Compromised dynamic cerebral autoregulation is a hemodynamic marker for predicting poor prognosis even with good recanalization after endovascular thrombectomy.

PURPOSE: In patients undergoing endovascular thrombectomy (EVT) with acute ischemic stroke (AIS), dynamic cerebral autoregulation (dCA) may minimize neurological injury from blood pressure fluctuations. This study set out to investigate the function of dCA in predicting clinical outcomes following EVT. METHODS: 43 AIS of the middle cerebral or internal carotid artery patients underwent with EVT, and 43 healthy individuals (controls) were enrolled in this case control research. The dCA was evaluated using transcranial Doppler 12 h and five days after EVT. The transfer function analysis was used to derive the dCA parameters, such as phase, gain, and coherence. The modified Rankin scale (mRS) at 3 months after EVT was used to assess the clinical outcomes. Thefavorable outcome group was defined with mRS ≤2 and the unfavorable outcome group was defined with mRS score of 3-6. Logistic regression analysis was performed to determine the risk factors of clinical outcomes. RESULTS: A significant impairment in dCA was observed on the ipsilateral side after EVT, particularly in patients with unfavorable outcomes. After 5 days, the ipsilateral phase was associated with poor functional outcomes (adjusted odds ratio [OR] = 0.911, 95% confidence interval [CI]: 0.854-0.972; P = 0.005) and the area under the curve (AUC) (AUC, 0.878, [95% CI: 0.756-1.000] P < 0.001) (optimal cutoff, 35.0°). Phase change was an independent predictor of clinical outcomes from 12 h to 5 days after EVT (adjusted OR = 1.061, 95% CI: 1.016-1.109, P = 0.008). CONCLUSIONS: dCA is impaired in patients with AIS after EVT. Change in dCA could be an independent factor related to the clinical outcomes.

Effects of electroacupuncture on postoperative cognitive dysfunction and its underlying mechanisms: a literature review of rodent studies.

With the aging of the population, the health of the elderly has become increasingly important. Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients following general anesthesia or surgery. It is characterized by cognitive decline that may persist for weeks, months, or even longer. Electroacupuncture (EA), a novel therapy that combines physical nerve stimulation with acupuncture treatment from traditional Chinese medicine, holds potential as a therapeutic intervention for preventing and treating POCD, particularly in elderly patients. Although the beneficial effects of EA on POCD have been explored in preclinical and clinical studies, the reliability of EA is limited by methodological shortcomings, and the underlying mechanisms remain largely unexplored. Therefore, we have synthesized existing evidence and proposed potential biological mechanisms underlying the effects of EA on neuroinflammation, oxidative stress, autophagy, the microbiota-gut-brain axis, and epigenetic modification. This review summarizes recent advances in EA and POCD, provides a theoretical foundation, explores potential molecular mechanisms for the prevention and treatment of POCD, and offers a basis for conducting relevant clinical trials.

Targeting the molecular chaperone CCT2 inhibits GBM progression by influencing KRAS stability.

Proper protein folding relies on the assistance of molecular chaperones post-translation. Dysfunctions in chaperones can cause diseases associated with protein misfolding, including cancer. While previous studies have identified CCT2 as a chaperone subunit and an autophagy receptor, its specific involvement in glioblastoma remains unknown. Here, we identified CCT2 promote glioblastoma progression. Using approaches of coimmunoprecipitation, mass spectrometry and surface plasmon resonance, we found CCT2 directly bound to KRAS leading to increased stability and upregulated downstream signaling of KRAS. Interestingly, we found that dihydroartemisinin, a derivative of artemisinin, exhibited therapeutic effects in a glioblastoma animal model. We further demonstrated direct binding between dihydroartemisinin and CCT2. Treatment with dihydroartemisinin resulted in decreased KRAS expression and downstream signaling. Highlighting the significance of CCT2, CCT2 overexpression rescued the inhibitory effect of dihydroartemisinin on glioblastoma. In conclusion, the study demonstrates that CCT2 promotes glioblastoma progression by directly binding to and enhancing the stability of the KRAS protein. Additionally, dihydroartemisinin inhibits glioblastoma by targeting the CCT2 and the following KRAS signaling. Our findings overcome the challenge posed by the undruggable nature of KRAS and offer potential therapeutic strategies for glioblastoma treatment.

HTRA1 promotes EMT through the HDAC6/Ac-α-tubulin pathway in human GBM cells.

BACKGROUND: The infiltrative nature of human gliomas renders complete surgical removal of tumors futile. Thus, illuminating mechanisms of their infiltrative properties may improve therapies and outcomes of glioma patients. METHODS: Comprehensive bioinformatic analyses of PRSS family were undertaken. Transfection of HTRA1 siRNAs was used to suppress HTRA1 expression. CCK-8, EdU, and colony formation assay were employed to assess cell viability, and cell migration/invasion was detected by transwell, wound healing, and 3D tumor spheroid invasion assays. Immunoprecipitation was applied to study the mechanism that HTRA1 affected cell migration. In addition, in situ xenograft tumor model was employed to explore the role of HTRA1 in glioma growth in vivo. RESULTS: HTRA1 knockdown could lead to suppression of cell viability, migration and invasion, as well as increased apoptosis. Immunoprecipitation results indicates HTRA1 might facilitate combination between HDAC6 and α-tubulin to enhance cell migration by decreasing α-tubulin acetylation. Besides, HTRA1 knockdown inhibited the growth of xenografts derived from orthotopic implantation of GBM cells and prolonged the survival time of tumor-bearing mice. CONCLUSION: Our results indicate that HTRA1 promotes the proliferation and migration of GBM cells in vitro and in vivo, and thus may be a potential target for treatment in gliomas.

Night shift work was associated with functional outcomes in acute ischemic stroke patients treated with endovascular thrombectomy.

Objective: This study aimed to explore the impact of late night shift work on the functional outcomes of patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT). Methods: Consecutive AIS patients who underwent EVT between June 2019 and June 2021 were enrolled and divided into non-night shift work and night shift work groups based on their occupational histories. The primary outcome was the modified Rankin Scale score defined 3-month functional outcome. The secondary outcomes were 3-month mortality, symptomatic intracerebral hemorrhage (sICH), ICH and early recanalization. Results: A total of 285 patients were enrolled, 35 patients (12.3%) were night shift workers, who were younger (P < 0.001) and had a significantly higher prevalence of smoking (P < 0.001), hyperlipidemia (P = 0.002), coronary heart disease (P = 0.031), and atrial fibrillation (P < 0.001). The 3-month favorable outcomes were achieved in 44.8% and 25.7% of patients in the non-night shift work and night shift work groups, respectively (adjusted odds ratio [OR]: 0.24, 95% CI: 0.10-0.57; adjusted P = 0.001). No difference was found in 3-month mortality (adjusted OR: 0.43; 95% CI: 0.14-1.25, adjusted P = 0.121), rates of ICH (adjusted OR: 0.73; 95% CI: 0.33-1.60; adjusted P = 0.430), sICH (adjusted OR: 0.75; 95% CI: 0.34-1.67; adjusted P = 0.487), or early successful recanalization (adjusted OR: 0.42; 95% CI: 0.12-1.56; adjusted P = 0.197). These results were consistent after PSM analysis. Conclusion: Our findings suggest that late night shift work is significantly associated with unfavorable outcomes in patients with AIS after EVT.

Clinical implications and predictive value of the creatinine­cystatin C ratio in patients with multiple myeloma and renal impairment.

The creatinine (Cr)-cystatin C ratio (CCR) at the time of cancer diagnosis is associated with survival; however, to the best of our knowledge, the association between this ratio and mortality in patients with multiple myeloma and renal impairment (RI) is unclear. Therefore, the present study aimed to assess this association, as well as disease prognosis and the clinical significance of the CCR in patients with multiple myeloma and RI. The present retrospective study included 191 patients diagnosed with multiple myeloma and RI between 2012 and 2022. The predictive value of the CCR was evaluated using area under the receiver operating characteristic curve (AUC) values. The factors affecting overall survival (OS) were assessed using uni- and multivariate logistic regression analyses. The effect of the CCR on survival was evaluated using a Cox regression model and the Kaplan-Meier method. There was a significant association between low CCR and poor progression-free survival (PFS) and overall survival (OS). The 1-, 2- and 3-year PFS and OS rates in patients with a low CCR were significantly lower than those in patients with a high CCR. The 1-, 2- and 3-year AUC values of the CCR were 0.712, 0.764 and 0.746 respectively. Multivariate analysis revealed sex, age, Cr levels, CCR and C-reactive protein levels as independent prognostic factors affecting OS rates. The CCR is a potential prognostic indicator in patients with multiple myeloma with RI and is associated with clinical stages.

The dopamine receptor D1 inhibitor, SKF83566, suppresses GBM stemness and invasion through the DRD1-c-Myc-UHRF1 interactions.

BACKGROUND: Extensive local invasion of glioblastoma (GBM) cells within the central nervous system (CNS) is one factor that severely limits current treatments. The aim of this study was to uncover genes involved in the invasion process, which could also serve as therapeutic targets. For the isolation of invasive GBM cells from non-invasive cells, we used a three-dimensional organotypic co-culture system where glioma stem cell (GSC) spheres were confronted with brain organoids (BOs). Using ultra-low input RNA sequencing (ui-RNA Seq), an invasive gene signature was obtained that was exploited in a therapeutic context. METHODS: GFP-labeled tumor cells were sorted from invasive and non-invasive regions within co-cultures. Ui-RNA sequencing analysis was performed to find a gene cluster up-regulated in the invasive compartment. This gene cluster was further analyzed using the Connectivity MAP (CMap) database. This led to the identification of SKF83566, an antagonist of the D1 dopamine receptor (DRD1), as a candidate therapeutic molecule. Knockdown and overexpression experiments were performed to find molecular pathways responsible for the therapeutic effects of SKF83566. Finally, the effects of SKF83566 were validated in orthotopic xenograft models in vivo. RESULTS: Ui-RNA seq analysis of three GSC cell models (P3, BG5 and BG7) yielded a set of 27 differentially expressed genes between invasive and non-invasive cells. Using CMap analysis, SKF83566 was identified as a selective inhibitor targeting both DRD1 and DRD5. In vitro studies demonstrated that SKF83566 inhibited tumor cell proliferation, GSC sphere formation, and invasion. RNA sequencing analysis of SKF83566-treated P3, BG5, BG7, and control cell populations yielded a total of 32 differentially expressed genes, that were predicted to be regulated by c-Myc. Of these, the UHRF1 gene emerged as the most downregulated gene following treatment, and ChIP experiments revealed that c-Myc binds to its promoter region. Finally, SKF83566, or stable DRD1 knockdown, inhibited the growth of orthotopic GSC (BG5) derived xenografts in nude mice. CONCLUSIONS: DRD1 contributes to GBM invasion and progression by regulating c-Myc entry into the nucleus that affects the transcription of the UHRF1 gene. SKF83566 inhibits the transmembrane protein DRD1, and as such represents a candidate small therapeutic molecule for GBMs.

Adsorption Process Optimization and Adsorbent Evaluation Based on Langmuir Isotherm Model.

Adsorption separation is considered one of the most commonly used gas purification methods. At present, the most widely used adsorption methods are mainly pressure swing adsorption (PSA) and temperature swing adsorption (TSA). In both adsorption methods, a comprehensive understanding of the equilibrium data and the adsorption capacity of the adsorbent is essential for process design and optimization, and the adsorption isotherm can provide a powerful aid in this regard. In this study, through mathematical analysis of the Langmuir isotherm model, the optimal cyclic adsorption conditions and the optimal thermodynamic parameters (entropy change and enthalpy change) under PSA and TSA were obtained. In addition, the isotherm model can be used to predict the isobaric adsorption capacity, and the objective function was established according to the cyclic adsorption capacity and the regeneration sensible heat consumption per unit adsorption capacity to calculate the optimal adsorption/desorption temperatures and optimal cyclic adsorption capacity of various adsorbents.

Development and validation of a nomogram for assessment postoperative sodium disturbance in PAs patients: a retrospective cohort study.

Background: Pituitary adenomas (PAs) are neuroendocrine tumors located in the sellar region. Surgery, being the primary treatment option for most PAs, is known to cause disruptions in sodium metabolism. Objective: To develop and validate a nomogram for assessment the incidence of postoperative sodium disturbance (SD) in patients with PAs. Methods: In this retrospective study, 208 patients with PAs who underwent resection surgery between 2013 and 2020 were included. Various demographic characteristics, clinical features and laboratory data were analyzed as potential predictors of postoperative sodium disturbance (SD). LASSO regression were used to identify independent preoperative variables associated with SD. Logistic regression was employed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). A nomogram was constructed to visualize these results and evaluated using metrics such as the area under the curve (AUC) for discrimination, the Hosmer-Lemeshow test for calibration and decision curve for usefulness assessment. Results: The incidence of SD was 44.23% (92 cases out of 208). Six preoperative factors, including sex, types of PAs, phosphocreatine kinase (CK), serum iron (Fe), free fatty acids (NEFA) and mean corpuscular volume (MCV), were identified for constructing a predictive nomogram. The nomogram showed high accuracy, with AUC values of 0.851 (95% CI [0.799-0.923]) and 0.771 (95% CI [0.681-0.861]) in the training and validation datasets, respectively. Calibration assessment and decision curve analysis confirmed its good agreement and clinical utility. Conclusion: A practical and effective nomogram for predicting SD after PAs surgery is presented in this study.

UCNPs-based nanoreactors with ultraviolet radiation-induced effect for enhanced ferroptosis therapy of tumor.

The limitations of light source limit the clinical application of optical therapy technology. How to improve the application efficiency of radiant light has become the focus of researchers. Here, we synthesize a kind of UCNPs@PVP-GOx-PpIX-Fe3+ (UPGPF) nanoreactors with rare earth upconversion nanoparticles (UCNPs) as the substrate for the enhancement of ferroptosis effect by the synergistic starvation/photodynamic therapies. Firstly, glucose oxidase (GOx) and Fe3+ loaded in UPGPF nanoreactors are used to directly face the problems of insufficient H2O2 level in tumor tissue and low Fenton reaction efficiency. Further, UCNPs can absorb NIR light at 980 nm and convert low-energy photons into high-energy photons, thereby cleverly generating ultraviolet (UV) radiation induction in vivo, which can produce a synergistic effect of enhancing iron death. The in vivo experimental results of breast cancer model mice show that the UPGPF nanoreactors have significant anticancer effect and good biosafety. With the help of the optical conversion characteristics of UCNPs, this kind of treatment idea of building a UV radiation-induced microplatform in the tumor microenvironment, which leads to the synergistic enhancement of iron death effect, provides a promising innovative design strategy for tumor research.

Synergistic therapeutic effect of nanomotors triggered by Near-infrared light and acidic conditions of tumor.

Due to the complexity of tumors, multimodal therapy for them has always been of concern to researchers. How to design a multifunctional drug nanoplatform with cascade effect and capable of responding to specific stimuli in the tumor microenvironment is the key to achieve efficient multimodal synergistic therapy of cancer. Here, we prepare a kind of GNRs@SiO2@PDA-CuO2-l-Arg (GSPRs-CL) nanomotors for systematic treatment of tumor. First, under near-infrared (NIR) irradiation, GSPRs-CL can generate heat and exhibit excellent photothermal therapy effect. Then under acidic conditions, CuO2 can be decomposed to release Cu2+ and generate H2O2, which not only complemented the limited endogenous H2O2 in cells, but also further triggered Fenton-like reaction, converting H2O2 into •OH to kill cancer cells, thereby achieving chemodynamic therapy. Furthermore, both endogenous and exogenous H2O2 can release nitric oxide (NO) in response to the occurrence of l-Arg of nanomotors to enhance gas therapy. In addition, as a dual-mode drive, NIR laser and NO can promote the penetration ability of nanomotors at tumor sites. The experimental results in vivo show that the drug nanoplatform had good biosafety and significant tumor killing effect triggered by NIR light and acidic conditions of tumor. It provide a promising strategy for the development of advanced drug nanoplatform for cancer therapy.

Malignant Middle Cerebral Artery Infarction during Early versus Late Endovascular Treatment in Acute Ischemic Stroke.

INTRODUCTION: Endovascular treatment (EVT) performed in the early time window has been shown to decrease the incidence of malignant middle cerebral artery infarction (MMI). However, the incidence of MMI in patients undergoing EVT during the late time window is unclear. This study aimed to investigate the prevalence of MMI in patients undergoing late EVT and compare it with that in patients undergoing early EVT. METHODS: We retrospectively analyzed consecutive patients with anterior large vessel occlusion stroke who underwent EVT at Xuanwu Hospital between January 2013 and June 2021. Eligible patients were divided into early EVT (within 6 h) and late EVT (6-24 h) groups according to the time from their stroke onset to puncture and compared. The occurrence of MMI post-EVT was the primary outcome. RESULTS: A total of 605 patients were recruited, of whom 300 (50.4%) underwent EVT within 6 h and 305 (49.6%) underwent EVT within 6-24 h. A total of 119 patients (19.7%) developed MMI. 68 patients (22.7%) in the early EVT group and 51 patients (16.7 %) in the late EVT group developed MMI (p = 0.066). After adjusting for covariate variables, late EVT was independently associated with a lower incidence of MMI (odds ratio, 0.404; 95% confidence interval, 0.242-0.675; p = 0.001). CONCLUSION: MMI is not an uncommon phenomenon in the modern thrombectomy era. Compared with the early time window, patients selected by stricter radiological criteria to undergo EVT in the late time window are independently associated with a lower incidence of MMI.

Visual Dysfunction is a Risk Factor of Postoperation Delirium in Parkinson Disease.

OBJECTIVE: To investigate the incidence of and factors influencing postoperative delirium (POD) in Parkinson disease after deep brain stimulation (DBS) surgery. METHODS: A total of 272 patients with Parkinson disease who underwent DBS completed the Visual Impairment in Parkinson Disease Questionnaire (VIPD-Q) and underwent neuro-ophthalmologic examinations including optical coherence tomography and fundus vessel analysis. We retrospect the prevalence of POD in groups with different VIPD-Q scores, retinal nerve fiber layer (RNFL) thicknesses, and vessel percentage areas (VPA). A predictive model based on the VIPD-Q was constructed using multivariate logistic regression and verified using bootstrap validation. RESULTS: POD was experienced by 65 (23.9%) of 272 patients. Patients with PD who had visual impairment (VIPD-Q > 6) had a higher incidence of POD (chi-square, P < 0.001). The thickness of the RNFL and VPA were also correlated with POD risk. Differences in implantation locations (subthalamic nucleus or pars interna of globus pallidus), operation times, and general anesthesia times did not affect the prevalence of DBS-related POD. A nomogram was constructed based on ophthalmic events to predict the risk of POD. CONCLUSIONS: The study findings provide convincing evidence of the relationship between visual dysfunction and the risk of POD. In view of the higher risk of POD, visually impaired patients with PD should undergo closer monitoring after DBS surgery.

Remote Ischemic Conditioning for Motor Recovery after Acute Ischemic Stroke.

BACKGROUND: Remote ischemic conditioning (RIC) has shown an impressive neuroprotective effect on acute ischemic stroke (AIS) in animal experiments. But whether chronic RIC improves long-term functional outcomes remains unclear. MATERIALS AND METHODS: We performed a non-randomized controlled trial. Eligible patients (aged 18 -80 y) with hemiplegia caused by AIS were allocated to the RIC group and the control group. All participants received normal protocol rehabilitation therapy. Patients in the RIC group underwent RIC twice daily for 90 days. The outcome included the 90-day Fugl-Meyer Assessment (FMA) scores and modified Rankin's scale (mRS) scores, as well as changes in angiogenesis-related factors in serum from baseline to 90 days. RESULTS: Twenty-seven patients were included in the analysis (13 in the RIC group and 14 in the control group). There was no significant difference in 90-day total FMA scores between the two groups. Lower limb FMA scores at day 90 were significantly higher in the RIC group (32.8±8.7 vs. 24.8±5.4, adjusted P =0.042). The proportion of favorable outcome (mRS<2) was higher in the RIC group than that in the control group, but no significant difference was detected (8 [61.5%] vs. 7 [50%], P =0.705). A significant increase has been found in the level of epidermal growth factor (EGF) in serum (9.4 [1.1 to 25.7] vs. -8.7 [-15.1 to 4.7], P =0.036) after chronic RIC procedure. CONCLUSION: This study investigated the role that RIC plays in AIS recovery, especially in motor function. RIC may have beneficial effects on lower limbs recovery by enhancing the EGF level. The effect of RIC on motor recovery should be further validated in future studies.

Biodegradable CuMoO4 Nanodots with Multienzyme Activities for Multimodal Treatment of Tumor.

Due to their complexity and variability, tumors need to be treated with multimodal combined therapy, which requires the development of therapeutic agents that can provide multimodal therapeutic effects. Herein, CuMoO4 nanodots smaller than 10 nm that can be prepared by simple hydrothermal method are reported. These nanodots can be well dispersed in water and have good biosafety and biodegradability. Further studies show that these nanodots also present multienzyme activities, such as catalase, peroxidase and glutathione peroxidase. In addition, CuMoO4 nanodots exhibit high photothermal conversion efficiency (41%) under 1064 nm near-infrared laser irradiation. In vitro and in vivo experimental results indicate that CuMoO4 nanodots can effectively inhibit the instinctive regulation of tumor cells to oxidative stress, provide sustained treatment to achieve photothermal synergistic ferroptosis, and trigger immune responses to immunogenic cell death. It is worth mentioning that the CuMoO4 nanodots also cause cuproptosis of tumor cells. This study provides a promising nanoplatform for multimodal combined therapy of cancer.

The posterior cruciate ligament index as a reliable indirect sign of anterior cruciate ligament rupture is associated with the course of knee joint injury.

PURPOSE: The objective of this study was to clarify the clinical value of the posterior cruciate ligament index (PCLI) in anterior cruciate ligament (ACL) rupture, to explore the relationship between the PCLI and course of disease, and to identify the influencing factors of the PCLI. METHODS: The PCLI was defined a quotient of the X (the tibial and femoral PCL attachments) and the Y (the maximum perpendicular distance from X to the PCL). A total of 858 patients were enrolled in this case-control study, including 433 patients with ACL ruptures who were assigned to the experimental group and 425 patients with meniscal tears (MTs) who were allocated to the control group. Some patients in the experimental group have collateral ligament rupture (CLR). Information, such as the patient's age, sex, and course of disease, was recorded. All patients underwent magnetic resonance imaging (MRI) preoperatively, and the diagnosis was confirmed with the aid of arthroscopy. The PCLI and the depth of the lateral femoral notch sign (LFNS) were calculated based on the MRI findings, and the characteristics of the PCLI were explored. RESULTS: The PCLI in the experimental group (5.1 ± 1.6) was significantly smaller than that in the control group (5.8 ± 1.6) (P < 0.05). The PCLI gradually decreased with time and was only 4.8 ± 1.4 in patients in the chronic phase (P < 0.05). This change was not due to the decrease in X but rather the increase in Y. The results also showed that the PCLI was not related to the depth of the LFNS or injuries of other structures in the knee joint. Furthermore, when the optimal cut-off point of the PCLI was 5.2 (area under the curve = 71%), the specificity and the sensitivity were 84% and 67%, respectively, but the Youden index was just 0.3 (P < 0.05). CONCLUSION: The PCLI decreases due to the increase in Y instead of the decrease in X with time, especially in the chronic phase. The change in X in this process may be offset during imaging. In addition, there are fewer influencing factors that lead to changes in the PCLI. Therefore, it can be used as a reliable indirect sign of ACL rupture. However, it is difficult to quantify the diagnostic criteria of the PCLI in clinical practice. Thus, the PCLI as a reliable indirect sign of ACL rupture is associated with the course of knee joint injury, and it can be used to describe the instability of the knee joint. LEVELS OF EVIDENCE: III.

Highly Penetrable Drug-Loaded Nanomotors for Photothermal-Enhanced Ferroptosis Treatment of Tumor.

A kind of drug-loaded nanomotors with deep penetration was developed to improve the therapeutic effect of ferroptosis on tumor. The nanomotors were constructed by co-loading hemin and ferrocene (Fc) on the surface of bowl-shaped polydopamine (PDA) nanoparticles. The near-infrared response of PDA makes the nanomotor have high tumor penetration capability. In vitro experiments show that the nanomotors can exhibit good biocompatibility, high light to heat conversion efficiency, and deep tumor permeability. It is worth noting that under the catalysis of H2O2 overexpressed in the tumor microenvironment, the Fenton-like reagents hemin and Fc loaded on the nanomotors can increase the concentration of toxic •OH. Furthermore, hemin can consume glutathione in tumor cells and trigger the up-regulation of heme oxygenase-1, which can efficiently decompose hemin to Fe2+, thus producing the Fenton reaction and causing a ferroptosis effect. Notably, thanks to the photothermal effect of PDA, it can enhance the generation of reactive oxygen species and thus intervene in the Fenton reaction process, thereby enhancing the ferroptosis effect photothermally. In vivo antitumor results show that the drug-loaded nanomotors with high penetrability showed an effective antitumor therapeutic effect.

Polydopamine nanomotors loaded indocyanine green and ferric ion for photothermal and photodynamic synergistic therapy of tumor.

The limited penetration depth of nanodrugs in the tumor and the severe hypoxia inside the tumor significantly reduce the efficacy of photothermal-photodynamic synergistic therapy (PTT-PDT). Here, we synthesized a methoxypolyethylene glycol amine (mPEG-NH2)-modified walnut-shaped polydopamine nanomotor (PDA-PEG) driven by near-infrared light (NIR). At the same time, it also loaded the photosensitizer indocyanine green (ICG) via electrostatic/hydrophobicinteractions and chelated with ferric ion (Fe3+). Under the irradiation of NIR, the asymmetry of PDA-PEG morphology led to the asymmetry of local photothermal effects and the formation of thermal gradient, which can make the nanomotor move autonomously. This ability of autonomous movement was proved to be used to improve the permeability of the nanomotor in three-dimensional (3D) tumor sphere. Fe3+ can catalyze endogenous hydrogen peroxide to produce oxygen, so as to overcome the hypoxia of tumor microenvironment and thereby generate more singlet oxygen to kill tumor cells. Animal experiments in vivo confirmed that the nanomotors had a good PTT-PDT synergistic treatment effect. The introduction of nanomotor technology has brought new ideas for cancer optical therapy.

Comprehensive characterization of TNFSF14/LIGHT with implications in prognosis and immunotherapy of human gliomas.

Glioblastoma multiforme (GBM) is a common central neural system malignant tumor among adults. Alongside its microscopic spread, immunosuppression in the tumor microenvironment also induces its refractoriness, which makes immunotherapy for GBM particularly important. Unfortunately, traditional immune checkpoint inhibitors (ICIs) often show limited therapeutic effects in GBM clinical trials, and new therapeutic strategies or targets are urgently needed. TNFSF14/LIGHT is a novel immune checkpoint molecule that plays essential roles in both innate and acquired immunity. Despite recent advances in our understanding of the function of TNFSF14/LIGHT in a variety of cancer types, the clinical and immunological importance of TNFSF14/LIGHT in human gliomas has not been fully explained. Here, we employed a comprehensive in silico analysis with publicly available data to analyze the molecular and immune characteristics of TNFSF14/LIGHT to explore its feasibility as an immunotherapy target. Totally, 2215 glioma cases were enrolled in the current study. Immunohistochemistry staining based on patient tissues (n = 34) was performed for the validation. TNFSF14/LIGHT was expressed higher in higher-WHO-grade gliomas and mesenchymal subtypes, and it was sensitive as a prognostic marker in GBM and low-grade glioma (LGG). A nomogram prognostic model was established based on TNFSF14/LIGHT expression together with other risk factors. Additionally, Gene Ontology and pathway analysis revealed that TNFSF14/LIGHT participated in T-cell activities and inflammatory processes. Moreover, analysis based on the structure and interactions of TNFSF14/LIGHT revealed its mutation sites in tumors as well as crucial interacting proteins. Analysis of IMvigor210 indicated the role of TNFSF14/LIGHT in immunotherapy. Altogether, our results reveal an underlying role of TNFSF14/LIGHT as an immunotherapy target in GBM.

A nomogram for predicting malignant cerebral artery infarction in the modern thrombectomy era.

Objective: This study aimed to develop and validate a nomogram to predict malignant cerebral artery infarction (MMI) after endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) in the modern thrombectomy era. Methods: We retrospectively analyzed data from a prospective cohort of consecutive patients with AIS who underwent EVT at Xuanwu hospital between January 2013 and June 2021. A multivariable logistic regression model was employed to construct the nomogram for predicting MMI after EVT. The discrimination and calibration of the nomogram were assessed both in the derivation and validation cohorts. Results: A total of 605 patients were enrolled in this study, with 425 in the derivation cohort and 180 in the validation cohort. The nomogram was developed based on admission systolic blood pressure (SBP), the National Institute of Health Stroke Score (NIHSS), the Alberta Stroke Program Early Computed Tomography Score (ASPECTS), vessel occlusion site, EVT time window, and recanalization status. The nomogram displayed good discrimination with the area under the receiver operating characteristics (ROCs) curve (AUC) of 0.783 [95% confidence interval (CI), 0.726-0.840] in the derivation cohort and 0.806 (95% CI, 0.738-0.874) in the validation cohort. The calibration of the nomogram was good as well, with the Hosmer-Lemeshow test of p = 0.857 in the derivation cohort and p = 0.275 in the validation cohort. Conclusion: In the modern thrombectomy era, a nomogram containing admission SBP, NIHSS, ASPECTS, vessel occlusion site, EVT time window, and recanalization status may predict the risk of MMI after EVT in patients with AIS.