The adjuvant treatment role of ω-3 fatty acids by regulating gut microbiota positively in the acne vulgaris.

Objectives:We aimed to explore the potential role of omega-3 (ω-3) fatty acids on acne vulgaris by modulating gut microbiota.Materials and Methods:We randomly divided the untreated acne patients into two groups with or without ω-3 fatty acids intervention for 12 weeks. The Sprague Dawley (SD) rats with acne model were given isotretinoin, ω-3 fatty acids or their combination respectively. Then the colonic contents samples of the drug intervention SD rats were transferred to the pseudo sterile rats with acne model. The severity of the disease was assessed by the Global Acne Grading System (GAGS) score of the patients, and the swelling rate of auricle and the pathological section of the rat with acne model. The 16S rDNA gene sequencing was performed to detect the alteration of the gut microbiota.Results:ω-3 fatty acids could increase the diversity of the gut microbiota and regulate the flora structure positively both in the patients and rats, increase the abundance of butyric acid producing bacteria and GAGS score in the patients, and alleviate the inflammation and comedones of rats.Conclusion:Supplementation of ω-3 fatty acids could alleviate the inflammation of acne vulgaris by increasing the abundance of butyric acid producing bacteria.

Introducing Spiro-locks into the Nitrogen/Carbonyl System towards Efficient Narrowband Deep-blue Multi-resonance TADF Emitters.

The current availability of multi-resonance thermally activated delayed fluorescence (MR-TADF) materials with excellent color purity and high device efficiency in the deep-blue region is appealing. To address this issue in the emerged nitrogen/carbonyl MR-TADF system, we propose a spiro-lock strategy. By incorporating spiro functionalization into a concise molecular skeleton, a series of emitters (SFQ, SOQ, SSQ, and SSeQ) can enhance molecular rigidity, blue-shift the emission peak, narrow the emission band, increase the photoluminescence quantum yield by over 92 %, and suppress intermolecular interactions in the film state. The referent CZQ without spiro structure has a more planar skeleton, and its bluer emission in the solution state redshifts over 40 nm with serious spectrum broadening and a low PLQY in the film state. As a result, SSQ achieves an external quantum efficiency of 25.5 % with a peak at 456 nm and a small full width at half maximum of 31 nm in a simple unsensitized device, significantly outperforming CZQ. This work discloses the importance of spiro-junction in modulating deep-blue MR-TADF emitters.

Inhibition of KMO Ameliorates Myocardial Ischemia Injury via Maintaining Mitochondrial Fusion and Fission Balance.

Looking for early diagnostic markers and therapeutic targets is the key to ensuring prompt treatment of myocardial ischemia (MI). Here, a novel biomarker xanthurenic acid (XA) was identified based on metabolomics and exhibited high sensitivity and specificity in the diagnosis of MI patients. Additionally, the elevation of XA was proved to induce myocardial injury in vivo by promoting myocardial apoptosis and ferroptosis. Combining metabolomics and transcriptional data further revealed that kynurenine 3-monooxygenase (KMO) profoundly increased in MI mice, and was closely associated with the elevation of XA. More importantly, pharmacological or heart-specific inhibition of KMO obviously suppressed the elevation of XA and profoundly ameliorated the OGD-induced cardiomyocytes injury and the ligation-induced MI injury. Mechanistically, KMO inhibition effectively restrained myocardial apoptosis and ferroptosis by modulating mitochondrial fission and fusion. In addition, virtual screening and experimental validation were adopted to identify ginsenoside Rb3 as a novel inhibitor of KMO and exhibited great cardioprotective effects by regulating mitochondrial dynamical balance. Taken together, targeting KMO may provide a new approach for the clinical treatment of MI through maintaining mitochondrial fusion and fission balance, and ginsenoside Rb3 showed great potential to be developed as a novel therapeutic drug targeting KMO.

Inhibition of OAT1/3 and CMPF uptake attenuates myocardial ischemia-induced chronic heart failure via decreasing fatty acid oxidation and the therapeutic effects of ruscogenin.

Chronic heart failure (CHF) as a long-term disease is highly prevalent in elder people worldwide. Early diagnosis and treatments are crucial for preventing the development of CHF. Herein, we aimed to identify novel diagnostic biomarker, therapeutic target and drug for CHF. Untargeted metabolomic analysis has been used to characterize the different metabolomic profile between CHF patients and healthy people. Meanwhile, the targeted metabolomic study demonstrated the elevation of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) in the serum of CHF patients and coronary artery ligation-induced CHF mice. Subsequently, we firstly observed that elevation of CMPF impaired cardiac function and aggravated myocardial injury by enhancing fatty acid oxidation (FAO). Interestingly, inhibition of responsible transporters organic anion transporter 1/3 (OAT1/3) has been found to decrease the CMPF level, and suppress FAO-related key protein expressions including peroxisome proliferator-activated receptor alpha, peroxisome proliferative activated receptor-α, carnitine palmitoyl transferase 1, and malonyl CoA decarboxylase in coronary artery ligation-induced CHF mice. Meanwhile, the inhibitor of OAT1/3 presented an excellent improvement in cardiac function and histological injury. Based on the above findings, molecular docking was adopted to screen the potential therapeutic drug targeting OAT1/3, and ruscogenin (RUS) exhibited a great binding affinity with OAT1 and OAT3. Next, it was verified that RUS could remarkedly decrease the expression of OAT1/3 and CMPF levels in heart tissue of CHF mice, as well as suppress the expression of FAO-related proteins. What's more, RUS can effectively improve cardiac function, myocardial fibrosis and morphological damage. Collectively, this study provided a potential metabolic marker CMPF and novel target OAT1/3 for CHF, which were demonstrated to be involved in FAO. And RUS was identified as a potential anti-FAO drug for CHF by regulating OAT1/3.

Cellular Senescence: Ageing and Androgenetic Alopecia.

Androgenetic alopecia (AGA) is the most common type of hair loss and features progressive miniaturization of hair follicles. Generally, the occurrence of AGA has long been thought to be driven by genetic and androgen predisposition. However, increasingly, data proposed ageing and AGA are intimately linked. Elevated senescent cell burden and androgen and oxidative stress-induced senescence mechanisms in ageing may be initial targets to improve AGA. This review summarizes the biological links between ageing and AGA, with special focus on cellular senescence. In addition, we discuss the potential therapeutic strategies for improving cellular senescence in AGA, such as inhibiting dermal papilla cells and hair follicle stem cells senescence driven by androgen and reactive oxygen species, removing senescent cell, and reducing senescence-associated secretory phenotype (SASP).

Effect of Proprietary Chinese Medicine on Coronary Microvascular Dysfunction in Patients with Microvascular Angina: A Systematic Review and Meta-Analysis.

Background: Microvascular angina (MVA) has received increasing attention and interest in recent years, but there are still some shortcomings in the diagnosis and treatments at current stage. In recent years, several studies have confirmed the efficacy of proprietary Chinese medicines (PCMs) in improving MVA symptoms; however, there is no systematic review and meta-analysis to comprehensively assess the efficacy of PCMs in this area. Objective: Investigating the clinical efficacy of proprietary Chinese medicines for treating MVA and coronary microvascular function. Methods: We looked up articles from January 1, 2012, to the present from eight databases. Then, we screened the literature and followed the 2019 version 2 of Cochrane risk of bias tool for systematic review. The Stata/SE 15.0 software was used for the meta-analysis. Results: There are 21 studies, including 1,641 patients who were included in this review. According to the results, the combination of PCMs and conventional MVA treatment was able to further enhance clinical efficacy [RR = 1.28, 95% CI (1.20, 1.36), p < 0.001], prolong the time of duration on the treadmill exercise testing (TET) [SMD = 1.49, 95% CI (0.63, 2.36), p = 0.001] and improve levels of NO [SMD = -1.77 95% CI (-2.11, -1.43), p < 0.001]. At the same time, PCMs could also decrease the microvascular resistance index (IMR) [SMD = -1.79, 95% CI (-2.58, -1.00), p < 0.001)], serum level of hs-CRP [SMD = -1.21, 95% CI (-1.84, -0.58), p < 0.001] and ET-1 [SMD = -1.77 95% CI (-2.11, -1.43), p < 0.001]. Regards to medication safety, a total of 27 adverse events occurred, including 10 cases in the intervention group and 17 cases in the control group. Conclusion: The study suggests that the combination of PCMs and conventional MVA treatment enhances clinical efficacy and could better improve coronary microvascular function. In the future, we expect more high-quality, randomized, double-blind clinical studies to validate the safety, and efficacy of PCMs to provide valuable evidence-based medicine (EBM) for the treatment of MVA with PCMs.

Plantamajoside alleviates hypoxia-reoxygenation injury through integrin-linked kinase/c-Src/Akt and the mitochondrial apoptosis signaling pathways in H9c2 myocardial cells.

Myocardial ischemia-reperfusion injury(MIRI) is one of the common complications after myocardial infarction surgery, Oxidative stress is among the main mechanisms of myocardial ischemia-reperfusion injury. Plantamajoside (PMS), the main effective ingredient in the genus Plantain, has been reported to possess an antioxidation, anti-inflammatory and anti-apoptosis role. However, whether PMS can attenuate myocardial ischemia-reperfusion injury is not yet known. Herein, we explored the effects of PMS on hypoxia-reoxygenation (H/R) injury in H9c2 cardiomyocytes and the underling molecular mechanisms of the treatment. Network pharmacological analysis screened the top 31 key genes in the treatment of MIRI disease treated with PMS, and the result of molecular docking further illustrated the roles that the PMS play in the treatment of MIRI through its interference with integrin-linked kinase (ILK) target protein. PMS was not cytotoxic in the concentration range of 5-40 µM and increased cell survival after H/R injury in a concentration-dependent manner without affecting proliferation or growth. PMS significantly reduced the levels of lactate dehydrogenase, malonic dialdehyde, reactive oxygen species and cell apoptosis, and increased soperoxide dismutase activity compared with those of the H/R injury group. PMS promoted the protein and mRNA expression of ILK and Bcl-2, the protein expression of p-Akt, and reduced the protein and mRNA expression of Bax, Caspase-3, and Cytochrome c, the protein expression of p-c-Src. PMS has protective effects against H/R injury in H9c2 cells, and its protective mechanism may be related to reactive oxygen species clearance, activation of the ILK/c-Src/Akt pathway and inhibition of the mitochondrial apoptosis.

Activation of NRF2 blocks HIV replication and apoptosis in macrophages.

Abnormal oxidative stress caused by human immunodeficiency virus (HIV) infection affects viral replication and causes non-acquired immune deficiency syndrome-related complications in infected individuals. The transcription factor NFE2-related factor 2 (NRF2), a key regulator of oxidative stress, responds to abnormal oxidative stress by regulating the expression of NRF2-dependent cytoprotective genes. The present study aimed to determine whether inhibition of oxidative stress could control HIV replication and improve cell survival. In this study, the NRF2 activator, methyl bardoxolone, was used to treat cells for HIV infection. The effects on HIV replication and apoptosis pathways were confirmed by NRF2 activation or knockdown. The results showed that NRF2 activation could block HIV replication in macrophages before the integration phase and inhibited the expression of apoptotic pathways in virus-exposed macrophages. The study presents an unconventional anti-viral strategy of activation antioxidant response for HIV infection blocking.

Ginsenoside Rd promotes omentin secretion in adipose through TBK1-AMPK to improve mitochondrial biogenesis via WNT5A/Ca2+ pathways in heart failure.

Ginsenoside Rd is an active ingredient in Panax ginseng CA Mey and can be absorbed into the adipose tissue. Adipokines play an important role in the treatment of cardiovascular diseases. However, the potential benefit of Rd on heart failure (HF) and the underlying mechanism associated with the crosstalk between adipocytes and cardiomyocytes remains to be illustrated. Here, the results identified that Rd improved cardiac function and inhibited cardiac pathological changes in transverse aortic constriction (TAC), coronary ligation (CAL) and isoproterenol (ISO)-induced HF mice. And Rd promoted the release of omentin from the adipose tissue and up-regulated omentin expression in lipopolysaccharide (LPS)-induced 3T3-L1 adipocytes. Further, Rd could increase TBK1 and AMPK phosphorylation in adipocytes. And also, the TBK1-AMPK signaling pathway regulated the expression of omentin in LPS-induced adipocytes. Moreover, the omentin mRNA expression was significantly decreased by TBK1 knockdown in LPS-induced 3T3-L1 adipocytes. Additionally, molecular docking and SPR analysis confirmed that Rd had a certain binding ability with TBK1, and co-treatment with TBK1 inhibitors or TBK1 knockdown partially abolished the effect of Rd on increasing the omentin expression and the ratio of p-AMPK to AMPK in adipocytes. Moreover, we found that circulating omentin level diminished in the HF patients compared with healthy subjects. Meanwhile, the adipose tissue-specific overexpression of omentin improved cardiac function, reduced myocardial infarct size and ameliorated cardiac pathological features in CAL-induced HF mice. Consistently, exogenous omentin reduced mtROS levels and restored ΔψM to improve oxygen and glucose deprivation (OGD)-induced cardiomyocytes injury. Further, omentin inhibited the WNT5A/Ca2+ signaling pathway and promoted mitochondrial biogenesis function to ameliorate myocardial ischemia injury. However, WNT5A knockdown inhibited the impairment of mitochondrial biogenesis and partially counteracted the cardioprotective effect of omentin in vitro. Therefore, this study indicated that Rd promoted omentin secretion from adipocytes through the TBK1-AMPK pathway to improve mitochondrial biogenesis function via WNT5A/Ca2+ signaling pathway to ameliorate myocardial ischemia injury, which provided a new therapeutic mechanism and potential drugs for the treatment of HF.

Carbonyl-Containing Thermally Activated Delayed Fluorescence Emitters for Narrow-Band Electroluminescence.

Carbonyl-containing derivatives show enduring vitality in the field of thermally activated delayed fluorescence (TADF) materials; they can realize high device efficiency by using both singlet and triplet excitons for electroluminescence. Recently, a system based on fused ketone/amine exhibited huge potential for constructing multi-resonance TADF (MR-TADF) emitters, which exhibit higher narrow-band emission than conventional TADF emitters with twisted donor-acceptor (D-A) structure. Herein, we summarize current research progress in both traditional and MR-type ketone derivatives with TADF characteristics for introducing the molecular design strategy of maintaining high device efficiency while keeping narrow-band emission profile. We hope this review can inspire the emergence of more high-performance narrow-band materials.

Development of a multi-recombinase polymerase amplification assay for rapid identification of COVID-19, influenza A and B.

The coronavirus disease 2019 (COVID-19) pandemic caused extensive loss of life worldwide. Further, the COVID-19 and influenza mix-infection had caused great distress to the diagnosis of the disease. To control illness progression and limit viral spread within the population, a real-time reverse-transcription PCR (RT-PCR) assay for early diagnosis of COVID-19 was developed, but detection was time-consuming (4-6 h). To improve the diagnosis of COVID-19 and influenza, we herein developed a recombinase polymerase amplification (RPA) method for simple and rapid amplification of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19 and Influenza A (H1N1, H3N2) and B (influenza B). Genes encoding the matrix protein (M) for H1N1, and the hemagglutinin (HA) for H3N2, and the polymerase A (PA) for Influenza B, and the nucleocapsid protein (N), the RNA-dependent-RNA polymerase (RdRP) in the open reading frame 1ab (ORF1ab) region, and the envelope protein (E) for SARS-CoV-2 were selected, and specific primers were designed. We validated our method using SARS-CoV-2, H1N1, H3N2 and influenza B plasmid standards and RNA samples extracted from COVID-19 and Influenza A/B (RT-PCR-verified) positive patients. The method could detect SARS-CoV-2 plasmid standard DNA quantitatively between 102 and 105 copies/ml with a log linearity of 0.99 in 22 min. And this method also be very effective in simultaneous detection of H1N1, H3N2 and influenza B. Clinical validation of 100 cases revealed a sensitivity of 100% for differentiating COVID-19 patients from healthy controls when the specificity was set at 90%. These results demonstrate that this nucleic acid testing method is advantageous compared with traditional PCR and other isothermal nucleic acid amplification methods in terms of time and portability. This method could potentially be used for detection of SARS-CoV-2, H1N1, H3N2 and influenza B, and adapted for point-of-care (POC) detection of a broad range of infectious pathogens in resource-limited settings.

Tryptophan, an important link in regulating the complex network of skin immunology response in atopic dermatitis.

Atopic dermatitis (AD) is a common chronic relapsing inflammatory skin disease, of which the pathogenesis is a complex interplay between genetics and environment. Although the exact mechanisms of the disease pathogenesis remain unclear, the immune dysregulation primarily involving the Th2 inflammatory pathway and accompanied with an imbalance of multiple immune cells is considered as one of the critical etiologies of AD. Tryptophan metabolism has long been firmly established as a key regulator of immune cells and then affect the occurrence and development of many immune and inflammatory diseases. But the relationship between tryptophan metabolism and the pathogenesis of AD has not been profoundly discussed throughout the literatures. Therefore, this review is conducted to discuss the relationship between tryptophan metabolism and the complex network of skin inflammatory response in AD, which is important to elucidate its complex pathophysiological mechanisms, and then lead to the development of new therapeutic strategies and drugs for the treatment of this frequently relapsing disease.

Effectiveness and safety of treating carotid atherosclerotic plaques with the method of nourishing qi, promoting blood circulation and expelling phlegm: A systematic review and meta-analysis.

Objectives: This meta-analysis aimed at evaluating the effectiveness and safety of Chinese medicine (TCM), which nourished qi, promoted blood circulation, and expelled phlegm (YQHXZT), in treating carotid atherosclerosis (CAS) from an immunological perspective. Background: The incidence of CAS has been increasing and tends to be younger. Although western medicine is effective, there are some limitations. TCM has certain advantages over the multichannel and multitarget treatment strategies in slowing down the process of CAS. However, there is no comprehensive review in this field. Methods: Nine databases were searched from January, 2012, to September, 2022. After applying the inclusion and exclusion criteria to the RCTs, research quality evaluation and data extraction were conducted, and a meta-analysis of the articles was performed. The GRADE was used to assess the quality of the evidence. Results: Fourteen RCTs involving 1,191 patients were identified. The results indicated that the experimental group was more effective in improving carotid intima-media thickness (CIMT)[SMD = -0.97, 95%CI(-.30,-0.65), p < 0.00001], reducing carotid plaque area [SMD = -1.98, 95%CI(-3.06,-0.89), p = 0.0003], lowering hs-CRP [SMD = -1.33, 95%CI(-1.59,-1.06), p < 0.00001] and LDL-C levels [SMD = -0.60, 95%CI(-0.83,-0.38), p < 0.00001]. Moreover, the experimental group was superior to peak systolic blood flow velocity (PSV) [SMD = -0.37, 95%CI(-0.59,-0.16), p = 0.0007], clinical efficacy [RR = 1.64, 95% CI (1.39, 1.94), p < 0.00001] and plaque area efficacy [RR = 1.36, 95% CI (1.22, 1.52), p < 0.0001]. The adverse reactions were not statistically significant in the two groups [RD = -0.01, 95% CI (-0.04.0.01), p = 0.17]. The results of grade evaluation suggested that the outcome indicators LDL-C, hs-CRP, plaque area efficacy, PSV, and adverse events were moderate. CIMT, plaque reduction area, and TCM clinical efficacy were low-quality. Conclusion: The combination of YQHXZT can alleviate the process of CAS by inhibiting the thickening of CIMT, reducing plaque area and lowering hs-CRP and LDL-C levels. The mechanism may possibly be related to reducing lipid deposition and inhibiting the inflammatory response. Besides, the combination did not increase the risk of adverse effects. However, more well-designed RCTs are needed in the future. Systematic review registration: CRD42022360529, https://www.crd.york.ac.uk/prospero/.

Omentin1 ameliorates myocardial ischemia-induced heart failure via SIRT3/FOXO3a-dependent mitochondrial dynamical homeostasis and mitophagy.

BACKGROUND: Adipose tissue-derived adipokines are involved in various crosstalk between adipose tissue and other organs. Omentin1, a novel adipokine, exerts vital roles in the maintenance of body metabolism, insulin resistance and the like. However, the protective effect of omentin1 in myocardial ischemia (MI)-induced heart failure (HF) and its specific mechanism remains unclear and to be elucidated. METHODS: The model of MI-induced HF mice and oxygen glucose deprivation (OGD)-injured cardiomyocytes were performed. Mice with overexpression of omentin1 were constructed by a fat-specific adeno-associated virus (AAV) vector system. RESULTS: We demonstrated that circulating omentin1 level diminished in HF patients compared with healthy subjects. Furthermore, the fat-specific overexpression of omentin1 ameliorated cardiac function, cardiac hypertrophy, infarct size and cardiac pathological features, and also enhanced SIRT3/FOXO3a signaling in HF mice. Additionally, administration with AAV-omentin1 increased mitochondrial fusion and decreased mitochondrial fission in HF mice, as evidenced by up-regulated expression of Mfn2 and OPA1, and downregulation of p-Drp1(Ser616). Then, it also promoted PINK1/Parkin-dependent mitophagy. Simultaneously, treatment with recombinant omentin1 strengthened OGD-injured cardiomyocyte viability, restrained LDH release, and enhanced the mitochondrial accumulation of SIRT3 and nucleus transduction of FOXO3a. Besides, omentin1 also ameliorated unbalanced mitochondrial fusion-fission dynamics and activated mitophagy, thereby, improving the damaged mitochondria morphology and controlling mitochondrial quality in OGD-injured cardiomyocytes. Interestingly, SIRT3 played an important role in the improvement effects of omentin1 on mitochondrial function, unbalanced mitochondrial fusion-fission dynamics and mitophagy. CONCLUSION: Omentin1 improves MI-induced HF and myocardial injury by maintaining mitochondrial dynamical homeostasis and activating mitophagy via upregulation of SIRT3/FOXO3a signaling. This study provides evidence for further application of omentin1 in cardiovascular diseases from the perspective of crosstalk between heart and adipose tissue.

Effectiveness and Safety of Treating Negative Emotions after PCI from the Perspective of Qi and Blood: A Systematic Review and Meta-Analysis.

Background: Many patients undergoing PCI have been reported to suffer from psychological distress and negative emotions. Several lines of evidence have indicated that PCI patients with negative emotions are particularly vulnerable to myocardial reperfusion injury when they face psychological challenges. As proven by clinical trials and research, traditional Chinese medicine (TCM) has certain advantages in alleviating psychological symptoms in PCI patients. The level of evidence for TCM is not yet high. There is no existing systematic review to evaluate the effectiveness and safety of TCM in post-PCI patients. Methods: PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, VIP, Wanfang Database, and CBM were searched to identify randomized controlled trials (RCTs) that treated negative emotions after PCI using qi and blood cotherapy. The search period was from database inception to March 1, 2022. After applying the inclusion and exclusion criteria to the RCTs, research quality evaluation and data extraction were conducted, and a meta-analysis of the articles was performed using Revman 5.3 and Stata 12.1. Results: A total of 14 RCTs involving 1314 patients were included. Meta-analysis results indicated that compared with the anti-anxiety and depression medications group, the qi-blood harmony group was more effective in clinical outcomes (RR = 1.19, 95% CI (1.13, 1.25), P < 0.00001), maintaining the stability of angina pectoris (SMD = 0.65, 95% CI (0.29, 1.01), P=0.0004), increasing the degree of patients' satisfaction (SMD = 0.95, 95% CI (0.25, 1.65), P=0.008), reducing the frequency of attacks (SMD = 0.64, 95% CI (0.11, 1.18), P=0.02), and the incidence of adverse reactions (RR = 0.54, 95% CI (0.43, 0.68), P < 0.00001). The HAMA and HAMD scores were significantly lower after treatment, and there was no significant difference between the two groups (HAMA: RR = 1.03, 95% CI (0.95, 1.12), P=0.4). The efficacy of the two groups was comparable. In terms of reduction of the HAMD score, after sensitivity analysis, the literature by Liang was found to be significantly influencing the results, and after excluding the results of Liang, the qi-blood harmony group was superior to the Western medicine group for reducing the HAMD score (RR = 1.12, 95% CI (1.01, 1.24), P < 0.05), which was significantly different. The results of this review, combined with the grade evaluation, suggest that the HAMA posttreatment score reduction, the efficacy of TCM treatment, and the incidence of adverse reactions were supported by moderate evidence, and the HAMD posttreatment score reduction and the SAQ score were supported by low-quality evidence. Conclusion: Treating negative emotions after PCI based on the idea of "harmonization of qi and blood" can effectively improve the clinical efficacy, the stability of angina pectoris and the degree of patient satisfaction, and can reduce the frequency of angina attacks and the incidence of adverse events. There was no significant difference between the two groups for reductions in the HAMA and HAMD scores. However, more high-quality, large sample, multicentre RCTs are still needed for further verification. PROSPERO Registration Number: PROSPERO CRD42022313169.

Aminoacylase-1 plays a key role in myocardial fibrosis and the therapeutic effects of 20(S)-ginsenoside Rg3 in mouse heart failure.

We previously found that the levels of metabolite N-acetylglutamine were significantly increased in urine samples of patients with heart failure (HF) and in coronary artery ligation (CAL)-induced HF mice, whereas the expression of its specific metabolic-degrading enzyme aminoacylase-1 (ACY1) was markedly decreased. In the current study, we investigated the role of ACY1 in the pathogenesis of HF and the therapeutic effects of 20(S)-ginsenoside Rg3 in HF experimental models in vivo and in vitro. HF was induced in mice by CAL. The mice were administered Rg3 (7.5, 15, 30 mg · kg-1· d-1, i.g.), or positive drug metoprolol (Met, 5.14 mg · kg-1· d-1, i.g.), or ACY1 inhibitor mono-tert-butyl malonate (MTBM, 5 mg · kg-1 · d-1, i.p.) for 14 days. We showed that administration of MTBM significantly exacerbated CAL-induced myocardial injury, aggravated cardiac dysfunction, and pathological damages, and promoted myocardial fibrosis in CAL mice. In Ang II-induced mouse cardiac fibroblasts (MCFs) model, overexpression of ACY1 suppressed the expression of COL3A1 and COL1A via inhibiting TGF-ß1/Smad3 pathway, whereas ACY1-siRNA promoted the cardiac fibrosis responses. We showed that a high dose of Rg3 (30 mg · kg-1· d-1) significantly decreased the content of N-acetylglutamine, increased the expression of ACY1, and inhibited TGF-ß1/Smad3 pathway in CAL mice; Rg3 (25 µM) exerted similar effects in Ang II-treated MCFs. Meanwhile, Rg3 treatment ameliorated cardiac function and pathological features, and it also attenuated myocardial fibrosis in vivo and in vitro. In Ang II-treated MCFs, the effects of Rg3 on collagen deposition and TGF-ß1/Smad3 pathway were slightly enhanced by overexpression of ACY1, whereas ACY1 siRNA partially weakened the beneficial effects of Rg3, suggesting that Rg3 might suppress myocardial fibrosis through ACY1. Our study demonstrates that N-acetylglutamine may be a potential biomarker of HF and its specific metabolic-degrading enzyme ACY1 could be a potential therapeutic target for the prevention and treatment of myocardial fibrosis during the development of HF. Rg3 attenuates myocardial fibrosis to ameliorate HF through increasing ACY1 expression and inhibiting TGF-ß1/Smad3 pathway, which provides some references for further development of anti-fibrotic drugs for HF.

The viral distribution and pathological characteristics of BALB/c mice infected with highly pathogenic Influenza H7N9 virus.

BACKGROUND: The highly pathogenic Influenza H7N9 virus is believed to cause multiple organ infections. However, there have been few systematic animal experiments demonstrating the virus distribution after H7N9 virus infection. The present study was carried out to investigate the viral distribution and pathological changes in the main organs of mice after experimental infection with highly pathogenic H7N9 virus. METHODS: Infection of mice with A/Guangdong/GZ8H002/2017(H7N9) virus was achieved via nasal inoculation. Mice were killed at 2, 3, and 7 days post infection. The other mice were used to observe their illness status and weight changes. Reverse transcription polymerase chain reaction and viral isolation were used to analyse the characteristics of viral invasion. The pathological changes of the main organs were observed using haematoxylin and eosin staining and immunohistochemistry. RESULTS: The weight of H7N9 virus-infected mice increased slightly in the first two days. However, the weight of the mice decreased sharply in the following days, by up to 20%. All the mice had died by the 8th day post infection and showed multiple organ injury. The emergence of viremia in mice was synchronous with lung infection. On the third day post infection, except in the brain, the virus could be isolated from all organs (lung, heart, kidney, liver, and spleen). On the seventh day post infection, the virus could be detected in all six organs. Brain infection was detected in all mice, and the viral titre in the heart, kidney, and spleen infection was high. CONCLUSION: Acute diffuse lung injury was the initial pathogenesis in highly pathogenic H7N9 virus infection. In addition to lung infection and viremia, the highly pathogenic H7N9 virus could cause multiple organ infection and injury.

Rapid and unconditional parametric reset protocol for tunable superconducting qubits.

Qubit initialization is a critical task in quantum computation and communication. Extensive efforts have been made to achieve this with high speed, efficiency and scalability. However, previous approaches have either been measurement-based and required fast feedback, suffered from crosstalk or required sophisticated calibration. Here, we report a fast and high-fidelity reset scheme, avoiding the issues above without any additional chip architecture. By modulating the flux through a transmon qubit, we realize a swap between the qubit and its readout resonator that suppresses the excited state population to 0.08% ± 0.08% within 34 ns (284 ns if photon depletion of the resonator is required). Furthermore, our approach (i) can achieve effective second excited state depletion, (ii) has negligible effects on neighboring qubits, and (iii) offers a way to entangle the qubit with an itinerant single photon, useful in quantum communication applications.

Quadruplet-Based Deep Cross-Modal Hashing.

Recently, benefitting from the storage and retrieval efficiency of hashing and the powerful discriminative feature extraction capability of deep neural networks, deep cross-modal hashing retrieval has drawn more and more attention. To preserve the semantic similarities of cross-modal instances during the hash mapping procedure, most existing deep cross-modal hashing methods usually learn deep hashing networks with a pairwise loss or a triplet loss. However, these methods may not fully explore the similarity relation across modalities. To solve this problem, in this paper, we introduce a quadruplet loss into deep cross-modal hashing and propose a quadruplet-based deep cross-modal hashing (termed QDCMH) method. Extensive experiments on two benchmark cross-modal retrieval datasets show that our proposed method achieves state-of-the-art performance and demonstrate the efficiency of the quadruplet loss in cross-modal hashing.