Innovations in intracranial aneurysm treatment: a pilot study on the Choydar flow diverter.

Background: The flow diverter (FD) has emerged as a promising treatment option for intracranial aneurysms. Recently, a novel flow-diverting stent, the Choydar FD device, has been developed within our nation. Objective: To introduce the newly developed Choydar FD device and present our preliminary clinical experience with its application in the treatment of intracranial aneurysms. Methods: A total of 23 patients with 23 unruptured intracranial aneurysms, comprising 20 (87.0%) aneurysms located at the internal carotid artery and 3 (13.0%) at the vertebral artery, were treated with the Choydar FD device between December 2021 and April 2022. Patient baseline data, clinical and angiographic outcomes were collected and analyzed. Results: The Choydar FD device was successfully deployed in all patients (100%), with 18 aneurysms (78.3%) additionally treated with coils. One patient experienced an ischemic event with sensory disturbance during the perioperative period. At the 1-year follow-up, all patients demonstrated good clinical outcomes. Of the 23 aneurysms with available angiographic follow-up, 22 (95.7%) achieved complete occlusion, and one patient exhibited in-stent stenosis without neurological deficits. Conclusion: The initial clinical results of the Choydar FD device are encouraging, and it appears to be a useful option for treating intracranial aneurysms with acceptable efficacy and safety. Future studies with larger sample sizes and longer follow-up durations are warranted to validate these findings.

Flow-Diverting Devices in the Treatment of Vertebral Artery Aneurysms: Insights into Efficacy and Safety from a Systematic Review and Meta-analysis.

The objective of this study is to conduct a systematic review and meta-analysis aimed at evaluating the efficacy and safety of flow-diverting devices (FDs) treatment for intracranial vertebral artery (VA) aneurysms. We searched PubMed, Web of Science, OVID, and Embase for English-language studies up to February 2024 and included clinical studies on FD treatment of intracranial VA aneurysms. Sensitivity analysis evaluated outcome stability. Of 2273 articles, 29 studies involving 541 aneurysms treated with FDs were included. Based on the Methodological Index for Non-Randomized Studies (MINORS), six were high-quality and 23 moderate quality. FD treatment showed a 95% rate of favorable clinical outcomes (95% CI, 89-99%), 81% (95% CI, 74-88%) complete aneurysmal occlusion, 4% (95% CI, 2-7%) ischemic complication incidence, 1% (95% CI, 0-3%) hemorrhagic complication incidence, 95% (95% CI, 87-100%) posterior inferior cerebellar artery (PICA) preservation, and 6% (95% CI, 3-10%) in-stent stenosis or occlusion across clinical and angiographic follow-up periods of 13.62 months (95% CI, 10.72-16.52) and 11.85 months (95% CI, 9.36-14.33), respectively. Subgroup analyses, based on a 12-month angiographic follow-up threshold, indicated no statistically significant differences in rates of complete aneurysm occlusion, PICA preservation, or in-stent stenosis or occlusion incidence (p > 0.05) between subgroups. Moreover, significant differences were observed in clinical and angiographic outcomes between ruptured and unruptured aneurysms, particularly in hemorrhagic complications (p < 0.05), without significant disparity in ischemic complications (p > 0.05). The results' stability was confirmed via sensitivity analysis. FDs treatment for VA aneurysms is efficacious and safe, offering high rates of positive clinical and angiographic outcomes with minimal complications, underscoring FDs' viability as a treatment option for VA aneurysms. The study was registered with PROSPERO (registration number: CRD42024499894).

Differences and Correlations of Morphological and Hemodynamic Parameters between Anterior Circulation Bifurcation and Side-wall Aneurysms.

OBJECTIVE: The objective of this research was to explore the difference and correlation of the morphological and hemodynamic features between sidewall and bifurcation aneurysms in anterior circulation arteries, utilizing computational fluid dynamics as a tool for analysis. METHODS: In line with the designated inclusion criteria, this study covered 160 aneurysms identified in 131 patients who received treatment at Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, China, from January 2021 to September 2022. Utilizing follow-up digital subtraction angiography (DSA) data, these cases were classified into two distinct groups: the sidewall aneurysm group and the bifurcation aneurysm group. Morphological and hemodynamic parameters in the immediate preoperative period were meticulously calculated and examined in both groups using a three-dimensional DSA reconstruction model. RESULTS: No significant differences were found in the morphological or hemodynamic parameters of bifurcation aneurysms at varied locations within the anterior circulation. However, pronounced differences were identified between sidewall and bifurcation aneurysms in terms of morphological parameters such as the diameter of the parent vessel (Dvessel), inflow angle (θF), and size ratio (SR), as well as the hemodynamic parameter of inflow concentration index (ICI) (P<0.001). Notably, only the SR exhibited a significant correlation with multiple hemodynamic parameters (P<0.001), while the ICI was closely related to several morphological parameters (R>0.5, P<0.001). CONCLUSIONS: The significant differences in certain morphological and hemodynamic parameters between sidewall and bifurcation aneurysms emphasize the importance to contemplate variances in threshold values for these parameters when evaluating the risk of rupture in anterior circulation aneurysms. Whether it is a bifurcation or sidewall aneurysm, these disparities should be considered. The morphological parameter SR has the potential to be a valuable clinical tool for promptly distinguishing the distinct rupture risks associated with sidewall and bifurcation aneurysms.

Navigating complexity: a comprehensive review of microcatheter shaping techniques in endovascular aneurysm embolization.

The endovascular intervention technique has gained prominence in the treatment of intracranial aneurysms due to its minimal invasiveness and shorter recovery time. A critical step of the intervention is the shaping of the microcatheter, which ensures its accurate placement and stability within the aneurysm sac. This is vital for enhancing coil placement and minimizing the risk of catheter kickback during the coiling process. Currently, microcatheter shaping is primarily reliant on the operator's experience, who shapes them based on the curvature of the target vessel and aneurysm location, utilizing 3D rotational angiography or CT angiography. Some researchers have documented their experiences with conventional shaping methods. Additionally, some scholars have explored auxiliary techniques such as 3D printing and computer simulations to facilitate microcatheter shaping. However, the shaping of microcatheters can still pose challenges, especially in cases with complex anatomical structures or very small aneurysms, and even experienced operators may encounter difficulties, and there has been a lack of a holistic summary of microcatheter shaping techniques in the literature. In this article, we present a review of the literature from 1994 to 2023 on microcatheter shaping techniques in endovascular aneurysm embolization. Our review aims to present a thorough overview of the various experiences and techniques shared by researchers over the last 3 decades, provides an analysis of shaping methods, and serves as an invaluable resource for both novice and experienced practitioners, highlighting the significance of understanding and mastering this technique for successful endovascular intervention in intracranial aneurysms.

SUMO1-regulated DBC1 promotes p53-dependent stress-induced apoptosis of lens epithelial cells.

Deleted in breast cancer 1 (DBC1) was initially identified from a homozygously deleted region in human chromosome 8p21. It has been well established that DBC1 plays a dual role during cancer development. Depending on the physiological context, it can promote or inhibit tumorigenesis. Whether it plays a role in lens pathogenesis remains elusive. In the present study, we demonstrated that DBC1 is highly expressed in lens epithelial cells from different vertebrates and in retina pigment epithelial cells as well. Moreover, DBC1 is SUMOylated through SUMO1 conjugation at K591 residue in human and mouse lens epithelial cells. The SUMOylated DBC1 is localized in the nucleus and plays an essential role in promoting stress-induced apoptosis. Silence of DBC1 attenuates oxidative stress-induced apoptosis. In contrast, overexpression of DBC1 enhances oxidative stress-induced apoptosis, and this process depends on p53. Mechanistically, DBC1 interacts with p53 to regulate its phosphorylation status at multiple sites and the SUMOylation of DBC1 enhances its interaction with p53. Together, our results identify that DBC1 is an important regulator mediating stress-induced apoptosis in lens, and thus participates in control of lens cataractogenesis.

A double-edged sword: Constructed wetland-microbial fuel cells promote organics removal via entrapment.

Recently, constructed wetland-microbial fuel cells (CW-MFCs) are found to enhance the organics removal via the connection of the external circuit. Yet, it is unclear why the energy output is unmatched with the enhancement of the organics removal. This study compared the dynamic changes of the organics in a CW-MFC microcosm operated under the close circuit and open circuit. As a result, the close circuit facilitated the organics removal by 9 % before the proportional discharge of carbon metabolites. This suggested that organics entrapment should account for the huge loss of carbon recovery; and closing the external circuit could further promote the organics entrapment. Besides, polyhydroxybutyrate was found accumulated in the MFC culture experiment, evidencing that the fed-batch mode of operation could result in a feast-famine pattern of microbial metabolism. Despite the fast organics entrapment during the first hours, prolonging the operation time would lead to continuous carbon gas emission, along with the substantially elevated coulombic efficiency. Together, these results explained the substantial COD removal enhancement with low electricity yield, and cautioned the safe use of the MFC integration to spare the system from overaccumulation of organics.

HSP90ß prevents aging-related cataract formation through regulation of the charged multivesicular body protein (CHMP4B) and p53.

Cataract is a leading ocular disease causing global blindness. The mechanism of cataractogenesis has not been well defined. Here, we demonstrate that the heat shock protein 90ß (HSP90ß) plays a fundamental role in suppressing cataractogenesis. HSP90ß is the most dominant HSP in normal lens, and its constitutive high level of expression is largely derived from regulation by Sp1 family transcription factors. More importantly, HSP90ß is significantly down-regulated in human cataract patients and in aging mouse lenses, whereas HSP90ß silencing in zebrafish causes cataractogenesis, which can only be rescued by itself but not other HSP90 genes. Mechanistically, HSP90ß can directly interact with CHMP4B, a newly-found client protein involved in control of cytokinesis. HSP90ß silencing causes upregulation of CHMP4B and another client protein, the tumor suppressor p53. CHMP4B upregulation or overexpression induces excessive division of lens epithelial cells without proper differentiation. As a result, these cells were triggered to undergo apoptosis due to activation of the p53/Bak-Bim pathway, leading to cataractogenesis and microphthalmia. Silence of both HSP90ß and CHMP4B restored normal phenotype of zebrafish eye. Together, our results reveal that HSP90ß is a critical inhibitor of cataractogenesis through negative regulation of CHMP4B and the p53-Bak/Bim pathway.

Case Report: A novel heterozygous nonsense mutation in KRIT1 cause hereditary cerebral cavernous malformation.

Cerebral cavernous malformation (CCM) is a vascular malformation of the central nervous system and mainly characterized by enlarged capillary cavities without intervening brain parenchyma. Genetic studies have identified three disease-causing genes (CCM1/KRIT1, CCM2/MGC4607 and CCM3/PDCD10) responsible for CCM. Here, we characterized a four-generation family diagnosed with CCM and identified a novel heterozygous mutation c.1159C>T, p.Q387X in KRIT1 gene by whole exome sequencing and Sanger sequencing. The Q387X mutation resulted in premature termination of KRIT1 protein, which was predicted to be deleterious by the ACMG/AMP 2015 guideline. Our results provide novel genetic evidence support that KRIT1 mutations cause CCM, and are helpful to the treatment and genetic diagnosis of CCM.

Utility of low-profile visualized intraluminal support (LVIS™) stent for treatment of acutely ruptured bifurcation aneurysms: A single-center study.

Objective: Stent-assisted coiling has been increasingly used in the treatment of intracranial aneurysms. However, its application in ruptured bifurcation aneurysms remains controversial and challenging. This study aimed to present the safety and feasibility of low-profile visualized intraluminal support (LVIS™, LVIS, and LVIS Jr.) stent for acutely ruptured bifurcation aneurysms. Methods: A total of 41 patients with acutely ruptured intracranial aneurysms arising at the bifurcation were treated with LVIS™ stent-assisted coiling in our hospital between January 2017 and December 2021. The clinical data and angiographic results of the patients were analyzed. Results: Among these patients, all stents were successfully implanted. According to the immediate angiographic results, 29 aneurysms (70.7%) were completely occluded. Intraoperative thrombosis and hemorrhage occurred in two and one cases, respectively. No post-operative thrombosis or rebleeding events were observed. The clinical follow-up of all patients revealed that 38 (92.7%) cases had favorable outcomes (modified Rankin scale: 0-2). The angiographic results available for the 36 patients during the follow-up period revealed complete occlusion was achieved in 30 patients (83.3%) and residual neck in six patients. Conclusion: The LVIS™ stent-assistant coiling is a safe and feasible option for acutely ruptured bifurcation aneurysms. Further studies with a prospective design, a larger sample size, and long-term follow-up are needed to validate these findings.

Predicting flow diverter sizing using the AneuGuideTM software: a validation study.

BACKGROUND: Stent sizing remains a challenging task for flow diverter implantation because of stent foreshortening. In this study, we aimed to quantify the change in length after implantation and assess the error in length prediction using AneuGuideTM software. METHODS: In a retrospective cohort of 101 patients with 102 aneurysms undergoing treatment with a pipeline embolization device (PED; Covidien, Irvine, California, USA), we used AneuGuideTM software to obtain measured lengths (ML) and calculated lengths (CL) after stent implantation. Stent elongation was defined as the ratio of ML-LL to the labeled length (LL). Simulation error was defined as the ratio of the absolute value of CL-ML to ML. The correlation and consistency between ML and LL and between ML and CL were analyzed using Pearson's correlation test and the Bland-Altman plot. Statistical significance was set at p<0.05. RESULTS: The mean elongation of ML was 32.6% (range 26.3-109.2%). Moderate consistency was observed between LL and ML (ρ=0.74, p<0.001). With the AneuGuideTM software, the mean simulation error was 6.6% (range 0.32-21.2%). Pearson's correlation test and the Bland-Altman plot showed a high correlation and consistency between ML and CL (ρ=0.96, p<0.001). CONCLUSION: Labeled length provides only a low reference value for predicting the actual length of the flow diverter after implantation. The high consistency between ML and CL obtained from AneuGuideTM software shows its great potential for the optimization of the flow diverter sizing process.

Use of covered stents to treat complex cerebrovascular diseases: Expert consensus.

The treatment of complex cerebrovascular diseases (CCVDs) at the skull base, such as complex intracranial aneurysms, carotid-cavernous sinus fistulas, and intracranial artery traumatic injuries, is a difficult clinical problem despite advances in endovascular and surgical therapies. Covered stents or stent graft insertion is a new concept for endovascular treatment that focuses on arterial wall defect reconstruction, differing from endovascular lesion embolization or flow diverter therapies. In recent years, covered stents specifically designed for cerebrovascular treatment have been applied in the clinical setting, allowing thousands of patients with CCVDs to undergo intraluminal reconstruction treatment and achieving positive results, even in the era of flow diverters. Since there is no unified reference standard for the application of covered stents for treating CCVDs, it is necessary to further standardize and guide the clinical application of this technique. Thus, we organized authoritative experts in the field of neurointervention in China to write an expert consensus, which aims to summarize the results of covered stent insertion in the treatment of CCVDs and propose suitable standards for its application in the clinical setting. Based on the contents of this consensus, clinicians can use individualized intraluminal reconstruction treatment techniques for patients with CCVDs.

Artificial Intelligence-Assisted Microcatheter Shaping for Intracranial Aneurysm Coiling: A Preliminary Study.

BACKGROUND: To evaluate the efficacy of artificial intelligence (AI) technology-assisted microcatheter shaping for coil embolization of intracranial aneurysms. METHODS: From June 2019 to May 2021, 30 aneurysms in 24 patients were treated with coiling embolization using computer software-assisted microcatheter shaping at our institution. All patients underwent digital subtraction angiography (DSA) before coiling embolization. After three-dimensional (3D) rotational angiography, digital imaging and communications in medicine (DICOM) data were extracted and imported into computer software based on an AI algorithm. 3D images of the parent artery and aneurysm were constructed with the software and data including the central axis of the parent artery, aneurysm location, aneurysm size, and 3D structure were automatically obtained. The optimal microcatheter path was calculated and the shape of the mandrel was automatically generated. Surgeons shaped the mandrel and microcatheter following the AI-generated template and completed the endovascular procedure. RESULTS: All patients successfully completed the endovascular procedure without perioperative complications. The microcatheters shaped as per the AI template accurately entered the aneurysm sacs in 1 attempt; 15 aneurysms required no microguidewire assistance in catheterizing the aneurysm sac and 15 did. The stability of the microcatheters during the procedures was satisfactory. No rebound incidence was observed and no reshaping was necessary. CONCLUSIONS: The AI-assisted microcatheter shaping technology provides a new method to generate the optimal shape for the mandrel and microcatheter during endovascular procedures. The technology facilitates microcatheter accuracy and stability during coiling embolization and provides technical support for surgeons.

Inhibition of cGAS-STING by JQ1 alleviates oxidative stress-induced retina inflammation and degeneration.

Atrophic ("dry") form of age-related macular degeneration (AMD) is a leading cause of vision loss characterized by macular retinal pigment epithelium (RPE) and the ensuing photoreceptor degeneration. cGAS-STING signaling is a key cytosolic DNA sensor system in innate immunity and have recently been shown promotes RPE degeneration. However, expression regulation and therapeutic potential of cGAS and STING are not explored in retina under dry AMD pathogenic conditions. Our analysis shows upregulated STING RNA and increased chromatin accessibility around cGAS and STING promoters in macular retinas from dry AMD patients. cGAS-STING activation was detected in oxidative stress-induced mouse retina degeneration, accompanied with cytosolic leakage of damaged DNA in photoreceptors. Pharmaceutical or genetic approaches indicates STING promotes retina inflammation and degeneration upon oxidative damage. Drug screening reveals that BRD4 inhibitor JQ1 reduces cGAS-STING activation, inflammation and photoreceptor degeneration in the injured retina. BRD4 inhibition epigenetically suppresses STING transcription, and promotes autophagy-dependent cytosolic DNA clearance. Together, our results show that activation of cGAS-STING in retina may present pivotal innate immunity response in GA pathogenesis, whereas inhibition of cGAS-STING signaling by JQ1 could serve as a potential therapeutic strategy.

MYPT1/PP1-Mediated EZH2 Dephosphorylation at S21 Promotes Epithelial-Mesenchymal Transition in Fibrosis through Control of Multiple Families of Genes.

The methyltransferase EZH2 plays an important role in regulating chromatin conformation and gene transcription. Phosphorylation of EZH2 at S21 by AKT kinase suppresses its function. However, protein phosphatases responsible for the dephosphorylation of EZH2-S21 remain elusive. Here, it is demonstrated that EZH2 is highly expressed in the ocular lens, and AKT-EZH2 axis is important in TGFß-induced epithelial-mesenchymal transition (EMT). More importantly, it is identified that MYPT1/PP1 dephosphorylates EZH2-S21 and thus modulates its functions. MYPT1 knockout accelerates EMT, but expression of the EZH2-S21A mutant suppresses EMT through control of multiple families of genes. Furthermore, the phosphorylation status and gene expression modulation of EZH2 are implicated in control of anterior subcapsular cataracts (ASC) in human and mouse eyes. Together, the results identify the specific phosphatase for EZH2-S21 and reveal EZH2 dephosphorylation control of several families of genes implicated in lens EMT and ASC pathogenesis. These results provide important novel information in EZH2 function and regulation.

Enhanced selective adsorption of lead(II) from complex wastewater by DTPA functionalized chitosan-coated magnetic silica nanoparticles based on anion-synergism.

Simultaneously removing heavy metal and dye from complex wastewater is of great significance to industrial wastewater treatment. Herein, a novel magnetic adsorbent, DTPA-modified chitosan-coated magnetic silica nanoparticle (FFO@Sil@Chi-DTPA), was successfully prepared and used to enhance the Pb(II) selective adsorption from multi-metal wastewater based on anion-synergism. In the competitive experiment conducted in a multi-ion solution, the type of selective adsorption of metals was changed by the adsorbents before and after amidation, in which FFO@Sil@Chi-DTPA exhibited an excellent selectively for capturing Pb(II), while FFO@Sil@Chi demonstrated highly selective adsorption of silver. More importantly, the selective adsorption of Pb(II)S by FFO@Sil@Chi-DTPA was enhanced from 111.71 to 268.01 mg g-1 when the coexisting MB concentrations ranged from 0 to 100 mg L-1 at pH 6.0. In the Pb(II)-MB binary system, Pb(II) and MB exhibited a synergistic effect, in which the presence of MB strengthened the adsorption effect of Pb(II) due to the sulfonic acid groups in MB molecules that create new specific sites for Pb(II) adsorption, while MB adsorption was also enhanced by the presence of Pb(II). This work provides a new strategy for exploring novel adsorbents that can enhance the selective removal of heavy metal in complex wastewater based on anion-synergism.

Potassium supplement enhanced cadmium removal in a Microcystis aeruginosa photobioreactor: Evidence from actual and simulated wastewater.

In this study, a Microcystis aeruginosa-based photobioreactor (M. aeruginosa-based PBR) was developed for the removal of cadmium (Cd2+) from diluted actual mine wastewater (DW) and Cd2+-contained simulated wastewater (SW), with a uniform Cd2+ concentration of 0.5 mg/L. For the DW and SW, both K+ -abundant (DWA & SWA) and K+-insufficient (DWB & SWB) treatments were conducted. It was found that continuous supplementation of K+ benefited Cd2+ removal. The Cd2+ removal efficiency in SWA reached 70% during the 41 days of operation, which was 20% higher than that in the SWB. The K+ addition triggered great higher Cd2+ removal efficiency (90%) in the DWA in comparison to the SWA. The Cd2+ assimilation by M. aeruginosa and Cd2+ retention on M. aeruginosa surface were the primary processes involved in the PBR system. The K+ starvation triggered a 45% and 43% loss of M. aeruginosa biomass in the DWA and the DWB, respectively. Hence, the Cd2+ removal efficiency in DWB increased significantly, and this was attributed to the increased abundance of non-living cells and enhanced bioretention of Cd2+. The results revealed that continuous K+ supplementation enhanced the Cd2+ removal efficiency in the M. aeruginosa-based PBR jointly by prompting algal cell growth, Cd2+ assimilation and biosorption, as well as Cd2+ retention on the algal cells.

Application of covered stent graft in the treatment of complex carotid artery lesions: A single center experience.

PURPOSE: To assess the clinical efficiency and imaging outcome of applying covered stent grafts for the treatment of complex carotid artery lesions. METHOD: A total of 39 consecutive patients with carotid artery lesions treated with covered stent grafts at our institution from December 2016 to December 2019 were reviewed. Two kinds of stent including self-expandable covered stent (Viabahn; W. L. Gore & Associates) and balloon-expandable covered stent (Willis; Microport) were applied. The angiograms immediately after the procedure, perioperative complications, and follow-up outcomes were recorded. RESULT: Based on imaging features, 11 patients exhibited pseudoaneurysms, 23 patients had blood blister-like aneurysms (BBAs), and five patients were carotid cavernous fistulas. A total of 40 stent implantations were performed, including nine Viabahn stents and 31 Willis stents. Two patients received double implants of Willis stents. Stent failed to perform for one patient due to tortuous parent artery. The angiography reports immediately after the procedure showed that the lesions in 36 patients were completely occluded, whereas two patients had minimal endoleaks. With respect to the occurrence of procedural complications, an aneurysm ruptured during the procedure in one case, which resulted in CCF, and acute in-stent thrombosis occurred in another case. Clinical and angiographic follow-up (11.2±2.4 months) sessions were conducted for 38 patients and a complete lesion exclusion was achieved in 36 patients. The minimal endoleak persisted in one patient and another patient experienced recurrence with stent migration, leading to ipsilateral blepharoptosis. However, none of the patients developed hemorrhage or ischemia and in-stent stenosis was not observed. CONCLUSION: Covered stent grafts appear to be a safe and feasible for the treatment of complex carotid artery lesions. Despite the potential for stent delivery failure as well as endoleak and procedure-related complications, covered stent grafts should be considered when selecting the optimal treatment strategy.

The E3 Ligase PIAS1 Regulates p53 Sumoylation to Control Stress-Induced Apoptosis of Lens Epithelial Cells Through the Proapoptotic Regulator Bax.

Protein sumoylation is one of the most important post-translational modifications regulating many biological processes (Flotho A & Melchior F. 2013. Ann Rev. Biochem. 82:357-85). Our previous studies have shown that sumoylation plays a fundamental role in regulating lens differentiation (Yan et al., 2010. PNAS, 107(49):21034-9.; Gong et al., 2014. PNAS. 111(15):5574-9). Whether sumoylation is implicated in lens pathogenesis remains elusive. Here, we present evidence to show that the protein inhibitor of activated STAT-1 (PIAS1), a E3 ligase for sumoylation, is implicated in regulating stress-induced lens pathogenesis. During oxidative stress-induced cataractogenesis, expression of PIAS1 is significantly altered at both mRNA and protein levels. Upregulation and overexpression of exogenous PIAS1 significantly enhances stress-induced apoptosis. In contrast, silence of PIAS1 with CRISPR/Cas9 technology attenuates stress-induced apoptosis. Mechanistically, different from other cells, PIAS1 has little effect to activate JNK but upregulates Bax, a major proapoptotic regulator. Moreover, Bax upregulation is derived from the enhanced transcription activity of the upstream transcription factor, p53. As revealed previously in other cells by different laboratories, our data also demonstrate that PIAS1 promotes SUMO1 conjugation of p53 at K386 residue in lens epithelial cells and thus enhances p53 transcription activity to promote Bax upregulation. Silence of Bax expression largely abrogates PIAS1-mediated enhancement of stress-induced apoptosis. Thus, our results demonstrated that PIAS1 promotes oxidative stress-induced apoptosis through positive control of p53, which specifically upregulates expression of the downstream proapoptotic regulator Bax. As a result, PIAS1-promoted apoptosis induced by oxidative stress is implicated in lens pathogenesis.

Aging-dependent loss of GAP junction proteins Cx46 and Cx50 in the fiber cells of human and mouse lenses accounts for the diminished coupling conductance.

The homeostasis of the ocular lens is maintained by a microcirculation system propagated through gap junction channels. It is well established that the intercellular communications of the lens become deteriorative during aging. However, the molecular basis for this change in human lenses has not been well defined. Here, we present evidence to show that over 90% of Cx46 and Cx50 are lost in the fiber cells of normal human lenses aged 50 and above. From transparent to cataractous lenses, while Cx43 was upregulated, both Cx46 and Cx50 were significantly down-regulated in the lens epithelia. During aging of mouse lenses, Cx43 remained unchanged, but both Cx46 and Cx50 were significantly downregulated. Under oxidative stress treatment, mouse lenses develop in vitro cataractogenesis. Associated with this process, Cx43 was significantly upregulated, in contrast, Cx46 and Cx50 were sharply downregulated. Together, our results for the first time reveal that downregulation in Cx46 and Cx50 levels appears to be the major reason for the diminished coupling conductance, and the aging-dependent loss of Cx46 and Cx50 promotes senile cataractogenesis.

Permanganate release from silica-based hollow mesoporous coagulant combined with UV for spatiotemporal enrichment and degradation of diclofenac sodium.

In this work, the novel hollow mesoporous coagulant was prepared by chitosan-polydopamine coating and permanganate loading into silica nanoparticles for investigating the simultaneous enrichment and degradation of diclofenac sodium (DCFS) combined with ultraviolet irradiation. The enrichment kinetic of DCFS was explained well with pseudo-second-order model, indicating the exist of hydrogen bonding. Based on the correlation coefficients, the enriched isotherms were fitted by models which accorded with the BET > Freundlich > Langmuir sequence. The result showed that, in addition to the coagulant and DCFS, there were aromatic stackings among DCFS molecules. Due to both effects of which, the DCFS enrichment could be realized significantly in the range of pH 4.0-9.0. It was degraded at the copresence of ultraviolet and permanganate released from coagulant in acidic aqueous medium. The release mechanism was simulated through Korsmayer-Peppas model, implying case-II transport and Fickian diffusion. Additionally, Mn (V) and •OH radicals were vital in the DCFS degradation process. The coagulant could be reloaded at least ten times and that from each cycle was used directly for DCFS removal for six times without rinse process, which provided a potential application in environmental remediation.