Immunogenicity and therapeutic effects of a Mycobacterium tuberculosis rv2190c DNA vaccine in mice

The Excel data file [FOLT] Figshare, [DOI: 10.6084/m9.figshare.4668148 and https://figshare.com/s/bd46c22986c673579bb6 ] includes all datasets supporting the conclusions of this article: IFN-Îł in spleen lymphocyte culture supernatants, IL-4 in spleen lymphocyte culture supernatants, CD4+ T cell subsets expressing intracellular IFN-Îł or IL-4, CFU in the lungs and spleens.. (XLS 143 kb

AI of Brain and Cognitive Sciences: From the Perspective of First Principles

Nowadays, we have witnessed the great success of AI in various applications, including image classification, game playing, protein structure analysis, language translation, and content generation. Despite these powerful applications, there are still many tasks in our daily life that are rather simple to humans but pose great challenges to AI. These include image and language understanding, few-shot learning, abstract concepts, and low-energy cost computing. Thus, learning from the brain is still a promising way that can shed light on the development of next-generation AI. The brain is arguably the only known intelligent machine in the universe, which is the product of evolution for animals surviving in the natural environment. At the behavior level, psychology and cognitive sciences have demonstrated that human and animal brains can execute very intelligent high-level cognitive functions. At the structure level, cognitive and computational neurosciences have unveiled that the brain has extremely complicated but elegant network forms to support its functions. Over years, people are gathering knowledge about the structure and functions of the brain, and this process is accelerating recently along with the initiation of giant brain projects worldwide. Here, we argue that the general principles of brain functions are the most valuable things to inspire the development of AI. These general principles are the standard rules of the brain extracting, representing, manipulating, and retrieving information, and here we call them the first principles of the brain. This paper collects six such first principles. They are attractor network, criticality, random network, sparse coding, relational memory, and perceptual learning. On each topic, we review its biological background, fundamental property, potential application to AI, and future development.Comment: 59 pages, 5 figures, review articl

Association between plasma trimethylamine N -oxide and neoatherosclerosis in patients with very late stent thrombosis

Abstract(#br)Background(#br)Trimethylamine N -oxide (TMAO) has been shown to promote the development of atherosclerosis. However, the relationship between plasma TMAO and neoatherosclerosis, an important underlying mechanism of very late stent thrombosis (VLST), is unknown.(#br)Methods(#br)This post hoc study investigated the association between TMAO and neoatherosclerosis in two independent cohorts. These included a control group of 50 healthy volunteers and a study cohort of 50 patients with VLST who presented with ST-segment elevation myocardial infarction and underwent optical coherence tomography examination. Of the 50 patients with VLST, 23 had neoatherosclerosis and 27 did not have neoatherosclerosis. Patients with neoatherosclerosis were further divided into two subgroups, including 14 patients with plaque rupture and 9 without plaque rupture.(#br)Results(#br)The plasma TMAO levels, detected using mass spectrometry, were significantly higher in patients with VLST than in healthy individuals (median [interquartile range]: 2.50 [1.67-3.84] vs. 1.32 [0.86-2.44] μM; P < 0.001). Among the VLST patients, the plasma TMAO levels were significantly higher in patients with neoatherosclerosis than in those without neoatherosclerosis (3.69 [2.46-5.29] vs. 1.96 [1.39-2.80] μM; P<0.001). In addition, in patients with neoatherosclerosis, patients with plaque rupture had significantly higher plasma TMAO concentrations than those without plaque rupture (4.51 [3.41-5.85] vs. 2.46 [2.05-3.55] μM; P=0.005). Multivariate analysis indicated that TMAO was an independent predictor of neoatherosclerosis (odds ratio 3.41; 95% confidence interval: 1.59-7.30; P=0.002). Moreover, the area under the receiver operating characteristic curve for TMAO, differentiated by neoatherosclerosis, was 0.85.(#br)Conclusions(#br)Plasma TMAO was significantly correlated with neoatherosclerosis and plaque rupture in patients with VLST

Primary Percutaneous Coronary Intervention in Patients With Type 2 Diabetes With Late/Very Late Stent Thrombosis and de novo Lesions: A Single-Center Observational Cohort Study of Clinical Outcomes and Influencing Factors

Background: This study compared differences in the risk factors and clinical outcomes of primary percutaneous coronary intervention (PCI) in type 2 diabetes mellitus (DM) and non-DM patients with de novo lesions (DNLs) and late or very late stent thrombosis (LST/VLST).Methods: We used angiography to screen 4,151 patients with acute coronary syndrome for DNL and LST/VLST lesions. Overall, 3,941 patients were included in the analysis and were allocated to the DM (n = 1,286) or non-DM (n = 2,665) group at admission. The primary endpoint was a composite of major adverse cardiovascular events (MACEs), defined as death, myocardial infarction, revascularization, and ischemic stroke, within a median follow-up period of 698 days.Results: In the group with a total white blood cell count &gt;10 × 109/L (P = 0.004), a neutral granular cell count &gt;7 × 109/L (P = 0.030), and neutrophil–lymphocyte ratio &gt;1.5 (P = 0.041), revascularization was better for DNL than for LST/VLST lesions. Among DM patients with DNLs, each unit increase in age was associated with a 53.6% increase in the risk of MACEs [hazard ratio (HR): 1.536, 95% confidence interval (CI), 1.300–1.815, P &lt; 0.0001]. Older age (≥65 years) was associated with a significantly greater risk of MACEs (P &lt; 0.0001). Furthermore, each standard deviation (SD) increase in the level of peak white blood cell counts was associated with a 50.1% increase in the risk of MACEs (HR, 1.501; 95% CI, 1.208–1.864; P = 0.0002). When stratifying the DM population with DNLs according to the D-dimer baseline and peak levels &lt;0.5 vs. ≥0.5 mg/L, the high D-dimer group at baseline had a 2.066-fold higher risk of MACEs (P &lt; 0.0001), and the high peak level D-dimer group had a 1.877-fold higher risk of MACEs (P = 0.001) compared to the low-level groups. Among DM patients with LST/VLST, each unit increase in age was associated with a 75.9% increase in the risk of MACEs (HR: 1.759, 95% CI, 1.052–2.940, P = 0.032). Furthermore, for each SD increase in the peak D-dimer level, the risk of MACEs increased by 59.7% (HR, 1.597; 95% CI, 1.110–2.295; P = 0.041).Conclusion: Following successful primary PCI, the measurement of baseline and peak D-dimer values may help identify individuals at high cardiovascular risk. This suggests a potential benefit of lowering D-dimer levels among T2DM patients with DNL. Furthermore, age and the peak D-dimer values may facilitate the risk stratification of T2DM patients with LST/VLST

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

Table_1_Sex differences in atrial remodeling and its relationship with myocardial fibrosis in hypertrophic obstructive cardiomyopathy.DOCX

BackgroundThis study aimed to explore the effect of sex on left atrial (LA) remodeling and its relationship with myocardial fibrosis in patients with hypertrophic obstructive cardiomyopathy (HOCM).Methods and resultsA total of 85 patients with HOCM were enrolled. Myocardial fibrosis was quantified by the collagen volume fraction (CVF) in myocardial samples. The early atrial peak of emptying rate (PER-E) was assessed by LA volume/time (V/t) curves derived from cardiac magnetic resonance (CMR) imaging analysis. The PER-E index was PER-E normalized by left ventricular (LV) filling volume. Patients with HOCM showed a lower PER-E index than healthy controls (P = 0.027). Compared with men, the PER-E (P 0.05). The CVF was correlated with the PER-E and PER-E indexes in both sexes (all P-values were ConclusionPatients with HOCM presented LA reverse remodeling. Impaired LA function was more common in female patients with HOCM due to their susceptibility to myocardial fibrosis.</p

Calycosin Alleviates Injury in Airway Epithelial Cells Caused by PM 2.5 Exposure via Activation of AMPK Signalling

Introdution. Calycosin, a major active component in Astragali radix, has antitumour and anti-inflammation properties, but its effects on PM 2.5-induced injury in vitro and in vivo have not been clarified. Methods. Phospho-AMP-activated protein kinase (p-AMPK) and AMP-activated protein kinase (AMPK) were detected by western blot. Immunofluorescence staining was used to validate changes in the levels of nuclear factor kappa B (NF-кB) p65 nuclear translocation. Mice were administered intraperitoneally with calycosin one hour before anaesthesia and endotracheal instillation of PM 2.5. The extent of lung injury was evaluated in the H&E-stained lung sections. Apoptotic cells were detected by TUNEL staining. Results. Administration of calycosin was increased in PM 2.5-treated B2B cells in a dose-dependent manner in vitro. Fluorescence signals from anti-NF-кB p65 were increased in nuclei of cells pretreated with calycosin. The level of p-AMPK was increased by calycosin in vitro and in vivo. After pretreatment with compound C, the inhibitory effects of calycosin on cytotoxicity, levels of inflammatory cytokines and p-AMPK, and levels of NF-кB p65 nuclear translocation were not significantly decreased in vitro or in vivo. Conclusions. Calycosin effectively decreased the release of inflammatory cytokines and alleviated injury caused by PM 2.5. These effects were mediated through activation of AMPK to suppress NF-κB signalling

Nonspherical Liquid Crystalline Assemblies with Programmable Shape Transformation

Liquid crystalline (LC) assemblies with tailored shape and programmable shape transformation were prepared via polymerization-induced self-assembly. The influence of polymerization temperature and solvent on the shape of the LC assemblies indicated that shape of the LC assemblies could be delicately regulated by the repulsive interaction among the solvophilic chains and LC ordering. Programmable shape transformation of ellipsoidal LC assemblies was achieved, taking advantage of the smectic-to-isotropic phase transition. The ellipsoidal assemblies could remain ellipsoids or transform to faceted spheres and spheres, depending on the temperature procedure used. Besides, the generated spheres could be reshaped to ellipsoids with high shape recovery ratio. Small angle X-ray scattering study indicated that the interplay of the reversible smectic-to-isotropic phase transition and kinetic trapping underpins the programmed shape transformation. As a general approach to LC assemblies with programmable shape transformation, our strategy would provide a reliable platform for nanoactuators, nanomotors, and adaptive colloidal devices

CX08005, a Protein Tyrosine Phosphatase 1B Inhibitor, Attenuated Hepatic Lipid Accumulation and Microcirculation Dysfunction Associated with Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is one of the common metabolic diseases characterized by hepatic lipid accumulation. Insulin resistance and microcirculation dysfunction are strongly associated with NAFLD. CX08005, an inhibitor of PTP1B with the IC50 of 0.75 ± 0.07 μM, has been proven to directly enhance insulin sensitivity. The present study aimed to investigate the effects of CX08005 on hepatic lipid accumulation and microcirculation dysfunction in both KKAy mice and diet-induced obesity (DIO) mice. Hepatic lipid accumulation was evaluated by hepatic triglyceride determination and B-ultrasound analysis in KKAy mice. Insulin sensitivity and blood lipids were assessed by insulin tolerance test (ITT) and triglyceride (TG)/total cholesterol (TC) contents, respectively. In addition, the hepatic microcirculation was examined in DIO mice by in vivo microscopy. The results showed that CX08005 intervention significantly reduced the TG and echo-intensity attenuation coefficient in the livers of KKAy mice. Furthermore, we found that CX08005 treatment significantly enhanced insulin sensitivity, and decreased plasma TG and/or TC contents in KKAy and DIO mice, respectively. In addition, CX08005 treatment ameliorated hepatic microcirculation dysfunction in DIO mice, as evidenced by increased RBCs velocity and shear rate of the blood flow in central veins and in the interlobular veins, as well as enhanced rate of perfused hepatic sinusoids in central vein area. Additionally, CX08005 administration decreased the adhered leukocytes both in the center veins and in the hepatic sinusoids area. Taken together, CX08005 exhibited beneficial effects on hepatic lipid accumulation and microcirculation dysfunction associated with NAFLD, which was involved with modulating insulin sensitivity and leukocyte recruitment, as well as restoration of normal microcirculatory blood flow