Observation and quantification of the pseudogap in unitary Fermi gases.

The microscopic origin of high-temperature superconductivity in cuprates remains unknown. It is widely believed that substantial progress could be achieved by better understanding of the pseudogap phase, a normal non-superconducting state of cuprates1,2. In particular, a central issue is whether the pseudogap could originate from strong pairing fluctuations3. Unitary Fermi gases4,5, in which the pseudogap-if it exists-necessarily arises from many-body pairing, offer ideal quantum simulators to address this question. Here we report the observation of a pair-fluctuation-driven pseudogap in homogeneous unitary Fermi gases of lithium-6 atoms, by precisely measuring the fermion spectral function through momentum-resolved microwave spectroscopy and without spurious effects from final-state interactions. The temperature dependence of the pairing gap, inverse pair lifetime and single-particle scattering rate are quantitatively determined by analysing the spectra. We find a large pseudogap above the superfluid transition temperature. The inverse pair lifetime exhibits a thermally activated exponential behaviour, uncovering the microscopic virtual pair breaking and recombination mechanism. The obtained large, temperature-independent single-particle scattering rate is comparable with that set by the Planckian limit6. Our findings quantitatively characterize the pseudogap in strongly interacting Fermi gases and they lend support for the role of preformed pairing as a precursor to superfluidity.

Ultrasensitive Electrochemiluminescence Biosensor to Detect Ampicillin Resistance Gene (ARGAMP) Based on a Novel Near-Infrared Ruthenium Carbene Complex/TPrA/PEI Ternary ECL System.

The establishment of rapid target identification and analysis methods for antibiotic resistance genes (ARGs) is urgently needed. In this study, we unprecedently designed a target-catalyzed hairpin assembly (CHA) electrochemiluminescent (ECL) biosensor for the ultrasensitive detection of ampicillin resistance genes (ARGAMP) based on a novel, efficient near-infrared ruthenium carbene complex/TPrA/PEI ternary ECL system with low oxidation potential. The ternary NIR-ECL system illustrated in this work displayed double ECL intensity in comparison with their corresponding traditional binary ECL system. The as-prepared ECL biosensor illustrated in this work demonstrates highly selective and sensitive determination of ARGAMP from 1 fM to 1 nM and a low detection limit of 0.23 fM. Importantly, it also exhibits good accuracy and stabilities to identify ARGAMP in plasmid and bacterial genome DNA, which demonstrates its excellent reliability and great potential in detecting ARGAMP in real environmental samples.

Bis-tridentate Iridium(III) Complex with the N-Heterocyclic Carbene Ligand as a Novel Efficient Electrochemiluminescence Emitter for the Sandwich Immunoassay of the HHV-6A Virus.

Human herpesvirus type 6A (HHV-6A) can cause a series of immune and neurological diseases, and the establishment of a sensitive biosensor for the rapid detection of HHV-6A is of great significance for public health and safety. Herein, a bis-tridentate iridium complex (BisLT-Ir-NHC) comprising the N-heterocyclic carbene (NHC) ligand as a novel kind of efficient ECL luminophore has been unprecedently reported. Based on its excellent ECL properties, a new sensitive ECL-based sandwich immunosensor to detect the HHV-6A virus was successfully constructed by encapsulating BisLT-Ir-NHC into silica nanoparticles and embellishing ECL sensing interface with MXene@Au-CS. Notably, the immunosensor illustrated in this work not only had a wide linear range of 102 to 107 cps/µL but also showed outstanding recoveries (98.33-105.11%) in real human serum with an RSD of 0.85-3.56%. Undoubtedly, these results demonstrated the significant potential of the bis-tridentate iridium(III) complex containing an NHC ligand in developing ECL-based sensitive analytical methods for virus detection and exploring novel kinds of efficient iridium-based ECL luminophores in the future.

Social support, attitudes toward own aging, loneliness and psychological distress among older Chinese adults: a longitudinal mediation model.

The current study aimed to explore the protective factors and underlying mechanisms associated with loneliness and psychological distress among older Chinese adults within the framework of a longitudinal design. This investigation specifically focused on the mediating role of attitudes toward own aging (ATOA) in the relationship between social support and the experience of loneliness and psychological distress (comprising depression, anxiety, and stress) amidst the backdrop of the COVID-19 pandemic. A cohort of 345 elderly individuals (mean age = 83.84 years, standard deviation = 8.49 years; 55.1% females) participated in this research endeavor. The participants were required to complete self-report instruments measuring their perceived levels of social support at Time 1 (T1), attitudes towards own aging, ATOA at Time 2 (T2), and their experiences of loneliness, and psychological distress (including depression, anxiety, and stress) at T1 and Time 3 (T3). The data collection timeline encompassed baseline data collection at T1 in September 2020, a subsequent six-month follow-up at T2 in March 2021, and a one-year follow up at T3 in September 2021. The findings of this investigation unveiled a negative predictive relationship between social support at T1 and psychological distress (encompassing depression, anxiety, and stress) at T3. Furthermore, it was discerned that ATOA at T2 acted as a mediating mechanism, elucidating the longitudinal association between social support at T1 and the manifestation of loneliness and psychological distress (including depression, anxiety, and stress) at T3. The discussion section of this paper delves into an exploration of the limitations and implications inherent in these conclusions, particularly concerning their relevance to potential intervention strategies.

Obacunone, a Promising Phytochemical Triterpenoid: Research Progress on Its Pharmacological Activity and Mechanism.

Obacunone, a natural triterpenoid, is an active component of the herbs Dictamnus dasycarpus Turcz. and Phellodendron amurense Rupr, and an indicator of the herbs' quality. Owing to its multiple health benefits, several studies have investigated the multi-targeting potential action mechanisms of obacunone. To summarize recent developments on the pharmacological actions of obacunone and focus on the underlying molecular mechanisms and signaling networks, we searched PubMed, Europe PMC, Wiley Online Library, Web of Science, Google Scholar, Wanfang Medical Network, and China National Knowledge Infrastructure for articles published prior to March 2024. Existing research indicates obacunone has great potential to become a promising therapeutic option against tumors, fibrotic diseases, bone and cholesterol metabolism diseases, and infections of pathogenic microorganisms, among others. The paper contributes to providing up-to-date references for further research and clinical applications of obacunone.

Role of ventrolateral part of ventromedial hypothalamus in post-myocardial infarction cardiac dysfunction induced by sympathetic nervous system.

Psychological stress has been recognized as a contributing factor to worsened prognosis in patients with cardiac failure following myocardial infarction (MI). Although the ventrolateral part of the ventromedial hypothalamus (VMHVL) has been implicated in emotional distress, its involvement in post-MI cardiac dysfunction remains largely unexplored. This study was designed to investigate the effect of the VMHVL activation in the MI rat model and its underlying mechanisms. Our findings demonstrate that activation of VMHVL neurons enhances the activity of the cardiac sympathetic nervous system through the paraventricular nucleus (PVN) and superior cervical ganglion (SCG). This activation leads to an elevation in catecholamine levels, which subsequently modulates myosin function and triggers the release of anti-inflammatory factors, to exacerbate the post-MI cardiac prognosis. The denervation of the superior cervical ganglion (SGN) effectively blocked the cardiac sympathetic effects induced by the VMHVL activation, and ameliorated the cardia fibrosis and dysfunction. Therefore, our study identified the role of the "VMHVL-PVN-SCG" sympathetic pathway in the post-MI heart, and proposed SGN as a promising strategy in mitigating cardiac prognosis in stressful rats.

Novel Electrochemiluminescent Biosensor to Ultrasensitively Detect U94 Gene in Human Herpesvirus 6 Using Metal-Organic Framework-Based Nanoemitters Comprising Iridium(III) Complexes via One-Pot Coordination Reaction Strategy.

The detection of the U94 gene in human herpesvirus 6 is crucial for early diagnosis of HHV-6 infections, which could induce acute febrile illness in infants. In this work, the first ultrasensitive electrochemiluminescence (ECL) biosensor for detecting U94 gene in Human Herpesvirus 6 was successfully designed by utilizing efficient novel metal-organic framework (MOF)-based ECL nanoemitters comprising iridium(III) complexes (Ir-ZIF-8-NH2) synthesized via one-pot coordination reaction strategy as an ECL indicator and a target-catalyzed hairpin assembly (CHA) signal amplification strategy. The as-prepared ECL indicator Ir-ZIF-8-NH2 exhibited an approximately 2.7-fold ECL intensity compared with its small molecular analogue of emissive iridium(III) complex named IrppymIM formed by in situ coordination reaction between iridium(III) solvent complex and imidazole ligands. In addition, a target-catalyzed hairpin assembly (CHA) strategy was employed to further improve the sensitivity of the proposed ECL biosensor, which demonstrated a wide linear range from 1 fM to 1 µM and the limit of detection as low as 0.113 fM (S/N = 3). Significantly, this biosensor was successfully applied to detect U94 gene in plasmids and real virus samples. The recoveries were in the range of 97.0-109.0% for plasmids and 95.7-107.5% for real virus samples with a relative standard deviation (RSD) of 1.87-2.53%. These satisfactory experimental results from the proposed ECL biosensor in this work would inevitably promote the development of new time/cost-effective and sensitive methods to detect HHV-6 with a major global health threat and substantial burden on healthcare in the future.

Phylogeny and adaptive evolution of subgenus Rhizirideum (Amaryllidaceae, Allium) based on plastid genomes.

The subgenus Rhizirideum in the genus Allium consists of 38 species worldwide and forms five sections (A. sect. Rhizomatosa, A. sect. Tenuissima, A. sect. Rhizirideum, A. sect. Eduardia, and A. sect. Caespitosoprason), A. sect. Caespitosoprason being merged into A. sect. Rhizomatosa recently. Previous studies on this subgenus mainly focused on separate sections. To investigate the inter-section and inter-subgenera phylogenetic relationships and adaptive evolution of A. subg. Rhizirideum, we selected thirteen representative species, which cover five sections of this subgenus and can represent four typical phenotypes of it. We conducted the comparative plastome analysis with our thirteen plastomes. And phylogenetic inferences with CDSs and complete sequences of plastomes of our thirteen species and another fifty-four related species were also performed. As a result, the A. subg. Rhizirideum plastomes were relatively conservative in structure, IR/SC borders, codon usage, and repeat sequence. In phylogenetic results, the inter-subgenera relationships among A. subg. Rhizirideum and other genus Allium subgenera were generally similar to the previous reports. In contrast, the inter-section relationships within our subgenus A. subg. Rhizirideum were newly resolved in this study. A. sect. Rhizomatosa and A. sect. Tenuissima were sister branches, which were then clustered with A. sect. Rhizirideum and A. sect. Eduardia successively. However, Allium Polyrhizum Turcz. ex Regel, type species of A. sect. Caespitosoprason, was resolved as the basal taxon of A. subg. Rhizirideum. Allium siphonanthum J. M. Xu was also found in clade A. subg. Cyathophora instead of clade A. subg. Rhizirideum. The selective pressure analysis was also conducted, and most protein-coding genes were under purifying selection. At the same time, just one gene, ycf2, was found under positive selection, and another three genes (rbcL, ycf1a, ycf1b) presented relaxed selection, which were all involved in the photosynthesis. The low temperature, dry climate, and high altitude of the extreme habitats where A. subg. Rhizirideum species grow might impose intense natural selection forces on their plastome genes for photosynthesis. In summary, our research provides new insights into the phylogeny and adaptive evolution of A. subg. Rhizirideum. Moreover, we suggest that the positions of the A. subg. Rhizirideum species A. polyrhizum and A. siphonanthum should be reconsidered.

Antifouling Slippery Surface against Marine Biofouling.

Titanium and its alloys have become the most excellent structure materials for naval seawater pipelines due to their high strength and good corrosion resistance. However, marine biofouling poses a serious threat to titanium alloy piping systems because of their good biocompatibility. Recently, the biomimetic antifouling coating, a novel antifouling method, has received great attention. Here, based on this biomimetic idea, we develop a nontoxic antifouling slippery surface (AFSS) using silicone oil, silane coupling agent, nanosilica, nanoceramic coating, epoxy resin, and capsaicin. The developed AFSS has excellent slippery performance for various droplets, good durability, and a superior self-cleaning property. Additionally, the antifouling performance of the AFSS was significantly enhanced, as confirmed by the reduced adhesion of proteins (70.7%), bacteria (97.2%), and algae (97.7%) compared to the ordinary titanium alloy. With these excellent properties, the AFSS was expected to be a promising candidate for protecting titanium alloy piping systems from marine biofouling.

Antiadhesion Superhydrophobic Bipolar Electrocoagulation Tweezers with High Conductivity and Stability.

Irregularly shaped electrosurgical devices face significant challenges in electrosurgery due to serious blood and tissue adhesion. Superhydrophobic surfaces inspired by lotus leaves have attracted great attention for their promising antiadhesion properties. However, there are few methods for efficiently preparing superhydrophobic irregularly shaped bipolar electrocoagulation tweezers (BETs). Herein, we propose a simple and environmentally friendly method to fabricate antiadhesion superhydrophobic surfaces on BETs. The superhydrophobicity is obtained by combining laser texturing to form rough structures and low surface energy modification via stearic acid. The formation mechanism of superhydrophobicity is investigated through analyzing microstructures and chemical compositions by scanning electron microscopy, white-light interferometry, and X-ray photoelectron spectroscopy. The functionalized BET surfaces exhibit excellent water repellency with a contact angle of 159.6°, a roll-off angle of 1°, and a surface energy of 14.3 mJ/m2, possessing excellent antiadhesion properties against blood, chicken breast tissue, and pork tissue. Compared with ordinary BETs, the mass of blood, pork tissue, and chicken breast tissue adhered to the superhydrophobic BET is reduced by 97.70, 70.34, and 75.35%, respectively. Moreover, the superhydrophobic BETs have excellent conductivity and maintain good antiadhesion properties after low-temperature storage for 2 weeks, after being impacted by sand and blood and 30 cycles of tape peeling tests. With outstanding antiadhesion performance, the superhydrophobic BET may have promising application prospects in the electrosurgery field.

Increased sympathetic outflow induced by emotional stress aggravates myocardial ischemia-reperfusion injury via activation of TLR7/MyD88/IRF5 signaling pathway.

BACKGROUND AND OBJECTIVE: Emotional stress substantially increases the risk of ischemic cardiovascular diseases. Previous study indicates that sympathetic outflow is increased under emotional stress. We aim to investigate the role of increased sympathetic outflow induced by emotional stress in myocardial ischemia-reperfusion (I/R) injury, and explore the underlying mechanisms. METHODS AND RESULTS: We used Designer Receptors Exclusively Activated by Designer Drugs technique to activate the ventromedial hypothalamus (VMH), a critical emotion-related nucleus. The results revealed that emotional stress stimulated by VMH activation increased sympathetic outflow, enhanced blood pressure, aggravated myocardial I/R injury, and exacerbated infarct size. The RNA-seq and molecular detection demonstrated that toll-like receptor 7 (TLR7), myeloid differentiation factor 88 (MyD88), interferon regulatory factor 5 (IRF5), and downstream inflammatory markers in cardiomyocytes were significantly upregulated. Emotional stress-induced sympathetic outflow further exacerbated the disorder of the TLR7/MyD88/IRF5 inflammatory signaling pathway. While inhibition of the signaling pathway partially alleviated myocardial I/R injury aggravated by emotional stress-induced sympathetic outflow. CONCLUSION: Increased sympathetic outflow induced by emotional stress activates TLR7/MyD88/IRF5 signaling pathway, ultimately aggravating I/R injury.

Singlet Oxygen Generation via an Electrochemical Reduction Method Assisted by a Ruthenium(II) Complex.

In this work, singlet oxygen (1O2) is unprecedently recorded in the electrochemical reduction of tris(2,2'-bipyridine)ruthenium(II) [Ru(bpy)32+] in an acetonitrile solution with dissolved oxygen, which is well characterized by the specific probe of Singlet Oxygen Sensor Greens and the technique of electron-spin resonance in this work. Importantly, this new electrochemical method to produce 1O2 shows higher efficiency than the conventional photodriven method. Furthermore, taken together with the inherent advantages of electrochemical techniques compared with the photochemical/chemical-driven method, this electrochemical method would inevitably show great promise in reactive-oxygen-species-related studies in the future.

Identification and characterization of microRNAs, especially gga-miR-181b-5p, in chicken macrophages associated with avian pathogenic E. coli infection.

Avian pathogenic E. coli (APEC) is a common pathogen in the poultry industry, which can cause substantial economic losses. Recently, emerging evidence showed that miRNAs were involved in various viral and bacterial infections. To elucidate the role of miRNAs in chicken macrophages in response to APEC infection, we attempted to investigate the miRNAs expression pattern upon APEC infection via miRNA-seq, and to identify the molecular mechanism of the important miRNAs by using RT-qPCR, western blotting, dual-luciferase reporter assay, and CCK-8. The results showed that a total of 80 differentially expressed (DE) miRNAs were identified in comparison of APEC vs. wild-type group, which corresponded to 724 target genes. Moreover, the target genes of the identified DE miRNAs were mainly significantly enriched in the MAPK signalling pathway, autophagy-bird, mTOR signalling pathway, ErbB signalling pathway, Wnt signalling pathway, and TGF-beta signalling pathway. Remarkably, gga-miR-181b-5p is able to participate in host immune and inflammatory responses against APEC infection via targeting of TGFBR1 to modulate the activation of TGF-beta signalling pathway. Collectively, this study provides a perspective of miRNA expression patterns in chicken macrophages upon APEC infection. These findings provide insight into miRNAs against APEC infection, and gga-miR-181b-5p might be a potential target for treating APEC infection.

Biosynthesis of diisooctyl 2,5-furandicarboxylate by Candida antarctica lipase B (CALB) immobilized on a macroporous epoxy resin.

Diisooctyl 2,5-furandicarboxylate (DEF), an ester derivative of 2,5-furandicarboxylic acid (FDCA, a bio-based platform chemical), resembles the physical and chemical properties of phthalates. Due to its excellent biodegradability, DEF is considered a safer alternative to the hazardous phthalate plasticizers. Although FDCA esters are currently mainly produced by chemical synthesis, the enzymatic synthesis of DEF is a green, promising alternative. The current study investigated the biosynthesis of DEF by Candida antarctica lipase B (CALB) immobilized on macroporous resins. Out of five macroporous resins (NKA-9, LX-1000EP, LX-1000HA, XAD-7HP, and XAD-8) evaluated, the LX-1000EP epoxy resin was identified as the best carrier for CALB, and the XAD-7HP weakly polar resin was identified as the second best. The optimal immobilization conditions were as follows: CALB (500 µL) and LX-1000EP (0.1 g) were incubated in phosphate butter (20 mM, pH 6.0) for 10 h at 35°C. The resulting immobilized CALB (EP-CALB) showed an activity of 639 U/g in the hydrolysis of p-nitrophenyl acetate, with an immobilization efficiency of 87.8% and an activity recovery rate of 56.4%. Using 0.02 g EP-CALB as the catalyst in 10 mL toluene, and the molar ratio of 2,5-dimethyl furanediformate (1 mmol/mL) and isooctyl alcohol (4 mmol/mL) that was 1:4, a DEF conversion rate of 91.3% was achieved after a 24-h incubation at 50°C. EP-CALB had similar thermal stability and organic solvent tolerance compared to Novozym 435, and both were superior to CALB immobilized on the XAD-7HP resin. EP-CALB also exhibited excellent operational stability, with a conversion rate of 52.6% after 10 repeated uses. EP-CALB could be a promising alternative to Novozym 435 in the biomanufacturing of green and safe plasticizers such as DEF.

Emotion regulation strategies and PTSS among children who experienced an explosion accident: the moderating role of trait mindfulness.

The purpose of this study was to investigate the moderating role of trait mindfulness in the relationship between emotion regulation strategies and post-traumatic stress symptoms (PTSS) among children and adolescents who experienced an explosion accident. A total of 712 participants, aged 7-15, (Mage = 11.45, SD = 1.77; 48.9% male) who have experienced an explosion accident completed the Emotion Regulation Questionnaire, the Trauma Screening Questionnaire and the Mindful Attention Awareness Scale. The results showed that trait mindfulness significantly moderated the relationship of the expressive suppression and PTSS under the control of sex, age, trauma exposure, and cognitive reappraisal strategy (ß = -0.27, p < 0.05). However, the moderating effect of trait mindfulness between cognitive reappraisal strategy and PTSS was not significant (p> 0.05). Findings suggested that traumatized children with low levels of mindfulness may report severer PTSS when they adopt expressive suppression strategy.

Catalpol Inhibits Autophagy to Ameliorate Doxorubicin-Induced Cardiotoxicity via the AKT-mTOR Pathway.

As a kind of anthracycline, doxorubicin (DOX) is commonly used as an antitumor drug, but its clinical application has been greatly hindered due to its severe cardiotoxicity. Hence, in this study, we investigated the role of catalpol (CTP) and its effect on DOX-induced cardiotoxicity.The cardiac function of mice was evaluated by assessing lactate dehydrogenase, creatine kinase isoenzyme, heart weight to body weight, and heart weight/tibia length levels. Histopathological changes were observed using hematoxylin and eosin staining, and the terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to examine myocardial apoptosis. Superoxide dismutase (SOD) activity, glutathione (GSH), and malondialdehyde (MDA) levels were measured to confirm the changes in oxidative stress. Western blotting showed the levels of autophagy- and pathway-related proteins. Expression of autophagy marker LC3 was examined using immunofluorescence staining.CTP alleviated DOX-induced cardiac damage in mice. We further observed upregulated SOD and GSH levels, and downregulated MDA level after the CTP treatment in DOX-treated mice, indicating the protective role of CTP against oxidative injury. DOX-induced myocardial apoptosis was also inhibited by CTP treatment in mice. In addition, CTP decreased the levels of Beclin1 and LC3II/LC3I, increased the levels of P62, and activated the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in DOX-treated mice.CTP ameliorated DOX-induced cardiotoxicity by inhibiting oxidative stress, myocardial apoptosis, and autophagy via the AKT-mTOR pathway.

Tracking Control for Output Probability Density Function of Stochastic Systems Using FPD Method.

Output probability density function (PDF) tracking control of stochastic systems has always been a challenging problem in both theoretical development and engineering practice. Focused on this challenge, this work proposes a novel stochastic control framework so that the output PDF can track a given time-varying PDF. Firstly, the output PDF is characterised by the weight dynamics following the B-spline model approximation. As a result, the PDF tracking problem is transferred to a state tracking problem for weight dynamics. In addition, the model error of the weight dynamics is described by the multiplicative noises to more effectively establish its stochastic dynamics. Moreover, to better reflect the practical applications in the real world, the given tracking target is set to be time-varying rather than static. Thus, an extended fully probabilistic design (FPD) is developed based on the conventional FPD to handle multiplicative noises and to track the time-varying references in a superior way. Finally, the proposed control framework is verified by a numerical example, and a comparison simulation with the linear-quadratic regulator (LQR) method is also included to illustrate the superiority of our proposed framework.

Guardianship from being present: the moderation of mindfulness in the longitudinal relationship of loneliness to quality of life and mental health problems among the oldest old.

Since the pace of population aging is getting faster than in the past, the population aging has been a serious social concern. The Quality of life (QOL) of the older adults, especially the oldest old, and their mental health problems need more public attention, for the purpose of enhancing their late well-being. Therefore, the current study aims to investigate the longitudinal relationship between loneliness to quality of life and mental health problems, considering the moderation effect of mindfulness among the oldest old. A total of 457 Chinese oldest-old completed questionnaires measuring mindfulness, loneliness, QOL, and mental health problems at baseline, and completed QOL and mental health problems again at six-month follow-up. Results showed that the longitudinal positive association between loneliness and mental health problems was significant (r = .401, p < .01). Nevertheless, loneliness was positively correlated with QOL (r = .242, p < .01). Additionally, mindfulness significantly moderated the association between loneliness and mental health problems. Specifically, higher mindfulness was associated with a weaker longitudinal relationship between loneliness and mental health problems. However, mindfulness did not moderate the relationship between loneliness and QOL. These findings indicated that loneliness can be a risk factor of mental health problems, and mindfulness can buffer the adverse effect of loneliness on mental health problems among the oldest old. Limitations and implications were discussed.

Metabolism regulator adiponectin prevents cardiac remodeling and ventricular arrhythmias via sympathetic modulation in a myocardial infarction model.

The stellate ganglia play an important role in cardiac remodeling after myocardial infarction (MI). This study aimed to investigate whether adiponectin (APN), an adipokine mainly secreted by adipose tissue, could modulate the left stellate ganglion (LSG) and exert cardioprotective effects through the sympathetic nervous system (SNS) in a canine model of MI. APN microinjection and APN overexpression with recombinant adeno-associated virus vector in the LSG were performed in acute and chronic MI models, respectively. The results showed that acute APN microinjection decreased LSG function and neural activity, and suppressed ischemia-induced ventricular arrhythmia. Chronic MI led to a decrease in the effective refractory period and action potential duration at 90% and deterioration in echocardiography performance, all of which was blunted by APN overexpression. Moreover, APN gene transfer resulted in favorable heart rate variability alteration, and decreased cardiac SNS activity, serum noradrenaline and neuropeptide Y, which were augmented after MI. APN overexpression also decreased the expression of nerve growth factor and growth associated protein 43 in the LSG and peri-infarct myocardium, respectively. Furthermore, RNA sequencing of LSG indicated that 4-week MI up-regulated the mRNA levels of macrophage/microglia activation marker Iba1, chemokine ligands (CXCL10, CCL20), chemokine receptor CCR5 and pro-inflammatory cytokine IL6, and downregulated IL1RN and IL10 mRNA, which were reversed by APN overexpression. Our results reveal that APN inhibits cardiac sympathetic remodeling and mitigates cardiac remodeling after MI. APN-mediated gene therapy may provide a potential therapeutic strategy for the treatment of MI.

Melatonin improves cardiac remodeling and brain-heart sympathetic hyperactivation aggravated by light disruption after myocardial infarction.

Light in the external environment might affect cardiovascular function. The light disruption seems to be related to changes in cardiovascular physiological functions, and disturbing light may be a risk factor for cardiovascular diseases. Prior studies have found that light disruption after myocardial infarction (MI) exacerbates cardiac remodeling, and the brain-heart sympathetic nervous system may be one of the key mechanisms. However, how to improve light-disrupted cardiac remodeling remains unclear. Melatonin is an indoleamine secreted by the pineal gland and controlled by endogenous circadian oscillators within the suprachiasmatic nucleus, which is closely associated with light/dark cycle. This study aimed to explore whether melatonin could improve light-disrupted cardiac remodeling and modulate the brain-heart sympathetic nervous system. Our study revealed that light disruption reduced serum melatonin levels, aggravated cardiac sympathetic remodeling, caused overactivation of the brain-heart sympathetic nervous system, exacerbated cardiac dysfunction, and increased cardiac fibrosis after MI, while melatonin treatment improved light disruption-exacerbated cardiac remodeling and brain-heart sympathetic hyperactivation after MI. Furthermore, RNA-Seq results revealed the significant changes at the cardiac transcription level. In conclusion, melatonin may be a potential therapy for light-disrupted cardiac remodeling.