Different ER-plasma membrane tethers play opposing roles in autophagy of the cortical ER.

The endoplasmic reticulum (ER) undergoes degradation by selective macroautophagy (ER-phagy) in response to starvation or the accumulation of misfolded proteins within its lumen. In yeast, actin assembly at sites of contact between the cortical ER (cER) and endocytic pits acts to displace elements of the ER from their association with the plasma membrane (PM) so they can interact with the autophagosome assembly machinery near the vacuole. A collection of proteins tether the cER to the PM. Of these, Scs2/22 and Ist2 are required for cER-phagy, most likely through their roles in lipid transport, while deletion of the tricalbins, TCB1/2/3, bypasses those requirements. An artificial ER-PM tether blocks cER-phagy in both the wild type (WT) and a strain lacking endogenous tethers, supporting the importance of cER displacement from the PM. Scs2 and Ist2 can be cross-linked to the selective cER-phagy receptor, Atg40. The COPII cargo adaptor subunit, Lst1, associates with Atg40 and is required for cER-phagy. This requirement is also bypassed by deletion of the ER-PM tethers, suggesting a role for Lst1 prior to the displacement of the cER from the PM during cER-phagy. Although pexophagy and mitophagy also require actin assembly, deletion of ER-PM tethers does not bypass those requirements. We propose that within the context of rapamycin-induced cER-phagy, Scs2/22, Ist2, and Lst1 promote the local displacement of an element of the cER from the cortex, while Tcb1/2/3 act in opposition, anchoring the cER to the plasma membrane.

ER-phagy requires the assembly of actin at sites of contact between the cortical ER and endocytic pits.

Fragments of the endoplasmic reticulum (ER) are selectively delivered to the lysosome (mammals) or vacuole (yeast) in response to starvation or the accumulation of misfolded proteins through an autophagic process known as ER-phagy. A screen of the Saccharomyces cerevisiae deletion library identified end3Δ as a candidate knockout strain that is defective in ER-phagy during starvation conditions, but not bulk autophagy. We find that loss of End3 and its stable binding partner Pan1, or inhibition of the Arp2/3 complex that is coupled by the End3-Pan1 complex to endocytic pits, blocks the association of the cortical ER autophagy receptor, Atg40, with the autophagosomal assembly scaffold protein Atg11. The membrane contact site module linking the rim of cortical ER sheets and endocytic pits, consisting of Scs2 or Scs22, Osh2 or Osh3, and Myo3 or Myo5, is also needed for ER-phagy. Both Atg40 and Scs2 are concentrated at the edges of ER sheets and can be cross-linked to each other. Our results are consistent with a model in which actin assembly at sites of contact between the cortical ER and endocytic pits contributes to ER sequestration into autophagosomes.

Superconducting nanowire single-photon detector with polarization insensitivity, ultrafast response, and high efficiency.

This study proposed what we believe to be a novel method for fabricating superconducting nanowire single-photon detectors (SNSPDs) with high efficiency, polarization insensitivity, and ultrafast response. To achieve these properties in niobium nitride (NbN) SNSPDs, the periodic four-split rings (PFSR) were positioned above the nanowires. This design uses the localized surface plasmon resonance to enhance the electric field around nanowires. For an incident light with a wavelength of 1550 nm, the PFSR-SNSPD structure achieved a polarization extinction ratio of 1.0064 and absorptions of 88.94% and 88.37% under TE and TM polarizations, respectively. The nanowire length was reduced by 85% using a meandering nanowire arrangement with a fill factor of 0.074.

Ultra-sensitive pressure sensor with low-temperature crosstalk based on the Vernier effect and helical structure.

What we believe to be a novel high-sensitivity fiber-optic pressure sensor based on the vernier effect and helical structure is proposed and experimentally verified. The sensor utilizes the superposition of higher-order mode Mach-Zehnder interference and Sagnac fundamental mode polarization interference in a single fiber ring to achieve the vernier effect. In addition, a non-invasive encapsulation structure was fabricated to convert the rise and fall of the pressure value into the change in the twist angle of the optical fiber. This approach reduces the interference of the detecting medium on the sensor signal while simultaneously increasing the sensitivity of the pressure sensor. According to experimental data, the detection sensitivity of the sensor can reach -67277 nm/MPa, which is 65 times higher than the sensitivity of the conventional vernier effect pressure sensor. It also solves the issue of temperature interference with the Vernier-effect structured fiber optic sensor. The sensor has a measured temperature cross-sensitivity of 0.000065 kPa/°C, which is significantly lower than that of comparable sensors. This makes the sensor highly sensitive and ideal for low crosstalk pressure measurement.

Predictive markers for infections after extracorporeal shockwave lithotripsy in patients with kidney stone based on a large prospective cohort.

OBJECTIVE: Infections in patients with kidney stones after extracorporeal shockwave lithotripsy (SWL) is a common clinical issue. However, the associated factors are unclear. Therefore, we aim to develop and validate a predictive model for infections after SWL in patients with kidney stone. METHODS: Between June 2020 and May 2022, consecutive kidney stone patients were enrolled. Of them, 553 patients comprised the development cohort. One hundred sixty-five patients comprised the validation cohort. The data were prospectively collected. The stepwise selection was applied using the likelihood ratio test with Akaike's information criterion as the stopping rule; A predictive model was constructed through multivariate logistic regression. The performance was evaluated regarding discrimination, calibration, and clinical usefulness. RESULTS: Predictors of infections after SWL in treating kidney stones included older age (OR = 1.026, p = 0.041), female (OR = 2.066, p = 0.039), higher BMI (OR = 1.072, p = 0.039), lower stone density (OR = 0.995, p < 0.001), and higher grade of hydronephrosis (OR = 5.148, p < 0.001). For the validation cohort, the model showed good discrimination with an area under the receiver operating characteristic curve of 0.839 (95% CI 0.736, 0.941) and good calibration. Decision curve analysis demonstrated that the model was also clinically useful. CONCLUSION: This study indicated that age, gender, BMI, stone density, and hydronephrosis grade were significant predictors of infections after SWL in treating kidney stones. It provided evidence in optimizing prevention and perioperative treatment strategies to reduce the risk of infection after SWL.

Perceptions, attitudes and barriers to effective obesity care among people living with obesity and healthcare professionals in China: The ACTION-China study.

AIMS: To identify perceptions, attitudes, behaviours and barriers to effective obesity care among people living with obesity (PLwO) and healthcare professionals (HCPs) across mainland China. MATERIALS AND METHODS: ACTION-China (ClinicalTrials.gov: NCT05428501) was a cross-sectional, observational, descriptive, online survey-based study of 7000 PLwO and 1000 HCPs (conducted between August and November 2022). RESULTS: The majority of PLwO (76.8% [5374/7000]) and HCPs (94.6% [946/1000]) agreed that obesity is a chronic disease. Only 40.8% of PLwO (2853/7000) had discussed their weight or talked about losing weight with an HCP in the past 5 years. The most frequent reason given by PLwO for not discussing weight management with an HCP was believing it was their responsibility to manage their weight (34.7% [2430/7000]), whereas the most frequent reason HCPs gave for not discussing obesity with their patients with obesity was having more important health issues to discuss (72.1% [721/1000]). A smaller proportion of PLwO (19.1%) than HCPs (53.6%) felt that weight management discussions with an HCP would be very or extremely helpful for the patient, and 30.7% of PLwO experienced negative feelings after their most recent discussion. Overall, 34.8% (2438/7000) of PLwO had been diagnosed with obesity by an HCP, while 30.0% (2101/7000) of PLwO did not recognize that they had obesity. CONCLUSIONS: This large, national survey conducted among PLwO and HCPs highlights key barriers to effective obesity care in China, including underestimation of weight status by PLwO and the need for increased communication between HCPs and PLwO regarding weight management.

Bubble Turbulent Gas-Permeable Membrane for Ammonia Recovery from Swine Wastewater: Mass Transfer Enhancement and Antifouling Mechanisms.

Recovering ammonium from swine wastewater employing a gas-permeable membrane (GM) has potential but suffers from the limitations of unattractive mass transfer and poor-tolerance antifouling properties. Turbulence is an effective approach to enhancing the release of volatile ammonia from wastewater while relying on interfacial disturbance to interfere with contaminant adhesion. Herein, we design an innovative gas-permeable membrane coupled with bubble turbulence (BT-GM) that enhances mass transfer while mitigating membrane fouling. Bubbles act as turbulence carriers to accelerate the release and migration of ammonia from the liquid phase, increasing the ammonia concentration gradient at the membrane-liquid interface. In comparison, the ammonium mass transfer rate of the BT-GM process applied to real swine wastewater is 38% higher than that of conventional GM (12 h). Through a computational fluid dynamics simulation, the turbulence kinetic energy of BT-GM system is 3 orders of magnitude higher than that of GM, and the effective mass transfer area is nearly 3 times that of GM. Seven batches of tests confirmed that the BT-GM system exhibits remarkable antifouling ability, broadens its adaptability to complex water quality, and practically promotes the development of sustainable resource recycling.

Boosting N2O Catalytic Decomposition by the Synergistic Effect of Multiple Elements in Cobalt-Based High-Entropy Oxides.

Nitrous oxide (N2O) has a detrimental impact on the greenhouse effect, and its efficient catalytic decomposition at low temperatures remains challenging. Herein, the cobalt-based high-entropy oxide with a spinel-type structure (Co-HEO) is successfully fabricated via a facile coprecipitation method for N2O catalytic decomposition. The obtained Co-HEO catalyst displays more remarkable catalytic performance and higher thermal stability compared with single and binary Co-based oxides, as the temperature of 90% N2O decomposition (T90) is 356 °C. A series of characterization results reveal that the synergistic effect of multiple elements enhances the reducibility and augments oxygen vacancy in the high-entropy system, thus boosting the activity of the Co-HEO catalyst. Moreover, density functional theory (DFT) calculations and the temperature-programmed surface reaction (TPSR) with isotope labeling demonstrate that N2O decomposition on the Co-HEO catalyst follows the Langmuir-Hinshelwood (L-H) mechanism with the promotion of abundant oxygen vacancies. This work provides a fundamental understanding of the synergistic catalytic effect in N2O decomposition and paves the way for the novel environmental catalytic applications of HEO.

Association between body mass index and mental health among nurses: a cross-sectional study in China.

PURPOSE: To examine the correlation between body mass index (BMI) and mental well-being in Chinese nurses during the COVID-19 epidemic. METHOD: This study was conducted in a tertiary hospital using a cross-sectional design. A total of 2,811 nurses were enlisted at Shengjing Hospital in China during the period from March to April, 2022. Information was gathered through a questionnaire that individuals completed themselves. The mental health of the participants was assessed using the Patient Health Questionnaire-9 and the Generalized Anxiety Disorder Assessment-7. Binary logistic regression was used to calculate adjusted odds ratios (ORs) and their corresponding 95% confidence intervals. RESULTS: The prevalence of nurses experiencing depression and anxiety was 7.8% (219) and 6.7% (189), respectively. Regarding depression after adjustment, the odds ratios (ORs) for each quartile, compared to the lowest quartile, were as follows: 0.91 (95% confidence interval [CI]: 0.53, 1.56), 2.28 (95% CI: 0.98, 3.77), and 2.32 (95% CI: 1.41, 3.83). The p-value for trend was found to be 0.001. The odds ratios (ORs) for anxiety after adjustment were 2.39 (0.83, 4.36), 4.46 (0.51, 7.93), and 2.81 (1.56, 5.08) when comparing the highest quartiles to the lowest quartile. The p-value for trend was 0.009. CONCLUSION: This study found a positive association between BMI and poor mental health among nurses during the COVID-19 pandemic, particularly in those who were overweight or obesity. The findings could assist in developing interventions and help policy-makers establish appropriate strategies to support the mental health of frontline nurses, especially those who are overweight or obesity.

Bioactivities and chemical profiling comparison and metabolomic variations of polyphenolics and steroidal glycoalkaloids in different parts of Solanum nigrum L.

INTRODUCTION: Solanum nigrum L. is a traditional medicinal herb and edible plant. Many studies provide evidence that S. nigrum L. is a nutritious vegetable. Polyphenols and steroidal glycoalkaloids are the main components. OBJECTIVES: This study aimed to systemically evaluate the phytochemical profile, quantification, and bioactivities of polyphenolics and glycoalkaloids in different parts of S. nigrum L. RESULTS: Total polyphenols (TPC) and total glycoalkaloids (TGK) were determined using the Folin-Ciocalteu and acid dye colorimetric methods, respectively. A total of 55 polyphenolic constituents (including 22 phenolic acids and 33 flavonoids) and 24 steroidal glycoalkaloids were identified from different parts using ultrahigh-performance liquid chromatography Q-exactive high-resolution mass spectrometry (UHPLC-QE-HRMS), of which 40 polyphenols (including 15 phenolic acids and 25 flavonoids) and one steroidal glycoalkaloid were characterised for the first time in S. nigrum L. Moreover, typical polyphenols and glycoalkaloids were determined using HPLC-UV and HPLC-evaporative light-scattering detector (ELSD), respectively. In addition, the TPC and TGK and their typical constituents were compared in different anatomical parts. Finally, the antioxidant capacities of polyphenolic extracts from different parts of S. nigrum L. were evaluated by ·OH, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and ferric-reducing antioxidant power (FRAP) assay in vitro. In addition, the antitumour effects of TGK from different parts of S. nigrum L. on the proliferation of PC-3 cells were investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Polyphenolic and glycoalkaloid extracts from different parts of S. nigrum L. showed different antioxidant and cytotoxic capacities in vitro. CONCLUSION: This is the first study to systematically differentiate between polyphenolic and glycoalkaloid profiles from different parts of S. nigrum L.

Mechanism of probiotics in the intervention of colorectal cancer: a review.

The human microbiome interacts with the host mainly in the intestinal lumen, where putrefactive bacteria are suggested to promote colorectal cancer (CRC). In contrast, probiotics and their isolated components and secreted substances, display anti-tumor properties due to their ability to modulate gut microbiota composition, promote apoptosis, enhance immunity, resist oxidation and alter metabolism. Probiotics help to form a solid intestinal barrier against damaging agents via altering the gut microbiota and preventing harmful microbes from colonization. Probiotic strains that specifically target essential proteins involved in the process of apoptosis can overcome CRC resistance to apoptosis. They can increase the production of anti-inflammatory cytokines, essential in preventing carcinogenesis, and eliminate cancer cells by activating T cell-mediated immune responses. There is a clear indication that probiotics optimize the antioxidant system, decrease radical generation, and detect and degrade potential carcinogens. In this review, the pathogenic mechanisms of pathogens in CRC and the recent insights into the mechanism of probiotics in CRC prevention and therapy are discussed to provide a reference for the actual application of probiotics in CRC.

Heterologous expression and characterization of a dye-decolorizing peroxidase from Ganoderma lucidum, and its application in decolorization and detoxifization of different types of dyes.

Dye-decolorizing peroxidases (DyPs) belong to a novel superfamily of heme peroxidases that can oxidize recalcitrant compounds. In the current study, the GlDyP2 gene from Ganoderma lucidum was heterologously expressed in Escherichia coli, and the enzymatic properties of the recombinant GlDyP2 protein were investigated. The GlDyP2 protein could oxidize not only the typical peroxidase substrate ABTS but also two lignin substrates, namely guaiacol and 2,6-dimethoxy phenol (DMP). For the ABTS substrate, the optimum pH and temperature of GlDyP2 were 4.0 and 35 °C, respectively. The pH stability and thermal stability of GlDyP2 were also measured; the results showed that GlDyP2 could function normally in the acidic environment, with a T50 value of 51 °C. Moreover, compared to untreated controls, the activity of GlDyP2 was inhibited by 1.60 mM of Mg2+, Ni2+, Mn2+, and ethanol; 0.16 mM of Cu2+, Zn2+, methanol, isopropyl alcohol, and Na2EDTA·2H2O; and 0.016 mM of Fe2+ and SDS. The kinetic constants of recombinant GlDyP2 for oxidizing ABTS, Reactive Blue 19, guaiacol, and DMP were determined; the results showed that the recombination GlDyP2 exhibited the strongest affinity and the most remarkable catalytic efficiency towards guaiacol in the selected substrates. GlDyP2 also exhibited decolorization and detoxification capabilities towards several dyes, including Reactive Blue 19, Reactive Brilliant Blue X-BR, Reactive Black 5, Methyl Orange, Trypan Blue, and Malachite Green. In conclusion, GlDyP2 has good application potential for treating dye wastewater.

Application of Miscanthus substrates in the cultivation of Ganoderma lingzhi.

Ganoderma lingzhi is a traditional Chinese medicine that has been used to improve health and longevity for thousands of years. It is usually cultivated on hardwood log- or sawdust-based formulations. Conversely, in this study, we used Miscanthus sacchariflorus (MSF), M. floridulus, and M. sinensis (MSS), fast-growing perennial grasses widely distributed in China, for G. lingzhi cultivation. Mycelial growth rate, activities of lignin-degrading enzymes on colonized mushroom substrates, and expression levels of CAZymes and laccase genes based on different substrates were analyzed. Total triterpenoids, sterols, and polysaccharides content of fruiting bodies obtained from different substrates were investigated. The activities of laccase and manganese peroxidase in mycelia increased in the MSF- and MSS-based formulations compared with that in the sawdust-based formulation. The results of mycelial growth- and cultivation-related experiments showed that the Miscanthus substrates could be used as the substrates for cultivating G. lingzhi. The content of active ingredients, namely triterpenoids, sterols, and polysaccharides, in fruiting bodies cultivated on the Miscanthus substrates did not decrease compared with those in substrate obtained from the sawdust-based formulation. Therefore, the present study provides alternative substrates for the cultivation of G. lingzhi, and a reference for better utilization of inexpensive substrate in future.

Self-Reconstruction of Fe-Doped Co-Metal-Organic Frameworks Boosted Electrocatalytic Performance for Oxygen Evolution Reaction.

Rational design of facile and low-cost efficient electrocatalysts for oxygen evolution reaction (OER) is crucial to solve the energy crisis. Benefiting from in situ self-reconstruction from metal-organic frameworks (MOFs) to (oxy)hydroxides in alkaline electrolytes, MOFs have become alternative OER catalysts. Thus, Fe-doped Co-MOF nanosheets (Co-MOF/Fe) were prepared and utilized straightforwardly as OER electrocatalysts. CoFe-layered bimetallic hydroxides (CoFe-LDHs) with abundant active sites are obtained from in situ conversion of Co-MOF/Fe after etching by the KOH electrolyte, which are generally actual active species. Meanwhile, the introduction of Fe ions will also produce a synergistic effect that greatly improves the electrocatalytic OER performance. The optimized catalyst (Co-MOF/Fe10) shows exceptional OER activity (η10 = 260 mV) and excellent durability over 50 h. The outstanding OER performance of Co-MOF/Fe10 can also be reflected in the two-electrode hydrolyzer (1.57 V at 10 mA cm-2). This study offers a pathway to probe the catalytic mechanism of MOFs and the rational construction of efficient MOF-derived catalysts.

Ce-Modified Flowerlike NiFe-MOF Nanostructure Based on Ion Competitive Coordination for Enhancing the Oxygen Evolution Reaction.

Metal-organic framework (MOF) has become a popular electrocatalyst for the oxygen evolution reaction (OER) because of its large specific surface area and adjustable porosity. Nevertheless, the electrochemical performance of MOFs has been greatly limited by poor intrinsic conductivity and catalytic activity. Herein, we report a Ce-doped nanoflower-like MOF material Ce@NiFe-MOF-5 via a facile ion competitive coordination effect and doping method. Benefiting from the nanoflower structure formed by the stacking of nanosheets, a large number of active sites can be exposed, which favors electron/mass transfer during water oxidation. The coordination substitution of Ce ions not only promoted an increase in the number of active sites on the surface of the nanosheets but also optimized the electronic structure of pristine NiFe-MOF. The well-designed Ce@NiFe-MOF-5 catalysts exhibited superior OER performance under basic conditions, which only required an overpotential of 258 mV at a current density of 10 mA cm-2 and a Tafel slope of 54.44 mV dec-1. Moreover, when Ce@NiFe-MOF-5 served as an anode and Pt/C as a cathode, the two-electrode system only needed 1.56 V to drive overall water splitting at 10 mA cm-2.

Transcription factors: switches for regulating growth and development in macrofungi.

Macrofungi (or mushrooms) act as an extraordinarily important part to human health due to their nutritional and/or medicinal value, but the detailed researches in growth and development mechanisms have yet to be explored further. Transcription factors (TFs) play indispensable roles in signal transduction and affect growth, development, and metabolism of macrofungi. In recent years, increasing research effort has been employed to probe the relationship between the development of macrofungi and TFs. Herein, the present review comprehensively summarized the functional TFs researched in macrofungi, including modulating mycelial growth, fructification, sclerotial formation, sexual reproduction, spore formation, and secondary metabolism. Meanwhile, the possible effect mechanisms of TFs on the growth and development of some macrofungi were also revealed. Specific examples of functional characterizations of TFs in macrofungi (such as Schizophyllum commune and Coprinopsis cinerea) were described to a better comprehension of regulatory effect. Future research prospects in the field of TFs of macrofungi are discussed. We illustrated the functional versatility of the TFs in macrofungi based on specific examples. A systematical realization of the interaction and possible mechanisms between TFs and macrofungi can supply possible solutions to regulate genetic characteristics, which supply novel insights into the regulation of growth, development and metabolism of macrofungi. KEY POINTS: • The functional TFs researched in macrofungi were summarized. • The possible effect mechanisms of TFs in macrofungal were described. • The multiple physiological functions of TFs in macrofungi were discussed.

Unusual presentation of a case of fetal hepatic mass: a case report.

BACKGROUND: Giant hepatic hemangiomas are rare and can cause serious complications that contribute to a high risk of perinatal mortality. The purpose of this article is to review the prenatal imaging features, treatment, pathology, and prognosis of an atypical fetal giant hepatic hemangioma and to discuss the differential diagnosis of fetal hepatic masses. CASE PRESENTATION: A gravida 9, para 0 woman at 32 gestational weeks came to our institution for prenatal ultrasound diagnosis. A complex, heterogeneous hepatic mass measuring 5.2 × 4.1 × 3.7 cm was discovered in the fetus using conventional two-dimensional ultrasound. The mass was solid and had both a high peak systolic velocity (PSV) of the feeding artery and intratumoral venous flow. Fetal magnetic resonance imaging (MRI) revealed a clear, hypointense T1-W and hyperintense T2-W solid hepatic mass. Prenatal diagnosis was very difficult due to the overlap of benign and malignant imaging features on prenatal ultrasound and MRI. Even postnatally, neither contrast-enhanced MRI nor contrast-enhanced computed tomography (CT) was useful in accurately diagnosing this hepatic mass. Due to persistently elevated Alpha-fetoprotein (AFP), a laparotomy was performed. Histopathological examination of the mass showed atypical features such as hepatic sinus dilation, hyperemia, and hepatic chordal hyperplasia. The patient was ultimately diagnosed with a giant hemangioma, and the prognosis was satisfactory. CONCLUSIONS: When a hepatic vascular mass is found in a third trimester fetus a hemangioma should be considered as a possible diagnosis. However, prenatal diagnosis of fetal hepatic hemangiomas can be challenging due to atypical histopathological findings. Imaging and histopathological assays can provide useful information for the diagnosis and treatment of fetal hepatic masses.

Exosome-derived circ_0001785 delays atherogenesis through the ceRNA network mechanism of miR-513a-5p/TGFBR3.

PURPOSE: Endothelial cell dysfunction is a major cause of early atherosclerosis. Although the role of extracellular vesicles in stabilizing atherosclerotic plaques is well established, the effect of circulating exosomes on plaque formation is still unknown. Here, we explored the effect of exosomes on atherosclerosis based on the function that exosomes can act on intercellular communication. PATIENTS AND METHODS: We extracted serum exosomes from the blood of CHD patients (CHD-Exo) and healthy individuals (Con-Exo). The obtained exosomes were co-cultured with human umbilical vein endothelial cells (HUVECs) in vitro. In addition, we determined that circ_0001785 functions as a competing endogenous RNA (ceRNAs) in coronary artery disease by dual luciferase reporter gene analysis. The protective effect of circ_0001785 against endothelial cell injury was also verified using over-expression lentiviral transfection functional assays. In vivo experiments, we injected over-expressed circ_0001785 lentivirus into the tail vein of mice to observe its therapeutic effect on a mouse model of atherosclerosis. RESULTS: The vitro co-cultured results showed that the amount of plasma-derived exosomes have an increase in patients with coronary artery disease, and the inflammation and apoptosis of endothelial cells were exacerbated. Over-expression of circ_0001785 reduced endothelial cell injury through the ceRNA network pathway of miR-513a-5p/TGFBR3. Quantitative reverse transcription-polymerase chain reaction identified that the expressed amount of circ_0001785 was reduced in the circulating peripheral blood of CHD patients and increased within human and mouse atherosclerotic plaque tissue. The results of in vivo experiments showed that circ_0001785 reduced aortic endothelial cell injury and the formation of intraplaque neo-vascularization, and enhanced left ventricular diastolic function, thereby delaying the development of atherosclerosis in mice. CONCLUSION: Our results demonstrated a new biomarker, exosome-derived circ_0001785, for atherogenesis, which can reduce endothelial cell injury and thus delay atherogenesis through the miR-513a-5p/TGFBR3 ceRNA network mechanism, providing an exosome-based intervention strategy for atherosclerosis.

gcType: a high-quality type strain genome database for microbial phylogenetic and functional research.

Taxonomic and functional research of microorganisms has increasingly relied upon genome-based data and methods. As the depository of the Global Catalogue of Microorganisms (GCM) 10K prokaryotic type strain sequencing project, Global Catalogue of Type Strain (gcType) has published 1049 type strain genomes sequenced by the GCM 10K project which are preserved in global culture collections with a valid published status. Additionally, the information provided through gcType includes >12 000 publicly available type strain genome sequences from GenBank incorporated using quality control criteria and standard data annotation pipelines to form a high-quality reference database. This database integrates type strain sequences with their phenotypic information to facilitate phenotypic and genotypic analyses. Multiple formats of cross-genome searches and interactive interfaces have allowed extensive exploration of the database's resources. In this study, we describe web-based data analysis pipelines for genomic analyses and genome-based taxonomy, which could serve as a one-stop platform for the identification of prokaryotic species. The number of type strain genomes that are published will continue to increase as the GCM 10K project increases its collaboration with culture collections worldwide. Data of this project is shared with the International Nucleotide Sequence Database Collaboration. Access to gcType is free at http://gctype.wdcm.org/.

Astragaloside IV restrains pyroptosis and fibrotic development of pulmonary artery smooth muscle cells to ameliorate pulmonary artery hypertension through the PHD2/HIF1α signaling pathway.

BACKGROUND: Astragaloside (AS)-IV, extracted from traditional Chinese medicine Astragalus mongholicus, has been widely used in the anti-inflammatory treatment for cardiovascular disease. However, the mechanism by which AS-IV affects pulmonary artery hypertension (PAH) development remains largely unknown. METHODS: Monocrotaline (MCT)-induced PAH model rats were administered with AS-IV, and hematoxylin-eosin staining and Masson staining were performed to evaluate the histological change in pulmonary tissues of rats. Pulmonary artery smooth muscle cells (PASMCs) were treated by hypoxia and AS-IV. Pyroptosis and fibrosis were assessed by immunofluorescence, western blot and enzyme-linked immunosorbent assay. RESULTS: AS-IV treatment alleviated pulmonary artery structural remodeling and pulmonary hypertension progression induced by MCT in rats. AS-IV suppressed the expression of pyroptosis-related markers, the release of pro-inflammatory cytokine interleukin (IL)-1ß and IL-18 and fibrosis development in pulmonary tissues of PAH rats and in hypoxic PAMSCs. Interestingly, the expression of prolyl-4-hydroxylase 2 (PHD2) was restored by AS-IV administration in PAH model in vivo and in vitro, while hypoxia inducible factor 1α (HIF1α) was restrained by AS-IV. Mechanistically, silencing PHD2 reversed the inhibitory effect of AS-IV on pyroptosis, fibrosis trend and pyroptotic necrosis in hypoxia-cultured PASMCs, while the HIF1α inhibitor could prevent these PAH-like phenomena. CONCLUSION: Collectively, AS-IV elevates PHD2 expression to alleviate pyroptosis and fibrosis development during PAH through downregulating HIF1α. These findings may provide a better understanding of AS-IV preventing PAH, and the PHD2/HIF1α axis may be a potential anti-pyroptosis target during PAH.