Pulmonary arterial hypertension (PAH), one subtype of pulmonary hypertension (PH), is a life-threatening condition characterized by pulmonary arterial remodeling, elevated pulmonary vascular resistance, and blood pressure in the pulmonary arteries, leading to right heart failure and increased mortality. The disease is marked by endothelial dysfunction, vasoconstriction, and vascular remodeling. The role of Sodium-Glucose Co-Transporter-2 (SGLT2) inhibitors, a class of medications originally developed for diabetes management, is increasingly being explored in the context of cardiovascular diseases, including PAH, due to their potential to modulate these pathophysiological processes. In this review, we systematically examine the burgeoning evidence from both basic and clinical studies that describe the effects of SGLT2 inhibitors on cardiovascular health, with a special emphasis on PAH. By delving into the complex interactions between these drugs and the potential pathobiology that underpins PH, this study seeks to uncover the mechanistic underpinnings that could justify the use of SGLT2 inhibitors as a novel therapeutic approach for PAH. We collate findings that illustrate how SGLT2 inhibitors may influence the normal function of pulmonary arteries, possibly alleviating the pathological hallmarks of PAH such as inflammation, oxidative stress, aberrant cellular proliferation, and so on. Our review thereby outlines a potential paradigm shift in PAH management, suggesting that these inhibitors could play a crucial role in modulating the disease's progression by targeting the potential dysfunctions that drive it. This comprehensive synthesis of existing research underscores the imperative need for further clinical trials to validate the efficacy of SGLT2 inhibitors in PAH and to integrate them into the therapeutic agents used against this challenging disease.
Acute myeloid leukemia (AML) is a malignant hematological tumor disease. Chromosomal abnormality is an independent prognostic factor in AML. AML with t(8:21) (q22; q22)/AML1-ETO (AE) is an independent disease group. In this research, a new method based on Raman spectroscopy is reported for label-free single-cell identification and analysis of AE fusion genes in clinical AML patients. Raman spectroscopy reflects the intrinsic vibration information of molecules in a label-free and non-destructive manner, and the fingerprint Raman spectrum of cells characterizes intracellular molecular types and relative concentration information, so as to realize the identification and molecular metabolism analysis of different kinds of cells. We collected the Raman spectra of bone marrow cells from clinically diagnosed AML M2 patients with and without the AE fusion gene. Through comparison of the average spectra and identification analysis based on multivariate statistical methods such as principal component analysis and linear discriminant analysis, the distinction between AE positive and negative sample cells in M2 AML patients was successfully achieved, and the single-cell identification accuracy was more than 90%. At the same time, the Raman spectra of the two types of cells were analyzed by the multivariate curve resolution alternating least squares decomposition method. It was found that the presence of the AE fusion gene may lead to the metabolic changes of lipid and nucleic acid in AML cells, which was consistent with the results of genomic and metabolomic multi-omics studies. The above results indicate that single-cell Raman spectroscopy has the potential for early identification of AE-positive AML.
To identify interesting relationships between anthocyanin degradation and color variation during food processing, black carrot slice (BCS) was dried by air-impingement jet drying (AIJD) and hot air drying (HAD). AIJD was a better technology for drying BCS than HAD. Results of colorimeter determination showed that the color of BCS was significantly changed during AIJD at 50, 60 and 70 °C. UHPLC-QqQ-MS/MS analysis found that AIJD-induced degradations of main BCS anthocyanins, cyanidin-3-xylosyl(feruloylglucosyl)galactoside and cyanidin-3-xylosyl(sinapoylglucosyl)galactoside, belonged to non-spontaneous endothermic reactions, which followed the 0.5- and 1-order kinetic equations, respectively. Anthocyanin content and colors obtained from colorimeter presented strong positive correlation, particularly the a* and chroma values. We further developed a Python script based on image recognition technology to visualize the correlation matrixes between the anthocyanin contents and colors of BSC images. The plots revealed that strong positive correlations between anthocyanins and colors primarily concentrated in the sample's periphery following a concentric pattern.
Anthocyanins , Color , Daucus carota , Food Handling , Daucus carota/chemistry , Daucus carota/metabolism , Anthocyanins/chemistry , Chromatography, High Pressure Liquid , Tandem Mass Spectrometry , Desiccation
BACKGROUND: Although the benefits of antiviral therapy for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) have been proven, researchers have not confirmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time (at least 24 wk) and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC. AIM: To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC. METHODS: A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi'an Jiaotong University from January 2016 to June 2019 was conducted. Considering the history of antiviral therapy, patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups. RESULTS: Kaplan-Meier analysis revealed significant differences in overall survival (P < 0.0001) and disease-free survival (P = 0.035) between the two groups. Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival (hazard ratio = 0.27; 95% confidence interval: 0.08-0.88; P = 0.030). CONCLUSION: In patients with HBV-related HCC, it is ideal to receive preoperative long-term antiviral therapy, which helps patients tolerate more extensive hepatectomy; however, remedial antiviral therapy, which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL, can also result in improved outcomes.
Absorption, distribution, metabolism, excretion and toxicity (ADMET) properties play a crucial role in drug discovery and chemical safety assessment. Built on the achievements of admetSAR and its successor, admetSAR2.0, this paper introduced the new version of the series, admetSAR3.0, as a comprehensive platform for chemical ADMET assessment, including search, prediction and optimization modules. In the search module, admetSAR3.0 hosted over 370 000 high-quality experimental ADMET data for 104 652 unique compounds, and supplemented chemical structure similarity search function to facilitate read-across. In the prediction module, we introduced comprehensive ADMET endpoints and two new sections for environmental and cosmetic risk assessments, empowering admetSAR3.0 to provide prediction for 119 endpoints, more than double numbers compared to the previous version. Furthermore, the advanced multi-task graph neural network framework offered robust and reliable support for ADMET prediction. In particular, a module named ADMETopt was added to automatically optimize the ADMET properties of query molecules through transformation rules or scaffold hopping. Finally, admetSAR3.0 provides user-friendly interfaces for multiple types of input data, such as SMILES string, chemical structure and batch molecule file, and supports various output types, including digital, chart displays and file downloads. In summary, admetSAR3.0 is anticipated to be a valuable and powerful tool in drug discovery and chemical safety assessment at http://lmmd.ecust.edu.cn/admetsar3/.
BACKGROUND: Cutaneous T-cell Lymphoma (CTCL) is a rare group of non-Hodgkin lymphoma originating from the skin, which is characterized by T-cell lymphoproliferative disorders. Chidamide, a Chinese original antineoplastic agent with independent intellectual property rights, and matrine, an extract of Chinese herbal medicine, both have been reported to exert effects on the treatment of tumors individually. However, chidamide combined with matrine has not been tested for the treatment of CTCL. METHODS: Both HH and Hut78 CTCL cell lines were treated with chidamide (0.4 µmol/L), matrine (0.6 g/L), or chidamide combined with matrine for 24, 48, and 72 h. Cell viability was estimated by MTS assay at each time point. Flow cytometry was then conducted to detect cell apoptosis. The exact mechanism of chidamide combined with matrine on CTCL cells was detected by Western blotting and further validated in xenograft models of NOD/SCID mice. RESULTS AND DISCUSSION: Compared to the single drug, chidamide combined with matrine showed a more significant effect on proliferation inhibition and apoptosis induction on CTCL cells both in vitro and in vivo. The results from the in vitro and in vivo studies suggested that matrine could enhance the anti-tumor effect of chidamide by increasing the protein expression of cleaved caspase- 3 and decreasing the expression of E-cadherin, NF-κB, p-Bad, and Bcl-2 to activate apoptosis. CONCLUSION: Our data have demonstrated chidamide combined with matrine to exhibit elevated antitumor activity in both CTCL cells and xenograft models of NOD/SCID mice, which may be a potential treatment option for CTCL.
A novel double-network conductive hydrogel based on lithium acetate/gelatin/polyacrylamide (PAAM) was synthesized by heating-cooling and subsequent γ-ray radiation-induced polymerization and cross-linking. Owing to the hydrogen bonding interaction between lithium acetate, physical cross-linked gelatin, and chemical cross-linked PAAM, the resultant hydrogel exhibited high tensile strength (1260 kPa), high ionic conductivity (35.2 mS cm-1), notch-insensitivity (tensile strength 415 kPa, elongation at break 872% with transverse notch), and extensive strain monitoring range (0.15-800%) under optimum conditions. The lithium acetate/gelatin/polyacrylamide hydrogel strain sensor attached to the skin can sensitively monitor the subtle movements of the human body. The strain sensor based on the resultant hydrogel with transverse notch can still work for 1200 cycles, due to that the covalent-cross-linked PAAm chain bridges the cracks and stabilizes the deformation, while the physical-cross-linked gelatin was unzipped to make the blunting of notch. The conductive hydrogel with high-sensitivity and high stability is expected to be used as materials for the preparation of flexible strain sensors in the future.
Prefrontal (PFC) and hippocampal (HPC) sequences of neuronal firing modulated by theta rhythms could represent upcoming choices during spatial memory-guided decision-making. How the PFC-HPC network dynamically coordinates theta sequences to predict specific goal locations and how it is interrupted in memory impairments induced by amyloid beta (Aß) remain unclear. Here, we detected theta sequences of firing activities of PFC neurons and HPC place cells during goal-directed spatial memory tasks. We found that PFC ensembles exhibited predictive representation of the specific goal location since the starting phase of memory retrieval, earlier than the hippocampus. High predictive accuracy of PFC theta sequences existed during successful memory retrieval and positively correlated with memory performance. Coordinated PFC-HPC sequences showed PFC-dominant prediction of goal locations during successful memory retrieval. Furthermore, we found that theta sequences of both regions still existed under Aß accumulation, whereas their predictive representation of goal locations was weakened with disrupted spatial representation of HPC place cells and PFC neurons. These findings highlight the essential role of coordinated PFC-HPC sequences in successful memory retrieval of a precise goal location.
Goals , Hippocampus , Prefrontal Cortex , Spatial Memory , Theta Rhythm , Prefrontal Cortex/physiology , Theta Rhythm/physiology , Animals , Hippocampus/physiology , Male , Spatial Memory/physiology , Neurons/physiology , Mice
Atorvastatin (ATV) is one of the most commonly prescribed lipid-lowering drugs detected frequently in the environment due to its high use and low degradation rate. However, the toxic effects of residual ATV in the aquatic environment on non-target organisms and its toxic mechanisms are still largely unknown. In the present study, embryos of a native estuarine benthic fish, Mugilogobius chulae, were employed to investigate the developmental and behavioral toxic effects of ATV including environmentally relevant concentrations. The aim of this study was to provide a scientific basis for ecological risk assessment of ATV in the aquatic environment by investigating the changes of biological endpoints at multiple levels in M. chulae embryos/larvae. The results showed that ATV had significantly lethal and teratogenic effects on M. chulae embryos/larvae and caused abnormal changes in developmental parameters including hatch rate, body length, heart rate, and spontaneous movement. ATV exposure caused oxidative stress in M. chulae embryos/larvae subsequently inhibited autophagy and activated apoptosis, leading to abnormal developmental processes and behavioral changes in M. chulae embryos/larvae. The disruptions of lipid metabolism, autophagy, and apoptosis in M. chulae embryos/larvae caused by ATV exposure may pose a potential ecological risk at the population level.
Atorvastatin , Autophagy , Embryo, Nonmammalian , Larva , Lipid Metabolism , Perciformes , Water Pollutants, Chemical , Animals , Atorvastatin/toxicity , Water Pollutants, Chemical/toxicity , Embryo, Nonmammalian/drug effects , Lipid Metabolism/drug effects , Autophagy/drug effects , Larva/drug effects , Behavior, Animal/drug effects , Oxidative Stress/drug effects , Apoptosis/drug effects , Embryonic Development/drug effects
Multi-exciton generation by multi-photon absorption under low-energy photons can be thought a reasonable method to reduce the risk of optical damage, especially in photoelectric quantum dot (QD) devices. The lifetime of the multi-exciton state plays a key role in the utilization of photon-induced carriers, which depends on the dynamics of the exciton generation process in materials. In this paper, the exciton generation dynamics of the photon absorption under low-frequency light in CdSe QDs are successfully detected and studied by the temporal resolution transient absorption (TA) spectroscopy method. Since the cooling time of hot excitons extends while the rate of auger recombination is accelerated when incident energy is increased, the filling time of defect states is irregular, and exciton generation experiences a transition from single-photon absorption to multi-photon absorption. This result shows how to change the excitation. Optical parameters can prolong the lifetime of excitons, thus fully extracting excitons and improving the photoelectric conversion efficiency of QD optoelectronic devices, which provides theoretical and experimental support for the development of QD optoelectronic devices.
As a member of the SMAD family, SMAD4 plays a crucial role in several cellular biological processes. However, its function in UVB radiation-induced keratinocyte damage is not yet clarified. Our study aims to provide mechanistic insight for the development of future UVB protective therapies and therapeutics involving SMAD4. HaCaT cells were treated with UVB, and the dose dependence and time dependence of UVB were measured. The cell function of UVB-treated HaCaT cells and the activity of epithelial-mesenchymal transition (EMT) after overexpression or silencing of SMAD4 was observed by flow cytometry, quantitative reverse transcription PCR (qRT-PCR) and Western Blots (WB). We found that a significant decrease in SMAD4 was observed in HaCaT cells induced by UVB. Our data confirm SMAD4 as a direct downstream target of miR-664. The down-regulation of SMAD4 preserved the viability of the UVB-treated HaCaT cells by inhibiting autophagy or apoptosis. Furthermore, the silencing of SMAD4 activated the EMT process in UVB-treated HaCaT cells. Down-regulation of SMAD4 plays a protective role in UVB-treated HaCaT cells via the activation of EMT.
Incorporating piezo-response into photocatalysis holds great promise for eco-friendly strategies in environmental remediation and sustainable energy conversion. Herein, flexible N-defect nanoporous g-C3N4 nanosheets (NPCNs) was prepared via one-step method, then whose surface was protonated. And existed dense 1T/2H phase and vertical interfaces in non-layer-dependent-piezo-response sailboat-like-MoS2 (Sv-MS) formed by in-situ stresses during nucleation and growth by experiments and MD-simulations. Noble-metal-free Z-scheme PC/VM heterojunction with broad-spectrum absorption, enhanced piezo-response and intimate triple-interface was established by electrostatic self-assembly, performing efficient hybrid-driven piezo-photocatalysis. With a systematic modification of morphology, grain size, phase composition, and surface condition of the components, the optimal PC(3.6H)/VM(u2) exhibited high piezo-photocatalytic rates for degradation of organic dyes and antibiotic (RhB (0.565 min-1), MO (0.052 min-1), MB (1.557 min-1), TC (0.062 min-1)) and hydrogen evolution (3528 µmolg-1h-1) under visible-light and ultrasonic-wave, with maintenance under NIR-light (λmax = 1000 nm) attributed to up-conversion effect (RhB: 0.212 min-1, H2: 2355 µmolg-1h-1). Furthermore, the piezo-photocatalytic mechanism was proposed by experiments and DFT-calculations for effective triple-interface Z-Scheme charge migration. This work provides a rational protocol for constructing diverse-energy-triggered, multiple-interfaces and broad-solar-spectrum (UV-Vis-NIR) piezo-photocatalysts in degradation and hydrogen evolution.
BACKGROUND: Phthalates are ubiquitous environmental endocrine disruptors. As the predominant phthalate, di-2-ethylhexyl phthalate (DEHP) has been considered possibly carcinogenic to humans but large-scale longitudinal evidence is needed to further clarify its carcinogenicity. OBJECTIVES: To examine the association between DEHP exposure and incidence of breast malignant neoplasm, carcinoma in situ and benign neoplasm. METHODS: A total of 273,295 women from UK Biobank cohort were followed up for a median of 13.5 years. Disease information was collected from National Health Service Cancer Registry and National Death Index. Baseline and yearly-average level of DEHP exposure were estimated for each individual by linking chemical monitoring record of European Environment Agency with home address of the participants by Kriging interpolation model. Cox proportional hazard model was employed to estimate the association between DEHP exposure and breast neoplasms. RESULTS: The median (IQR) of baseline and yearly-average DEHP concentration were 8000.25 (interquartile range: 6657.85-11,948.83) and 8000.25 (interquartile range: 1819.93-11,359.55) µg/L. The highest quartile of baseline DEHP was associated with 1.11 fold risk of carcinoma in situ (95 % CI, 1.00, 1.23, p < 0.001) and 1.27 fold risk of benign neoplasm (95 % CI, 1.05, 1.54, p < 0.001). As for yearly-average exposure, each quartile of DEHP was positively associated with higher risk of malignant neoplasm (HR, 1.05; 95 % CI, 1.03, 1.07, p < 0.001), carcinoma in situ (HR, 1.08; 95 % CI, 1.04, 1.11, p < 0.001) and benign neoplasm (HR, 1.13; 95 % CI, 1.07, 1.20, p < 0.001). Stratification analysis showed no significant modification effects on the DEHP-neoplasm relationship by menopausal status or ethnicity but a suggestive higher risk in younger women and those who underwent oral contraceptive pill therapy. In sensitivity analysis, the associations remained when excluding the cases diagnosed within 2 years post baseline. CONCLUSIONS: Real-world level of DEHP exposure was associated with higher risk of breast neoplasms. Because of the health risks associated with DEHP, its release to the environment should be managed.
Breast Neoplasms , Carcinoma in Situ , Diethylhexyl Phthalate , Phthalic Acids , Humans , Female , Diethylhexyl Phthalate/toxicity , Diethylhexyl Phthalate/analysis , Cohort Studies , State Medicine , Breast Neoplasms/chemically induced , Breast Neoplasms/epidemiology , Environmental Exposure/analysis
Catecholamines (CAs), which include adrenaline, noradrenaline, and dopamine, are neurotransmitters and hormones that critically regulate the cardiovascular system, metabolism, and stress response in the human body. The abnormal levels of these molecules can lead to the development of various diseases, including pheochromocytoma and paragangliomas, Alzheimer's disease, and Takotsubo cardiomyopathy. Due to their low cost, high sensitivity, flexible detection strategies, ease of integration, and miniaturization, electrochemical techniques have been extensively employed in the detection of CAs, surpassing traditional analytical methods. Electrochemical detection of CAs in real samples is challenging due to the tendency of poisoning electrode. Chemically modified electrodes have been widely used to solve the problems of poor sensitivity and selectivity faced by bare electrodes. There are a few articles that provide an overview of electrochemical detection and efficient enrichment of CAs, but there is a dearth of updates on the role of CAs in the pathogenesis of diseases. Additionally, there is still a lack of systematic synthesis with a focus on modified electrodes for electrochemical detection. Thus, this review provides a summary of the recent clinical pathogenesis of CAs and the modified electrodes for electrochemical detection of CAs published between 2017 and 2022. Moreover, challenges and future perspectives are also highlighted. This work is expected to provide useful guidance to researchers entering this interdisciplinary field, promoting further development of CAs pathogenesis, and developing more novel chemically modified electrodes for the detection of CAs.
Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. fruits (ESF), as a natural edible fruit, has long been popularized. However, few studies have conducted comprehensive chemical analyses of it. This study aimed to assess nonvolatile, volatile, and fatty oil components of ESF and to preliminarily explore the antioxidant activities. The qualitative and quantitative analyses of volatile and fatty oil components of ESF from 15 different regions were performed by the gas chromatography-mass spectrometry (GC-MS). Totally, 37 and 28 compounds were identified from volatile oil and fatty oil, respectively. The ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was used to accurately detect 43 compounds of nonvolatile components. The volatile and fatty oil components and nonvolatile components of ESF were used as samples to determine the antioxidant activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) in vitro. The components of ESF had antioxidant activity, and the nonvolatile components had stronger antioxidant activity. The results revealed that the proposed method, which is of great significance for the screening of new active ingredients, is valuable for the identification of pharmaceutical component and further development of food industry.
This study aimed to investigate the causal role of diabetes mellitus (DM), glycemic traits, and sodium-glucose cotransporter 2 (SGLT2) inhibition in pulmonary arterial hypertension (PAH). Utilizing a two-sample two-step Mendelian randomization (MR) approach, we determined the causal influence of DM and glycemic traits (including insulin resistance, glycated hemoglobin, and fasting insulin and glucose) on the risk of PAH. Moreover, we examined the causal effects of SGLT2 inhibition on the risk of PAH. Genetic proxies for SGLT2 inhibition were identified as variants in the SLC5A2 gene that were associated with both levels of gene expression and hemoglobin A1c. Results showed that genetically inferred DM demonstrated a causal correlation with an increased risk of PAH, exhibiting an odds ratio (OR) of 1.432, with a 95% confidence interval (CI) of 1.040-1.973, and a p-value of 0.028. The multivariate MR analysis revealed comparable outcomes after potential confounders (OR = 1.469, 95%CI = 1.021-2.115, p = 0.038). Moreover, genetically predicted SGLT2 inhibition was causally linked to a reduced risk of PAH (OR = 1.681*10-7, 95%CI = 7.059*10-12-0.004, p = 0.002). Therefore, our study identified the suggestively causal effect of DM on the risk of PAH, and SGLT2 inhibition may be a potential therapeutic target in patients with PAH.
Diabetes Mellitus, Type 2 , Pulmonary Arterial Hypertension , Humans , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/complications , Blood Glucose , Pulmonary Arterial Hypertension/complications , Mendelian Randomization Analysis , Sodium-Glucose Transporter 2/genetics , Sodium-Glucose Transporter 2/therapeutic use , Glycated Hemoglobin , Polymorphism, Single Nucleotide
OBJECTIVE: The study aimed to compare the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and surgery in treating recurrent cervical high-grade squamous intraepithelial lesions (HSIL) after surgery due to precancerous lesions. METHODS: A total of 41 patients with recurrent cervical HSIL after surgery for precancerous lesions were studied retrospectively. Patients underwent ALA-PDT or surgery and were followed up at 3, 6, 9 and 12 months and then every six months after that. Clinical data were collected and the efficacy and safety of the two treatment methods were compared. RESULTS: Of the 41 patients with recurrent cervical HSIL after conization, 15 cases received ALA-PDT and 26 received surgery. At the six-month follow-up, the lesions' complete remission (CR) rate was 93.33 % in ALA-PDT group and 88.46 % in the surgery group. The human papillomavirus (HPV) clearance rates were 66.67 % and 73.08 %, respectively. No significant differences concerning the lesions' CR rate and the HPV clearance rate were observed between the two groups (P>0.05). At the twelve-month follow-up, the HPV clearance rates were 80.00 % and 91.67 %. No significant differences concerning the HPV clearance rate were observed between the two groups (P>0.05). In the surgery group, the HPV clearance rate and the lesions' CR rate were lower in patients over 45 years of age (25.00% vs. 81.82 %, P = 0.031; 50.00% vs. 95.45 %, P = 0.052). During the follow-up, there was no significant difference in the recurrence rate between the two groups (P>0.05). In addition, none of the patients progressed. In women treated with ALA-PDT, there was no vaginal bleeding, and no harmful effects on the cervical organizational structure or functions compared to the surgery group, and two women delivered successfully after ALA-PDT treatment. CONCLUSIONS: The efficacy of ALA-PDT was similar to that of surgery in treating recurrent cervical HSIL following surgery, with fewer side effects.
Aminolevulinic Acid , Photochemotherapy , Photosensitizing Agents , Uterine Cervical Neoplasms , Humans , Aminolevulinic Acid/therapeutic use , Female , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Adult , Middle Aged , Retrospective Studies , Uterine Cervical Neoplasms/drug therapy , Neoplasm Recurrence, Local , Administration, Topical , Squamous Intraepithelial Lesions/drug therapy
BACKGROUND: Endometrial carcinoma (EC) is one of the most prevalent gynecological malignancies and the onset age of EC tends to be younger. This case report explored the feasibility of surgery combined with photodynamic therapy (PDT) in two young patients with early-stage EC. METHODS: A 31 years old patient and a 24 years old patient were treated with surgery and PDT, respectively. The intraoperative PDT was performed 3 h after oral administration of 5-aminolevulinic acid (ALA) with intrauterine light irradiation of 630 nm laser light. RESULTS: The patients were followed up for 3 years and 4 months, respectively. There were no signs of recurrence. CONCLUSION: Intraoperative and intrauterine PDT was feasible and might be used for EC patients who attempt to preserve fertility.
Aminolevulinic Acid , Endometrial Neoplasms , Photochemotherapy , Photosensitizing Agents , Humans , Female , Photochemotherapy/methods , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/therapy , Aminolevulinic Acid/therapeutic use , Photosensitizing Agents/therapeutic use , Adult , Young Adult , Combined Modality Therapy
Transporters play an indispensable role in facilitating the transport of nutrients, signaling molecules and the elimination of metabolites and toxins in human cells. Contemporary computational methods have been employed in the prediction of transporter inhibitors. However, these methods often focus on isolated endpoints, overlooking the interactions between transporters and lacking good interpretation. In this study, we integrated a comprehensive dataset and constructed models to assess the inhibitory effects on seven transporters. Both conventional machine learning and multi-task deep learning methods were employed. The results demonstrated that the MLT-GAT model achieved superior performance with an average AUC value of 0.882. It is noteworthy that our model excels not only in prediction performance but also in achieving robust interpretability, aided by GNN-Explainer. It provided valuable insights into transporter inhibition. The reliability of our model's predictions positioned it as a promising and valuable tool in the field of transporter inhibition research. Related data and code are available at https://gitee.com/wutiantian99/transporter_code.git.
Machine Learning , Humans , Reproducibility of Results
In recent years, research on ventilating tunnels has become increasingly important. However, the impact of external disturbances on ventilating systems has been largely ignored. To address this issue of frequent airflow fluctuations caused by external perturbations, which cannot be fully compensated using conventional control methods, this study proposes a perturbation-compensated ventilation control approach. A disturbance compensator is developed by incorporating the tunnel's airflow velocity and the number of jet fan start-stop events as input parameters. By compensating for external disturbances, the disturbance to the system is reduced. The Simulink model of the tunnel controller was used for simulation experiments. The compensator demonstrated good tracking results in comparison experiments with different disturbances. The ventilation approach based on disturbance compensator is capable of regulating the fluctuation of CO concentration within a justifiable range compared to using PID control and ADRC. This not only improves the stability of the entire control system but also significantly prolongs the service life of the jet fan by reducing the frequency of start-stop cycles.
