NAMPT is a metabolic checkpoint of IFNγ-producing CD4+ T cells in lupus nephritis.

Interferon γ (IFNγ) produced by T cells represents the featured cytokine and is central to the pathogenesis of lupus nephritis (LN). Here, we identified nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the salvage NAD+ biosynthetic pathway, as playing a key role in controlling IFNγ production by CD4+ T cells in LN. Our data revealed that CD4+ T cells from LN showed an enhanced NAMPT-mediated NAD+ biosynthetic process, which was positively correlated with IFNγ production in CD4+ T cells. NAMPT promoted aerobic glycolysis and mitochondrial respiration in CD4+ T cells from patients with LN or MRL/lpr mice through the production of NAD+. By orchestrating metabolic fitness, NAMPT promoted translational efficiency of Ifng in CD4+ T cells. In vivo, knockdown of NAMPT by small interfering RNA (siRNA) or pharmacological inhibition of NAMPT by FK866 suppressed IFNγ production in CD4+ T cells, leading to reduced inflammatory infiltrates and ameliorated kidney damage in lupus mice. Taken together, this study uncovers a metabolic checkpoint of IFNγ-producing CD4+ T cells in LN in which therapeutically targeting NAMPT has the potential to normalize metabolic competence and blunt pathogenicity of CD4+ T cells in LN.

Concentrations, Sources and Health Risk Assessment of Polycyclic Aromatic Hydrocarbons in Chinese Herbal Medicines.

The determination and evaluation of 16 polycyclic aromatic hydrocarbons (PAHs) in seven Chinese herbal medicines (CHMs) were conducted through a rapid and straightforward extraction and purification method, coupled with GC-MS. A sample-based solid-phase extraction (SPE) pretreatment technique, incorporating isotopic internal standards, was employed for detecting various medicinal parts of CHMs. The assay exhibited linearity within the range of 5 to 500 ng/mL, with linear coefficients (R2) for PAHs exceeding 0.999. The recoveries of spiked standards ranged from 63.37% to 133.12%, with relative standard deviations (RSDs) ranging from 0.75% to 14.54%. The total PAH content varied from 176.906 to 1414.087 µg/kg. Among the 16 PAHs, phenanthrene (Phe) was consistently detected at the highest levels (47.045-168.640 µg/kg). Characteristic ratio analysis indicated that oil, coal, and biomass combustion were the primary sources of PAHs in CHMs. The health risk associated with CHMs was assessed using the lifetime carcinogenic risk approach, revealing potential health risks from the consumption of honeysuckle, while the health risks of consuming Lycium chinense berries were deemed negligible. For the other five CHMs (glycyrrhizae, Coix lacryma, ginseng, lotus seed, seed of Sterculia lychnophora), the health risk from consumption fell within acceptable ranges. Furthermore, sensitivity analyses utilizing Monte Carlo exposure assessment methods identified PAH levels in CHMs as health risk sensitizers. It is crucial to recognize that the consumption of herbal medicines is not a continuous process but entails potential health risks. Hence, the monitoring and risk assessment of PAH residues in CHMs demand careful attention.

Computational and functional studies of the PI(4,5)P2 binding site of the TRPM3 ion channel reveal interactions with other regulators.

Transient receptor potential melastatin 3 (TRPM3) is a heat-activated ion channel expressed in peripheral sensory neurons and the central nervous system. TRPM3 activity depends on the membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), but the molecular mechanism of activation by PI(4,5)P2 is not known. As no experimental structure of TRPM3 is available, we built a homology model of the channel in complex with PI(4,5)P2via molecular modeling. We identified putative contact residues for PI(4,5)P2 in the pre-S1 segment, the S4-S5 linker, and the proximal C-terminal TRP domain. Mutating these residues increased sensitivity to inhibition of TRPM3 by decreasing PI(4,5)P2 levels. Changes in ligand-binding affinities via molecular mechanics/generalized Born surface area (MM/GBSA) showed reduced PI(4,5)P2 affinity for the mutants. Mutating PI(4,5)P2-interacting residues also reduced sensitivity for activation by the endogenous ligand pregnenolone sulfate, pointing to an allosteric interaction between PI(4,5)P2 and pregnenolone sulfate. Similarly, mutating residues in the PI(4,5)P2 binding site in TRPM8 resulted in increased sensitivity to PI(4,5)P2 depletion and reduced sensitivity to menthol. Mutations of most PI(4,5)P2-interacting residues in TRPM3 also increased sensitivity to inhibition by Gßγ, indicating allosteric interaction between Gßγ and PI(4,5)P2 regulation. Disease-associated gain-of-function TRPM3 mutations on the other hand resulted in no change of PI(4,5)P2 sensitivity, indicating that mutations did not increase channel activity via increasing PI(4,5)P2 interactions. Our data provide insight into the mechanism of regulation of TRPM3 by PI(4,5)P2, its relationship to endogenous activators and inhibitors, as well as identify similarities and differences between PI(4,5)P2 regulation of TRPM3 and TRPM8.

The structural basis for an on-off switch controlling Gßγ-mediated inhibition of TRPM3 channels.

TRPM3 channels play important roles in the detection of noxious heat and in inflammatory thermal hyperalgesia. The activity of these ion channels in somatosensory neurons is tightly regulated by µ-opioid receptors through the signaling of Gßγ proteins, thereby reducing TRPM3-mediated pain. We show here that Gßγ directly binds to a domain of 10 amino acids in TRPM3 and solve a cocrystal structure of this domain together with Gßγ. Using these data and mutational analysis of full-length proteins, we pinpoint three amino acids in TRPM3 and their interacting partners in Gß1 that are individually necessary for TRPM3 inhibition by Gßγ. The 10-amino-acid Gßγ-interacting domain in TRPM3 is subject to alternative splicing. Its inclusion in or exclusion from TRPM3 channel proteins therefore provides a mechanism for switching on or off the inhibitory action that Gßγ proteins exert on TRPM3 channels.

Self-Supporting Carbon Nanofibers with Ni-Single-Atoms and Uniformly Dispersed Ni-Nanoparticles as Scalable Multifunctional Hosts for High Energy Density Lithium-Sulfur Batteries.

The energy density of lithium-sulfur batteries (LSBs) is currently hampered by modest sulfur loadings and high electrolyte/sulfur ratios (E/S). These limitations can potentially be overcome using easy-to-infiltrate sulfur hosts with high catalytic materials. However, catalytic materials in such hosts are very susceptible to agglomeration due to the lack of efficient confinement in easy-to-infiltrate structures. Herein, using carbon dots as an aggregation limiting agent, the successful fabrication of self-supporting carbon nanofibers (CNF) containing Ni-single-atoms (NiSA ) and uniformly dispersed Ni-nanoparticles (NiNP ) of small sizes as multifunctional sulfur hosts is reported. The NiSA sites coordinated by such NiNP offer outstanding catalytic activity for sulfur reactions and CNF is an easy-to-infiltrate sulfur host with a large-scale preparation method. Accordingly, such hosts that can be prepared on a large scale enable sulfur cathodes to exhibit high sulfur utilization (66.5 mAh cm-2 at ≈0.02 C) and cyclic stability (≈86.1% capacity retention after 100 cycles at ≈0.12 C) whilst operating at a high sulfur loading (50 mg cm-2 ) and low E/S (5 µL mg-1 ). This work provides a blueprint toward practical LSBs with high energy densities.

In Situ Anchoring Co-N-C Nanoparticles on Co4 N Nanosheets toward Ultrastable Flexible Self-Supported Bifunctional Oxygen Electrocatalyst Enables Recyclable Zn-Air Batteries Over 10 000 Cycles and Fast Charging.

Zn-air batteries (ZABs) are very promising for flexible energy storage, but their application is limited to the primary battery. Developing an efficient and non-noble metal cathode toward oxygen reduction/evolution reactions (ORR/OER) is of great significance for the commercial application of rechargeable ZABs. Herein, a flexible self-supported integrated bifunctional cathode is presented in which the Co-N-C nanoparticles are in situ anchored on Co4 N nanosheets via a facile and scalable strategy. Benefiting from integrated 3D architecture with adequate active sites, porous structure, high conductivity originating from the metal substrate, and the synergistic effects of Co-N-C and Co4 N, the cathode exhibits excellent bifunctional activity (low overpotential of 275 mV at 10 mA cm-2 for OER, high half-wave potential of 0.833 V for ORR), and ultralong durability for ORR/OER in the alkaline medium. Impressively, this cathode enables the recyclable aqueous ZABs a record overall lifespan over 10 000 cycles at 20 mA cm-2 , and a superior fast-charging feature at an ultrahigh charging current density of 100 mA cm-2 . Furthermore, such a flexible integrated cathode can be directly used as a self-supported cathode for flexible solid-state ZABs, with excellent reversibility for 300 cycles, demonstrating its feasibility for practical application.

Electrokinetic Insights into the Triple Ionic and Electronic Conductivity of a Novel Nanocomposite Functional Material for Protonic Ceramic Fuel Cells.

Triple ionic and electronic conductivity (TIEC) in cathode materials for protonic ceramic fuel cells (PCFCs) is a desirable feature that enhances the spatial expansion of active reaction sites for electrochemical oxygen reduction reaction. The realization of optimal TIEC in single-phase materials, however, is challenging. A facile route that facilitates the optimization of TIEC in PCFC cathodes is the strategic development of multiphase cathode materials. In this study, a cubic-rhombohedral TIEC nanocomposite material with the composition Ba(CeCo)0.4 (FeZr)0.1 O3- δ (BCCFZ) is designed via self-assembly engineering. The material consists of a mixed ionic and electronic conducting phase, BaCo1-( x + y + z ) Cex Fey Zrz O3- δ (M-BCCFZ), and a dominant proton-conducting phase, BaCe1-( x + y + z ) Cox Zry Fez O3- δ (H-BCCZF). The dominant cerium-rich H-BCCFZ phase enhances the material's oxygen vacancy concentration and the proton defects formation and transport with a low enthalpy of protonation of -30 ± 9 kJ mol-1 . The area-specific resistance of the BCCFZ symmetrical cell is 0.089 Ω cm2 at 650 °C in 2.5% H2 O-air. The peak power density of the anode-supported single cell based on BCCFZ cathode reaches 1054 mW cm-2 at 650 °C with good operation stability spanning over 500 h at 550 °C. These promote BCCFZ as a befitting cathode material geared toward PCFC commercialization.

Nano-drug delivery system with enhanced tumour penetration and layered anti-tumour efficacy.

The low delivery efficiency of nano-drugs and limited tumour penetration are still huge challenges in treating solid tumours. Herein, we developed a pH-responsive nano-drug delivery system, CALS/PDMA@DOX, with a size conversion-layered delivery function. The system is composed of a pH-responsive cationic liposome loaded with DOX (CALS) and a polyamidoamine dendrimer loaded with DOX (PAMAM@DOX) modified with 2,3-dimethylmaleic anhydride (PDMA@DOX) using electrostatic adsorption. In the tumour microenvironment, the positively-charged large-size CALS and the positively-charged small-size PAMAM@DOX were dissociated to exert anti-tumour effects. CALS preferentially targeted tumour angiogenesis endothelial cells. Because of its small size and positive charge, PAMAM@DOX showed excellent tumour penetration. Significant tumour suppression by the system in vivo was confirmed in a 4T1 tumour xenograft mouse model. This pH-triggered size-switching layered delivery nanosystem is a safe and effective cancer treatment delivery platform that improves drug permeability and therapeutic efficacy.

Pathogenesis and Therapeutic Strategies Related to Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD), one of the most common types of chronic liver disease, is strongly correlated with obesity, insulin resistance, metabolic syndrome, and genetic components. The pathological progression of NAFLD, consisting of non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), and liver cirrhosis, is characterized by a broad spectrum of clinical phenotypes. Although patients with mild NAFL are considered to show no obvious clinical symptoms, patients with long-term NAFL may culminate in NASH and further liver fibrosis. Even though various drugs are able to improve NAFLD, there are no FDA-approved medications that directly treat NAFLD. In this paper, the pathogenesis of NAFLD, the potential therapeutic targets, and their underlying mechanisms of action were reviewed.

Hydrogen Sulfide and Its Donors: Keys to Unlock the Chains of Nonalcoholic Fatty Liver Disease.

Hydrogen sulfide (H2S) has emerged as the third "gasotransmitters" and has a crucial function in the diversity of physiological functions in mammals. In particular, H2S is considered indispensable in preventing the development of liver inflammation in the case of excessive caloric ingestion. Note that the concentration of endogenous H2S was usually low, making it difficult to discern the precise biological functions. Therefore, exogenous delivery of H2S is conducive to probe the physiological and pathological roles of this gas in cellular and animal studies. In this review, the production and metabolic pathways of H2S in vivo, the types of donors currently used for H2S release, and study evidence of H2S improvement effects on nonalcoholic fatty liver disease are systematically introduced.

Circulating TFH cells is correlated with disease activity in anti-MDA5 antibody positive idiopathic inflammatory myopathies.

OBJECTIVES: Idiopathic inflammatory myopathies (IIM) are a group of disorders characterised by the production of autoantibodies and inflammatory infiltrates in the skeletal muscles. Follicular T helper (TFH) cells are known to be crucial for B cell differentiation and autoantibody production in autoimmune diseases. The aim of this study was to investigate the involvement of TFH cells in IIM. METHODS: Circulating TFH cells in 44 IIM patients or 11 age- and gender-matched healthy controls (HCs) were measured by flow cytometry. ICOS, PD-1, active caspase-1 and Ki-67 expression in TFH cells was examined. The correlations between the frequency of TFH cells and clinical disease activities were also analysed. RESULTS: The frequency of TFH cells was 16.6% in IIM patients with anti-melanoma differentiation-associated gene (MDA5) antibody compared to 10.6% and 12.9% in anti-MDA5 negative patients or HCs, respectively (both p<0.05). The frequency of TFH cells was positively correlated with clinical disease activities: patient/parent's assessment VAS (r=0.51, p<0.05), physician's assessment VAS (r=0.59, p<0.05) and MYOACT scores (total systems: r=0.62, p<0.05; extramuscular system: r=0.56, p<0.05; pulmonary system, r=0.55, p<0.05). The percentage of PD-1highICOShigh TFH cells was 3.68% in anti-MDA5 positive patients compared to 2.70% and 1.96% in anti-MDA5 negative patients or HCs, respectively (both p<0.05). The percentage of Ki-67 positive TFH cells was 3.50% in anti-MDA5 positive patients compared to 2.36% and 1.76% in anti-MDA5 negative patients or HCs, respectively (p<0.05). Interestingly, active caspase-1 was significantly increased in TFH cells in anti-MDA5 positive patients compared to the patients without anti-MDA5 or HCs (3.30% vs. 1.67% and 3.30% vs. 1.02%, both p<0.001). CONCLUSIONS: These data suggest a role for TFH cells in the pathogenesis of anti-MDA5 positive IIM and TFH cells might serve as a disease biomarker for this subset of patients.

JAK/STAT signaling controls the fate of CD8+CD103+ tissue-resident memory T cell in lupus nephritis.

Autoimmune mediated inflammation and renal damage in lupus nephritis (LN) depends partly on the infiltration of lymphocytes in glomeruli and renal interstitium. Here we identified a population of CD8+ T cells with a CD103+-phenotype in the healthy kidneys of human and mouse. These cells were typically CD69+CD103+ tissue-resident memory T cells (TRM) in the kidney. CD8+ TRM cells were expanded in the kidneys of patients with LN or MRL/lpr mice. The expansion of renal CD8+ TRM cells correlated significantly with kidney disease activity. These cells were active in producing cytokines, perforin and granzyme B in the kidney of MRL/lpr mice. Importantly, renal CD8+ TRM cells underwent proliferation and self-renewal to maintain a stable TRM pool in the kidney of MRL/lpr mice, contributing to renal inflammation and damage. JAK/STAT signaling in the MRL/lpr mice was required for renal TRM self-renewal as well as maintenance of effector functions. Targeting JAK/STAT signaling by tofacitinib effectively suppressed effector functions and impaired the survival of renal TRM cells in the kidney, contributing to improved kidney function in MRL/lpr mice. These results provided evidences that renal CD8+ TRM cells play a role in the pathogenesis of LN. They could serve as a therapeutic target for LN.

Soft and MRI Compatible Neural Electrodes from Carbon Nanotube Fibers.

Soft and magnetic resonance imaging (MRI) compatible neural electrodes enable stable chronic electrophysiological measurements and anatomical or functional MRI studies of the entire brain without electrode interference with MRI images. These properties are important for many studies, ranging from a fundamental neurophysiological study of functional MRI signals to a chronic neuromodulatory effect investigation of therapeutic deep brain stimulation. Here we develop soft and MRI compatible neural electrodes using carbon nanotube (CNT) fibers with a diameter from 20 µm down to 5 µm. The CNT fiber electrodes demonstrate excellent interfacial electrochemical properties and greatly reduced MRI artifacts than PtIr electrodes under a 7.0 T MRI scanner. With a shuttle-assisted implantation strategy, we show that the soft CNT fiber electrodes can precisely target specific brain regions and record high-quality single-unit neural signals. Significantly, they are capable of continuously detecting and isolating single neuronal units from rats for up to 4-5 months without electrode repositioning, with greatly reduced brain inflammatory responses as compared to their stiff metal counterparts. In addition, we show that due to their high tensile strength, the CNT fiber electrodes can be retracted controllably postinsertion, which provides an effective and convenient way to do multidepth recording or potentially selecting cells with particular response properties. The chronic recording stability and MRI compatibility, together with their small size, provide the CNT fiber electrodes unique research capabilities for both basic and applied neuroscience studies.

Synchronous Nutrient Controlled-Release of Greenhouse Gases During Mineralization of Sediments from Different Lakes.

Lake sediments, as an important emission source of nutrients and greenhouse gases, play a crucial role during the biogeochemical cycle processes. However, the impact mechanisms of different nutrient levels on greenhouse gas emission from lakes are still insufficient. In this study, the sediments from eight shallow lakes in the middle and lower reaches of the Yangtze River were cultured to study the release characteristics of greenhouse gases more than one month. Results showed that the greenhouse gases during the mineralization processes of sediments were mainly released to the atmosphere instead of being dissolved in the overlying water. The released concentrations of CH4 and CO2 were as high as 1 × 103 µmol L-1 in the later stage of the experiment, while the concentration of N2O was relatively low with a maximal value of about 10 µmol L-1. In addition, all the lake sediments displayed a nutrient release to the overlying water, where the concentrations of TC, TOC, TN, NH4+-N and TP were up to 173.0, 102.7, 36.7, 30.8 and 6.34 mg L-1, respectively. The nutrient levels of different lake sediments are symmetrical to the released nutrients concentrations in the overlying water. The further statistical analysis illustrated a synchronous nutrient controlled-release of greenhouse gases, that is, the higher the levels of nutrients in the sediments, the higher the concentrations of greenhouse gases released. These findings provide a better understanding that the control of endogenous nutrient levels of sediments is extremely important for lacustrine management, which can play a positive role in mitigating the greenhouse gas emissions from lake sediments.

Innate lymphoid cell disturbance with increase in ILC1 in systemic lupus erythematosus.

The innate lymphoid cell (ILC) is a group of effector cells with diverse important cellular functions in both health and disease states. In comparison with healthy controls, there were increases in circulating ILC in SLE patients. The proportion of ILC1 significantly increased with significant decreases of ILC2 in SLE patients and ILC3 in SLE patients with moderate to severe activity. IL-12, IL-18, IL-25, IL-33, IL-23, IL-1ß and IFN-γ were significantly increased in SLE patients. Moreover, IL-12, IL-18 and IL-1ß but not IFN-γ correlated significantly with SLEDAI. Successful treatments rapidly reduced them and with certain normalization of the ILC subsets. In addition to increases in ILC1 numbers, ~ 80% of the ILC1 in SLE patients were positive for synthesis of IFN-γ. Plasma from SLE patients were shown to be potent in inducing ILC1. Thus, increased circulating ILC1 might contribute to the pathogenesis of SLE through mounting type 1 immune response.

[Research progress on computed tomography image detection and classification of pulmonary nodule based on deep learning].

Computer-aided diagnosis based on computed tomography (CT) image can realize the detection and classification of pulmonary nodules, and improve the survival rate of early lung cancer, which has important clinical significance. In recent years, with the rapid development of medical big data and artificial intelligence technology, the auxiliary diagnosis of lung cancer based on deep learning has gradually become one of the most active research directions in this field. In order to promote the deep learning in the detection and classification of pulmonary nodules, we reviewed the research progress in this field based on the relevant literatures published at domestic and overseas in recent years. This paper begins with a brief introduction of two widely used lung CT image databases: lung image database consortium and image database resource initiative (LIDC-IDRI) and Data Science Bowl 2017. Then, the detection and classification of pulmonary nodules based on different network structures are introduced in detail. Finally, some problems of deep learning in lung CT image nodule detection and classification are discussed and conclusions are given. The development prospect is also forecasted, which provides reference for future application research in this field.

Identification and characterization of cell-bound membrane vesicles.

In contrast to the released/circulating membrane vesicles (extracellular vesicles), cell-bound membrane vesicles are poorly identified and characterized. In this study, cell-bound membrane vesicles on human umbilical vein endothelial cells (HUVECs) and human hepatoma HepG-2 cells were investigated. We identified that cell-bound membrane vesicles are not co-localized with the major markers for extracellular vesicles (e.g. phosphatidylserine, CD63, CD107α, CD31, and DNA fragments for the three well-known types of extracellular vesicles) and for intracellular organelles with similar sizes (e.g. MitoTracker and LAMP1/LAMP3 for mitochondria and multivesicular bodies or lysosomes, respectively). The data imply that cell-bound membrane vesicles are neither the precursors of extracellular vesicles nor a false structure pushed up by an intracellular organelle but probably a novel unknown structure in the plasma membrane. Moreover, we revealed that cell-bound membrane vesicles are resistant to various detergents including but probably not limited to Triton X-100, SDS, and saponin. We further characterized that these unique vesicles are soluble in organic solvents (e.g. chloroform-methanol mixture and ethanol) which can be prevented by a lipid-stabilizing fixative (e.g. OsO4) and that they are co-localized with, but do not monopolize, the major markers (e.g. caveolin-1 and GM1) for lipid rafts (a nano-sized detergent-resistant domains in the plasma membrane). The data imply that cell-bound membrane vesicles contain the lipid component and lipid rafts. Involvement of other specific unknown components might explain the detergent resistance of cell-bound membrane vesicles. Further research will mainly depend on the establishment of an effective approach for isolation/purification of these vesicles from the plasma membrane.

Graphene Encapsulated Copper Microwires as Highly MRI Compatible Neural Electrodes.

Magnetic resonance imaging (MRI) compatible neural electrodes are important for combining high-resolution electrophysiological measurements with more global MRI mapping of brain activity, which is critical for fundamental neuroscience studies, as well as clinical evaluation and monitoring. Copper is a favorable material to use in MRI because it has magnetic susceptibility close to water and tissues. However, the cytotoxicity of copper precludes its direct implantation for neural recording. Here, we overcome this limitation by developing a graphene encapsulated copper (G-Cu) microelectrode. The toxicity of copper is largely eliminated, as evidenced by the in vitro cell tests and in vivo histology studies. Local field potentials and single-unit spikes were recorded from rodent brains with the G-Cu microelectrodes. Notably, the G-Cu microelectrodes show no image artifacts in a 7.0 T MRI scanner, indicating minimal magnetic field distortion in their vicinity. This high MRI compatibility of our G-Cu probes would open up new opportunities for fundamental brain activity studies and clinical applications requiring continuous MRI and electrophysiological recordings.

Geochemical mass balance and elemental transport during the weathering of the black shale of Shuijingtuo formation in Northeast Chongqing, China.

An understanding of the processes that control the behavior of major elements with respect to weathering profile is essential to calculate the mobility, redistribution, and mass fluxes of elements. Hence, this study aims to determine the geochemical mass balance, strain, elemental correlation, and transport in weathering profiles. We constructed three weathering profiles for the black shale of Shujingtuo formation. As per the principal component analysis of major elements, density, and pH values, the first component represents the "elemental factor" and the second denotes the "external factor." The "depletion" pattern is a mass transportation pattern, and Na, K, and Mg are depleted along transect relative to the composition of fresh rock. Fe is redeposited at the bottom half of the saprock zone, whereas Al is accumulated at the regolith zone. The Fe and Al patterns are attributed to the "depletion-addition" and "addition" patterns, respectively. The strain in profiles A and B demonstrates the expansion at the regolith zone and part of the saprock zone. In profile C, however, these zones collapsed at all depths. In chemical weathering, Na, K, Ca, Mg, and Si are depleted in the following order: valley (C) > near mountaintop (B) > ridge (A).

Emodin improves the cardiac function in the rats with chronic heart failure through regulation of the miR-26b-5p/PTEN pathway.

Introduction: Chronic heart failure (CHF) is a leading cause of deaths induced by cardiovascular disease. This study aimed to investigate the protective effects of emodin in CHF rats and explore the related mechanisms. Material and methods: A total of 56 Wistar rats were used to construct CHF model using the coronary artery ligation. The effects of emodin on cardiac function and inflammation were analyzed in the CHF rats. Expression of miR-26b-5p in the CHF model before and after emodin treatment was estimated by quantitative real-time polymerase chain reaction. The effects of miR-26b-5p on cardiac function and inflammation were also assessed, and its target gene was predicted and confirmed in rat cardiomyocyte H9c2. Results: Emodin treatment could significant improve the cardiac function and inflammation evidenced by the increased increased ejection fraction (EF), fractional shortening (FS), left ventricular systolic pressure (LVSP) and maximum of the first differentiation of left ventricular pressure (+LV dP/dtmax) and decreased atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), left ventricular end diastolic pressure (LVEDP), interleukin (IL)-6, tumor necrosis factor α (TNF-α) levels. Expression of miR-26b-5p was downregulated in the CHF rats (CHF 0.442 ±0.131 vs. Sham 1.044 ±0.160), and this suppressive effect was rescued by emodin (Emodin 0.902 ±0.132 vs. CHF 0.442 ±0.131). The overexpression of miR-26b-5p in CHF rats led to improved cardiac function and inflammatory response. In addition, the emodin-induced increased EF, FS, LVSP and +LV dP/dtmax and decreased ANP, BNP, LVEDP, IL-6 and TNF-α were all abrogated by the knockdown of miR-26b-5p. The target prediction results revealed that PTEN was a target gene of miR-26b-5p in H9c2 cells. Conclusions: All the results indicated that emodin serves a protective role in CHF via regulation of the miR-26b-5p/PTEN pathway. Emodin may be an effective therapeutic agent for CHF treatment.