Fermented tea leave extract against oxidative stress and ageing of skin in vitro and in vivo.

OBJECTIVE: The objective is to develop a natural and stable anti-oxidative stress and anti-ageing ingredient. In this study, we evaluated the changes in white tea leaves fermented with Eurotium cristatum PLT-PE and Saccharomyces boulardii PLT-HZ and their efficacy against skin oxidative stress. METHODS: We employed untargeted metabolomics technology to analyse the differential metabolites between tea extract (TE) and fermented tea extract (FTE). In vitro, using H2O2-induced HaCaT cells, we evaluated cell vitality, ROS, and inflammatory factors (TNF-α, IL-1ß, and IL-6). Additionally, we verified the effects on the extracellular matrix and nuclear DNA using fibroblasts or reconstructed skin models. We measured skin hydration, elasticity, wrinkle area, wrinkle area ratio, erythema area, and erythema area ratio in volunteers after using an emulsion containing 3% FTE for 28 and 56 days. RESULTS: Targeted metabolomics analysis of white tea leaves yielded more than 20 differential metabolites with antioxidant and anti-inflammatory activities, including amino acids, polypeptides, quercetin, and liquiritin post-fermentation. FTE, compared to TE, can significantly reduce reactive oxygen species (ROS) and protect against oxidative stress-induced skin damage in H2O2-induced HaCaT cells. FTE can inhibit H2O2-induced collagen degradation by suppressing the MAPK/c-Jun signalling pathway and can also mitigate the reactive oxygen species damage to nuclear DNA. Clinical studies showed that the volunteers' stratum corneum water content, skin elasticity, wrinkle area, wrinkle area ratio, erythema area, and erythema area ratio significantly improved from the baseline after 28 and 56 days of FTE use. CONCLUSION: This study contributes to the growing body of literature supporting the protective effects against skin oxidative stress and ageing from fermented plant extracts. Moreover, our findings might inspire multidisciplinary efforts to investigate new fermentation techniques that could produce even more potent anti-ageing solutions.

OBJECTIF: L'objectif est de développer un ingrédient naturel et stable contre le stress oxydatif et anti­âge. Dans cette étude, nous avons évalué les modifications dans les feuilles de thé blanc fermentées avec la PLT­PE Eurotium cristatum et la PLT­HZ Saccharomyces boulardii et leur efficacité contre le stress oxydatif cutané. MÉTHODES: Nous avons utilisé une technologie de métabolomique non ciblée pour analyser les métabolites différentiels entre l'extrait de thé (ET) et l'extrait de thé fermenté (ETF). In vitro, à l'aide de cellules HaCaT induites par l'H2O2, nous avons évalué la vitalité cellulaire, les ERO et les facteurs inflammatoires (TNF­α, IL­1ß, and IL­6). Nous avons également vérifié les effets sur la matrice extracellulaire et l'ADN nucléaire à l'aide de fibroblastes ou de modèles cutanés reconstruits. Nous avons mesuré l'hydratation de la peau, l'élasticité, la surface de rides, le rapport des surfaces de rides, la surface d'érythème, et le rapport des surfaces d'érythème chez des volontaires ayant utilisé une émulsion contenant 3% d'ETF pendant 28 et 56 jours. RÉSULTATS: L'analyse métabolomique ciblée des feuilles de thé blanc a révélé plus de 20 métabolites différentiels ayant des activités antioxydantes et anti­inflammatoires, notamment des acides aminés, des polypeptides, de la quercétine et de la liquiritine après fermentation. Par rapport à l'ET, l'ETF peut réduire significativement les espèces réactives de l'oxygène (ERO) et protéger contre les lésions cutanées induites par le stress oxydatif dans les cellules HaCaT induites par l'H2O2. L'ETF peut inhiber la dégradation du collagène induite par l'H2O2 en supprimant la voie de signalization MAPK/c­Jun et peut également atténuer les dommages causés par les espèces réactives de l'oxygène à l'ADN nucléaire. Les études cliniques ont montré que la teneur en eau de la couche cornée des volontaires, l'élasticité de la peau, la surface de rides, le rapport des surfaces de rides, la surface d'érythème et le rapport des surfaces d'érythème se sont significativement améliorés par rapport à la référence après 28 et 56 jours d'utilisation d'ETF. CONCLUSION: Cette étude contribue au corpus croissant de littérature soutenant les effets protecteurs des extraits de plantes fermentées contre le stress oxydatif cutané et le vieillissement. En outre, nos résultats pourraient inspirer des efforts pluridisciplinaires pour étudier de nouvelles techniques de fermentation susceptibles de produire des solutions anti­âge encore plus puissantes.

The genetic architecture of age at menarche and its causal effects on other traits.

Age at menarche (AAM) is a sign of puberty of females. It is a heritable trait associated with various adult diseases. However, the genetic mechanism that determines AAM and links it to disease risk is poorly understood. Aiming to uncover the genetic basis for AAM, we conducted a joint association study in up to 438,089 women from 3 genome-wide association studies of European and East Asian ancestries. A series of bioinformatical analyses and causal inference were then followed to explore in-depth annotations at the associated loci and infer the causal relationship between AAM and other complex traits/diseases. This largest meta-analysis identified a total of 21 novel AAM associated loci at the genome wide significance level (P < 5.0 × 10-8), 4 of which were European ancestry-specific loci. Functional annotations prioritized 33 candidate genes at newly identified loci. Significant genetic correlations were observed between AAM and 67 complex traits. Further causal inference demonstrated the effects of AAM on 13 traits, including forced vital capacity (FVC), high blood pressure, age at first live birth, etc, indicating that earlier AAM causes lower FVC, worse lung function, hypertension and earlier age at first (last) live birth. Enrichment analysis identified 5 enriched tissues, including the hypothalamus middle, hypothalamo hypophyseal system, neurosecretory systems, hypothalamus and retina. Our findings may provide useful insights that elucidate the mechanisms determining AAM and the genetic interplay between AAM and some traits of women.

Ginsenoside compound K alleviates D-galactose-induced mild cognitive impairment by modulating gut microbiota-mediated short-chain fatty acid metabolism.

The occurrence and progression of mild cognitive impairment (MCI) are closely related to dysbiosis of the gut microbiota. Ginsenoside compound K (CK), a bioactive component of ginseng, has been shown to alleviate gut microbiota dysbiosis and neural damage. However, the mechanisms by which CK regulates the gut microbiota to improve MCI remain unexplored. In this study, an MCI mouse model induced by D-galactose was used, and 16S rRNA gene sequencing, metabolomics, transcriptomics, and integrative multi-omics analyses were employed to investigate the potential mechanisms by which CK alleviates MCI through modulation of the gut microbiota. The results demonstrated that CK repaired intestinal barrier dysfunction caused by MCI, improved blood-brain barrier (BBB) integrity, inhibited activation of microglial cells and astrocytes, and significantly ameliorated MCI. Furthermore, CK enhanced gut microbiota diversity, notably enriched beneficial bacteria such as Akkermansia, and modulated the levels of short-chain fatty acids (SCFAs), particularly increasing propionate, thereby alleviating gut microbiota dysbiosis caused by MCI. Germ-free experiments confirmed that gut microbiota is a key factor for ginsenoside CK in relieving MCI. Further investigation revealed that CK regulated the TLR4-MyD88-NF-κB signaling pathway through modulation of gut microbiota-mediated propionate metabolism, significantly reducing systemic inflammation and alleviating MCI. Our findings provide a new theoretical basis for using CK as a potential means of modulating the gut microbiota for the treatment of MCI.

Metabolomic insights into Monascus-fermented rice products: Implications for monacolin K content and nutritional optimization.

This study aims to elucidate the detailed metabolic implications of varying monacolin K levels and sterilization methods on Monascus-fermented rice products (MFRPs), acclaimed for their health benefits and monacolin K content. Advanced metabolite profiling of various MFRP variants was conducted using ultrahigh-performance liquid chromatography coupled with tandem time-of-flight mass spectrometry (UHPLC-Q-TOF MS). Statistical analysis encompassed t-tests, ANOVA, and multivariate techniques including PCA, PLS-DA, and OPLS-DA. Notable variations in metabolites were observed across MFRPs with differing monacolin K levels, particularly in variants such as MR1-S, MR1.5-S, MR2-S, and MR3-S. Among the 524 identified metabolites, significant shifts were noted in organic acids, derivatives, lipids, nucleosides, and organic oxygen compounds. The study also uncovered distinct metabolic changes resulting from different sterilization methods and the use of highland barley as a fermentation substitute for rice. Pathway analysis shed light on affected metabolic pathways, including those involved in longevity regulation, cGMP-PKG signaling, and the biosynthesis of unsaturated fatty acids. The research provides critical insights into the complex metabolic networks of MFRPs, underscoring the impact of fermentation substrates and conditions on monacolin K levels and their health implications. This study not only guides the nutritional optimization of MFRPs but also emphasizes the strategic importance of substrate choice and sterilization techniques in enhancing the nutritional and medicinal value of these functional foods.

Triple-Phosphorescent Gold Nanoclusters Enabled by Isomerization of Terminal Thiouracils in the Surface Motifs.

Metal nanoclusters (NCs) hold great promise for expressing multipeak emission based on their well-defined total structure with diverse luminescent centers. Herein, we report the surface motif-dictated triple phosphorescence of Au NCs with dynamic color turning. The deprotonation-triggered isomerization of terminal thiouracils can evolve into a mutual transformation among their hierarchical motifs, thus serving a multipeak-emission expression with good tailoring. More importantly, the underlying electron transfer is thoroughly identified by excluding the radiative and nonradiative energy transfer, where electrons flow from the first phosphorescent state to the last two ones. The findings shed light on finely tailing motifs at the molecular level to motivate studies on customizable luminescence characteristics of metal NCs.

Structurally diverse ent-clerodanoids from the aerial parts of Isodon scoparius.

Scoparodane C (1), a diterpenoid with a rare 3,4-seco-3-nor-2,11-epoxy-ent-clerodane scaffold, was obtained from the aerial parts of Isodon scoparius, along with isocopariusines A-E (2-6), five ent-clerodanoids featuring a 5/6-fused ring system, and isocopariusines F-H (7-9), three common ent-clerodanoids. The structures of these previously undescribed compounds were established by a combination of spectroscopic analysis, X-ray diffraction, chemical derivatization, and quantum chemical calculation. Remarkably, isocopariusine B (3) showed strong resistance reversal activity against fluconazole-resistant Candida albicans.

Microwave detection technique combined with deep learning algorithm facilitates quantitative analysis of heavy metal Pb residues in edible oils.

The heavy metal content in edible oils is intricately associated with their suitability for human consumption. In this study, standard soybean oil was used as a sample to quantify the specified concentration of heavy metals using microwave sensing technique. In addition, an attention-based deep residual neural network model was developed as an alternative to traditional modeling methods for predicting heavy metals in edible oils. In the process of microwave data processing, this work continued to discuss the impact of depth on convolutional neural networks. The results demonstrated that the proposed attention-based residual network model outperforms all other deep learning models in all metrics. The performance of this model was characterized by a coefficient of determination (R2) of 0.9605, a relative prediction deviation (RPD) of 5.0479, and a root mean square error (RMSE) of 3.1654 mg/kg. The research findings indicate that the combination of microwave detection technology and chemometrics holds significant potential for assessing heavy metal levels in edible oils.

A comparative study examining the impact of coronary artery bypass grafting surgery with non-extracorporeal circulation on heart function and structure in patients with various forms of coronary heart diseases.

The aim of this study is to assess alterations in heart function and structure in patients diagnosed with non-ST segment elevation acute myocardial infarction (NSTEAMI), unstable angina (UA), and stable angina (SA) 1 year after undergoing off-pump coronary artery bypass grafting (OPCABG) performed without extracorporeal circulation. A total of 182 patients who underwent OPCABG were included and classified into 3 groups based on their preoperative diagnosis: the NSTEAMI group (n = 68), the UA group (n = 64), and the SA group (n = 50). Cardiac ultrasonography data were collected for all groups both preoperatively and 1 year postoperatively. Clinical data were subjected to statistical analysis. In the NSTEAMI group, postoperative observations revealed increases in left ventricular stroke volume and left ventricular end-systolic diameter, along with reductions in left ventricular end-diastolic volume (LVEDV) and left ventricular end-diastolic diameter (LVEDD) 1-year post-surgery. The UA group demonstrated decreases in LVEDV and LVEDD 1-year post-surgery. Similarly, the SA group exhibited an increase in left ventricular ejection fraction (LVEF) and reductions in LVEDV and LVEDD 1-year post-surgery. Comparative analysis of cardiac ultrasonography data revealed that the NSTEAMI group displayed significantly lower left ventricular stroke volume and notably higher left ventricular end-systolic diameter and volume compared to the UA and SA groups 1-year post-surgery. Furthermore, the SA group exhibited significantly elevated LVEF compared to the UA and NSTEAMI groups 1-year post-surgery. Cardiac ultrasonography findings indicate that all 3 groups exhibited improvements in cardiac function and left ventricular structure 1-year post-surgery. However, the NSTEAMI group demonstrated more substantial improvements in comparison to the UA and SA groups.

Identification of formation mechanism and key elements of quality geriatric care behavior of nursing assistants in nursing homes: a grounded theory study.

Objectives: This study aimed to identify the key elements and develop a formation mechanism model of quality geriatric care behavior for nursing assistants. Methods: This qualitative research employed the strategy of grounded theory proposed by Strauss and Corbin. Furthermore, the data was collected by participatory observation and semi-structured interviews. A total of 12 nursing managers, 63 nursing assistants, and 36 older people from 9 nursing homes in 6 cities were interviewed, whereas for the observatory survey, participants were recruited from 2 nursing homes. Results: The comparative and analysis process revealed 5 key elements of quality geriatric care behavior, including holistic care, personalized care, respect, positive interaction, and empowerment. Based on the Capability-Opportunity-Motivation-Behavior (COM-B) model, key elements and the 3 stages of quality geriatric care behavior (negative behavior cognition stage, practice exchange run-in stage, and positive behavior reinforcement stage), the theoretical framework of the formation mechanism was established. Conclusion: The results indicated that nursing assistants' capabilities, motivation, and organizational and environmental support are vital for quality care behaviors. The theoretical framework established in this study provides theoretical support and practical reference to policymakers, institutional administrators, and healthcare professionals for improving nursing assistant's care behaviors.

SDS3 regulates microglial inflammation by modulating the expression of the upstream kinase ASK1 in the p38 MAPK signaling pathway.

BACKGROUND: Microglia, the main innate immune cells in the central nervous system, are key drivers of neuroinflammation, which plays a crucial role in the pathogenesis of neurodegenerative diseases. The Sin3/histone deacetylase (HDAC) complex, a highly conserved multiprotein co-repressor complex, primarily performs transcriptional repression via deacetylase activity; however, the function of SDS3, which maintains the integrity of the complex, in microglia remains unclear. METHODS: To uncover the regulatory role of the transcriptional co-repressor SDS3 in microglial inflammation, we used chromatin immunoprecipitation to identify SDS3 target genes and combined with transcriptomics and proteomics analysis to explore expression changes in cells following SDS3 knocking down. Subsequently, we validated our findings through experimental assays. RESULTS: Our analysis revealed that SDS3 modulates the expression of the upstream kinase ASK1 of the p38 MAPK pathway, thus regulating the activation of signaling pathways and ultimately influencing inflammation. CONCLUSIONS: Our findings provide important evidence of the contributions of SDS3 toward microglial inflammation and offer new insights into the regulatory mechanisms of microglial inflammatory responses.

Eddy Current Sensor Array for Electromagnetic Sensing and Crack Reconstruction with High Lift-Off in Railway Tracks.

A reliable and efficient rail track defect detection system is essential for maintaining rail track integrity and avoiding safety hazards and financial losses. Eddy current (EC) testing is a non-destructive technique that can be employed for this purpose. The trade-off between spatial resolution and lift-off should be carefully considered in practical applications to distinguish closely spaced cracks such as those caused by rolling contact fatigue (RCF). A multi-channel eddy current sensor array has been developed to detect defects on rails. Based on the sensor scanning data, defect reconstruction along the rails is achieved using an inverse algorithm that includes both direct and iterative approaches. In experimental evaluations, the EC system with the developed sensor is used to measure defects on a standard test piece of rail with a probe lift-off of 4-6 mm. The reconstruction results clearly reveal cracks at various depths and spacings on the test piece.

Ginsenoside Rh4 inhibits colorectal cancer via the modulation of gut microbiota-mediated bile acid metabolism.

INTRODUCTION: Dysbiosis of the gut microbiota is emerging as a pivotal factor in the pathogenesis of colorectal cancer (CRC). Ginsenoside Rh4 (Rh4) is an active compound isolated from ginseng with beneficial effects in modulating intestinal inflammation and gut microbiota dysbiosis, but how Rh4 regulates the gut microbiota to alleviate CRC remains underexplored. OBJECTIVES: We investigated the impact of Rh4 on CRC and the mechanism of its action in inhibiting CRC via modulation of gut microbiota. METHODS: We used the AOM/DSS model and employed transcriptomics, genomics and metabolomics techniques to explore the inhibitory impact of Rh4 on CRC. Furthermore, we employed experiments involving antibiotic treatment and fecal microbiota transplantation (FMT) to investigate the role of the gut microbiota. Finally, we elucidated the pivotal role of key functional bacteria and metabolites regulated by Rh4 in CRC. RESULTS: Our research findings indicated that Rh4 repaired intestinal barrier damage caused by CRC, alleviated intestinal inflammation, and inhibited the development of CRC. Additionally, Rh4 inhibited CRC in a gut microbiota-dependent manner. Rh4 increased the diversity of gut microbiota, enriched the probiotic Akkermansia muciniphila (A. muciniphila), and alleviated gut microbiota dysbiosis caused by CRC. Subsequently, Rh4 regulated A. muciniphila-mediated bile acid metabolism. A. muciniphila promoted the production of UDCA by enhancing the activity of 7α-hydroxysteroid dehydrogenase (7α-HSDH). UDCA further activated FXR, modulated the TLR4-NF-κB signaling pathway, thus inhibiting the development of CRC. CONCLUSION: Our results confirm that Rh4 inhibits CRC in a gut microbiota-dependent manner by modulating gut microbiota-mediated bile acid metabolism and promoting the production of UDCA, which further activates the FXR receptor and regulates the TLR4-NF-κB signaling pathway. Our results confirm that Rh4 has the potential to be used as a modulator of gut microbiota for preventing and treatment of CRC.

Low-temperature subcritical water dechlorination composites of waste PVC/coal fly ash with powerful sensing activity for chemiluminescent detection of acetamiprid and imidacloprid.

Pesticide residues in agricultural products are serious threat to people's health. Real-time monitoring of pesticides residues in the environment and agricultural products posed challenges to sustainable methods with high analytical performance for pesticide detection. Herein, waste PVC/coal fly ash (the mass ratio of PVC and coal fly ash was 4:1) was dechlorinated in subcritical water at low temperature to achieve nearly 100 % dechlorination of PVC and obtain carbon-based composite materials (CM-Fe/Al/Si-dPVC) with strong sening activity. For CM-Fe/Al/Si-dPVC, CFe bonding resulted in strong electron migration, and nano/µm SiO2 and Al2O3 doping in the layered polyene C matrix provided large specific surface area, and silicon hydroxyl created good heterogeneous catalytic interfaces. CM-Fe/Al/Si-dPVC could strongly trigger luminol chemiluminescence (CL) reaction and produce intense CL signals. Neonicotinoid pesticides (acetamiprid and imidacloprid) bonded with CM-Fe/Al/Si-dPVC through coordination chelation and hydrogen bonding, which shielded the catalytic active site and increased the Fermi level of system, thus quenching CL reaction. Inspired by these, a cheap CL assay was constructed for detecting neonicotinoids combinations of acetamiprid and imidacloprid (NICs). The detection limits of NICs were 0.7 ng/L. Satisfactory recoveries were obtained for real agricultural products and environmental samples. The results of life cycle evaluation (LCA) revealed that the strategy had significantly small global warming potential (GWP). This work presented a sustainable method with environmental benefits for the detection of neonicotinoids, and also opened up new way for the recycling of organic solid wastes.

A novel EPID-based MLC QA method with log files achieving submillimeter accuracy.

The purpose of this study is to develop an electronic portal imaging device-based multi-leaf collimator calibration procedure using log files. Picket fence fields with 2-14 mm nominal strip widths were performed and normalized by open field. Normalized pixel intensity profiles along the direction of leaf motion for each leaf pair were taken. Three independent algorithms and an integration method derived from them were developed according to the valley value, valley area, full-width half-maximum (FWHM) of the profile, and the abutment width of the leaf pairs obtained from the log files. Three data processing schemes (Scheme A, Scheme B, and Scheme C) were performed based on different data processing methods. To test the usefulness and robustness of the algorithm, the known leaf position errors along the direction of perpendicular leaf motion via the treatment planning system were introduced in the picket fence field with nominal 5, 8, and 11 mm. Algorithm tests were performed every 2 weeks over 4 months. According to the log files, about 17.628% and 1.060% of the leaves had position errors beyond ± 0.1 and ± 0.2 mm, respectively. The absolute position errors of the algorithm tests for different data schemes were 0.062 ± 0.067 (Scheme A), 0.041 ± 0.045 (Scheme B), and 0.037 ± 0.043 (Scheme C). The absolute position errors of the algorithms developed by Scheme C were 0.054 ± 0.063 (valley depth method), 0.040 ± 0.038 (valley area method), 0.031 ± 0.031 (FWHM method), and 0.021 ± 0.024 (integrated method). For the efficiency and robustness test of the algorithm, the absolute position errors of the integration method of Scheme C were 0.020 ± 0.024 (5 mm), 0.024 ± 0.026 (8 mm), and 0.018 ± 0.024 (11 mm). Different data processing schemes could affect the accuracy of the developed algorithms. The integration method could integrate the benefits of each algorithm, which improved the level of robustness and accuracy of the algorithm. The integration method can perform multi-leaf collimator (MLC) quality assurance with an accuracy of 0.1 mm. This method is simple, effective, robust, quantitative, and can detect a wide range of MLC leaf position errors.

The Combination of Molecular Hydrogen and Heme Oxygenase 1 Effectively Inhibits Neuropathy Caused by Paclitaxel in Mice.

Chemotherapy-provoked peripheral neuropathy and its associated affective disorders are important adverse effects in cancer patients, and its treatment is not completely resolved. A recent study reveals a positive interaction between molecular hydrogen (H2) and a heme oxygenase (HO-1) enzyme inducer, cobalt protoporphyrin IX (CoPP), in the inhibition of neuropathic pain provoked by nerve injury. Nevertheless, the efficacy of CoPP co-administered with hydrogen-rich water (HRW) on the allodynia and emotional disorders related to paclitaxel (PTX) administration has not yet been assessed. Using male C57BL/6 mice injected with PTX, we examined the effects of the co-administration of low doses of CoPP and HRW on mechanical and thermal allodynia and anxiodepressive-like behaviors triggered by PTX. Moreover, the impact of this combined treatment on the oxidative stress and inflammation caused by PTX in the amygdala (AMG) and dorsal root ganglia (DRG) were studied. Our results indicated that the antiallodynic actions of the co-administration of CoPP plus HRW are more rapid and higher than those given by each of them when independently administered. This combination inhibited anxiodepressive-like behaviors, the up-regulation of the inflammasome NLRP3 and 4-hydroxynonenal, as well as the high mRNA levels of some inflammatory mediators. This combination also increased the expression of NRF2, HO-1, superoxide dismutase 1, glutathione S-transferase mu 1, and/or the glutamate-cysteine ligase modifier subunit and decreased the protein levels of BACH1 in the DRG and/or AMG. Thus, it shows a positive interaction among HO-1 and H2 systems in controlling PTX-induced neuropathy by modulating inflammation and activating the antioxidant system. This study recommends the co-administration of CoPP plus HRW as an effective treatment for PTX-provoked neuropathy and its linked emotive deficits.

GluOC promotes proliferation and metastasis of TNBC through the ROCK1 signaling pathway.

BACKGROUND: Triple negative breast cancer (TNBC) is a type of breast cancer that is negative for oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, is highly malignant and aggressive, lacks of corresponding targeted therapy, and has a relatively poor prognosis. Therefore, understanding the mechanism of TNBC development and formulating effective treatment strategies for inducing cell death are still urgent tasks in the treatment of TNBC. Research has shown that uncarboxylated osteocalcin can promote the proliferation of prostate cancer, lung adenocarcinoma and TNBC cells, but the mechanism by which GluOC affects TNBC growth and metastasis needs further study. METHODS: MDA-MB-231 breast cancer cells were used for in vitro cell analysis. Key target molecules or pathways were identified by RNA sequencing, and migration ability was detected by scratch assays, Transwell assays, cell adhesion assays and western blot analysis. Fluorescence staining, colony detection, qRT‒PCR and flow cytometry were used to detect apoptosis, oxidative stress, the cell cycle and the stemness of cancer cells, and a xenotransplantation model in BALB/C nude mice was used for in vivo analysis. RESULTS: This study demonstrated that GluOC facilitates the migration of MDA-MB-231 breast cancer cells through the ROCK1/MYPT1/MLC2 signalling pathway and promotes the proliferation of TNBC cells via the ROCK1/JAK2/PIK3CA/AKT signalling pathway. Experiments in nude mice demonstrated that GluOC promoted tumour cell proliferation and metastasis in tumour-bearing mice, which further clarified the molecular mechanism of TNBC growth and invasion. CONCLUSION: Our findings highlight the importance of GluOC in driving TNBC progression and its association with poor patient outcomes. This study clarifies the functional effects of GluOC on TNBC growth, providing insight into the molecular basis of TNBC and potentially providing new ideas for developing targeted therapies to improve patient outcomes.

Development of Bivalent Aptamer-DNA Carrier-Doxorubicin Conjugates for Targeted Killing of Esophageal Squamous Cell Carcinoma Cells.

Esophageal cancer ranks the seventh in cancer incidence and the sixth in cancer death. Esophageal squamous cell carcinoma (ESCC) accounts for approximately 90% of the total cases of esophageal cancer. Chemotherapy is the most effective drug-based method for treatment of esophageal cancer. However, severe side effects of traditional chemotherapy limit its treatment efficacy. Targeted chemotherapy can deliver chemotherapeutic drugs to cancer cells and specifically kill these cells with reduced side effects. In the work, the bivalent aptamer-DNA carrier (BAD) was designed by using an ESCC cell-specific aptamer as the recognition molecule and a GC base-rich DNA sequence as the drug carrier. With doxorubicin (Dox) as chemotherapeutic drugs, the bivalent aptamer-DNA-Dox conjugate (BADD) was constructed for targeted killing of ESCC cells. Firstly, the truncated A2(35) aptamer with a retained binding ability was obtained through optimization of an intact A2(80) aptamer and was used to fuse with DNA carrier sequences for constructing the BAD through simple DNA hybridization. The results of gel electrophoresis and flow cytometry analysis showed that the BAD was successfully constructed and had a stronger binding affinity than monovalent A2(35). Then, the BAD was loaded with Dox drugs to construct the BADD through noncovalent intercalation. The results of fluorescence spectra and flow cytometry assays showed that the BADD was successfully constructed and can bind to target cells strongly. Confocal imaging further displayed that the BADD can be specifically internalized into target cells and release Dox. The results of CCK-8 assays, Calcein AM/PI staining, and wound healing assays demonstrated that the BADD can specifically kill target cells, but not control cells. Our results demonstrate that the developed BADD can specifically deliver doxorubicin to target ESCC cells and selectively kill these cells, offering a potentially effective strategy for targeted chemotherapy of ESCC.