IGSF8 is an innate immune checkpoint and cancer immunotherapy target.

Antigen presentation defects in tumors are prevalent mechanisms of adaptive immune evasion and resistance to cancer immunotherapy, whereas how tumors evade innate immunity is less clear. Using CRISPR screens, we discovered that IGSF8 expressed on tumors suppresses NK cell function by interacting with human KIR3DL2 and mouse Klra9 receptors on NK cells. IGSF8 is normally expressed in neuronal tissues and is not required for cell survival in vitro or in vivo. It is overexpressed and associated with low antigen presentation, low immune infiltration, and worse clinical outcomes in many tumors. An antibody that blocks IGSF8-NK receptor interaction enhances NK cell killing of malignant cells in vitro and upregulates antigen presentation, NK cell-mediated cytotoxicity, and T cell signaling in vivo. In syngeneic tumor models, anti-IGSF8 alone, or in combination with anti-PD1, inhibits tumor growth. Our results indicate that IGSF8 is an innate immune checkpoint that could be exploited as a therapeutic target.

Target mediated bioreaction to engineer surface vacancy effect on Bi2O2S nanosheets for photoelectrochemical detection of FEN1.

Photoelectrochemistry represents a promising technique for bioanalysis, though its application for the detection of Flap endonuclease 1 (FEN1) has not been tapped. Herein, this work reports the exploration of creating oxygen vacancies (Ov) in situ onto the surface of Bi2O2S nanosheets via the attachment of dopamine (DA), which underlies a new anodic PEC sensing strategy for FEN1 detection in label-free, immobilization-free and high-throughput modes. In connection to the target-mediated rolling circle amplification (RCA) reaction for modulating the release of the DA aptamer to capture DA, the detection system showed good performance toward FEN1 analysis with a linear detection range of 0.001-10 U/mL and a detection limit of 1.4 × 10-4 U/mL (S/N = 3). This work features the bioreaction engineered surface vacancy effect of Bi2O2S nanosheets as a PEC sensing strategy, which allows a simple, easy to perform, sensitive and selective method for the detection of FEN1. This sensing strategy might have wide applications in versatile bioasssays, considering the diversity of a variety of biological reactions may produce the DA aptamer.

Thioredoxin Reductase-Mediated Reaction Evokes In Situ Surface Polarization Effect on BiOIO3: Toward a New Sensing Strategy for Cathodic Photoelectrochemistry.

We have witnessed the fast progress of cathodic photoelectrochemistry over the past decades, though its signal transduction tactic still lacks diversity. Exploring new sensing strategies for cathodic photoelectrochemistry is extremely demanding yet hugely challenging. This article puts forward a unique idea to incorporate an enzymatic reaction-invoked surface polarization effect (SPE) on the surface of BiOIO3 to implement an innovative cathodic photoelectrochemical (PEC) bioanalysis. Specifically, the thioredoxin reductase (TrxR)-mediated reaction produced the polar glutathione (GSH), which spontaneously coordinated to the surface of BiOIO3 and induced SPE by forming a polarized electric field, resulting in improved electron (e-) and hole (h+) pair separation efficiency and an enhanced photocurrent output. Correlating this phenomenon with the detection of TrxR exhibited a high performance in terms of sensitivity and selectivity, achieving a linear range of 0.007-0.5 µM and a low detection limit of 2.0 nM (S/N = 3). This study brings refreshing inspiration for the cathodic PEC signal transduction tactic through enzyme-mediated in situ reaction to introduce SPE, which enriches the diversity of available signaling molecules. Moreover, this study unveils the potential of in situ generated SPE for extended and futuristic applications.

The Potential of Gut Microbiota in Prediction of Stroke-Associated Pneumonia.

BACKGROUND: Stroke-associated pneumonia (SAP) is a common stroke complication, and the changes in the gut microbiota composition may play a role. Our study aimed to evaluate the predictive ability of gut microbiota for SAP. METHODS: Acute ischemic stroke patients were prospectively enrolled and divided into two groups based on the presence or absence of SAP. The composition of gut microbiota was characterized by the 16S RNA Miseq sequencing. The gut microbiota that differed significantly between groups were incorporated into the conventional risk scores, the Acute Ischemic Stroke-Associated Pneumonia Score (AIS-APS), and the Age, Atrial fibrillation, Dysphagia, Sex, Stroke Severity Score (A2DS2). The predictive performances were assessed in terms of the area under the curve (AUC), the Net Reclassification Improvement (NRI), and the Integrated Discrimination Improvement (IDI) indices. RESULTS: A total of 135 patients were enrolled, of whom 43 had SAP (31%). The short-chain fatty acids (SCFAs)-producing bacteria, such as Bacteroides, Fusicatenibacter, and Butyricicoccus, were decreased in the SAP group. The integrated models showed better predictive ability for SAP (AUC = 0.813, NRI = 0.333, p = 0.052, IDI = 0.038, p = 0.018, for AIS-APS; AUC = 0.816, NRI = 0.575, p < 0.001, IDI = 0.043, p = 0.007, for A2DS2) in comparison to the differential genera (AUC = 0.699) and each predictive score (AUCAISAPS = 0.777; AUCA2DS2 = 0.777). CONCLUSIONS: The lower abundance of SCFAs-producing gut microbiota after acute ischemic stroke was associated with SAP and may play a role in SAP prediction.

Alleviate environmental concerns with biochar as a container substrate: a review.

Peat moss has desirable properties as a container substrate, however, harvesting it from peatland for greenhouse/nursery production use has disturbed peatland ecosystem and caused numerous environmental concerns. More recently, many nations have taken actions to reduce or ban peat moss production to reach the carbon neutral goal and address the environmental concerns. Also, the overuse of fertilizers and pesticides with peat moss in greenhouse/nursery production adds extra environmental and economic issues. Thus, it is urgent to find a peat moss replacement as a container substrate for greenhouse/nursery production. Biochar, a carbon-rich material with porous structure produced by the thermo-chemical decomposition of biomass in an oxygen-limited or oxygen-depleted atmosphere, has drawn researchers' attention for the past two decades. Using biochar to replace peat moss as a container substrate for greenhouse/nursery production could provide environmental and economic benefits. Biochar could be derived from various feedstocks that are regenerated faster than peat moss, and biochar possesses price advantages over peat moss when local feedstock is available. Certain types of biochar can provide nutrients, accelerate nutrient adsorption, and suppress certain pathogens, which end up with reduced fertilizer and pesticide usage and leaching. However, among the 36,474 publications on biochar, 1,457 focused on using biochar as a container substrate, and only 68 were used to replace peat moss as a container substrate component. This study provides a review for the environmental and economic concerns associated with peat moss and discussed using biochar as a peat moss alternative to alleviate these concerns.

Sex differences in outcomes after endovascular treatment of patients with vertebrobasilar artery occlusion.

BACKGROUND: Current studies on the role of sex in the prognosis of acute vertebrobasilar artery occlusion (VBAO) are limited. We aimed to explore whether there are sex differences on outcomes in patients treated with endovascular therapy (EVT) for VBAO. METHODS: Patients from December 2015 to December 2018 with acute VBAO within 24 h of the estimated occlusion time in 21 stroke centers in China were retrospectively analyzed. Baseline data between sexes were compared in the total population cohort and propensity score (PS)-matched cohort. Multivariate logistic regression and ordinal regression were used to analyze the association of sex with outcomes. Mixed-effects regression model was performed for changes in modified Rankin Scale (mRS) scores in men and women from 90 days to 1 year after discharge. RESULTS: A total of 577 patients (28.4% women) were finally included. Multivariate logistic regression showed that women had a lower probability of favorable outcome (mRS score 0-3 at 90 days; OR 0.544; 95% CI 0.329-0.899) and functional independence (mRS score 0-2 at 90 days; OR 0.391; 95% CI 0.228-0.670) as well as a higher possibility of shifting to worse mRS (OR 1.484; 95% CI 1.020-2.158) than men. After PS matching, 391 patients (39.4% women) were analyzed, confirming the same results regarding favorable outcome (OR 0.580; 95% CI 0.344-0.977), functional independence (OR 0.394; 95% CI 0.218-0.712), and shift mRS (OR 1.504; 95% CI 1.023-2.210). However, the results of repeated ANOVA showed that men and women had a comparable functional recovery from 90 days to 1 year. CONCLUSIONS: Stroke due to VBAO treated with EVT is associated with worse outcomes in women than in men. However, men and women showed similar long-term improvement trends.

Malnutrition and poststroke depression in patients with ischemic stroke.

BACKGROUND: Identifying high-risk patients based on modifiable clinical characteristics, such as malnutrition, is critical to intervening with these variables to reduce the risk of post-stroke depression (PSD). The aim of this study was to investigate the effect of nutritional status on the risk of incident PSD and the trajectory of PSD risk. METHODS: Consecutive patients with acute ischemic stroke were recruited in this observational cohort and followed up for 1 year. Multivariate logistic regressions and multilevel mixed-effects logistic regressions with random intercepts and slopes were used to investigate the effects of nutritional indexes [the Controlling Nutritional Status (CONUT) score, the Nutritional Risk Index (NRI), and the Prognostic Nutritional Index (PNI)] and body mass index (BMI) on the risk of incident PSD and the trajectory of PSD risk over the 12-month observation period. RESULTS: A total of 538 patients were included in the final analysis. Worsening CONUT [odds ratio (OR) = 1.36; confidence interval (CI): 1.15-1.61], NRI (OR = 0.91; CI: 0.87-0.96) and PNI (OR = 0.89; CI: 0.84-0.95) scores were significantly associated with an increased risk of incident PSD. Moderate and severe risk malnutrition statuses were associated with higher incidences of PSD regardless of the malnutrition index (CONUT, NRI or PNI). Additionally, PSD risk decreased over time with a significant two-way interaction between time and CONUT, NRI, and PNI, implying that patients with elevated exposure to malnutrition showed a slower decline in PSD risk. BMI had no significant effect on the occurrence and development of PSD. CONCLUSION: Malnutrition, but not BMI, was associated with a higher probability of incident PSD and was more likely to lead to a slower rate of decline in PSD risk.

Catechol exerts an in situ surface oxygen vacancy effect on BiOI: an innovative signal transduction mode for cathodic photoelectrochemistry.

Cathodic photoelectrochemistry, a research hotspot in state-of-art bioassays, is generally circumscribed by its monotonous signal transduction tactic of photoinduced electron transfer (PET) mechanism, which significantly narrows the scope of its applications. In this study, we reveal the surface oxygen vacancy (VO) formation elicited by the spontaneous coordination of catechol (CA) onto the surface of BiOI nanoplates for the innovative operation of the cathodic PEC signal transduction tactic. The in situ-generated VO functions as a carrier separation center to efficiently promote photocurrent generation. Taking tyrosinase (TYR) and Escherichia coli O157:H7 (E. coli O157:H7) as model targets, the established signal transduction tactic was validated as efficient and sensitive for the detection of the two targets with linear ranges from 1.0 × 10-4 to 1.0 U mL-1 and 5.0 to 1.0 × 106 CFU mL-1, respectively. Low-detection limits of 1.0 × 10-4 U mL-1 and 3.0 CFU mL-1 were achieved for TYR and E. coli O157:H7, respectively. This study opens up a new perspective of in situ generated surface VO on semiconductors, which underlies an innovative PEC signal transduction mechanism with convincing analytical performance. Hopefully, it might encourage more explorations of new methodologies for introducing surface vacancies with exquisite applications.

2,3-Dihydroxynaphthalene invoked surface oxygen vacancy effect on Fe2O3 nanorods for photoanodic signal transduction tactic.

The state-of-art signal transduction mechanism of anodic photoelectrochemistry is constrained to the hole oxidation reaction, which greatly hinders its application for prospective biosensing applications. Herein, we present an innovative strategy for signal transduction by exploiting the in situ formation of surface oxygen vacancies (VOs) on Fe2O3 nanorods (NRs) through the self-coordination of 2,3-dihydroxynaphthalene (2,3-DHN) on their surfaces. The 2,3-DHN was connected with Fe(Ⅲ) on the surface of Fe2O3 NRs vis the formation of the five-membered ring structures accompanied by the generation of VOs. And the generated VOs introduced a new defect energy level for trapping the photogenerated holes, which enhanced the charge separation and realized the enhancement of photocurrent signal. The developed signal transduction strategy was validated by the first photoelectrochemical (PEC) sensing platform for ß-glucoside (ß-Glu) and lipase (LPS), which can catalyze the hydrolysis of 3-hydroxy-2-naphthalenyl-ß-D-glucoside and naphthalene-2,3-diol diacetate, respectively, to produce 2,3-DHN for signal stimuli. The ß-Glu and LPS were detected with linear ranges of 0.01-10.0 U/mL and 0.001-5.0 mg/mL, respectively. Detection limits of 3.3 × 10-3 U/mL and 0.32 µg/mL (S/N = 3) were achieved, for ß-Glu and LPS, respectively. The present study not only provides a new strategy for spontaneous induction of VOs in situ for n-type semiconductors, but also innovates the anodic PEC signal transduction strategy with broadened biosensing applications.

Trap remediation of CuBi2O4 nanopolyhedra via surface self-coordination by H2O2: an innovative signaling mode for cathodic photoelectrochemical bioassay.

This work conveys a new philosophy of surface self-coordination mediated trap remediation for innovative cathodic photoelectrochemical (PEC) signal transduction. Initially, the surface trap states of CuBi2O4 nanopolyhedra resulting from dangling bonds can function as charge carrier recombination centers, which suppress the carrier separation efficiency and result in a low photocurrent output. Particularly, hydrogen peroxide (H2O2) spontaneously interacts with the uncoordinated Cu(II) on the surface of CuBi2O4, enabling efficient elimination of dangling bonds and remedy of trap states, thereby outputting intensified photocurrent readout. Exemplified by Flap endonuclease 1 (FEN1) as a model target, a tetrahedron DNA (THD)-based strand displacement amplification (SDA) was introduced to manipulate the formation of hemin impregnated G-quadruplex (G-quadruplex/hemin) DNAzyme and the resultant catalytic reduction for H2O2. In addition, a highly efficient and ultra-sensitive PEC sensing platform was achieved for FEN1 detection with a wide linear range from 1.0 fM to 100.0 pM and a detection limit of 0.3 fM (S/N = 3). This work not only establishes a new idea of cathodic PEC signal transduction, but also offers an efficient biosensing platform for FEN1.

3D hollow NiCo LDH nanocages anchored on 3D CoO sea urchin-like microspheres: A novel 3D/3D structure for hybrid supercapacitor electrodes.

The research on the structure of advanced electrode materials is significant in the field of supercapacitors. Herein, for the first time, we propose a novel 3D/3D composite structure by a multi-step process, in which 3D hollow NiCo LDH nanocages are immobilized on 3D sea urchin-like CoO microspheres. Results show that the 3D CoO acts as an efficient and stable channel for ion diffusion, while the hollow NiCo LDH provides abundant redox-active sites. The calculated results based on density function theory (DFT) show that the CoO@NiCo LDH heterostructure has an enhanced density of states (DOS) near the Fermi level and strong adsorption capacity for OH-, indicating its excellent electrical conductivity and electrochemical reaction kinetics. As a result, the CoO@NiCo LDH electrode has an areal specific capacity of 4.71C cm-2 at a current density of 3 mA cm-2 (440.19C g-1 at 0.28 A g-1) and can still maintain 88.76 % of the initial capacitance after 5000 cycles. In addition, the assembled hybrid supercapacitor has an energy density of 5.59 mWh cm-3 at 39.54 mW cm-3.

Effects of admission systemic inflammatory indicators on clinical outcomes in patients with vertebrobasilar artery occlusion: insight from the PERSIST registry.

BACKGROUND: Few studies have focused on the effect of systemic inflammation in vertebrobasilar artery occlusion (VBAO). The aim of this study was to investigate the relationship between inflammatory indicators and the prognosis of VBAO patients receiving endovascular treatment (EVT). METHOD: Patients with VBAO who were treated with EVT within 24 hours of the estimated occlusion time were included in this study. Multivariate logistic regression and elastic net regularization were performed to analyze the effects of inflammatory indicators on the prognosis of patients with VBAO. The primary outcome was unfavorable outcome (a modified Rankin Scale score of 4-6) at 90 days. Secondary outcomes included symptomatic intracranial hemorrhage, in-hospital mortality, 90 day mortality, 1 year unfavorable outcome, and mortality. RESULTS: 560 patients were included in the study. Multivariate analysis showed that white blood cells (W), neutrophils (N), neutrophil to lymphocyte ratio (NLR), platelet to neutrophil ratio, platelet to white blood cell ratio, and NLR to platelet ratio were associated with the primary outcome. Elastic net regularization indicated that W, N, and NLR were the major inflammatory predictors of unfavorable outcome at 90 days. For long term prognosis, we found that the inflammatory indicators that predicted 1 year outcomes were consistent with those that predicted 90 day outcomes. CONCLUSION: Inflammatory indicators, especially W, N, and NLR, were associated with moderate and long term prognosis of patients with VBAO treated with EVT.

Effects of perioperative glycemic indicators on outcomes of endovascular treatment for vertebrobasilar artery occlusion.

Objective: Endovascular treatment (EVT) is, to date, the most promising treatment of vertebrobasilar artery occlusion (VBAO). The study aimed to determine the influence of perioperative glucose levels on clinical outcomes in patients with acute VBAO treated with EVT. Methods: We retrospectively collected consecutive VBAO patients received EVT in 21 stroke centers in China. The associations between perioperative glycemic indicators (including fasting blood glucose[FBG], admission hyperglycemia, stress hyperglycemia ratio [SHR] and short-term glycemic variability [GV]) and various clinical outcomes were analyzed in all patients and subgroups stratified by diabetes mellitus (DM). Results: A total of 569 patients were enrolled. Admission hyperglycemia significantly correlated with increased risk of symptomatic intracranial hemorrhage (sICH) (odds ratio [OR] 3.24, 95% confidence interval [CI]: 1.40-7.46), poor functional outcomes at 90 days (OR 1.91, 95%CI: 1.15-3.18) and 1 year (OR 1.96, 95%CI: 1.20-3.22). Similar significant correlations exist between FBG, SHR, GV and all the adverse outcomes except higher levels GV was not associated with increased risk of sICH (OR 1.04, 95% CI: 0.97-1.12). Subgroup analyses showed that admission hyperglycemia, FBG and SHR were significantly associated with adverse outcomes in non-diabetic patients, but not in DM patients. While, GV was associated with poor functional outcomes regardless of diabetes history. Conclusions: Admission hyperglycemia, FBG, SHR and short-term GV in VBAO patients treated with EVT were associated with adverse outcomes. The results suggested that comprehensive evaluation and appropriate management of perioperative glucose might be important for patients with VBAO and treatment with EVT.

Association of Trimethylamine N-Oxide with Normal Aging and Neurocognitive Disorders: A Narrative Review.

Aging-related neurocognitive disorder (NCD) is a growing health concern. Trimethylamine-N-oxide (TMAO), a gut microbiota-derived metabolite from dietary precursors, might emerge as a promising biomarker of cognitive dysfunction within the context of brain aging and NCD. TMAO may increase among older adults, Alzheimer's disease patients, and individuals with cognitive sequelae of stroke. Higher circulating TMAO would make them more vulnerable to age- and NCD-related cognitive decline, via mechanisms such as promoting neuroinflammation and oxidative stress, and reducing synaptic plasticity and function. However, these observations are contrary to the cognitive benefit reported for TMAO through its positive effects on blood-brain barrier integrity, as well as from the supplementation of TMAO precursors. Hence, current disputable evidence does not allow definite conclusions as to whether TMAO could serve as a critical target for cognitive health. This article provides a comprehensive overview of TMAO documented thus far on cognitive change due to aging and NCD.

Association of Lesion Location and Fatigue Symptoms After Ischemic Stroke: A VLSM Study.

Background: Poststroke fatigue (PSF) is a common symptom in stroke survivors, yet its anatomical mechanism is unclear. Our study was aimed to identify which brain lesions are related to the PSF in patients with acute stroke. Method: Patients with first-ever acute ischemic stroke consecutively admitted from the first affiliated hospital of the University of Science and Technology of China (USTC) between January 2017 and June 2020. Fatigue was scored using the Fatigue Severity Scale. All the participants were assessed by 3.0 T brain MRI including diffusion-weighted imaging. The infarct lesions were delineated manually and transformed into a standard template. Voxel-based lesion-symptom mapping (VLSM) was applied to investigate the association between lesion location and the occurrence and severity of fatigue. The same analyses were carried out by flipping the left-sided lesions. Multivariate logistic regressions were applied to verify the associations. Results: Of the 361 patients with acute stroke, 142 (39.3%) patients were diagnosed with fatigue in the acute phase and 116 (35.8%) at 6 months after the index stroke. VLSM analysis indicated clusters in the right thalamus which was significantly associated with the occurrence and severity of PSF at 6-month follow-up. In contrast, no significant cluster was found in the acute phase of stroke. The flipped analysis did not alter the results. Multivariate logistic regression verified that lesion load in the right thalamus (OR 2.67, 95% CI 1.46-4.88) was an independent predictor of 6-month PSF. Conclusion: Our findings indicated that lesions in the right thalamus increased the risk of fatigue symptoms 6 months poststroke.

Life table construction for crapemyrtle bark scale (Acanthococcus lagerstroemiae): the effect of different plant nutrient conditions on insect performance.

Crapemyrtle Bark Scale (Acanthococcus lagerstroemiae; CMBS) is an invasive pest species that primarily infest crapemyrtles (Lagerstroemia spp.) in the United States. Recent reports have revealed the dire threat of CMBS to attack not only crapemrytles but also the U.S. native species with expanded host plants such as American beautyberry (Callicarpa spp.) and Hypericum kalmianum L. (St. Johnswort). A better understanding of plant-insect interaction will provide better and environmental-friendly pest management strategies. In this study, we constructed the first comprehensive life table for CMBS to characterize its biological parameters, including developmental stages, reproductive behavior, and fecundity. The indirect effects of three plant nutrient conditions (water, 0.01MS, and 0.1MS) on CMBS populations were examined using the age-stage, two-sex life table. The demographic analyses revealed that the plant nutrient conditions had significantly altered CMBS development in terms of the intrinsic rate of increase (r), the finite rate of increase (λ), the net reproductive rate (R0), and mean generation time (T). Higher r, λ, and R0 were recorded under nutrient-deficient conditions (water), while CMBS reared on plants with healthier growing conditions (0.1MS) had the most prolonged T. Overall, CMBS shows better insect performance when reared on plants under nutrient-deficient conditions.

Real-Time Feeding Behavior Monitoring by Electrical Penetration Graph Rapidly Reveals Host Plant Susceptibility to Crapemyrtle Bark Scale (Hemiptera: Eriococcidae).

Host range confirmation of invasive hemipterans relies on the evaluation of plant susceptibility though greenhouse or field trials, which are inefficient and time-consuming. When the green industry faces the fast-spreading threat of invasive pests such as crapemyrtle bark scale (Acanthococcus lagerstroemiae), it is imperative to timely identify potential host plants and evaluate plant resistance/susceptibility to pest infestation. In this study, we developed an alternative technology to complement the conventional host confirmation methods. We used electrical penetration graph (EPG) based technology to monitor the A. lagerstroemiae stylet-tip position when it was probing in different plant tissues in real-time. The frequency and relative amplitude of insect EPG waveforms were extracted by an R programming-based software written to generate eleven EPG parameters for comparative analysis between plant species. The results demonstrated that the occurrences of phloem phase and xylem phase offered conclusive evidence for host plant evaluation. Furthermore, parameters including the percentage of insects capable of accessing phloem tissue, time duration spent on initiating phloem phase and ingesting phloem sap, provided insight into why host plant susceptibility differs among similar plant species. In summary, this study developed a novel real-time diagnostic tool for quick A. lagerstroemiae host confirmation, which laid the essential foundation for effective pest management.

Initial symptoms of vertebrobasilar artery occlusions and the outcomes after endovascular treatment.

BACKGROUND: Acute vertebrobasilar artery occlusion (VBAO) is a devastating disease in stroke patients. This study was aimed to identify the initial symptoms of patients with acute VBAO receiving endovascular treatment and determine its associations with clinical outcomes. METHODS: Patients with VBAO receiving endovascular treatment at 21 stroke centres in China were recruited for this derivation cohort A data-driven approach of latent class analysis was applied to identify distinct symptom typologies of VBAO patients. Multivariable binary and ordinary logistic regressions were used to evaluate the associations between symptom subtypes and clinical outcomes. RESULTS: A total of 548 patients were analysed in this study. Four distinct subgroups were defined: the vestibular symptom group (32.8%), anterior circulation mimic group (26.5%), non-specific symptom group (14.8%) and severe VBAO symptom group (25.9%). Compared with severe VBAO symptoms, non-specific symptoms were independently associated with higher rates of favourable outcome and functional independence at the 3 months [odds ratio (OR) 2.46, 95% confidence interval (CI) 1.15-5.28; OR 3.46, 95% CI 1.54-7.79]and 1 year follow-up (OR 2.25, 95% CI 1.05-4.82; OR 2.69, 95% CI 1.22-5.92), and better functional improvement (shift in mRS score) at the 3 months (OR 2.05, 95% CI 1.15-3.67). CONCLUSION: We identified four distinctive subtypes based on the initial symptoms of VBAO patients. Severe VBAO symptoms were associated with poor outcomes while non-specific and vestibular symptoms were indicators of a favourable outcome.

Black Phosphorus Quantum Dots Enhance the Radiosensitivity of Human Renal Cell Carcinoma Cells through Inhibition of DNA-PKcs Kinase.

Renal cell carcinoma (RCC) is one of the most aggressive urological malignancies and has a poor prognosis, especially in patients with metastasis. Although RCC is traditionally considered to be radioresistant, radiotherapy (RT) is still a common treatment for palliative management of metastatic RCC. Novel approaches are urgently needed to overcome radioresistance of RCC. Black phosphorus quantum dots (BPQDs) have recently received great attention due to their unique physicochemical properties and good biocompatibility. In the present study, we found that BPQDs enhance ionizing radiation (IR)-induced apoptotic cell death of RCC cells. BPQDs treatment significantly increases IR-induced DNA double-strand breaks (DSBs), as indicated by the neutral comet assay and the DSBs biomarkers γH2AX and 53BP1. Mechanistically, BPQDs can interact with purified DNA-protein kinase catalytic subunit (DNA-PKcs) and promote its kinase activity in vitro. BPQDs impair the autophosphorylation of DNA-PKcs at S2056, and this site phosphorylation is essential for efficient DNA DSBs repair and the release of DNA-PKcs from the damage sites. Consistent with this, BPQDs suppress nonhomologous end-joining (NHEJ) repair and lead to sustained high levels of autophosphorylated DNA-PKcs on the damaged sites. Moreover, animal experiments indicate that the combined approach with both BPQDs and IR displays better efficacy than monotreatment. These findings demonstrate that BPQDs have potential applications in radiosensitizing RCC cells.