Potential-Regulated Design for Direct Recycling of Degraded LiFePO4 Cathode.

The rapid proliferation of power sources equipped with lithium-ion batteries poses significant challenges in terms of post-scrap recycling and environmental impacts, necessitating urgent attention to the development of sustainable solutions. The cathode direct regeneration technologies present an optimal solution for the disposal of degraded cathodes, aiming to non-destructively re-lithiate and straightforwardly reuse degraded cathode materials with reasonable profits and excellent efficiency. Herein, a potential-regulated strategy is proposed for the direct recycling of degraded LiFePO4 cathodes, utilizing low-cost Na2SO3 as a reductant with lower redox potential in the alkaline systems. The aqueous re-lithiation approach, as a viable alternative, not only enables the re-lithiation of degraded cathode while ignoring variation in Li loss among different feedstocks but also utilizes the rapid sintering process to restore the cathode microstructure with desirable stoichiometry and crystallinity. The regenerated LiFePO4 exhibits enhanced electrochemical performance with a capacity of 144 mA h g-1 at 1 C and a high retention of 98% after 500 cycles at 5 C. Furthermore, this present work offers considerable prospects for the industrial implementation of directly recycled materials from lithium-ion batteries, resulting in improved economic benefits compared to conventional leaching methods.

CircNSD1 promotes cardiac fibrosis through targeting the miR-429-3p/SULF1/Wnt/ß-catenin signaling pathway.

Cardiac fibrosis is a detrimental pathological process, which constitutes the key factor for adverse cardiac structural remodeling leading to heart failure and other critical conditions. Circular RNAs (circRNAs) have emerged as important regulators of various cardiovascular diseases. It is known that several circRNAs regulate gene expression and pathological processes by binding miRNAs. In this study we investigated whether a novel circRNA, named circNSD1, and miR-429-3p formed an axis that controls cardiac fibrosis. We established a mouse model of myocardial infarction (MI) for in vivo studies and a cellular model of cardiac fibrogenesis in primary cultured mouse cardiac fibroblasts treated with TGF-ß1. We showed that miR-429-3p was markedly downregulated in the cardiac fibrosis models. Through gain- and loss-of-function studies we confirmed miR-429-3p as a negative regulator of cardiac fibrosis. In searching for the upstream regulator of miR-429-3p, we identified circNSD1 that we subsequently demonstrated as an endogenous sponge of miR-429-3p. In MI mice, knockdown of circNSD1 alleviated cardiac fibrosis. Moreover, silence of human circNSD1 suppressed the proliferation and collagen production in human cardiac fibroblasts in vitro. We revealed that circNSD1 directly bound miR-429-3p, thereby upregulating SULF1 expression and activating the Wnt/ß-catenin pathway. Collectively, circNSD1 may be a novel target for the treatment of cardiac fibrosis and associated cardiac disease.

M3 subtype of muscarinic acetylcholine receptor inhibits cardiac fibrosis via targeting microRNA-29b/beta-site app cleaving enzyme 1 axis.

Background: Previous studies have confirmed that choline exerts anti-fibrotic effect in the heart by activating the M3 subtype of muscarinic acetylcholine receptor (M3 receptor), but the mechanism remains to be clarified. MicroRNA-29b (miR-29b) plays an important role in the fibrotic process and can directly target collagen to resist myocardial fibrosis. This study investigated whether miR-29b is involved in the anti-fibrotic effect of activating M3 receptor. Methods: Proliferation of cardiac fibroblasts was induced by transforming growth factor (TGF)-ß1 in vitro. The expression of miR-29b in cardiac fibroblasts was detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Protein levels of collagens I, connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA) and beta-site app cleaving enzyme 1 (BACE1) were determined by Western blot analysis. Fibroblast-myofibroblast transition was identified by immunofluorescence staining. Proliferation and migration of cardiac fibroblasts as indicated by transwell and scratch assays. Results: The expression of miR-29b decreased when treated with TGF-ß1 (P=0.0389) and increased after choline stimulated (P=0.0001). Overexpression of miR-29b could reverse the high expression of collagen I (P<0.0001), α-SMA (P=0.0007), and CTGF (P=0.0038) induced by TGF-ß1, whereas inhibition of miR-29b had a tendency to even further increase the expression of fibrosis markers. Meanwhile, inhibition of miR-29b could reverse the anti-fibrotic effect of choline, increasing the expression of collagen I (P=0.0040), α-SMA (P=0.0001), and CTGF (P=0.0185), and promoting the fibroblast proliferation and migration. Moreover, BACE1 protein level, increased after TGF-ß1 treatment (P=0.0037) and reversed by overexpression of miR-29b (P=0.0493). Choline could reduce the increase of BACE1 induced by TGF-ß1 (P=0.0264), and 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP) increased the expression of BACE1 (P=0.0060). Furthermore, overexpression of BACE1 could reverse the protective effect of miR-29b in cardiac fibrosis, increasing the protein level of collagen I (P=0.0404). Conclusions: The results suggested that M3 receptor activation could exert cardioprotective effects in cardiac fibrosis by mediating miR-29b/BACE1 axis.

Virulence and Molecular characterization reveal sign of sexual genetic recombination of Puccinia striiformis f. sp. tritici and Puccinia striiformis f. sp. hordei in Tibet.

Stripe rust of wheat and stripe rust of barley are caused by different formae speciales, Puccinia striiformis f. sp. tritici (Pst) and P. striiformis f. sp. hordei (Psh), respectively. To understand the relationship between the populations of the two formae speciales, a total of 260 P. striiformis isolates, including 140 from barley and 120 from wheat collected from Linzhi, Tibet, China from 2018 to 2020, were tested on 18 barley and 13 wheat genotypes, and genotyped with 26 single-nucleotide polymorphism (SNP)-based Kompetitive Allele Specific PCR (KASP) markers. As a result, 260 isolates were identified as 83 virulence phenotypes (VPs), 115 of which as 9 VPs and can only infect wheat (wheat population), 111 as 54 VPs and can only infect barley (barley population), and 34 belonged to 20 VPs that can attack both wheat and barley (mixed population). Of 149 multi-locus genotypes (MLGs) that were identified, 92 were from wheat, 56 from barley, and 1 from both wheat and barley. Phenotypic and genotypic diversity was high in the populations from wheat and barley. Low linkage disequilibrium was found in most of sampling sites of both crops, indicating strong signs of sexual reproduction (|¬r(_)d| = 0.022-0.393, P = 0.004-0.847). Whereas, it was not observed in the overall population (wheat and barley sources), and the wheat, barley, and mixed populations, which may be due to complex composition of isolates. Population structure analyses based on phenotyping and SNP-KASP genotypes supported the separations of the two formae speciales. However, MLGs and clusters containing isolates from both wheat and barley indicated obvious indication of sexual genetic recombination between the two formae speciales. The results of the study provided an insight into evolution of Pst and Psh, and showed the importance of management strategy for stripe rust of wheat and barley in regions where both crops are grown.

The impact of visit-to-visit heart rate variability on all-cause mortality in atrial fibrillation.

OBJECTIVE: We aimed to investigate the association between visit-to-visit heart rate variability (VVHRV) and all-cause mortality in patients diagnosed with atrial fibrillation (AF). Previous studies have shown a positive correlation between VVHRV and several adverse outcomes. However, the relationship between VVHRV and the prognosis of AF remains uncertain. METHODS: In our study, we aimed to examine the relationship between VVHRV and mortality rates among 3983 participants with AF, who were part of the AFFIRM study (Atrial Fibrillation Follow-Up Investigation of Rhythm Management). We used the standard deviation of heart rate (HRSD) to measure VVHRV and divided the patients into four groups based on quartiles of HRSD (1st, <5.69; 2nd, 5.69-8.00; 3rd, 8.01-11.01; and 4th, ≥11.02). Our primary endpoint was all-cause death, and we estimated the hazard ratios for mortality using the Cox proportional hazard regressions. RESULTS: Our analysis included 3983 participants from the AFFIRM study and followed for an average of 3.5 years. During this period, 621 participants died from all causes. In multiple-adjustment models, we found that the lowest and highest quartiles of HRSD independently predicted an increased risk of all-cause mortality compared to the other two quartiles, presenting a U-shaped relationship (1st vs 2nd, hazard ratio = 2.28, 95% CI = 1.63-3.20, p < .01; 1st vs. 3rd, hazard ratio = 2.23, 95% CI = 1.60-3.11, p < .01; 4th vs. 2nd, hazard ratio = 1.82, 95% CI = 1.26-2.61, p < .01; and 4th vs. 3rd, hazard ratio = 1.78, 95% CI = 1.25-2.52, p < .01). CONCLUSION: In patients with AF, we found that both lower VVHRV and higher VVHRV increased the risk of all-cause mortality, indicating a U-shaped curve relationship.

LncRNA CCRR Attenuates Postmyocardial Infarction Inflammatory Response by Inhibiting the TLR Signalling Pathway.

BACKGROUND: Timely and proper suppression of inflammation can effectively reduce myocardial injury and promote the postmyocardial infarction (post-MI) wound-healing process. We have previously found that cardiac conduction regulatory RNA (CCRR), a long noncoding RNA (lncRNA) transcribed by the gene located on chromosome 9, with abundant expression in the heart, elicits antiarrhythmic effects in heart failure, and this is a continuing study on the role of CCRR in MI. METHODS: CCRR was overexpressed in CCRR transgenic mice or after injection of adeno-associated virus-9 (AAV-9). MI surgery was performed, and cardiac function was assessed in vivo by echocardiography, followed by histologic analyses. Western blot analysis and qRT-PCR were performed to investigate the effects of CCRR on macrophages, cardiomyocytes, and cardiomyocytes cocultured with macrophages. Through microarray analysis and RNA-binding protein immunoprecipitation (RIP) and other related techniques were also employed to study the effects of CCRR on Toll-like receptor (TLR)2 and TLR4. RESULTS: We found that CCRR level was significantly decreased with increases in proinflammatory cytokines and activation of the TLR signalling pathway in the heart of the 3-day MI mice. CCRR overexpression downregulated TLR2 and TLR4 in MI and effectively inhibited the inflammatory responses in primary cardiomyocytes and macrophages cultured under hypoxic conditions. Downregulation of CCRR induced excessive inflammatory responses by activating the TLR signalling pathway. CCRR acted by suppressing TLR2 and TLR4 to inhibit the secretion of proinflammatory factors to reduce infarct size, thereby improving cardiac function. CONCLUSIONS: CCRR protected cardiomyocytes against MI injury by suppressing inflammatory response through targeting the TLR signalling pathway.

Hypoxic Bone Marrow Stromal Cells Secrete miR-140-5p and miR-28-3p That Target SPRED1 to Confer Drug Resistance in Multiple Myeloma.

Bone marrow stromal cell (BMSC)-derived small extracellular vesicles (sEV) promote drug resistance to bortezomib in multiple myeloma cells. Elucidating the components of BMSC sEV that induce drug resistance in multiple myeloma cells could help identify strategies to overcome resistance. Considering the hypoxic nature of the myeloma microenvironment, we explored the role of hypoxia in regulating BMSC sEV cargo and investigated whether hypoxia-driven sEV miRNAs contribute to the drug resistance in multiple myeloma cells. Hypoxia increased the release of sEVs from BMSCs, and these sEVs more strongly attenuated bortezomib sensitivity in multiple myeloma cells than sEVs from BMSCs under normoxic conditions. RNA sequencing revealed that significantly elevated levels of miR-140-5p and miR-28-3p were enclosed in hypoxic BMSC-derived sEVs. Both miR-140-5p and miR-28-3p conferred bortezomib resistance in multiple myeloma cells by synergistically targeting SPRED1, a member of the Sprouty protein family that regulates MAPK activation. SPRED1 inhibition reduced sensitivity to bortezomib in multiple myeloma cells through activating MAPK-related pathways and significantly promoted multiple myeloma bortezomib resistance and tumor growth in a mouse model. These findings shed light on the role of hypoxia-induced miRNAs shuttled in BMSC-derived sEVs to multiple myeloma cells in inducing drug resistance and identify the miR-140-5p/miR-28-3p/SPRED1/MAPK pathway as a potential targetable axis for treating multiple myeloma. SIGNIFICANCE: Hypoxia induces stromal cells to secrete extracellular vesicles with increased miR-140-5p and miR-28-3p that are transferred to multiple myeloma cells and drive drug resistance by increasing the MAPK signaling.

High hydrostatic pressure participates in atrial fibrosis through the p300/p53/Smad3 pathway.

As an independent risk factor of atrial fibrillation (AF), hypertension (HTN) can induce atrial fibrosis through cyclic stretch and hydrostatic pressure. The mechanism by which high hydrostatic pressure promotes atrial fibrosis is unclear yet. p300 and p53/Smad3 play important roles in the process of atrial fibrosis. This study investigated whether high hydrostatic pressure promotes atrial fibrosis by activating the p300/p53/Smad3 pathway. Biochemical experiments were used to study the expression of p300/p53/Smad3 pathway in left atrial appendage (LAA) tissues of patients with sinus rhythm (SR), AF, AF + HTN, and C57/BL6 mice, hypertensive C57/BL6 mice and atrial fibroblasts of mice. To investigate the roles of p300 and p53 in the process of atrial fibrosis, p300 and p53 in mice atrial fibroblasts were knocked in or knocked down, respectively. The expression of p300/p53/Smad3 and fibrotic factors was higher in patients with AF and AF + HTN than those with SR only. The expressions of p300/p53/Smad3 and fibrotic factors increased in hypertensive mice. Curcumin (Cur) and knocking down of p300 reversed the expressions of these factors. 40 mmHg hydrostatic pressure/overexpression of p300 upregulated the expressions of p300/p53/Smad3 and fibrotic factors in mice LAA fibroblasts. While Cur or knocking down p300 reversed these changes. Knocking down/overexpression of p53, the expressions of p53/Smad3 and fibrotic factors also decreased/increased, correspondingly. High hydrostatic pressure promotes atrial fibrosis by activating the p300/p53/Smad3 pathway, which further increases the susceptibility to AF.

Diagnosis of hypertrophic cardiomyopathy accompanied with primary aldosteronism-Case report.

Hypertrophic cardiomyopathy (HCM) is known to be the most prevalent genetic cardiac condition. However, there have been limited reports on the diagnosis of HCM accompanied by secondary hypertension and the subsequent systematic therapy. In this case report, we present the case of a 65-year-old male patient who presented with recurring chest discomfort during physical activity, along with refractory hypertension. Cardiac magnetic resonance imaging (MRI) and transthoracic echocardiogram(TTE) revealed the presence of HCM in this individual. Further investigation revealed hypokalemia, elevated aldosterone levels, decreased plasma renin activity, and an aldosterone-to-renin ratio above 30. These findings strongly indicated primary aldosteronism (PA) as an additional condition affecting this patient. Through the utilization of whole exome sequencing, we successfully identified a suspected pathogenic gene TTN as the underlying cause of the patient's condition. The presence of HCM accompanied by secondary hypertension due to PA resulted in significant enlargement of the left ventricle, particularly the ventricular septum. While certain genetic mutations may suggest a potential link to cardiomyopathy development, they cannot definitively establish a direct association between HCM and PA.

Aloe-Emodin Derivative, an Anthraquinone Compound, Attenuates Pyroptosis by Targeting NLRP3 Inflammasome in Diabetic Cardiomyopathy.

Diabetic cardiomyopathy (DCM) is widely recognized as a major contributing factor to the development of heart failure in patients with diabetes. Previous studies have demonstrated the potential benefits of traditional herbal medicine for alleviating the symptoms of cardiomyopathy. We have chemically designed and synthesized a novel compound called aloe-emodin derivative (AED), which belongs to the aloe-emodin (AE) family of compounds. AED was formed by covalent binding of monomethyl succinate to the anthraquinone mother nucleus of AE using chemical synthesis techniques. The purpose of this study was to investigate the effects and mechanisms of AED in treating DCM. We induced type 2 diabetes in Sprague-Dawley (SD) rats by administering a high-fat diet and streptozotocin (STZ) injections. The rats were randomly divided into six groups: control, DCM, AED low concentration (50 mg/kg/day), AED high concentration (100 mg/kg/day), AE (100 mg/kg/day), and positive control (glyburide, 2 mg/kg/day) groups. There were eight rats in each group. The rats that attained fasting blood glucose of ˃16.7 mmol/L were considered successful models. We observed significant improvements in cardiac function in the DCM rats with both AED and AE following four weeks of intragastric treatment. However, AED had a more pronounced therapeutic effect on DCM compared to AE. AED exhibited an inhibitory effect on the inflammatory response in the hearts of DCM rats and high-glucose-treated H9C2 cells by suppressing the pyroptosis pathway mediated by the nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain 3 (NLRP3) inflammasome. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of differentially expressed genes showed a significant enrichment in the NOD-like receptor signaling pathway compared to the high-glucose group. Furthermore, overexpression of NLRP3 effectively reversed the anti-pyroptosis effects of AED in high-glucose-treated H9C2 cells. This study is the first to demonstrate that AED possesses the ability to inhibit myocardial pyroptosis in DCM. Targeting the pyroptosis pathway mediated by the NLRP3 inflammasome could provide a promising therapeutic strategy to enhance our understanding and treatment of DCM.

CDR1as promotes arrhythmias in myocardial infarction via targeting the NAMPT-NAD+ pathway.

Cardiac ventricular arrhythmia triggered by acute myocardial infarction (AMI) is a major cause of sudden cardiac death. We have reported previously that an increased serum level of circular RNA CDR1as is a potential biomarker of AMI. However, the possible role of CDR1as in post-infarct arrhythmia remains unclear. This study in MI mice investigated the effects and underlying mechanism of CDR1as in ventricular arrhythmias associated with MI. We showed that knockdown of CDR1as abbreviated the duration of the abnormally prolonged QRS complex and QTc intervals and decreased susceptibility to ventricular arrhythmias. Optical mapping demonstrated knockdown of CDR1as also reduced post-infarct arrhythmia by increasing the conduction velocity and decreasing dispersion of repolarization. Mechanistically, CDR1as led to the depletion of NAD+ and caused mitochondrial dysfunction by directly targeting the NAMPT protein and repressing its expression. Moreover, CDR1as aggravated dysregulation of the NaV1.5 and Kir6.2 channels in cardiomyocytes, a change which was alleviated by the replenishment of NAD+. These findings suggest that anti-CDR1as is a potential therapeutic approach for ischemic arrhythmias.

Simplified Rapid Hydration Prevents Contrast-Associated Acute Kidney Injury Among CKD Patients Undergoing Coronary Angiography.

BACKGROUND: Patients with chronic kidney disease (CKD) undergoing coronary angiography (CAG) are at high risk of contrast-associated acute kidney injury (CA-AKI) and mortality. Therefore, there is a clinical need to explore safe, convenient, and effective strategies for preventing CA-AKI. OBJECTIVES: This study sought to assess whether simplified rapid hydration is noninferior to standard hydration for CA-AKI prevention in patients with CKD. METHODS: This multicenter, open-label, randomized controlled study was conducted across 21 teaching hospitals and included 1,002 patients with CKD. Patients were randomized to either simplified hydration (SH) (SH group, with normal saline from 1 hour before to 4 hours after CAG at a rate of 3 mL/kg/h) or standard hydration (control group, with normal saline 12 hours before and 12 hours after CAG at a rate of 1 mL/kg/h). The primary endpoint of CA-AKI was a ≥25% or 0.5-mg/dL rise in serum creatinine from baseline within 48 to 72 hours. RESULTS: CA-AKI occurred in 29 of 466 (6.2%) patients in the SH group and in 38 of 455 (8.4%) patients in the control group (relative risk: 0.8; 95% CI: 0.5-1.2; P = 0.216). In addition, the risk of acute heart failure and 1-year major adverse cardiovascular events did not differ significantly between the groups. However, the median hydration duration was significantly shorter in the SH group than in the control group (6 vs 25 hours; P < 0.001). CONCLUSIONS: In CKD patients undergoing CAG, SH is noninferior to standard hydration in preventing CA-AKI with a shorter hydration duration.

Investigation and Improvement of Pushing Dislocation in Ceramsite Sand Three-Dimensional Printing.

Three-dimensional printing (3DP) is considered to be one of the important technologies for a new manufacturing mode. When ceramsite sand is used as a 3DP material to produce a mold (core), the printed layer is prone to deviation from the original location. In this study, the continuous stacking of the printed part deviation was termed as pushing dislocation, and a physical model was designed to investigate the pushing dislocation mechanism. When the gravity of the printing layer and the pressure of the sand scraper decreased, or when the supporting force increased, the angle of the sand scraper and the maximum friction of the prelaying layer on the printed part will reduce the pushing dislocation. To optimize the quality of the ceramsite sand mold, experiments on the pushing dislocation were conducted by altering the recoater speed, layer thickness, and bottom support condition (with or without bottom supporting plate). The sample dimensions were obtained by a 3D imaging scanner, and the gas evolution and ignition loss were measured. The results revealed that the dimensional difference of samples continuously decreased and the pushing dislocation was gradually reduced as the recoater speed and layer thickness increased. The pushing dislocation of the X-direction sample was more severe compared with that of the Y-direction sample. Increasing the layer thickness is an effective way of reducing the pushing dislocation. The bottom supporting plate can reduce the pushing dislocation, but the effect was insignificant.

Enhanced degradation of phthalate esters (PAEs) by biochar-sodium alginate immobilised Rhodococcus sp. KLW-1.

In this study, a new strain of bacteria, named Rhodococcus sp. KLW-1, was isolated from farmland soil contaminated by plastic mulch for more than 30 years. To improve the application performance of free bacteria and find more ways to use waste biochar, KLW-1 was immobilised on waste biochar by sodium alginate embedding method to prepare immobilised pellet. Response Surface Method (RSM) predicted that under optimal conditions (3% sodium alginate, 2% biochar and 4% CaCl2), di (2-ethylhexyl) phthalate (DEHP) degradation efficiency of 90.48% can be achieved. Under the adverse environmental conditions of pH 5 and 9, immobilisation increased the degradation efficiency of 100 mg/L DEHP by 16.42% and 11.48% respectively, and under the high-stress condition of 500 mg/L DEHP concentration, immobilisation increased the degradation efficiency from 71.52% to 91.56%, making the immobilised pellets have strong stability and impact load resistance to environmental stress. In addition, immobilisation also enhanced the degradation efficiency of several phthalate esters (PAEs) widely existing in the environment. After four cycles of utilisation, the immobilised particles maintained stable degradation efficiency for different PAEs. Therefore, immobilised pellets have great application potential for the remediation of the actual environment.

Aloe-emodin ameliorated MI-induced cardiac remodeling in mice via inhibiting TGF-ß/SMAD signaling via up-regulating SMAD7.

BACKGROUND: Aloe-emodin (AE), a natural anthraquinone extract from traditional Chinese medicinal plants, has been certified to protect against acute myocardial ischemia. However, its effect on cardiac remodeling after chronic myocardial infarction (MI) and the possible mechanism remain unclear. PURPOSE: This study investigated the effect of AE on cardiac remodeling and oxidative damage induced by myocardial infarction (MI) in vitro and explored the underlying mechanisms. METHODS: Echocardiography and Masson staining were used to demonstrate myocardial dysfunction and fibrosis. Cell apoptosis was detected by TUNEL staining. The expressions of fibrosis-related factors such as type I collagen, α-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) were detected by Western blot. RESULTS: Our data demonstrated that AE treatment significantly improved cardiac function, reduced structural remodeling, and reduced cardiac apoptosis and oxidative stress in mice with myocardial infarction. In vitro, AE could protect neonatal mouse cardiomyocytes (NMCM) from angiotensin II (Ang II)-induced cardiomyocyte hypertrophy and apoptosis, and significantly inhibited (p < 0.05) Ang II-induced reactive oxygen species (ROS) increase. Furthermore, AE treatment significantly reversed the Ang ii-induced upregulation. CONCLUSION: In summary, our work reveals for the first time that AE activates the TGF-ß signaling pathway by up-regulating Smad7 expression, which in turn regulates the expression of fibrosis-related genes, ultimately improving cardiac function, inhibiting the development of cardiac fibrosis and hypertrophy in rats with chronic MI.

Tumour-derived small extracellular vesicles contribute to the tumour progression through reshaping the systemic immune macroenvironment.

BACKGROUND: Tumour-derived small extracellular vesicles (sEVs) play a crucial role in cancer immunomodulation. In addition to tumour immune microenvironment, the peripheral immune system also contributes significantly to cancer progression and is essential for anticancer immunity. However, a comprehensive definition of which and how peripheral immune lineages are regulated by tumour-derived sEVs during cancer development remains incomplete. METHODS: In this study, we used mass cytometry with extensive antibody panels to comprehensively construct the systemic immune landscape in response to tumour development and tumour-derived sEVs. RESULTS: Systemic immunity was dramatically altered by tumour growth and tumour-derived sEVs. Tumour-derived sEVs significantly and extensively affected immune cell population composition as well as intracellular pathways, resulting in an immunosuppressive peripheral and tumour immune microenvironment, characterised by increased myeloid-derived suppressor cells and decreased Ly6C+CD8 T cells. These sEVs largely promoted hematopoietic recovery and accelerate the differentiation towards myeloid-derived suppressor cells. The knockdown of Rab27a reduced sEV secretion from tumour cells and delayed tumour growth and metastasis in vivo. CONCLUSIONS: These results highlight that tumour-derived sEVs function as a bridge between peripheral immunity regulation and the tumour microenvironment, and contribute to cancer progression through altering the composition and function of the global immune macroenvironment.

Himalayan mountains imposing a barrier on gene flow of wheat yellow rust pathogen in the bordering regions of Pakistan and China.

The wheat yellow rust pathogen has been shown to be diverse and potentially originated in the Himalayan region. Although Himalayan populations of Pakistan, Nepal and Bhutan have been previously compared, little is known about the relative divergence and diversity in Puccinia striiformis populations in the bordering regions of Pakistan and China. To assess the relative diversity and divergence in these regions of Pakistan (Gilgit-Baltistan, Hazara and Azad Jammu Kashmir) and China (Xinjiang, Qinghai, Tibet, Sichuan, Guizhou and Yunnan), a total of 1245 samples were genotyped using 17 microsatellite SSR markers. A clear divergence was observed between the bordering regions of Pakistan and China (FST = 0.28) without any resampling of genetic groups and multilocus genotypes across two sides of the Himalayan mountains. The closest subpopulations across the two countries were Xinjiang and Gilgit-Baltistan (Nei's distance = 0.147), which were close geographically. A very high diversity and recombinant population structure was observed in both populations, though slightly higher in China (Genotypic diversity = 0.970; r¯d = 0.000) than in Pakistan (Genotypic diversity = 0.902; r¯d = 0.065). The distribution of genetic groups and resampling of MLGs revealed more gene flow across Yunnan, Guizhou and Sichuan regions in China, while between Hazara and Azad-Jammu Kashmir in Pakistan. The lack of gene flow between Pakistan and China populations is due to geographical barriers and a large patch of land without wheat. The information on the relative diversity and divergence in different geographical zones of the pathogen center of diversity and neighboring region should be considered in resistant wheat deployment while considering the invasion potential of the pathogen at regional and global contexts.

7,8-Dihydroxyflavone alleviates cardiac fibrosis by restoring circadian signals via downregulating Bmal1/Akt pathway.

Brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) pathway is a therapeutic target in cardiac diseases. A BDNF mimetic, 7,8-dihydroxyflavone (7,8-DHF), is emerging as a protective agent in cardiomyocytes; however, its potential role in cardiac fibroblasts (CFs) and fibrosis remains unknown. Thus, we aimed to explore the effects of 7,8-DHF on cardiac fibrosis and the possible mechanisms. Myocardial ischemia (MI) and transforming growth factor-ß1 (TGF-ß1) were used to establish models of cardiac fibrosis. Hematoxylin & eosin and Masson's trichrome stains were used for histological analysis and determination of collagen content in mouse myocardium. Cell viability kit, EdU (5-ethynyl-2'-deoxyuridine) assay and immunofluorescent stain were employed to examine the effects of 7,8-DHF on the proliferation and collagen production of CFs. The levels of collagen I, α-smooth muscle actin (α-SMA), TGF-ß1, Smad2/3, and Akt as well as circadian rhythm-related signals including brain and muscle Arnt-like protein 1 (Bmal1), period 2 (Per2), and cryptochrome 2 (Cry2) were analyzed. Treatment with 7,8-DHF markedly alleviated cardiac fibrosis in MI mice. It inhibited the activity of CFs accompanied by decreasing number of EdU-positive cells and downregulation of collagen I, α-SMA, TGF-ß1, and phosphorylation of Smad2/3. 7,8-DHF significantly restored the dysregulation of Bmal1, Per2, and Cry2, but inhibited the overactive Akt. Further, inhibition of Bmal1 by SR9009 effectively attenuated CFs proliferation and collagen production of CFs. In summary, these findings indicate that 7,8-DHF attenuates cardiac fibrosis and regulates circadian rhythmic signals, at least partly, by inhibiting Bmal1/Akt pathway, which may provide new insights into therapeutic cardiac remodeling.

Genetic Characteristics and Linkage of Virulence Genes of the Puccinia striiformis f. sp. tritici TSA-6 Isolate to Yr5 Host Resistance.

To understand the inheritance of the TSA-6 Puccinia striiformis f. sp. tritici (Pst) isolate that is virulent to Yr5 and was recently detected in China, we analyzed avirulence and virulence of 120 selfed progeny lines from Berberis shensiana. The results showed that the TSA-6 isolate is virulent against the Yr5 resistance gene, and overall progeny lines were categorized into 73 virulence phenotypes (VPs); of these, 72 VPs differed from the isolate TSA-6, and only one VP, including three progeny, was identical to the parental isolate. The analyses indicated that the TSA-6 isolate is homozygous for avirulence at the Yr10, Yr15, and Yr26 resistance loci and virulence at the YrA resistance locus. The TSA-6 isolate is heterozygous for avirulence at the Yr2, Yr3, Yr5, Yr7, and Yr8 resistance loci, which are controlled by a dominant/recessive relationship. The Yr1, Yr6, Yr9, Yr17, Yr27, Yr25, Yr28, Yr29, Yr32, YrTr1, and YrSP resistance loci are governed by two complementary dominant/recessive genes. Avirulence against heterozygous Yr4, Yr43, Yr44, Yr76, and YrExp2 resistance loci is regulated by a dominant and recessive or a dominant and suppressor gene pair. In total, 117 multilocus genotypes were detected at 24 KASP-SNP marker loci among the 120 progenies. Using these marker loci, we constructed a linkage map with a genetic distance interval spanning 624.5 cM. Quantitative trait loci corresponding to phenotypic segregation for virulence at 20 Yr resistance loci in addition to the Yr1 resistance locus were identified. These results facilitate our understanding of Pst virulence evolution and simplify breeding of wheat cultivars with effective resistance to wheat stripe rust.

Applying deep learning-based regional feature recognition from macro-scale image to assist energy saving and emission reduction in industrial energy systems.

INTRODUCTION: Image recognition technology has immense potential to be applied in industrial energy systems for energy conservation. However, the low recognition accuracy and generalization ability under actual operation conditions limit its commercial application. OBJECTIVES: To improve the recognition accuracy and generalization ability, a novel image recognition method integrating deep learning and domain knowledge was applied to assist energy saving and emission reduction for industrial energy systems. METHODS: As a typical industrial scenario, the defrosting control in the refrigeration system was selected as the specific optimization object. By combining deep learning algorithm with domain knowledge, a residual-based convolutional neural network model (RCNN) was proposed specifically for frosty state recognition, which features the residual input and average pooling output. Based on the real-time recognition of frosty levels, a defrosting control optimization method was proposed to initiate and terminate the defrosting operation on demand. RESULTS: By combining the advanced image recognition technique with specific energy domain knowledge, the proposed RCNN enables both high recognition accuracy and strong generalization ability. The recognition accuracy of RCNN reached 95.06% for the trained objects and 93.67% for non-trained objects while that of only 75.86% for the conventional CNN. By adopting the presented system optimization method assisted by RCNN, the defrosting frequency, accumulated time and energy consumption were 53.8%, 57.02% and 34.5% less than the original control method. Furthermore, the environmental and cost analysis illustrated that the annual reduction in CO2 emissions is 2145.21 to 3412.84 kg and the payback time was less than 2.5 years which was far below the service life. CONCLUSION: The technical feasibility and significant energy-saving benefits of deep learning-based image recognition method were demonstrated through the field experiment. Our study shows the great application potential of image recognition technology and promotes carbon neutrality in industrial energy systems.