Ca2+-triggered Atg11-Bmh1/2-Snf1 complex assembly initiates autophagy upon glucose starvation.

Autophagy is essential for maintaining glucose homeostasis. However, the mechanism by which cells sense and respond to glucose starvation to induce autophagy remains incomplete. Here, we show that calcium serves as a fundamental triggering signal that connects environmental sensing to the formation of the autophagy initiation complex during glucose starvation. Mechanistically, glucose starvation instigates the release of vacuolar calcium into the cytoplasm, thus triggering the activation of Rck2 kinase. In turn, Rck2-mediated Atg11 phosphorylation enhances Atg11 interactions with Bmh1/2 bound to the Snf1-Sip1-Snf4 complex, leading to recruitment of vacuolar membrane-localized Snf1 to the PAS and subsequent Atg1 activation, thereby initiating autophagy. We also identified Glc7, a protein phosphatase-1, as a critical regulator of the association between Bmh1/2 and the Snf1 complex. We thus propose that calcium-triggered Atg11-Bmh1/2-Snf1 complex assembly initiates autophagy by controlling Snf1-mediated Atg1 activation in response to glucose starvation.

Intracranial Aneurysms Managed by Parent Artery Reconstruction Using Tubridge Flow Diverter study: 1-year outcomes.

OBJECTIVE: Previous randomized controlled trials have reported a significantly higher occlusion rate of large and giant aneurysms when utilizing the Tubridge flow diverter (FD). In the present trial, the safety and efficacy of the Tubridge FD in treating unruptured internal carotid artery (ICA) or vertebral artery (VA) aneurysms were assessed in a real-world setting. METHODS: The Intracranial Aneurysms Managed by Parent Artery Reconstruction Using Tubridge Flow Diverter (IMPACT) study is a prospective, multicenter, single-arm clinical trial assessing the efficacy of the Tubridge FD in the management of unruptured aneurysms located in the ICA or VA. The primary endpoint was the complete occlusion (Raymond-Roy class 1) rate at the 1-year follow-up. The secondary endpoints included the technical success rate, the successful occlusion rate of the aneurysm, which is the degree of aneurysm embolization scored as Raymond-Roy class 1 or 2, major (> 50%) in-stent stenosis, and incidence of disabling stroke or neurological death associated with the target aneurysms. RESULTS: This study included 14 interventional neuroradiology centers, with 200 patients and 240 aneurysms. According to angiographic core laboratory assessment, 205 (85.4%) aneurysms were located in the ICA, 34 (14.2%) in the VA, and 1 (0.4%) in the middle cerebral artery. Additionally, 189 (78.8%) aneurysms were small (< 10 mm). At the 12-month follow-up, the total occlusion rate was 79.0% (166/210, 95% CI 72.91%-84.34%). Additionally, the occurrence of disabling stroke or neurological death related to the specified aneurysms was 1% (2/200). CONCLUSIONS: The 1-year results from the IMPACT trial affirm the safety record of use of the Tubridge FD in the treatment of intracranial aneurysms in real-world scenarios. These results reveal low morbidity and mortality rates of 3.5% and 1.5%, respectively. Furthermore, they provide evidence of the effectiveness of the Tubridge FD, as demonstrated by the complete occlusion achieved in 166 of 210 (79%) cases.

The essential link: How STAT3 connects tumor metabolism to immunity.

Immunotherapy is a promising and long-lasting tumor treatment method, but it is challenged by the complex metabolism of tumors. To optimize immunotherapy, it is essential to further investigate the key proteins that regulate tumor metabolism and immune response. STAT3 plays a crucial role in regulating tumor dynamic metabolism and affecting immune cell function by responding to various cytokines and growth factors, which can be used as a potential target for immunotherapy. This review focuses on the crosstalk between STAT3 and tumor metabolism (including glucose, lipid, and amino acid metabolism) and its impact on the differentiation and function of immune cells such as T cells, tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs), and reveals potential treatment strategies.

Effects of an Early Intensive Blood Pressure-lowering Strategy Using Remifentanil and Dexmedetomidine in Patients with Spontaneous Intracerebral Hemorrhage: A Multicenter, Prospective, Superiority, Randomized Controlled Trial.

BACKGROUND: Although it has been established that elevated blood pressure and its variability worsen outcomes in spontaneous intracerebral hemorrhage, antihypertensives use during the acute phase still lacks robust evidence. A blood pressure-lowering regimen using remifentanil and dexmedetomidine might be a reasonable therapeutic option given their analgesic and antisympathetic effects. The objective of this superiority trial was to validate the efficacy and safety of this blood pressure-lowering strategy that uses remifentanil and dexmedetomidine in patients with acute intracerebral hemorrhage. METHODS: In this multicenter, prospective, single-blinded, superiority randomized controlled trial, patients with intracerebral hemorrhage and systolic blood pressure (SBP) 150 mmHg or greater were randomly allocated to the intervention group (a preset protocol with a standard guideline management using remifentanil and dexmedetomidine) or the control group (standard guideline-based management) to receive blood pressure-lowering treatment. The primary outcome was the SBP control rate (less than 140 mmHg) at 1 h posttreatment initiation. Secondary outcomes included blood pressure variability, neurologic function, and clinical outcomes. RESULTS: A total of 338 patients were allocated to the intervention (n = 167) or control group (n = 171). The SBP control rate at 1 h posttreatment initiation in the intervention group was higher than that in controls (101 of 161, 62.7% vs. 66 of 166, 39.8%; difference, 23.2%; 95% CI, 12.4 to 34.1%; P < 0.001). Analysis of secondary outcomes indicated that patients in the intervention group could effectively reduce agitation while achieving lighter sedation, but no improvement in clinical outcomes was observed. Regarding safety, the incidence of bradycardia and respiratory depression was higher in the intervention group. CONCLUSIONS: Among intracerebral hemorrhage patients with a SBP 150 mmHg or greater, a preset protocol using a remifentanil and dexmedetomidine-based standard guideline management significantly increased the SBP control rate at 1 h posttreatment compared with the standard guideline-based management.

Corrigendum: Comparison of cardiac function between single left ventricle and tricuspid atresia: assessment using echocardiography combined with computational fluid dynamics.

[This corrects the article DOI: 10.3389/fped.2023.1159342.].

Irpex lacteus polysaccharide exhibits therapeutic potential for ovarian fibrosis in PCOS rats via the TGF-ß1/smad pathway.

Polycystic ovarian syndrome (PCOS) is one of the commonest endocrinopathies in childbearing women. The research was conducted to assess the impact of Irpex lacteus polysaccharide (ILP, 1000 mg/kg) on the letrozole (1 mg/kg)-induced PCOS model in female rats. Metformin (Met, 265 mg/kg) as the positive control. The study suggested that ILP restored the estrous cycle in rats with PCOS as well as lowered relative ovarian weight and body weight, in comparison to normal. Rats with PCOS showed improvement in ovarian structure and fibrosis when given ILP. ILP decreased the testosterone (T), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC), luteinizing hormone (LH), homeostasis model assessment-insulin resistance (HOMA-IR), fasting blood glucose (FBG), and insulin (INS) levels and elevated the follicle-stimulating hormone (FSH) and estrogen (E2) levels in PCOS rats. In addition, ILP increased the content of superoxide dismutase (SOD) in serum and the antioxidant enzymes (Prdx3, Sod1, Gsr, Gsta4, Mgst1, Gpx3, Sod2 and Cat) expression levels in the ovaries and decreased the serum expression of malondialdehyde (MDA). In addition, ILP treatment slowed down the process of the fibrosis-associated TGF-ß1/Smad pathway and downregulated α-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) levels in PCOS rats ovaries. According to these findings, ILP may be able to treat letrozole-induced PCOS in rats by ameliorating metabolic disturbances, sex hormone levels, oxidative stress, and ovarian fibrosis.

Diabetes duration or age at onset and mortality in insulin-dependent diabetics: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis was conducted given the contradictory findings from studies on the influence of diabetes duration or age at onset on mortality in patients with insulin-dependent diabetes mellitus (IDDM). METHODS: Electronic databases (PubMed, Embase, Cochrane, Web of Knowledge, Scopus, and CINHAL) were comprehensively searched to identify relevant studies until October 31, 2022. All of the selected articles contained statistics on hazard ratios, relative risks (RRs), or odds ratios, or data for estimating the association between diabetes duration or age at onset and total mortality in IDDM patients. Regardless the heterogeneity assessed by the I2 statistic, pooled RRs and 95% confidence intervals (CI) for total mortality were acquired via random effect meta-analysis with inverse variance weighting. RESULTS: This meta-analysis finally included 19 studies involving 122, 842 individuals. Both age at onset and diabetes duration were positively associated with an increased mortality rate in IDDM patients. Specifically, the pooled RRs for age at onset and diabetes duration were 1.89 (95%CI 1.43-2.50) and 1.89 (95%CI 1.16-3.09) respectively. Subgroup analyses revealed that only prepubertal onset was associated with a greater survival advantage than pubertal or postpubertal onset. CONCLUSIONS: The findings of this meta-analysis and systematic review suggest that a later age at onset or longer diabetes duration is associated with increased risk of total mortality in IDDM patients. However, this conclusion shall be interpreted with caution due to the possibility of residual confounding and be confirmed in the future by well-designed studies.

[Comprehensive Quality Assessment of Soil-Maize Heavy Metals in High Geological Background Area].

The aim of this study was to analyze the pollution degree and causes of soil and agricultural products in high geological background areas and to provide a basis for the safe production of agricultural products and the risk control of soil heavy metals. A total of 36 sets of soil-corn collaborative samples were collected in the farming area of Baolong Town, Wushan County, Chongqing City; the contents of heavy metals (Cd, Hg, Pb, As, and Cr) and soil pH in the soil-maize were analyzed, the pollution degree of heavy metals in the soil-maize was evaluated using the Nemerow comprehensive pollution index method (PN) and comprehensive quality impact index (IICQ). The sources of heavy metals in the soil and the influencing factors of heavy metal excess in corn were also analyzed. The results showed that the average value of soil heavy metal content in the study area was higher than the national and Chongqing soil background values, and the soil heavy metal enrichment effect was obvious. Cd was the main factor of soil-maize exceeding the standard, and the overall exceeding rates of soil and corn Cd were 91.67% and 30.55%, respectively. The evaluation results of the Nemerow comprehensive pollution index showed that the soil was dominated by heavy pollution, accounting for 63.89%. The soil-maize comprehensive quality impact index was dominated by moderate and severe pollution, accounting for 44.44% and 47.22%, respectively. From the perspective of the spatial distribution of heavy metal pollution, corn and soil pollution areas were inconsistent. Soil heavy metal pollution was mainly affected by the Permian and Triassic strata and was related to the secondary enrichment of black rock series and limestone areas. The Cd content of maize was mainly affected by soil pH, and maize was relatively safe under alkaline conditions. It is suggested that the soil in the study area should be divided into risk zones according to the stratum distribution, and the planting structure should be adjusted in the high-risk areas. For the low- and medium-risk areas, it is recommended to strengthen the monitoring of agricultural inputs and reduce the input of heavy metals in the soil. Additionally, we recommend carrying out agronomic regulation in acidic soil areas to improve soil acidification, plant corn varieties with low accumulation of heavy metals, and reduce the risk of agricultural products exceeding the standard.

[Source Analysis of Soil Heavy Metals in Agricultural Land Around the Mining Area Based on APCS-MLR Receptor Model and Geostatistical Method].

In order to identify the source of heavy metals in the soil around a mining area and provide effective suggestions for the prevention and control of regional soil pollution, 118 topsoil samples (0-20 cm) were collected in the northern part of Wuli Township, Qianjiang District, Chongqing. The heavy metal (Cd, Hg, Pb, As, Cr, Cu, Zn, and Ni) contents in the soil and soil pH were analyzed, and the spatial distribution and sources of heavy metals in the soil were studied using the geostatistical method and APCS-MLR receptor model. The results showed that the content of heavy metals in the soil was significantly higher than the background value in Chongqing; there was obvious surface accumulation; and Hg, Pb, Cd, As, and Zn showed strong variation. The proportions of soil Cd, Hg, Pb, As, and Zn exceeding the risk screening values were 47.11%, 6.61%, 4.96%, 5.79%, and 7.44%, respectively, and the proportions of soil Cd, Hg, Pb, and As exceeding the risk control values were 0.83%, 4.13%, 0.83%, and 0.83%; thus, the problem of excessive heavy metals in the soil was significant. Soil Cd, As, Cr, Cu, and Ni were mainly affected by soil parent materials, and their contribution rates to the total soil elements were 77.65%, 68.55%, 71.98%, 90.83%, and 82.19%, respectively. Soil Hg, Pb, and Zn were mainly affected by the mining of mercury mines and lead-zinc mines, with the contribution rates of 86.59%, 88.06%, and 91.34%, respectively. In addition, agricultural activities also affected soil Cd and As contents. It is recommended to strengthen the safety monitoring of agricultural products and agricultural inputs, plant varieties with a low accumulation of heavy metals, reduce the use of livestock manure, and grow non-edible agricultural products in areas that exceed the control value of heavy metal pollution risk.

Nuclear transport maintenance of USP22-AR by Importin-7 promotes breast cancer progression.

The translocation of biological macromolecules between cytoplasm and nucleus is of great significance to maintain various life processes in both normal and cancer cells. Disturbance of transport function likely leads to an unbalanced state between tumor suppressors and tumor-promoting factors. In this study, based on the unbiased analysis of protein expression differences with a mass spectrometer between human breast malignant tumors and benign hyperplastic tissues, we identified that Importin-7, a nuclear transport factor, is highly expressed in breast cancer (BC) and predicts poor outcomes. Further studies showed that Importin-7 promotes cell cycle progression and proliferation. Mechanistically, through co-immunoprecipitation, immunofluorescence, and nuclear-cytoplasmic protein separation experiments, we discovered that AR and USP22 can bind to Importin-7 as cargoes to promote BC progression. In addition, this study provides a rationale for a therapeutic strategy to restream the malignant progression of AR-positive BC by inhibiting the high expression state of Importin-7. Moreover, the knockdown of Importin-7 increased the responsiveness of BC cells to the AR signaling inhibitor, enzalutamide, suggesting that targeting Importin-7 may be a potential therapeutic strategy.

Comparison of cardiac function between single left ventricle and tricuspid atresia: assessment using echocardiography combined with computational fluid dynamics.

Patients with single left ventricle (SLV) and tricuspid atresia (TA) have impaired systolic and diastolic function. However, there are few comparative studies among patients with SLV, TA and children without heart disease. The current study includes 15 children in each group. The parameters measured by two-dimensional echocardiography, three-dimensional speckle tracking echocardiography (3DSTE), and vortexes calculated by computational fluid dynamics were compared among these three groups. Twist is best correlated with ejection fraction measured by 3DSTE. Twist, torsion, apical rotation, average radial strain, peak velocity of systolic wave in left lateral wall by tissue Doppler imaging (sL), and myocardial performance index are better in the TA group than those in the SLV group. sL by tissue Doppler imaging in the TA group are even higher than those in the Control group. In patients with SLV, blood flow spreads out in a fan-shaped manner and forms two small vortices. In the TA group, the main vortex is similar to the one in a normal LV chamber, but smaller. The vortex rings during diastolic phase are incomplete in the SLV and TA groups. In summary, patients with SLV or TA have impaired systolic and diastolic function. Patients with SLV had poorer cardiac function than those with TA due to less compensation and more disordered streamline. Twist may be good indicator for LV function.

Proteomic analysis of exosome-like vesicles from Fasciola gigantica adult worm provides support for new vaccine targets against fascioliasis.

BACKGROUND: Extracellular vesicles (EVs) released by helminths play an important role in parasite-host communication. However, little is known about the characteristics and contents of the EVs of Fasciola gigantica, a parasitic flatworm that causes tropical fascioliasis. A better understanding of EVs released by F. gigantica will help elucidate the mechanism of F. gigantica-host interaction and facilitate the search for new vaccine candidates for the control and treatment of fascioliasis. METHODS: Two different populations of EVs (15k EVs and 100k EVs) were purified from adult F. gigantica culture media by ultracentrifugation. The morphology and size of the purified EVs were determined by transmission electron microscopy (TEM) and by the Zetasizer Nano ZSP high performance particle characterization system. With the aim of identifying diagnostic markers or potential vaccine candidates, proteins within the isolated 100k EVs were analyzed using mass spectrometry-based proteomics (LC-MS/MS). Mice were then vaccinated with excretory/secretory products (ESPs; depleted of EVs), 15k EVs, 100k EVs and recombinant F. gigantica heat shock protein 70 (rFg-HSP70) combined with alum adjuvant followed by challenge infection with F. gigantica metacercariae. Fluke recovery and antibody levels were used as measures of vaccine protection. RESULTS: TEM analysis and nanoparticle tracking analysis indicated the successful isolation of two subpopulations of EVs (15k EVs and 100k EVs) from adult F. gigantica culture supernatants using differential centrifugation. A total of 755 proteins were identified in the 100k EVs. Exosome biogenesis or vesicle trafficking proteins, ESCRT (endosomal sorting complex required for transport) pathway proteins and exosome markers, heat shock proteins and 14-3-3 proteins were identified in the 100k EVs. These results indicate that the isolated 100k EVs were exosome-like vesicles. The functions of the identified proteins may be associated with immune regulation, immune evasion and virulence. Mice immunized with F. gigantica ESPs, 15k EVs, 100k EVs and rFg-HSP70 exhibited a reduction in fluke burden of 67.90%, 60.38%, 37.73% and 56.6%, respectively, compared with the adjuvant control group. The vaccination of mice with F. gigantica 100k EVs, 15k EVs, ESP and rFg-HSP70 induced significant production of specific immunoglobulins in sera, namely IgG, IgG1 and IgG2a. CONCLUSION: The results of this study suggest that proteins within the exosome-like vesicles of F. gigantica have immunomodulatory, immune evasion and virulence functions. This knowledge may lead to new strategies for immunotherapy, vaccination and the diagnosis of fascioliasis.

Modulation of Rac1/PAK1/connexin43-mediated ATP release from astrocytes contributes to retinal ganglion cell survival in experimental glaucoma.

Connexin43 (Cx43) is a major gap junction protein in glial cells. Mutations have been found in the gap-junction alpha 1 gene encoding Cx43 in glaucomatous human retinas, suggestive of the involvement of Cx43 in the pathogenesis of glaucoma. However, how Cx43 is involved in glaucoma is still unknown. We showed that increased intraocular pressure in a glaucoma mouse model of chronic ocular hypertension (COH) downregulated Cx43, which was mainly expressed in retinal astrocytes. Astrocytes in the optic nerve head where they gather and wrap the axons (optic nerve) of retinal ganglion cells (RGCs) were activated earlier than neurons in COH retinas and the alterations in astrocytes plasticity in the optic nerve caused a reduction in Cx43 expression. A time course showed that reductions of Cx43 expression were correlated with the activation of Rac1, a member of the Rho family. Co-immunoprecipitation assays showed that active Rac1, or the downstream signaling effector PAK1, negatively regulated Cx43 expression, Cx43 hemichannel opening and astrocyte activation. Pharmacological inhibition of Rac1 stimulated Cx43 hemichannel opening and ATP release, and astrocytes were identified to be one of the main sources of ATP. Furthermore, conditional knockout of Rac1 in astrocytes enhanced Cx43 expression and ATP release, and promoted RGC survival by upregulating the adenosine A3 receptor in RGCs. Our study provides new insight into the relationship between Cx43 and glaucoma, and suggests that regulating the interaction between astrocytes and RGCs via the Rac1/PAK1/Cx43/ATP pathway may be used as part of a therapeutic strategy for managing glaucoma.

Injectable MMP1-sensitive microspheres with spatiotemporally controlled exosome release promote neovascularized bone healing.

Bone marrow mesenchymal stromal cell-derived exosomes (BMSC-Exos) can recruit stem cells for bone repair, with neovessels serving as the main migratory channel for stem cells to the injury site. However, existing exosome (Exo) delivery strategies cannot reach the angiogenesis phase following bone injury. To that end, an enzyme-sensitive Exo delivery material that responds to neovessel formation during the angiogenesis phase was designed in the present study to achieve spatiotemporally controlled Exo release. Herein, matrix metalloproteinase-1 (MMP1) was found to be highly expressed in neovascularized bone; as a result, we proposed an injectable MMP1-sensitive hydrogel microspheres (KGE) made using a microfluidic chip prepared by mixing self-assembling peptide (KLDL-MMP1), GelMA, and BMSC-Exos. The results revealed that KGE microspheres had a uniform diameter of 50-70 µm, ideal for minimally invasive injection and could release exosomes in response to MMP1 expression. In vitro experiments demonstrated that KGE had less cytotoxicity and could promote the migration and osteodifferentiation of BMSCs. Furthermore, in vivo experiments confirmed that KGE could promote bone repair during angiogenesis by recruiting CD90+ stem cells via neovessels. Collectively, our results suggest that injectable enzyme-responsive KGE microspheres could be a promising Exo-secreting material for accelerating neovascularized bone healing. STATEMENT OF SIGNIFICANCE: Exosomes can spread through blood vessels and activate stem cells to participate in bone repair, but under normal circumstances, exosomes lacking sustained-release delivery materials cannot be maintained until the angiogenesis phase. In this study, we found that MMP1 was highly expressed in neovascularized bone, then we proposed an MMP1-sensitive injectable microsphere that carries exosomes and responds temporally and spatially to neovascularization, which maximizes the ability of exosomes to recruit stem cells. Different from previous strategies that focus on promoting angiogenesis to accelerate bone healing, this is a brand new delivery strategy that is stimuli-responsive to neovessel formation. In addition, the preparation of self-assembled peptide microspheres by a microfluidic chip is also proposed for the first time.

Spiked Helmet Sign: An Uncommon Electrocardiographic Marker.

The spiked helmet sign (SHS) is a rare electrocardiographic marker associated with an increased risk of lethal ventricular tachyarrhythmias and sudden cardiac death. To our knowledge, this is the first study aimed at reviewing recent research progress on this electrocardiogram (ECG) pattern to summarize its electrophysiological mechanisms, epidemiological features, clinical characteristics, and clinical significance. SHS formation is attributed to sympathetic hyperactivity, which mediates increased dispersion of ventricular repolarization, leading to marked QT prolongation and macroscopic T-wave alternans. This pattern can be observed in critically ill patients with cardiac or noncardiac conditions. In particular, immediate identification of this ECG abnormality is crucial in recognizing and treating noncardiac conditions in older male patients.

Use of covered stents to treat complex cerebrovascular diseases: Expert consensus.

The treatment of complex cerebrovascular diseases (CCVDs) at the skull base, such as complex intracranial aneurysms, carotid-cavernous sinus fistulas, and intracranial artery traumatic injuries, is a difficult clinical problem despite advances in endovascular and surgical therapies. Covered stents or stent graft insertion is a new concept for endovascular treatment that focuses on arterial wall defect reconstruction, differing from endovascular lesion embolization or flow diverter therapies. In recent years, covered stents specifically designed for cerebrovascular treatment have been applied in the clinical setting, allowing thousands of patients with CCVDs to undergo intraluminal reconstruction treatment and achieving positive results, even in the era of flow diverters. Since there is no unified reference standard for the application of covered stents for treating CCVDs, it is necessary to further standardize and guide the clinical application of this technique. Thus, we organized authoritative experts in the field of neurointervention in China to write an expert consensus, which aims to summarize the results of covered stent insertion in the treatment of CCVDs and propose suitable standards for its application in the clinical setting. Based on the contents of this consensus, clinicians can use individualized intraluminal reconstruction treatment techniques for patients with CCVDs.

Property of arylsulfatase and ß-glucuronidase extracted from digestive tracts of Cipangopaludina chinensis and their cleavage performance on conjugated natural estrogens.

Arylsulfatase and ß-glucuronidase are the two substantial enzymes having a significant role in the cleavage of conjugated natural estrogens (C-NEs). The present study reports that arylsulfatase and ß-glucuronidase have been abundantly found in the digestive tracts of Cipangopaludina chinensis; in which, their corresponding activities were 60 and 5 U/g wet waste, respectively. The arylsulfatase from Cipangopaludina chinensis could show high activity at low temperatures. Hence, its activity still remained at 53.2% of maximal activity even at an extremely low temperature of 4 ℃; while the corresponding activities of arylsulfatase from Helix pomatia or activated sludge were less than 20% and 10%, respectively. The arylsulfatase and ß-glucuronidase from Cipangopaludina chinensis could efficiently cleave C-NEs suggesting that they could be alternative enzymes derived from Helix pomatia that are used for cleavage of conjugated compounds in environmental or biological sample analysis. Meanwhile, they might also be used to enhance the cleavage of C-NEs in municipal wastewater.

Activity measurement of arylsulfatase and ß-glucuronidase in activated sludge: HPLC-based versus classical spectrophotometric method.

Arylsulfatase and ß-glucuronidase are two important enzymes in wastewater and surface water, which play important roles on cleavage of sulfate/glucuronide estrogens. In this work, a high-performance liquid chromatography (HPLC)-based new method was firstly established for arylsulfatase/ß-glucuronidase with determination of p-nitrophenyl sulfate (pNPS)/p-nitrophenyl-ß-D-glucuronide (pNPG). The limits of detections (LODs) of the developed method for pNPS and pNPG were 0.164 and 0.098 µM, respectively. Intraday and interday reproducibility expressed as relative standard deviation (RSD) values of retention times and peak areas was 0.39%-3.68% and 0.23%-4.74%, respectively. The respective recovery efficiencies of this HPLC-based method spiking at three different concentrations for p-nitrophenol (pNP), pNPS, and pNPG in activated sludge were 76.5%-88.1%, 79.2%-93.1%, and 84.2%-96.1%, with RSD below 3.9%. The HPLC-based method was finally applied to estimate the enzyme activity of arylsulfatase/ß-glucuronidase in one activated sludge system and along which the classical spectrophotometric method was also evaluated. Compared with the classic spectrophotometric analytical method, the HPLC-based new method could simultaneously measure arylsulfatase/ß-glucuronidase one time, which was convenient and time-saving. Moreover, the developed method could effectively avoid possible underestimation that the spectrophotometric method might encounter. PRACTITIONER POINTS: A new HPLC-based method for activity estimation of arylsulfatase and ß-glucuronidase was developed. The HPLC-based method can simultaneously estimate enzyme activity of both arylsulfatase and ß-glucuronidase. The HPLC-based method can avoid possible underestimation that spectrophotometric method may encounter.

Association of early repolarization pattern and ventricular fibrillation in patients with vasospastic angina: A systematic review and meta-analysis.

BACKGROUND: An early repolarization (ER) pattern is a risk factor for ventricular fibrillation (VF) in patients with vasospastic angina (VSA) caused by a coronary artery spasm. However, its detailed characteristics and prognostic value for VF remain unclear. Thus, we investigated the relationship between ER and VF in patients with VSA. HYPOTHESIS: The ER pattern is associated with VF in patients with VSA. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane Library, and Web of Science databases for eligible studies published between January 2011 and December 2020; 8 studies with 1761 patients were included in the final analysis. RESULTS: The ER pattern significantly predicted adverse cardiovascular events (ACEs) and VF (odds ratio [OR] = 5.13, 95% confidence interval [95% CI]: 3.16-8.35, p < .00001 and OR = 5.20, 95% CI: 3.05-8.87, p < .00001). The presence of ER in the inferior leads increased the VF risk (OR = 7.80, 95% CI: 4.04-15.05, p < .00001), regardless of the J-point morphology or type of ST-segment elevation in the ER pattern. A horizontal/descending ST-segment elevation was significantly associated with VF in patients with or without an ER pattern during a coronary spasm (OR = 2.28, 95% CI: 1.07-4.88, p = .03). However, obstructive coronary artery disease was unrelated to the ER pattern (OR = 0.82, 95% CI: 0.27-2.53, p = .73). CONCLUSIONS: An ER pattern is significantly associated with an increased risk of ACE in patients with VSA. An inferior ER pattern with horizontal/descending ST-segment elevation confers the highest risk for VF during VSA onset. Nevertheless, the ER pattern is not associated with obstructive coronary artery disease.

Sulfite may disrupt estrogen homeostasis in human via inhibition of steroid arylsulfatase.

Steroid arylsulfatase is an important enzyme in human, which plays an important role in dynamic equilibrium of natural estrogens. On the other hand, sulfite can be endogenously produced as a consequence of human body's metabolism of sulfur-containing amino acids, while its main sources to human are mainly derived from food as it is a widely used additive. Sulfite-sensitivity is a well-known phenomenon to a small proportion of populations. However, its potential adverse effects on healthy individuals have been hardly reported. It was for the first time reported in this study that sulfite could effectively inhibit arylsulfatase, and its IC50 values for the snail- and human urine-derived arylsulfatase were determined to be 71.9 and 142.8 µM, which were lower than the concentration of sulfite in some healthy population. Consequently, it appears that sulfite might disrupt estrogen homeostasis in human, and this deserves further investigation.