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Exosomes derived from tumor cells play a key role in tumor development. In the present study, we identified the bioactivity of exosomes released from WERI-Rb1 retinoblastoma cells in tumor angiogenesis, as well as the underlying mechanism, through biochemical methods and animal experiments. Our in vitro data showed that exosomes could be engulfed by human vesicle endothelial cells (HUVECs), significantly promote cell viability and induce an inflammatory response in HUVECs by increasing the expression of a series of related genes, such as IL-1, IL-6, IL-8, MCP-1, VCAM1, and ICAM1. Significant increases in migration and tube formation were also observed in the HUVECs incubated with exosomes. Moreover, experiments with a nude mouse xenotransplantation model showed that exosomes injected near tumors could be strongly absorbed by tumor cells. The numbers of endothelial cells and blood vessels were significantly increased in tumor tissues treated with exosomes compared to control tissues. Furthermore, to reveal the mechanism underlying exosome-mediated angiogenesis in retinoblastoma, we analyzed the levels of 12 microRNAs in the exosomes. Specifically, our data showed that miR-92a-3p was enriched in RB exosomes. Accordingly, miR-92a-3p was increased in the HUVECs incubated with these exosomes. After treatment with a miR-92a-3p inhibitor, the promoting effect of exosomes on the migration and tube formation of HUVECs was significantly abrogated. The expression of the angiogenesis-related genes mentioned above was markedly decreased in HUVECs. Similarly, treatment with a microRNA mimic also demonstrated that miR-92a-3p was involved in the angiogenesis of HUVECs. More importantly, bioinformatics analysis predicted that Krüppel-like factor 2 (KLF2), a member of the KLF family of zinc-finger transcription factors, might be an active target of miR-92a-3p. Notably, this prediction was confirmed both in vitro and in vivo. Thus, our work suggests that exosomal miR-92a-3p is involved in tumor angiogenesis and might be a promising therapeutic candidate for retinoblastoma.

Conversational systems based on large language models (LLMs) are being increasingly used as advisors in mental health and self-regulation contexts, yet causal evidence remains limited about whether such guidance strengthens human agency rather than shifting responsibility to the system. We propose a dual framework in which the advice style reflects two dimensions, namely a structural stance (power distance) and a relational stance (psychological safety). In an online vignette experiment in China (N = 980), participants sought job search guidance from an LLM and read either a baseline reply or one of eight discourse variants, while holding the advice content constant. Relative to the baseline, a low power distance and a high psychological safety increased the self-efficacy, whereas a high power distance and a low psychological safety decreased it. Combination conditions revealed an asymmetric constraint: when the power distance was high, the self-efficacy declined even when the psychological safety was high, suggesting that authority allocation can override relational reassurance. Mediation analyses showed that the perceived self-control accounted for 26.3% of the low power distance effect and perceived belongingness accounted for 40.9% of the high psychological safety effect, with no cross-mediation. Although mental health outcomes were not directly measured, our results position conversational stances as actionable levers that shape self-efficacy and agency-related mechanisms, which are critical for persistence and adherence in mental health-relevant behavior change.

Background Frosted branch angiitis (FBA) is a rare retinal vasculitis characterized by diffuse perivascular sheathing that resembles frosted branches. This condition is classified into masquerade, frosted branch response, and idiopathic forms. Streptococcal infection is a recognized but infrequent trigger for FBA. We present a novel case of bilateral FBA associated with serologically confirmed streptococcal infection, which demonstrated a rapid response to combined corticosteroid and antibiotic therapy. Case presentation A 45-year-old male presented with acute bilateral vision loss occurring three days after an upper respiratory infection. On initial examination, best-corrected visual acuity (BCVA) was 0.25 in the right eye and 1.0 in the left eye. Fundoscopy revealed bilateral frosted branch-like perivascular sheathing with retinal hemorrhages. Fluorescein angiography (FFA) revealed optic disc hyperfluorescence and intense perivascular leakage, along with widespread capillary non-perfusion, particularly in the nasal periphery of the right eye. Serological testing showed a significantly elevated anti-streptolysin O titer of 619 IU/mL. The patient was diagnosed with streptococcal-associated secondary FBA (Kleiner Type II). The initial regimen comprised intravenous methylprednisolone (500 mg daily for 3 days) combined with oral azithromycin (500 mg daily). Within three days, BCVA in the right eye improved to 0.8, and vitreous haze resolved. At the one-month follow-up, BCVA had fully recovered to 1.0 in both eyes, with near-complete resolution of vascular sheathing on fundoscopy and normalized macular architecture on optical coherence tomography. Regarding laboratory findings, the anti-streptolysin O (ASO) titer had also significantly improved, decreasing to 421 IU/mL. Conclusions This case demonstrates that streptococcal infection can trigger bilateral FBA. Early intervention with combined immunosuppressive and antimicrobial therapy led to complete visual recovery. We recommend serial anti-streptolysin O testing and close ophthalmic monitoring in cases of post-infectious retinal vasculitis.

Can wars truly build states and rationalize their structures? This study focuses on the administrative origin of state-building and finds historical evidence that seems contrary to the idea of \"war-making states\". As states acquire more territory, they become increasingly vulnerable to setbacks in subsequent military activities, even when facing state failure or demise. Drawing upon geospatial data spanning from 906 to 969 AD during Chinas Five Dynasties and utilizing a difference-in-differences method, our study reveals that (1) states did not progressively expand in size due to continuous warfare, and (2) larger territorial acquisitions were associated with decreased probabilities of state survival, as expanding net territorial areas corresponded to higher likelihoods of state failure in the following years. (3) The relationship between civilian and military systems within a state profoundly impacts the validity of the \"war-making states\" hypothesis. This study highlights that war makes states more susceptible to collapse if the military system dominates the civilian bureaucracy. Conversely, if the civilian system controls the military and forms a centralized regime, the \"war-making states\" hypothesis holds true. These findings revise the prevailing hypothesis of \"war-making states\" in historical sociology, showing that the \"war-making states\" hypothesis depends on a specific political structure and bureaucratic system.

To enhance the microbiologically influenced corrosion (MIC) resistance of FeCoNiCrMn high entropy alloy (HEAs), a series of Fe x Cu (1− x ) CoNiCrMn ( x = 1, 0.75, 0.5, and 0.25) HEAs were prepared. Microstructural characteristics, corrosion behavior (morphology observation and electrochemical properties), and antimicrobial performance of Fe x Cu (1− x ) CoNiCrMn HEAs were evaluated in a medium inoculated with typical corrosive microorganism Pseudomonas aeruginosa . The aim was to identify copper-containing FeCoNiCrMn HEAs that balance corrosion resistance and antimicrobial properties. Results revealed that all Fe x Cu (1− x ) CoNiCrMn ( x = 1, 0.75, 0.5, and 0.25) HEAs exhibited an FCC (face centered cubic) phase, with significant grain refinement observed in Fe 0.75 Cu 0.25 CoNiCrMn HEA. Electrochemical tests indicated that Fe 0.75 Cu 0.25 CoNiCrMn HEA demonstrated lower corrosion current density ( i corr ) and pitting potential ( E pit ) compared to other Fe x Cu (1− x ) CoNiCrMn HEAs in P. aeruginosa -inoculated medium, exhibiting superior resistance to MIC. Anti-microbial tests showed that after 14 d of immersion, Fe 0.75 Cu 0.25 CoNiCrMn achieved an antibacterial rate of 89.5%, effectively inhibiting the adhesion and biofilm formation of P. aeruginosa , thereby achieving resistance to MIC.

Thrombospondin-1 (Tsp-1), a matricellular protein, could protect retinal neurons from endogenous or exogenous insults; however, its underlying mechanism remains unclear. Thus, this study aimed to investigate Tsp-1-mediated neuron-protection effect in retinal cells. Our data showed that Tsp-1 downregulation would aggravate UV irradiation-induced DNA damage in 661 W cells and cone photoreceptor cells. The increasing levels of poly (ADP ribose) polymer (PAR) and γ-H2AX in Tsp-1-silenced 661 W cells indicate severe DNA single-strand breaks (SSBs) and double-strand breaks (DSBs). By utilizing an error-prone substrate, Tsp-1 silencing significantly increased deleted DNA end joining in 661 W cells with spontaneous DNA damage (SDD). Moreover, Tsp-1 is indirectly involved in DNA stability in 661 W cells as UV treatment caused a significant Tsp-1 decreasing in cytoplasm, but no obvious Tsp-1 alteration in cell nuclear of 661 W cells. Furthermore, our data indicate that Tgf-β1 activation domain in Tsp-1 plays a critical role in DNA stability in 661 W cells through expressing mutated exogenous Tsp-1 and Tgf-β inhibitor, LSKL. Therefore, this study provides new insights into the mechanism of the neuroprotective action positively mediated by Tsp-1, which might be a therapeutic target for the treatment of retinal pathology.

Down-the-hole (DTH) hammer drilling has high rock-breaking efficiency and a decisive advantage in hard rock drilling, which can reduce the cost of geothermal drilling. However, when the drill bit rotation speed and the DTH percussion frequency do not match properly, especially when the drill bit diameter is large and the ball button diameter is small, while drilling a high-strength formation, the edge buttons of the drill bit are prone to fracture and break, leading to the failure of the drill bit and a significant reduction in its lifespan. This paper investigates the failure modes firstly, then analyzes the failure mechanism of the large-diameter DTH bit, and finally proposes a novel method of cluster edge buttons of the DTH hammer drill bit in a large-diameter geothermal well with high-strength rock. The drill bit has been tested in a high-compressive-strength formation, and we will continue to do more testing and research in various geological conditions. Field application shows that this technology significantly improves the bit life and drilling efficiency and reduces the drilling costs.

Thrombospondin-1 (Tsp-1), a matricellular protein, could protect retinal neurons from endogenous or exogenous insults; however, its underlying mechanism remains unclear. Thus, this study aimed to investigate Tsp-1-mediated neuron-protection effect in retinal cells. Our data showed that Tsp-1 downregulation would aggravate UV irradiation-induced DNA damage in 661 W cells and cone photoreceptor cells. The increasing levels of poly (ADP ribose) polymer (PAR) and [gamma]-H2AX in Tsp-1-silenced 661 W cells indicate severe DNA single-strand breaks (SSBs) and double-strand breaks (DSBs). By utilizing an error-prone substrate, Tsp-1 silencing significantly increased deleted DNA end joining in 661 W cells with spontaneous DNA damage (SDD). Moreover, Tsp-1 is indirectly involved in DNA stability in 661 W cells as UV treatment caused a significant Tsp-1 decreasing in cytoplasm, but no obvious Tsp-1 alteration in cell nuclear of 661 W cells. Furthermore, our data indicate that Tgf-[beta]1 activation domain in Tsp-1 plays a critical role in DNA stability in 661 W cells through expressing mutated exogenous Tsp-1 and Tgf-[beta] inhibitor, LSKL. Therefore, this study provides new insights into the mechanism of the neuroprotective action positively mediated by Tsp-1, which might be a therapeutic target for the treatment of retinal pathology.

PURPOSE: To compare small incision lenticule extraction (SMILE) and femtosecond laser–assisted in situ keratomileusis (FS-LASIK) in terms of the predictability of central stromal thickness reduction in eyes with high myopia. METHODS: In this prospective, randomized contralateral eye trial, 42 patients received SMILE in one eye and FS-LASIK (using the Amaris 750S excimer laser [SCHWIND eye-tech-solutions]) in the fellow eye for the correction of high myopia (manifest refraction spherical equivalent: < −6.00 diopters). Spectral-domain optical coherence tomography was used to measure the central corneal and epithelial thickness. Pre-operative and postoperative values were compared to determine the amount of central stromal reduction achieved. RESULTS: At the 6-month follow-up visit, the amount of central stromal reduction was overestimated by 20.05 ± 5.92 µm in the SMILE group (P < .0001) and underestimated by 8.21 ± 8.14 µm in the FS-LASIK group (P < .0001). The mean actual central stromal reduction achieved with SMILE was significantly less than that achieved with FS-LASIK (10.10 ± 18.01 µm, range: 1.90 to 18.29 µm, P < .001). The discrepancy between the planned and achieved central corneal stromal reduction was not associated with refractive overcorrection or undercorrection in either the SMILE group or the FS-LASIK group (P = .9743 vs P = .0777). CONCLUSIONS: In patients with high myopia, the laser software platform may underestimate and overestimate the amount of actual corneal reduction in eyes treated with FS-LASIK and SMILE, respectively. SMILE required less corneal stroma compared to FS-LASIK in the studied cohort using the Amaris 750S excimer laser when correcting a similar spherical equivalent refraction. [J Refract Surg. 2022;38(2):90–97.]

Cu-bearing high-entropy alloys (HEAs) have been proposed for use as structural materials in the marine environment due to their superior mechanical and antimicrobial properties. However, the Al, Cu-enriched precipitations in HEAs damage their corrosion resistance. In this study, we used ultrasonic shot peening (USSP) technology to solve this problem. USSP caused severe plastic deformation of the Al0.3Cu0.5CoCrFeNi HEA surface and dispersed the long-strip Al, Cu-enriched phases into scattered dots, which reduced the galvanic corrosion of the HEA and enhanced passive film formation. The Al, Cu-enriched scattered precipitations also increased the number of Cu2+ ion dissolution sites, leading to the improvement of the alloy’s antibacterial properties.