RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

Ultrasound-guided fascia iliaca compartment block combined with general anesthesia for amputation in an acute myocardial infarction patient after percutaneous coronary intervention: A case report

BACKGROUND Fascia iliaca compartment block is a technique that blocks three nerves,similar to a 3-in-1 nerve block.This block provides analgesia for patients undergoing lower limb surgery,and is a simple technique that is easy to implement.Here,we report a case of fascia iliaca compartment block in a patient with myocardial infarction who underwent emergency middle thigh amputation.CASE SUMMARY A 78-year-old female patient weighing 38 kg with gangrene and occlusive peripheral atherosclerosis of the right leg underwent an emergency middle thigh amputation.The patient had a history of hypertension,coronary heart disease,cerebral infarction,anterior wall myocardial infarction,and had recently undergone percutaneous coronary intervention consisting of coronary angiography and right coronary artery stent implantation.Considering the patient's condition,an ultrasound-guided fascia iliaca compartment block combined with general anesthesia was implemented for amputation.The fascia iliaca compartment block provided analgesia for the operation,and reduced the dosage of general anesthetics.It also alleviated adverse cardiovascular effects caused by pain stress,and ensured the safety of the patient during the perioperative period.This block also provided postoperative analgesia.The patient had a good prognosis,and was subsequently discharged from hospital.CONCLUSION Fascia iliaca compartment block provides surgical analgesia.It also alleviates adverse cardiovascular effects,and ensures patient safety during the perioperative period.

Dynamical analysis,geometric control and digital hardware implementation of a complex-valued laser system with a locally active memristor

In order to make the peak and offset of the signal meet the requirements of artificial equipment,dynamical analysis and geometric control of the laser system have become indispensable.In this paper,a locally active memristor with non-volatile memory is introduced into a complex-valued Lorenz laser system.By using numerical measures,complex dynamical behaviors of the memristive laser system are uncovered.It appears the alternating appearance of quasi-periodic and chaotic oscillations.The mechanism of transformation from a quasi-periodic pattern to a chaotic one is revealed from the perspective of Hamilton energy.Interestingly,initial-values-oriented extreme multi-stability patterns are found,where the coexisting attractors have the same Lyapunov exponents.In addition,the introduction of a memristor greatly improves the complexity of the laser system.Moreover,to control the amplitude and offset of the chaotic signal,two kinds of geometric control methods including amplitude control and rotation control are designed.The results show that these two geometric control methods have revised the size and position of the chaotic signal without changing the chaotic dynamics.Finally,a digital hardware device is developed and the experiment outputs agree fairly well with those of the numerical simulations.

Effect of lipopolysaccharide on the hemocyte apoptosis of Eriocheir sinensis

In the present study, we investigated the possible toxicity mechanism of lipopolysaccharide （LPS） extracted from Gram-negative bacteria in Eriocheir sinensis hemocytes. Apoptotic hemocytes and reactive oxygen species （ROS） production induced by the LPS were monitored by the combination of flow cytometry and microscope observation. It was shown that LPS induced serious damage on the DNA and morphological changes in hemocytes, including cell shrinkage, fracture of nucleus membrane, margination, condensation and fragmentation of chromatin, and formation of apoptotic bodies indicating obvious hemocyte apoptosis. As compared with the control group, the apoptotic cell ratio increased to 30.61% and 39.01% after 1-h exposure and 57.72% and 75.01% after 2-h exposure to 1 and 10 μg/ml LPS, respectively （P〈0.05）. Significant outburst of ROS production was observed in LPS-treated hemocytes with approximately 176.6% of relative dichlorofluorescein mean fluorescence at 1-h exposure, followed by a drastic decline （P〈0.05）. These results indicated that LPS would induce oxidative stress on hemocytes from E. sinensis and cause ROS burst, DNA damage, and subsequently apoptosis. The process of ROS-mediated apoptosis might be one of the potential toxicity mechanisms of LPS on crustacean hemocytes.

Synthesis of novel β-propanamides to inhibit cholesteryl ester transfer protein(CETP)

A novel series of β-propanamide derivatives as inhibitors of cholesteryl ester transfer protein（CETP）were synthesized.Previously,H3（IC_（50） 2 μmol/L） was observed to inhibit CETP moderately（Xie et ah,2016）.Structural modifications based on H3 led to discovery of the successful CETP inhibitor,known as 1-methyl-4-arylpyrazole.Using a similar approach,compound Q08 was identified as a highly potent CETP inhibitor with an IC_（50） of 490 nmol/L in vitro.