Decanoylcarnitine Inhibits Triple-Negative Breast Cancer Progression via Mmp9 in an Intermittent Fasting Obesity Mouse.

Purpose: Treatment of triple-negative breast cancer (TNBC) remains challenging. Intermittent fasting (IF) has emerged as a promising approach to improve metabolic health of various metabolic disorders. Clinical studies indicate IF is essential for TNBC progression. However, the molecular mechanisms underlying metabolic remodeling in regulating IF and TNBC progression are still unclear. Methods: In this study, we utilized a robust mouse model of TNBC and exposed subjects to a high-fat diet (HFD) with IF to explore its impact on the metabolic reprogramming linked to cancer progression. To identify crucial serum metabolites and signaling events, we utilized targeted metabolomics and RNA sequencing (RNA-seq). Furthermore, we conducted immunoblotting, real-time quantitative polymerase chain reaction (RT-qPCR), cell migration assays, lentivirus-mediated Mmp9 overexpression, and Mmp9 inhibitor experiments to elucidate the role of decanoylcarnitine/Mmp9 in TNBC cell migration. Results: Our observations indicate that IF exerts notable inhibitory effects on both the proliferation and cancer metastasis. Utilizing targeted metabolomics and RNA-seq, we initially identified pivotal serum metabolites and signaling events in the progression of TNBC. Among the 349 serum metabolites identified, decanoylcarnitine was picked out to inhibit TNBC cell proliferation and migration. RNA-seq analysis of TNBC cells treated with decanoylcarnitine revealed its suppressive effects on extracellular matrix-related protein components, with a notable reduction observed in Mmp9. Further investigations confirmed that decanoylcarnitine could inhibit Mmp9 expression in TNBC cells, primary tumors, lung, and liver metastasis tissues. Mmp9 overexpression abolished the inhibitory effect of decanoylcarnitine on cell migration. Conclusion: This study pioneers the exploration of IF intervention and the role of decanoylcarnitine/Mmp9 in the progression of TNBC in obese mice, enhancing our comprehension of the potential roles of various dietary patterns in the process of cancer treatment.

Efficacy of apatinib+radiotherapy vs radiotherapy alone in patients with advanced multiline therapy failure for non small cell lung cancer with brain metastasis.

OBJECTIVE: Lung cancer is the leading cause of cancer-associated mortality worldwide. Central nervous system (CNS) metastasis is a prevalent and serious complication. The most common treatment for brain metastasis (BM) is still radiation therapy (RT). An increasing number of drugs have been shown to have intracranial activity or to sensitize tumours to radiotherapy. METHODS: Consecutive advanced multiline therapy failure in patients with non-small-cell lung cancer (NSCLC) with BM at the authors' hospital were retrospectively reviewed. Eligible patients were divided into two groups: Apatinib+RT group and RT group. Intracranial progression-free survival (PFS) and overall survival (OS) were analysed using the Kaplan-Meier method. RESULTS: The median intracranial PFS for the RT group and Apatinib+RT group was 5.83 months and 11.81 months (p = 0.034). The median OS for the RT group and Apatinib+RT group was 9.02 months and 13.62 months (p = 0.311). The Apatinib+RT group had a better intracranial PFS, but there were no significant differences between the two arms in OS. The Apatinib+RT group had significantly reduced symptoms caused by BM. CONCLUSION: RT combined with apatinib could help to control intracranial metastases. The Apatinib+RT group had significantly reduced symptoms caused by BM and improved quality of life for patients, the safety of the two treatments was similar. ADVANCES IN KNOWLEDGE: Here, we propose that RT combined with apatinib can significantly relieve brain symptoms and tolerate side-effects without affecting OS in patients with BM following failure of multiline therapy for NSCLC. Of course, this paper is a retrospective origin study, and more powerful evidence is needed to demonstrate.

Metabolic Intervention Liposome Boosted Lung Cancer Radio-Immunotherapy via Hypoxia Amelioration and PD-L1 Restraint.

At present, radiotherapy (RT) still acquires limited success in clinical due to the lessened DNA damage under hypoxia and acquired immune tolerance owing to the amplified programmed death ligand-1 (PD-L1) expression. Incredibly, intracellular PD-L1 expression depression is proven to better sensitize RT by inhibiting DNA damage repair. However, the disability of the clinically used antibodies in disrupting the extracellular PD-L1function still limits the effectiveness of radio-immunotherapy. Therefore, better PD-L1 regulation strategies are still urgently needed to better sensitize radio-immunotherapy. Hence, for this purpose, TPP-LND is synthesized by linking mitochondrial-targeted triphenylphosphine cations (TPP+ ) to the antineoplastic agent lonidamine (LND), which significantly reduces the dose needed for LND to induce effective oxidative phosphorylation inhibition (2 vs 300 µM). Then, TPP-LND is wrapped with liposomes to form TPP-LND@Lip nanoparticles. By doing this, TPP-LND@Lip nanoparticles can sensitize RT by reversing the hypoxic microenvironment of tumors to generate more DNA damage and reducing the expression of PD-L1 via enhancing the adenosine 5'-monophosphate-activated protein kinase activation. As expected, these well-designed economical TPP-LND@Lip nanoparticles are more effective than conventional anti-PD-L1 antibodies to some extent.

Biao and Ben Acupoints Regulate Mitochondrial Function Through P2X Receptor to Improve Myocardial Ischemia.

Context: Ischemic heart disease is a common disease in older surgical patients. The current treatments for myocardial ischemia mainly restore blood flow to an extent, but reperfusion inevitably causes reperfusion injury. Single-point acupuncture and moxibustion can strengthen the body's resistance and eliminate pathogenic factors, but medical practitioners haven't considered matching acupoints in treatments for myocardial ischemia. Objective: The study intended to examine the effects of electroacupuncture using the Biao and Ben acupoints on the structure and function of myocardial mitochondria, the changes in the expression of related proteins, and the intraoperative circulation of rats with myocardial ischemia and to provide a theoretical basis for the clinical use of the Biao-Ben acupoints. Design: The research team performed an animal study. Setting: The study took place in Lanzhou Maternal and Child Health Hospital. Animals: The animals were 84 male Sprague-Dawley (SD) rats, weighing 160-220 g. Intervention: The research team divided the rats into seven groups, with 12 rats in each group. The study evaluated two types of interventions: (1) zinc chloride (ZnCl2) and (2) electroacupuncture. The team used two versions of each type of intervention, for four groups in total: (1) a low dose of ZnCl2, the low-dose ZnCl2 group; (2) a high dose of ZnCl2, the high-dose ZnCl2 group; (3) electroacupuncture using a single acupoint, the Neiguan point, for the Neiguan group; and (4) electroacupuncture using three acupoints, the Neiguan point and the Biao and Ben points, for the Biao-Ben group. The study included three control groups-the control group, a positive control group; the sham group, a ZnCl2 control group; and the model group, a negative control group. The team collectively called five of the groups the operation group, which included all four intervention groups and the model group, in which the team induced ischemic heart disease. Outcome Measures: The research team measured: (1) the relative changes in the mitochondrial ultrastructure of the rat cardiomyocytes for each group using a laser confocal, fluorescent indicator assay to detect the concentration of calcium(2+) [Ca2+] in the cytoplasm of cardiomyocytes; (2) the content of adenosine triphosphate (ATP) in myocardial tissue using ATP-detection technology; (3) mitochondrial activity using the fluorescent probe method; and (4) the protein levels of P2X purinoceptor 7 (P2X7) and mitochondria-related oxidative stress factors on the myocardial cell membrane using Western blot technology. The team monitored the physiology of the rats in each group. Results: Compared with the model group, the two ZnCl2 groups and the two electroacupuncture groups showed: (1) a significantly improved mitochondrial structure and function of the ischemic cardiomyocytes, (2) a significant increase in the mitochondrial activity, (3) a significant increase in the permeability of the membrane and thus an increase the concentration of Ca2+ in the cytoplasm, (4) a significant increase in the content of ATP inside and outside the myocardium, (5) at the same time, a significant reduction in the protein levels of the P2X7 receptors on the myocardial cell membrane and the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and manganese superoxide dismutase (MnSOD) in mitochondria, and (6) a significant reduction in the protein levels of nitric oxide (NO) and cytochrome C (CytC). Conclusions: The Biao and Ben electroacupuncture can improve the structure and function of mitochondria in the myocardial cells of rats with myocardial ischemia, reduce the expression levels of the P2X7 receptor, NO, and CytC proteins, increase the expression levels of PGC-1α and MnSOD, and improve the intraoperative circulation, thus having a positive effect on myocardial ischemia.

Development and validation of an interpretable radiomic nomogram for severe radiation proctitis prediction in postoperative cervical cancer patients.

Background: Radiation proctitis is a common complication after radiotherapy for cervical cancer. Unlike simple radiation damage to other organs, radiation proctitis is a complex disease closely related to the microbiota. However, analysis of the gut microbiota is time-consuming and expensive. This study aims to mine rectal information using radiomics and incorporate it into a nomogram model for cheap and fast prediction of severe radiation proctitis prediction in postoperative cervical cancer patients. Methods: The severity of the patient's radiation proctitis was graded according to the RTOG/EORTC criteria. The toxicity grade of radiation proctitis over or equal to grade 2 was set as the model's target. A total of 178 patients with cervical cancer were divided into a training set (n = 124) and a validation set (n = 54). Multivariate logistic regression was used to build the radiomic and non-raidomic models. Results: The radiomics model [AUC=0.6855(0.5174-0.8535)] showed better performance and more net benefit in the validation set than the non-radiomic model [AUC=0.6641(0.4904-0.8378)]. In particular, we applied SHapley Additive exPlanation (SHAP) method for the first time to a radiomics-based logistic regression model to further interpret the radiomic features from case-based and feature-based perspectives. The integrated radiomic model enables the first accurate quantitative assessment of the probability of radiation proctitis in postoperative cervical cancer patients, addressing the limitations of the current qualitative assessment of the plan through dose-volume parameters only. Conclusion: We successfully developed and validated an integrated radiomic model containing rectal information. SHAP analysis of the model suggests that radiomic features have a supporting role in the quantitative assessment of the probability of radiation proctitis in postoperative cervical cancer patients.

Accelerating Triple Transport in Zinc-Air Batteries and Water Electrolysis by Spatially Confining Co Nanoparticles in Breathable Honeycomb-Like Macroporous N-Doped Carbon.

Rational engineering electrode structure to achieve an efficient triple-phase contact line is vital for applications such as in zinc-air batteries and water electrolysis. Herein, a facile "MOF-in situ-leaching and confined-growth-MOF" strategy is developed to construct a breathable trifunctional electrocatalyst based on N-doped graphitic carbon with Co nanoparticles spatially confined in an inherited honeycomb-like macroporous structure (denoted as Co@HMNC). The unique orderly arranged macroporous channels and the "ships in a bottle" confinement effect jointly expedite the triple transport, endowing the catalysts with fast reaction kinetics. As a result, the obtained Co@HMNC catalyst presents superb trifunctional performance with a positive half-wave potential (E1/2 ) of 0.90 V for oxygen reduction reaction (ORR), and low overpotentials of 318 and 51 mV for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) at 10 mA cm-2 , respectively. The Co@HMNC-based liquid Zn-air battery reaches a large specific capacity of 859 mA h gZn -1 , a high-power density of 198 mW cm-2 , and long-term stability for 375 h, suggesting its promise for actual applications.

A one-pot "shielding-to-etching" strategy to synthesize amorphous MoS2 modified CoS/Co0.85Se heterostructured nanotube arrays for boosted energy-saving H2 generation.

In this study, a facile one-pot "shielding-to-etching" strategy has been designed for the synthesis of amorphous MoS2 modified CoS/Co0.85Se heterostructured nanotube arrays (a-MoS2/CoS/Co0.85Se HNTs) as a highly efficient electrocatalyst for boosted energy-saving H2 production, using Co(OH)x(CO3)y nanorods as the template. Interestingly, these multi-composition and hollow structured products were achieved in a controllable manner via only a one-pot synthesis, in which the nanorods with shielding layers were firstly obtained and then converted into nanotubes through further etching reaction. Benefiting from the combined nature of multiple-component hollow nanostructures, the electronic structure of the electrocatalyst is efficiently modulated, the electron transfer and ion diffusion pathways are effectively shortened and abundant active sites are created, which leads to excellent activity for urea oxidation and hydrogen evolution reactions with the as-prepared a-MoS2/CoS/Co0.85Se HNTs being employed as the electrodes. As a result, the whole urea electrolysis cell exhibits a driven voltage of only 1.42 V to achieve a current density of 10 mA cm-2, surpassing most reported transition-metal-based electrocatalysts. Moreover, a battery-assisted urea electrolyzer was assembled as well to demonstrate the feasibility of practical less-energy-intensive H2 generation. The method developed in this work is expected to broaden the way of designing and synthesizing multiple-component hollow nanostructures for various applications.

Effect of propionamide on the growth of Microcystis flos-aquae colonies and the underlying physiological mechanisms.

Reducing the formation and growth of Microcystis colonies is an important prerequisite for the effective prevention and treatment of cyanobacterial blooms. Microcystis flos-aquae colonies was selected to investigate the potential of propionamide for use in controlling cyanobacterial blooms. Propionamide, one of the major allelochemicals in the root exudates of E. crassipes, was tested using different concentrations (0, 0.2, 1, and 2mgL-1) and dosing methods (one-time addition, semi-continuous addition, and continuous addition) to assess its effect on the growth of M. flos-aquae colonies. The results showed that in the presence of different concentrations of propionamide, the growth of M. flos-aquae colonies followed a logistic growth model, with a higher degree of fit at lower propionamide concentrations. With the semi-continuous addition of 2mgL-1 propionamide, the growth of M. flos-aquae colonies was markedly inhibited; the relative inhibition ratio of algal cells reached >90% at day 7 of co-culture, and the colonial form gradually disintegrated, transforming mainly into unicellular and bicellular forms and small colonies (average diameter<50µm). Following the semi-continuous addition of 2mgL-1 propionamide, the exopolysaccharide content, the chlorophyll-a concentration, and the maximum photochemical efficiency of photosystem II (Fv/Fm) trended downward in M. flos-aquae colonies, whereas the relative expression of the microcystin (MC) biosynthetic genes, mcyA and mcyH, was upregulated overall. Importantly, the synthesis of intracellular microcystin-LR (MC-LR) was decreased after an initial increase, and the extracellular MC-LR concentration did not differ significantly from that in the control group (p>0.05). Moreover, an acute toxicity test showed that 2mgL-1 propionamide was generally non-toxic to Daphnia magna. In conclusion, appropriate use of propionamide could effectively control the expansion of M. flos-aquae colonies without potential risks to the ecological safety of aquatic environments; therefore, propionamide can actually be used to regulate cyanobacterial blooms in natural waters.

[Application characteristics and situation analysis of volatile oils in database of Chinese patent medicine].

Aromatic traditional Chinese medicines have a long history in China, with wide varieties. Volatile oils are active ingredients extracted from aromatic herbal medicines, which usually contain tens or hundreds of ingredients, with many biological activities. Therefore, volatile oils are often used in combined prescriptions and made into various efficient preparations for oral administration or external use. Based on the sources from the database of Newly Edited National Chinese Traditional Patent Medicines (the second edition), the author selected 266 Chinese patent medicines containing volatile oils in this paper, and then established an information sheet covering such items as name, dosage, dosage form, specification and usage, and main functions. Subsequently, on the basis of the multidisciplinary knowledge of pharmaceutics, traditional Chinese pharmacology and basic theory of traditional Chinese medicine, efforts were also made in the statistics of the dosage form and usage, variety of volatile oils and main functions, as well as the status analysis on volatile oils in terms of the dosage form development, prescription development, drug instruction and quality control, in order to lay a foundation for the further exploration of the market development situations of volatile oils and the future development orientation.

[Research status and translational application of new extraction techniques of traditional Chinese medicine].

Extraction is the critical link during pharmaceutical process of traditional Chinese medicine (TCM), which is directly related to the quality of drugs. So the key to technology upgrading of pharmaceutical equipment in Chinese materia medica enterprise is the development of new extraction techniques, which concerns the modernization of TCM. In this paper, fundamentals, traits, and development status of new extraction technologies were firstly introduced, including ultrasound extraction, microwave extraction, super fluid extraction, semi-bionic extraction method, enzymatic treatment extraction, continuous countercurrent extraction, vacuum extraction. Then information of projects supported by the National Natural Science Foundation of China was analyzed in order to recognize the assistance and research results of new extraction techniques. The patents authorized by the State Intellectual Property Office were also summarized for the purpose of understanding the achievement transformation. The information about extraction equipments was collected and screened to acquire the characteristics and market situation. The results showed that there are still problems about new extraction technologies, such as weak basic study, hard transformation of achievements, and the disconnection between research study and practical application. It is necessary to discuss the approaches and methods for accelerating the transformation of fundamental research, which will provide references for the long-term development of new extraction techniques of TCM.