Biomedical subjects

Y Cai

Publications and source records attributed to Y Cai.

At least 73 records · Page 4Linked to original sources

PubMed2001

[Analysis of alloy tool steel using X-ray fluorescence spectrometer].

This report briefly introduces the analysis of Mn, Cr, V, W, Ti, Nb, Co, Zr, Ni, Mo, S, P, Si and Cu in alloy tool steel with X-ray florescence spectrometer. After being polished with grinding well and being cleaned with ethly alcohol, the test samples can be directly measured, and the results agree well with the standard values of the laboratory standards. The precision of the method (RSD) is in the range of 0.13%-9.56% (n = 8) for all elements except W, Ti, Nb and Zr. The method can be applied to many kinds of steel, such as chrome vanadium steel, manganese steel, die steel, middle-low alloy steel, tool steel. The measure instrument should be rectified with two or three standard samples which the quantity contained is suitable. The standard samples include 1Cr18Ni9Ti, C17Ni2, 25CrMo1V, 30CrMnSiA, 3CrW8V, Gx-8, Cr12MoV, chrome vanadium steel, manganese-boron steel, middle-low alloy steel and other kinds of steel. If there is not conditions to make work curves for all kinds steel separately, sometimes we don't know what kind of steel for one complex sample, the more real way will be to make an overall work curves which contains more kinds of steel as far as possible.

English Abstract↗

PubMed2001

[FTIR study of transition metal 2-acrylamido-2-methyl-1-propanesulfonates].

Compounds of transition metal ion (Cu2+, Co2+, Ni2+) 2-acrylamidomethyl-2-methyl-1-propanesulfonates were studied by FTIR and X-ray powder diffraction techniques. The FTIR spectra of Co and Ni compound are similar but are different from that of Cu compound. The results of X-ray diffraction indicated that the crystal structure of Co and Ni compound are different.

Acrylamides↗

PubMed2001

[The effects of long-term domiciliary oxygen therapy on patients of chronic obstructive pulmonary disease with hypoxaemia].

OBJECTIVE: To observe the effects of long-term domiciliary oxygen therapy (LTDOT) on patients of chronic obstructive pulmonary disease (COPD) with hypoxaemia. METHODS: Sixty-one hypoxemic cases with stable COPD were divided into two groups--the LTDOT group of 30 patients and the control group of 31 patents. Before LTDOT and one year or two years later, the lung function test, blood routine, electrocardiography and ultra-echocardiography were tested, the psychological status and quality of life (QOL) were evaluated with the hospital anxiety and depression score and QOL questionnaire respectively. Both groups received routine treatment. In addition,the LTDOT group received oxygen therapy at home with nasal cannula with the oxygen flow of (0.5 - 2.5) L/min for at least 15 hrs every day. RESULTS: Thirteen patients in the LTDOT group died two years later, the mortality rate was 43%; eleven patients in the control group died. In LTDOT group hemoglobin, red blood cell count and hematocrit did not change after one year and two years, the hemoglobin, red blood cell count and hematocrit in the control group did not change after one year but the hemoglobin and red blood cell count increased significantly after two years (P < 0.05); ECG showed that the value of RV1 + SV5 in the LTDOT group remained stable (P > 0.05), which in the control group increased (P < 0.05). After one year and two years, mean pulmonary artery pressure in the LTDOT group declined significantly (P < 0.05). The internal diameter of right ventricle of the heart and the outlet of right ventricle of the heart declined significantly (P < 0.05), but those in the control group increased significantly (P < 0.05). In the LTDOT group, the anxiety and depression scores were significantly improved (P < 0.05) after one year or two years, the total mean score of QOL, general activity score, social activity score, depression and anxiety scores were significantly improved (P < 0.05), but in the control group the anxiety and depression scores did not change (P > 0.05), the total mean score of QOL, social activity score, the anxiety score were significantly worse(P < 0.05). CONCLUSIONS: Long-term domiciliary oxygen therapy could reduce the load of the right heart, improve the patients's psychological status and quality of life.

Aged↗

PubMed2001

[The efficacy of controlling of house dusts in attacks of mite sensitive asthmatics].

OBJECTIVE: To study the effect of controlling of house dusts in attacks of mite sensitive asthmatics (DMSA). METHODS: Dust in mattresses, sofas, beddings and pillows were calculated for 43 cases of DMSA every season meanwhile the asthmatic symptoms, amount of drugs taken, PEF value in morning and evening were daily recorded by patients, then the patients were divided into two groups i.e. treatment group (A group, 22 cases) and no treatment group ( B group, 21 cases) randomly. The controlling measures included well-ventilation, washing clothes and bedclothes and catching dust frequently and exposing of clothing or bedclothes in the sun. RESULTS: Correlation was found between house dust density and asthmatic attacks. The number of dust mites was lower after treatment than before in A group [(N/g): spring 62 vs 103, summer 105 vs 132, autumn 163 vs 231, winter 9 vs 13]. Concomitant asthmatic symptoms and amount of drugs taken and total IgE reduced [(0.6 vs 1.6) mg/L] and PEF values or PEF difference improved. CONCLUSION: Control of dust mites growth could alleviate the asthmatic symptoms and decrease the attacks.

Adolescent↗

PubMed2000

Transglutaminase-3, an esophageal cancer-related gene.

Transglutaminase-3 (TGase-3) is an enzyme with the ability to catalyze the irreversible cross-linking of peptide-bound glutamine residues either with peptide-bound lysines or with primary amines. It has been implicated in the formation and assembly of the cornified cell envelope of the epidermis, hair follicle and perhaps other stratified squamous epithelia. We show here the involvement of TGase-3 in human esophageal cancer. In an initial study, mRNA differential display was performed with 3 pairs of esophageal cancer tissues and matched normal adjacent mucosa by a 10-mer arbitrary primer and mixed anchored primers (GT15N, N = A, C and G). Four differentially expressed cDNA bands were consistently observed in all 3 normal tissues but barely detected in their tumor counterparts. One of them was identified to be the 3; end of TGase-3. Northern blot and dot blot analyses of 14 samples confirmed the down-regulation of TGase-3 in malignant tissues compared with normal epithelia. RT-PCR revealed that TGase-3 expression was lost in 3 esophageal carcinoma cell lines and decreased in 35/38 tumors compared with adjacent normal mucosa. Taken together, 49/52 (94.2%) esophageal tumors presented down-regulation of the gene. Our data suggest that alteration of TGase-3 expression is a common event in the development of human esophageal cancer.

Adenocarcinoma↗

PubMed2000

Glial cells contribute more to iron and aluminum accumulation but are more resistant to oxidative stress than neuronal cells.

Iron (Fe) and aluminum (Al) have been implicated in the pathogenesis of Alzheimer's disease (AD). In this study, we examined neuronal and glial cells to clarify which contributes most to metal accumulation after internalization through the transferrin-independent iron uptake (Tf-IU) systems in primary neuronal and glial predominant (NP and GP) cells from rat cerebral cortex, which affect the accumulation of transition metals in a variety of cultured cells. Al more significantly upregulated the Tf-IU activity in GP cells than in NP cells. GP cells were more resistant to Fe and Al exposure than NP cells. However, a chemiluminescence analysis specific for reactive oxygen species (ROS) showed that ROS levels in Fe- or Al-loaded NP cells were twice as high as in Fe- or Al-loaded GP cells. Northern blot analysis and gel retardation assay showed that the Al and Fe exposure taken up by the cells suppress Tf receptor mRNA expression to a greater extent in GP than NP cells, indicating that Al and Fe more markedly accumulate in glial than in neuronal cells. These results suggest that glial cells rather than neuronal cells contribute to the metal accumulation and are more resistant to oxidative stress caused by metals than neuronal cells. The present study may help to explain the pathogenesis of neurodegeneration in AD disorders caused by metal-generated oxidative stress.

Aluminum↗

PubMed2000

Novel human esophagus-specific gene c1orf10: cDNA cloning, gene structure, and frequent loss of expression in esophageal cancer.

We have identified a novel human gene, designated C1orf10, using modified differential display PCR. The C1orf10 gene, which spans 5 kb in length, is composed of three exons. The deduced protein contains 495 amino acids with one transmembrane domain. The amino acid sequence of C1orf10 is characterized by the presence of a calcium-binding motif of about 90 amino acids at its N-terminal and a conserved consecutive repeat sequence of 60 amino acids that was identified previously only in bacterial ice nucleation proteins. In normal adult tissues, C1orf10 is highly expressed only in the esophagus and was undetectable in a total of 15 other tissues examined, suggesting its important role in esophageal cells. The expression of C1orf10 is either dramatically reduced or absent in esophageal cancer cell lines (3/3) as well as primary esophageal cancer tissues (35/37) compared with the corresponding normal esophageal mucosa. Using a radiation hybrid panel, C1orf10 was found to be located on chromosome 1q21. These findings suggest that expression of C1orf10 is unique to esophageal cells and that loss of its expression may play a role in the development of esophageal cancer.

Adult↗

PubMed2000

Identification of retinoic acid-responsive elements on the HNF1alpha and HNF4alpha genes.

Hepatocyte nuclear factor 1alpha (HNF1alpha) and HNF4alpha are liver-selective transcription factors and are essential for hepatocyte differentiation. This study demonstrates that HNF1alpha as well as HNF4alpha genes contain a direct repeat with a space of one nucleotide (DR1)-retinoic acid (RA) response element that can be bound and regulated by RA and retinoid x receptor alpha (RXRalpha) complex. Transient transfection experiments showed that RA increased the promoter activity of the HNF1alpha and HNF4alpha genes in Hep3B cells. Overexpression of RXRalpha further enhanced the activities of both genes. Two putative RXRalpha binding sites on the HNF1alpha (-295 to -276) and HNF4alpha (-418 to -399) genes have been characterized. By transient transfection, both sites positively responded to RA, and overexpression of RXRalpha in Hep3B cells increased the regulatory effect. Gel mobility shift assay demonstrated that these two DR-1 sites could be bound by RXRalpha specifically. These data suggest that the differentiation effect of RA on hepatocyte may be due to direct interaction of RXRalpha with the RA-responsive elements on the HNF1alpha and HNF4alpha genes.

Alitretinoin↗

PubMed2000

Effect of O6-benzylguanine on alkylating agent-induced toxicity and mutagenicity. In Chinese hamster ovary cells expressing wild-type and mutant O6-alkylguanine-DNA alkyltransferases.

The DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) has been shown to protect cells from the toxic and mutagenic effect of alkylating agents by removing lesions from the O6 position of guanine. O6-Benzylguanine (BG) is a potent inactivator of AGT, resulting in an increase in the sensitivity of cells to the toxic effects of chemotherapeutic alkylating agents. Chinese hamster ovary (CHO) cells and CHO cells transfected with wild-type AGT (CHOWTAGT) and a mutant AGT [P138 M/V139I/P140K (CHOMIK)] known to be resistant to BG were treated with BG and various alkylating agents. BG treatment alone dramatically decreased AGT activity in CHOWTAGT cells but resulted in no depletion in AGT activity in CHOMIK cells. In the absence of AGT, these cells are highly sensitive to the toxic and mutagenic effects of temozolomide and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), and no further sensitization occurs in the presence of BG. In contrast, CHOWTAGT cells are resistant to temozolomide and BCNU, and treatment with BG resulted in a significantly higher cell killing and mutation frequency. CHOMIK cells were completely resistant to temozolomide or BCNU in the presence and absence of BG. Both cell killing and mutation frequency of 4-hydroperoxycyclophosphamide (4-HC) in CHO, CHOWTAGT, and CHOMIK cells were increased in the presence of BG. 4-HC generates two active metabolites, phosphoramide mustard (PM) and acrolein. BG had no effect on 4hydroperoxydidechlorocyclophosphamide (which generates acrolein and a nonalkylating form of PM) in CHO cells and CHOMIK cells, but enhancement of toxicity was observed with PM in both these cell lines. Therefore, we attribute the enhancement to the PM metabolite of 4-HC. Our results demonstrate that wild-type AGT plays an important role in protecting against the toxic and mutagenic effect of O6 alkylating agents and that a mutant AGT resistant to inactivation by BG effectively prevents BG-enhanced toxicity and mutagenicity induced by these agents. Expression of the AGT protein contributes to resistance of 4-HC. BG also enhances the toxicity of 4-HC and PM by a mechanism that may not involve the AGT repair protein.

Animals↗

PubMed2000

Homocysteine-responsive ATF3 gene expression in human vascular endothelial cells: activation of c-Jun NH(2)-terminal kinase and promoter response element.

Activating transcription factor (ATF) 3 is a member of ATF/cyclic adenosine monophosphate (cAMP)-responsive element binding protein (ATF/CREB) family of transcription factors and functions as a stress-inducible transcriptional repressor. To understand the stress-induced gene regulation by homocysteine, we investigated activation of the ATF3 gene in human endothelial cells. Homocysteine caused a rapid induction of ATF3 at the transcriptional level. This induction was preceded by a rapid and sustained activation of c-Jun NH(2)-terminal kinase/stress-activated protein kinase (JNK/SAPK), and dominant negative mitogen-activated protein kinase kinase 4 and 7 abolished these effects. The effect of homocysteine appeared to be specific, because cysteine or homocystine had no appreciable effect, but it was mimicked by dithiothreitol and beta-mercaptoethanol as well as tunicamycin. The homocysteine effect was not inhibited by an active oxygen scavenger. Deletion analysis of the 5' flanking sequence of the ATF3 gene promoter revealed that one of the major elements responsible for the induction by homocysteine is an ATF/cAMP responsive element (CRE) located at -92 to -85 relative to the transcriptional start site. Gel shift, immunoprecipitation, and cotransfection assays demonstrated that a complex (or complexes) containing ATF2, c-Jun, and ATF3 increased binding to the ATF/CRE site in the homocysteine-treated cells and activated the ATF3 gene expression, while ATF3 appeared to repress its own promoter. These data together suggested a novel pathway by which homocysteine causes the activation of JNK/SAPK and subsequent ATF3 expression through its reductive stress. Activation of JNK/SAPK and ATF3 expression in response to homocysteine may have a functional role in homocysteinemia-associated endothelial dysfunction.

Activating Transcription Factor 3↗

PubMed2000

Peroxisome proliferator-activated receptor alpha-mediated pathways are altered in hepatocyte-specific retinoid X receptor alpha-deficient mice.

Retinoid x receptor alpha (RXRalpha) serves as an active partner of peroxisome proliferator-activated receptor (PPARalpha). In order to dissect the functional role of RXRalpha and PPARalpha in PPARalpha-mediated pathways, the hepatocyte RXRalpha-deficient mice have been challenged with physiological and pharmacological stresses, fasting and Wy14,643, respectively. The data demonstrate that RXRalpha and PPARalpha deficiency are different in several aspects. At the basal untreated level, RXRalpha deficiency resulted in marked induction of apolipoprotein A-I and C-III (apoA-I and apoC-III) mRNA levels and serum cholesterol and triglyceride levels, which was not found in PPARalpha-null mice. Fasting-induced PPARalpha activation was drastically prevented in the absence of hepatocyte RXRalpha. Wy14,643-mediated pleiotropic effects were also altered due to the absence of hepatocyte RXRalpha. Hepatocyte RXRalpha deficiency did not change the basal acyl-CoA oxidase, medium chain acyl-CoA dehydrogenase, and malic enzyme mRNA levels. However, the inducibility of those genes by Wy14,643 was markedly reduced in the mutant mouse livers. In contrast, the basal cytochrome P450 4A1, liver fatty acid-binding protein, and apoA-I and apoC-III mRNA levels were significantly altered in the mutant mouse livers, but the regulatory effect of Wy14,643 on expression of those genes remained the same. Wy14,643-induced hepatomegaly was partially inhibited in hepatocyte RXRalpha-deficient mice. Wy14,643-induced hepatocyte peroxisome proliferation was preserved in the absence of hepatocyte RXRalpha. These data suggested that in comparison to PPARalpha, hepatocyte RXRalpha has its unique role in lipid homeostasis and that the effect of RXRalpha, -beta, and -gamma is redundant in certain aspects.

Acyl-CoA Dehydrogenase↗

PubMed2000

Study of the Adsorption of Glutathione on a Gold Electrode by Using Electrochemical Quartz Crystal Impedance, Electrochemical Impedance Spectroscopy, and Cyclic Voltammetry.

Adsorption of a biological peptide, glutathione, on a gold electrode was studied by using electrochemical quartz crystal impedance (EQCI), electrochemical impedance spectroscopy (EIS), and cyclic voltammetry (CV) techniques. The time courses of responses of piezoelectric and electrochemical impedance parameters were simultaneously obtained during the adsorption processes of the two forms of peptide, oxidized and reduced glutathione. It was found that the frequency curve due to the oxidized glutathione (GSSG) adsorption exhibited a character of a sum of two exponential functions. For reduced glutathione (GSH), the frequency adsorption curve could be expressed by a first-order reaction kinetic model and the corresponding kinetic parameters at different amounts of GSH were obtained. The heterogeneous charge-transfer rate constants of ferricyanide/ferrocyanide before and after the peptide adsorption were determined by CV and EIS methods, respectively. According to the simple equivalent electric network of the electrochemical interface, the electrochemical impedance parameters were also obtained. The results showed that the proposed method should be found in wider applications in interfacial biochemistry studies since these combined techniques have advantages in real time multidimensional information including electrochemical and electrochemical impedance parameters. Copyright 2000 Academic Press.

Journal Article↗

PubMed2000

Repression of TNF-alpha-induced E-selectin expression by PPAR activators: involvement of transcriptional repressor LRF-1/ATF3.

Peroxisome proliferator-activated receptor (PPAR) activators were shown to inhibit the expression of E-selectin of human vascular endothelial cells in response to tumor necrosis factor-alpha (TNF-alpha). Troglitazone, pioglitazone, alpha-clofibrate, and 15-deoxy-Delta12,14-prostaglandin J2 all inhibited the TNF-alpha-stimulated E-selectin gene transcription in reporter assay. To further clarify the underlying transcriptional regulation, nuclear factor(s) that binds to the nuclear factor-endothelial leukocyte adhesion molecule 1 (NF-ELAM1) site of the E-selectin gene promoter was investigated. The activators caused a significant induction of liver regenerating factor 1 (LRF1)/activating transcription factor 3 (ATF3), which bound to the NF-ELAM1 site and repressed the TNF-alpha-induced E-selectin gene expression. From these data, the effect of PPAR activators was mediated, in part, through the induction of LRF1/ATF3. This might provide a novel molecular mechanism of anti-inflammatory effect of PPAR activators.

Activating Transcription Factor 3↗

PubMed2000

alpha-Amylase immobilized on bulk acoustic-wave sensor by UV-curing coating.

A new method for immobilization of alpha-amylase by UV-curing coating is proposed in this paper. The immobilization procedure of UV-curing coating on piezoelectric quartz crystal is simple and convenient, and causes less loss of enzymatic activity. The activity of the immobilized alpha-amylase is monitored by a technique based on bulk acoustic-wave (BAW) sensor. The frequency shift of BAW sensor can reflect the degree of hydrolysis of starch by the immobilized alpha-amylase. It is appropriate for the immobilized alpha-amylase to hydrolyze the soluble starch under pH 7.0 condition, which is similar to that of the free alpha-amylase. Kinetic parameters (the Michaelis constant, K(m), and the maximum initial rate V(max)) of the enzymatic hydrolysis of starch by the immobilized alpha-amylase are estimated by using a linear method of Lineweaver-Burk plot. K(m)=12.7mgml(-1) and V(max)=15.9Hzmin(-1). And the experimental results show that the immobilized alpha-amylase entrapped by the UV-curing coating retains adequate enzymatic activity and can be reused more than 50 times under certain experimental conditions.

Journal Article↗

PubMed2000

Cloning and characterization of the murine pkd2 promoter.

Pkd2, the mouse homologue of PKD2, the gene responsible for the second form of autosomal dominant polycystic kidney disease, is highly expressed in fetal and adult mouse tissues. The expression of Pkd2 is developmentally regulated. To begin to dissect out the regulatory mechanism of Pkd2 expression, we characterized the basic features of the gene structure and identified potential cis-regulatory elements of Pkd2 transcription. Pkd2 spans 42 kb with a transcription start site 165 bp upstream of the translation start codon. Exon 1 of Pkd2 is 755 bp long, and the full-length transcript is 5215 bp. The Pkd2 promoter region is GC-rich and lacks a consensus TATA or CCAAT box. Consensus binding sites for the transcription factors Sp-1, NF-1, and Ap-2 lie in the 5' upstream region of Pkd2. The Sp-1 binding site is conserved in 5' upstream sequences of both the mouse and the human genes. The CAT activity of a series of upstream segments from +178 to -2749 was assessed in MDCK, LLCPK1, COS-7, and HEK293 cells. Deletion analysis identified a 409-bp fragment from position -221 to +178 responsible for basal promoter activity. A 922-bp fragment from -744 to +178 showed the highest level of CAT activity in the cell lines tested. These data define a functional promoter candidate region for Pkd2.

Animals↗

PubMed2000

Fatty acyl-CoAs inhibit retinoic acid-induced apoptosis in Hep3B cells.

Retinoic acid (RA) induces apoptosis in Hep3B human hepatoma cells. 9-Cis-RA (c-RA) had a similar effect as all-trans-RA (t-RA) in inducing cell death in Hep3B cells. RA-induced Hep3B-cell death was associated with inhibited expression of the hepatocyte nuclear factor 4 (HNF-4) gene. Palmitoyl-CoA ((C16:0)-CoA), the reported HNF-4 ligand, prevented RA-induced apoptosis. The effect of (C16:0)-CoA was specific, since palmitic acid and co-enzyme A had no effect in preventing RA-induced apoptosis. Bovine serum albumin (BSA) also prevented RA-induced apoptosis. However, in contrast to BSA, which induced cell growth, (C16:0)-CoA alone had no effect on cell growth. Investigating the possible role of HNF-4 in apoptosis, the reported HNF-4 antagonist (C18:0)-CoA was employed, and it also prevented RA-induced apoptosis. By transient transfection, overexpression of HNF-4 did not prevent RA-induced apoptosis. The induction and prevention of apoptosis caused by RA and (C16:0)-CoA were associated, respectively with the induction and inhibition of the expression of transforming growth factor beta (TGFbeta), which is known to play a role in apoptosis. Furthermore, RA and (C16:0)-CoA can regulate AP-1, which is a key regulator of the TGFbeta gene. Our data indicate that fatty acyl-CoAs can prevent RA-induced apoptosis and that TGFbeta, rather than HNF-4, may play a role in these regulatory processes. Our data also suggest that (C16:0)-CoA and (C18:0)-CoA are not the agonist and antagonist for HNF4, respectively in the Hep3B cell system.

Alitretinoin↗

PubMed2000

Gas chromatographic determination of organomercury following aqueous derivatization with sodium tetraethylborate and sodium tetraphenylborate. Comparative study of gas chromatography coupled with atomic fluorescence spectrometry, atomic emission spectrometry and mass spectrometry.

Several hyphenated analytical techniques, including gas chromatography (GC) coupled with atomic fluorescence spectrometry (AFS), microwave-induced plasma atomic emission spectrometry (AES), and mass spectrometry (MS), have been evaluated for methylmercury and ethylmercury analysis following aqueous derivatization with both sodium tetraethylborate and sodium tetraphenylborate. Both GC-AFS and GC-AES were shown to be excellent techniques with detection limits in the range of sub-picogram levels (0.02-0.04 pg as Hg). Both techniques have wide linear ranges, although setting of the AFS sensitivity has to be selected manually based on the concentration of mercury in the sample. Phenylation seems to be more favorable in this study because of its capability of distinguishing between ethylmercury and inorganic mercury, and low cost compared to ethylation. Although sensitivity of GC-MS is poor with detection limits ranging from 30 to 50 pg as Hg, it is an essential technique for confirmation of the derivatization products.

Borates↗

PubMed2000

Analysis of partner of inscuteable, a novel player of Drosophila asymmetric divisions, reveals two distinct steps in inscuteable apical localization.

Asymmetric localization is a prerequisite for inscuteable (insc) to function in coordinating and mediating asymmetric cell divisions in Drosophila. We show here that Partner of Inscuteable (Pins), a new component of asymmetric divisions, is required for Inscuteable to asymmetrically localize. In the absence of pins, Inscuteable becomes cytoplasmic and asymmetric divisions of neuroblasts and mitotic domain 9 cells show defects reminiscent of insc mutants. Pins colocalizes with Insc and interacts with the region necessary and sufficient for directing its asymmetric localization. Analyses of pins function in neuroblasts reveal two distinct steps for Insc apical cortical localization: A pins-independent, bazooka-dependent initiation step during delamination (interphase) and a later maintenance step during which Baz, Pins, and Insc localization are interdependent.

Amino Acid Sequence↗