Global metabolic responses of the lenok (Brachymystax lenok) to thermal stress

High temperature is a powerful stressor for fish living in natural and artificial environments, especially for cold water species. Understanding the impact of thermal stress on physiological processes of fish is crucial for better cultivation and fisheries management. However, the metabolic mechanism of cold water fish to thermal stress is still not completely clear. In this study, a NMR-based metabonomic strategy in combination with high throughput RNA-Seq was employed to investigate global metabolic changes of plasma and liver in a typical cold water fish species lenok (Brachymystax lenok) subjected to a sub-lethal high temperature. Our results showed that thermal stress caused multiple dynamic metabolic alterations of the lenok with prolonged stress, including repression of energy metabolism, shifts in lipid metabolism, alterations in amino acid metabolism, changes in choline and nucleotide metabolisms. Specifically, thermal stress induced an activation of glutamate metabolism, indicating that glutamate could be an important biomarker associated with thermal stress. Evidence from Hsp 70 gene expression, blood biochemistry and histology confirmed that high temperature exposure had negative effects on health of the lenok. These findings imply that thermal stress has a severe adverse effect on fish health and demonstrate that the integrated analyses combining NMR-based metabonomics and transcriptome strategy is a powerful approach to enhance our understanding of metabolic mechanisms of fish to thermal stress.</p

Preparation and Evaluation of Topically Applied Azithromycin Based on Sodium Hyaluronate in Treatment of Conjunctivitis

Azithromycin (AZI) eye drops containing sodium hyaluronate (SH) were developed to improve the bioavailability of AZI. Interaction between AZI and SH in the AZI-SH formulation was investigated by differential scanning calorimetry, X-ray diffraction, and 1H-nuclear magnetic resonance spectroscopy analyses. Moreover, advantages of using SH as an excipient were investigated by comparing physiological properties and pharmacokinetic behaviors of SH-containing AZI eye drops with that of hydroxypropyl methylcellulose (HPMC)-containing formulation. In addition, safety of the developed AZI-SH eye drops was evaluated by in vitro 3-(4,5-dimethyl-2-Thiazyl)-2, 5-diphenyl-2H-tetrazolium bromide assay (MTT assay) and neutral red uptake assay as well as in vivo eye irritation test and acute toxicity test. The results indicated that AZI formed a complex with SH under a slightly acidic condition. The area under the curve (AUC) of AZI in SH-containing formulation was 1.58-fold higher (P &lt; 0.01) than that in HPMC-containing formulation due to the interaction between the amine group of AZI and the carboxyl group of SH, despite of the higher viscosity of HPMC-containing formulation. Safety evaluation showed that AZI-SH eye drops caused no obvious eye irritation and acute toxicity. In conclusion, the developed SH-containing AZI formulation possessing advantages of longer retention time and higher drug availability was a promising drug formulation for topical ocular therapy

Robustness of Learning from Task Instructions

Traditional supervised learning mostly works on individual tasks and requires training on a large set of task-specific examples. This paradigm seriously hinders the development of task generalization since preparing a task-specific example set is costly. To build a system that can quickly and easily generalize to new tasks, task instructions have been adopted as an emerging trend of supervision recently. These instructions give the model the definition of the task and allow the model to output the appropriate answer based on the instructions and inputs. However, task instructions are often expressed in different forms, which can be interpreted from two threads: first, some instructions are short sentences and are pretrained language model (PLM) oriented, such as prompts, while other instructions are paragraphs and are human-oriented, such as those in Amazon MTurk; second, different end-users very likely explain the same task with instructions of different textual expressions. A robust system for task generalization should be able to handle any new tasks regardless of the variability of instructions. However, the system robustness in dealing with instruction-driven task generalization is still unexplored. This work investigates the system robustness when the instructions of new tasks are (i) manipulated, (ii) paraphrased, or (iii) from different levels of conciseness. To our knowledge, this is the first work that systematically studies how robust a PLM is when it is supervised by instructions with different factors of variability.Comment: ACL'23 Finding Accepte

Treatment strategy for spontaneous coronary artery dissection based on anatomical characteristics

Abstract Objectives To compare the clinical and angiographic characteristics of high-risk and low-risk spontaneous coronary artery dissection (SCAD) patients to determine the optimal treatment strategy. Background SCAD is a rare and emerging cause of acute coronary syndrome and sudden cardiac death, especially in young female patients. However, the indication of percutaneous coronary intervention (PCI) in patients with SCAD remains elusive. Methods We evaluated the clinical and angiographic characteristics of all SCAD patients admitted to our center from 2012 to 2020. The outcomes of the high-risk and low-risk SCAD patients according to the location of the lesion segment with dissection or intramural hematoma were compared. Further analyses were performed to evaluate the vessel healing or residual dissection in the patients receiving the follow-up angiography. Results A total of 81 SCAD patients were enrolled in the present study, in which 38 patients were categorized as high-risk group, defined as involvement of the left main artery or proximal segment of any main coronary artery. PCI was the more common treatment approach in the high-risk group (68.4%), while conservative treatment was more common in the low-risk group (62.8%). The incidence of major adverse cardiac events, defined as cardiac death, myocardial infarction, unstable angina pectoris, severe arrhythmias, or heat failure, within 1 year follow-up was similar between the two groups. 57 patients (70.4%) received the follow-up angiography after 1 year. The high- and low-risk groups had a similar rate of vessel healing among the PCI treatment patients. However, more patients achieved spontaneous healing in the low-risk group than the high-risk group among the conservative treatment patients (86.4% vs. 33.3%, p < 0.05). Conclusions Conservative management remains the recommended treatment strategy for the low-risk SCAD patients. PCI could be considered in high-risk SCAD patients with favorable clinical outcomes and vessel healing. Characterization of lesion anatomy may be an important indicator for treatment decision

Quality Evaluation of Mahonia bealei (Fort.) Carr. Using Supercritical Fluid Chromatography with Chemical Pattern Recognition

Mahonia bealei (Fort.) Carr. (M. bealei) plays an important role in the treatment of many diseases. In the present study, a comprehensive method combining supercritical fluid chromatography (SFC) fingerprints and chemical pattern recognition (CPR) for quality evaluation of M. bealei was developed. Similarity analysis, hierarchical cluster analysis (HCA), principal component analysis (PCA) were applied to classify and evaluate the samples of wild M. bealei, cultivated M. bealei and its substitutes according to the peak area of 11 components but an accurate classification could not be achieved. PLS-DA was then adopted to select the characteristic variables based on variable importance in projection (VIP) values that responsible for accurate classification. Six characteristics peaks with higher VIP values (&ge;1) were selected for building the CPR model. Based on the six variables, three types of samples were accurately classified into three related clusters. The model was further validated by a testing set samples and predication set samples. The results indicated the model was successfully established and predictive ability was also verified satisfactory. The established model demonstrated that the developed SFC coupled with PLS-DA method showed a great potential application for quality assessment of M. bealei

Formation of silver nanoparticles by human gut microbiota

Metal nanoparticles have received global attention and one of the most promising nanotechnologies is the use of microorganisms for synthesizing nanoparticles. The oral exposure study has demonstrated the formation of silver (Ag) nanoparticles with in vivo animal models. However, there is limitation in the effect of in vitro cultured human gut microbiota on silver. Here, the phenomenon of biosynthesis of Ag nanoparticles by human gut microbiota has been reported. The size, shape, and morphology of the nanoparticles were characterized using transmission electron microscopy (TEM). Exposure to aqueous AgNO3 solution resulted in the intracellular reduction of Ag+ions and the formation of approximately spherical Ag nanoparticles with dimensions of 34 ± 10 nm. Electron microscopy analysis of the gut microbial cells by TEM images of thin sections and scanning electron microscopy (SEM), indicated that most of Ag nanoparticles were located on the cytoplasmic membrane and within the cytoplasm, where abundant silver reductases were present. In addition, some nanoparticles were bound to the cell wall, likely via exocytosis. The oral exposure to Ag+led to in vivo formation of nanoparticles by gut microbiota, and their biological effects and potential applications in human body warrant further investigation

The standard versus prolonged dual antiplatelet therapy after the XINSORB bioresorbable scaffold implantation (SPARTA) trial: study protocol for a randomized controlled trial

Abstract Background Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is the standard of care after coronary stenting, including coronary stenting involving bioresorbable scaffolds (BRSs). Current clinical guidelines recommend at least 12 months of DAPT after BRS implantation. However, the correlation between prolonged DAPT and net clinical benefits remains unknown. Methods The SPARTA trial is designed to be a prospective, randomized, parallel-group, clinical trial. It aims to compare the benefits and risks of DAPT applied for either 12 or 36 months after XINSORB BRS implantation. The primary endpoints are the incidence of the composite endpoint of major adverse cardiac events (MACEs), including all-cause death, any myocardial infarction (MI), and all revascularizations, as well as Bleeding Academic Research Consortium Definition (BARC) type 3 or 5 bleeding events. The secondary endpoints of the study include the device-oriented composite endpoint of target lesion failure (defined as cardiac death, target vessel-related MI, or ischemia-driven target lesion revascularization), target vessel failure (defined as cardiac death, MI, or ischemia-driven target vessel revascularization), scaffold thrombosis, and minor bleeding events. This trial will enroll 2106 subjects treated with the XINSORB BRS only. All subjects will receive DAPT after the index procedure for 12 (± 1) months. Subjects without MACEs or major bleeding will be randomized to receive either 24 additional months of DAPT or aspirin alone. Discussion This trial is designed to investigate the impact of extending the duration of DAPT up to 3 years after XINSORB BRS implantation by investigating the balance of risks and benefits in a broad population of treated patients. Trial registration ClinicalTrials.gov NCT04501900 . Registered on 6 August 2020

Thermal Stability of YSZ Coatings Deposited by Plasma Spray–Physical Vapor Deposition

The plasma spray&ndash;physical vapor deposition (PS&ndash;PVD) process has received considerable attention due to its non-line of sight deposition ability, high deposition rates, and cost efficiency. Compared with electron beam&ndash;physical vapor deposition (EB&ndash;PVD), PS&ndash;PVD can also prepare thermal barrier coatings (TBCs) with columnar microstructures. In this paper, yttria-stabilized zirconia (YSZ) coatings were fabricated by PS&ndash;PVD. Results showed that the as-deposited coating presented a typical columnar structure and was mainly composed of metastable tetragonal (t&prime;-ZrO2) phase. With thermal exposure, the initial t&prime; phase of YSZ evolved gradually into monoclinic (m-ZrO2) phase. Significant increase in hardness (H) and the Young&rsquo;s modulus (E) of the coating was attributed to the sintering effect of the coating during the thermal exposure, dependent on exposure temperature and time. However, the values of H and E decreased in the coatings thermally treated at 1300&ndash;1500 &deg;C for 24 h, which is mainly affected by the formation of m-ZrO2 phase

Inverse Relationship between Serum VEGF Levels and Late In-Stent Restenosis of Drug-Eluting Stents

Late in-stent restenosis (ISR) has raised concerns regarding the long-term efficacy of drug-eluting stents (DES). The role of vascular endothelial growth factor (VEGF) in the pathological process of ISR is controversial. This retrospective study aimed to investigate the relationship between serum VEGF levels and late ISR in patients with DES implantation. A total of 158 patients who underwent angiography follow-up beyond 1 year after intervention were included. The study population was classified into ISR and non-ISR groups. The ISR group was further divided according to follow-up duration and Mehran classification. VEGF levels were significantly lower in the ISR group than in the non-ISR group [96.34 (48.18, 174.14) versus 179.14 (93.59, 307.74) pg/mL, p<0.0001]. Multivariate regression revealed that VEGF level, procedure age, and low-density lipoprotein cholesterol were independent risk factors for late ISR formation. Subgroup analysis demonstrated that VEGF levels were even lower in the very late (≥5 years) and diffuse ISR group (Mehran patterns II, III, and IV) than in the late ISR group (1–4 years) and the focal ISR group (Mehran pattern I), respectively. Furthermore, significant difference was found between diffuse and focal ISR groups. Serum VEGF levels were inversely associated with late ISR after DES implantation