Achieving High-Performance Electrocatalytic Water Oxidation on Ni(OH)2 with Optimized Intermediate Binding Energy Enabled by S-Doping and CeO2 -Interfacing.

The adsorption energy of the reaction intermediates has a crucial influence on the electrocatalytic activity. Ni-based materials possess high oxygen evolution reaction (OER) performance in alkaline, however too strong binding of *OH and high energy barrier of the rate-determining step (RDS) severely limit their OER activity. Herein, a facile strategy is shown to fabricate novel vertical nanorod-like arrays hybrid structure with the interface contact of S-doped Ni(OH)2 and CeO2 in situ grown on Ni foam (S-Ni(OH)2 /CeO2 /NF) through a one-pot route. The alcohol molecules oxidation reaction experiments and theoretical calculations demonstrate that S-doping and CeO2 -interfacing significantly modulate the binding energies of OER intermediates toward optimal value and reduce the energy barrier of the RDS, contributing to remarkable OER activity for S-Ni(OH)2 /CeO2 /NF with an ultralow overpotential of 196 mV at 10 mA cm-2 and long-term durability over 150 h for the OER. This work offers an efficient doping and interfacing strategy to tune the binding energy of the OER intermediates for obtaining high-performance electrocatalysts.

Landscape of T cell epitopes displays hot mutations of SARS-CoV-2 variant spikes evading cellular immunity.

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been accompanied by the emergence of viral mutations that pose a great challenge to existing vaccine strategies. It is not fully understood with regard to the role of mutations on the SARS-CoV-2 spike protein from emerging viral variants in T cell immunity. In the current study, recombinant eukaryotic plasmids were constructed as DNA vaccines to express the spike protein from multiple SARS-CoV-2 strains. These DNA vaccines were used to immunize BALB/c mice, and cross-T cell responses to the spike protein from these viral strains were quantitated using interferon-γ (IFN-γ) Elispot. Peptides covering the full-length spike protein from different viral strains were used to detect epitope-specific IFN-γ+ CD4+ and CD8+ T cell responses by fluorescence-activated cell sorting. SARS-CoV-2 Delta and Omicron BA.1 strains were found to have broad T cell cross-reactivity, followed by the Beta strain. The landscapes of T cell epitopes on the spike protein demonstrated that at least 30 mutations emerging from Alpha to Omicron BA.5 can mediate the escape of T cell immunity. Omicron and its sublineages have 19 out of these 30 mutations, most of which are new, and a few are inherited from ancient circulating variants of concerns. The cross-T cell immunity between SARS-CoV-2 prototype strain and Omicron strains can be attributed to the T cell epitopes located in the N-terminal domain (181-246 aa [amino acids], 271-318 aa) and C-terminal domain (1171-1273 aa) of the spike protein. These findings provide in vivo evidence for optimizing vaccine manufacturing and immunization strategies for current or future viral variants.

Knockout of nuclear receptor HR38 gene impairs pupal-adult development in silkworm Bombyx mori.

Nuclear receptors are ligand-regulated transcription factors that play important role in regulating insect metamorphosis through the ecdysone signalling pathway. In this study, we investigated the nuclear receptor HR38 gene in Bombyx mori (BmHR38), belonging to the NR4A subfamily. BmHR38 mRNA was highly expressed in the head and epidermis at the pupal stage. The expression of the BmHR38 gene was influenced by different doses of 20E at different times. A BmHR38 deletion mutant silkworm was generated using the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system. Compared with the wild-type B. mori, the BmHR38 deletion mutant resulted in abnormal development during the pupal stage, leading to either failed eclosion or the formation of abnormal adult wings. After silencing of BmHR38 in the pupal stage, the phenotype of pupa or moth had no significant change, but it did result in reduced egg production. The mRNA levels of USP, E75 and E74 were significantly increased, while the transcript levels of FTZ-F1 were suppressed after RNA interference. Furthermore, interference with BmHR38 also inhibited the expressions of chitin metabolism genes, including Chs1, Chs2, Chi, Chi-h and CDA. Our results suggest that BmHR38 is essential for pupal development and pupa-adult metamorphosis in B. mori by regulating the expression of NRs and chitin metabolism genes.

Photophysical Studies of Helicate and Mesocate Double-Stranded Dinuclear Ru(II) Complexes.

The metal-ligand charge transfer (3MLCT) and phosphorescence-quenching metal-centered (3MC) states of the helicate and mesocate diastereoisomers of a double-stranded dinuclear polypyridylruthenium(II) complex have been investigated using ultrafast transient absorption spectroscopy. At 294 K, transient signals of the helicate decayed significantly slower than those of the mesocate, whereas at 77 K, no clear contrast in kinetics was observed. Contributions to excited-state decay from high-lying 3MLCT states were identified at both temperatures. Spectroscopic data (294 K) suggest that the 3MC state of the helicate lies above the 3MLCT and that the reverse is true for the mesocate; this was further validated by density functional theory calculations. The stabilization of the 3MC state relative to the 3MLCT state in the mesocate was explained by a reduction in ligand field strength due to distortion near the ligand bridge, which causes further deviation from octahedral geometry compared to the helicate. This work illustrates how minor structural differences can significantly influence excited state dynamics.

Microfluidization improved hempseed yogurt's physicochemical and storage properties.

BACKGROUND: Plant-based yogurts are suffering from the common problems, such as an unattractive color, stratified texture state and rough taste. Therefore, it is urgent to develop a novel processing method to improve the quality and extend the storage life of hempseed yogurt. In the present study, hempseed yogurt was microfluidized prior to fermentation. The effects of microfluidization on microstructure, particle size, mechanical properties, sensory acceptability, variations in pH and titratable acidity, lactic acid bacteria (LAB) counts, and stability of hempseed yogurt during 20 days of storage were investigated. RESULTS: Microfluidization contributed to the production of hempseed yogurt as a result of the better physicochemical properties compared to normal homogenization. Specifically, microfluidization reduced the particle size of hempseed yogurt with a uniform particle distribution, increased water holding capacity, and improved texture and rheological properties. These advancements resulted in higher sensory scores for the yogurt. Furthermore, during storage, microfluidization effectively inhibited the post-acidification process of hempseed yogurt, and increased LAB counts and storage stability. CONCLUSION: Microfluidization improved the physicochemical properties and storage stability of hempseed yogurt. Our findings support the application of microfluidization in hempseed yogurt and provide a new approach for enhancing the quality of plant-based alternatives that meet consumers' demands for high-quality food products. © 2023 Society of Chemical Industry.

Assessment of Wound-Related Pain Experiences of Patients With Chronic Wounds: A Multicenter Cross-Sectional Study in Eastern China.

PURPOSE: The primary aims of this study were to evaluate the prevalence of wound-related pain (WRP) in patients with chronic wounds and assess the use of pain relief measures. DESIGN: A cross-sectional study. SUBJECTS AND SETTING: A convenience sample of patients with chronic wounds was recruited from outpatient clinics of 12 hospitals covering 7 of 13 cities in the Jiangsu province located in eastern China from July 10 to August 25, 2020. The sample comprised 451 respondents, and their mean age was 54.85 (SD 19.16) years; 56.1% (253/451) patients were male. METHODS: An investigator-designed questionnaire was used to collect pain-related information from patients. The questionnaire consisted of 4 parts: (1) basic demographic and clinical information (patient and wound characteristics); (2) wound baseline pain; (3) wound-related procedural pain and pain relief method; and (4) the effect of WRP on the patient. Pain was assessed using the Numerical Rating Scale (NRS) scored from 0 (no pain) to 10 (worst pain). Severity of pain was based on NRS scores' classification as mild (1-3), moderate (4-6), and severe (7-10). The survey was conducted from July 10 to August 25, 2020. Participants were instructed on use of the NRS and then completed the questionnaire following dressing change independently. RESULTS: The 3 most common types of chronic wounds were traumatic ulcers, surgical wounds, and venous leg ulcers. The 3 most prevalent locations were lower limbs, feet, and thorax/abdomen. Of all patients, 62.5% (282/451) and 93.8% (423/451) patients experienced wound baseline pain and wound-related procedural pain, respectively. The mean score of wound baseline pain was 3.76 (SD 1.60) indicating moderate pain. During wound management, the highest pain score was 6.45 (SD 2.75) indicating severe pain; the most severe pain scores were associated with debridement. The use of drugs to relieve wound pain was low, while the use of nondrug-based analgesia was relatively high. Because of WRP, patients with chronic wounds feared dressing changes, hesitated to move, and showed a decline in sleep quality. CONCLUSIONS: Wound baseline pain and wound-related procedural pain were very common in patients with chronic wounds. In the future, targeted intervention plans should be developed by combining drug-based and nondrug-based analgesia according to pain severity.

Structure/function relationships of bean polysaccharides: A review.

Beans are a rich source of high quality protein and oil, and have attracted increasing interest from both nutrition researchers and health-conscious consumers. This review aims to provide a foundation for the future research and development of bean polysaccharides, by summarizing the sources, structure, and functions of bioactive bean polysaccharides. Structure/function relationships are described, for biological activities, such as immunological, antioxidant and anti-diabetes. This will provide useful guidance for further optimization of polysaccharide structure and the development of bean polysaccharides as a novel functional material.

Exploring the Complexities of Dissolved Organic Matter Photochemistry from the Molecular Level by Using Machine Learning Approaches.

Dissolved organic matter (DOM) sustains a substantial part of the organic matter transported seaward, where photochemical reactions significantly affect its transformation and fate. The irradiation experiments can provide valuable information on the photochemical reactivity (photolabile, photoresistant, and photoproduct) of molecules. However, the inconsistency of the fate of irradiated molecules among different experiments curtailed our understanding of the roles the photochemical reactions have played, which cannot be properly addressed by traditional approaches. Here, we conducted irradiation experiments for samples from two large estuaries in China. Molecules that occurred in irradiation experiments were characterized by the Fourier transform ion cyclotron resonance mass spectrometry and assigned probabilistic labels to define their photochemical reactivity. These molecules with probabilistic labels were used to construct a learning database for establishing a suitable machine learning (ML) model. We further applied our well-trained ML model to "un-matched" (i.e., not detected in our irradiation experiments) molecules from five estuaries worldwide, to predict their photochemical reactivity. Results showed that numerous molecules with strong photolability can be captured solely by the ML model. Moreover, comparing DOM photochemical reactivity in five estuaries revealed that the riverine DOM chemistry largely determines their subsequent photochemical transformation. We offer an expandable and renewable approach based on ML to compatibly integrate existing irradiation experiments and shed insight into DOM transformation and degradation processes.

Effect of Panax quinquefolius extract on Mycobacterium abscessus biofilm formation.

Mycobacterium abscessus (M. abscessus) can exist either as planktonic bacteria or as a biofilm. Biofilm formation is one of the important causes of conversion to resistance to antibiotics of bacteria that were previously sensitive when in their planktonic form, resulting in infections difficult to manage. Panax quinquefolius and its active ingredient ginsenosides have the potential ability in fighting pathogenic infections. In this study, the P. quinquefolius extract (PQE) showed good antibacterial/bactericidal activity against the M. abscessus planktonic cells. The extract reduced the biomass, thickness, and number of M. abscessus in the biofilm and altered its morphological characteristics as well as the spatial distribution of dead/alive bacteria. Moreover, the ginsenoside CK monomer had a similar inhibitory effect on M. abscessus planktonic bacteria and biofilm formation. Therefore, PQE and its monomer CK might be potential novel antimicrobial agents for the clinical prevention and treatment of M. abscessus, including biofilms in chronic infections.

BRT: An Efficient and Scalable Blockchain-Based Revocation Transparency System for TLS Connections.

Log-based public key infrastructure(PKI) refers to a robust class of CA-attack-resilient PKI that enhance transparency and accountability in the certificate revocation and issuance process by compelling certificate authorities (CAs) to submit revocations to publicly and verifiably accessible logs. However, log-based PKIs suffer from a reliance on centralized and consistent sources of information, rendering them susceptible to split-world attacks, and they regrettably fail to provide adequate incentives for recording or monitoring CA behavior. Blockchain-based PKIs address these limitations by enabling decentralized log audits through automated financial incentives. However, they continue to face challenges in developing a scalable revocation mechanism suited for lightweight clients. In this paper, we introduce BRT, a scalable blockchain-based system for certificate and revocation transparency. It serves to log, audit, and validate the status of certificates within the transport layer security (TLS)/secure sockets layer(SSL) PKI domain. We designed an audit-on-chain framework, coupled with an off-chain storage/computation system, to enhance the efficiency of BRT when operating in a blockchain environment. By implementing a blockchain-based prototype, we demonstrate that BRT achieves storage-efficient log recording with a peak compression rate reaching 8%, cost-effective log updates for large-scale certificates, and near-instantaneous revocation checks for users.

Defatted hempseed meal altered the metabolic profile of fermented yogurt and enhanced the ability to alleviate constipation in rats.

BACKGROUND: Hempseeds (Cannabis sativa L.) are rich in easily digestible proteins, fats, polyunsaturated fatty acids, and insoluble fiber and are of high nutritional value. Probiotics have been found to relieve constipation, which solves a health problem that constantly troubles a lot of people. Therefore, the changes in the metabolites of fermented yogurt with or without 10% defatted hempseed meal (10% SHY or 0% SHY respectively) were studied and their laxative effects were examined through animal experiments. RESULTS: Amino acids and peptides, terpene glycosides, carbohydrates, lineolic acids, and fatty acids were found to be the major contributors to the discrimination of the metabolic profile between 0% SHY and 10% SHY. The differentially accumulated metabolites may lead to the discrepancy in the yogurt's functionality. Animal experiments showed that the 10% SHY treatment prevented constipation by increasing feces number, fecal water content, and small intestinal transit rate and reducing inflammatory injury in loperamide-induced constipated rats. Further analysis of the gut microbiota revealed that 10% SHY gavage increased the relative abundances of the Lactobacillus, Allobaculum, Turicibacter, Oscillibacter, Ruminococcus, and Phascolarctobacterium genera in the constipated rats, whereas Akkermansia, Clostridium_XIVa, Bacteroides, Staphylococcus, and Clostridium_IV were decreased. The combination of defatted hempseed meal and probiotics was found to be effective in relieving constipation, probably due to the enriched amino acids and peptides, such as Thr-Leu and lysinoalanine through correlation analysis. CONCLUSION: Our findings indicated that defatted hempseed meal in yogurt altered the metabolic profile and effectively alleviated constipation in rats, which is a promising therapeutic candidate for constipation. © 2023 Society of Chemical Industry.

Functional analysis of nuclear receptor HR96 gene in Bombyx mori exposed to phoxim.

The nuclear receptor (NRs) gene family functions as ligand-dependent transcription factors in a variety of animals, which participates in a variety of biological processes, such as cell differentiation, metabolic regulation, reproduction, development, insect metamorphosis. In this study, a nuclear receptor HR96 gene in silkworm Bombyx mori (BmHR96) was identified, and the responses of BmHR96 gene to 20-hydroxyecdysone (20E), three insecticides, and two disinfectants were analyzed and its function in phoxim exposure was explored.  Quantitative real-time polymerase chain reaction indicated that the expression of BmHR96 mRNA was the highest in ovary of 5th instar Day 3 silkworm larvae and in silk gland of the wandering stage. The expression patterns of BmHR96 gene in ovary, head, testis, and midgut of different stages were different. After injecting 20E into B. mori, the expression of BmHR96 mRNA had no significant difference compared with control. Three insecticides and two disinfectants were used to treat B. mori, respectively, and it was found that they had different influence patterns on the expression level of BmHR96. siRNA of BmHR96 was injected into silkworm larvae and the expression of BmHR96 was decreased significantly after injecting 72 h. After silencing of BmHR96, B. mori was fed with phoxim-treated leaves. The results showed that the mortality of B. mori after silencing of BmHR96 was significantly higher than the control. Our results indicated that HR96 plays an important role in regulating the stress response of phoxim.

Liddle syndrome misdiagnosed as primary aldosteronism is caused by inaccurate aldosterone-rennin detection while a novel SCNN1G mutation is discovered.

PURPOSE: Through describing the confusing misdiagnosis process of Liddle syndrome, we try to reveal the importance of accurate aldosterone-renin detection and a genetic test for Liddle syndrome. METHODS: We found a family of hypertension and hypokalaemia with the proband of a 21-year-old female who had been misdiagnosed as primary aldosteronism (PA). She presented with high aldosterone and low renin levels. Aldosterone is not suppressed in the saline infusion test and captopril challenge test. However, treatment with a standard dose of spironolactone has no blood pressure improvement effect. A heterozygous variant of SCNN1G was found with whole exome sequencing and Liddle syndrome is indicated. Treatment with amiloride was effective. We rechecked aldosterone-renin levels with two different aldosterone and renin test kits. Clinical features and the mutant gene SCNN1G of each family member were determined by the Sanger method. RESULTS: The two kits had nearly opposite results. Among those Liddle syndrome patients confirmed by a genetic test, for Test kit A all ARR were screened positive while for test kit B negative. It seems Test kit B is consistent with the diagnosis while test kit A misleads the diagnosis. A novel SCNN1G mutation, c.1729 C > T, was found in this family, which introduce a premature stop codon in the γ subunit in the epithelial Na+ channel (ENaC) and resulted in a deletion of 72 amino acids at the carboxyl end. CONCLUSION: inaccurate ARR detection might misdiagnose Liddle syndrome. A Gene test is an important method for the diagnosis of Liddle syndrome. A novel SCNN1G missense mutation, c.1729 C > T, is found in a Chinese family.

Elevated AST/ALT ratio is associated with all-cause mortality and cancer incident.

BACKGROUND: The aspartate transaminase (AST)-to-alanine aminotransferase (ALT) ratio, which is used to measure liver injury, has been found to be associated with some chronic diseases and mortality. However, its relevance to cancer incidence resulting from population-based prospective studies has rarely been reported. In this study, we investigated the correlation of the AST/ALT ratio as a possible predictor of mortality and cancer incidence. METHODS: A total of 9,946 participants fulfilled the inclusion criteria for a basic public health service project of the Health Checkup Program conducted by the BaiYun Community Health Service Center, Taizhou. Deceased participants and cancer incident cases were from The Taizhou Chronic Disease Information Management System. Odds ratios (ORs) and interval of quartile range (IQR) computed by logistic regression analysis and cumulative incidence rate were calculated by the Kaplan-Meier survival method and compared with log-rank test statistics. RESULTS: Serum ALT and AST levels were both increased in patients with chronic diseases, but the ratio of AST/ALT was generally decreased. The cancer incident cases (488 new cases) had a greater baseline ratio (median =1.23, IQR: 0.96-1.54) than noncancer cases (median =1.15, IQR: 0.91-1.44). Compared to the first quartile of the AST/ALT ratio, the population in the top quartile had a higher cumulative cancer incidence rate (7.54% vs. 4.44%) during follow-up period. Furthermore, an elevated AST/ALT ratio increased the risk of all-cause mortality. CONCLUSIONS: The ratio of AST/ALT is a potential biomarker to assess healthy conditions and long-term mortality. Especially for cancer, the AST/ALT ratio not only increases at baseline but also predicts the future development of cancer. The clinical value and potential mechanism deserve further research.

Mechanochemical Divergent Syntheses of Oxindoles and α-Arylacylamides via Controllable Construction of C-C and C-N Bonds by Copper and Piezoelectric Materials.

Herein, we present the divergent syntheses of α-arylacylamides and oxindoles via mechanoredox chemistry by using easily accessible α-bromo N-sulfonyl amides as starting materials. Our system consists of a catalytic amount of CuII precatalyst and piezoelectric materials. The highly polarized BaTiO3 or PbTiO3 under mechanical agitation can act as an electron donor to realize the recycling of CuII and CuI . Control experiments and density functional theory calculations have been performed to support the proposed mechanistic rationale for the cascade reactions.

Lithography-free synthesis of periodic, vertically-aligned, multi-walled carbon nanotube arrays.

Until now, the growth of periodic vertically aligned multi-walled carbon nanotube (VA-MWCNT) arrays was dependent on at least one lithography step during fabrication. Here, we demonstrate a lithography-free fabrication method to grow hexagonal arrays of self-standing VA-MWCNTs with tunable pitch and MWCNT size. The MWCNTs are synthesized by plasma enhanced chemical vapor deposition (PECVD) from Ni catalyst particles. Template guided dewetting of a thin Ni film on a hexagonally close-packed silica particle monolayer provides periodically distributed Ni catalyst particles as seeds for the growth of the periodic MWCNT arrays. The diameter of the silica particles directly controls the pitch of the periodic VA-MWCNT arrays from 600 nm to as small as 160 nm. The diameter and length of the individual MWCNTs can also be readily adjusted and are a function of the Ni particle size and PECVD time. This unique method of lithography-free growth of periodic VA-MWCNT arrays can be utilized for the fabrication of large-scale biomimetic materials.

LBBAP in patients with normal intrinsic QRS duration: Electrical and mechanical characteristics.

BACKGROUND: Left bundle branch area pacing (LBBAP) is an innovative pacing technology, which needs further study. METHODS: Seventy LBBAP patients with intrinsic QRS duration (QRSd) less than 120 ms were consecutively enrolled in our center. According to whether the left bundle branch potential (LBBp) was recorded or not, the patients were divided into the potential positive group (LBBAP+) and the potential negative group (LBBAP-). Electrocardiographic and echocardiographic parameters were used to evaluate electrical and mechanical characteristics. Lead parameters and complications were followed-up. RESULTS: There were 52 patients in LBBAP+ and 18 patients in LBBAP-. The QRSd and the left ventricular activation time (LVAT) were wider after LBBAP. QRSd showed no significant difference between LBBAP+ and LBBAP-. LVAT was significantly shorter in LBBAP+ than in LBBAP-. Frontal QRS axis shifted leftward and the V1 morphologies changed after LBBAP. QRS axis and V1 morphologies showed no significant differences between two groups. Paced R-wave transition moved forward compared with intrinsic R-wave transition in both groups. Peak systolic strain of left ventricle (LVPSS) increased, and peak systolic dispersion of left ventricle (LVPSD) did not change significantly after LBBAP. Systolic and diastolic function as well as mechanical synchronism had no significant differences between two groups. LBBAP had great pacing parameters. CONCLUSION: LBBAP changes electrical and mechanical characteristics and has good safety in patients with normal intrinsic QRSd. LBBAP+ and LBBAP- show no significant differences in mechanical synchronization and interventricular electrical synchronization. The LBBAP+ shows better left ventricular electrical synchronicity.

CD13 Induces Autophagy to Promote Hepatocellular Carcinoma Cell Chemoresistance Through the P38/Hsp27/CREB/ATG7 Pathway.

The chemoresistance of hepatocellular carcinoma (HCC) is a serious problem that directly hinders the effect of chemotherapeutic agents. We previously reported that Aminopeptidase N (CD13) inhibition can enhance the cytotoxic efficacy of chemotherapy agents. In the present study, we use liver cancer cells to explore the molecular mechanism accounting for the relationship between CD13 and chemoresistance. We demonstrate that CD13 overexpression activates the P38/heat shock protein 27/cAMP response element-binding protein (CREB) signaling pathway to limit the efficacy of cytotoxic agents. Moreover, blockade of P38 or CREB sensitizes HCC cells to 5-fluorouracil. Then we reveal that CREB binds to the autophagy related 7 (ATG7) promoter to induce autophagy and promote HCC cell chemoresistance. CD13 inhibition also downregulates the expression of ATG7, autophagy, and tumor cell growth in vivo. Overall, the combination a CD13 inhibitor and chemotherapeutic agents may be a potential strategy for overcoming drug resistance in HCC. SIGNIFICANCE STATEMENT: Our study demonstrates that Aminopeptidase N (CD13) promotes hepatocellular carcinoma (HCC) cell chemoresistance via the P38/heat shock protein 27/cAMP response element-binding protein (CREB) pathway. CREB regulates autophagy related 7 transcription and expression to induce autophagy. Our results collectively suggest that CD13 may serve as a potential target for overcoming HCC resistance.

M2 Macrophages Enhance the Cementoblastic Differentiation of Periodontal Ligament Stem Cells via the Akt and JNK Pathways.

Although macrophage (Mφ) polarization has been demonstrated to play crucial roles in cellular osteogenesis across the cascade of events in periodontal regeneration, how polarized Mφ phenotypes influence the cementoblastic differentiation of periodontal ligament stem cells (PDLSCs) remains unknown. In the present study, human monocyte leukemic cells (THP-1) were induced into M0, M1, and M2 subsets, and the influences of these polarized Mφs on the cementoblastic differentiation of PDLSCs were assessed in both conditioned medium-based and Transwell-based coculture systems. Furthermore, the potential pathways and cyto-/chemokines involved in Mφ-mediated cementoblastic differentiation were screened and identified. In both systems, M2 subsets increased cementoblastic differentiation-related gene/protein expression levels in cocultured PDLSCs, induced more PDLSCs to differentiate into polygonal and square cells, and enhanced alkaline phosphatase activity in PDLSCs. Furthermore, Akt and c-Jun N-terminal Kinase (JNK) signaling was identified as a potential pathway involved in M2 Mφ-enhanced PDLSC cementoblastic differentiation, and cyto-/chemokines (interleukin (IL)-10 and vascular endothelial growth factor [VEGF]) secreted by M2 Mφs were found to be key players that promoted cell cementoblastic differentiation by activating Akt signaling. Our data indicate for the first time that Mφs are key modulators during PDLSC cementoblastic differentiation and are hence very important for the regeneration of multiple periodontal tissues, including the cementum. Although the Akt and JNK pathways are involved in M2 Mφ-enhanced cementoblastic differentiation, only the Akt pathway can be activated via a cyto-/chemokine-associated mechanism, suggesting that players other than cyto-/chemokines also participate in the M2-mediated cementoblastic differentiation of PDLSCs. Stem Cells 2019;37:1567-1580.

Ghrelin protects against obesity-induced myocardial injury by regulating the lncRNA H19/miR-29a/IGF-1 signalling axis.

BACKGROUND: Obesity is associated with the impairment of cardiac fitness and consequent ventricular dysfunction and heart failure. Ghrelin has been largely documented to be cardioprotective against ischaemia/reperfusion injury. However, the role of ghrelin in obesity-induced myocardial injury is largely unknown. This study sought to determine the cardiac effect of ghrelin against obesity-induced injury and the underlying mechanisms. METHODS: The effect of ghrelin was evaluated in a mouse model of obesity and a palmitic acid (PA)-treated cardiomyocyte cell line with or without ghrelin transfection. Gene and protein expression levels were determined by real-time PCR and western blot, respectively. Cell apoptosis was measured by flow cytometry analysis. RESULTS: In the present study, we found that both a high-fat diet (HFD) and PA treatment caused myocardial injury by increasing apoptosis and the expression of inflammatory cytokines. Overexpression of ghrelin reversed the effects induced by HFD or PA treatment. Knockdown of lncRNA H19 or overexpression of miR-29a abrogated the cardioprotective effects of ghrelin against apoptosis and inflammation. We also found that IGF-1 was a target gene of miR-29a and that H19 regulated IGF-1 expression via miR-29a. Overexpression of IGF-1 partially reversed the apoptosis and inflammation promoting effects of miR-29a. CONCLUSIONS: Our findings suggested that ghrelin protected against obesity-induced myocardial injury by regulating the H19/miR-29a/IGF-1 signalling axis, providing further evidence for the clinical application of ghrelin.