The discovery of in situ thrombus attached to the patent foramen ovale channel in myocardial infarction with normal coronary arteries.

OBJECTIVE: Paradoxical embolism caused by a patent foramen ovale (PFO) is a rare cause of myocardial infarction (MI) in individuals presenting with normal coronary arteries on angiography; however, the deduction is often made due to the inability to identify the exact thrombus that penetrates the atrial septum. Previous studies using optical coherence tomography (OCT) have reported in situ thrombi attached to PFO tunnel in patients with cryptogenic stroke. However, the presence of such thrombi in patients with cryptogenic MI (without a definite cause) remains uncertain. METHOD: We retrospectively analyzed OCT data collected from February to July 2023 on PFO tunnels in MI adults with normal coronary arteries on angiography. RESULTS: Three patients diagnosed with cryptogenic MI and a PFO underwent OCT examination. These patients exhibited varying OCT findings. White thrombi and endocardial abnormalities in the channel were observed in two patients with MI. No thrombus or anomalous morphology on the endocardial surface was noted in the third patient. PFO closure was performed on all patients, and follow-up was completed by October 1, 2023. None of the patients reported recurrence of chest pain. CONCLUSION: In situ thrombus was identified within the PFO channel in patients with cryptogenic MI, potentially serving as a novel etiological factor for coronary thrombosis.

Pd/Cu Dual Metal-Catalyzed Regioselective [2 + 2 + 2] Cycloaddition of Malononitriles with Alkynes to Densely Substituted Pyridines.

Transition metal-catalyzed [2 + 2 + 2] cycloaddition of nitriles and two alkynes is an efficient method for assembling pyridines. However, examples employing palladium catalysis have rarely been disclosed, and the processes of reactivity and selectivity remain unclear. We report here a palladium/copper dual metal-catalyzed [2 + 2 + 2] cycloaddition of diynyl-tethered malononitriles and terminal alkynes to synthesize densely substituted pyridines. This method features a good substrate scope, synthetically useful yields, and perfect regioselectivity. The derivatization of the pyridine products demonstrates the potential application of this method in synthesizing heterocycles and as ligands in photocatalysis. Preliminary mechanistic studies suggest that the reaction undergoes aza-oxidative cycloaddition of Pd(0) with nitrile and alkyne, followed by alkyne insertion and reductive elimination. The presence of copper is crucial to its reactivity and regioselectivity.

SARS-CoV-2 N protein-induced Dicer, XPO5, SRSF3, and hnRNPA3 downregulation causes pneumonia.

Though RNAi and RNA-splicing machineries are involved in regulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, their precise roles in coronavirus disease 2019 (COVID-19) pathogenesis remain unclear. Herein, we show that decreased RNAi component (Dicer and XPO5) and splicing factor (SRSF3 and hnRNPA3) expression correlate with increased COVID-19 severity. SARS-CoV-2 N protein induces the autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, inhibiting miRNA biogenesis and RNA splicing and triggering DNA damage, proteotoxic stress, and pneumonia. Dicer, XPO5, SRSF3, and hnRNPA3 knockdown increases, while their overexpression decreases, N protein-induced pneumonia's severity. Older mice show lower expression of Dicer, XPO5, SRSF3, and hnRNPA3 in their lung tissues and exhibit more severe N protein-induced pneumonia than younger mice. PJ34, a poly(ADP-ribose) polymerase inhibitor, or anastrozole, an aromatase inhibitor, ameliorates N protein- or SARS-CoV-2-induced pneumonia by restoring Dicer, XPO5, SRSF3, and hnRNPA3 expression. These findings will aid in developing improved treatments for SARS-CoV-2-associated pneumonia.

The prediction model of fall risk for the elderly based on gait analysis.

INTRODUCTION: Early screening and identification are crucial for fall prevention, and developing a new method to predict fall risk in the elderly can address the current lack of objectivity in assessment tools. METHODS: A total of 132 elderly individuals over 80 years old residing in some nursing homes in Shanghai were selected using a convenient sampling method. Fall history information was collected, and gait data during a 10-meter walk were recorded. Logistic regression was employed to establish the prediction model, and a nomogram was used to assess the importance of the indicators. The Bootstrap method was utilized for internal validation of the model, while the verification set was used for external validation. The predictive performance of the model was evaluated using the area under the ROC curve, calibration curve, and decision curve analysis (DCA) to assess clinical benefits. RESULTS: The incidence of falls in the sample population was 36.4%. The Tinetti Gait and Balance Test (TGBT) score (OR = 0.832, 95% CI: 0.734,0.944), stride length (OR = 0.007, 95% CI: 0.000,0.104), difference in standing time (OR = 0.001, 95% CI: 0.000,0.742), and mean stride time (OR = 0.992, 95% CI:0.984,1.000) were identified as significant factors. The area under the ROC curve was 0.878 (95% CI: 0.805, 0.952), with a sensitivity of 0.935 and specificity of 0.726. The Brier score was 0.135, and the Hosmer-Lemeshow test (χ2 = 10.650, P = 0.222) indicated a good fit and calibration of the model. CONCLUSION: The TGBT score, stride length, difference in standing time, and stride time are all protective factors associated with fall risk among the elderly. The developed risk prediction model demonstrates good discrimination and calibration, providing valuable insights for early screening and intervention in fall risk among older adults.

Cadherin-18 loss in prospermatogonia and spermatogonial stem cells enhances cell adhesion through a compensatory mechanism.

Extracellular membrane proteins are crucial for mediating cell attachment, recognition, and signal transduction in the testicular microenvironment, particularly germline stem cells. Cadherin 18 (CDH18), a type II classical cadherin, is primarily expressed in the nervous and reproductive systems. Here, we investigated the expression of CDH18 in neonatal porcine prospermatogonia (ProSGs) and murine spermatogonial stem cells (SSCs). Disruption of CDH18 expression did not adversely affect cell morphology, proliferation, self-renewal, or differentiation in cultured porcine ProSGs, but enhanced cell adhesion and prolonged cell maintenance. Transcriptomic analysis indicated that the down-regulation of CDH18 in ProSGs significantly up-regulated genes and signaling pathways associated with cell adhesion. To further elucidate the function of CDH18 in germ cells, Cdh18 knockout mice were generated, which exhibited normal testicular morphology, histology, and spermatogenesis. Transcriptomic analysis showed increased expression of genes associated with adhesion, consistent with the observations in porcine ProSGs. The interaction of CDH18 with ß-catenin and JAK2 in both porcine ProSGs and murine SSCs suggested an inhibitory effect on the canonical Wnt and JAK-STAT signaling pathways during CDH18 deficiency. Collectively, these findings highlight the crucial role of CDH18 in regulating cell adhesion in porcine ProSGs and mouse SSCs. Understanding this regulatory mechanism provides significant insights into the testicular niche.

Abnormal late postprandial glucagon response in type 1 diabetes is a function of differences in stimulated C-peptide concentrations.

Background: The functional changes in alpha cells in patients with type 1 diabetes (T1D) with different residual beta cell functions remain poorly elucidated. The study aimed to investigate the relationship between glucagon secretion and C-peptide levels and to explore the relationship between glucagon response and glucose increment in respond to a secretagogue in a steamed bread meal tolerance test (BMTT) in T1D. Methods: The study enrolled 43 adult patients with T1D and 24 healthy control subjects. Patients with T1D who underwent BMTT were divided into two groups based on peak C-peptide levels: C peptide low (CPL; C-peptide < 200 pmol/L; n=14) and high (CPH; C peptide ≥ 200 pmol/L; n=29). Plasma glucose, C-peptide, glucagon levels at 0, 30, 60, 120, and 180 min were measured. The glucagon response to the BMTT was defined by areas under the curve (AUC) as early (AUC0-30), late (AUC30-180), or total (AUC0-180) glucagon. Results: Compared to healthy individuals, fasting plasma glucagon was lower and postprandial plasma glucagon level was increased in patients with T1D. Glucagon levels after BMTT between the CPL and CPH group showed significant group by time interaction. Peak glucagon and glucagon at 60-180 min, total and late glucagon response were higher in CPL than CPH group, while fasting glucagon and early glucagon response adjusted for glucose were comparable between CPL and CPH group. The higher late glucagon response and late glucagon response adjusted for glucose were associated with lower peak C-peptide in T1D. The higher late glucagon response and lower peak C-peptide were associated with the higher value of ▵glucose at 180 min. Conclusion: Stimulated C-peptide levels affect the paradoxical increase in postprandial glucagon secretion in patients with T1D, especially late glucagon response. The exaggerated postprandial glucagon secretion further stimulates the elevation of postprandial glucose in patients with T1D.

Reliability of Metformin's protective effects against doxorubicin-induced cardiotoxicity: a meta-analysis of animal studies.

Background: The protective effects of metformin (Met) against doxorubicin (Dox)-induced cardiotoxicity via potential hypotheses of mechanisms of action with unknown reliability and credibility. Objectives: This study aimed to investigate the protective effects of Met against Dox-induced cardiotoxicity and the underlying mechanisms of action, as well as examine their reliability and credibility. Methods: A comprehensive search was conducted within the PubMed, Embase, Web of Science, Science Direct, Scopus, and CNKI databases from inception to 31 December 2023. Animal experiments evaluating the efficacy of Met against Dox-induced cardiotoxicity were included in this study. The primary efficacy outcomes were markers of myocardial injury. Effect size was measured using the standardized mean difference for continuous variables. Data were pooled using a random-effects model in the Stata 18 statistical software package. Results: Twenty-one studies involving 203-208 animals treated with Dox and 271-276 animals treated with Dox and Met were included in this analysis. Quality assessment revealed high-quality scores. Pooled results favored Met treatment based on the serum lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTnI), and aspartate aminotransferase levels. Sensitivity analysis using the leave-one-out method demonstrated stable results. Funnel plots, Egger's test, and Begg's test confirmed potential publication bias. The oxidative stress hypothesis has been investigated extensively based on abundant evidence. Conclusion: Met is effective and safe for protecting against Dox-induced cardiotoxicity, thus making it an appropriate drug for clinical investigation. The oxidative stress hypothesis of mechanism of action is well established with highest reliability and credibility.

Rapid progress of an iris metastasis from esophageal cancer: a case report and review of literature.

This case report details a rare instance of rapid iris metastasis from esophageal cancer in a 59-year-old man. A literature review was conducted to explore recent advances in detecting, diagnosing, and treating intraocular metastatic malignancies. Positron emission tomography-computed tomography played a crucial role in identifying primary sites and systemic metastases. Local treatment combined with systemic therapy effectively reduced tumor size, preserved useful vision, and improved the patient's survival rate. A comparison was made of the characteristics of iris metastases from esophageal cancer and lung cancer, including age, gender, tumor characteristics, and treatment. The challenges associated with diagnosis and treatment are discussed, highlighting the implications for clinical practice.

Digital anatomical features of morphological development in C2-C7 neurocentral synchondrosis in children aged 1-6 years: a retrospective study of CT images.

BACKGROUND: With the continuous improvement of diagnosis and treatment technology for cervical spine-related diseases in children at home and abroad, the demand for exploring the developmental anatomy and function of children's cervical spine of different ages is increasing. So the aim of this study was to investigate the changes of anatomical indicators in neurocentral synchondrosis (NCS) of C2-C7 with age and the developmental characteristics of different vertebrae in children aged 1-6 years old. METHOD: A retrospective collection of 160 cases of normal cervical spine CT images of children aged 1-6 years old in provincial tertiary hospitals, according to the age group of 1-year-old into 6 groups. The original data of continuously scanned cervical spine tomography images were imported into Mimics16.0 software, under the two-dimensional image window, selected the measurement tool under the Measurements toolbar to measure and statistically analyzed the anatomical indicators such as cross diameter, sagittal diameter, height, perimeter and area of NCS in the C2-C7 segment of the cervical spine on the coronal plane and cross-section. RESULTS: There was no significant difference in the anatomical indexes of cervical spine NCS in children compared with the left and right sides of the same vertebrae (P > 0.05). The same cervical spine generally had differences between the age groups of 1-4 years old and 5-6 years old (P < 0.05).The transverse diameter and circumference gradually decreased with age; the sagittal diameter and height showed a slight increase trend; there was a maximum area at 2 years of age. In different cervical vertebrae of the same age group, the NCS values of C3, C4, and C5 varied greatly, which showed that the ossification process of cervical cartilage was faster than that at the upper and lower ends. There were obvious differences between C2 and the rest of the cervical vertebral segments' NCS ossification process. C7 was also very different from the rest of the cervical vertebrae segments, presumably more similar to the thoracic spine. CONCLUSIONS: The anatomical indexes of C2-C7 NCS in children have obvious developmental regularities at different ages, and there are also regularities between cervical segments.

Fighting ferroptosis: Protective effects of dexmedetomidine on vital organ injuries.

Vital organ injury is one of the leading causes of global mortality and socio-economic burdens. Current treatments have limited efficacy, and new strategies are needed. Dexmedetomidine (DEX) is a highly selective α2-adrenergic receptor that protects multiple organs by reducing inflammation and preventing cell death. However, its exact mechanism is not yet fully understood. Understanding the underlying molecular mechanisms of its protective effects is crucial as it could provide a basis for designing highly targeted and more effective drugs. Ferroptosis is the primary mode of cell death during organ injury, and recent studies have shown that DEX can protect vital organs from this process. This review provides a detailed analysis of preclinical in vitro and in vivo studies and gains a better understanding of how DEX protects against vital organ injuries by inhibiting ferroptosis. Our findings suggest that DEX can potentially protect vital organs mainly by regulating iron metabolism and the antioxidant defense system. This is the first review that summarizes all evidence of ferroptosis's role in DEX's protective effects against vital organ injuries. Our work aims to provide new insights into organ therapy with DEX and accelerate its translation from the laboratory to clinical settings.

Associations of personal PM2.5-bound heavy metals and heavy metal mixture with lung function: Results from a panel study in Chinese urban residents.

BACKGROUND: There are a few reports on the associations between fine particulate matter (PM2.5)-bound heavy metals and lung function. OBJECTIVES: To evaluate the associations of single and mixed PM2.5-bound heavy metals with lung function. METHODS: This study included 316 observations of 224 Chinese adults from the Wuhan-Zhuhai cohort over two study periods, and measured participants' personal PM2.5-bound heavy metals and lung function. Three linear mixed models, including the single constituent model, the PM2.5-adjusted constituent model, and the constituent residual model were used to evaluate the association between single metal and lung function. Mixed exposure models including Bayesian kernel machine regression (BKMR) model, weighted quantile sum (WQS) model, and Explainable Machine Learning model were used to assess the relationship between PM2.5-bound heavy metal mixtures and lung function. RESULTS: In the single exposure analyses, significant negative associations of PM2.5-bound lead, antimony, and cadmium with peak expiratory flow (PEF) were observed. In the mixed exposure analyses, significant decreases in forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC), maximal mid-expiratory flow (MMF), and forced expiratory flow at 75% of the pulmonary volume (FEF75) were associated with the increased PM2.5-bound heavy metal mixture. The BKMR models suggested negative associations of PM2.5-bound lead and antimony with lung function. In addition, PM2.5-bound copper was positively associated with FEV1/FVC, MMF, and FEF75. The Explainable Machine Learning models suggested that FEV1/FVC, MMF, and FEF75 decreased with the elevated PM2.5-bound lead, manganese, and vanadium, and increased with the elevated PM2.5-bound copper. CONCLUSIONS: The negative relationships were detected between PM2.5-bound heavy metal mixture and FEV1/FVC, MMF, as well as FEF75. Among the PM2.5-bound heavy metal mixture, PM2.5-bound lead, antimony, manganese, and vanadium were negatively associated with FEV1/FVC, MMF, and FEF75, while PM2.5-bound copper was positively associated with FEV1/FVC, MMF, and FEF75.

Preliminary effects of risk-adapted PSA screening for prostate cancer after integrating PRS-specific and age-specific variation.

Background: Although the risk of prostate cancer (PCa) varies across different ages and genetic risks, it's unclear about the effects of genetic-specific and age-specific prostate-specific antigen (PSA) screening for PCa. Methods: Weighed and unweighted polygenic risk scores (PRS) were constructed to classify the participants from the PLCO trial into low- or high-PRS groups. The age-specific and PRS-specific cut-off values of PSA for PCa screening were determined with time-dependent receiver-operating-characteristic curves and area-under-curves (tdAUCs). Improved screening strategies integrating PRS-specific and age-specific cut-off values of PSA were compared to traditional PSA screening on accuracy, detection rates of high-grade PCa (Gleason score ≥7), and false positive rate. Results: Weighted PRS with 80 SNPs significantly associated with PCa was determined as the optimal PRS, with an AUC of 0.631. After stratifying by PRS, the tdAUCs of PSA with a 10-year risk of PCa were 0.818 and 0.816 for low- and high-PRS groups, whereas the cut-off values were 1.42 and 1.62 ng/mL, respectively. After further stratifying by age, the age-specific cut-off values of PSA were relatively lower for low PRS (1.42, 1.65, 1.60, and 2.24 ng/mL for aged <60, 60-64, 65-69, and ≥70 years) than high PRS (1.48, 1.47, 1.89, and 2.72 ng/mL). Further analyses showed an obvious interaction of positive PSA and high PRS on PCa incidence and mortality. Very small difference in PCa risk were observed among subgroups with PSA (-) across different age and PRS, and PCa incidence and mortality with PSA (+) significantly increased as age and PRS, with highest risk for high-PRS/PSA (+) in participants aged ≥70 years [HRs (95%CI): 16.00 (12.62-20.29) and 19.48 (9.26-40.96)]. The recommended screening strategy reduced 12.8% of missed PCa, ensured high specificity, but not caused excessive false positives than traditional PSA screening. Conclusion: Risk-adapted screening integrating PRS-specific and age-specific cut-off values of PSA would be more effective than traditional PSA screening.

Impact of Physiological Characteristics on Chylomicron Pathway-Mediated Absorption of Nanocrystals in the Pediatric Population.

Nanocrystals exhibit significant advantages in improving the oral bioavailability of poorly soluble drugs. However, the complicated absorption properties of nanocrystals and the differences in physiological characteristics between children and adults limit pediatric applications of nanocrystals. To elucidate the absorption differences and the underlying mechanisms between children and adults, the pharmacokinetics and tissue distribution of aprepitant crystals with different particle sizes (NC200, NC500, and MC2.5) in rats and mice at different ages were studied, and their absorption mechanisms were investigated in Caco-2 cells, mice, and rats. It was found that childhood animals demonstrated higher bioavailability compared with adolescent and adult animals, which was related to higher bile salt concentration and accelerated drug dissolution in the intestine of childhood animals. The majority of nanocrystals were dissolved and formed micelles under the influence of bile salts. Compared with intact nanocrystals, the bile salt micelle-associated aprepitant was absorbed through the chylomicron pathway, wherein Apo B assisted in the reassembling of the aprepitant micelles after endocytosis. Higher bile salt concentration and Apo B expression in the intestines of childhood animals are both responsible for the higher chylomicron transport pathways. Elucidation of the chylomicron pathway in the varied absorption of nanocrystals among children, adolescents, and adults provides strong theoretical guidance for promoting the rational and safe use of nanocrystals in pediatric populations.

The acoustic change complex evoked by location-change sounds in the elderly.

OBJECTIVE: We have shown that the acoustic change complex (ACC) can be elicited by changing the horizontal sound location in young individuals. In this study, we aimed to evaluate the application of ACC within the elderly and its relationship with behavioural results. DESIGN: The minimum audible angle (MAA), as well as onset cortical auditory evoked potentials (onset-CAEPs) and ACC elicited by the stimuli of location-change white noise (±45 to ±2 degrees) were recorded. Latencies and amplitudes were analysed using repeated-measures ANOVA. Pearson correlation analysis was conducted to examine the relationship between ACC and MAA. STUDY SAMPLE: Ten older adults with normal hearing (NH) and twenty with presbycusis. RESULTS: The ACC was effectively elicited with angular variations in elderly participants. The onset-CAEP N1 latency, ACC N1'-P2' amplitude, and N1' latency were all associated with the angle shifts, with the N1' latency being the most predictive factor for angle discrimination. The consistency between MAA and ACC made them complementary for the clinical evaluation of sound localisation. CONCLUSIONS: The utilisation of ACC, evoked by location-change sounds, presented a promising clinical objective measure for evaluating sound localisation abilities in the elderly.

Associations of prenatal exposure to individual and mixed organophosphate esters with ADHD symptom trajectories in preschool children: The modifying effects of maternal Vitamin D.

BACKGROUND: Organophosphate esters (OPEs) are a class of environmental chemicals with endocrine-disrupting properties. Epidemiologic studies have demonstrated that prenatal OPEs exposure is associated with neurodevelopmental disorders in offspring. However, studies assessing the effects of prenatal OPEs exposure on the dynamic changes in attention deficit hyperactivity disorder (ADHD) symptoms in preschoolers are scarce. Since vitamin D has been demonstrated to have a "neuroprotective" effect, the modifying effects of maternal vitamin D were estimated. METHODS: The present study included 2410 pregnant women from the Ma'anshan Birth Cohort. The levels of OPEs in the mothers' urine were examined in the three trimesters. The Chinese version of the Conners Abbreviated Symptom Questionnaire was used to examine preschoolers' ADHD symptoms at 3, 5, and 6 years of age. ADHD symptom trajectories were fitted via group-based trajectory modeling. We used multinomial logistic regression, Bayesian kernel machine regression, quantile-based g-computation, and generalized linear models to assess individual and mixed relationships between OPEs during pregnancy and preschoolers' ADHD symptoms and trajectories. RESULTS: Preschoolers' ADHD symptom scores were fitted to 3 trajectories, including the low-score, moderate-score, and high-score groups. First-trimester dibutyl phosphate (DBP), second-trimester bis(2-butoxyethyl) phosphate (BBOEP), and third-trimester diphenyl phosphate (DPHP) were associated with an increased risk in the high-score group (p < 0.05). BBOEP in the third trimester was associated with decreased risk in the moderate-score group (OR = 0.89, 95% CI: 0.79, 1.00). For mothers with 25(OH)D deficiency, a positive relationship was observed between OPEs during pregnancy and symptom trajectories. Our results did not reveal any mixed effects of OPEs on ADHD symptom trajectories. CONCLUSION: Prenatal exposure to OPEs had heterogeneous associations with ADHD symptom trajectories in preschoolers. Additionally, the effect of individual OPEs on symptom trajectories was intensified by vitamin D deficiency.

Broadband stepped-frequency radar waveform generation by Fourier domain mode-locking period-one laser dynamics.

A stepped-frequency (SF) radar waveform generation method based on Fourier domain mode-locking (FDML) period-one laser dynamics is proposed and demonstrated. By fast controlling the optical injection strength of a semiconductor laser through electro-optical modulation, a broadband SF signal is generated. By further introducing an optoelectronic feedback loop with its round trip time delay matched with the temporal period of the SF signal, FDML is enabled through which the frequency stability, accuracy, and in-band signal-to-noise ratio are greatly improved. In the experiment, SF signals with a bandwidth of 6 GHz (12-18 GHz) and a frequency step of 150 MHz are generated. By comparing the qualities of signals generated with and without FDML, advantages of the proposed SF signal generation method are verified. Based on the proposed SF signal generation method, high-resolution inverse synthetic aperture radar (ISAR) imaging is also demonstrated, in which the 2D imaging resolution reaches 2.6 cm × 3.82 cm.

Role of N6-methyladenosine in tumor neovascularization.

Tumor neovascularization is essential for the growth, invasion, and metastasis of tumors. Recent studies have highlighted the significant role of N6-methyladenosine (m6A) modification in regulating these processes. This review explores the mechanisms by which m6A influences tumor neovascularization, focusing on its impact on angiogenesis and vasculogenic mimicry (VM). We discuss the roles of m6A writers, erasers, and readers in modulating the stability and translation of angiogenic factors like vascular endothelial growth factor (VEGF), and their involvement in key signaling pathways such as PI3K/AKT, MAPK, and Hippo. Additionally, we outline the role of m6A in vascular-immune crosstalk. Finally, we discuss the current development of m6A inhibitors and their potential applications, along with the contribution of m6A to anti-angiogenic therapy resistance. Highlighting the therapeutic potential of targeting m6A regulators, this review provides novel insights into anti-angiogenic strategies and underscores the need for further research to fully exploit m6A modulation in cancer treatment. By understanding the intricate role of m6A in tumor neovascularization, we can develop more effective therapeutic approaches to inhibit tumor growth and overcome treatment resistance. Targeting m6A offers a novel approach to interfere with the tumor's ability to manipulate its microenvironment, enhancing the efficacy of existing treatments and providing new avenues for combating cancer progression.

Comparison of nanovesicles derived from Panax notoginseng at different size: physical properties, composition, and bioactivity.

Aim: Plant-derived nanovesicles have emerged as potential agents for combating tumors. In this study, we investigated the inhibitory effects of Panax notoginseng-derived nanovesicles (PnNVs) on the proliferation and migration of squamous cell carcinoma. Additionally, we explored the relationship between plant tuber size and the physical properties, composition and bioactivity of these nanovesicles. Methods: We isolated PnNVs from Panax notoginseng tubers of varying sizes: small-sized (s_PnNVs), medium-sized (m_PnNVs) and large-sized (l_PnNVs), and evaluated for size, potential, and morphology. Cellular uptake efficiency was assessed using confocal microscopy and flow cytometry. The ability of different PnNVs to inhibit oral squamous cell carcinoma cells was evaluated using plate cloning, CCK8 assay, and scratch healing assay. Off-target metabolomics was used to compare metabolic compounds of different PnNVs. Results: Our findings revealed that s_PnNVs exhibited lower potential but had the highest cellular uptake efficiency, whereas m_PnNVs were characterized by the smallest size and lowest cellular uptake efficiency. Notably, m_PnNVs demonstrated the most effective inhibition of squamous cell carcinoma growth and migration. Compositional analyses showed that PnNVs were rich in proteins and contained lower levels of RNA, with l_PnNVs having the highest protein content. Furthermore, untargeted metabolomics analysis revealed a significant increase in the expression of specific antitumour-related metabolites in m_PnNVs compared to s_PnNVs and l_PnNVs. Conclusion: Overall, our results underscore the influence of plant tuber size on the bioactivity of the nanovesicles from which they are derived, emphasizing its importance for experimental design and study reproducibility.

Synergistic promotion of nitrogen vacancies and single atomic dopants on Pt/C3N4 for photocatalytic hydrogen evolution.

C3N4 is widely applied in the synthesis of single-atom catalysts. However, understanding on the active site and the reaction mechanism is not fully in consensus. Especially, bare studies have considered the coordination environment of the single-atomic dopant and the effect of nitrogen vacancy on C3N4. In this study, we found that the presence of nitrogen vacancies promotes the activation of water and reduces the activation energy barrier for hydrogen generation. The results show that a synergistic effect between single-atom Pt and nitrogen vacancies enables the catalyst to achieve a superior hydrogen production rate of 3,890 µmol/g/h, which is 16.8 times higher than that of pristine C3N4. Moreover, the catalyst is also applicable for photocatalytic hydrogen production from seawater without significantly decreased hydrogen production rate. This study paves the way for the rational design and optimization of next-generation photocatalysts for sustainable energy applications, particularly in solar-driven hydrogen production.