Choriocapillaris reduction accurately discriminates against early-onset Alzheimer's disease.

INTRODUCTION: This study addresses the urgent need for non-invasive early-onset Alzheimer's disease (EOAD) prediction. Using optical coherence tomography angiography (OCTA), we present a choriocapillaris model sensitive to EOAD, correlating with serum biomarkers. METHODS: Eighty-four EOAD patients and 73 controls were assigned to swept-source OCTA (SS-OCTA) or the spectral domain OCTA (SD-OCTA) cohorts. Our hypothesis on choriocapillaris predictive potential in EOAD was tested and validated in these two cohorts. RESULTS: Both cohorts revealed diminished choriocapillaris signals, demonstrating the highest discriminatory capability (area under the receiver operating characteristic curve: SS-OCTA 0.913, SD-OCTA 0.991; P < 0.001). A sparser SS-OCTA choriocapillaris correlated with increased serum amyloid beta (Aß)42, Aß42/40, and phosphorylated tau (p-tau)181 levels (all P < 0.05). Apolipoprotein E status did not affect choriocapillaris measurement. DISCUSSION: The choriocapillaris, observed in both cohorts, proves sensitive to EOAD diagnosis, and correlates with serum Aß and p-tau181 levels, suggesting its potential as a diagnostic tool for identifying and tracking microvascular changes in EOAD. HIGHLIGHTS: Optical coherence tomography angiography may be applied for non-invasive screening of Alzheimer's disease (AD). Choriocapillaris demonstrates high sensitivity and specificity for early-onset AD diagnosis. Microvascular dynamics abnormalities are associated with AD.

Vascular smooth muscle-specific LRRC8A knockout ameliorates angiotensin II-induced cerebrovascular remodeling by inhibiting the WNK1/FOXO3a/MMP signaling pathway.

Hypertensive cerebrovascular remodeling involves the enlargement of vascular smooth muscle cells (VSMCs), which activates volume-regulated Cl- channels (VRCCs). The leucine-rich repeat-containing family 8 A (LRRC8A) has been shown to be the molecular identity of VRCCs. However, its role in vascular remodeling during hypertension is unclear. In this study, we used vascular smooth muscle-specific LRRC8A knockout (CKO) mice and an angiotensin II (Ang II)-induced hypertension model. The results showed that cerebrovascular remodeling during hypertension was ameliorated in CKO mice, and extracellular matrix (ECM) deposition was reduced. Based on the RNA-sequencing analysis of aortic tissues, the level of matrix metalloproteinases (MMPs), such as MMP-9 and MMP-14, were reduced in CKO mice with hypertension, which was further verified in vivo by qPCR and immunofluorescence analysis. Knockdown of LRRC8A in VSMCs inhibited the Ang II-induced upregulation of collagen I, fibronectin, and matrix metalloproteinases (MMPs), and overexpression of LRRC8A had the opposite effect. Further experiments revealed an interaction between with-no-lysine (K)-1 (WNK1), which is a "Cl--sensitive kinase", and Forkhead transcription factor O3a (FOXO3a), which is a transcription factor that regulates MMP expression. Ang II induced the phosphorylation of WNK1 and downstream FOXO3a, which then increased the expression of MMP-2 and MMP-9. This process was inhibited or potentiated when LRRC8A was knocked down or overexpressed, respectively. Overall, these results demonstrate that LRRC8A knockout in vascular smooth muscle protects against cerebrovascular remodeling during hypertension by reducing ECM deposition and inhibiting the WNK1/FOXO3a/MMP signaling pathway, demonstrating that LRRC8A is a potential therapeutic target for vascular remodeling-associated diseases such as stroke.

Rapid determination of total flavonoid content, xanthine oxidase inhibitory activities, and antioxidant activity in Prunus mume by near-infrared spectroscopy.

Evaluating the quality of herbal medicine based on the content and activity of its main components is highly beneficial. Developing an eco-friendly determination method has significant application potential. In this study, we propose a new method to simultaneously predict the total flavonoid content (TFC), xanthine oxidase inhibitory (XO) activity, and antioxidant activity (AA) of Prunus mume using near-infrared spectroscopy (NIR). Using the sodium nitrite-aluminum nitrate-sodium hydroxide colorimetric method, uric acid colorimetric method, and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) free radical scavenging activity as reference methods, we analyzed TFC, XO, and AA in 90 P. mume samples collected from different locations in China. The solid samples were subjected to NIR. By employing spectral preprocessing and optimizing spectral bands, we established a rapid prediction model for TFC, XO, and AA using partial least squares regression (PLS). To improve the model's performance and eliminate irrelevant variables, competitive adaptive reweighted sampling (CARS) was used to calculate the pretreated full spectrum. Evaluation model indicators included the root mean square error of cross-validation (RMSECV) and determination coefficient (R2) values. The TFC, XO, and AA model, combining optimal spectral preprocessing and spectral bands, had RMSECV values of 0.139, 0.117, and 0.121, with RCV2 values exceeding 0.92. The root mean square error of prediction (RMSEP) for the TFC, XO, and AA model on the prediction set was 0.301, 0.213, and 0.149, with determination coefficient (RP2) values of 0.915, 0.933, and 0.926. The results showed a strong correlation between NIR with TFC, XO, and AA in P. mume. Therefore, the established model was effective, suitable for the rapid quantification of TFC, XO, and AA. The prediction method is simple and rapid, and can be extended to the study of medicinal plant content and activity.

Cross-Cultural Generalizability of the First Year Inventory for Early ASD Screening in China.

The First Year Inventory (FYI) is a parent report screening measure, aimed at identifying the risk of autism spectrum disorder (ASD) in 12-month-old infants. This study aimed to investigate the utility of FYI within the Chinese community and develop a short version, encompassing both a low-risk sample and a high-risk sample comprising infants with older siblings diagnosed with ASD. Parents of 53 high-risk (HR) infants and 519 low-risk (LR) infants, aged 11 to 13 months, were recruited. After comparing response distributions across Chinese and American samples, a new factorial structure was developed according to the factor analyses. The construct validity and internal consistency of the two FYI versions were examined. The implementation of FYI in the HR sample was also assessed. Noteworthy disparities in response distribution were observed between the Chinese and American samples. Both FYI 2.0 and the FYI short version demonstrated moderate construct validity and internal consistency, with the FYI short version exhibiting better predictive ability in the HR sample. Significant lower risk scores was observed in the HR sample compared to the LR sample. These findings substantiate the applicability and validity of the Chinese short version of FYI. Future research should include follow-up assessments with the Chinese sample to evaluate cutoff scores, considering the cutoff between sensitivity and specificity and the sample?s characteristics.

Role of the microbiota-gut-heart axis between bile acids and cardiovascular disease.

Bile acid (BA) receptors (e.g., farnesoid X-activated receptor, muscarinic receptor) are expressed in cardiomyocytes, endothelial cells, and vascular smooth muscle cells, indicating the relevance of BAs to cardiovascular disease (CVD). Hydrophobic BAs are cardiotoxic, while hydrophilic BAs are cardioprotective. For example, fetal cardiac insufficiency in maternal intrahepatic cholestasis during pregnancy, and the degree of fetal cardiac abnormality, is closely related to the level of hydrophobic BAs in maternal blood and infant blood. However, ursodeoxycholic acid (the most hydrophilic BA) can reverse/prevent these detrimental effects of increased levels of hydrophobic BAs on the heart. The gut microbiota (GM) and GM metabolites (especially secondary BAs) have crucial roles in hypertension, atherosclerosis, unstable angina, and heart failure. Herein, we describe the relationship between CVD and the GM at the BA level. We combine the concept of the "microbiota-gut-heart axis" (MGHA) and postulate the role and mechanism of BAs in CVD development. In addition, the strategies for treating CVD with BAs under the MGHA are proposed.

Continuous peripheral electrical nerve stimulation improves cardiac function via autonomic nerve regulation in MI rats.

BACKGROUND: Peripheral electrical nerve stimulation (PENS) reportedly improves cardiac function after myocardial ischemia (MI) by rebalancing the cardiac autonomic nervous system. The dynamic and continuous influence of PENS on autonomic and cardiac functioning based on cardiac self-repair is not well understood. OBJECTIVES: This study aimed to explore the relationship between autonomic nervous balance and functional cardiac repair after MI and to clarify the optimal acupoint selection and time course for PENS. METHODS: The activities of the superior cervical cardiac sympathetic nerve and vagus nerve were recorded to reflect the autonomic tone directly. The Millar pressure-volume loop system was used for left ventricular diastolic and systolic function. Noninvasive continuous electrocardiography and echocardiography were performed to analyze heart rate, heart rate variability, and left ventricular function. The effect of continuous PENS (cPENS) or instant PENS (iPENS) on autonomic and cardiac indications was tested. RESULTS: Sympathetic nerve activity and vagus nerve activity increased as compensatory self-regulation on days 7 and 14 post-MI, followed by an imbalance of autonomic tone and cardiac dysfunction on day 28. cPENS-PC6 maintained autonomic hyperexcitability, improved myocardial systolic and diastolic abilities, and reduced myocardial fibrosis on day 28 post-MI, whereas cPENS-ST36 had a limited effect. Both iPENS-PC6 and iPENS-ST36 improved the autonomic and cardiac function of rats in the cPENS groups. CONCLUSION: Rats showed autonomic fluctuations and cardiac dysfunction 28 days post-MI. cPENS produced sympathomimetic action to sustain cardiac self-compensation, but with acupoint specificity. On the basis of cPENS, iPENS evoked autonomic regulation and cardiac benefits without acupoint differentiation.

Gut microbiota derived from fecal microbiota transplantation enhances body weight of Mimas squabs.

Objective: Compared to Mimas pigeons, Shiqi pigeons exhibit greater tolerance to coarse feeding because of their abundant gut microbiota. Here, to investigate the potential of utilizing intestinal flora derived from Shiqi pigeons, the intestinal flora and body indices of Mimas squabs were evaluated after fecal microbiota transplantation (FMT) from donors. Methods: A total of 90 one-day-old squabs were randomly divided into the control group (CON), the low-concentration group (LC) and the high-concentration group (HC): gavaged with 200 µL of bacterial solution at concentrations of 0, 0.1 and 0.2 g/15 mL, respectively. Results: The results suggested that FMT improved the body weight of Mimas squabs in the HC and LC groups (p < 0.01), and 0.1 g/15 mL was the optimal dose during FMT. After 16S rRNA sequencing was performed, compared to those in the CON group, the abundance levels of microflora, especially Lactobacillus, Muribaculaceae and Megasphaera (p < 0.05), in the FMT-treated groups were markedly greater. Random forest analysis indicated that the main functions of key microbes involve pathways associated with metabolism, further illustrating their important role in the host body. Conclusion: FMT has been determined to be a viable method for augmenting the weight and intestinal microbiota of squabs, representing a unique avenue for enhancing the economic feasibility of squab breeding.

An immune sandwich electrochemical biosensor based on triple-modified zirconium derivatives for detection of CD146 in serum.

CD146, also known as melanoma cell adhesion molecule (MCAM), is overexpressed in various cancer patients, making it a valuable predictor for early diagnosis. In this work, an immune sandwich electrochemical biosensor is proposed for sensitive and non-invasive quantitative detection of CD146 in serum. Zirconium-based MOF (UIO-66) was modified by simultaneous copper atom doping, in situ growth carbon-based support and physical embedding of platinum nanoparticles (PtNPs). Triple-modified Cu-UIO-66@SWCNT/PtNPs nanocomposites with high stability and excellent electrochemical properties, serve as surface modification materials for glassy carbon electrodes. Anti-CD146 antibody (Ab1) was grafted onto the electrode surface via Pt-S bond. Meanwhile, the secondary antibody (Ab2) was conjugated with silver nanoparticles (AgNPs) to cooperate for CD146 capture and achieve secondary electrical signal amplification. Under optimal conditions, square wave voltammetry was employed to determine CD146 in the concentration range of 10-9-10-4 mg/mL and a limit of detection of 12 fg/mL was obtained. Finally, it was successfully applied to the analysis of CD146 in lung and liver cancer patients' serum samples.

Iron status and sarcopenia-related traits: a bi-directional Mendelian randomization study.

Although serum iron status and sarcopenia are closely linked, the presence of comprehensive evidence to establish a causal relationship between them remains insufficient. The objective of this study is to employ Mendelian randomization techniques to clarify the association between serum iron status and sarcopenia. We conducted a bi-directional Mendelian randomization (MR) analysis to investigate the potential causal relationship between iron status and sarcopenia. MR analyses were performed using inverse variance weighted (IVW), MR-Egger, and weighted median methods. Additionally, sensitivity analyses were conducted to verify the reliability of the causal association results. Then, we harvested a combination of SNPs as an integrated proxy for iron status to perform a MVMR analysis based on IVW MVMR model. UVMR analyses based on IVW method identified causal effect of ferritin on appendicular lean mass (ALM, ß = - 0.051, 95% CI - 0.072, - 0.031, p = 7.325 × 10-07). Sensitivity analyses did not detect pleiotropic effects or result fluctuation by outlying SNPs in the effect estimates of four iron status on sarcopenia-related traits. After adjusting for PA, the analysis still revealed that each standard deviation higher genetically predicted ferritin was associated with lower ALM (ß = - 0.054, 95% CI - 0.092, - 0.015, p = 0.006). Further, MVMR analyses determined a predominant role of ferritin (ß = - 0.068, 95% CI - 0.12, - 0.017, p = 9.658 × 10-03) in the associations of iron status with ALM. Our study revealed a causal association between serum iron status and sarcopenia, with ferritin playing a key role in this relationship. These findings contribute to our understanding of the complex interplay between iron metabolism and muscle health.

The lack of PPARα exacerbated the progression of non-alcoholic steatohepatitis in mice with spleen deficiency syndrome by triggering an inflammatory response.

Background: In addition to abnormal liver inflammation, the main symptoms of non-alcoholic steatohepatitis (NASH) are often accompanied by gastrointestinal digestive dysfunction, consistent with the concept of spleen deficiency (SD) in traditional Chinese medicine. As an important metabolic sensor, whether peroxisome proliferator-activated receptor alpha (PPARα) participates in regulating the occurrence and development of NASH with SD (NASH-SD) remains to be explored. Methods: Clinical liver samples were collected for RNA-seq analysis. C57BL/6J mice induced by folium sennae (SE) were used as an SD model. qPCR analysis was conducted to evaluate the inflammation and metabolic levels of mice. PPARα knockout mice (PPARαko) were subjected to SE and methionine-choline-deficient (MCD) diet to establish the NASH-SD model. The phenotype of NASH and the inflammatory indicators were measured using histopathologic analysis and qPCR as well. Results: The abnormal expression of PPARα signaling, coupled with metabolism and inflammation, was found in the results of RNA-seq analysis from clinical samples. SD mice showed a more severe inflammatory response in the liver evidenced by the increases in macrophage biomarkers, inflammatory factors, and fibrotic indicators in the liver. qPCR results also showed differences in PPARα between SD mice and control mice. In PPARαko mice, further evidence was found that the lack of PPARα exacerbated the inflammatory response phenotype as well as the lipid metabolism disorder in NASH-SD mice. Conclusion: The abnormal NR signaling accelerated the vicious cycle between lipotoxicity and inflammatory response in NAFLD with SD. Our results provide new evidence for nuclear receptors as potential therapeutic targets for NAFLD with spleen deficiency.

Active Dendrite Suppression by Ferroelectric Membrane Separators in Rechargeable Batteries.

Anodic dendrite formation is a critical issue in rechargeable batteries and often leads to poor cycling stability and quick capacity loss. Prevailing strategies for dendrite suppression aim at slowing down the growth rate kinetically but still leaving possibilities for dendrite evolution over time. Herein, we report a complete dendrite elimination strategy using a mesoporous ferroelectric polymer membrane as the battery separator. The dendrite suppression is realized by spontaneously reversing the surface energetics for metal ion reduction at the protrusion front, where a positive piezoelectric polarization is generated and superimposed as the protrusion compresses the separator. This effect is demonstrated first in a Zn electroplating process, and further in Zn-Zn symmetric cells and Zn-NaV3O8·1.5H2O full cells, where the dendritic Zn anode surfaces are completely turned into featureless flat surfaces. Consequently, a substantially longer charging/discharging cycle is achieved. This study provides a promising pathway toward high-performance dendrite-free rechargeable batteries.

Synergism between two BLA-to-BNST pathways for appropriate expression of anxiety-like behaviors in male mice.

Understanding how distinct functional circuits are coordinated to fine-tune mood and behavior is of fundamental importance. Here, we observe that within the dense projections from basolateral amygdala (BLA) to bed nucleus of stria terminalis (BNST), there are two functionally opposing pathways orchestrated to enable contextually appropriate expression of anxiety-like behaviors in male mice. Specifically, the anterior BLA neurons predominantly innervate the anterodorsal BNST (adBNST), while their posterior counterparts send massive fibers to oval BNST (ovBNST) with moderate to adBNST. Optogenetic activation of the anterior and posterior BLA inputs oppositely regulated the activity of adBNST neurons and anxiety-like behaviors, via disengaging and engaging the inhibitory ovBNST-to-adBNST microcircuit, respectively. Importantly, the two pathways exhibited synchronized but opposite responses to both anxiolytic and anxiogenic stimuli, partially due to their mutual inhibition within BLA and the different inputs they receive. These findings reveal synergistic interactions between two BLA-to-BNST pathways for appropriate anxiety expression with ongoing environmental demands.

Integrating Traditional Machine Learning and Deep Learning for Precision Screening of Anticancer Peptides: A Novel Approach for Efficient Drug Discovery.

The rapid and effective identification of anticancer peptides (ACPs) by computer technology provides a new perspective for cancer treatment. In the identification process of ACPs, accurate sequence encoding and effective classification models are crucial for predicting their biological activity. Traditional machine learning methods have been widely applied in sequence analysis, but deep learning provides a new approach to capture sequence complexity. In this study, a two-stage ACPs classification model was innovatively proposed. Three novel coding strategies were explored; two mainstream Natural Language Processing (NLP) models and 11 machine learning models were fused to identify ACPs, which significantly improved the prediction accuracy of ACPs. We analyzed the correlation between peptide chain amino acids and evaluated the relevant performance of the model by the ROC curve and t-SNE dimensionality reduction technique. The results indicated that the deep learning and machine learning fusion models of M3E-base and KNeighborsDist models, especially when considering the semantic information on amino acid sequences, achieved the highest average accuracy (AvgAcc) of 0.939, with an AUC value as high as 0.97. Then, in vitro cell experiments were used to verify that the two ACPs predicted by the model had antitumor efficacy. This study provides a convenient and effective method for screening ACPs. With further optimization and testing, these strategies have the potential to play an important role in drug discovery and design.

Joint association and interaction of birth weight and lifestyle with hypertension: A cohort study in UK Biobank.

Low birth weight and unhealthy lifestyle are both associated with an increased risk of hypertension. The authors aimed to assess the joint association and interaction of birth weight and lifestyle with incident hypertension. The authors included 205 522 participants free of hypertension at baseline from UK Biobank. A healthy lifestyle score was constructed using information on body mass index, physical activity, diet, smoking status and alcohol intake. Cox proportional hazard models were used to investigate the impact of birth weight, healthy lifestyle score and their joint effect on hypertension. The authors documented 13 548 (6.59%) incident hypertension cases during a median of 8.6 years of follow-up. The multivariate adjusted hazard ratios and 95% confidence intervals were 1.12 (1.09, 1.15) per kg lower birth weight and 0.76 (0.75, 0.77) per score increment in healthy lifestyle score. Healthy lifestyle reduced the risk of hypertension in any category of different birth weight groups. The preventive effect of healthy lifestyle on hypertension was the most pronounced at lower birth weight with <2500 g and 2500-2999 g, respectively. Addictive interaction between birth weight and healthy lifestyle score was observed with the relative excess risk due to interaction of 0.04 (0.03, 0.05). Our findings emphasized the importance of healthy lifestyle for hypertension prevention, especially among the high-risk population with lower birth weight.

Immunological profile of lactylation-related genes in Crohn's disease: a comprehensive analysis based on bulk and single-cell RNA sequencing data.

BACKGROUND: Crohn's disease (CD) is a disease characterized by intestinal immune dysfunction, often accompanied by metabolic abnormalities. Disturbances in lactate metabolism have been found in the intestine of patients with CD, but studies on the role of lactate and related Lactylation in the pathogenesis of CD are still unknown. METHODS: We identified the core genes associated with Lactylation by downloading and merging three CD-related datasets (GSE16879, GSE75214, and GSE112366) from the GEO database, and analyzed the functions associated with the hub genes and the correlation between their expression levels and immune infiltration through comprehensive analysis. We explored the Lactylation levels of different immune cells using single-cell data and further analyzed the differences in Lactylation levels between inflammatory and non-inflammatory sites. RESULTS: We identified six Lactylation-related hub genes that are highly associated with CD. Further analysis revealed that these six hub genes were highly correlated with the level of immune cell infiltration. To further clarify the effect of Lactylation on immune cells, we analyzed single-cell sequencing data of immune cells from inflammatory and non-inflammatory sites in CD patients and found that there were significant differences in the levels of Lactylation between different types of immune cells, and that the levels of Lactylation were significantly higher in immune cells from inflammatory sites. CONCLUSIONS: These results suggest that Lactylation-related genes and their functions are closely associated with changes in inflammatory cells in CD patients.

Decoding gene regulatory circuitry underlying TNBC chemoresistance reveals biomarkers for therapy response and therapeutic targets.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype characterised by extensive intratumoral heterogeneity, high rates of metastasis and chemoresistance, leading to poor clinical outcomes. Despite progress, the mechanistic basis of chemotherapy resistance in TNBC patients remains poorly understood. Here, leveraging single-cell transcriptome datasets of matched longitudinal TNBC chemoresponsive and chemoresistant patient cohorts, we unravel distinct cell subpopulations intricately associated with chemoresistance and the signature genes defining these populations. Notably, using genome-wide mapping of the H3K27ac mark, we show that the expression of these chemoresistance genes is driven via a set of TNBC super-enhancers and associated transcription factor networks across TNBC subtypes. Furthermore, genetic screens reveal that a subset of these transcription factors is essential for the survival of TNBC cells, and their loss increases sensitivity to chemotherapeutic agents. Overall, our study has revealed epigenetic and transcription factor networks underlying chemoresistance and suggests novel avenues to stratify and improve the treatment of patients with a high risk of developing resistance.

Evaluation of ChatGPT in providing appropriate fracture prevention recommendations and medical science question responses: A quantitative research.

Currently, there are limited studies assessing ChatGPT ability to provide appropriate responses to medical questions. Our study aims to evaluate ChatGPT adequacy in responding to questions regarding osteoporotic fracture prevention and medical science. We created a list of 25 questions based on the guidelines and our clinical experience. Additionally, we included 11 medical science questions from the journal Science. Three patients, 3 non-medical professionals, 3 specialist doctor and 3 scientists were involved to evaluate the accuracy and appropriateness of responses by ChatGPT3.5 on October 2, 2023. To simulate a consultation, an inquirer (either a patient or non-medical professional) would send their questions to a consultant (specialist doctor or scientist) via a website. The consultant would forward the questions to ChatGPT for answers, which would then be evaluated for accuracy and appropriateness by the consultant before being sent back to the inquirer via the website for further review. The primary outcome is the appropriate, inappropriate, and unreliable rate of ChatGPT responses as evaluated separately by the inquirer and consultant groups. Compared to orthopedic clinicians, the patients' rating on the appropriateness of ChatGPT responses to the questions about osteoporotic fracture prevention was slightly higher, although the difference was not statistically significant (88% vs 80%, P = .70). For medical science questions, non-medical professionals and medical scientists rated similarly. In addition, the experts' ratings on the appropriateness of ChatGPT responses to osteoporotic fracture prevention and to medical science questions were comparable. On the other hand, the patients perceived that the appropriateness of ChatGPT responses to osteoporotic fracture prevention questions was slightly higher than that to medical science questions (88% vs 72·7%, P = .34). ChatGPT is capable of providing comparable and appropriate responses to medical science questions, as well as to fracture prevention related issues. Both the inquirers seeking advice and the consultants providing advice recognize ChatGPT expertise in these areas.

Comparative efficacy of interventional therapies and devices for coronary in-stent restenosis: A systematic review and network meta-analysis of randomized controlled trials.

Background: In-stent restenosis (ISR) has become a significant obstacle to interventional therapy for atherosclerotic cardiovascular disease. The optimal percutaneous coronary intervention (PCI) strategy for patients with coronary ISR remains controversial. This network meta-analysis (NMA) was aimed to compare and estimate the effectiveness of different PCI strategies and commercial devices for the treatment of patients with coronary ISR. Methods: In present study, we systematically searched PubMed, Embase, Web of Science, and Cochrane Library from database inception to October 20, 2022, to identify randomized controlled trials. We included studies comparing various PCI strategies for the treatment of any type of coronary ISR. The study was registered with PROSPERO, CRD 42022364308. Results: We included 44 eligible trials including 8479 patients, 39 trials comparing the treatment effects of 10 PCIs, and 5 trials comparing the efficacy between different types of drug-eluting stent (DES) or drug-coated balloon (DCB) devices. Among the PCIs, everolimus-eluting stent was the optimal strategy considering target lesion revascularization (TLR), percent diameter stenosis (%DS), and binary restenosis (BR), and sirolimus-coated balloon was the optimal strategy considering late lumen loss (LLL). In the comparison of commercial devices, the combination strategy excimer laser coronary angioplasty plus SeQuent Please paclitaxel-coated balloon showed promising therapeutic prospects. Conclusions: DCB and DES remain the preferred treatment strategies for coronary ISR, considering both the primary clinical outcome (TLR) and the angiographic outcomes (LLL, BR, %DS). Personalized combination interventions including DCB or DES hold promise as a novel potential treatment pattern for coronary ISR.

OH2 oncolytic virus: A novel approach to glioblastoma intervention through direct targeting of tumor cells and augmentation of anti-tumor immune responses.

Glioblastoma (GBM), the deadliest central nervous system cancer, presents a poor prognosis and scant therapeutic options. Our research spotlights OH2, an oncolytic viral therapy derived from herpes simplex virus 2 (HSV-2), which demonstrates substantial antitumor activity and favorable tolerance in GBM. The extraordinary efficacy of OH2 emanates from its unique mechanisms: it selectively targets tumor cells replication, powerfully induces cytotoxic DNA damage stress, and kindles anti-tumor immune responses. Through single-cell RNA sequencing analysis, we discovered that OH2 not only curtails the proliferation of cancer cells and tumor-associated macrophages (TAM)-M2 but also bolsters the infiltration of macrophages, CD4+ and CD8+ T cells. Further investigation into molecular characteristics affecting OH2 sensitivity revealed potential influencers such as TTN, HMCN2 or IRS4 mutations, CDKN2A/B deletion and IDO1 amplification. This study marks the first demonstration of an HSV-2 derived OV's effectiveness against GBM. Significantly, these discoveries have driven the initiation of a phase I/II clinical trial (ClinicalTrials.gov: NCT05235074). This trial is designed to explore the potential of OH2 as a therapeutic option for patients with recurrent central nervous system tumors following surgical intervention.

Ca2LaTaO6:Bi3+/Mn4+ Phosphors with High Brightness Far-Red Emitting and Luminescence Enhancement for Plant Growth LED Lights and Temperature Sensor.

Herein, Bi3+/Mn4+ doped Ca2LaTaO6 phosphors with a double-perovskite structure were successfully synthesized with solid-state reaction at high temperature. The photoluminescence (PL) performances were investigated in detail. The blue radiation (∼465 nm) from the Bi3+ ion and the red radiation (∼686 nm) originating from the Mn4+ ion were obtained under 313 nm excitation. Especially, the pathway of energy transfer (Bi3+ → Mn4+) contributes to enhance the red emission intensity (Mn4+: ∼686 nm) in Ca2LaTaO6:Bi3+/Mn4+ system. The PL mechanism of Ca2LaTaO6:Bi3+/Mn4+ was analyzed through luminescence lifetimes and PL spectra. Moreover, the emitting bands of Ca2LaTaO6:Bi3+/Mn4+ were primarily matched with the absorbing bands of carotenoids and phytochrome PFR on behalf of plant growth, so the phosphors were suitable for the design of a plant growth light under near-ultraviolet to blue excitation. At last, the optical temperature dependent performances of the Ca2LaTaO6:Bi3+/Mn4+ were analyzed with luminescence intensity ratio technology. The sample has presented excellent temperature measuring relative sensitivity (SR = 2.106% K-1). The results illustrated that the Ca2LaTaO6:Bi3+/Mn4+ phosphor also can be used to develop an optical temperature sensor.