Two-way 5G NR FSO-HCF-UWOC converged systems with R/G/B 3-wavelength and SLM-based beam-tracking scheme.

A two-way fifth-generation (5G) new radio (NR) free-space optical (FSO)-hollow-core fibre (HCF)-underwater wireless optical communication (UWOC) converged systems with a red/green/blue (R/G/B) 3-wavelengths and spatial light modulator (SLM)-based beam-tracking scheme is practically built. It is the first to practically build a two-way FSO-HCF-UWOC converged system with high-speed and long-distance optical wireless-wired-underwater wireless communication characteristics. It shows a 5G NR FSO-HCF-UWOC convergence from drone or buildings to undersea, using R/G/B 3-wavelengths and an SLM as a demonstration. The R/G/B 3-wavelengths are used to enhance the downstream and upstream aggregate transmission rates. An SLM with electrical comparator is used to adjust the laser beam and mitigate laser beam misalignment caused by drone movement or ocean flow. Over a hybrid of 1-km FSO, 10-m HCF, and 10.44-m ocean water-air-ocean water medium, downstream/upstream 5G-millimeter-wave (MMW) 9.1-Gb/s/24-GHz signals are transmitted with satisfactorily low bit error rates and error vector magnitudes, as well as distinct constellations. This demonstrated that the 5G NR FSO-HCF-UWOC converged system exhibits promising potential as it advances the scenario implemented by the 5G-MMW signals over FSO, HCF, and UWOC convergence, paving the way for high-speed and long-distance communications across diverse media.

Association between pre-stroke frailty status and stroke risk and impact on outcomes: a systematic review and meta-analysis of 1,660,328 participants.

The prevalence of frailty is increasing, and it is associated with increased risk of diseases and adverse outcomes. Although substantial research has focused on post-stroke frailty, understanding of pre-stroke frailty remains limited. Our aim was to synthesize literature on pre-stroke frailty and stroke risk to explore their relationship and impact on prognosis. A systematic search of multiple databases was conducted to identify cohort studies published until October 28, 2023. Meta-analysis was conducted using a random effects model. Heterogeneity was assessed with the I² statistic, and publication bias was evaluated using Begg's test. Finally, we included 11 studies (n = 1,660,328 participants). The pooled hazard ratios (HRs) for stroke risk associated with pre-stroke frailty compared to non-frail individuals was 1.72 (95% confidence interval, CI: 1.46-2.02, p = 0.002, I2 = 69.2%, Begg's test: p = 0.536). The pooled HRs for mortality and the pooled relative risk (RRs) modified Rankin Scale (mRs) associated with pre-stroke frailty were 1.68 (95% CI: 1.10-2.56, p = 0.136, I2 = 49.9%, Begg's test: p = 0.296) and 3.11 (95% CI: 1.77-5.46, p = 0.192, I2 = 39.4%, Begg's test: p = 1.000), respectively. In conclusion, pre-stroke frailty is strongly associated with stroke risk and impacts its prognosis, irrespective of the measurement method. Future research should focus on prospective studies to assess the effects of early intervention for frailty. This has significant implications for primary healthcare services and frailty management.

Bidirectional wavelength-division-multiplexing fibre-free-space optical communications using polarisation multiplexing technique and tunable optical vestigial sideband filter.

To address the growing demand from emerging applications, high transmission capacity is essential for both fibre backbones and last-mile communications. This can be achieved by integrating optical fibre with optical wireless technologies, facilitating the development of fibre-free-space optical communications. Here we report a bidirectional wavelength-division-multiplexing fibre-free-space optical communication employing polarisation multiplexing technique and tunable optical vestigial sideband filter. The transmission capacity is considerably increased by integrating the polarisation multiplexing technique with the wavelength-division-multiplexing scheme. The transmission performance is extensively enhanced by using a tunable optical vestigial sideband filter and vestigial sideband-four-level pulse amplitude modulation. Moreover, the optical wireless link is substantially extended through the operation of triplet lenses. Low bit error rates and clear vestigial sideband-four-level pulse amplitude modulation eye diagrams are attained with a high aggregate transmission capacity of 480 Gb/s for downstream/upstream transmission. This capability of bidirectional fibre-free-space optical communications holds substantial potential for enhancing advanced wired-wireless communications.

HINT2 protects against pressure overload-induced cardiac remodelling through mitochondrial pathways.

Histidine triad nucleotide-binding protein 2 (HINT2) is an enzyme found in mitochondria that functions as a nucleotide hydrolase and transferase. Prior studies have demonstrated that HINT2 plays a crucial role in ischemic heart disease, but its importance in cardiac remodelling remains unknown. Therefore, the current study intends to determine the role of HINT2 in cardiac remodelling. HINT2 expression levels were found to be lower in failing hearts and hypertrophy cardiomyocytes. The mice that overexpressed HINT2 exhibited reduced myocyte hypertrophy and cardiac dysfunction in response to stress. In contrast, the deficiency of HINT2 in the heart of mice resulted in a worsening hypertrophic phenotype. Further analysis indicated that upregulated genes were predominantly associated with the oxidative phosphorylation and mitochondrial complex I pathways in HINT2-overexpressed mice after aortic banding (AB) treatment. This suggests that HINT2 increases the expression of NADH dehydrogenase (ubiquinone) flavoprotein (NDUF) genes. In cellular studies, rotenone was used to disrupt mitochondrial complex I, and the protective effect of HINT2 overexpression was nullified. Lastly, we predicted that thyroid hormone receptor beta might regulate HINT2 transcriptional activity. To conclusion, the current study showcased that HINT2 alleviates pressure overload-induced cardiac remodelling by influencing the activity and assembly of mitochondrial complex I. Thus, targeting HINT2 could be a novel therapeutic strategy for reducing cardiac remodelling.

The Silencing of GhPIP5K2 and GhPIP5K22 Weakens Abiotic Stress Tolerance in Upland Cotton (Gossypium hirsutum).

Phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks), essential enzymes in the phosphatidylinositol signaling pathway, are crucial for the abiotic stress responses and the overall growth and development of plants. However, the GhPIP5Ks had not been systematically studied, and their function in upland cotton was unknown. This study identified a total of 28 GhPIP5Ks, and determined their chromosomal locations, gene structures, protein motifs and cis-acting elements via bioinformatics analysis. A quantitative real-time PCR (qRT‒PCR) analysis showed that most GhPIP5Ks were upregulated under different stresses. A virus-induced gene silencing (VIGS) assay indicated that the superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities were significantly decreased, while malondialdehyde (MDA) content were significantly increased in GhPIP5K2- and GhPIP5K22-silenced upland cotton plants under abiotic stress. Furthermore, the expression of the stress marker genes GhHSFB2A, GhHSFB2B, GhDREB2A, GhDREB2C, GhRD20-1, GhRD29A, GhBIN2, GhCBL3, GhNHX1, GhPP2C, GhCBF1, GhSnRK2.6 and GhCIPK6 was significantly decreased in the silenced plants after exposure to stress. These results revealed that the silencing of GhPIP5K2 and GhPIP5K22 weakened the tolerance to abiotic stresses. These discoveries provide a foundation for further inquiry into the actions of the GhPIP5K gene family in regulating the response and resistance mechanisms of cotton to abiotic stresses.

Genome-Wide Identification of the GhANN Gene Family and Functional Validation of GhANN11 and GhANN4 under Abiotic Stress.

Annexins (ANNs) are a structurally conserved protein family present in almost all plants. In the present study, 27 GhANNs were identified in cotton and were unevenly distributed across 14 chromosomes. Transcriptome data and RT-qPCR results revealed that multiple GhANNs respond to at least two abiotic stresses. Similarly, the expression levels of GhANN4 and GhANN11 were significantly upregulated under heat, cold, and drought stress. Using virus-induced gene silencing (VIGS), functional characterization of GhANN4 and GhANN11 revealed that, compared with those of the controls, the leaf wilting of GhANN4-silenced plants was more obvious, and the activities of catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) were lower under NaCl and PEG stress. Moreover, the expression of stress marker genes (GhCBL3, GhDREB2A, GhDREB2C, GhPP2C, GhRD20-2, GhCIPK6, GhNHX1, GhRD20-1, GhSOS1, GhSOS2 and GhSnRK2.6) was significantly downregulated in GhANN4-silenced plants after stress. Under cold stress, the growth of the GHANN11-silenced plants was significantly weaker than that of the control plants, and the activities of POD, SOD, and CAT were also lower. However, compared with those of the control, the elasticity and orthostatic activity of the GhANN11-silenced plants were greater; the POD, SOD, and CAT activities were higher; and the GhDREB2C, GhHSP, and GhSOS2 expression levels were greater under heat stress. These results suggest that different GhANN family members respond differently to different types of abiotic stress.

Treatment of lacrimal gland adenoid cystic carcinoma: a systematic review and Meta-analysis.

AIM: To evaluate lacrimal gland adenoid cystic carcinoma (LGACC) of prognosis in patients who underwent different treatment regimens. METHODS: We searched PubMed, EMBASE, and the Cochrane Library for studies done on the treatment of LGACC, between January 1987 and April 2022. A Meta-analysis was conducted to pool the 5-year overall survival rate (OR), and the 5-year recurrence rate (RR) and 5-year metastasis rate (MR) were assessed. RESULTS: The 30 studies involved 585 patients were included in the Meta-analysis. The pooled 5-year OR with surgery alone was 50%, the 5-year RR was 63%, and the 5-year MR was 34%. The pooled 5-year OR with surgery and adjuvant radiotherapy combined was 67% (95%CI 61%,73%), the 5-year RR was 41%, and the 5-year MR was 35%. The pooled 5-year OR with surgery and adjuvant chemoradiotherapy combined was 72% (95%CI 59%, 84%), the 5-year RR was 48%, and the 5-year MR was 36%. The pooled 5-year OR with surgery, intra-arterial cytoreductive chemotherapy, and adjuvant chemoradiotherapy combined was 78% (95%CI 68%, 89%), the 5-year RR was 15%, and the 5-year MR was 27%. CONCLUSION: Comprehensive treatment is more effective than surgery alone. Surgery combined with intra-arterial chemotherapy and adjuvant chemoradiotherapy seems to add value to the therapeutic effect of comprehensive treatment of LGACC but further high-quality research is required to validate this.

Magnolol supplementation alleviates diquat-induced oxidative stress via PI3K-Akt in broiler chickens.

This experiment was conducted to investigate the effects of magnolol on the oxidative parameters and jejunum injury induced by diquat in broiler chickens. This test adopts a 2 × 2 factors design, a total of 288 one-day-old male AA broiler chicks randomly allocated to four groups, consisting of six replicates of 12 birds each, which was then denoted as CON group, diquat (DIQ) group (16 mg/kg BW diquat was injected into birds at the age of 21 days), magnolol (MAG) group (basic bird diet supplemented with 300 mg/kg magnolol), and MAG + DIQ group. At 21 days of age, broilers in the DIQ group and the MAG + DIQ group were intraperitoneally injected with 16 mg/kg BW diquat. Results showed that diet supplementing with MAG could alleviate the decrease of ADG to a certain extent after exposure to DIQ. Addition of magnolol to the diet alleviated the decrease of ADG during injection, antioxidant enzymes, and gene expression and increased the markers of oxidative damage induced by diquat induction. Magnolol supplement reversed the increase of apoptotic cells in the diquat-induced chicken jejunum. RNA sequencing showed that PI3K-Akt, calcium, and NF-kappa B signaling pathways were the main enrichment pathways between the DIQ group and the MAG + DIQ group. Our findings revealed that magnolol may improve antioxidant enzyme activity and expression of related genes through the PI3K-Akt pathway to alleviate oxidative stress.

Lonicerin alleviates ovalbumin-induced asthma of mice via inhibiting EZH2/NF-κB signaling pathway.

Asthma is the most common chronic disease in the respiratory system of children caused by abnormal immunity that responses to common antigens. Lonicerin exerts anti-inflammatory activity in other inflammatory models through targeting enhancer of zeste homolog 2 (EZH2) that is related to asthma. We sought to explore the role and mechanism of lonicerin in regulating allergic airway inflammation. Mice were intraperitoneally injected 10 µg ovalbumin (OVA) on postnatal day 5 (P5) and P10, and then inhaled 3% aerosolized OVA for 10 min every day on P18-20, to establish asthmatic mice model. Lonicerin (10 or 30 mg/kg) was given to mice by intragastric administration on P16-P20. Notably, the administration of lonicerin amended infiltration of inflammatory cells and mucus hypersecretion. OVA-specific IgE level, inflammatory cell count and inflammatory cytokines in asthmatic mice were reduced after lonicerin treatment. Moreover, it suppressed the activity of EZH2 and activation of nuclear factor-kappa B (NF-ĸB) as evidenced by decreasing tri-methylation of histone H3 at lysine 27 and reducing nuclear translocation of NF-κB p65. In a word, Lonicerin may attenuate asthma by inhibiting EZH2/NF-κB signaling pathway.

p21 promotes gemcitabine tolerance in A549 cells by inhibiting DNA damage and altering the cell cycle.

Gemcitabine is one of the most widely used chemotherapy drugs for advanced malignant tumors, including non-small cell lung cancer. However, the clinical efficacy of gemcitabine is limited due to drug resistance. The aim of the present study was to investigate the role of p21 in gemcitabine-resistant A549 (A549/G+) lung cancer cells. IC50 values were determined using a Cell Counting Kit-8 (CCK-8) assay. mRNA and protein expression levels of genes were measured by reverse transcription-quantitative PCR and western blotting, respectively. The cell cycle distribution and apoptosis rate were analyzed by flow cytometry. DNA damage in cells was evaluated by single-cell gel electrophoresis. The results of western blot analysis and the CCK-8 assay demonstrated that the expression of p21 was higher in A549/G+ cells than in gemcitabine-sensitive cells. Knockdown of p21 expression in gemcitabine-resistant cells sensitized these cells to gemcitabine (with the IC50 decreasing from 84.2 to 26.7 µM). Cell cycle analysis revealed different changes in the cell cycle distribution in A549/G+ cells treated with the same concentration of gemcitabine, and decreased expression of p21 was shown to promote G1 arrest. The apoptosis assay and comet assay results revealed that decreased p21 expression resulted in accumulation of unrepaired DNA double-strand breaks (DSBs) and induction of apoptosis by gemcitabine. The present study demonstrated that knockout of p21 mRNA expression in A549/G+ cells promotes apoptosis and DNA DSB accumulation, accompanied by G1 arrest. These results indicated that p21 is involved in regulating the response of A549 cells to gemcitabine.

Transmission of sub-terahertz signals over a fiber-FSO-5†G NR hybrid system with an aggregate net bit rate of 227.912 Gb/s.

Transmission of sub-terahertz (sub-THz) signals over a fiber-free-space optical (FSO)-fifth-generation (5 G) new radio (NR) hybrid system is successfully realized. It is a promising system that utilizes multiple media of optical fiber, optical wireless, and 5 G NR wireless to achieve a 227.912-Gb/s record-high aggregate net bit rate. The system concurrently transmits a 59.813-Gb/s net bit rate in the 150-GHz sub-THz frequency, 74.766-Gb/s in the 250-GHz sub-THz frequency, and 93.333-Gb/s in the 325-GHz sub-THz frequency through the fiber-FSO-wireless convergence, including 25-km single-mode fiber, 100-m FSO, and 30-m/25-m/20-m sub-THz-wave transmissions. This system achieves sufficiently low bit error rates (< hard-decision forward error correction (FEC) threshold of 3.8 × 10-3 at 16 and 20 Gbaud symbol rates; < soft-decision FEC threshold of 2 × 10-2 at 28 Gbaud symbol rate) and clear and distinct constellation diagrams, meeting the demands of 5 G NR communications in the sub-THz band. The development of fiber-FSO-5 G NR hybrid system represents a substantial development in the field of advanced communications. It has the ability to enhance the way we communicate in the future.

Low polarization-sensitive ultra-broadband anti-reflection coatings with improved reliability.

Broader spectra, lower reflectivity and higher reliability are the performance requirements for broadband antireflective (BBAR) films. In this work, a BBAR film structure was proposed, which maintains extremely low reflectivity, ultra-wide spectra, low polarization sensitivity and practical reliability. The BBAR film consists of a dense multilayer interference stack on the bottom and a nano-grass-like alumina (NGLA) layer with a gradient low refractive index distribution on the top. The film was deposited by atomic layer deposition, while the NGLA layer was formed by means of a hot water bath on Al2O3 layer. The top NGLA layer has extremely high porosity and ultra-low refractive index, along with extremely fragile structure. To surmount the fragility of NGLA layer, a sub-nano layer of SiO2 was grown by atomic layer deposition to solidify its structure and also to adjust the refractive index with different thicknesses of SiO2. Finally, in the wide wavelength range of 400-1100 nm, the average transmittance of the double-sided coated fused quartz reaches 99.2%. The absorption, light scattering, reliability and polarization characteristics of BBAR films were investigated. An optimized BBAR film with low polarization-sensitivity and improved reliability was realized, which should be potentially promising for application in optical systems.

Activation of AMPKα2 attenuated doxorubicin-induced cardiotoxicity via inhibiting lipid peroxidation associated ferroptosis.

Ferroptosis has been suggested to involve in doxorubicin (DOX)-induced cardiotoxicity. However, the underlying mechanisms and regulatory targets of cardiomyocyte ferroptosis remains to be understood. This study demonstrated that the up-regulation of ferroptosis associated proteins genes were accompanied with the down-regulation of AMPKα2 phosphorylation in DOX treated mouse heart or neonatal rat cardiomyocytes (NRCMs). AMPKα2 knockout (AMPKα2-/-) significantly exacerbated mouse cardiac dysfunction, increased mortality, promoting ferroptosis associated mitochondrial injuries, enhanced ferroptosis associated proteins and genes expression, and lead to accumulation of lactate dehydrogenase (LDH) and malondialdehyde (MDA) in mouse serum and hearts respectively. Ferrostatin-1 administration markedly improved cardiac function, decreased mortality, inhibited mitochondrial injuries and ferroptosis associated proteins and genes expression, and depressed accumulation of LDH and MDA in DOX treated AMPKα2-/- mouse. Moreover, Adeno-associated virus serotype 9 AMPKα2 (AAV9-AMPKα2) or AICAR treatment mediated AMPKα2 activation could significantly improve cardiac function and depress ferroptosis in mouse. AMPKα2 activation or silence could also inhibit or promote ferroptosis associated injuries in DOX treated NRCMs respecitively. Mechanistically, AMPKα2/ACC mediated lipid metabolism has been suggested to involve in regulating DOX-treatment induced ferroptosis other than mTORC1 or autophagy dependent pathway. The metabolomics analysis exhibited that AMPKα2-/- significantly enhanced accumulation of polyunsaturated fatty acids (PFAs), oxidized lipid, and phosphatidylethanolamine (PE). Finally, this study also demonstrated that metformin (MET) treatment could inhibit ferroptosis and improve cardiac function via activating AMPKα2 phosphorylation. The metabolomics analysis exhibited that MET treatment significantly depressed PFAs accumulation in DOX treated mouse hearts. Collectively, this study suggested that AMPKα2 activation might protect against anthracycline chemotherapeutic drugs mediated cardiotoxicity via inhibiting ferroptosis.

RIP2 inhibition alleviates lipopolysaccharide-induced septic cardiomyopathy via regulating TAK1 signaling.

PURPOSE: RIP2 is a member of the receptor-interacting protein family that has been associated with various pathophysiological processes, including immunity, apoptosis, and autophagy. However, no studies have hitherto reported the role of RIP2 in lipopolysaccharide (LPS)-induced septic cardiomyopathy (SCM). This study was designed to illustrate the role of RIP2 in LPS-induced SCM. METHODS: C57 and RIP2 knockout mice received intraperitoneal injections of LPS to establish models of SCM. Echocardiography was used to assess the cardiac function of the mice. Real-time-PCR, cytometric bead array and immunohistochemical staining were used to detect the inflammatory response. Immunoblotting was used to determine the protein expression of relevant signaling pathways. Our findings were validated by treatment with a RIP2 inhibitor. Neonatal rats cardiomyocytes (NRCMs) and cardiac fibroblasts (CFs) were transfected with Ad-RIP2 to further explore the role of RIP2 in vitro. RESULTS: RIP2 expression was upregulated in our mice models of septic cardiomyopathy and LPS-stimulated cardiomyocytes and fibroblasts. RIP2 knockout or RIP2 inhibitors attenuated LPS-induced cardiac dysfunction and reduced the inflammatory response in mice. Overexpression of RIP2 in vitro enhanced the inflammatory response, and TAK1 inhibitors attenuated the inflammatory response caused by overexpression of RIP2. CONCLUSION: Our findings substantiate that RIP2 induces an inflammatory response by regulating the TAK1/IκBα/NF-κB signaling pathway. RIP2 inhibition by genetic or pharmacological approaches has huge prospects for application as a potential treatment strategy for inhibiting inflammation, alleviating cardiac dysfunction, and improving survival.

Cryptotanshinone Attenuated Pathological Cardiac Remodeling In Vivo and In Vitro Experiments.

Objective: Cardiac remodeling has been demonstrated to be the early stage and common pathway for various types of cardiomyopathy, but no specific treatment has been suggested to prevent its development and progress. This study was aimed at assessing whether Cryptotanshinone (CTS) treatment could effectively attenuate cardiac remodeling in vivo and in vitro. Methods: Aortic banding (AB) surgery was performed to establish a pressure-overload-induced mouse cardiac remodeling model. Echocardiography and pressure-volume proof were used to examine mouse cardiac function. Hematoxylin and eosin (HE) and Picro-Sirius Red (PSR) staining were used to assess cardiac remodeling in vivo. Mouse hearts were collected to analysis signaling pathway and cardiac remodeling markers, respectively. Furthermore, neonatal rat cardiomyocyte (NRCMs) and cardiac fibroblast (CF) were isolated to investigate the roles and mechanisms of CTS treatment in vitro. Results: CTS administration significantly alleviated pressure-overload-induced mouse cardiac dysfunction, inhibited cardiac hypertrophy, and reduced cardiac fibrosis. Mechanically, CTS treatment significantly inhibited the STAT3 and TGF-ß/SMAD3 signaling pathways. In vitro experiments, CTS treatment markedly inhibited AngII-induced cardiomyocyte hypertrophy and TGF-ß-induced myofibroblast activation via inhibiting STAT3 phosphorylation and its nuclear translocation. Finally, CTS treatment could not protect against pressure overload-induced mouse cardiac remodeling after adenovirus-associated virus (AAV)9-mediated STAT3 overexpression in mouse heart. Conclusion: CTS treatment might attenuate pathological cardiac remodeling via inhibiting STAT3-dependent pathway.

Drosophila as a toolkit to tackle cancer and its metabolism.

Cancer is one of the most severe health problems worldwide accounting for the second leading cause of death. Studies have indicated that cancers utilize different metabolic systems as compared with normal cells to produce extra energy and substances required for their survival, which contributes to tumor formation and progression. Recently, the fruit fly Drosophila has been attracting significant attention as a whole-body model for elucidating the cancer mechanisms including metabolism. This tiny organism offers a valuable toolkit with various advantages such as high genetic conservation and similar drug response to mammals. In this review, we introduce flies modeling for cancer patient genotypes which have pinpointed novel therapeutic targets and drug candidates in the salivary gland, thyroid, colon, lung, and brain. Furthermore, we introduce fly models for metabolic diseases such as diabetes mellitus, obesity, and cachexia. Diabetes mellitus and obesity are widely acknowledged risk factors for cancer, while cachexia is a cancer-related metabolic condition. In addition, we specifically focus on two cancer metabolic alterations: the Warburg effect and redox metabolism. Indeed, flies proved useful to reveal the relationship between these metabolic changes and cancer. Such accumulating achievements indicate that Drosophila offers an efficient platform to clarify the mechanisms of cancer as a systemic disease.

Liquiritin Attenuates Pathological Cardiac Hypertrophy by Activating the PKA/LKB1/AMPK Pathway.

Background: Liquiritin (LQ) is one of the main flavonoids extracted from the roots of Glycyrrhiza spp., which are widely used in traditional Chinese medicine. Studies in both cellular and animal disease models have shown that LQ attenuates or prevents oxidative stress, inflammation, and apoptosis. However, the potential therapeutic effects of LQ on pressure overload-induced cardiac hypertrophy have not been so far explored. Therefore, we investigated the cardioprotective role of LQ and its underlying mechanisms in the aortic banding (AB)-induced cardiac hypertrophy mouse model. Methods and Results: Starting 3 days after AB surgery, LQ (80 mg/kg/day) was administered daily over 4 weeks. Echocardiography and pressure-volume loop analysis indicated that LQ treatment markedly improved hypertrophy-related cardiac dysfunction. Moreover, hematoxylin and eosin, picrosirius red, and TUNEL staining showed that LQ significantly inhibited cardiomyocyte hypertrophy, interstitial fibrosis, and apoptosis. Western blot assays further showed that LQ activated LKB1/AMPKα2/ACC signaling and inhibited mTORC1 phosphorylation in cardiomyocytes. Notably, LQ treatment failed to prevent cardiac dysfunction, hypertrophy, and fibrosis in AMPKα2 knockout (AMPKα2-/-) mice. However, LQ still induced LKB1 phosphorylation in AMPKα2-/- mouse hearts. In vitro experiments further demonstrated that LQ inhibited Ang II-induced hypertrophy in neonatal rat cardiomyocytes (NRCMs) by increasing cAMP levels and PKA activity. Supporting the central involvement of the cAMP/PKA/LKB1/AMPKα2 signaling pathway in the cardioprotective effects of LQ, inhibition of Ang II-induced hypertrophy and induction of LKB1 and AMPKα phosphorylation were no longer observed after inhibiting PKA activity. Conclusion: This study revealed that LQ alleviates pressure overload-induced cardiac hypertrophy in vivo and inhibits Ang II-induced cardiomyocyte hypertrophy in vitro via activating cAMP/PKA/LKB1/AMPKα2 signaling. These findings suggest that LQ might be a valuable adjunct to therapeutic approaches for treating pathological cardiac remodeling.

Alternative autophagy: mechanisms and roles in different diseases.

As an important mechanism to maintain cellular homeostasis, autophagy exerts critical functions via degrading misfolded proteins and damaged organelles. Recent years, alternative autophagy, a new type of autophagy has been revealed, which shares similar morphology with canonical autophagy but is independent of Atg5/Atg7. Investigations on different diseases showed the pivotal role of alternative autophagy during their physio-pathological processes, including heart diseases, neurodegenerative diseases, oncogenesis, inflammatory bowel disease (IBD), and bacterial infection. However, the studies are limited and the precise roles and mechanisms of alternative autophagy are far from clear. It is necessary to review current research on alternative autophagy and get some hint in order to provide new insight for further study. Video Abstract.

Neutrophil degranulation and myocardial infarction.

Myocardial infarction (MI) is one of the most common cardiac emergencies with high morbidity and is a leading cause of death worldwide. Since MI could develop into a life-threatening emergency and could also seriously affect the life quality of patients, continuous efforts have been made to create an effective strategy to prevent the occurrence of MI and reduce MI-related mortality. Numerous studies have confirmed that neutrophils play important roles in inflammation and innate immunity, which provide the first line of defense against microorganisms by producing inflammatory cytokines and chemokines, releasing reactive oxygen species, and degranulating components of neutrophil cytoplasmic granules to kill pathogens. Recently, researchers reported that neutrophils are closely related to the severity and prognosis of patients with MI, and neutrophil to lymphocyte ratio in post-MI patients had predictive value for major adverse cardiac events. Neutrophils have been increasingly recognized to exert important functions in MI. Especially, granule proteins released by neutrophil degranulation after neutrophil activation have been suggested to involve in the process of MI. This article reviewed the current research progress of neutrophil granules in MI and discusses neutrophil degranulation associated diagnosis and treatment strategies. Video abstract Neutrophils played a crucial role throughout the process of MI, and neutrophil degranulation was the crucial step for the regulative function of neutrophils. Both neutrophils infiltrating and neutrophil degranulation take part in the injury and repair process immediately after the onset of MI. Since different granule subsets (e g. MPO, NE, NGAL, MMP-8, MMP-9, cathelicidin, arginase and azurocidin) released from neutrophil degranulation show different effects through diverse mechanisms in MI. In this review, we reviewed the current research progress of neutrophil granules in MI and discusses neutrophil degranulation associated diagnosis and treatment strategies. Myeloperoxidase (MPO); Neutrophil elastase (NE); Neutrophil gelatinase-associated lipocalin (NGAL); Matrix metalloproteinase 8 (MMP-8); Matrix metalloproteinase 9 (MMP-9).