Elevated cortical blood flow insufficiency volume as a predictor of adverse outcomes in aneurysmal subarachnoid hemorrhage: a large prospective quantitative computed tomography perfusion study.

PURPOSE: Early hypoperfusion changes exist in patients with aneurysmal subarachnoid hemorrhage (aSAH). We aimed to investigate a readily obtainable quantitative computed tomography perfusion (CTP) parameter that could assist in quickly identifying patients at risk of delayed cerebral ischemia (DCI) and poor 90-day functional outcomes on admission. METHODS: We prospectively collected data between 2021.04 and 2022.12. Preoperative CTP data were post-processed using RAPID software. The cortical blood flow insufficiency (CBFI) was defined as Time-to-maximum > 4.0 s. Patients were categorized into four groups according to CBFI volume distribution. To minimize differences among the groups, we employed stabilized inverse probability of treatment weighting (sIPTW). The primary outcome was DCI and poor 90-day functional outcomes (modified Rankin Scale, 3-6) was the secondary outcome. Multivariable Cox or Logistic analysis were performed to estimate the association between CBFI volume and the study outcomes, both before and after sIPTW. RESULTS: At baseline, the mean (SD) age of the 493 participants was 55.0 (11.8) years, and 299 (60.6%) were female. One hundred and seven participants with DCI and eighty-six participants with poor 90-day functional outcomes were identified. After sIPTW, CBFI volume demonstrated a significant association with DCI (Cox regression: Group 4 versus Group 1, HR 3.69, 95% CI 1.84-7.01) and poor 90-day functional outcomes (Logistic regression: Group 4 versus Group 1, OR 4.61, 95% CI 2.01-12.50). CONCLUSION: In this study, an elevated preoperative CBFI volume was associated with adverse outcomes in aSAH patients. More well-designed studies are needed to confirm this association.

Can thick metal-halide perovskite single crystals have narrower optical bandgaps with near-infrared absorption?

Metal-halide perovskite (MHP) single crystals are emerging as potential competitors to their polycrystalline thin-film counterparts. These materials have shown the specific feature of extended absorbance towards the near-infrared (NIR) region, which promises further extension of their applications in the field of photovoltaics and photodetectors. This notable expansion of absorbance has been explained by the narrower effective optical bandgap of MHP single crystals promoted by their large thickness over several micrometres to millimetres. Herein, the attributes of the material's thickness and the measurement technique used to estimate these characteristics are discussed to elucidate the actual origins of the extended absorbance of MHP single crystals. Contrary to the general belief of the narrower bandgap of the MHP single crystals, we demonstrate that the extended NIR absorption in the MHP single crystals mainly originates from the combination of unique below-bandgap absorption of MHPs, the thickness of single crystals, and the technical limitation of the spectrophotometer, with the key attributes of (i) significantly large thickness of the MHP single crystals by suppressing the transmitted light and (ii) the detector's limited dynamic range. Combining the theoretical and experimental characterizations, we clarify the significant role of the large thickness together with the limited sensitivity of the detector in promoting the well-known red shift of the absorption onset of the MHP single crystals. The observations evidently show that in some special circumstances, the acquired absorption spectrum cannot reliably represent the optical bandgap of MHP materials. This highlights some misinterpretations in the estimation of the narrower optical bandgap of the MHP single crystals from conventional optical methods, while the optical bandgap is an inherent property independent of the thickness. The proposed broad applications of the MHP single crystals are dictated by their fascinating properties, and therefore, a deep insight into these features should be considered besides device applications, because much of their property-function relationships are still ambiguous and a subject of debate.

Regulating Surface Defects to Achieve More Positive Light Soaking Effect in Perovskite Solar Cells.

The dynamic defect tolerance under light soaking is a crucial aspect of halide perovskites. However, the underlying physics of light soaking remains elusive and is subject to debate, exhibiting both positive and negative effects. In this investigation, we demonstrated that surface defects in perovskite films significantly impact the performance and stability of perovskite solar cells, closely correlated with light soaking behaviors. Removing the top surface layer through adhesive tape, the surface defect density noticeably decreases, leading to enhanced photoluminescence (PL) efficiency, prolonged carrier lifetime, and higher conductivity. Consequently, the power conversion efficiency (PCE) of solar cells improves from 17.70% to 20.5%. Furthermore, we confirmed a positive correlation between surface defects and the light soaking effect. Perovskite films with low surface defects surprisingly exhibit a 3-fold increase in PL intensity and an 85% increase in carrier lifetime under 500 s of continuous illumination at an intensity of 100 mW/cm2. Beyond the conventional strategy of suppressing defect trapping, we propose increasing the capability of dynamic defect tolerance as an effective strategy to enhance the optoelectronic properties and performance of perovskite solar cells.

Treatment Modalities and Outcomes in Brainstem Cavernous Malformations: A Large Multicenter Observational Cohort Study.

BACKGROUND: Symptomatic brainstem cavernous malformations (BSCMs) pose a high risk of morbidity and mortality due to recurrent hemorrhage, warranting aggressive management. However, few studies have compared the effectiveness of different treatment modalities for BSCMs. We aimed to assess the association of treatment modalities with recurrent hemorrhage and neurological outcomes in patients with BSCM. METHODS: We conducted a retrospective cohort study using an observational registry database covering population of southwest and southeast China. Adult patients with BSCM were included and followed up between March 1, 2011, to March 31, 2023. We compared outcomes between microsurgery and stereotactic radiosurgery (SRS) in propensity score-matched case pairs, incorporating demographic, medical history, and lesion characteristics. The outcomes studied included recurrent hemorrhage and poor prognosis (defined as a Glasgow Outcome Scale score, <4). Absolute rate differences and hazard ratios (HRs) with 95% CIs were calculated using Cox models. RESULTS: Among 736 diagnosed patients with BSCM, 96 (48 matched pairs) were included after exclusions and propensity score matching (mean age, 43.1 [SD, 12.1] years; 50% women). During the median 5-year follow-up, no significant differences in recurrent hemorrhage (4.2% [microsurgery] versus 14.6% [SRS], HR, 3.90 [95% CI, 0.46-32.65]; P=0.21) and poor prognosis (12.5% [microsurgery] versus 8.3% [SRS], HR, 0.29 [95% CI, 0.08-1.08]; P=0.07) were observed between microsurgery and SRS recipients. Furthermore, either microsurgery or SRS correlated with fewer recurrent hemorrhage (HR, 0.09 [95% CI, 0.02-0.39]; P=0.001; HR, 0.21 [95% CI, 0.07-0.69]; P=0.01) compared with conservative treatment. CONCLUSIONS: In this study, both microsurgery and SRS were safe and effective for BSCM, demonstrated comparable outcomes in recurrent hemorrhage and poor prognosis. However, interpretation should be cautious due to the potential for residual confounding. REGISTRATION: URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR2300070907.

Pipeline Embolization Device for intracranial aneurysms presenting with mass effect: a large Chinese cohort.

BACKGROUND: Unruptured intracranial aneurysm treatment aims to reduce the risk of aneurysm rupture and bleeding, relieves symptoms and improve the quality of life for patients. This study aimed to assess the safety and efficacy of Pipeline Embolization Device (PED, Covidien/Medtronic, Irvine, CA) treatment for intracranial aneurysms presenting with mass effect in real-world settings. METHODS: We selected patients from the PED in China Post-Market Multi-Center Registry Study with mass effect presentation. The study endpoints included postoperative mass effect deterioration and mass effect relief at follow-up (3-36 months). We conducted multivariate analysis to identify factors associated with mass effect relief. Subgroup analyses by aneurysm location, size and form were also performed. RESULTS: This study included 218 patients with a mean age of 54.3±11.8 years and a female predominance of 74.0% (162/218). The postoperative mass effect deterioration rate was 9.6% (21/218). During a median follow-up period of 8.4 months, the mass effect relief rate was 71.6% (156/218). Notably, immediate aneurysm occlusion following treatment was significantly associated with mass effect relief (OR 0.392, 95% CI, 0.170 to 0.907, p=0.029). Subgroup analysis demonstrated that adjunctive coiling contributed to mass effect relief in cavernous aneurysms, while dense embolism impeded symptom relief in aneurysms<10 mm and saccular aneurysms. CONCLUSIONS: Our data confirmed the efficacy of PED in relieving mass effect. The findings of this study provide support for endovascular treatment to alleviate mass effect in unruptured intracranial aneurysms. TRIAL REGISTRATION NUMBER: NCT03831672.

Establishment of a prognostic model to predict chemotherapy response and identification of RAC3 as a chemotherapeutic target in bladder cancer.

Cisplatin-based chemotherapy is considered the primary treatment option for patients with advanced bladder cancer (BCa). However, the objective response rate to chemotherapy is often unsatisfactory, leading to a poor 5-year survival rate. Furthermore, current strategies for evaluating chemotherapy response and prognosis are limited and inefficient. In this study, we aimed to address these challenges by establishing a chemotherapy response type gene (CRTG) signature consisting of 9 genes and verified the prognostic value of this signature using TCGA and GEO BCa cohorts. The risk scores based on the CRTG signature were found to be associated with advanced clinicopathological status and demonstrated favorable predictive power for chemotherapy response in the TCGA cohort. Meanwhile, tumors with high risk scores exhibited a tendency toward a "cold tumor" phenotype. These tumors showed a low abundance of T cells, CD8+ T cells and cytotoxic lymphocytes, along with a high abundance of cancer-associated fibroblasts. Moreover, they displayed higher mRNA levels of these immune checkpoints: CD200, CD276, CD44, NRP1, PDCD1LG2 (PD-L2), and TNFSF9. Furthermore, we developed a nomogram that integrated the CRTG signature with clinicopathologic risk factors. This nomogram proved to be a more effective tool for predicting the prognosis of BCa patients. Additionally, we identified Rac family small GTPase 3 (RAC3) as a biomarker in our model. RAC3 was found to be overexpressed in chemoresistant BCa tissues and enhance the chemotherapeutic resistance of BCa cells in vitro and in vivo by regulating the PAK1-ERK1/2 pathway. In conclusion, our study presents a novel CRTG model for predicting chemotherapy response and prognosis in BCa. We also highlight the potential of combining chemotherapy with immunotherapy as a promising strategy for chemoresistant BCa and that RAC3 might be a latent target for therapeutic intervention.

Rational Atom Substitution to Obtain Efficient, Lead-Free Photocatalytic Perovskites Assisted by Machine Learning and DFT Calculations.

Inorganic lead-free halide perovskites, devoid of toxic or rare elements, have garnered considerable attention as photocatalysts for pollution control, CO2 reduction and hydrogen production. In the extensive perovskite design space, factors like substitution or doping level profoundly impact their performance. To address this complexity, a synergistic combination of machine learning models and theoretical calculations were used to efficiently screen substitution elements that enhanced the photoactivity of substituted Cs2 AgBiBr6 perovskites. Machine learning models determined the importance of d10 orbitals, highlighting how substituent electron configuration affects electronic structure of Cs2 AgBiBr6 . Conspicuously, d10 -configured Zn2+ boosted the photoactivity of Cs2 AgBiBr6 . Experimental verification validated these model results, revealing a 13-fold increase in photocatalytic toluene conversion compared to the unsubstituted counterpart. This enhancement resulted from the small charge carrier effective mass, as well as the creation of shallow trap states, shifting the conduction band minimum, introducing electron-deficient Br, and altering the distance between the B-site cations d band centre and the halide anions p band centre, a parameter tuneable through d10 configuration substituents. This study exemplifies the application of computational modelling in photocatalyst design and elucidating structure-property relationships. It underscores the potential of synergistic integration of calculations, modelling, and experimental analysis across various applications.

Insular cortex Hounsfield units predict postoperative neurocardiogenic injury in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Our study aims to investigate the association between the Hounsfield unit (Hu) value of the insular cortex (IC) during emergency admission and the subsequent occurrence of post-operative neurocardiogenic injury (NCI) among patients afflicted with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Patients baseline characteristics were juxtaposed between those with and without NCI. The significant variables were incorporated into a multivariable stepwise logistic regression model. Receiver operating characteristic (ROC) curves were drafted for each significant variable, yielding cutoff values and the area under the curve (AUC). Subgroup and sensitivity analyses were performed to assess the predictive performance across various cohorts and ascertain result stability. Propensity score matching (PSM) was ultimately employed to redress any baseline characteristic disparities. RESULTS: Patients displaying a right IC Hu value surpassing 28.65 exhibited an escalated risk of postoperative NCI upon confounder adjustment (p < 0.001). The ROC curve eloquently manifested the predictive capacity of right IC Hu in relation to NCI (AUC = 0.650, 95%CI, 0.591-0.709, p < 0.001). Further subgroup analysis revealed significant interactions between right IC Hu and factors such as age, history of heart disease, and Graeb 5-12 score. Sensitivity analysis further upheld the results' significant (p = 0.002). The discrepancy in NCI incidence between the two groups, both prior (p < 0.002) and post (p = 0.039) PSM, exhibited statistical significance. After PSM implementation, the likelihood of NCI displayed an ascending trend with increasing right IC Hu values, from the Hu1 cohort onward, receding post the Hu4 cohort. CONCLUSION: This study definitively establishes an elevated right IC Hu value in the early stages of emergency admission as an autonomous predictor for ensuing NCI subsequent to aSAH.

Establishment of a novel indicator of pyroptosis regulated gene transcription level and its application in pan-cancer.

Pyroptosis is a type of programmed cell death and plays a dual role in distinct cancers. It is elusive to evaluate the activation level of pyroptosis and to appraise the involvement of pyroptosis in the occurrence and development of diverse tumors. Accordingly, we herein established an indicator to evaluate pyroptosis related gene transcription levels based on the expression level of genes involved in pyroptosis and tried to elaborated on the association between pyroptosis and tumors across diverse tumor types. We found that pyroptosis related gene transcription levels could predict the prognosis of patients, which could act as either a favorable or a dreadful factor in diverse cancers. According to signaling pathway analyses we observed that pyroptosis played a significant role in immune regulation and tumorigenesis and had strong links with other forms of cell death. We also performed analysis on the crosstalk between pyroptosis and immune status and further investigated the predictive potential of pyroptosis level for the efficacy of immunotherapy. Lastly, we manifested that pyroptosis status could serve as a biomarker to the efficacy of chemotherapy across various cancers. In summary, this study established a quantitative indicator to evaluate pyroptosis related gene transcription levels, systematically explored the role of pyroptosis in pan-cancer. These results could provide potential research directions targeting pyroptosis, and highlighted that pyroptosis may be used to develop a novel strategy for the treatment of cancer.

Long-term outcomes of microsurgery and stereotactic radiosurgery as the first-line treatment for arteriovenous malformations: a propensity score-matched analysis using nationwide multicenter prospective registry data.

BACKGROUND: This study aimed to compare the risk and benefit profile of microsurgery (MS) and stereotactic radiosurgery (SRS) as the first-line treatment for unruptured and ruptured arteriovenous malformations (AVMs). MATERIALS AND METHODS: The authors included AVMs underwent MS or SRS as the first-line treatment from a nationwide prospective multicenter registry in mainland China. The authors used propensity score-matched methods to balance baseline characteristics between the MS and SRS groups. The primary outcomes were long-term hemorrhagic stroke or death, and the secondary outcomes were long-term obliteration and neurological outcomes. Subgroup analyses and sensitivity analyses with different study designs were performed to confirm the stability of our findings. RESULTS: Of the 4286 consecutive AVMs in the registry from August 2011 to December 2021; 1604 patients were eligible. After matching, 244 unruptured and 442 ruptured AVMs remained for the final analysis. The mean follow-up duration was 7.0 years in the unruptured group and 6.1 years in the ruptured group. In the comparison of primary outcomes, SRS was associated with a higher risk of hemorrhagic stroke or death both in the unruptured and ruptured AVMs (unruptured: hazard ratio 4.06, 95% CI: 1.15-14.41; ruptured: hazard ratio 4.19, 95% CI: 1.58-11.15). In terms of the secondary outcomes, SRS was also observed to have a significant disadvantage in long-term obliteration [unruptured: odds ratio (OR) 0.01, 95% CI: 0.00-0.04; ruptured: OR 0.09, 95% CI: 0.05-0.15]. However, it should be noted that SRS may have advantages in preventing neurofunctional decline (unruptured: OR 0.56, 95% CI: 0.27-1.14; ruptured: OR 0.41, 95% CI: 0.23-0.76). The results of subgroup analyses and sensitivity analyses were consistent in trend but with slightly varied powers. CONCLUSIONS: This clinical practice-based real-world study comprehensively compared MS and SRS for AVMs with long-term outcomes. MS is more effective in preventing future hemorrhage or death and achieving obliteration, while the risk of neurofunctional decline should not be ignored.

Inflammatory Burden Index: Association Between Novel Systemic Inflammatory Biomarkers and Prognosis as Well as in-Hospital Complications of Patients with Aneurysmal Subarachnoid Hemorrhage.

Purpose: Systemic inflammation plays an important role in the pathophysiology and progression of aneurysmal subarachnoid hemorrhage (aSAH). In this study, we aimed to investigate the association between a new biomarker, the inflammatory burden index (IBI) and the prognosis as well as in-hospital complications of aSAH patients. Patients and Methods: We analyzed data from patients with aSAH between January 2019 and September 2022 who were included in the LongTEAM (Long-term Prognosis of Emergency Aneurysmal Subarachnoid Hemorrhage) registry study. The IBI was formulated as C-reactive protein × neutrophils/lymphocytes. The unfavorable functional prognosis was assessed by the modified Rankin Scale (mRS). Receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal cut-off values for IBI to distinguish the unfavorable functional prognosis. Multivariate logistic regression was applied to investigate the association between IBI and in-hospital complications. Propensity score matching was adjusted for imbalances in baseline characteristics to assess the effect of IBI on prognosis. Results: A total of 408 consecutive patients with aSAH enrolled in the study, of which 235 (57.6%) were female patients and the mean age was 55.28 years old. An IBI equal to 138.03 was identified as the best cut-off threshold to distinguish the unfavorable prognosis at 3 months (area under the curve [AUC] [95% CI] 0.637 [0.568-0.706]). ln IBI was independently associated with 3-month functional prognosis (OR [95% CI] 1.362 [1.148-1.615]; P<0.001), pneumonia (OR [95% CI] 1.427 [1.227-1.659]; P<0.001) and deep venous thrombosis (DVT). (OR [95% CI] 1.326 [1.124-1.564]; P=0.001). After propensity score matching (57:57), an increased proportion of patients with IBI ≥138.03 had a poor functional prognosis at 3 months and in-hospital complications including developed pneumonia and DVT. Conclusion: In patients with aSAH, high IBI level at admission was associated with unfavorable functional prognosis as well as pneumonia and deep vein thrombosis.

Comparison of Long-Term Outcomes in Ruptured Diffuse Brain Arteriovenous Malformations Between Interventional Therapy and Conservative Management.

Brain arteriovenous malformations (AVMs) with a diffuse nidus structure present a therapeutic challenge due to their complexity and elevated risk of hemorrhagic events. This study examines the long-term effectiveness of interventional therapy versus conservative management in reducing hemorrhagic stroke or death in patients with ruptured diffuse AVMs. The analysis was conducted based on a multi-institutional database in China. Patients were divided into two groups: conservative management and interventional therapy. Using propensity score matching, patients were compared for the primary outcome of hemorrhagic stroke or death and the secondary outcomes of disability and neurofunctional decline. Out of 4286 consecutive AVMs in the registry, 901 patients were eligible. After matching, 70 pairs of patients remained with a median follow-up of 4.0 years. The conservative management group showed a trend toward higher rates of the primary outcome compared to the interventional group (4.15 vs. 1.87 per 100 patient-years, P = 0.090). While not statistically significant, intervention reduced the risk of hemorrhagic stroke or death by 55% (HR, 0.45 [95% CI 0.18-1.14], P = 0.094). No significant differences were observed in secondary outcomes of disability (OR, 0.89 [95% CI 0.35-2.26], P = 0.813) and neurofunctional decline (OR, 0.65 [95% CI 0.26 -1.63], P = 0.355). Subgroup analysis revealed particular benefits in interventional therapy for AVMs with a supplemented S-M grade of II-VI (HR, 0.10 [95% CI 0.01-0.79], P = 0.029). This study suggests a trend toward lower long-term hemorrhagic risks with intervention when compared to conservative management in ruptured diffuse AVMs, especially within supplemented S-M grade II-VI subgroups. No evidence indicated that interventional approaches worsen neurofunctional outcomes.

Effective Suppressing Phase Segregation of Mixed-Halide Perovskite by Glassy Metal-Organic Frameworks.

Lead mixed-halide perovskites offer tunable bandgaps for optoelectronic applications, but illumination-induced phase segregation can quickly lead to changes in their crystal structure, bandgaps, and optoelectronic properties, especially for the Br-I mixed system because CsPbI3 tends to form a non-perovskite phase under ambient conditions. These behaviors can impact their performance in practical applications. By embedding such mixed-halide perovskites in a glassy metal-organic framework, a family of stable nanocomposites with tunable emission is created. Combining cathodoluminescence with elemental mapping under a transmission electron microscope, this research identifies a direct relationship between the halide composition and emission energy at the nanoscale. The composite effectively inhibits halide ion migration, and consequently, phase segregation even under high-energy illumination. The detailed mechanism, studied using a combination of spectroscopic characterizations and theoretical modeling, shows that the interfacial binding, instead of the nanoconfinement effect, is the main contributor to the inhibition of phase segregation. These findings pave the way to suppress the phase segregation in mixed-halide perovskites toward stable and high-performance optoelectronics.

A clinically practical model for the preoperative prediction of lymph node metastasis in bladder cancer: a multicohort study.

BACKGROUND: The aim of this study was to construct a clinically practical model to precisely predict lymph node (LN) metastasis in bladder cancer patients. METHODS: Four independent cohorts were included. The least absolute shrinkage and selection operator regression with multivariate logistic regression were applied. The diagnostic efficacy of LN score and CT/MRI was compared by accuracy, sensitivity, specificity, and area under curve (AUC). RESULTS: A total of 606 patients were included to develop a basic prediction model. After multistep gene selection, the LN metastasis prediction model was constructed with 5 genes. The model can accurately predict LN metastasis with an AUC of 0.781. For clinically practical use, we transformed the model into a Fast LN Scoring System using the SYSMH cohort (n = 105). High LN score patients exhibited a 72.2% LN metastasis rate, while low LN score patients showed a 3.4% LN metastasis rate. The LN score achieved a superior accuracy than CT/MRI (0.882 vs. 0.727). Application of LN score can correct the diagnosis of 88% (22/25) patients who were misdiagnosed by CT/MRI. DISCUSSION: The clinically practical LN score can precisely, rapidly, and conveniently predict LN status, which will assist preoperative diagnosis for LN metastasis and guide precise therapy.

Synthesis of Layered Lead-Free Perovskite Nanocrystals with Precise Size and Shape Control and Their Photocatalytic Activity.

Halide perovskites have attracted enormous attention due to their potential applications in optoelectronics and photocatalysis. However, concerns over their instability, toxicity, and unsatisfactory efficiency have necessitated the development of lead-free all-inorganic halide perovskites. A major challenge in designing efficient halide perovskites for practical applications is the lack of effective methods for producing nanocrystals with precise size and shape control. In this work, a layered perovskite, Cs4ZnSb2Cl12 (CZS), is found from calculations to exhibit size- and facet-dependent optoelectronic properties in the nanoscale, and thus, a colloidal method is used to synthesize the CZS nanoparticles with size-tunable morphologies: zero- (nanodots), one- (nanowires and nanorods), two- (nanoplates), and three-dimensional (nanopolyhedra). The growth kinetics of the CZS nanostructures, along with the effects of surface ligands, reaction temperature, and time were investigated. The optoelectronic properties of the nanocrystals varied with size due to quantum confinement effects and with shape due to anisotropy within the crystals and the exposure of specific facets. These properties could be modulated to enhance the visible-light photocatalytic performance for toluene oxidation. In particular, the 9.7 nm CZS nanoplates displayed a toluene to benzaldehyde conversion rate of 1893 µmol g-1 h-1 (95% selectivity), 500 times higher than the bulk synthesized CZS, and comparable with the reported photocatalysts. This study demonstrates the integration of theoretical calculations and synthesis, revealing an approach to the design and fabrication of novel, high-performance colloidal perovskite nanocrystals for optoelectronic and photocatalytic applications.

UBE2S interacting with TRIM21 mediates the K11-linked ubiquitination of LPP to promote the lymphatic metastasis of bladder cancer.

Lymphatic metastasis is the most common pattern of bladder cancer (BCa) metastasis and has an extremely poor prognosis. Emerging evidence shows that ubiquitination plays crucial roles in various processes of tumors, including tumorigenesis and progression. However, the molecular mechanisms underlying the roles of ubiquitination in the lymphatic metastasis of BCa are largely unknown. In the present study, through bioinformatics analysis and validation in tissue samples, we found that the ubiquitin-conjugating E2 enzyme UBE2S was positively correlated with the lymphatic metastasis status, high tumor stage, histological grade, and poor prognosis of BCa patients. Functional assays showed that UBE2S promoted BCa cell migration and invasion in vitro, as well as lymphatic metastasis in vivo. Mechanistically, UBE2S interacted with tripartite motif containing 21 (TRIM21) and jointly induced the ubiquitination of lipoma preferred partner (LPP) via K11-linked polyubiquitination but not K48- or K63-linked polyubiquitination. Moreover, LPP silencing rescued the anti-metastatic phenotypes and inhibited the epithelial-mesenchymal transition of BCa cells after UBE2S knockdown. Finally, targeting UBE2S with cephalomannine distinctly inhibited the progression of BCa in cell lines and human BCa-derived organoids in vitro, as well as in a lymphatic metastasis model in vivo, without significant toxicity. In conclusion, our study reveals that UBE2S, by interacting with TRIM21, degrades LPP through K11-linked ubiquitination to promote the lymphatic metastasis of BCa, suggesting that UBE2S represents a potent and promising therapeutic target for metastatic BCa.

Fabrication and Characterization of 2D Layered Perovskites with a Gradient Band Gap.

Vertical gradient band-gap heterostructures of two-dimensional (2D) layered perovskites have attracted considerable research interest due to their superior optoelectronic properties and demonstrated potential for use in optical devices. However, its fabrication has been challenging. In this investigation, 2D Ruddlesden-Popper mixed halide perovskite single crystals with a vertical gradient band gap were synthesized by using a solid-state halide diffusion process. X-ray diffraction (XRD) and scanning electron microscopy (SEM) measurements after diffusion confirm that the crystalline and morphology remain intact. The transmittance and photoluminescence (PL) spectra show the formation of a vertical gradient band gap that is ascribed to gradient halide distribution through halide intermixing. The mixed halide crystal exhibits high stability with completely suppressed phase segregation in the time-dependent PL measurement. The time-resolved photoluminescence (TRPL) spectra prove that the mixed halide sample has an enhanced carrier transport due to the Förster resonance energy transfer (FRET) effect. Besides, the halide diffusion behavior is found to be different from the previously proposed "layer-by-layer" diffusion model in exfoliated crystals. The gradient band-gap structure is critical for various applications in which vertical carrier transport is demanded.

Prevalence and Procedural Risk of Intracranial Atherosclerotic Stenosis Coexisting With Unruptured Intracranial Aneurysm.

BACKGROUND: Coexistence of intracranial atherosclerotic stenosis (ICAS) and unruptured intracranial aneurysms (UIAs) is increasingly encountered in clinical practice. This study aims to determine the prevalence of ICAS in patients with UIAs and procedural ischemic risk associated with ICAS when treating UIAs. METHODS: Based on the CAIASA study (Coexistence of Atherosclerotic Intracranial Arterial Stenosis With Intracranial Aneurysms), we prospectively included patients undergoing treatment procedures for UIAs from October 2015 to December 2020 at Beijing Tiantan Hospital, China. We used computed tomography angiography or digital subtraction angiography to diagnose ICAS (stenosis≥50%). Multivariable logistic regression and propensity-score matching were performed to evaluate the risk of procedure-related ischemic stroke and unfavorable outcome associated with ICAS. The ICAS score was used to explore the association between different burden of ICAS and procedure-related ischemic risk. RESULTS: Among 3949 patients who underwent endovascular or open surgical procedures for UIAs, 245 (6.2%) had ICAS. After exclusion, 15.7% (32/204) of patients with ICAS experienced procedure-related ischemic stroke compared with 5.0% (141/2825) of patients without ICAS. From the unmatched and matched cohort, ICAS was significantly associated with increased risk of procedure-related ischemic stroke (unmatched: adjusted odds ratio=3.11 [1.89-5.11]; and matched: adjusted odds ratio=2.99 [1.38-6.48]). This association became more evident among patients not receiving antiplatelet therapy (Pinteraction=0.022). For patients undergoing different treatment modalities, similar increased risks were observed (clipping: adjusted odds ratio=3.43 [1.73-6.79]; and coiling: adjusted odds ratio=3.59 [1.94-6.65]). Higher ICAS score was correlated with higher procedural ischemic risk (Ptrend<0.001). CONCLUSIONS: The occurrence of ICAS is not infrequent in patients with UIAs. ICAS confers an ~2-fold increased procedural ischemic risk, irrespective of clipping or coiling. Previous antiplatelet therapy may decrease the risk. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02795078.

Learning curve in pipeline embolization device: results from the pipeline embolization device in China post-market multicentre registry study.

BACKGROUND: Intracranial aneurysms pose a significant health issue, affecting 3-5% of the adult population. The pipeline embolization device (PED) has emerged as a promising treatment for these lesions. This study aimed to investigate the impact of operator experience on complication and poor outcome rates, as well as the learning curve for PED. METHODS: A total of 217 patients were consecutively enroled from four eligible centres and divided into three groups based on the number of procedures performed: group 1 (first 10 procedures), group 2 (11-20 procedures), and group 3(>20 procedures). Major complications include operation-related ischaemic or haemorrhagic events and mass effect deterioration. Poor outcome was defined as a modified Rankin Scale score greater than 2 at discharge. Cumulative summation (CUSUM) analysis was generated to assess the learning curve according to major complications and poor outcome. RESULTS: The study found that major complications and poor outcomes occurred in 5.1% and 2.3% of cases, respectively. The rate of major complications decreased from 10.0% in group 1 to 2.9% in group 3 ( P =0.053), while the rate of poor outcomes decreased from 7.5% in group 1 to 0.7% in group 3 ( P =0.015). Multivariable regression analysis adjusted for covariates showed that operator experience was associated with a lower rate of poor outcomes ( P =0.034). CUSUM analysis demonstrated that the learning curve for avoiding major complications and poor outcomes required 27 (mean=13) and 40 (mean=20) cases, respectively. CONCLUSIONS: These findings suggest that PED treatment requires a learning curve of 40 cases to achieve reproducibility regarding complications and functional results. Additionally, major complications and poor outcomes significantly decreases after the first 20 procedures. CUSUM analysis can serve as a useful tool for monitoring and assessing surgical performance.