Cross-site prognosis prediction for nasopharyngeal carcinoma from incomplete multi-modal data.

Accurate prognosis prediction for nasopharyngeal carcinoma based on magnetic resonance (MR) images assists in the guidance of treatment intensity, thus reducing the risk of recurrence and death. To reduce repeated labor and sufficiently explore domain knowledge, aggregating labeled/annotated data from external sites enables us to train an intelligent model for a clinical site with unlabeled data. However, this task suffers from the challenges of incomplete multi-modal examination data fusion and image data heterogeneity among sites. This paper proposes a cross-site survival analysis method for prognosis prediction of nasopharyngeal carcinoma from domain adaptation viewpoint. Utilizing a Cox model as the basic framework, our method equips it with a cross-attention based multi-modal fusion regularization. This regularization model effectively fuses the multi-modal information from multi-parametric MR images and clinical features onto a domain-adaptive space, despite the absence of some modalities. To enhance the feature discrimination, we also extend the contrastive learning technique to censored data cases. Compared with the conventional approaches which directly deploy a trained survival model in a new site, our method achieves superior prognosis prediction performance in cross-site validation experiments. These results highlight the key role of cross-site adaptability of our method and support its value in clinical practice.

Carbon-reinforced Ni3S2/Ti3C2Tx MXene composite as an anode for superior-performance lithium-ion capacitors.

Lithium ion capacitors (LICs) are a new generation of energy storage devices that combine the super energy storage capability of lithium ion batteries with the satisfactory power density of supercapacitors. The development of high-performance LICs still faces great challenges due to the unbalanced reaction kinetics at the anode and cathode. Therefore, it is an inevitable need to enhance the electron/ion transfer capability of the anode materials. In this paper, to obtain a superior-rate and high-capacity Ni3S2-based anode, highly conductive Ti3C2Tx MXene sheets were introduced to sever as the carrier of Ni3S2 nanoparticles and simultaneously an amorphous carbon layer which coats onto the surface of Ni3S2 nanoparticles was in-situ generated by the carbonization of dopamine reactant. The as-synthesized Ni3S2/Ti3C2Tx/C composite exhibits a high specific surface area (112.6 m2/g) because of the addition of Ti3C2Tx that can reduce the aggregation of Ni3S2 nanoparticles and the in-situ generated amorphous carbon layer that can suppress the growth of Ni3S2 nanoparticles. The Ni3S2/Ti3C2Tx/C anode possesses a remarkable reversible discharge specific capacity (626.0 mAh/g under 0.2 A/g current density), which increases to 1150.8 mAh/g after 400-cycle charge/discharge measurement at the same measurement condition indicating eminent cyclability, along with superior rate capability. To construct a superior-performance LIC device, a sterculiae lychnophorae derived porous carbon (SLPC) cathode with an average discharge specific capacity of 73.4 mAh/g@0.1A/g was prepared. The Ni3S2/Ti3C2Tx/C//SLPC LIC device with optimal cathode/anode mass ratio has a satisfactory energy density ranging from 32.8 to 119.1 Wh kg-1 at the corresponding power density of 8799.4 to 157.5 W kg-1, together with a prominent capacity retention (95.5 %@1 A/g after 10,000 cycles).

Pharmacological mechanisms underlying the interaction of the nucleoside analogue gemcitabine with the c-MET inhibitor tivantinib in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy with limited treatment options, highlighting the urgent need for innovative approaches. A promising target for new anticancer therapies across various tumor types is the receptor tyrosine kinase c-MET. Here, we examined the impact of the c-MET inhibitor tivantinib in combination with gemcitabine on both primary and immortalized PDAC cells, and we investigated the mechanism underlying this combined treatment's effects. Our findings demonstrate that tivantinib is synergistic with gemcitabine, which is not related to cytidine deaminase but to inhibition of the polymerization of tubulin. Moreover, these drugs affected the expression of microRNAs miR-21 and miR-34, which regulate key oncogenic pathways. These findings might have an impact on the selection of patients for future trials.

Exploring the association of glioma tumor residuals from incongruent [18F]FET PET/MR imaging with tumor proliferation using a multiparametric MRI radiomics nomogram.

PURPOSE: The study aimed to using multiparametric MRI radiomics to predict glioma tumor residuals (TRFET over MR) derived from incongruent [18F]fluoroethyl-L-tyrosine ([18F]FET) PET/MR imaging. METHODS: One hundred ten patients with gliomas who underwent [18F]FET PET/MR scanning were retrospectively analyzed. The TRFET over MR was identified by the discrepancy-PET that the extent of resection (EOR) based on MRI subtracted the biological tumor volume on PET images. The MRI parameters and radiomics features were extracted based on EOR and selected by the least absolute shrinkage and selection operator to construct radiomics score (Rad-score). The correlation network analysis of all features was analyzed by Spearman's correlation tests. The methods for evaluating the clinical usefulness consisted of the receiver operating characteristic curve, the calibration curve, and decision curve analysis. RESULTS: The Rad-score of the patients with the TRFET over MR was significantly higher than those with the non TRFET over MR (p < 0.001). The Rad-score was significantly correlated with the discrepancy-PET (r = 0.72, p < 0.001), Ki-67 level (r = 0.76, p < 0.001), and epidermal growth factor receptor (EGFR) of gliomas (r = 0.75, p < 0.001), respectively. Moreover, there was a difference of the correlation network analysis between the TRPET over MR group and non TRFET over MR group. The nomogram combing Rad-score and clinical features had the greatest performance in predicting TRFET over MR (AUC = 0.90/0.87, training/testing). There was a significant difference in prognosis (median OS, 17 m vs. 43 m) between patients with TRFET over MR and non TRFET over MR based on nomogram prediction (p < 0.001). CONCLUSION: The nomogram based on MRI radiomics would predict gliomas tumor residuals caused by the absence of 18F-PET PET examination and adjust EOR to improve prognosis.

Field recovery from digital inline holographic images of composite propellant combustion base on denoising diffusion model.

Digital inline holography has gained extensive application in the optical diagnosis of solid propellant combustion. However, this method confronts several challenges. Firstly, the calculation time required for reconstruction and depth of field extension is excessively long. Secondly, the excessive smoke, airflow, and flame during combustion cause significant interference and poor reconstruction quality, which reduces the accuracy of particle identification. To address these issues, we have developed a holographic image reconstruction technique for aluminum particle combustion based on the Attention Mechanism, U-net, and Diffusion models. This approach enables end-to-end reconstruction of aluminum particle combustion holographic images, while effectively circumventing the interference of airflow combustion and flame.

Investigation of sponge medium for efficient concurrent tumor treating fields and radiotherapy for glioblastomas.

Realizing precise therapy for glioblastomas (GBMs), a kind of high-frequency malignant brain tumor, is of great importance in improving the overall survival (OS) of patients. With relentless efforts made in the past few years, a sponge medium has been introduced into concurrent tumor treating fields (TTFields) and radiotherapy to enhance therapy efficacy for GBMs, and some progresses have been witnessed. However, the specific physical and chemical characteristics of the sponge that can be used for GBMs have not been reported as far as we know. Therefore, this study aims to develop a simple yet robust method to select a candidate sponge medium and verify its safety in advanced concurrent TTFields and radiotherapy for GBMs through interdisciplinary investigation among materials science, medical physics, and clinical radiation oncology. Significantly, latex-free polyurethane (PU) sponges with a Hounsfield unit (HU) value lower than -750, which exhibit almost no negative influence on planning computed tomography (CT) imaging and radiotherapy dosimetry, are demonstrated to be available for concurrent TTFields and radiotherapy for GBMs. Moreover, in clinical research, the achieved clear CT images, negligible scalp toxicity, lower residual positioning errors, and high compliant rate of 82% over the selected representative sponge sample corroborate the availability and safety of PU sponges in practical applications for GBM treatment.

1,3,4-Oxadiazole and 1,3,4-Thiadiazole Nortopsentin Derivatives against Pancreatic Ductal Adenocarcinoma: Synthesis, Cytotoxic Activity, and Inhibition of CDK1.

A new series of nortopsentin analogs, in which the central imidazole ring of the natural lead was replaced by a 1,3,4-oxadiazole or 1,3,4-thiadiazole moiety, was efficiently synthesized. The antiproliferative activity of all synthesized derivatives was evaluated against five pancreatic ductal adenocarcinoma (PDAC) cell lines, a primary culture and a gemcitabine-resistant variant. The five more potent compounds elicited EC50 values in the submicromolar-micromolar range, associated with a significant reduction in cell migration. Moreover, flow cytometric analysis after propidium iodide staining revealed an increase in the G2-M and a decrease in G1-phase, indicating cell cycle arrest, while a specific ELISA demonstrated the inhibition of CDK1 activity, a crucial regulator of cell cycle progression and cancer cell proliferation.

Amorphous Co-Mo-S nanospheres fabricated via room-temperature vulcanization for asymmetric supercapacitors.

Ternary metal sulfides employed in supercapacitors exhibit better electrochemical performances than their counterpart oxides due to their superior conductivity. However, the insertion/extraction of electrolyte ions can lead to a significant volume change in electrode materials, which can result in poor cycling stability. Herein, novel amorphous Co-Mo-S nanospheres were fabricated through a facile room-temperature vulcanization method. It involves the conversion of crystalline CoMoO4 by reacting it with Na2S at room temperature. In addition to the conversion of the crystalline state into an amorphous structure with more grain boundaries, which is beneficial for the transport of electron/ion and can accommodate the volume change generated by the insertion/extraction of electrolyte ions, the production of more pores led to an increased specific surface area. The electrochemical results indicate that the as-prepared amorphous Co-Mo-S nanospheres had a specific capacitance of up to 2049.7F/g@1 A/g together with good rate capability. The amorphous Co-Mo-S nanospheres can be used as the cathode of supercapacitors and assembled with an activated carbon anode into an asymmetric supercapacitor possessing a satisfactory energy density of 47.6 Wh kg-1@1012.9 W kg-1. One of the prominent features exhibited by this asymmetric device is its remarkable cyclic stability, with a capacitance retention of 107% after 10,000 cycles.

Time-Concentration Superposition for Linear Viscoelasticity of Polymer Solutions.

The concentration dependence of linear viscoelastic properties of polymer solutions is a well-studied topic in polymer physics. Dynamic scaling theories allow qualitative predictions of polymer solution rheology, but quantitative predictions are still limited to model polymers. Meanwhile, the scaling properties of non-model polymer solutions must be determined experimentally. In present paper, the time-concentration superposition (TCS) of experimental data is shown to be a robust procedure for studying the concentration scaling properties of binary and ternary polymer solutions. TCS can not only identify whether power law scaling may exist or not, and over which concentration range, but also unambiguously estimate the concentration scaling exponents of linear viscoelastic properties for a range of non-model polymer solutions.

Automatic bundle-specific white matter fiber tracking tool using diffusion tensor imaging data: A pilot trial in the application of language-related glioma resection.

Cerebral neoplasms like gliomas may cause intracranial pressure increasing, neural tract deviation, infiltration, or destruction in peritumoral areas, leading to neuro-functional deficits. Novel tracking technology, such as DTI, can objectively reveal and visualize three-dimensional white matter trajectories; in combination with intraoperative navigation, it can help achieve maximum resection whilst minimizing neurological deficit. Since the reconstruction of DTI raw data largely relies on the technical engineering and anatomical experience of the operator; it is time-consuming and prone to operator-induced bias. Here, we develop new user-friendly software to automatically segment and reconstruct functionally active areas to facilitate precise surgery. In this pilot trial, we used an in-house developed software (DiffusionGo) specially designed for neurosurgeons, which integrated a reliable diffusion-weighted image (DWI) preprocessing pipeline that embedded several functionalities from software packages of FSL, MRtrix3, and ANTs. The preprocessing pipeline is as follows: 1. DWI denoising, 2. Gibbs-ringing removing, 3. Susceptibility distortion correction (process if opposite polarity data were acquired), 4. Eddy current and motion correction, and 5. Bias correction. Then, this fully automatic multiple assigned criteria algorithms for fiber tracking were used to achieve easy modeling and assist precision surgery. We demonstrated the application with three language-related cases in three different centers, including a left frontal, a left temporal, and a left frontal-temporal glioma, to achieve a favorable surgical outcome with language function preservation or recovery. The DTI tracking result using DiffusionGo showed robust consistency with direct cortical stimulation (DCS) finding. We believe that this fully automatic processing pipeline provides the neurosurgeon with a solution that may reduce time costs and operating errors and improve care quality and surgical procedure quality across different neurosurgical centers.

Concentration Scaling on Linear Viscoelastic Properties of Cellular Suspensions and Effects of Equilibrium Phase Behavior.

Concentration scaling on linear viscoelastic properties of cellular suspensions has been studied by rheometric characterisation of Phormidium suspensions and human blood in a wide range of volume fraction under small amplitude oscillatory shear experiments. The rheometric characterisation results are analysed by the time-concentration superposition (TCS) principle and show a power law scaling of characteristic relaxation time, plateau modulus and the zero-shear viscosity over the concentration ranges studied. The results show that the concentration effect of Phormidium suspensions on their elasticity is much stronger than that of human blood due to its strong cellular interactions and a high aspect ratio. For human blood, no obvious phase transition could be observed over the range of hematocrits studied here and with respect to a high-frequency dynamic regime, only one concentration scaling exponent could be identified. For Phormidium suspensions with respect to a low-frequency dynamic regime, three concentration scaling exponents in the volume fraction Region I (0.36≤ϕ/ϕref≤0.46), Region II (0.59≤ϕ/ϕref≤2.89) and Region III (3.11≤ϕ/ϕref≤3.44) are identified. The image observation shows that the network formation of Phormidium suspensions occurs as the volume fraction is increased from Region I to Region II; the sol-gel transition takes place from Region II to Region III. In combination with analysis of other nanoscale suspensions and liquid crystalline polymer solutions reported in the literature, it is revealed that such a power law concentration scaling exponent depends on colloidal or molecular interactions mediated with solvent and is sensitive to the equilibrium phase behaviour of complex fluids. The TCS principle is an unambiguous tool to give a quantitative estimation.

Treatment of high-grade brain arteriovenous malformations using a hybrid operating room: A prospective single-arm study.

BACKGROUND: Optimal treatment of patients with high Spetzler-Martin (S-M) grade brain arteriovenous malformations (BAVMs) remains controversial. Few studies have investigated outcomes in such patients treated in a hybrid operating room (hOR). OBJECTIVE: To examine outcomes of one-stop hybrid BAVM treatment in patients with high-grade lesions. METHODS: We prospectively enrolled patients with high-grade BAVMs (S-M grade ≥3) aged 18-65 years who underwent one-stop hybrid BAVM treatment at our hospital between October 2016 and March 2021. High-grade BAVM patients who underwent surgery from 2010 to 2016 served as historical controls. RESULTS: Forty-one high-grade BAVM patients underwent one-stop hybrid treatment in a hOR. Sixty-one propensity score-matched patients comprised the historical control group. The groups did not significantly differ in patient and BAVM characteristics. Intraoperative angiography in four patients of the hOR group demonstrated residual nidus that required further immediate resection. Main procedural complications included hemorrhage, neurologic deficit, and seizure. In the historical control group, diffuse angioarchitecture and arteriovenous fistula were independent risk factors for incomplete resection. CONCLUSIONS: One-stop hybrid BAVM treatment is safe and effective for removal of high-grade BAVMs, especially those with diffuse or complex angioarchitecture. Preoperative embolization can effectively reduce blood flow while preserving motor and language function. The combined application of functional magnetic resonance imaging, electrophysiological monitoring, and awake craniotomy can successfully avoid causing neurological injury.

Gestational bisphenol A exposure advances puberty onset in female offspring: Critical time window identification.

Increasing evidence shows that the early onset of puberty in female offspring may be caused by maternal prenatal exposure to bisphenol A (BPA) during pregnancy; however, the critical time window of maternal prenatal BPA exposure remains unknown. Here, we identify the critical time window of gestational BPA exposure that induces early onset of puberty in female offspring. Pregnant CD-1 mice were gavaged with BPA (8 mg/kg) daily during the early gestational stage (GD1-GD6), middle gestational stage (GD7-GD12) or late gestational stage (GD13-GD18). We show that maternal BPA exposure during the early and middle gestational stages could advance the vaginal opening time and increase the serum levels of kisspeptin-10 and GnRH in the female offspring at PND 34. Mechanistically, maternal BPA exposure during early and middle gestation could significantly increase CpG island methylation in the Eed gene promoters but reduce the mRNA expression of Eed in the hypothalamus tissues of the female offspring. In conclusion, the critical period of maternal BPA exposure-induced early onset of puberty in female offspring is early and middle gestation; this BPA-induced early onset of puberty might be partly attributed to epigenetic programming of the Eed gene in the hypothalamus. This study provides important insights regarding the relationship and the mechanisms between BPA and offspring pubertal development.

Five-year remission without disease progression in a patient with relapsed/refractory multiple myeloma with extramedullary disease treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study: a case report.

BACKGROUND: Multiple myeloma remains incurable despite treatment advancements over the last 20 years. LCAR-B38M Cells in Treating Relapsed/Refractory Multiple Myeloma was a phase 1, first-in-human, investigator-initiated study in relapsed/refractory multiple myeloma conducted at four sites in China. The study used LCAR-B38M chimeric antigen receptor-T cells expressing two B-cell maturation antigen-targeting single-domain antibodies designed to confer avidity, and a CD3ζ signaling domain with a 4-1BB costimulatory domain to optimize T-cell activation and proliferation. This chimeric antigen receptor construct is identical to ciltacabtagene autoleucel. In the LEGEND-2 study (n = 57, Xi'an site), overall response rate was 88%; median (95% CI) progression-free survival and overall survival were 19.9 (9.6-31.0) and 36.1 (26.4-not evaluable) months, respectively; and median follow-up was 25 months. This case study reports on a patient with relapsed/refractory multiple myeloma (λ light chain type) who was treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study (Xi'an site); he had received five prior lines of treatment and had extensive extramedullary lesions. CASE PRESENTATION: The patient, a 56-year-old Asian male, received cyclophosphamide (500 mg daily × 3 days) as lymphodepletion therapy and a total dose of 0.5 × 106 chimeric antigen receptor + T cells/kg split into three infusions (days 1, 24, and 84 from June to August 2016). He experienced grade 2 cytokine release syndrome after the first infusion; all symptoms resolved with treatment. No cytokine release syndrome occurred following the second and third infusions. His λ light chain levels decreased and normalized 20 days after the first infusion, and extramedullary lesions were healed as of January 2018. He has sustained remission for 5 years and received no other multiple myeloma treatments after LCAR-B38M chimeric antigen receptor T cell infusion. As of 30 October 2020, the patient is still progression-free and has maintained minimal residual disease-negative (10-4) complete response status for 52 months. CONCLUSIONS: This case provides support that treatment with LCAR-B38M chimeric antigen receptor T cells can result in long-term disease remission of 5 or more years without disease progression in a heavily pretreated patient with extensive extramedullary disease and no other treatment options.

Synthesis and in vivo evaluation of new steviol derivatives that protect against cardiomyopathy by inhibiting ferroptosis.

Cardiovascular diseases (CVDs) remain the leading cause of death globally. Inhibiting ferroptosis and thus preventing cardiac cell death is a promising and effective strategy for cardiomyopathy prevention and therapy. Steviol, an ent-kaurene diterpenoid, possesses broad-spectrum bioactivity. In the present study, with the aim to discover new agents for CVDs treatment, 30 derivatives of steviol, including 22 new ones, were synthesized, and evaluated their protective activity in vivo using the doxorubicin (DOX) induced zebrafish cardiomyopathy model. Our results firstly demonstrated that steviol has promising cardioprotective activity and further modification of steviol can greatly improve the activity. Among the new derivatives, 16d and 16e show the most potent activity. Both 16d (1 µM) and 16e (0.1 µM) effectively maintain the normal heart shape and prevent the cardiac dysfunction impaired by DOX in zebrafish. Their therapeutic efficacy is much superior to the parent natural product, steviol, and positive drug, levosimendan. Further study demonstrated that 16d and 16e inhibit DOX-induced ferroptosis and thus protect cardiomyopathy, by suppressing the glutathione depletion, iron accumulation, and lipid peroxidation, decreasing reactive oxygen species overaccumulation, and restoring the mitochondrial membrane potential. Consequently, due to their unique structure and significant cardioprotective activity with ferroptosis inhibition, new steviol derivatives 16d and 16e merit further research for the development of new cardioprotective drug candidates.

Role of drug catabolism, modulation of oncogenic signaling and tumor microenvironment in microbe-mediated pancreatic cancer chemoresistance.

Pancreatic ductal adenocarcinoma (PDAC) has one of the highest incidence/death ratios among all neoplasms due to its late diagnosis and dominant chemoresistance. Most PDAC patients present with an advanced disease characterized by a multifactorial, inherent and acquired resistance to current anticancer treatments. This remarkable chemoresistance has been ascribed to several PDAC features including the genetic landscape, metabolic alterations, and a heterogeneous tumor microenvironment that is characterized by dense fibrosis, and a cellular contexture including functionally distinct subclasses of cancer-associated fibroblasts, immune suppressive cells, but also a number of bacteria, shaping a specific tumor microbiome microenvironment. Thus, recent studies prompted the emergence of a new research avenue, by describing the role of the microbiome in gemcitabine resistance, while next-generation-sequencing analyses identified a specific microbiome in different tumors, including PDAC. Functionally, the contribution of these microbes to PDAC chemoresistance is only beginning to be explored. Here we provide an overview of the studies demonstrating that bacteria have the capacity to metabolically transform and hence inactivate anticancer drugs, as exemplified by the inhibition of the efficacy of 10 out of 30 chemotherapeutics by Escherichia coli. Moreover, a number of bacteria modulate specific oncogenic pathways, such as Fusobacterium nucleatum, affecting autophagy and apoptosis induction by 5-fluorouracil and oxaliplatin. We hypothesize that improved understanding of how chemoresistance is driven by bacteria could enhance the efficacy of current treatments, and discuss the potential of microbiome modulation and targeted therapeutic approaches as well as the need for more reliable models and biomarkers to translate the findings of preclinical/translational research to the clinical setting, and ultimately overcome PDAC chemoresistance, hence improving clinical outcome.

A review on biodiesel production from microalgae: Influencing parameters and recent advanced technologies.

Microalgae are the important part of carbon cycle in the nature, and they could utilize the carbon resource in water and soil efficiently. The abilities of microalgae to mitigate CO2 emission and produce oil with a high productivity have been proven. Hence, this third-generation biodiesel should be popularized. This review firstly introduce the basic characteristics and application fields of microalgae. Then, the influencing parameters and recent advanced technologies for the microalgae biodiesel production have been discussed. In influencing parameters for biodiesel production section, the factors of microalgae cultivation, lipid accumulation, microalgae harvesting, and lipid extraction have been summarized. In recent advanced technologies for biodiesel production section, the microalgae cultivation systems, lipid induction technologies, microalgae harvesting technologies, and lipid extraction technologies have been reviewed. This review aims to provide useful information to help future development of efficient and commercially viable technology for microalgae-based biodiesel production.

Synthesis and Biological Evaluation of Steviol Derivatives with Improved Cytotoxic Activity and Selectivity.

Steviol is an ent-kaurene diterpenoid with interesting pharmacological activity. Several steviol derivatives with an exo-methylene cyclopentanone unit were discovered as potent antitumor agents. However, their poor selectivity for tumor cells relative to normal cells reduces their prospects as potential anticancer drugs. In this study, based on previous work, 32 steviol derivatives, including 28 new analogues, were synthesized. Their cytotoxicity against tumor cells and normal cells was evaluated. Several new derivatives, such as 7a, 7h, and 8f, with improved cytotoxic selectivity and antiproliferative activity were obtained, and the structure-activity relationship correlations were investigated. The new compound 8f displayed potent antiproliferative activity against Huh7 cells (IC50 = 2.6 µM) and very weak cytotoxicity against the corresponding normal cells HHL5 (IC50 = 97.0 µM). Further investigation showed that 8f arrested the cell cycle at the G0/G1 phase and caused reactive oxygen species overproduction, decreased mitochondrial membrane potential, and induced apoptosis of Huh7 cells through inhibition of the PI3K/Akt/mTOR and NF-κB pathway as well as upregulation of Bax/Bcl-2 ratio. The present study suggested that 8f is a promising lead compound for new cancer therapies, and the results presented herein may encourage the further modification of steviol for additional derivatives with enhanced efficacy and selectivity.

Synthesis and in†Vivo Evaluation of Triphenylphosphonium Conjugated Trimetazidine with Enhanced Cardioprotection and Ability to Restore Mitochondrial Function.

Trimetazidine exhibits great therapeutic potential in cardiovascular diseases and mitochondria-mediated cardioprotection by trimetazidine has been widely reported. In this study, to enhance its cardioprotection, the triphenylphosphonium-based modification of trimetazidine was conducted to deliver it specifically to mitochondria. Fifteen triphenylphosphonium (TPP) conjugated trimetazidine analogs were designed and synthesized. Their protective effects were evaluated in vivo using a tert-butyl hydroperoxide (t-BHP) induced zebrafish injury model. Structure-activity relationship correlations revealed the best way to couple the TPP moiety to trimetazidine, and led to a new conjugate (18a) with enhanced therapeutic properties. Compared to trimetazidine, 18a effectively protects against heart injury in the zebrafish model at a much lower concentration. Further study in t-BHP treated zebrafish and H9c2 cells demonstrated that 18a protects against cardiomyocyte death and damage by inhibiting excessive production of ROS, maintaining mitochondrial morphology, and preventing mitochondrial dysfunction. Consequently, 18a can be regarded as a potential therapeutic agent for cardioprotection.

Enhanced removal of tetracycline via advanced oxidation of sodium persulfate and biochar adsorption.

Advanced oxidation of antibiotic tetracycline (TC) is becoming an accessible and efficient technology. The removal of TC from the complex wastewater needs to be lucubrated. In this study, a TC removal system involving degradation and adsorption was established. TC degradation was accomplished by enhanced advanced oxidation via the addition of sodium persulfate (SP) and biochar into simulated wastewater containing Mn2+ and TC wastewater. The adsorption of TC and its derivatives was removed by biochar. The results indicate that the optimized reaction parameters were 3.0 g/L of biochar prepared at 600 °C (B600) and 400 mg/L of SP under acidic condition, and the removal percentage of TC was 87.48%, including 74.23% of degradation and 13.28% of adsorption; the anions Cl-, NO3-, and H2PO4- had negligible effects on the removal of TC in this Mn2+/B600/SP system. The system also functioned well with an aqueous solution with a high chemical oxygen demand (COD) concentration. Electron paramagnetic resonance (EPR) analysis indicated that ·OH and SO4- free radicals were present in the Mn2+/B600/SP system. Based on the testing and analysis results, a removal mechanism and potential TC degradation pathway for this system were proposed. TC can be degraded by ·OH and SO4- via three degradation pathways. Mn2+ can be precipitated as MnO2, and a part of the TC and its derivatives can be adsorbed on the biochar surface. The Mn2+/B600/SP system also performed satisfactorily for a complex aqueous solution with various cations and antibiotics.