Differentiating lung neuroendocrine neoplasms from tumor-like infection using CT in patients with ectopic ACTH syndrome.

OBJECTIVES: Pulmonary neuroendocrine neoplasms (NENs) are the most frequent cause of ectopic adrenocorticotropic hormone syndrome (EAS); lung infection is common in EAS. An imaging finding of infection in EAS patients can mimic NENs. This retrospective study investigated EAS-associated pulmonary imaging indicators. METHODS: Forty-five pulmonary NENs and 27 tumor-like infections from 59 EAS patients (45 NEN and 14 infection patients) were included. Clinical manifestations, CT features, 18F-FDG, or 68Ga-DOTATATE-PET/CT images and pathological results were collected. RESULTS: High-sensitivity C-reactive protein (p < 0.001) and expectoration occurrence (p = 0.04) were higher, and finger oxygen saturation (p = 0.01) was lower in the infection group than the NENs group. Higher-grade NENs were underrepresented in our cohort. Pulmonary NENs were solitary primary tumors, 80% of which were peripheral tumors. Overlying vessel sign and airway involvement were more frequent in the NENs group (p < 0.001). Multifocal (p = 0.001) and peripheral (p = 0.02) lesions, cavity (p < 0.001), spiculation (p = 0.01), pleural retraction (p < 0.001), connection to pulmonary veins (p = 0.02), and distal atelectasis or inflammatory exudation (p = 0.001) were more frequent in the infection group. The median CT value increment between the non-contrast and arterial phases was significantly higher in NENs lesions (p < 0.001). Receiver operating characteristic curve analysis indicated a moderate predictive ability at 48.3 HU of delta CT value (sensitivity, 95.0%; specificity, 54.1%). CONCLUSION: Chest CT scans are valuable for localizing and characterizing pulmonary lesions in rare EAS, thereby enabling prompt differential diagnosis and treatment. CRITICAL RELEVANCE STATEMENT: Thin-slice CT images are valuable for the localization and identification of pulmonary ectopic adrenocorticotropic hormone syndrome lesions, leading to prompt differential diagnosis and effective treatment. KEY POINTS: Lung tumor-like infections can mimic neuroendocrine neoplasms (NENs) in ectopic adrenocorticotropic hormone syndrome (EAS) patients. NENs are solitary lesions, whereas infections are multiple peripheral pseudotumors each with identifying imaging findings. Typical CT signs aid in localization and creating an appropriate differential diagnosis.

Research Progress on Flavonoids in Traditional Chinese Medicine to Counteract Cardiotoxicity Associated with Anti-Tumor Drugs.

The development of anti-tumor drugs has notably enhanced the survival rates and quality of life for patients with malignant tumors. However, the side effects of these drugs, especially cardiotoxicity, significantly limit their clinical application. The cardiotoxicity associated with anti-tumor drugs has been a subject of extensive attention and research. Traditional to mitigate these side effects have included reducing drug dosages, shortening treatment duration, modifying administration methods, and opting for drugs with lower toxicity. However, either approach may potentially compromise the anti-tumor efficacy of the medications. Therefore, exploring other effective methods for anti-cardiotoxicity will be the focus of future research. The potential of traditional Chinese medicine (TCM) in managing cardiovascular diseases and cancer treatment has gained widespread recognition. TCM is valued for its minimal side effects, affordability, and accessibility, offering promising avenues in the prevention and treatment of cardiotoxicity caused by anti-tumor drugs. Among its constituents, flavonoids, which are present in many TCMs, are particularly notable. These monomeric compounds with distinct structural components have been shown to possess both cardiovascular protective properties and anti-tumor capabilities. In this discussion, we will delve into the classification of anti-tumor drugs and explore the underlying mechanisms of their associated cardiotoxicity. Additionally, we will examine flavonoids found in TCM and investigate their mechanisms of cardiovascular protection. This will include an analysis of how these natural compounds can mitigate the cardiac side effects of anti-tumor therapies while potentially enhancing overall patient health and treatment outcomes.

Cascade Effect of a Dimerized Thermally Activated Delayed Fluorescence Dendrimer.

Thermally activated delayed fluorescence (TADF) emitters with a high horizontal orientation are highly essential for improving the external quantum efficiency (EQE) of organic light-emitting diodes; however, pivotal molecular design strategies to improve the horizontal orientation of solution processable TADF emitters are still scarce and challenging. Herein, a phenyl bridge is adopted to connect the double TADF units, and a dimerized TADF dendrimer, D4CzBNPh-SF, is successfully constructed. Compared to counterpart with single TADF unit, the proof-of-the-concept molecule not only exhibits an improved horizontal dipole ratio (78%) due to the π-delocalization-induced extended molecular conjugation, but also displays a faster reversed intersystem crossing rate constant (6.08×106 s-1) and a high photoluminescence quantum yield of 95% in neat film. Consequently, the non-doped solution-processed device with D4CzBNPh-SF as the emitter, achieves an ultra-high maximum EQE of 32.6%, which remains at 26.6% under a luminance of 1000 cd/m2. Furthermore, using D4CzBNPh-SF as a sensitizer, the TADF-sensitized fluorescence device exhibits a high maximum EQE of 30.7% at a luminance of 575 cd/m2 and a full width at half maximum of 36 nm.

PRMT6-mediated ADMA promotes p62 phase separation to form a negative feedback loop in ferroptosis.

Purpose: Due to intrinsic defensive response, ferroptosis-activating targeted therapy fails to achieve satisfactory clinical benefits. Though p62-Keap1-Nrf2 axis is activated to form a negative feedback loop during ferroptosis induction, how p62 is activated remains largely unknown. Methods: MTS assay was applied to measure cell growth. Lipid ROS was detected with C11-BODIPY reagent by flow cytometer. Quantitative real-time PCR (qPCR) and western blotting were performed to determine mRNA and protein level. Immunofluorescence (IF) was performed to examine the distribution of proteins. Fluorescence recovery after photobleaching (FRAP) was adopted to evaluate p62 phase separation. Immunoprecipitation (IP), co-IP and Proximal ligation assay (PLA) were performed to detected protein posttranslational modifications and protein-protein interactions. Tumor xenograft model was employed to inspect in vivo growth of pancreatic cancer cells. Results: Upon ferroptosis induction, Nuclear Factor E2 Related Factor 2 (Nrf2) protein and its downstream genes such as HMOX1 and NQO1 were upregulated. Knockdown of p62 significantly reversed Nrf2 upregulation and Keap1 decrease after ferroptosis induction. Knockdown of either p62 or Nrf2 remarkably sensitized ferroptosis induction. Due to augmented p62 phase separation, formation of p62 bodies were increased to recruit Keap1 after ferroptosis induction. Protein arginine methyltransferase 6 (PRMT6) mediated asymmetric dimethylarginine (ADMA) of p62 to increase its oligomerization, promoting p62 phase separation and p62 body formation. Knockdown of p62 or PRMT6 notably sensitized pancreatic cancer cells to ferroptosis both in vitro and in vivo through suppressing Nrf2 signaling. Conclusion: During ferroptosis induction, PRMT6 mediated p62 ADMA to promote its phase separation, sequestering Keap1 to activate Nrf2 signaling and inhibit ferroptosis. Therefore, targeting PRMT6-mediated p62 ADMA could be a new option to sensitize ferroptosis for cancer treatment.

Mechanistic and therapeutic perspectives of non-coding RNA-modulated apoptotic signaling in diabetic retinopathy.

Diabetic retinopathy (DR), a significant and vision-endangering complication associated with diabetes mellitus, constitutes a substantial portion of acquired instances of preventable blindness. The progression of DR appears to prominently feature the loss of retinal cells, encompassing neural retinal cells, pericytes, and endothelial cells. Therefore, mitigating the apoptosis of retinal cells in DR could potentially enhance the therapeutic approach for managing the condition by suppressing retinal vascular leakage. Recent advancements have highlighted the crucial regulatory roles played by non-coding RNAs (ncRNAs) in diverse biological processes. Recent advancements have highlighted that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs), act as central regulators in a wide array of biogenesis and biological functions, exerting control over gene expression associated with histogenesis and cellular differentiation within ocular tissues. Abnormal expression and activity of ncRNAs has been linked to the regulation of diverse cellular functions such as apoptosis, and proliferation. This implies a potential involvement of ncRNAs in the development of DR. Notably, ncRNAs and apoptosis exhibit reciprocal regulatory interactions, jointly influencing the destiny of retinal cells. Consequently, a thorough investigation into the complex relationship between apoptosis and ncRNAs is crucial for developing effective therapeutic and preventative strategies for DR. This review provides a fundamental comprehension of the apoptotic signaling pathways associated with DR. It then delves into the mutual relationship between apoptosis and ncRNAs in the context of DR pathogenesis. This study advances our understanding of the pathophysiology of DR and paves the way for the development of novel therapeutic strategies.

Clinical Course, Therapy, and Long-Term Outcomes of Children With Moyamoya Disease and Posterior Cerebral Artery Involvement.

BACKGROUND AND OBJECTIVES: Posterior cerebral artery involvement (PCAi) has been identified as an important factor related to poor prognosis in moyamoya disease (MMD). This study summarized the characteristics of children with MMD and PCAi, clarified the clinical course, identified prognostic predictors, and investigated the long-term effect of encephaloduroarteriosynangiosis for posterior circulation (EDAS-p). METHODS: We retrospectively reviewed all our pediatric MMD cases with follow-up angiograms from November 2003 to December 2016. PCAi was classified as early-onset at initial diagnosis and delayed-onset after anterior circulation revascularization. Multivariable data including clinical features, radiographic findings, and surgical outcomes were analyzed. RESULTS: Among 570 children with MMD, 246 (43.2%) had PCAi, with 176 (30.9%) classified as early-onset PCAi. During a median follow-up period of 10 years, 17.8% (70/394) of patients without initial PCAi developed delayed-onset PCAi. The median time to detection of a new PCA lesion was 15.5 (range 7-110) months from initial diagnosis, with a median age of 10.5 (3-22). Younger age at onset, familial occurrence, advanced Suzuki stages, and preoperative infarctions were predictors of delayed-onset PCAi. EDAS-p was performed on 294 hemispheres of 195 patients with PCAi. Stroke-free survival was significantly higher in the EDAS-p group than in the non-EDAS-p group (99.0% vs 90.2%; p < 0.001 [Breslow test]; p = 0.001 [log-rank test]; median follow-up: 101 months). DISCUSSION: PCAi is not uncommon in children with MMD, underscoring the need for long-term close clinical monitoring, especially in patients with high-risk factors for PCA progression. EDAS-p may be a safe and effective procedure for preventing subsequent stroke in children with MMD and PCAi.

Children's oppositional defiant disorder symptoms and neural synchrony in mother-child interactions: An fNIRS study.

Interpersonal neural synchrony (INS) between mothers and children responds to the temporal similarity of brain signals in joint behavior between dyadic partners and is considered an important neural indicator of the formation of adaptive social interaction bonds. Parent-child interactions are particularly important for the development and maintenance of oppositional defiant disorder (ODD) in children, but the underlying neurocognitive mechanisms are unknown. Therefore, in the current study we measured INS between mothers and children in interactions by using simultaneous functional Near-infrared Spectroscopy (fNIRS), and explored its association with ODD symptoms in children. Seventy-two mother-child dyads were recruited to participate in the study, including 35 children with ODD and 37 healthy children to be used as a control. Each mother-child dyad was measured for neural activity in frontal, parietal, and temporal lobe regions while completing free-play as well as positive, and negative topic discussion tasks. We used Phase-locked value to calculate the synchrony strength and then used the K-means algorithm and k-space based alignment tests to confirm the specific patterns of parent-child synchrony in different brain areas. The results showed that, in free-play (right MFG and bilateral SFG), positive (left TPJ and bilateral SFGdor), and negative (bilateral SFGmed, right ANG, and left MFG) topic discussions, the mother-child pairs showed different patterns of INS. These specific INS patterns were significantly lower in the ODD group compared to the control group and were negatively associated with ODD symptoms in children. Network analyses showed that these INS patterns were connected to different nodes in the ODD symptom network. Our findings suggest that ODD mother-child dyads exhibit lower neural synchrony across a wide range of parent-child interactions. Neural synchrony in the context of interpersonal interactions provides new insights into understanding the neural mechanisms of ODD and can be used as an indicator of neural and socio-environmental factors in the network of psychological disorder symptoms.

Chiral Co-Assembly with Narrowband Multi-Resonance Characteristics for High-Performance Circularly Polarized Organic Light-Emitting Diodes.

A promising kind of ternary chiral co-assemblies with high PLQY, large dissymmetry factor (glum), and narrowband multi-resonance characteristics are achieved by codoped-thermal annealing treatments of achiral luminescent polymer F8BT, chiral inducers R/S-5011, and achiral FRET acceptor DBN-ICZ. The optimized co-assemblies (F8BT)0.9-(R/S-5011)0.1-(DBN-ICZ)0.005 display narrowband yellow emission with full-width half maximum (FWHM) of 37 nm, PLQY of 79%, and intense CPL signals with |glum| of up to 0.26. Meaningfully, solution-processed CP-OLEDs by using those ternary chiral co-assemblies as emitting layer are successfully fabricated, which display yellow circularly polarized electroluminescence (CPEL) with EQEmax of 4.6% and gEL of up to 0.16. The corresponding Q-factor could reach up to 7.36 × 10-3, which is the highest of all the reported CP-OLEDs. Moreover, the devices also exhibit excellent comprehensive device performance with low Von of 7.0 V, high Lmax of about 25 000 cd m-2, extremely low efficiency roll-off with EQE of 4.3% at 10 000 cd m-2, as well as narrowband EL with FWHM of only 39 nm. The proposed ternary co-assembly strategy in fabricating CP-OLED provides the possibility to achieve high comprehensive device performance such as balancing high EQE and large gEL value, as well as narrowband emission, high brightness and low efficiency roll-off simultaneously.

Chinese herbal compound preparation Qing-Xin-Jie-Yu granules for intermediate coronary lesions in patients with stable coronary artery disease: Study protocol for a multicenter, randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Despite the available secondary preventive treatments, the management of stable coronary artery disease (SCAD) remains challenging. Intermediate coronary lesion (ICL), defined as luminal stenosis between 50% and 70%, is a key stage of SCAD. However, existing therapeutic strategies are limitated in delaying plaque progression and associated with various adverse effects and economic burdens. Qing-Xin-Jie-Yu Granules (QXJYG) with proven anti-platelet, anti-inflammatory, and lipid-lowering effects may compensate for the drawbacks of current treatments and can be tested as a complementary therapy. Therefore, this study aims to investigate the efficacy and safety of QXJYG in treating ICL, with a particular focus on its impact on myocardial ischemia and plaque progression. MATERIALS AND METHODS: This is a multicenter, randomized, double-blind, placebo-controlled trial. A total of 120 participants with ICL will be randomly assigned to two groups in a 1:1 ratio. In addition to basic medications, the intervention group will receive QXJYG, while the control group will receive a placebo for over 6 months, followed by a 12-month follow-up. The primary efficacy outcome is computed tomography-derived fractional flow reserve. The secondary outcomes include the degree of coronary stenosis, coronary artery calcification score, Gensini score, Seattle Angina Questionnaire score, high-sensitivity C-reactive protein, matrix metalloproteinase-9, blood lipids, and carotid artery ultrasound parameters. Major adverse cardiovascular events are recorded as endpoints. The safety outcomes include composite events of bleeding, laboratory test results, and adverse events. Clinical visits are scheduled at baseline, every 2 months during the treatment, and after a 12-month follow-up. DISCUSSION: This trial is anticipated to yield reliable results to verify the efficacy and safety of QXJYG in the treatment of ICL, which will provide novel insights to help address the prevailing therapeutic dilemma of ICL, thereby facilitating for the management of SCAD. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200059262. Registered on April 27, 2022.

Encephaloduroarteriosynangiosis for Symptomatic Intracranial Atherosclerotic Arterial Steno-Occlusive Disease: Clinical and Radiological Outcomes.

BACKGROUND: This study investigated the long-term clinical and angiographic outcomes of encephaloduroarteriosynangiosis treatment for symptomatic intracranial atherosclerotic arterial steno-occlusive disease to further evaluate the potential therapeutic role of encephaloduroarteriosynangiosis in this population. METHODS AND RESULTS: A total of 152 adult patients with symptomatic intracranial atherosclerotic arterial steno-occlusive disease who were treated with encephaloduroarteriosynangiosis and intensive medical management across 3 tertiary centers in China between January 2011 and September 2019 were retrospectively included. The primary outcomes were defined as postoperative cerebrovascular events, including ischemic and hemorrhagic stroke. The postoperative neovascularization was analyzed qualitatively and quantitatively by using angiography. Clinical, radiological, and long-term follow-up data were analyzed using Cox regression, logistic regression, and linear regression analyses. Primary outcome rates were 3.2% (5/152) within 30 days, 6.6% (10/152) within 2 years, 9.2% (14/152) within 5 years, and 11.1% (17/152) during a median 9.13 years follow-up. Initial infarction symptoms were positively associated with recurrent ischemic stroke. Additionally, posterior circulation involvement and coexisting cardiac disease indicated poorer neurological status, whereas encephaloduroarteriosynangiosis neovascularization efficacy was negatively associated with older age and vascular risk factors but positively associated with posterior circulation involvement. CONCLUSIONS: Encephaloduroarteriosynangiosis plus intensive medical management appears efficacious and safe for symptomatic intracranial atherosclerotic arterial steno-occlusive disease, with low perioperative risk and favorable long-term results. Further prospective trials are needed to verify its efficacy and determine the optimal patient selection criteria.

Suspected silent pituitary somatotroph neuroendocrine tumor associated with acromegaly-like bone disorders: a case report.

BACKGROUND: Growth hormone (GH) positive pituitary neuroendocrine tumors do not always cause acromegaly. Approximately one-third of GH-positive pituitary tumors are classified as non-functioning pituitary tumors in clinical practice. They typically have GH and serum insulin-like growth factor 1 (IGF-1) levels in the reference range and no acromegaly-like symptoms. However, normal hormone levels might not exclude the underlying hypersecretion of GH. This is a rare and paradoxical case of pituitary tumor causing acromegaly-associated symptoms despite normal GH and IGF-1 levels. CASE PRESENTATION: We report a case of a 35-year-old woman with suspicious acromegaly-associated presentations, including facial changes, headache, oligomenorrhea, and new-onset diabetes mellitus and dyslipidemia. Imaging found a 19 × 12 × 8 mm pituitary tumor, but her serum IGF-1 was within the reference, and nadir GH was 0.7ng/ml after glucose load at diagnosis. A thickened skull base, increased uptake in cranial bones in bone scan, and elevated bone turnover markers indicated abnormal bone metabolism. We considered the pituitary tumor, possibly a rare subtype in subtle or clinically silent GH pituitary tumor, likely contributed to her discomforts. After the transsphenoidal surgery, the IGF-1 and nadir GH decreased immediately. A GH and prolactin-positive pituitary neuroendocrine tumor was confirmed in the histopathologic study. No tumor remnant was observed three months after the operation, and her discomforts, glucose, and bone metabolism were partially relieved. CONCLUSIONS: GH-positive pituitary neuroendocrine tumors with hormonal tests that do not meet the diagnostic criteria for acromegaly may also cause GH hypersecretion presentations. Patients with pituitary tumors and suspicious acromegaly symptoms may require more proactive treatment than non-functioning tumors of similar size and invasiveness.

Qualifying Event and Recurrence of Ischemic Stroke in Symptomatic Artery Occlusion: A Post Hoc Analysis of CMOSS.

BACKGROUND: The authors aimed to elucidate the relationship between latest ischemic event and the incidence of subsequent ischemic stroke in patients with symptomatic artery occlusion. METHODS AND RESULTS: We analyzed the association between qualifying event-the latest ischemic event (transient ischemic attack [TIA] or stroke)-and the incidence of ipsilateral ischemic stroke in patients with symptomatic artery occlusion treated with medical therapy alone in CMOSS (Carotid or Middle Cerebral Artery Occlusion Surgery Study). The incidence of CMOSS primary outcomes, including any stroke or death within 30 days after randomization or ipsilateral ischemic stroke between 30 days and 2 years, between the bypass surgical and medical groups, stratified by qualifying events, was also compared. Of the 165 patients treated with medical therapy alone, 75 had a TIA and 90 had a stroke as their qualifying event. The incidence of ipsilateral ischemic stroke did not significantly differ between patients with a TIA and those with a stroke as their qualifying event (13.3% versus 6.7%, P=0.17). In multivariate analysis, the qualifying event was not associated with the incidence of ipsilateral ischemic stroke. There were no significant differences in the CMOSS primary outcomes between the surgical and medical groups, regardless of the qualifying event being TIA (10.1% versus 12.2%, P=0.86) or stroke (6.7% versus 8.9%, P=0.55). CONCLUSIONS: Among patients with symptomatic artery occlusion and hemodynamic insufficiency, the risk of subsequent ipsilateral ischemic stroke does not appear to be lower in patients presenting with a TIA compared with those with a stroke. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01758614.

Potential of body mass index as a screening indicator for extracranial-intracranial bypass surgery in patients with symptomatic artery occlusion: a post-hoc analysis of the CMOSS trial.

BACKGROUND: To investigate the association between body mass index (BMI) and the incidence of ischemic stroke in patients with symptomatic artery occlusion, and further to evaluate the utility of BMI as a screening tool for identifying candidates for extracranial-intracranial bypass surgery. MATERIALS AND METHODS: We analyzed the relationship between BMI and the occurrence of ipsilateral ischemic stroke (IIS) among patients receiving only medical management in the Carotid or Middle cerebral artery Occlusion Surgery Study (CMOSS). Additionally, we compared the primary endpoint of CMOSS-stroke or death within 30 days, or IIS after 30 days up to two years-among patients with varying BMIs who underwent either surgery or medical treatment. RESULTS: Of the 165 patients who treated medically only, 16 (9.7%) suffered an IIS within two years. BMI was independently associated with the incidence of IIS (hazard ratio: 1.16 per kg/m2; 95% confidence interval: 1.06-1.27). The optimal BMI cutoff for predicting IIS was 24.5 kg/m2. Patients with BMI ≥24.5 kg/m2 experienced a higher incidence of IIS compared to those with BMI <24.5 kg/m2 (17.4% vs. 0.0%, P<0.01). The incidence of the CMOSS primary endpoint was significantly different between the surgical and medical groups for patients with BMI ≥24.5 kg/m2 (5.3% vs. 19.8%, P<0.01) and those with BMI <24.5 kg/m2 (10.6% vs. 1.4%; P=0.02). Surgical intervention was independently associated with a reduced rate of the CMOSS primary endpoint in patients with BMI ≥24.5 kg/m2. CONCLUSION: Data from the CMOSS trial indicate that patients with BMI ≥24.5 kg/m2 are at a higher risk of IIS when treated medically only and appear to derive greater benefit from bypass surgery compared to those with lower BMIs. Given the small sample size and the inherent limitations of retrospective analyses, further large-scale, prospective studies are necessary to confirm these findings.

Machine learning-based QSAR and LB-PaCS-MD guided design of SARS-CoV-2 main protease inhibitors.

The global outbreak of the COVID-19 pandemic caused by the SARS-CoV-2 virus had led to profound respiratory health implications. This study focused on designing organoselenium-based inhibitors targeting the SARS-CoV-2 main protease (Mpro). The ligand-binding pathway sampling method based on parallel cascade selection molecular dynamics (LB-PaCS-MD) simulations was employed to elucidate plausible paths and conformations of ebselen, a synthetic organoselenium drug, within the Mpro catalytic site. Ebselen effectively engaged the active site, adopting proximity to H41 and interacting through the benzoisoselenazole ring in a π-π T-shaped arrangement, with an additional π-sulfur interaction with C145. In addition, the ligand-based drug design using the QSAR with GFA-MLR, RF, and ANN models were employed for biological activity prediction. The QSAR-ANN model showed robust statistical performance, with an r2training exceeding 0.98 and an RMSEtest of 0.21, indicating its suitability for predicting biological activities. Integration the ANN model with the LB-PaCS-MD insights enabled the rational design of novel compounds anchored in the ebselen core structure, identifying promising candidates with favorable predicted IC50 values. The designed compounds exhibited suitable drug-like characteristics and adopted an active conformation similar to ebselen, inhibiting Mpro function. These findings represent a synergistic approach merging ligand and structure-based drug design; with the potential to guide experimental synthesis and enzyme assay testing.

New Application of Multiresonance Organic Delayed Fluorescence Dyes: High-Performance Photoinitiating Systems for Acrylate and Epoxy Photopolymerization and Photoluminescent Pattern Preparation.

The primary focus of photopolymerization research is to advance highly efficient visible photoinitiating systems (PISs) as alternatives to conventional ultraviolet (UV) photoinitiators. We developed four multiresonance emitters (BIC-pCz, BNO1, BO-DICz, and TPABO-DICz) to sensitize iodonium salt (Iod) and initiate free-radical and cationic photopolymerization under visible light for the first time. The TPABO-DICz/Iod system achieved a double-bond conversion of over 70% within just 4 s of exposure to green light (520 nm), while the BNO1/Iod system achieved a double-bond conversion exceeding 50% with 10 s of exposure to red light (630 nm). The photochemical properties were studied through thermodynamic research, steady-state photolysis, and electron spin resonance. Photolithography techniques were employed to fabricate photoluminescent films and micrometer-scale patterns utilizing the blue-emitting BIC-pCz dye, showcasing the potential of photolithography in the production of photoluminescent pixels. Additionally, the BIC-pCz/Iod and TPABO-DICz/Iod systems have been employed to rapidly fabricate photoluminescent polymer patterns using a digital-light-processing 3D printer with a low-intensity light (3.2 mW cm-2). These multiresonance emitters show exceptional photosensitizing effects and can act as fluorescent dyes in photoluminescent patterns, highlighting the potential of utilizing photopolymerization for OLED applications.

Development and validation of a novel nomogram for predicting long-term rebleeding risk among patients with hemorrhagic moyamoya disease: a 10-year multicenter retrospective cohort study.

OBJECTIVE: The aim of this study was to develop and validate a predictive nomogram model for long-term rebleeding events in patients with hemorrhagic moyamoya disease (HMMD). METHODS: In total, 554 patients with HMMD from the Fifth Medical Center of the Chinese PLA General Hospital (5-PLAGH cohort) were included and randomly divided into training (390 patients) and internal validation (164 patients) sets. An independent cohort from the First Medical Center and Eighth Medical Center of Chinese PLA General Hospital (the 1-PLAGH and 8-PLAGH cohort) was used for external validation (133 patients). Univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression algorithm were used to identify significant factors associated with rebleeding, which were used to develop a nomogram for predicting 5- and 10-year rebleeding. RESULTS: Intraventricular hemorrhage was the most common type of cerebral hemorrhage (39.0% of patients in the 5-PLAGH cohort and 42.9% of the 1-PLAGH and 8-PLAGH cohort). During the mean ± SD follow-up period of 10.4 ± 2.9 years, 91 (16.4%) patients had rebleeding events in the 5-PLAGH cohort. The rebleeding rates were 12.3% (68 patients) at 5 years and 14.8% (82 patients) at 10 years. Rebleeding events were observed in 72 patients (14.3%) in the encephaloduroarteriosynangiosis (EDAS) surgery group, whereas 19 patients (37.3%) experienced rebleeding events in the conservative treatment group. This difference was statistically significant (p < 0.001). We selected 4 predictors (age at onset, number of episodes of bleeding, posterior circulation involvement, and EDAS surgery) for nomogram development. The concordance index (C-index) values of the nomograms of the training cohort, internal validation cohort, and the external validation cohort were 0.767 (95% CI 0.704-0.830), 0.814 (95% CI 0.694-0.934), and 0.718 (95% CI 0.661-0.775), respectively. The nomogram at 5 years exhibited a sensitivity of 48.1% and specificity of 87.5%. The positive and negative predictive values were 38.2% and 91.3%, respectively. The nomogram at 10 years exhibited a sensitivity of 47.1% and specificity of 89.1%. The positive and negative predictive values were 48.5% and 88.5%, respectively. CONCLUSIONS: EDAS may prevent rebleeding events and improve long-term clinical outcomes in patients with HMMD. The nomogram accurately predicted rebleeding events and assisted clinicians in identifying high-risk patients and devising individual treatments. Simultaneously, comprehensive and ongoing monitoring should be implemented for specific patients with HMMD throughout their entire lifespan.

Optimizing removal of antiretroviral drugs from tertiary wastewater using chlorination and AI-based prediction with response surface methodology.

Chemical and pharmaceutical chemicals found in water sources create substantial risks to human health and the environment. The presence of pharmaceutical contaminants in water can cause antibiotic resistance development, toxicity to aquatic organisms, and endocrine disruption. Hence, the elimination of chemicals and other contaminants from wastewater prior to its release is a burgeoning concern in the domains of engineering and science. The use of treatment technologies in wastewater treatment plants can remove pharmaceutical contaminants through the oxidation process. However, many traditional wastewater treatment plants lack the advanced monitoring tools required to detect low concentrations of pharmaceuticals. Without the ability to detect these compounds, it's challenging to treat them effectively. The goal of this study was to use Response Surface Methodology (RSM) and Artificial Neural Networks (ANN) algorithms to model and improve how Nevirapine and Efavirenz break down in different chlorination conditions. The RSM analysis revealed statistically significant models (F-values: Nevirapine, pH-t: 108.15, T-t: 76.55, ICC-t: 110.84), indicating a strong correlation between operational parameters (pH, temperature, and initial chlorine concentration) and degradation behavior. The ANN model accurately predicted the degradation of both Nevirapine and Efavirenz under various chlorination conditions, as confirmed by analyzing actual-predicted graphs, residual plots, and Mean Squared Error (MSE) values. The ANN model using ICC-t achieved the highest MOD value of 31.31 % for Nevirapine. The ANN model based on ICC-t yielded a maximum MOD value of 16.06 % for Efavirenz. These findings provide valuable insights into optimizing chlorination processes for better removal of these pharmaceutical contaminants from water.

A long-term prognosis study of human USP8-mutated ACTH-secreting pituitary neuroendocrine tumours.

OBJECTIVE: Somatic variants in the ubiquitin-specific protease 8 (USP8) gene are the most common genetic cause of Cushing disease. We aimed to explore the relationship between clinical outcomes and USP8 status in a single centre. DESIGN, PATIENTS AND MEASUREMENTS: We investigated the USP8 status in 48 patients with pituitary corticotroph tumours. A median of 62 months of follow-up was conducted after surgery from November 2013 to January 2015. The clinical, biochemical and imaging features were collected and analysed. RESULTS: Seven USP8 variants (p.Ser718Pro, p.Ser719del, p.Pro720Arg, p.Pro720Gln, p.Ser718del, p.Ser718Phe, p.Lys713Arg) were identified in 24 patients (50%). USP8 variants showed a female predominance (100% vs. 75% in wild type [WT], p = .022). Patients with p.Ser719del showed an older age at surgery compared to patients with the p.Pro720Arg variant (47- vs. 24-year-olds, p = .033). Patients with p.Pro720Arg showed a higher rate of macroadenoma compared to patients harbouring the p.Ser718Pro variant (60% vs. 0%, p = .037). No significant differences were observed in serum and urinary cortisol and adrenocorticotropin hormone (ACTH) levels. Immediate surgical remission (79% vs. 75%) and long-term hormone remission (79% vs. 67%) were not significantly different between the two groups. The recurrence rate was 21% (4/19) in patients harbouring USP8 variants and 13% (2/16) in WT patients. Recurrence-free survival presented a tendency to be shorter in USP8-mutated individuals (76.7 vs. 109.2 months, p = .068). CONCLUSIONS: Somatic USP8 variants accounted for 50% of the genetic causes in this cohort with a significant female frequency. A long-term follow-up revealed a tendency toward shorter recurrence-free survival in USP8-mutant patients.