill and spleen post bacterial challenge with Edwardsiella tarda. Moreover, the up-regulated expression of Japanese flounder TNF-α following the enhanced expression of PoLITAF was detected as early as 4h in both gill and head kidney tissues and 12h in spleen after the bacterial infection in vivo. Our findings suggest that PoLITAF is a novel inducible gene possibly involved in Japanese flounder innate immunity.

Verrucisidinol and verrucosidinol acetate, two pyrone-type polyketides isolated from a marine derived fungus, Penicillium aurantiogriseum.

The new secondary metabolites verrucosidinol (1) and its derivative verrucosidinol acetate (2), together with a potent neurotoxin verrucosidin (3), a congener norverrucosidin (4) and a mixture of two known phytotoxic metabolites terrestric acids (5 and 6), were isolated from the marine derived fungus Penicillium aurantiogriseum. Verrucosidinol has a ring-opened ethylene oxide moiety in the polyene α-pyrone skeleton, and verrucosidinol acetate is its acetate derivative. The chemical structures were determined by comparing with literature data and a combination of spectroscopic techniques, including high resolution mass spectrum and two-dimentional nuclear magnetic resonance spectroscopic analysis.

Response of mucosal and systemic sIgM-positive cells in turbot (Scophthalmus maximus L.) immunization with Edwardsiella tarda.

Indirect fluorescence analyze technology (IFAT) and fluorescence-activated cell sorter (FACS) analysis were used to detect surface IgM positive cells (sIgM+ cells) in lymphoid tissues of unvaccinated turbots and vaccinated ones with inactivated Edwardsiella tarda. The results were as follows: (1) The percentage of sIgM+ cells respectively was 0+/-0.00% of skin, 1.58+/-0.40% of gills, 17.05+/-0.39% of peripheral blood (PBL), 21.06+/-1.79% of kidney in unvaccinated healthy turbots (average length: 7.12+/-0.5 cm; average height: 3.8+/-0.2 cm). (2) After direct immersion (d.i.), the response of sIgM+ cells was produced at first in the gills and thereafter in the kidney and PBL, and a significant increase of the number of sIgM+ cells was found in gills. (3) After immunization via intraperitoneal injection (i.p.), the response of sIgM+ cells was produced simultaneously in the gills, kidney and PBL after i.p., and a significant increase of the number of sIgM+ cells was found in PBL and kidney instead of in gills. These results strongly supported the different immunological role of gills, PBL and kidney upon the different administration routes, and the presence of two compartmental models for immune response in turbot.