Role of exosomes in the communication and treatment between OSCC and normal cells.

Oral squamous cell carcinoma (OSCC) is a prevalent cancer that needs new therapeutic targets due to the poor postoperative prognosis in patients. Exosomes are currently one of important research areas owing to their unique properties. Exosomes are capable of acting as drug transporters, as well as facilitating interactions between OSCC and normal cells. Exosomes can be detected in body fluids such as blood, urine, cerebrospinal fluid, and bile. When exosomes are released from donor cells, they can carry various bioactive molecules to recipient cells, where these molecules participate in biological processes. This review highlights the mechanisms of exosome transfer between normal and OSCC cells. Exosomes isolated from donor OSCC cells can carry circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs) and play a role in signaling processes in the recipient OSCC cells, human umbilical vein endothelial cells, and macrophages. Exosomes secreted by carcinoma-associated fibroblasts, macrophages, and stem cells can also enter the recipient OSCC cells and modulate signaling events in these cells. Exosomes isolated from OSCC plasma, serum, and saliva are also associated with OSCC prognosis. Furthermore, while exosomes were shown to be associated with chemotherapy resistance in OSCC, they can also be used for drug delivery during OSCC treatment. In this paper, we reviewed the molecular mechanisms and functions of exosomes from different cell sources in OSCC cells, providing a basis for diagnosis and prognosis prediction in OSCC patients, and offering guidance for the design of molecular targets carried by exosomes in OSCC.

Case Report: TRPV4 gene mutation causing neuronopathy, distal hereditary motor, type VIII.

Neuronopathy, distal hereditary motor, type VIII is an exceedingly rare autosomal dominant genetic disorder, also known as congenital non-progressive distal spinal muscular atrophy. It is characterized by progressive weakness in distal motor function and atrophy of muscles, without accompanying sensory impairment. Presently, there is limited literature on this condition, and accurate epidemiological data regarding its incidence remains unavailable. We report a paediatric case of distal hereditary motor, type VIII that is caused by a heterozygous missense mutation in the TRPV4 gene (NM_021625): c.805C>T. The proband is a 7-year-old male child. During pregnancy, his mother had prenatal ultrasound revealing "inward turning of the feet", a condition persisting after birth. The proband is currently unable to stand independently, exhibiting bilateral clubfoot deformity. Although possessing normal cognitive function, he cannot walk unaided. Computed radiography findings reveal pelvic tilt, bilateral knee joint valgus, and bilateral clubfoot. The patient underwent familial exome sequencing, revealing a mutation in the TRPV4 gene (NM_021625): c.805C>T (p.Arg269Cys). Considering the patient's medical history, clinical manifestations, imaging studies, and genetic test results, the diagnosis for this individual is Neuronopathy, distal hereditary motor, type VIII. This report documents a case involving the TRPV4 gene mutation associated with Neuronopathy, distal hereditary motor, type VIII, contributing valuable case reference for the early diagnosis of this condition.

Design and rationale of the Comprehensive intelligent Hypertension managEment SyStem (CHESS) evaluation study: a cluster randomized controlled trial for hypertension management in primary care.

BACKGROUND: Hypertension management in China is suboptimal with high prevalence and low control rate due to various barriers, including lack of self-management awareness of patients and inadequate capacity of physicians. Digital therapeutic interventions including mobile health and computational device algorithms such as clinical decision support systems (CDSS) are scalable with the potential to improve blood pressure (BP) management and strengthen the healthcare system in resource-constrained areas, yet their effectiveness remains to be tested. The aim of this report is to describe the protocol of the Comprehensive intelligent Hypertension managEment SyStem (CHESS) evaluation study assessing the effect of a multi-faceted hypertension management system for supporting patients and physicians on BP lowering in primary care settings. MATERIALS AND METHODS: The CHESS evaluation study is a parallel-group, cluster-randomized controlled trial conducted in primary care settings in China. 41 primary care sites from 3 counties of China are randomly assigned to either the usual care or the intervention group with the implementation of the CHESS system, more than 1600 patients aged 35-80 years with uncontrolled hypertension and access to a smartphone by themselves or relatives are recruited into the study and followed up for 12 months. In the intervention group, participants receive patient-tailored reminders and alerts via messages or intelligent voice calls triggered by uploaded home blood pressure monitoring data and participants' characteristics, while physicians receive guideline-based prescription instructions according to updated individual data from each visit, and administrators receive auto-renewed feedback of hypertension management performance from the data analysis platform. The multiple components of the CHESS system can work synergistically and have undergone rigorous development and pilot evaluation using a theory-informed approach. The primary outcome is the mean change in 24-hour ambulatory systolic BP from baseline to 12-month. DISCUSSION: The CHESS trial will provide evidence and novel insight into the effectiveness and feasibility of an implementation strategy using a comprehensive digital BP management system for reducing hypertension burden in primary care settings. TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov, NCT05605418.

Correction: Influence of Environmental Factors and Genome Diversity on Cumulative COVID-19 Cases in the Highland Region of China: Comparative Correlational Study.

[This corrects the article DOI: .].

Groundwater hydrochemical signatures, nitrate sources, and potential health risks in a typical karst catchment of North China using hydrochemistry and multiple stable isotopes.

Nitrate pollution in aquatic ecosystems has received growing concern, particularly in fragile karst basins. In this study, hydrochemical compositions, multiple stable isotopes (δ2H-H2O, δ18Ο-Η2Ο, δ15Ν-ΝΟ3-, and δ18Ο-ΝΟ3-), and Bayesian stable isotope mixing model (MixSIAR) were applied to elucidate nitrate pollution sources in groundwater of the Yangzhuang Basin. The Durov diagram identified the dominant groundwater chemical face as Ca-HCO3 type. The NO3- concentration ranged from 10.89 to 90.45 mg/L (average 47.34 mg/L), showing an increasing trend from the upstream forest and grassland to the downstream agricultural dominant area. It is worth noting that 47.2% of groundwater samples exceeded the NO3- threshold value of 50 mg/L for drinking water recommended by the World Health Organization. The relationship between NO3-/Cl- and Cl- ratios suggested that most groundwater samples were located in nitrate mixed endmember from agricultural input, soil organic nitrogen, and manure & sewage. The Self-Organizing Map (SOM) and Pearson correlations analysis further indicated that the application of calcium fertilizer, sodium fertilizer, and livestock and poultry excrement in farmland elevated NO3- level in groundwater. The output results of the MixSIAR model showed that the primary sources of NO3- in groundwater were soil organic nitrogen (55.3%), followed by chemical fertilizers (28.5%), sewage & manure (12.7%), and atmospheric deposition (3.4%). Microbial nitrification was a dominant nitrogen conversion pathway elevating NO3- levels in groundwater, while the denitrification can be neglectable across the study area. The human health risk assessment (HHRA) model identified that about 88.9%, 77.8%, 72.2%, and 50.0% of groundwater samples posing nitrate's non-carcinogenic health hazards (HQ > 1) through oral intake for infants, children, females, and males, respectively. The findings of this study can offer useful biogeochemical information on nitrogen pollution in karst groundwater to support sustainable groundwater management in similar human-affected karst regions.

Correlation between spleen density and prognostic outcomes in patients with colorectal cancer after curative resection.

OBJECTIVE: The objective of this study was to investigate the correlation between spleen density and the prognostic outcomes of patients who underwent curative resection for colorectal cancer (CRC). METHODS: The clinical data of patients who were diagnosed with CRC and underwent radical resection were retrospectively analyzed. Spleen density was determined using computed tomography. Analysis of spleen density in relation to overall survival (OS) and disease-free survival (DFS) utilizing the Kaplan-Meier method. Univariate and multivariate Cox regression models were used to screen for independent prognostic factors, and a nomogram was constructed to predict OS and DFS. Moreover, internally validated using a bootstrap resamplling method. RESULTS: Two hundred twelve patients were included, of whom 23 (10.85%) were defined as having a diffuse reduction of spleen density (DROSD) based on diagnostic cutoff values (spleen density≦37.00HU). Kaplan-Meier analysis indicated that patients with DROSD had worse OS and DFS than those non-DROSD (P < 0.05). Multivariate Cox regression analysis revealed that DROSD, carbohydrate antigen 199 (CA199) > 37 U/mL, tumor node metastasis (TNM) stage III-IV, laparoscopy-assisted operation and American Society of Anesthesiology (ASA) score were independent risk factors for 3-year DFS. DROSD, CA199 > 37 U/mL, TNM stage III-IV, hypoalbuminemia, laparoscopy-assisted operation and ASA score were chosen as predictors of for 3-year OS. Nomograms showed satisfactory accuracy in predicting OS and DFS using calibration curves, decision curve analysis and bootstrap resamplling method. CONCLUSION: Patients with DROSD who underwent curative resection have worse 3-year DFS and OS. The nomogram demonstrated good performance, particularly in predicting 3-year DFS with a net clinical benefit superior to well-established risk calculator.

Characterization, antioxidant activity and in vitro digestion of hawthorn pectin prepared by gradient ethanol precipitation.

Four modified hawthorn pectin fractions (MHPs), named MHP-30, MHP-50, MHP-70 and MHP-90, were obtained by ultrasonic-assisted pectin methyl esterase modification and gradient ethanol precipitation. The results indicated that all four MHPs were composed of galacturonic acid, galactose, xylose, arabinose, glucose and mannose in different proportions. With the increase of the ethanol concentration, the molecular weight, esterification degree and galacturonic acid content of MHPs all decreased, whereas the arabinose content and branching degree increased. The structural characterization from XRD, SEM, and FT-IR showed that four MHPs exhibited amorphous structure, similar functional groups, diverse surface morphologies. Besides, in vitro antioxidant assays confirmed that MHP-70 and MHP-90 exhibited stronger total antioxidant activities than MHP-30 and MHP-50. The results of simulated saliva-gastrointestinal digestion showed that the molecular weight of MHP-70 and MHP-90 remained stable, yielded small amounts of reducing sugars, and were resistant to digestion in the human upper digestive tract. Overall, MHP-70 and MHP-90 shown great potential as novel natural antioxidants, which are expected to be good carbon sources for the utilization of intestinal microorganisms.

Application value of a hybrid tracer during sentinel lymph node biopsy for head and neck malignancies: A systematic review and meta-analysis.

To address the limitations of conventional sentinel lymph node biopsy (SLNB), a novel hybrid tracer (indocyanine green [ICG]-99mTc-nanocolloid) has been developed. This meta-analysis aimed to compare the differences between the novel hybrid tracer and conventional methods using ICG or radioisotope (RI) for SLNB in head and neck malignancies. This study was registered in the International Prospective Register of Systematic Reviews (CRD42023409127). PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched. This study included raw data on the number of sentinel lymph nodes (SLNs) identified using different modalities during surgery for head and neck malignancies. The identification rate of SLNs was the main outcome of interest. Prognostic data and complication rate cannot be deduced from this article. The heterogeneity test (I2) determined the use of a fixed- or random-effects model for the pooled risk ratio (RR). Overall, 1275 studies were screened, of which 11 met the inclusion criteria for the meta-analysis. In SLN identification of head and neck malignancies, ICG-99mTc-nanocolloid was superior to ICG or RI. In the subgroup analyses, the detection rates of ICG and RI tracers in SLNB were comparable, regardless of the device, tumor type, or tumor stage. In conclusion, in SLN identification of head and neck malignancies, the use of ICG-99mTc-nanocolloid is superior to the single technique of ICG or RI. This study suggests that Hospitals using ICG or RI may find it beneficial to change their practice to ICG-99mTc-nanocolloid, especially in the head and neck area, owing to its superior effectiveness.

Targeting NKAα1 to treat Parkinson's disease through inhibition of mitophagy-dependent ferroptosis.

Dysfunction of the Na+/K+-ATPase (NKA) has been documented in various neurodegenerative diseases, yet the specific role of NKAα1 in Parkinson's disease (PD) remains incompletely understood. In this investigation, we utilized NKAα1 haploinsufficiency (NKAα1+/-) mice to probe the influence of NKAα1 on dopaminergic (DA) neurodegeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Our findings reveal that NKAα1+/- mice displayed a heightened loss of DA neurons and more pronounced motor dysfunction compared to the control group when exposed to MPTP. Intriguingly, this phenomenon coincided with the activation of ferroptosis and impaired mitophagy both in vivo and in vitro. To scrutinize the role and underlying mechanism of NKAα1 in PD, we employed DR-Ab, an antibody targeting the DR-region of the NKA α subunit. Our study demonstrates that the administration of DR-Ab effectively reinstated the membrane abundance of NKAα1, thereby mitigating MPTP-induced DA neuron loss and subsequent improvement in behavioral deficit. Mechanistically, DR-Ab heightened the formation of the surface NKAα1/SLC7A11 complex, inhibiting SLC7A11-dependent ferroptosis. Moreover, DR-Ab disrupted the cytosolic interaction between NKAα1 and Parkin, facilitating the translocation of Parkin to mitochondria and enhancing the process of mitophagy. In conclusion, this study establishes NKAα1 as a key regulator of ferroptosis and mitophagy, identifying its DR-region as a promising therapeutic target for PD.

CD58 alterations govern antitumor immune responses by inducing PD-L1 and IDO in diffuse large B-cell lymphoma.

Recurrent abnormalities in immune surveillance-related genes affect the progression of diffuse large B-cell lymphoma (DLBCL) and modulate the response to therapeutic interventions. CD58 interacts with the CD2 receptor on T cells and natural killer (NK) cells and is recurrently mutated and deleted in DLBCL, suggesting it may play a role in regulating antitumor immunity. Herein, we comprehensively analyzed the genomic characteristics of CD58 through targeted next-generation sequencing, RNA-sequencing, whole-exome sequencing, and single-cell RNA-sequencing in patients with newly diagnosed DLBCL. The CD58 mutation rate was 9.1%, and the copy number loss rate was 44.7% among all enrolled DLBCL patients. Notably, CD58 genetic alterations, along with low CD58 expression, significantly correlated with reduced rates of response to R-CHOP therapy and inferior progression-free and overall survival. Single-cell RNA sequencing revealed that CD58 expression in tumor cells was negatively correlated with CD8+ T cell exhaustion/dysfunction status. Insufficient T-cell activation resulting from CD58 alterations could not be attributed solely to CD2 signaling. CD58 inhibited the activity of the JAK2/STAT1 pathway by activating the Lyn/CD22/SHP1 axis, thereby limiting PD-L1 and IDO expression. Elevated PD-L1 and IDO expression in CD58 deficient DLBCL cells led to immune evasion and tumor-intrinsic resistance to CAR T-cell therapy. Direct activation of CD58-CD2 costimulatory signaling in combination with anti-PD-L1 blockade or IDO inhibitor sensitized CD58-deficient DLBCL to CAR T-cell therapy. Collectively, this work identified the multiple roles of CD58 in regulating antitumor immune responses in DLBCL.

Preparation of AIEgen-based near-infrared afterglow luminescence nanoprobes for tumor imaging and image-guided tumor resection.

Fluorescence imaging represents a vital tool in modern biology, oncology and biomedical applications. Afterglow luminescence (AGL), which circumvents the light scattering and tissue autofluorescence interference associated with real-time excitation source, shows remarkably increased imaging sensitivity and depth. Here we present a protocol for the design and synthesis of AGL nanoprobes with an aggregation-induced emission (AIE) effect to simultaneously red shift and amplify the afterglow signal for tumor imaging and image-guided tumor resection. The nanoprobe (AGL AIE dot) is composed of an enol ether format of Schaap's agent and a near-infrared AIE fluorogen (AIEgen) (tetraphenylethylene-phenyl-dicyanomethylene-4H-chromene, TPE-Ph-DCM) to suppress the nonradiative dissipation pathway. Pre-irradiating AGL AIE dots with white light could generate singlet oxygen to convert Schaap's agent to its 1,2-dioxetane format, thus initializing the AGL process. With the aid of AIEgen, the AGL shows simultaneously red shifted emission maximum (from ~540 nm to ~625 nm) and enhanced intensity (by 3.2-fold), facilitating better signal-to-background ratio, imaging sensitivity and depth. Intriguingly, the activated AGL can last for over 10 days. Compared with conventional approaches, our method provides a new solution to concurrently red shift and amplify afterglow signals for better in vivo imaging outcomes. The preparation of AGL AIE dots takes ~2 days, the in vitro characterization takes ~10 days (less than 1 day if not involving afterglow kinetic profile study) and the tumor imaging and image-guided tumor resection takes ~7 days. These procedures can be easily reproduced and amended after standard laboratory training in chemical synthesis and animal handling.

Effects of C and Al Alloying on Constitutive Model Parameters and Hot Deformation Behavior of Medium-Mn Steels.

Single-pass isothermal hot compression tests on four medium-Mn steels with different C and Al contents were conducted using a Gleeble-3500 thermal simulation machine at varying deformation temperatures (900-1150 °C) and strain rates (0.01-5 s-1). Based on friction correction theory, the friction of the test stress-strain data was corrected. On this basis, the Arrhenius constitutive model of experimental steels considering Al content and strain compensation and hot processing maps of different experimental steels at a strain of 0.9 were established. Moreover, the effects of C and Al contents on constitutive model parameters and hot processing performance were analyzed. The results revealed that the increase in C content changed the trend of the thermal deformation activation energy Q with the true strain. The Q value of 2C7Mn3Al increased by about 50 KJ/mol compared with 7Mn3Al at a true strain greater than 0.4. In contrast, increasing the Al content from 0 to 1.14 wt.% decreased the activation energy of thermal deformation in the true strain range of 0.4-0.9. Continuing to increase to 3.30 wt.% increased the Q of 7Mn3Al over 7Mn by about 65 KJ/mol over the full strain range. In comparison, 7Mn1Al exhibited the best hot processing performance under the deformation temperature of 975-1125 °C and strain rate of 0.2-5 s-1. This is due to the addition of C element reduces the δ-ferrite volume fraction, which leads to the precipitation of κ-carbides and causes the formation of microcracks; an increase in Al content from 0 to 1.14 wt.% reduces the austenite stability and improves the hot workability, but a continued increase in the content up to 3.30 wt.% results in the emergence of δ-ferrite in the microstructure, which slows down the austenite DRX and not conducive to the hot processing performance.

Ultra-processed food consumption and chronic kidney disease risk: a systematic review and dose-response meta-analysis.

Background: High intake of ultra-processed food (UPF) has been associated with increased risk of chronic kidney disease(CKD), but the results remain inconsistent. We therefore performed this systematic review and dose­response meta-analysis of observational studies that shed light on the association between UPF consumption and the risk of CKD. Methods: A systematic literature search of PubMed, Embase, Web of Science, Scopus and China National Knowledge Infrastructure (CNKI) databases was carried out to find the eligible articles published up to October 31, 2023. Random-effects or fixed-effects models were used to pool the relative risks(RRs) and their 95% confidence intervals (CIs).The potential sources of heterogeneity across studies were examined using the Cochran's Q test and I-square(I2). Publication bias was examined using the visual inspection of asymmetry in funnel plots and quantified by Begg's and Egger's tests. Results: Eight studies (six cohort and two cross-sectional studies) exploring the association between UPF consumption and risk of CKD, were included in the final analysis. The pooled analyses revealed that high consumption of UPF was associated with an increased risk of CKD (RR = 1.25; 95%CI: 1.09­1.42, p < 0.0001). Moreover, a 10% increase of UPF consumption was associated with a 7% higher risk of CKD (RR = 1.07; 95%CI: 1.04­1.10, p < 0.001). Dose­response analysis of all included studies showed a linear association between UPF consumption and the risk of CKD (RR = 1.02; 95%CI:0.99­1.05, Pdose­response = 0.178, Pnonlinearity = 0.843). Conclusion: Our findings indicate that high consumption of UPF is significantly associated with an increased risk of CKD. Future research with prospective design is required to confirm this positive association.Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023478483, PROSPERO identifier CRD42023478483.

Empagliflozin in children with glycogen storage disease-associated inflammatory bowel disease: a prospective, single-arm, open-label clinical trial.

Glycogen storage disease type Ib (GSD-Ib) is a rare inborn error of glycogen metabolism caused by mutations in SLC37A4. Patients with GSD-Ib are at high risk of developing inflammatory bowel disease (IBD). We evaluated the efficacy of empagliflozin, a renal sodium‒glucose cotransporter protein 2 (SGLT2) inhibitor, on colonic mucosal healing in patients with GSD-associated IBD. A prospective, single-arm, open-label clinical trial enrolled eight patients with GSD-associated IBD from Guangdong Provincial People's Hospital in China from July 1, 2022 through December 31, 2023. Eight patients were enrolled with a mean age of 10.34 ± 2.61 years. Four male and four female. The endoscopic features included deep and large circular ulcers, inflammatory hyperplasia, obstruction and stenosis. The SES-CD score significantly decreased at week 48 compared with before empagliflozin. Six patients completed 48 weeks of empagliflozin therapy and endoscopy showed significant improvement or healing of mucosal ulcers, inflammatory hyperplasia, stenosis, and obstruction. One patient had severe sweating that required rehydration and developed a urinary tract infection. No serious or life-threatening adverse events. This study suggested that empagliflozin may promote colonic mucosal healing and reduce hyperplasia, stenosis, and obstruction in children with GSD-associated IBD.

Exenatide for obesity in children and adolescents: Systematic review and meta-analysis.

Objectives: There is no curative treatment for childhood obesity. We aim to synthesize published Randomized Controlled Trials (RCTs) evidence on the efficacy of exenatide in obese children and adolescents. Methods: We conducted a comprehensive search and analysis of relevant studies in popular databases such as PubMed, Web of Science, Embase, and Cochrane Library. Our focus was on RCTs that examined the effectiveness of exenatide for treating obesity in children. We primarily assessed changes in body weight, body mass index (BMI), fasting plasma glucose (FPG), or HbA1c levels. Additionally, we considered any adverse events reported during the treatment period, with particular attention to hypoglycemia. To evaluate the quality of RCTs included in our study, we employed the Cochrane bias assessment tool. Results: Five studies met the inclusion criteria. A group of 100 children were assigned to receive treatment with exenatide. Compared with controls, exenatide therapy reduced body weight and BMI by -0.6% (95% CI -0.93, -0.27), -1.11% (95% CI -1.91, -0.31), respectively. Undesirable consequences encompass gastrointestinal symptoms, with the majority of instances being characterized by mild severity. Conclusion: Exenatide demonstrates efficacy in the treatment of pediatric and adolescent obesity. Systematic Review Registration: PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=413706.

Role of prostaglandin E2 and its receptors in chronic liver disease.

Chronic liver disease (CLD) is a major global health burden in terms of growing morbidity and mortality. Although many conditions can cause CLD, leading to cirrhosis and hepatocellular carcinoma (HCC), viral hepatitis, drug-induced liver injury (DILI), alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are the most common culprits. Prostaglandin E2 (PGE2), produced in the liver, is an important lipid mediator derived from the ω-6 polyunsaturated fatty acid, arachidonic acid, and plays a critical role in hepatic homeostasis. The physiological effects of PGE2 are mediated through four classes of E-type prostaglandin (EP) receptors, namely EP1, EP2, EP3 and EP4. In recent years, an increasing number of studies has been done to clarify the effects of PGE2 and EP receptors in regulating liver function and the pathogenesis of CLD to create a new potential clinical impact. In this review, we overview the biosynthesis and regulation of PGE2 and discuss the role of its synthesizing enzymes and receptors in the maintenance of normal liver function and the development and progress of CLD. We also discuss the potential of the PGE2-EP receptors system in treating CLD with various etiologies.

Progress of medicinal plants and their active metabolites in ischemia-reperfusion injury of stroke: a novel therapeutic strategy based on regulation of crosstalk between mitophagy and ferroptosis.

The death of cells can occur through various pathways, including apoptosis, necroptosis, mitophagy, pyroptosis, endoplasmic reticulum stress, oxidative stress, ferroptosis, cuproptosis, and disulfide-driven necrosis. Increasing evidence suggests that mitophagy and ferroptosis play crucial regulatory roles in the development of stroke. In recent years, the incidence of stroke has been gradually increasing, posing a significant threat to human health. Hemorrhagic stroke accounts for only 15% of all strokes, while ischemic stroke is the predominant type, representing 85% of all stroke cases. Ischemic stroke refers to a clinical syndrome characterized by local ischemic-hypoxic necrosis of brain tissue due to various cerebrovascular disorders, leading to rapid onset of corresponding neurological deficits. Currently, specific therapeutic approaches targeting the pathophysiological mechanisms of ischemic brain tissue injury mainly include intravenous thrombolysis and endovascular intervention. Despite some clinical efficacy, these approaches inevitably lead to ischemia-reperfusion injury. Therefore, exploration of treatment options for ischemic stroke remains a challenging task. In light of this background, advancements in targeted therapy for cerebrovascular diseases through mitophagy and ferroptosis offer a new direction for the treatment of such diseases. In this review, we summarize the progress of mitophagy and ferroptosis in regulating ischemia-reperfusion injury in stroke and emphasize their potential molecular mechanisms in the pathogenesis. Importantly, we systematically elucidate the role of medicinal plants and their active metabolites in targeting mitophagy and ferroptosis in ischemia-reperfusion injury in stroke, providing new insights and perspectives for the clinical development of therapeutic drugs for these diseases.

Phytoalexin sakuranetin attenuates endocytosis and enhances resistance to rice blast.

Phytoalexin sakuranetin functions in resistance against rice blast. However, the mechanisms underlying the effects of sakuranetin remains elusive. Here, we report that rice lines expressing resistance (R) genes were found to contain high levels of sakuranetin, which correlates with attenuated endocytic trafficking of plasma membrane (PM) proteins. Exogenous and endogenous sakuranetin attenuates the endocytosis of various PM proteins and the fungal effector PWL2. Moreover, accumulation of the avirulence protein AvrCO39, resulting from uptake into rice cells by Magnaporthe oryzae, was reduced following treatment with sakuranetin. Pharmacological manipulation of clathrin-mediated endocytic (CME) suggests that this pathway is targeted by sakuranetin. Indeed, attenuation of CME by sakuranetin is sufficient to convey resistance against rice blast. Our data reveals a mechanism of rice against M. oryzae by increasing sakuranetin levels and repressing the CME of pathogen effectors, which is distinct from the action of many R genes that mainly function by modulating transcription.