Appraising the Accuracy of Ischaemia-Modified Albumin in Diagnosing Stroke: A Systematic Review and Meta-Analysis.

INTRODUCTION: Ischaemia-modified albumin (IMA) is a new, sensitive marker of ischaemic diseases that has been approved for diagnosing myocardial ischaemia. However, the accuracy of IMA in the diagnosis of stroke remains to be clarified. The study's purpose is to assess the potential role of IMA as a diagnostic indicator in stroke. METHODS: We carried out a systematic search in Medline, the Cochrane Library, Embase, Scopus, Science Direct, ISI Web of Knowledge, and the reference lists of relevant articles from the databases' inception to September 1, 2019. Studies that appraised the diagnostic accuracy of IMA for acute stroke patients were included in our study. Two reviewers extracted data independently and assessed the quality of the retrieved studies, and disagreements were resolved through discussions with a third reviewer. Sensitivities and specificities were pooled by using bivariate diagnostic meta-analysis. We calculated I2 to test the heterogeneity and used meta-regression to identify potential sources of heterogeneity. This systematic review and meta-analysis is registered in international prospective register of systematic reviews (number CRD42020149174). RESULTS: Six studies with 605 patients were eligible for inclusion. Our meta-analysis produced the following outcomes: the mean sensitivity of IMA in diagnosing acute stroke was 0.80 (95% confidence interval [CI], 0.69-0.88) and the specificity was 0.80 (95% CI, 0.71-0.87). The area under the receiver operating characteristic curve was 0.86 (95% CI, 0.83-0.89), and the pooled diagnostic odds ratio was 16 (95% CI, 8-33). There was obvious heterogeneity between studies (I2 = 78%, 95% CI, 53-100). Sensitivity analysis and meta-regression could account for the heterogeneity. CONCLUSION: IMA is a helpful marker for consideration in the early diagnosis of stroke.

High-quantum-efficiency ultraviolet solar-blind AlGaN photocathode detector with a sharp spectral sensitivity threshold at 300 nm.

At present, most of the existing practical ultraviolet (UV) solar-blind detectors are based on Te-Cs photocathode image intensifiers. However, limited by their photoemission characteristics, it is difficult for the Te-Cs-based photocathodes to achieve both high quantum efficiency in the application band and high cutoff ratio in the non-applied band simultaneously. In this paper, a high-quantum-efficiency UV solar-blind detector based on AlGaN photocathodes with a sharp spectral sensitivity threshold at 300 nm is reported. The proposed AlGaN photocathode has extremely high quantum efficiency (i.e., 20%) in the 210-275 nm band, while the efficiency curve steeply reduces to 2% at 300 nm, showing obviously superior performance than the existing Te-Cs photocathodes.

Some questions on the use of Xuebijing in treating patients with sepsis.

A meta-analysis of randomized controlled trials on evaluating the clinical efficacy of Xuebijing in treating patients with sepsis had been recently published in this journal, however, in our opinion, at least 6 questions or doubts existed about the content and methodology of the systematic review, thus, we write this letter to the journal to share these questions with the editor and readers with the hope of getting these questions solved and learning more about the true effects which Xuebijing should have on in treating patients with sepsis.

Go2 G protein mediates galanin inhibitory effects on insulin release from pancreatic ß cells.

The neuropeptide galanin regulates numerous physiological activities in the body, including feeding and metabolism, learning and memory, nociception and spinal reflexes, and anxiety and related behaviors. Modulation of blood glucose levels by suppressing insulin release was the first reported activity for galanin. This inhibition was mediated by one or more pertussis toxin-sensitive G proteins of the G(i/o) subfamily. However, the molecular identities of the specific G protein(s) and intracellular effectors have not been fully revealed. Recently, we demonstrated that mice lacking G(o)2, but not other members of the G(i/o) protein family, secrete more insulin than controls upon glucose challenge, indicating that G(o)2 is a major transducer for the inhibitory regulation of insulin secretion. In this study, we investigated galanin signaling mechanisms in ß cells using cell biological and electrophysiological approaches. We found that islets lacking G(o)2, but not other G(i/o) proteins, lose the inhibitory effect of galanin on insulin release. Potentiation of ATP-sensitive potassium (K(ATP)) and inhibition of calcium currents by galanin were disrupted by anti-G(o)2α antibodies. Galanin actions on K(ATP) and calcium currents were completely lost in G(o)2(-/-) ß cells. Furthermore, the hyperglycemic effect of galanin is also blunted in G(o)2(-/-) mice. Our results demonstrate that G(o)2 mediates the inhibition of insulin release by galanin by regulating both K(ATP) and Ca(2+) channels in mice. Our findings provide insight into galanin's action in glucose homeostasis. The results may also be relevant to the understanding of galanin signaling in other biological systems, especially the central nervous system.

Association of mental disorders with sepsis: a bidirectional Mendelian randomization study.

Background: Substantial research evidence supports the correlation between mental disorders and sepsis. Nevertheless, the causal connection between a particular psychological disorder and sepsis remains unclear. Methods: For investigating the causal relationships between mental disorders and sepsis, genetic variants correlated with mental disorders, including anorexia nervosa (AN), attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), panic disorder (PD), posttraumatic stress disorder (PTSD), schizophrenia (SCZ), and tourette syndrome (TS), were all extracted from the Psychiatric Genomics Consortium (PGC). The causal estimates and direction between these mental disorders and sepsis were evaluated employing a two-sample bidirectional MR strategy. The inverse variance weighted (IVW) method was the primary approach utilized. Various sensitivity analyses were performed to confirm the validity of the causal effect. Meta-analysis, multivariable MR, and mediation MR were conducted to ensure the credibility and depth of this research. Results: The presence of AN was in relation to a greater likelihood of sepsis (OR 1.08, 95% CI 1.02-1.14; p = 0.013). A meta-analysis including validation cohorts supported this observation (OR 1.06, 95% CI 1.02-1.09). None of the investigated mental disorders appeared to be impacted when sepsis was set as the exposure factor. Even after adjusting for confounding factors, AN remained statistically significant (OR 1.08, 95% CI 1.02-1.15; p = 0.013). Mediation analysis indicated N-formylmethionine levels (with a mediated proportion of 7.47%), cystatin D levels (2.97%), ketogluconate Metabolism (17.41%) and N10-formyl-tetrahydrofolate biosynthesis (20.06%) might serve as mediators in the pathogenesis of AN-sepsis. Conclusion: At the gene prediction level, two-sample bidirectional MR analysis revealed that mental disorder AN had a causal association with an increased likelihood of sepsis. In addition, N-formylmethionine levels, cystatin D levels, ketogluconate metabolism and N10-formyl-tetrahydrofolate biosynthesis may function as potential mediators in the pathophysiology of AN-sepsis. Our research may contribute to the investigation of novel therapeutic strategies for mental illness and sepsis.

Insights into the enhanced mechanism of selenium-doped iron nitride carbon catalysts for elemental mercury removal in flue gas.

This study developed a novel selenium-doped metal nitride carbon, Fe-NC-Se, via pyrolysis and impregnated hydrothermal methods for elemental mercury removal from coal-fired flue gas. The Fe-NC-Se demonstrated a remarkable mercury removal performance, achieving an average efficiency of 96.98% within 60 min at an optimal Se/Fe ratio of 2:1 and temperature of 110 °C, which was 2.5 times higher than that of the pristine Fe-NC (iron nitride carbon). Notably, Fe-NC-Se maintained an 84% efficiency in a high SO2 environment (1600 ppm), indicating strong resistance to SO2 poisoning. Long-term testing over 24 h showed a consistent removal efficiency of 84.75%, suggesting potential for recyclability. Advanced characterization techniques, including TEM (transmission electron microscopy) and XPS (X-ray photoelectron spectrometer), along with Density Functional Theory calculations, were employed to explore the removal mechanism. Results indicated that selenium doping enhanced surface charge transfer and the reactivity of surface atoms, facilitating mercury oxidation and sequestration. The oxidized Hg2+ was anchored by Se and partially stabilized by C, N, and Fe atoms, enhancing the catalyst's effectiveness. This work not only advances the design of mercury abatement catalysts but also supports the industrial applicability of Fe-NC-Se in flue gas treatment.

Knockdown of membrane-bound complement regulatory proteins suppresses colon cancer growth in mice through inducing tumor cell apoptosis.

CD46, CD55 and CD59 are membrane-bound complement regulatory proteins (mCRPs) and highly expressed in many tumor tissues. Our analysis by RNA sequencing and qRT-PCR revealed that the expression of mCRPs was significantly elevated in cancer tissues of 15 patients with colon cancer. To further investigate the role of mCRPs in the development of colon cancer, we suppressed the expression of mCRPs by CD46-shRNA, CD55-shRNA and CD59-shRNA in colon cancer cell lines, SW620 and HT-29 cells. The results indicated that CD46-shRNA, CD55-shRNA and CD59-shRNA effectively reduced the expression of mCRPs, accompanied with the increased LDH release and the percentage of Annexin V + 7-AAD- early phase of apoptotic cells. The similar cytotoxic effects were also observed in the cells treated with CD46 neutralizing antibody (aCD46), associated with the increased C5b-9 deposition, cleaved caspase-3 and Bax expression in the treated cells. The cytotoxic effects by mCRPs knock-down were potentiated in the cells co-treated with doxorubicin (Dox). In addition, STAT3, STAT6, and p38 MAPK inhibitors, including C188-9, AS1517499 and SB203580 effectively reduced the expression of CD46 in the treated colon cells, associated with increased cell apoptosis and LDH release. Further study with mouse model revealed that mCRPs knockdown by mCRPs-shRNA significantly reduced colon cancer growth, associated with increased expression of Bax, cleaved caspase-3 and C5b-9 deposition, but reduced expression of Bcl-2, IL-6 and IL-1beta in tumor tissues of nude mice transplanted with SW620 cells. Thereby, mCRPs expression in human colon cancer cells were upregulated by STAT3/STAT6/p38 MAPK signaling and mCRPs knockdown reduced colon cancer growth in mice through inducing tumor cell apoptosis.

Increased neointimal formation in cystathionine gamma-lyase deficient mice: role of hydrogen sulfide in α5ß1-integrin and matrix metalloproteinase-2 expression in smooth muscle cells.

The physiological and pathological roles of hydrogen sulfide (H(2)S) in the regulation of cardiovacular functions have been recognized. Vascular smooth muscle cells (SMCs) express cystathionine gamma-lyase (CSE) and produce significant amount of H(2)S. Although growing evidence demonstated the anti-atherosclerotic effect of H(2)S, less is known about the contribution of the endogenous CSE/H(2)S pathway to the development of vascular remodeling. This study investigated the roles of the CSE/H(2)S pathway on SMC migration and neoimtimal formation by using CSE knockout (KO) mice. SMCs and aortic explants isolated from CSE KO mice exhibited more migration and outgrowth compared with that from wild-type (WT) mice, and exogenously applied NaHS (a H(2)S donor) at 100 µM significantly inhibited SMC migration and outgrowth. SMCs became more elongated and spread in the absence of CSE, and fibronectin significantly stimulated adhesion and migration of SMCs from CSE KO mice (KO-SMCs) in comparison with SMCs from WT mice (WT-SMCs). The expressions of α5- and ß1-integrins were significantly higher in KO-SMCs, and functional blocking of α5ß1-integrin effectively abrogated KO-SMC migration. CSE deficiency also enhanced matrix metalloproteinase-2 (MMP-2) expression, and the selective blocking of MMP-2 decreased KO-SMC migration. NaHS treatment decreased both the expressions of α5- and ß1-integrins and MMP-2. We further found that the expressions of α5- and ß1-integrins as well as MMP-2, were stimulated by fibronectin, and that the blockage of α5ß1-integrin reduced but overexpression of α5ß1-integrin induced MMP-2 expression in both WT-SMCs and KO-SMCs. We also noticed that CSE deficiency in mice led to increased neointima formation in carotid arteries 4 weeks after ligation, which were attenuated by NaHS administration. In conclusion, inhibition of SMC migration by H(2)S may be a novel target for the treatment of vascular occlusive disorder.

The pathogenic role of cystathionine γ-lyase/hydrogen sulfide in streptozotocin-induced diabetes in mice.

Reduced ß-cell mass and increased activities of ATP-sensitive K(+) channels in pancreatic ß cells are associated with the pathogenesis of diabetes. Cystathionine γ-lyase (CSE) is a major hydrogen sulfide (H(2)S)-producing enzyme in pancreatic ß cells. Herein, we examine the effects of genetic and pharmacologic ablation of CSE on ß-cell functions and their correlation with streptozotocin (STZ)-induced diabetes. Compared with wild-type mice, CSE knockout (CSE KO) mice that received STZ injections exhibited a delayed onset of diabetic status. The application of dl-propargylglycine (PPG) to inhibit CSE activity protected wild-type mice from STZ-induced hyperglycemia and hypoinsulinemia. STZ significantly increased pancreatic H(2)S production in wild-type mice but not in CSE KO mice. STZ induced more apoptotic ß-cell death in wild-type mice than in CSE KO mice. STZ exposure decreased the viability of cultured INS-1E cells, which was partly reversed by PPG co-treatment. STZ also significantly stimulated H(2)S production in cultured INS-1E cells. In addition, STZ stimulated ATP-sensitive K(+) currents in pancreatic ß cells from wild-type mice but not in the presence of PPG or in ß cells from CSE KO mice. Sodium hydrosulfide injection instantly increased blood glucose, decreased plasma insulin, and deteriorated glucose tolerance in mice. Take together, these results provide evidence that the CSE/H(2)S system plays a critical role in regulating ß-cell functions.

Identification of a novel bacterial K(+) channel.

In an attempt to explore unknown K(+) channels in mammalian cells, especially ATP-sensitive K(+) (K(ATP)) channels, we compared the sequence homology of Kir6.1 and Kir6.2, two pore-forming subunits of mammalian K(ATP) channel genes, with bacterial genes that code for selective proteins with confirmed or putative ion transport properties. BLAST analysis revealed that a prokaryotic gene (ydfJ) expressed in Escherichia coli K12 strain shared 8.6% homology with Kir6.1 and 8.3% with Kir6.2 genes. Subsequently, we cloned and sequenced ydfJ gene from E. coli K12 and heterologously expressed it in mammalian HEK-293 cells. The whole-cell patch-clamp technique was used to record ion channel currents generated by ydfJ-encoded protein. Heterologous expression of ydfJ gene in HEK-293 cells yielded a novel K(+) channel current that was inwardly rectified and had a reversal potential close to K(+) equilibrium potential. The expressed ydfJ channel was blocked reversibly by low concentration of barium in a dose-dependent fashion. Specific K(ATP) channel openers or blockers did not alter the K(+) current generated by ydfJ expression alone or ydfJ coexpressed with rvSUR1 or rvSUR2B subunits of K(ATP) channel complex. Furthermore, this coexpressed ydfJ/rvSUR1 channels were not inhibited by ATP dialysis. On the other hand, ydfJ K(+) currents were inhibited by protopine (a nonspecific K(+) channel blocker) but not by dofetilide (a HERG channel blocker). In summary, heterologously expressed prokaryotic ydfJ gene formed a novel functional K(+) channel in mammalian cells.

Interaction of hydrogen sulfide with ion channels.

1. Hydrogen sulfide (H(2)S) is a signalling gasotransmitter. It targets different ion channels and receptors, and fulfils its various roles in modulating the functions of different systems. However, the interaction of H(2)S with different types of ion channels and underlying molecular mechanisms has not been reviewed systematically. 2. H(2)S is the first identified endogenous gaseous opener of ATP-sensitive K(+) channels in vascular smooth muscle cells. Through the activation of ATP-sensitive K(+) channels, H(2)S lowers blood pressure, protects the heart from ischemia and reperfusion injury, inhibits insulin secretion in pancreatic beta cells, and exerts anti-inflammatory, anti-nociceptive and anti-apoptotic effects. 3. H(2)S inhibited L-type Ca(2+) channels in cardiomyocytes but stimulated the same channels in neurons, thus regulating intracellular Ca(2+) levels. H(2)S activated small and medium conductance K(Ca) channels but its effect on BK(Ca) channels has not been consistent. 4. H(2)S-induced hyperalgesia and pro-nociception seems to be related to the sensitization of both T-type Ca(2+) channels and TRPV(1) channels. The activation of TRPV(1) and TRPA(1) by H(2)S is believed to result in contraction of nonvascular smooth muscles and increased colonic mucosal Cl(-) secretion. 5. The activation of Cl(-) channel by H(2)S has been shown as a protective mechanism for neurons from oxytosis. H(2)S also potentiates N-methyl-d-aspartic acid receptor-mediated currents that are involved in regulating synaptic plasticity for learning and memory. 6. Given the important modulatory effects of H(2)S on different ion channels, many cellular functions and disease conditions related to homeostatic control of ion fluxes across cell membrane should be re-evaluated.

[Research on in-situ monitoring of SO2 concentration in the flue gases with DOAS method based on algorithm fusion].

Valuable achievements on differential optical absorption spectroscopy (DOAS) for monitoring atmospheric pollutants gas have been made in the past decades. Based on the idea of setting the threshold according to the maximum value, symbolized as OD'm, of differential optical density, the algorithm of traditional DOAS was combined with the DOAS algorithm based on the kalman filtering to improve the detection limit without losing measurement accuracy in the present article. Two algorithms have different inversion accuracy at the same ratio of signal to noise and the problem of inversion accuracy was well resolved by combining two algorithms at short light path length. Theoretical and experimental research on the concentration measurement of SO2 in the flue gases was carried out at the normal temperature and atmospheric pressure. The research results show that with the OD'm less than 0.0481, the measurement precision is very high for SO2 with the improved DOAS algorithm. The measurement lower limit of SO2 is less than 28.6 mg x m(-3) and the zero drift of the system is less than 2.9 mg x m(-3). If the OD'm is between 0.0481 and 0.9272, the measurement precision is high with the traditional DOAS algorithm. However, if the OD'm is more than 0.922, the errors of measurement results for both two DOAS algorithms are very large and the linearity correction must be performed.