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Monoterpenoid indole alkaloid (MIA) biosynthesis in Catharanthus roseus is a paragon of the spatiotemporal complexity achievable by plant specialized metabolism. Spanning a range of tissues, four cell types, and five cellular organelles, MIA metabolism is intricately regulated and organized. This high degree of metabolic differentiation requires inter-cellular and organellar transport, which remains understudied. Here, we have characterized a vacuolar importer of secologanin belonging to the multidrug and toxic compound extrusion (MATE) family, named CrMATE1. Phylogenetic analyses of MATEs suggested a role in alkaloid transport for CrMATE1, and in planta silencing in two varieties of C. roseus resulted in a shift in the secoiridoid and MIA profiles. Subcellular localization of CrMATE1 confirmed tonoplast localization. Biochemical characterization was conducted using the Xenopus laevis oocyte expression system to determine substrate range, directionality, and rate. We can confirm that CrMATE1 is a vacuolar importer of secologanin, translocating 1 mM of substrate within 25 min. The transporter displayed strict directionality and specificity for secologanin and did not accept other secoiridoid substrates. The unique substrate-specific activity of CrMATE1 showcases the utility of transporters as gatekeepers of pathway flux, mediating the balance between a defense arsenal and cellular homeostasis.
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Catharanthus , Protéines végétales , Alcaloïdes formés par condensation de sécologanine et de tryptamine , Vacuoles , Catharanthus/métabolisme , Catharanthus/génétique , Protéines végétales/métabolisme , Protéines végétales/génétique , Vacuoles/métabolisme , Alcaloïdes formés par condensation de sécologanine et de tryptamine/métabolisme , Animaux , Phylogenèse , Xenopus laevis/métabolisme , Transport biologique , Ovocytes/métabolisme , Glucosides d'iridoïdesRÉSUMÉ
Wearable sensors designed for continuous, non-invasive monitoring of physicochemical signals are important for portable healthcare. Oxide field-effect transistor (FET)-type biosensors provide high sensitivity and scalability. However, they face challenges in mechanical flexibility, multiplexed sensing of different modules, and the absence of integrated on-site signal processing and wireless transmission functionalities for wearable sensing. In this work, a fully integrated wearable oxide FET-based biosensor array is developed to facilitate the multiplexed and simultaneous measurement of ion concentrations (H+, Na+, K+) and temperature. The FET-sensor array is achieved by utilizing a solution-processed ultrathin (≈6 nm thick) In2O3 active channel layer, exhibiting high compatibility with standard semiconductor technology, good mechanical flexibility, high uniformity, and low operational voltage of 0.005 V. This work provides an effective method to enable oxide FET-based biosensors for the fusion of multiplexed physicochemical information and wearable health monitoring applications.
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Artificial spiking neurons capable of interpreting ionic information into electrical spikes are critical to mimic biological signaling systems. Mott memristors are attractive for constructing artificial spiking neurons due to their simple structure, low energy consumption, and rich neural dynamics. However, challenges remain in achieving ion-mediated spiking and biohybrid-interfacing in Mott neurons. Here, a biomimetic spiking chemical neuron (SCN) utilizing an NbOx Mott memristor and oxide field-effect transistor-type chemical sensor is introduced. The SCN exhibits both excitation and inhibition spiking behaviors toward ionic concentrations akin to biological neural systems. It demonstrates spiking responses across physiological and pathological Na+ concentrations (1-200 × 10-3 m). The Na+-mediated SCN enables both frequency encoding and time-to-first-spike coding schemes, illustrating the rich neural dynamics of Mott neuron. In addition, the SCN interfaced with L929 cells facilitates real-time modulation of ion-mediated spiking under both normal and salty cellular microenvironments.
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Potentiels d'action , Neurones , Sodium , Neurones/physiologie , Sodium/métabolisme , Sodium/composition chimique , Potentiels d'action/physiologie , Animaux , Souris , Oxydes/composition chimique , Transistors électroniques , Lignée cellulaire , Ions/composition chimique , Niobium/composition chimiqueRÉSUMÉ
Human visual neurons rely on event-driven, energy-efficient spikes for communication, while silicon image sensors do not. The energy-budget mismatch between biological systems and machine vision technology has inspired the development of artificial visual neurons for use in spiking neural network (SNN). However, the lack of multiplexed data coding schemes reduces the ability of artificial visual neurons in SNN to emulate the visual perception ability of biological systems. Here, we present an artificial visual spiking neuron that enables rate and temporal fusion (RTF) coding of external visual information. The artificial neuron can code visual information at different spiking frequencies (rate coding) and enables precise and energy-efficient time-to-first-spike (TTFS) coding. This multiplexed sensory coding scheme could improve the computing capability and efficacy of artificial visual neurons. A hardware-based SNN with the RTF coding scheme exhibits good consistency with real-world ground truth data and achieves highly accurate steering and speed predictions for self-driving vehicles in complex conditions. The multiplexed RTF coding scheme demonstrates the feasibility of developing highly efficient spike-based neuromorphic hardware.
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Potentiels d'action , , Neurones , Perception visuelle , Humains , Neurones/physiologie , Potentiels d'action/physiologie , Perception visuelle/physiologie , Modèles neurologiquesRÉSUMÉ
BACKGROUND: Hepatocellular carcinoma (HCC), a major contributor to cancer-related deaths, is particularly prevalent in Asia, largely due to hepatitis B virus infection. Its prognosis is generally poor. This case report contributes to the medical literature by detailing a unique approach in treating a large HCC through multidisciplinary collaboration, particularly in patients with massive HCC complicated by ruptured bleeding, a scenario not extensively documented previously. CASE SUMMARY: The patient presented with large HCC complicated by intratumoral bleeding. Treatment involved a multidisciplinary approach, providing individualized care. The strategy included drug-eluting bead transarterial chemoembolization, sorafenib-targeted therapy, laparoscopic partial hepatectomy, and standardized sintilimab monoclonal antibody therapy. Six months after treatment, the patient achieved complete radiological remission, with significant symptom relief. Imaging studies showed no lesions or recurrence, and clinical assessments confirmed complete remission. This report is notable as possibly the first documented case of successfully treating such complex HCC conditions through integrated multidisciplinary efforts, offering new insights and a reference for future similar cases. CONCLUSION: This study demonstrated effective multidisciplinary treatment for massive HCC with intratumoral bleeding, providing insights for future similar cases.
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CD44 is a ubiquitous leukocyte adhesion molecule involved in cell-cell interaction, cell adhesion, migration, homing and differentiation. CD44 can mediate the interaction between leukemic stem cells and the surrounding extracellular matrix, thereby inducing a cascade of signaling pathways to regulate their various behaviors. In this review, we focus on the impact of CD44s/CD44v as biomarkers in leukemia development and discuss the current research and prospects for CD44-related interventions in clinical application.
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Marqueurs biologiques tumoraux , Antigènes CD44 , Leucémies , Cellules souches tumorales , Humains , Cellules souches tumorales/métabolisme , Cellules souches tumorales/immunologie , Antigènes CD44/métabolisme , Leucémies/métabolisme , Leucémies/thérapie , Leucémies/immunologie , Marqueurs biologiques tumoraux/métabolisme , Animaux , Transduction du signal , Thérapie moléculaire cibléeRÉSUMÉ
Background: The overall survival rate is notably low for esophageal cancer patients with lung metastases (LM), presenting significant challenges in their treatment. Methods: Through the Surveillance, Epidemiology, and End Results (SEER) program, individuals diagnosed with esophageal cancer between 2010 and 2015 were enrolled. Based on whether esophageal cancer metastasized to the lungs, we used propensity score matching (PSM) to balance correlated variables. Propensity score matching was a critical step in our study that helped to minimize the impact of possible confounders on the study results. We balanced variables related to lung metastases using the PSM method to ensure more accurate comparisons between the study and control groups. Specifically, we performed PSM in the following steps. First, we performed a univariate logistic regression analysis to screen for variables associated with lung metastasis. For each patient, we calculated their propensity scores using a logistic regression model, taking into account several factors, including gender, T-stage, N-stage, surgical history, radiotherapy history, chemotherapy history, and bone/brain/liver metastases. We used a 1:1 matching ratio based on the propensity score to ensure more balanced baseline characteristics between the study and control groups after matching. After matching, we validated the balance of baseline characteristics to ensure that the effect of confounders was minimized. We used logistic regression to identify risk variables for LM, while Cox regression was used to find independent prognostic factors. We then created nomograms and assessed their accuracy using the calibration curve, receiver operating curves (ROC), and C index. Results: In the post-PSM cohort, individuals diagnosed with LM experienced a median overall survival (OS) of 5.0 months (95% confidence interval [CI] 4.3-5.7), which was significantly lower than those without LM (P<0.001). LM has been associated to sex, T stage, N stage, surgery, radiation, chemotherapy, and bone/brain/liver metastases. LM survival was affected by radiation, chemotherapy, and bone/liver metastases. The nomograms' predictive power was proved using the ROC curve, C-index, and validation curve. Conclusion: Patients with LM have a worse chance of surviving esophageal cancer. The nomograms can effectively predict the risk and prognosis of lung metastases from esophageal cancer.
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Despite significant advancements in multiple myeloma (MM) treatment in recent years, most patients will eventually develop resistance or experience relapse. Matrine, a primary active compound of traditional Chinese medicinal herb Sophora flavescens Ait, has been found to have anti-tumor properties in various types of malignant tumors. Whether autophagy plays a crucial role in the anti-MM effect of matrine remain unknown. Herein, we found that matrine could trigger apoptosis and cell cycle arrest, and meanwhile induce autophagy in MM cells in vitro. We further ascertained the role of autophagy by using ATG5 siRNA or the autophagy inhibitor spautin-1, which partially reversed matrine's inhibitory effect on MM cells. Conversely, the combination of matrine with the autophagy inducer rapamycin enhanced their anti-tumor activity. These findings suggest that autophagy induced by matrine can lead to cell death in MM cells. Further mechanism investigation revealed that matrine treatment increased the levels of reactive oxygen species (ROS) and AMPKα1 phosphorylation and decreased the phosphorylation of mTOR in MM cells. Additionally, co-treatment with AMPKα1 siRNA or the ROS scavenger N-acetyl-1-cysteine weakened the increase in autophagy that was induced by matrine. Finally, we demonstrated a synergistic inhibitory effect of matrine and rapamycin against MM in a xenograft mouse model. Collectively, our findings provided novel insights into the anti-MM efficacy of matrine and suggest that matrine induces autophagy by triggering ROS/AMPK/mTOR axis in MM cells, and combinatorial treatment of matrine and rapamycin may be a promising therapeutic strategy against MM.
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AMP-Activated Protein Kinases , Alcaloïdes , Apoptose , Mort cellulaire par autophagie , , Myélome multiple , Quinolizines , Espèces réactives de l'oxygène , Transduction du signal , Sérine-thréonine kinases TOR , Quinolizines/pharmacologie , Myélome multiple/traitement médicamenteux , Myélome multiple/anatomopathologie , Myélome multiple/métabolisme , Alcaloïdes/pharmacologie , Espèces réactives de l'oxygène/métabolisme , Humains , Apoptose/effets des médicaments et des substances chimiques , Animaux , Sérine-thréonine kinases TOR/métabolisme , Lignée cellulaire tumorale , AMP-Activated Protein Kinases/métabolisme , Mort cellulaire par autophagie/effets des médicaments et des substances chimiques , Transduction du signal/effets des médicaments et des substances chimiques , Tests d'activité antitumorale sur modèle de xénogreffe , Souris , Autophagie/effets des médicaments et des substances chimiquesRÉSUMÉ
Organic photoluminescent macrocyclic hosts have been widely advanced in many fields. Phosphorescent hosts with the ability to bind organic guests have rarely been reported. Herein, acyclic cucurbituril modified with four carboxylic acids (ACB-COOH) is mined to present uncommon purely organic room-temperature phosphorescence (RTP) at 510 nm with a lifetime of 1.86 µs. Its RTP properties are significantly promoted with an extended lifetime up to 2.12 s and considerable quantum yield of 6.29% after assembly with a polyvinyl alcohol (PVA) matrix. By virtue of the intrinsic self-crimping configuration of ACB-COOH, organic guests, including fluorescence dyes (Rhodamine B (RhB) and Pyronin Y (PyY)) and a drug molecule (morphine (Mor)), could be fully encapsulated by ACB-COOH to attain energy transfer involving phosphorescent acyclic cucurbituril. Ultimately, as-prepared systems are successfully exploited to establish multicolor afterglow materials and visible sensing of morphine. As an expansion of phosphorescent acyclic cucurbituril, the host afterglow color can be readily regulated by attaching different aromatic sidewalls. This study develops the fabrication strategies and application scope of a supramolecular phosphorescent host and opens up a new direction for the manufacture of intelligent long-lived luminescent materials.
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This research explores the causal link between dietary habits and hypertension through Mendelian randomization, providing distinct perspectives on the role of diet in addressing this worldwide health issue. Utilizing instrumental variables, we applied advanced statistical methods, including the weighted median, inverse variance weighted, and MR-Egger, to evaluate the impact of 17 dietary elements on hypertension. These elements ranged across various food groups, such as fruits, meats, vegetables, and beverages, both alcoholic and nonalcoholic. Our results identified a significant positive association of hypertension with weekly alcohol consumption (OR 1.340 [95%CI 1.0001 to 1.794], p = .0499) and poultry intake (OR 2.569 [95%CI 1.305 to 5.057], p = .00631). Conversely, a negative association was observed with lamb/mutton (OR 0.550 [95%CI 0.343 to 0.881], p = .0129), cheese (OR 0.650 [95%CI 0.519 to 0.813], p = .000159), tea (OR 0.797 [95%CI 0.640 to 0.993], p = .0433), cereal (OR 0.684 [95%CI 0.494 to 0.948], p = .0227), and dried fruit consumption (OR 0.492 [95%CI 0.343 to 0.707], p = .000127). These findings suggest that dietary modifications, such as increasing consumption of specific foods like cheese, lamb/mutton, tea, cereals, and dried fruits, could potentially reduce hypertension risk while reducing intake of alcoholic beverages and poultry might mitigate its increase. No direct causal relationships were established between other dietary factors and hypertension. The study highlights the importance of specific dietary modifications for the prevention and control of hypertension, making a substantial contribution to public health tactics and recommendations.
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OBJECTIVES: Nausea and vomiting in pregnancy (NVP) is a common condition that reduces the quality of life by negatively affecting work and family life, physical and mental health, and economic well-being. However, its risk factors remain unclear. This study aimed to explore the association between NVP and verbal rating scale (VRS)-measured dysmenorrhea and to explore potential protective factors. METHODS: This retrospective cohort study was conducted from June 2018 to December 2020 at Tongji Hospital in Wuhan. Information on baseline characteristics, pregnancy-related history, periconceptional micronutrient supplementation, and obstetric outcomes were collected. The severity of dysmenorrhea was assessed using VRS. RESULTS: A total of 443 pregnant women were recruited and divided into the NVP group (n = 76) and the control group (n = 367). A significant association was observed between NVP and VRS-measured dysmenorrhea (c2=10.038, P = 0.007). After adjusting for covariates, the association between moderate/severe dysmenorrhea and NVP remained significant (OR 2.384; 95% CI 1.104-5.148, P = 0.004). First-trimester docosahexaenoic acid supplement (OR 0.443; 95% CI 0.205-0.960, P = 0.039) may be beneficial in reducing the risk of NVP. CONCLUSIONS: Women with moderate to severe dysmenorrhea have a higher risk of experiencing NVP during the first trimester. Periconceptional docosahexaenoic acid supplementation may play a protective role.
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Dysménorrhée , Humains , Femelle , Grossesse , Études rétrospectives , Adulte , Nausée , Maladie gravidique précoce , Études de cohortes , Complications de la grossesse , Chine , Indice de gravité de la maladie , VomissementRÉSUMÉ
Using updated National Health and Nutrition Examination Survey (NHANES) follow-up data, and a large nationwide representative sample of adult U.S. citizens, the aim of this study was to explore the relationship between dietary flavonol intake, all-cause and cause-specific mortality risks. In this prospective cohort study based on NHANES (2007-2008, 2009-2010, and 2017-2018), a total of 11,679 participants aged 20 years and above were evaluated. The amount and type of food taken during a 24-h dietary recall were used to estimate dietary flavonol intake, which includes total flavonol, isorhamnetin, kaempferol, myricetin, and quercetin. Each analysis of the weighted data was dealt with in accordance with the NHANES reporting requirements' intricate stratification design. The Cox proportional risk regression model or Fine and Gray competing risks regression model were applied to evaluate all-cause and cause-specific mortality risks, respectively. The follow-up period was calculated using the time interval between the baseline and the death date or December 31, 2019 (whichever occurs first). Each data analysis was performed between October 1, 2023, and October 22, 2023. Dietary flavonol intake included total flavonol, isorhamnetin, kaempferol, myricetin, and quercetin. Up to December 31, 2019, National Death Index (NDI) mortality data were used to calculate mortality from all causes as well as cause-specific causes. A total of 11,679 individuals, which represents 44,189,487 U.S. non-hospitalized citizens, were included in the study; of these participants, 49.78% were male (n = 5816), 50.22% were female (n = 5, 863); 47.56% were Non-Hispanic White (n = 5554), 18.91% were Non-Hispanic Black (n = 2209), 16.23% were Mexican American (n = 1895), and 17.30% were other ethnicity (n = 2021); The mean [SE] age of the sample was 46.93 [0.36] years, with a median follow-up of 7.80 years (interquartile range, 7.55-8.07 years). After adjusting covariates, Cox proportional hazards models and fine and gray competing risks regression models for specific-cause mortality demonstrated that total flavonol intake was associated with all-cause (HR 0.64, 95% CI 0.54-0.75), cancer-specific (HR 0.45, 95% CI 0.28-0.70) and CVD-specific (HR 0.67, 95% CI 0.47-0.96) mortality risks; isorhamnetin intake was associated with all-cause (HR 0.72, 95% CI 0.60-0.86), and cancer-specific (HR 0.62, 95% CI 0.46-0.83) mortality risks; kaempferol intake was associated with all-cause (HR 0.74, 95% CI 0.63-0.86), and cancer-specific (HR 0.62, 95% CI 0.40-0.97) mortality risks; myricetin intake was associated with all-cause (HR 0.77, 95% CI 0.67-0.88), AD-specific (HR 0.34, 95% CI 0.14-0.85), and CVD-specific (HR 0.61, 95% CI 0.47-0.80) mortality risks; quercetin intake was associated with all-cause (HR 0.66, 95% CI 0.54-0.81), cancer-specific (HR 0.54, 95% CI 0.35-0.84), and CVD-specific (HR 0.61, 95% CI 0.40-0.93) mortality risks; there was no correlation observed between dietary flavonol intake and DM-specific mortality. According to the current study, all-cause, AD, cancer, and CVD mortality risks declined with increased dietary flavonoid intake in the U.S. adults. This finding may be related to the anti-tumor, anti-inflammatory, and anti-oxidative stress properties of flavonol.
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Maladies cardiovasculaires , Tumeurs , Adulte , Humains , Mâle , Femelle , Enquêtes nutritionnelles , Kaempférols , Études prospectives , Quercétine , FlavonolsRÉSUMÉ
The combination of immune-checkpoint blockade with chemotherapy for the first-line treatment of advanced triple-negative breast cancer (TNBC) has generated mixed results. TORCHLIGHT is a randomized, double-blinded phase 3 trial evaluating the efficacy and safety of first-line toripalimab and nab-paclitaxel (nab-P) (n = 353; experimental arm) versus placebo and nab-P (n = 178; control arm) for the treatment of women with metastatic or recurrent TNBC. The primary end point was progression-free survival (PFS) assessed by a blinded independent central review in the PD-L1-positive and intention-to-treat populations. The secondary end points included overall survival and safety. Overall, 200 and 100 patients, in the toripalimab and placebo arm respectively had PD-L1-positive TNBC. At the prespecified interim analysis, a statistically significant improvement in PFS assessed by a blinded independent central review was demonstrated in the experimental arm in the PD-L1-positive population (median PFS 8.4 versus 5.6 months; hazard ratio (HR) = 0.65, 95% confidence interval (CI) 0.470-0.906, P = 0.0102). The median overall survival was 32.8 versus 19.5 months (HR = 0.62, 95% CI 0.414-0.914, P = 0.0148). Similar incidences of treatment-emergent adverse events (AEs) (99.2% versus 98.9%), grade ≥3 treatment-emergent AEs (56.4% versus 54.3%) and fatal AEs (0.6% versus 3.4%) occurred in the experimental and control arms. The addition of toripalimab to nab-P provided a significant improvement in PFS for PD-L1-positive patients with metastatic or recurrent TNBC with an acceptable safety profile. ClinicalTrial.gov identifier NCT03777579 .
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Albumines , Anticorps monoclonaux humanisés , Tumeurs du sein triple-négatives , Humains , Femelle , Tumeurs du sein triple-négatives/traitement médicamenteux , Tumeurs du sein triple-négatives/anatomopathologie , Antigène CD274/usage thérapeutique , Récidive tumorale locale/traitement médicamenteux , Paclitaxel/effets indésirables , Protocoles de polychimiothérapie antinéoplasique/effets indésirablesRÉSUMÉ
BACKGROUND: Neoadjuvant trastuzumab/pertuzumab (HP) plus chemotherapy for HER2-positive breast cancer (BC) achieved promising efficacy. The additional cardiotoxicity still existed. Brecan study evaluated the efficacy and safety of neoadjuvant pegylated liposomal doxorubicin (PLD)/cyclophosphamide and sequential nab-paclitaxel based on HP (PLD/C/HP-nabP/HP). PATIENTS AND METHODS: Brecan was a single-arm phase II study. Eligible patients with stages IIA-IIIC HER2-positive BC received 4 cycles of PLD, cyclophosphamide, and HP, followed by 4 cycles of nab-paclitaxel and HP. Definitive surgery was scheduled after 21 days for patients completing treatment or experiencing intolerable toxicity. The primary endpoint was the pathological complete response (pCR). RESULTS: Between January 2020 and December 2021, 96 patients were enrolled. Ninety-five (99.0%) patients received 8 cycles of neoadjuvant therapy and all underwent surgery with 45 (46.9%) breast-conserving surgery and 51 (53.1%) mastectomy. The pCR was 80.2% (95%CI, 71.2%-87.0%). Four (4.2%) experienced left ventricular insufficiency with an absolute decline in LVEF (43%-49%). No congestive heart failure and ≥grade 3 cardiac toxicity occurred. The objective response rate was 85.4% (95%CI, 77.0%-91.1%), including 57 (59.4%) complete responses and 25 (26.0%) partial responses. The disease control rate was 99.0% (95%CI, 94.3%-99.8%). For overall safety, ≥grade 3 AEs occurred in 30 (31.3%) and mainly included neutropenia (30.2%) and asthenia (8.3%). No treatment-related deaths occurred. Notably, age of >30 (P = .01; OR = 5.086; 95%CI, 1.44-17.965) and HER2 IHC 3+ (P = .02; OR = 4.398; 95%CI, 1.286-15.002) were independent predictors for superior pCR (ClinicalTrials.gov Identifier NCT05346107). CONCLUSION: Brecan study demonstrated the encouraging safety and efficacy of neoadjuvant PLD/C/HP-nabP/HP, suggesting a potential therapeutic option in HER2-positive BC.
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Tumeurs du sein , Humains , Femelle , Tumeurs du sein/anatomopathologie , Traitement néoadjuvant/effets indésirables , Récepteur ErbB-2/usage thérapeutique , Mastectomie , Résultat thérapeutique , Paclitaxel , Cyclophosphamide/usage thérapeutique , Trastuzumab/effets indésirables , Protocoles de polychimiothérapie antinéoplasique/effets indésirablesRÉSUMÉ
The dynamic landscape of public health occurrences presents a formidable challenge to the emotional well-being of college students, necessitating a precise appraisal of their mental health (MH) status. A pivotal metric in this realm is the Mental Health Assessment Index, a prevalent gauge utilized to ascertain an individual's psychological well-being. However, prevailing indices predominantly stem from a physical vantage point, neglecting the intricate psychological dimensions. In pursuit of a judicious evaluation of college students' mental health within the crucible of public health vicissitudes, we have pioneered an innovative metric, underscored by temporal perception, in concert with a hybrid clustering algorithm. This augmentation stands poised to enrich the extant psychological assessment index framework. Our approach hinges on the transmutation of temporal perception into a quantifiable measure, harmoniously interwoven with established evaluative metrics, thereby forging a novel composite evaluation metric. This composite metric serves as the fulcrum upon which we have conceived a pioneering clustering algorithm, seamlessly fusing the fireworks algorithm with K-means clustering. The strategic integration of the fireworks algorithm addresses a noteworthy vulnerability inherent to K-means-its susceptibility to converging onto local optima. Empirical validation of our paradigm attests to its efficacy. The proposed hybrid clustering algorithm aptly captures the dynamic nuances characterizing college students' mental health trajectories. Across diverse assessment stages, our model consistently attains an accuracy threshold surpassing 90%, thus outshining existing evaluation techniques in both precision and simplicity. In summation, this innovative amalgamation presents a formidable stride toward an augmented understanding of college students' mental well-being during times of fluctuating public health dynamics.
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INTRODUCTION: Preeclampsia (PE) is a multisystemic disorder attributed to the excessive presentation of placenta-derived immunoinflammatory factors. PTEN-induced putative kinase 1 (PINK1)-mediated mitophagy participates in the development and persistence of the inflammation. We hypothesized that dysregulated mitophagy might be involved in the pathogenesis of PE by promoting the activation of trophoblast pyroptosis that augment inflammation. METHODS: The morphology of mitochondrial in placenta were observed by transmission electron microscopy. The localization of PINK1 in the placenta was determined by immunohistochemistry. The expression levels of PINK1, PARKIN, LC3B, and SQSTM1 and pyroptosis-related molecules were compared between normal pregnancies and PE. We used hypoxia/reoxygenation (H/R) to stimulate the trophoblast hypoxia environment. HTR-8/SVneo cells were transfected with PINK1 plasmid and si-PINK1, respectively, and then were treated with H/R, to determine whether PINK1 regulated ROS and HTR-8/Svneo pyroptosis. Finally, ROS production was inhibited by MitoTEMPO to observe whether the pro-pyroptosis effect of PINK1 knockdown is alleviated. RESULTS: Swollen mitochondrial were accumulated in the PE placentae. PINK1 is localized on villus trophoblast (VTs) and extravillous trophoblast (EVTs). PINK1-mediated mitophagy was abolished in the PE placenta, while the levels of pyroptosis were induced. H/R stimulation aggravated the downregulation of mitophagy and the up-regulation of pyroptosis. Overexpression of PINK1 mitigated H/R-induced upregulation of ROS and pyroptosis while silencing PINK1 did the opposite. Reducing ROS production can effectively resist the pro-pyroptosis effect of PINK1 knockdown. DISCUSSION: This study demonstrated that PINK1-mediated mitophagy might played a protective role in PE by reducing ROS and trophoblast pyroptosis.
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Mitophagie , Pré-éclampsie , Pyroptose , Trophoblastes , Femelle , Humains , Hypoxie , Inflammation , Mitophagie/physiologie , Protein kinases/génétique , Protein kinases/métabolisme , Protein kinases/pharmacologie , Espèces réactives de l'oxygène/métabolisme , Trophoblastes/métabolisme , Trophoblastes/anatomopathologie , Ubiquitin-protein ligases/génétique , Ubiquitin-protein ligases/métabolismeRÉSUMÉ
LINE-1s are the major clade of retrotransposons with autonomous retrotransposition activity. Despite the potential genotoxicity, LINE-1s are highly activated in early embryos. Here we show that a subset of young LINE-1s, L1Md_Ts, are marked by the RNA polymerase II elongation factor ELL3, and function as enhancers in mouse embryonic stem cells. ELL3 depletion dislodges the DNA hydroxymethylase TET1 and the co-repressor SIN3A from L1Md_Ts, but increases the enrichment of the Bromodomain protein BRD4, leading to loss of 5hmC, gain of H3K27ac, and upregulation of the L1Md_T nearby genes. Specifically, ELL3 occupies and represses the L1Md_T-based enhancer located within Akt3, which encodes a key regulator of AKT pathway. ELL3 is required for proper ERK activation and efficient shutdown of naïve pluripotency through inhibiting Akt3 during naïve-primed transition. Our study reveals that the enhancer function of a subset of young LINE-1s controlled by ELL3 in transcription regulation and mouse early embryo development.
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Protéines nucléaires , Facteurs de transcription , Animaux , Souris , Régions 5' non traduites , Protéines nucléaires/génétique , Facteurs de transcription/génétique , Cellules souches embryonnaires , Facteurs élongation chaîne peptidiqueRÉSUMÉ
OBJECTIVE: The global aim to lower preterm birth rates has been hampered by the insufficient and incomplete understanding of its etiology, classification, and diagnosis. This study was designed to evaluate the association of phenotypically classified preterm syndromes with neonatal outcomes; to what extent would these outcomes be modified after the obstetric interventions, including use of glucocorticoid, magnesium sulfate, and progesterone. METHODS: This was a retrospective cohort study conducted at Tongji Hospital (composed of Main Branch, Optical Valley Branch and Sino-French New City Branch) in Wuhan. A total of 900 pregnant women and 1064 neonates were retrospectively enrolled. The outcomes were the distribution of different phenotypes among parturition signs and pathway to delivery, the association of phenotypically classified clusters with short-term unfavorable neonatal outcomes, and to what extent these outcomes could be modified by obstetric interventions. RESULTS: Eight clusters were identified using two-step cluster analysis, including premature rupture of fetal membranes (PPROM) phenotype, abnormal amniotic fluid (AF) phenotype, placenta previa phenotype, mixed condition phenotype, fetal distress phenotype, preeclampsia-eclampsia & hemolysis, elevated liver enzymes, and low platelets syndrome (PE-E&HELLP) phenotype, multiple fetus phenotype, and no main condition phenotype. Except for no main condition phenotype, the other phenotypes were associated with one or more complications, which conforms to the clinical practice. Compared with no main condition phenotype, some phenotypes were significantly associated with short-term adverse neonatal outcomes. Abnormal AF phenotype, mixed condition phenotype, PE-E&HELLP phenotype, and multiple fetus phenotype were risk factors for neonatal small-for gestation age (SGA); placenta previa phenotype was not associated with adverse outcomes except low APGAR score being 0-7 at one min; mixed condition phenotype was associated with low APGAR scores, SGA, mechanical ventilation, and grade HI-W intraventricular hemorrhage (IVH); fetal distress phenotype was frequently associated with neonatal SGA and mechanical ventilation; PE-E&HELLP phenotype was correlated with low APGAR score being 0-7 at one min, SGA and neonatal intensive care unit (NICU) admission; multiple fetus phenotype was not a risk factor for the outcomes included except for SGA. Not all neonates benefited from obstetric interventions included in this study. CONCLUSION: Our research disclosed the independent risk of different preterm phenotypes for adverse pregnancy outcomes. This study is devoted to putting forward the paradigm of classifying preterm birth phenotypically, with the ultimate purpose of defining preterm phenotypes based on multi-center studies and diving into the underlying mechanisms.
Sujet(s)
HELLP syndrome , Placenta previa , Complications de la grossesse , Naissance prématurée , Nouveau-né , Grossesse , Femelle , Humains , Études rétrospectives , Souffrance foetaleRÉSUMÉ
BACKGROUND: Progressive resistance inspiratory muscle training is the principle of inspiratory air-flow resistance loading training to restore diaphragm function, increase alveolar compliance, and further improve respiratory function. However, there is a lack of research on the effectiveness of progressive resistance inspiratory training in post-lobectomy rehabilitation and the accurate assessment of lung volumes. METHODS: In this study, 79 subjects diagnosed with lung cancer and undergoing thoracoscopic lobectomy were retrospectively analyzed. The subjects were divided into a control group (n = 40) and an observation group (n =39) according to the different training modalities. The control group received conventional respiratory training. The observation group received progressive resistance inspiratory muscle training based on conventional breathing training. The primary outcome indicators were the following: lung function and lung volume. The secondary outcome indicators were the following: the number of postoperative hospital days, duration of drain retention, and incidence of postoperative pulmonary complications. RESULTS: Baseline data on age, sex, body mass index, smoking history, education level, underlying disease, type of pathology, lung cancer stages, surgical site, preoperative lung volume, and preoperative lung function were not statistically different between the 2 groups (P > .05). The subjects in the observation group had median (interquartile range [IQR]) lung volumes at 1 month after surgery (3.22 [3.12-3.37] L vs 3.14 [2.95-3.24] L; P = .031), median (IQR) FEV1 (2.11 [1.96-2.21] L vs 2.01 [1.81-2.12] L; P = .031), and mean ± SD peak expiratory flow (5.07 ± 0.62 L/s vs 4.66 ± 0.64 L/s; P = .005) were higher than those in the control group. The median (IQR) postoperative hospital stays (5 [4-5] d vs 5 [4-6] d; P = .030) and the median (IQR) chest drain retention times were shorter in the observation group versus the control group (74 [72-96] h vs 96 [84-96] h; P = .02). There was no significant difference in the incidence of postoperative atelectasis (5.1% vs 10.0%; P = .41) and pneumonia (7.7% vs 12.5%; P = .48). CONCLUSIONS: Progressive resistance inspiratory muscle training was effective in improving lung volume and lung function, and in reducing the length of hospital stay and chest drain closure time after lobectomy.