Percutaneous closure of a post-traumatic ventricular septal defect with a patent ductus arteriosus occluder

OBJECTIVE: Ventricular septal defects resulting from post-traumatic cardiac injury are very rare. Percutaneous closure has emerged as a method for treating this disorder. We wish to report our experience in three patients who underwent percutaneous closure of a post-traumatic ventricular septal defect with a patent ductus arteriosus occluder. METHODS: We treated three patients with post-traumatic ventricular septal defects caused by stab wounds with knives. After the heart wound was repaired, patient examinations revealed ventricular septal defects with pulmonary/systemic flow ratios (Qp/Qs) of over 1.7. The post-traumatic ventricular septal defects were closed percutaneously with a patent ductus arteriosus occluder (Lifetech Scientific (Shenzhen) Co., LTD, Guangdong, China) utilizing standard techniques. RESULTS: Post-operative transthoracic echocardiography revealed no residual left-to-right shunt and indicated normal ventricular function. In addition, 320-slice computerized tomography showed that the occluder was well placed and exhibited normal morphology. CONCLUSION: Our experiences indicate that closure of a post-traumatic ventricular septal defect using a patent ductus arteriosus occluder is feasible, safe, and effective

CROP: Conservative Reward for Model-based Offline Policy Optimization

Offline reinforcement learning (RL) aims to optimize policy using collected data without online interactions. Model-based approaches are particularly appealing for addressing offline RL challenges due to their capability to mitigate the limitations of offline data through data generation using models. Prior research has demonstrated that introducing conservatism into the model or Q-function during policy optimization can effectively alleviate the prevalent distribution drift problem in offline RL. However, the investigation into the impacts of conservatism in reward estimation is still lacking. This paper proposes a novel model-based offline RL algorithm, Conservative Reward for model-based Offline Policy optimization (CROP), which conservatively estimates the reward in model training. To achieve a conservative reward estimation, CROP simultaneously minimizes the estimation error and the reward of random actions. Theoretical analysis shows that this conservative reward mechanism leads to a conservative policy evaluation and helps mitigate distribution drift. Experiments on D4RL benchmarks showcase that the performance of CROP is comparable to the state-of-the-art baselines. Notably, CROP establishes an innovative connection between offline and online RL, highlighting that offline RL problems can be tackled by adopting online RL techniques to the empirical Markov decision process trained with a conservative reward. The source code is available with https://github.com/G0K0URURI/CROP.git

Total Flavonoids from Clinopodium chinense

Doxorubicin has cardiotoxic effects that limit its clinical benefit in cancer patients. This study aims to investigate the protective effects of the total flavonoids from Clinopodium chinense (Benth.) O. Ktze (TFCC) against doxorubicin- (DOX-) induced cardiotoxicity. Male rats were intraperitoneally injected with a single dose of DOX (3 mg/kg) every 2 days for three injections. Heart samples were collected 2 weeks after the last DOX dose and then analyzed. DOX delayed body and heart growth and caused cardiac tissue injury, oxidative stress, apoptotic damage, mitochondrial dysfunction, and Bcl-2 expression disturbance. Similar experiments in H9C2 cardiomyocytes showed that doxorubicin reduced cell viability, increased ROS generation and DNA fragmentation, disrupted mitochondrial membrane potential, and induced apoptotic cell death. However, TFCC pretreatment suppressed all of these adverse effects of doxorubicin. Signal transduction studies indicated that TFCC suppressed DOX-induced overexpression of p53 and phosphorylation of JNK, p38, and ERK. Studies with LY294002 (a PI3K/AKT inhibitor) demonstrated that the mechanism of TFCC-induced cardioprotection also involves activation of PI3K/AKT. These findings indicated the potential clinical application of TFCC in preventing DOX-induced cardiac oxidative stress

Luteolin Ameliorates Hypertensive Vascular Remodeling through Inhibiting the Proliferation and Migration of Vascular Smooth Muscle Cells

Objectives. Preliminary researches showed that luteolin was used to treat hypertension. However, it is still unclear whether luteolin has effect on the hypertensive complication such as vascular remodeling. The present study was designed to investigate the effect of luteolin on the hypertensive vascular remodeling and its molecular mechanism. Method and Results. We evaluated the effect of luteolin on aorta thickening of hypertension in spontaneous hypertensive rats (SHRs) and found that luteolin could significantly decrease the blood pressure and media thickness of aorta in vivo. Luteolin could inhibit angiotensin II- (Ang II-) induced proliferation and migration of vascular smooth muscle cells (VSMCs). Dichlorofluorescein diacetate (DCFH-DA) staining result showed that luteolin reduced Ang II-stimulated ROS production in VSMCs. Furthermore, western blot and gelatin zymography results showed that luteolin treatment leaded to a decrease in ERK1/2, p-ERK1/2, p-p38, MMP2, and proliferating cell nuclear antigen (PCNA) protein level. Conclusion. These data support that luteolin can ameliorate hypertensive vascular remodeling by inhibiting the proliferation and migration of Ang II-induced VSMCs. Its mechanism is mediated by the regulation of MAPK signaling pathway and the production of ROS

The Kalanchoe genome provides insights into convergent evolution and building blocks of crassulacean acid metabolism

Crassulacean acid metabolism (CAM) is a water-use efficient adaptation of photosynthesis that has evolved independently many times in diverse lineages of flowering plants. We hypothesize that convergent evolution of protein sequence and temporal gene expression underpins the independent emergences of CAM from C3 photosynthesis. To test this hypothesis, we generate a de novo genome assembly and genome-wide transcript expression data for Kalanchoë fedtschenkoi, an obligate CAM species within the core eudicots with a relatively small genome (~260 Mb). Our comparative analyses identify signatures of convergence in protein sequence and re-scheduling of diel transcript expression of genes involved in nocturnal CO2 fixation, stomatal movement, heat tolerance, circadian clock, and carbohydrate metabolism in K. fedtschenkoi and other CAM species in comparison with non-CAM species. These findings provide new insights into molecular convergence and building blocks of CAM and will facilitate CAM-into-C3 photosynthesis engineering to enhance water-use efficiency in crops

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead