Taxifolin protects rat against myocardial ischemia/reperfusion injury by modulating the mitochondrial apoptosis pathway

Background Taxifolin (TAX), is an active flavonoid, that plays an underlying protective role on the cardiovascular system. This study aimed to evaluate its effect and potential mechanisms on myocardial ischemia/reperfusion (I/R) injury. Methods Healthy rat heart was subjected to I/R using the Langendorff apparatus. Hemodynamic parameters, including heart rate, left ventricular developed pressure (LVDP), maximum/minimum rate of the left ventricular pressure rise (+dp/dtmax and −dp/dtmin) and rate pressure product (RPP) were recorded during the perfusion. Histopathological examination of left ventricular was measured by hematoxylin-eosin (H&E) staining. Creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) activities in the effluent perfusion, and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) in the tissue were assayed. Apoptosis related proteins, such as B-cell lymphoma-2 (Bcl-2), Bcl2-associated X (Bax), and cytochrome c (Cyt-c) were also assayed by ELISA. Western blot was employed to determine apoptosis-executive proteins, including caspase 3 and 9. Transferase-mediated dUTP-X nick end labeling assay was performed to evaluate the effect TAX on myocardial apoptosis. Results Taxifolin significantly improved the ventricular functional recovery, as evident by the increase in LVDP, +dp/dtmax, −dp/dtmin and RPP, the levels of SOD, GSH-PX were also increased, but those of LDH, CK-MB, and MDA were decreased. Furthermore, TAX up-regulated the Bcl-2 protein level but down-regulated the levels of Bax, Cyt-c, caspase 3 and 9 protein, thereby inhibits the myocardial apoptosis. Discussion Taxifolin treatment remarkably improved the cardiac function, regulated oxidative stress and attenuated apoptosis. Hence, TAX has a cardioprotective effect against I/R injury by modulating mitochondrial apoptosis pathway

Integrated Metagenomic and Transcriptomic Analyses Reveal the Dietary Dependent Recovery of Host Metabolism From Antibiotic Exposure

The balance of gut microbiome is essential for maintaining host metabolism homeostasis. Despite widespread antibiotic use, the potential long-term detrimental consequences of antibiotics for host health are getting more and more attention. However, it remains unclear whether diet affects the post-antibiotic recovery of gut microbiome and host metabolism. In this study, through metagenomic sequencing and hepatic transcriptome analysis, we investigated the divergent impacts of short-term vancomycin (Vac), or combination of ciprofloxacin and metronidazole (CM) treatment on gut microbiome and host metabolism, as well as their recovery extent from antibiotic exposure on chow diet (CD) and high-fat diet (HFD). Our results showed that short-term Vac intervention affected insulin signaling, while CM induced more functional changes in the microbiome. However, Vac-induced long-term (45 days) changes of species were more apparent when recovered on CD than HFD. The effects of antibiotic intervention on host metabolism were long-lasting, antibiotic-specific, and diet-dependent. The number of differentially expressed gene was doubled by Vac than CM, but was comparable after recovery on CD as revealed by the hepatic transcriptomic analysis. In contrast, HFD intake during recovery could worsen the extent of post-antibiotic recovery by altering infection, immunity, and cancer-related pathways in short-term Vac-exposed rats and by shifting endocrine system-associated pathways in CM-exposed rats. Together, the presented data demonstrated the long-term recovery extent after different antibiotic exposure was diet-related, highlighting the importance of dietary management during post-antibiotic recovery

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

A novel variation of the recurrent laryngeal nerve

Abstract Background Injury to the recurrent laryngeal nerve is one of the most severe complications of thyroid surgery. Several anatomic variations of the nerve increase the likelihood of iatrogenic damage. Case presentation A 50-year-old woman was presented to our department with a nodule in the right thyroid lobe, and she reported no voice changes. She had no history of surgery or radiation to the head or neck. Fine-needle aspiration was recorded as papillary thyroid carcinoma. The preoperative laryngoscopy revealed left vocal cord paralysis. Right thyroid lobectomy was performed. A scarce course of the left recurrent laryngeal nerve was found during the operation that ascended along the medial edge of the superior thyroid pole and finally disappeared beneath the superior cornu of the thyroid cartilage without any tracheal, esophageal, or laryngeal branches. The patient was discharged on the third postoperative day with the diagnoses of papillary thyroid carcinoma and congenital left vocal cord paralysis. Conclusions The novel variation of the recurrent laryngeal nerve may challenge the current concept of the anatomy of the nerve. The vocal folds mobility should be examined routinely before surgery in patients undergoing thyroid operation

OK-432 (Sapylin) Reduces Seroma Formation After Axillary Lymphadenectomy in Breast Cancer

Purpose/aim: Modified radical mastectomy is the standard surgery for breast cancer in developing countries. However, seroma formation regarded as the most frequent postoperative complication limits the therapeutic benefit of mastectomy and axillary surgery. The purpose of this study was to evaluate the efficacy of OK-432 in reducing seroma formation after axillary dissection. Methods: This prospective cohort study included 80 patients with advanced breast cancer who underwent modified radical mastectomy. Patients were randomized into two groups, which differed with the OK-432 administration. N = 40 patients per group were treated with either OK-432 plus closed suction drainage or drainage-only. Result: In comparison with the drainage-only group, we found that patients in the OK-432 group had a lower drainage volume (p = .030) and a shorter duration of axillary drainage (p < .01). Besides, the use of OK-432 could reduce the incidence of seroma formation (p < .01) and the volume of seroma (p = .040). There were also significant differences in reducing the chance of evacuative punctures (p = .036) and the healing time (p < .01) between control and OK-432 group. Conclusion: OK-432 not only shortened the suction drainage duration, but also significantly reduced seroma formation as well as the needs for aspiration punctures after modified radical mastectomy

The retinal determination gene network: from developmental regulator to cancer therapeutic target.

Although originally identified for its function in Drosophila melanogaster eye specification, the Retinal Determination Gene Network (RDGN) is essential for the development of multiple organs in mammals. The RDGN regulates proliferation, differentiation and autocrine signaling, and interacts with other key signaling pathways. Aberrant expression of RDGN members such as DACH, EYA and SIX contributes to tumor initiation and progression; indeed, the levels of RDGN members are clinically prognostic factors in various cancer types. Stimulation or suppression of the activities of these crucial components can block cancer cell proliferation, prevent cancer stem cell expansion and even reverse the EMT process, thereby attenuating malignant phenotypes. Thus, cancer therapeutic interventions targeting RDGN members should be pursued in future studies

Improving the Data Quality of Untargeted Metabolomics through a Targeted Data-Dependent Acquisition Based on an Inclusion List of Differential and Preidentified Ions

Metabolomics based on high-resolution mass spectrometry has become a powerful technique in biomedical research. The development of various analytical tools and online libraries has promoted the identification of biomarkers. However, how to make mass spectrometry collect more data information is an important but underestimated research topic. Herein, we combined full-scan and data-dependent acquisition (DDA) modes to develop a new targeted DDA based on the inclusion list of differential and preidentified ions (dpDDA). In this workflow, the MS1 datasets for statistical analysis and metabolite preidentification were first obtained using full-scan, and then, the MS/MS datasets for metabolite identification were obtained using targeted DDA of quality control samples based on the inclusion list. Compared with the current methods (DDA, data-independent acquisition, targeted DDA with time-staggered precursor ion list, and iterative exclusion DDA), dpDDA showed better stability, higher characteristic ion coverage, higher differential metabolites’ MS/MS coverage, and higher quality MS/MS spectra. Moreover, the same trend was verified in the analysis of large-scale clinical samples. More surprisingly, dpDDA can distinguish patients with different severities of coronary heart disease (CHD) based on the Canadian Cardiovascular Society angina classification, which we cannot distinguish through conventional metabolomics data collection. Finally, dpDDA was employed to differentiate CHD from healthy control, and targeted metabolomics confirmed that dpDDA could identify a more complete metabolic pathway network. At the same time, four unreported potential CHD biomarkers were identified, and the area under the receiver operating characteristic curve was greater than 0.85. These results showed that dpDDA would expand the discovery of biomarkers based on metabolomics, more comprehensively explore the key metabolites and their association with diseases, and promote the development of precision medicine

Ubiquitin-Specific Peptidase 8 Modulates Cell Proliferation and Induces Cell Cycle Arrest and Apoptosis in Breast Cancer by Stabilizing Estrogen Receptor Alpha

Breast cancer (BC) is the most common neoplastic and lethal malignancy in women. Although antiendocrine therapy is the main treatment for estrogen receptor alpha (ERα)-positive BC, the development of resistance is a major clinical complication. In this study, we aimed to explore the role of ubiquitin-specific peptidase 8 (USP8) in ERα signaling and identify potential targets for endocrine resistance. Public databases were used to analyze USP8 expression, prognosis, clinical characteristics, and immune cell infiltration. Immunohistochemistry and western blot assays were used to detect protein levels and ERα signaling. Quantitative reverse transcription-PCR was used to measure ERα target gene expression. The cell counting kit-8, wound-healing, clone formation, and Transwell assays were used to investigate the effects of USP8 depletion or inhibition on cell proliferation, migration, and invasion. An immunofluorescence assay was used for localizing USP8 and ERα, and a protein stability assay was performed for detecting the degradation of ERα protein. The cell cycle and apoptosis were assessed using flow cytometry. USP8 was highly expressed in the luminal subtype of BC and was associated with poor prognosis. The infiltration levels of many immune cells were positively correlated with USP8 expression. Depletion of USP8 dramatically decreased the ERα signaling activity and weakened the proliferation, migration, and invasion capabilities of BC cells. USP8 knockdown markedly induced apoptosis and cell cycle arrest (G0/G1). Colocalization analysis and protein stability assays indicated a probable mechanism by which USP8 regulates ERα. Our study demonstrates that USP8 might be crucial in BC development and may be considered a potential target for treating ER-positive BC malignancies in vitro

Layered‐Perovskite Nanowires with Long‐Range Orientational Order for Ultrasensitive Photodetectors

2D layered metal-halide perovskites combine efficient exciton radiative recombination in crystal interior with long-distance free-carrier conduction at layer edges, which are promising candidates for realizing high-performance photovoltaic, light-emission and photodetection devices. The anisotropic electrical conductivity in layered perovskites imposes an additional requirement of orientational control for enabling favorable charge transport. However, rational fabrication of single-crystalline nanostructures with pure crystallographic orientation is still elusive. Herein, large-scale pure (101)-orientated 2D-perovskite single-crystalline nanowire arrays are realized by combining solvent engineering with the capillary-bridge lithography technique. Ordered nucleation at liquid-air interface and unidirectional growth along the dewetting direction are demonstrated by fluorescence microscopy and grazing-incidence X-ray scattering in discrete capillary bridges. In consideration of crystal interior exhibiting high resistance arising from the serial insulating organic barriers and ultrafast dissociation of excitons to generate long-lived free carriers at layer edges, ultrasensitive photodetectors are demonstrated with average responsivity exceeding 1.1 × 10⁴ A W⁻¹ and detectivity exceeding 9.1 × 10¹⁵ Jones.The authors acknowledge the National Natural Science Foundation (21703268 and 21633014), the Beijing Natural Science Foundation (2182081), and the MOST of China (2017YFA0204504 and 2018YFA0208502)