Soybean(Glycine max)rhizosphere organic phosphorus recycling relies on acid phosphatase activity and specific phosphorusmineralizing-related bacteria in phosphate deficient acidic soils

Bacteria play critical roles in regulating soil phosphorus(P) cycling. The effects of interactions between crops and soil P-availability on bacterial communities and the feedback regulation of soil P cycling by the bacterial community modifications are poorly understood. Here, six soybean(Glycine max) genotypes with differences in P efficiency were cultivated in acidic soils with long-term sufficient or deficient P-fertilizer treatments. The acid phosphatase(AcP) activities, organic-P concentrations and associated bacterial community compositions were determined in bulk and rhizosphere soils. The results showed that both soybean plant P content and the soil AcP activity were negatively correlated with soil organic-P concentration in P-deficient acidic soils. Soil P-availability affected the ɑ-diversity of bacteria in both bulk and rhizosphere soils. However, soybean had a stronger effect on the bacterial community composition, as reflected by the similar biomarker bacteria in the rhizosphere soils in both P-treatments. The relative abundance of biomarker bacteria Proteobacteria was strongly correlated with soil organic-P concentration and AcP activity in low-P treatments. Further high-throughput sequencing of the phoC gene revealed an obvious shift in Proteobacteria groups between bulk soils and rhizosphere soils, which was emphasized by the higher relative abundances of Cupriavidus and Klebsiella, and lower relative abundance of Xanthomonas in rhizosphere soils. Among them, Cupriavidus was the dominant phoC bacterial genus, and it was negatively correlated with the soil organic-P concentration. These findings suggest that soybean growth relies on organic-P mineralization in P-deficient acidic soils, which might be partially achieved by recruiting specific phoCharboring bacteria, such as Cupriavidus.

Inhibiting phosphatase and actin regulator 1 expression is neuroprotective in the context of traumatic brain injury

Studies have found that the phosphatase actin regulatory factor 1 expression can be related to stroke,but it remains unclear whether changes in phosphatase actin regulatory factor 1 expression also play a role in traumatic brain injury.In this study we found that,in a mouse model of traumatic brain injury induced by controlled cortical impact,phosphatase actin regulatory factor 1 expression is increased in endothelial cells,neurons,astrocytes,and microglia.When we overexpressed phosphatase actin regulatory factor 1 by injection an adeno-associated virus vector into the contused area in the traumatic brain injury mice,the water content of the brain tissue increased.However,when phosphatase actin regulatory factor 1 was knocked down,the water content decreased.We also found that inhibiting phosphatase actin regulatory factor 1 expression regulated the nuclear factor kappa B signaling pathway,decreased blood-brain barrier permeability,reduced aquaporin 4 and intercellular adhesion molecule 1 expression,inhibited neuroinflammation,and neuronal apoptosis,thereby improving neurological function.The findings from this study indicate that phosphatase actin regulatory factor 1 may be a potential therapeutic target for traumatic brain injury.

Root phosphatase activity is a competitive trait affiliated with the conservation gradient in root economic space

Background:The diversity of resource acquisition strategies of plant roots determines the species coexistence patterns to a certain extent.However,few root physiological traits have been investigated,such as root phosphatase activity(PA)that affects plant phosphorus(P)uptake.Methods:Root PA and classical root functional traits were investigated for 21 coexisting species in a deciduous broad-leaved forest in warm temperate-subtropical transition zone,China.We analyzed the root order variation of absorptive fine root PA,clarified the attribution of root PA in root economic space(RES)and the different P acquisition strategies of co-occurring species based on the multidimensional RES theory,and determined the dominant factors affecting interspecific variation in root PA.Results:There was no distinct pattern of PA variation with root order in the first three root orders of absorptive fine roots,and root PA was constrained by phylogeny.Root PA is a competitive trait affiliated with the conservation gradient in RES.The tight linkages among root PA,mycorrhizal colonization,diameter,specific root length,and nitrogen concentration suggested trade-offs among P acquisition strategies of co-occurring species,i.e.species with long and fine roots acquire inorganic P by actively exploring the soil and secreting phosphatase to mineralize and hydrolyze organic P,while species with short and thick roots obtain P mainly by investing C in mycorrhizal partners.Conclusions:Collectively,our study provides an insight into the forest species coexistence in climatic transition zones,i.e.species coexistence mechanisms based on diverse phosphorus acquisition strategies.

Overexpression of mitogen-activated protein kinase phosphatase-1 in endothelial cells reduces blood-brain barrier injury in a mouse model of ischemic stroke

Ischemic stroke can cause blood-brain barrier(BBB)injury,which worsens brain damage induced by stroke.Abnormal expression of tight junction proteins in endothelial cells(ECs)can increase intracellular space and BBB leakage.Selective inhibition of mitogen-activated protein kinase,the negative regulatory substrate of mitogen-activated protein kinase phosphatase(MKP)-1,improves tight junction protein function in ECs,and genetic deletion of MKP-1 aggravates ischemic brain injury.However,whether the latter affects BBB integrity,and the cell type-specific mechanism underlying this process,remain unclear.In this study,we established an adult male mouse model of ischemic stroke by occluding the middle cerebral artery for 60 minutes and overexpressed MKP-1 in ECs on the injured side via lentiviral transfection before stroke.We found that overexpression of MKP-1 in ECs reduced infarct volume,reduced the level of inflammatory factors interleukin-1β,interleukin-6,and chemokine C-C motif ligand-2,inhibited vascular injury,and promoted the recovery of sensorimotor and memory/cognitive function.Overexpression of MKP-1 in ECs also inhibited the activation of cerebral ischemia-induced extracellular signal-regulated kinase(ERK)1/2 and the downregulation of occludin expression.Finally,to investigate the mechanism by which MKP-1 exerted these functions in ECs,we established an ischemic stroke model in vitro by depriving the primary endothelial cell of oxygen and glucose,and pharmacologically inhibited the activity of MKP-1 and ERK1/2.Our findings suggest that MKP-1 inhibition aggravates oxygen and glucose deprivation-induced cell death,cell monolayer leakage,and downregulation of occludin expression,and that inhibiting ERK1/2 can reverse these effects.In addition,co-inhibition of MKP-1 and ERK1/2 exhibited similar effects to inhibition of ERK1/2.These findings suggest that overexpression of MKP-1 in ECs can prevent ischemia-induced occludin downregulation and cell death via deactivating ERK1/2,thereby protecting the integrity of BBB,alleviating brain injury,and improving post-stroke prognosis.

Antagonizing adipose tissue-derived exosome miR-103-hepatocyte phosphatase and tensin homolog pathway alleviates autophagy in non-alcoholic steatohepatitis:A trans-cellular crosstalk

BACKGROUND Obesity plays a vital role in the occurrence and development of non-alcoholic steatohepatitis(NASH).However,the underlining mechanism is still unclear,where adipose tissue(AT)derived exosomes may actively participate.MicroRNAs(miRNAs)are commonly secreted from exosomes for cell communication.Though the regulation of miR-103 on insulin sensitivity has been reported,the specific role of AT-derived exosomes miR-103 in NASH is still vague and further investigation may provide novel therapeutic choices.AIM To determine the specific role of AT-derived exosomes miR-103 in developing NASH through various methods.METHODS The expression levels of miR-103 in the AT-derived exosomes and livers were detected and compared between NASH mice and control.The effect of miR-103 on NASH progression was also explored by antagonizing miR-103,including steatosis and inflammation degree changes.The interaction between miR-103 and the autophagy-related gene phosphatase and tensin homolog(PTEN)was confirmed by dual-luciferase reporter assay.The role of the interaction between miR-103 and PTEN on autophagy was verified in NASH-like cells.Finally,the effects of miR-103 from adipose-derived exosomes on NASH and autophagy were analyzed through animal experiments.RESULTS The expression of miR-103 was increased in NASH mice,compared to the control,and inhibition of miR-103 could alleviate NASH.The results of the dual-luciferase reporter assay showed miR-103 could interact with PTEN.MiR-103-anta decreased p-AMPKa,p-mammalian target of rapamycin(mTOR),and p62 but increased the protein levels of PTEN and LC3-II/I and the number of autophagosomes in NASH mice.Similar results were also observed in NASH-like cells,and further experiments showed PTEN silencing inhibited the effect of miR-103-anta.AT derivedexosome miR-103 aggravated NASH and increased the expressions of p-AMPKa,p-mTOR,and p62 but decreased the protein levels of PTEN and LC3-II/I and the number of autophagosomes in mice.CONCLUSION AT derived-exosome increased the levels of miR-103 in the liver,and miR-103 aggravated NASH.Mechanically,miR-103 could interact with PTEN and inhibit autophagy.

Cancerous inhibitor of protein phosphatase 2A enhances chemoresistance of gastric cancer cells to oxaliplatin

BACKGROUND Cancerous inhibitor of protein phosphatase 2A(CIP2A)is a newly discovered oncogene.It is an active cell proliferation regulatory factor that inhibits tumor apoptosis in gastric cancer(GC)cells.CIP2A is functionally related to chemoresistance in various types of tumors according to recent studies.The underlying mechanism,however,is unknown.Further,the primary treatment regimen for GC is oxaliplatin-based chemotherapy.Nonetheless,it often fails due to chemoresistance of GC cells to oxaliplatin.AIM The goal of this study was to examine CIP2A expression and its association with oxaliplatin resistance in human GC cells.METHODS Immunohistochemistry was used to examine CIP2A expression in GC tissues and adjacent normal tissues.CIP2A expression in GC cell lines was reduced using small interfering RNA.After confirming the silencing efficiency,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium and flow cytometry assays were used to evaluate cell proliferation and apoptosis caused by oxaliplatin treatment.Further,the key genes and protein changes were verified using realtime quantitative reverse transcription PCR and Western blotting,respectively,before and after intervention.For bioinformatics analysis,we used the R software and Bioconductor project.For statistical analysis,we used GraphPad Prism 6.0 and the Statistical Package for the Social Sciences software version 20.0(IBM,Armonk,United States).RESULTS A high level of CIP2A expression was associated with tumor size,T stage,lymph node metastasis,Tumor Node Metastasis stage,and a poor prognosis.Further,CIP2A expression was higher in GC cells than in normal human gastric epithelial cells.Using small interfering RNA against CIP2A,we discovered that CIP2A knockdown inhibited cell proliferation and significantly increased GC cell sensitivity to oxaliplatin.Moreover,CIP2A knockdown enhanced oxaliplatin-induced apoptosis in GC cells.Hence,high CIP2A levels in GC may be a factor in chemoresistance to oxaliplatin.In human GC cells,CIP2A regulated protein kinase B phosphorylation,and chemical inhibition of the protein kinase B signaling pathway was significantly associated with increased sensitivity to oxaliplatin.Therefore,the protein kinase B signaling pathway was correlated with CIP2Aenhanced chemoresistance of human GC cells to oxaliplatin.CONCLUSION CIP2A expression could be a novel therapeutic strategy for chemoresistance in GC.

Single-cell analysis identifies phospholysine phosphohistidine inorganic pyrophosphate phosphatase as a target in ulcerative colitis

BACKGROUND Ulcerative colitis(UC)is a chronic gastrointestinal disorder characterized by inflammation and ulceration,representing a significant predisposition to colorectal cancer.Recent advances in single-cell RNA sequencing(scRNA-seq)technology offer a promising avenue for dissecting the complex cellular interactions and molecular signatures driving UC pathology.AIM To utilize scRNA-seq technology to dissect the complex cellular interactions and molecular signatures that underlie UC pathology.METHODS In this research,we integrated and analyzed the scRNA-seq data from UC patients.Moreover,we conducted mRNA and protein level assays as well as pathology-related staining tests on clinical patient samples.RESULTS In this study,we identified the sustained upregulation of inflammatory response pathways during UC progression,characterized the features of damaged endothelial cells in colitis.Furthermore,we uncovered the downregulation of phospholysine phosphohistidine inorganic pyrophosphate phosphatase(LHPP)has a negative correlation with signal transducer and activator of transcription 3.Significant downregulation of LHPP in UC patient tissues and plasma suggests that LHPP may serve as a potential therapeutic target for UC.This paper highlights the importance of LHPP as a potential key target in UC and unveils its potential role in inflammation regulation.CONCLUSION The findings suggest that LHPP may serve as a potential therapeutic target for UC,emphasizing its importance as a potential key target in UC and unveiling its role in inflammation regulation.

Transient hyperphosphatasemia in a toddler with COVID-19 infection:A case report and literature review

BACKGROUND Transient hyperphosphatasemia(TH)is a condition characterized by elevated serum alkaline phosphatase(ALP)in the clinical setting with no evidence of bone or liver disease among children under the age of 5.Typically,it will resolve spontaneously in a few months in the majority of cases.TH has been found to be associated with viral infections.Two cases of TH associated with coronavirus disease 2019(COVID-19)infection in toddlers have been previously reported.CASE SUMMARY A previously healthy 2-year-old boy presented with fever and positive real-time polymerase chain reaction for COVID-19.Prior to his illness,the patient had been in close contact with his grandfather,who later developed COVID-19.The physical examination on admission was unremarkable.He remained asymptomatic throughout 7 d of hospitalization.On the 5th day of his illness,blood tests showed markedly elevated serum ALP(4178 U/L).Results from the simultaneous testing of the remaining liver profiles and metabolic bone panels were normal.Two months after discharge from the hospital,the patient continued to thrive well.The skeletal surveys revealed no significant abnormalities.The serum ALP declined into the normal range adjusted for his age.This evidence is consistent with the diagnosis of TH.CONCLUSION TH can occur in COVID-19-infected toddlers.Serial measurements of ALP levels have been shown to gradually decline into the normal range within a few months.Therefore,being aware of this transient abnormality will help clinicians to avoid additional unnecessary investigations.

Effects of heat shock on change of HSC70/HSP68,acid and alkaline phosphatases before and after rat partial hepatectomy

INTRODUCTIONOnly the liver has the great capability ofregeneration in mammal.Few hepatocytes are inthe phase of division in the normal liver of an adultmammal (including human beings),but theremaining hepatocytes can be induced to proliferatequickly by partial hepatectomy (PH),and,to somedegree,they stop dividing and re-differentiate intocells functioning as hepatocytes.This shows

Nerve growth factor pretreatment against glutamate-induced hippocampal neuronal injury Action mechanism of phosphatase and tensin homologue deleted on chromosome 10

BACKGROUND: Nerve growth factor (NGF) attenuates glutamate-induced injury to hippocampal neurons, and the human tumor suppressor gene phosphatase and tensin homologue deleted on chromosome 10 (PTEN) promotes neuronal apoptosis. However, effects of PTEN in NGF-mediated neuroprotection against glutamate excitotoxicity remain poorly understood. OBJECTIVE: To investigate the relationship between NGF inhibition of glutamate-induced injury and PTEN. DESIGN, TIME AND SETTING: The randomized, controlled, in vitro study was performed at the Department of Pathophysiology, Medical School of Nantong University, China from October 2007 to March 2008. MATERIALS: Glutamate, NGF, 4, 6-diamidino-2-phenyl-indolediacetate, 3-[4, 5-dimethylthiazol-2-yl]- 2, 5-diphenyl tetrazoliumbromide (MTT), and lactate dehydrogenase kit (Sigma, USA), fluorescence microscope and inverted phase contrast microscope (Olympus, Japan) were used in this study. METHODS: Hippocampal neurons were obtained from newborn (< 24 hours) Sprague Dawley rats and cultured for 7 days. The control group was not treated with any intervention factor, the glutamate group was treated with glutamate (0.2 mmol/L), and NGF groups were treated with NGF (10, 50, 100, and 200 μg/L, respectively) prior to glutamate treatment. MAIN OUTCOME MEASURES: The MTT and lactate dehydrogenase assays were applied to evaluate viability of hippocampal neurons. Morphological changes in hippocampal neurons were observed using an inverted phase-contrast microscope, and neuronal apoptosis was detected by 4, 6-diamidino-2-phenyl-indolediacetate staining. PTEN mRNA and protein expression were measured by reverse transcription-polymerase chain reaction and Western blot analysis, respectively. RESULTS: Glutamate (0.2 mmol/L) induced significantly decreased neuronal viability and greater lactate dehydrogenase efflux compared with the control group (P < 0.01). However, compared with the glutamate group, cell viability significantly increased and lactate dehydrogenase efflux decreased in the NGF group with increasing NGF concentrations (P < 0.05 or P < 0.01). The apoptotic ratio and PTEN mRNA and protein expression decreased in the NGF group compared with the glutamate group (P < 0.01). CONCLUSION: Pretreatment with NGF exerted neuroprotective effects against glutamate-induced injury, partially through inhibition of PTEN expression and neuronal apoptosis.

Combination of serum gamma-glutamyltransferase and alkaline phosphatase in predicting the diagnosis of asymptomatic choledocholithiasis secondary to cholecystolithiasis

BACKGROUND Gamma-glutamyltransferase(GGT) is one of the most important laboratory tests for the evaluation of liver damage. Through a long-term clinical observation of patients with secondary asymptomatic choledocholithiasis, we found that most patients had abnormal GGT serum levels.AIM To investigate the combination of serum GGT and alkaline phosphatase(ALP) in predicting the diagnosis of asymptomatic choledocholithiasis secondary to cholecystolithiasis.METHODS In this retrospective cohort study, the clinical data of 829 patients with cholecystolithiasis admitted to the Third Affiliated Hospital of Zunyi Medical College from August 2014 to August 2017 were collected. Among these patients,151 patients had secondary asymptomatic choledocholithiasis and served as the observation group, and the remaining 678 cholecystolithiasis patients served as the control group. Serum liver function indexes were detected in both groups,and the receiver operating characteristic(commonly known as ROC) curves were constructed for markers showing statistical significances. The cutoff value,sensitivity, and specificity of each marker were calculated according to the ROC curves.RESULTS The overall incidence of asymptomatic choledocholithiasis secondary to cholecystolithiasis was 18.2%. The results of liver function indexes including serum aspartate aminotransferase, alanine aminotransferase, direct bilirubin and total bilirubin levels showed no significant differences between the two groups(P> 0.05). However, the serum GGT and ALP levels were significantly higher in the observation group than in the control group(P < 0.05). The ROC curve analysis showed that the area under the curve was 0.881(95%CI: 0.830-0.932), 0.647(95%CI: 0.583-0.711) and 0.923(0.892-0.953) for GGT, ALP, and GGT + ALP,respectively. The corresponding cut-off values of GGT and ALP were 95.5 U/L and 151.5 U/L, sensitivity were 90.8% and 65.1%, and specificity were 83.6% and59.8%, respectively. The sensitivity and specificity of GGT + ALP were 93.5% and85.1%, respectively.CONCLUSION An abnormally elevated serum GGT level has an important value in the diagnosis of asymptomatic choledocholithiasis secondary to cholecystolithiasis.The combination of serum GGT and ALP has better diagnostic performance. As a convenient, rapid and inexpensive test, it should be applied in secondary asymptomatic choledocholithiasis routine screening.

Model based on γ-glutamyltransferase and alkaline phosphatase for hepatocellular carcinoma prognosis

AIM: To determine the prognostic value of alkaline phosphatase(ALP) and γ-glutamyltransferase(GGT) for hepatocellular carcinoma(HCC).METHODS: We analyzed the outcome of 172 HCC patients who underwent liver resection. Receiver operating characteristic(ROC) curve analysis was performed to determine the cut-off value of ALP and GGT. Then, preoperative risk factors for survival were evaluated by multivariate analysis. Based on the significant factors, aprognostic score model was established.RESULTS: By ROC curve analysis, ALP > 120 U/L and GGT > 115 U/L were considered elevated. Overall survival(OS) and tumor-free survival(TFS) for patients with elevated ALP and GGT were significantly worse than for patients with ALP and GGT within the normal range. Multivariate analysis showed that the elevated levels of ALP, GGT and tumor size were independent prognostic factors. Giving each positive factor as a score of 1, we established a preoperative prognostic score model. The 5-year OS for patients with a score of 0, 1, 2 and 3 were 84.0%, 45.9%, 44.1% and 0%, respectively, while the TFS was 80.6%, 40.0%, 38.8% and 0%, respectively. When combining patients with scores of 1 and 2 into the middle risk group, and patients with scores of 0 and 3 into the low-risk and highrisk groups, respectively, different outcomes would be significantly distinguished by the risk groups.CONCLUSION: Elevated ALP and GGT levels were risk predictors in HCC patients. Our prognostic model might vary the outcomes of patients from different risk groups.

3D-QSAR and Surflex Docking Studies of a Series of Alkaline Phosphatase Inhibitors

Alkaline phosphatases(APs) include the placental AP(PLAP), germ cell AP(GCAP), intestinal AP(IAP) and tissue nonspecific AP(TNAP). Over expression of TNAP in smooth muscle cells of kidney and vessels provokes the progress of such serious diseases as end-stage renal disease, idiopathic infantile arterial calcification, ankylosis, osteoarthritis and diabetes. In order to design and optimize the potent TNAP inhibitors, comparative molecular field analysis(CoMFA) and comparative molecular similarity indices analysis(CoMSIA) were used to analyze 3D structure-activity relationships(3D-QSAR) of TNAP inhibitors. The 3D-QSAR model(CoMFA with q^2 = 0.521, r^2 = 0.930; CoMSIA with q^2 = 0.529, r^2 = 0.933) had a good predictability. Surflex-dock was used to reveal the binding mode between the inhibitors and TNAP protein. CoMFA, CoMSIA and docking results provide guidance for the discovery of TNAP inhibitors. Finally, eight new compounds as potential TNAP inhibitors were designed.

Interplay between intestinal alkaline phosphatase, diet, gut microbes and immunity

Intestinal alkaline phosphatase(IAP) plays an essential role in intestinal homeostasis and health through interactions with the resident microbiota, diet and the gut. IAP's role in the intestine is to dephosphorylate toxic microbial ligands such as lipopolysaccharides, unmethylated cytosine-guanosine dinucleotides and flagellin as well as extracellular nucleotides such as uridine diphosphate. IAP's ability to detoxify these ligands is essential in protecting the host from sepsis during acute inflammation and chronic inflammatory conditions such as inflammatory bowel disease. Also important in these complications is IAP's ability to regulate the microbial ecosystem by forming a complex relationship between microbiota, diet and the intestinal mucosal surface. Evidence reveals that diet alters IAP expression and activity and this in turn can influence the gut microbiota and homeostasis. IAP's ability to maintain a healthygastrointestinal tract has accelerated research on its potential use as a therapeutic agent against a multitude of diseases.Exogenous IAP has been shown to have beneficial effects when administered during ulcerative colitis,coronary bypass surgery and sepsis.There are currently a handful of human clinical trials underway investigating the effects of exogenous IAP during sepsis,rheumatoid arthritis and heart surgery.In light of these findings IAP has been marked as a novel agent to help treat a variety of other inflammatory and infectious diseases.The purpose of this review is to highlight the essential characteristics of IAP in protection and maintenance of intestinal homeostasis while addressing the intricate interplay between IAP,diet,microbiota and the intestinal epithelium.

Silencing Fas-associated phosphatase 1 expression enhances efficiency of chemotherapy for colon carcinoma with oxaliplatin

AIM:To investigate whether silencing Fas-associated phosphatase 1(FAP-1)expression enhances the efficiency of chemotherapy for colon carcinoma with oxaliplatin.METHODS:Expression of FAP-1 in mRNA and protein was detected by reverse transcription polymerase chain reaction(RT-PCR)and flow cytometry.Small interfering RNA(siRNA)was designed according to the FAP-1 mRNA sequence.Cell proliferation was evaluated by methyl thiazolyl tetrazolium(MTT)assay.Anenxin V-and propidine iodine(PI)were assayed by flow cytometry for the detection of apoptosis. RESULTS:The expression of FAP-1 was increased in SW480 cells after chemotherapy with oxaliplatin. Transfection of FAP-1 siRNA into SW480 cells silenced the expression of FAP-1 and consequently abolished the inhibitory function of Fas/FasL-mediated apoptosis pathway,thus increasing the efficacy of chemotherapy for colon carcinoma with oxaliplatin. CONCLUSION:RNA interference combined with conventional chemotherapy is more effective against colon cancer.

Association between Serum Alkaline Phosphatase and Carotid Atherosclerosis in a Chinese Population: A Community-based Cross-sectional Study

Objective This study aimed to investigate the relationship between alkaline phosphatase(ALP) and common carotid intima media thickness(IMT), carotid plaque, and extracranial carotid artery stenosis(ECAS). Methods A total of 3,237 participants aged ≥ 40 years were recruited from Jidong community in 2013-2014. Participants were divided into five quintile groups based on their serum ALP levels. Carotid atherosclerosis was assessed using ultrasound. Abnormal IMT, carotid plaque, and ECAS were defined as IMT > 0.9 mm, IMT > 1.5 mm, and ≥ 50% stenosis in at least one extracranial carotid artery, respectively. Results Common carotid IMT values and the prevalence of carotid plaque increased across serum ALP quintiles. Higher ALP quintiles were correlated with an increased risk of abnormal IMT [fourth quintile: odds ratio(OR) 1.78, 95% confidence interval(CI) 1.13-2.82, P = 0.0135;fifth quintile: OR = 1.82, 95% CI: 1.15-2.87, P = 0.0110] and ECAS compared to the lowest quintile(fifth quintile: OR = 1.47, 95% CI: 1.09-1.97, P = 0.0106). The association between ALP and prevalence of carotid plaque became insignificant after adjustment for confounders. Conclusion Serum ALP levels were independently associated with abnormal common carotid IMT and ECAS. These conclusions need to be further corroborated in future prospective cohort studies.

Use of the alkaline phosphatase to prealbumin ratio as an independent predictive factor for the prognosis of gastric cancer

BACKGROUND Gastric cancer(GC)is characterized by a low 5-year survival rate.The prognosis is still not satisfactory although it has significantly improved due to developments in medicine.Thus,the identification of more efficient indices for the evaluation of GC prognosis is required.We propose,for the first time,that the alkaline phosphatase(ALP)to prealbumin(PA)ratio(APR)can be used as an independent prognostic factor in GC.AIM To evaluate the prognostic value the APR in GC.METHODS According to the exclusion strategy,we collected the preoperative serologic examination results and clinical information of 409 GC patients treated in Shandong Provincial Hospital from January to December,2016.By calculating the APR,the neutrophil and lymphocyte ratio(NLR),C-reactive protein(CRP)and albumin(ALB)ratio,platelet and lymphocyte ratio,lymphocyte and monocyte ratio,and the relationship with clinical information,we verified the role of preoperative APR ratio in the prognosis of GC.In addition,we used a Cox model combined with the APR and tumor stage to demonstrate its efficacy in assessing the prognosis of GC patients.RESULTS Preoperative APR was an independent prognostic factor for GC.The median age of patients in the APR-high group was greater compared with that in the APR-low group.Patients with a higher APR had a more advanced clinical stage,higher neutrophil to lymphocyte,CRP to ALB,and platelet to lymphocyte ratios,but a lower lymphocyte to monocyte ratio(P<0.05).The APR-high group also had higher glycoprotein antigen 199 and carbohydrate antigen 125 levels than the APR-low group(P<0.05).Median overall survival and disease-free survival were significantly longer in the APR-low group than in the APR-high group.In addition,a Cox model based on the APR and tumor stage was more effective in evaluating the prognosis of patients than models based on stage alone or stage plus the NLR.CONCLUSION A higher APR is an independent and negative prognostic factor for GC.The prognosis of GC can be better evaluated using a Cox model based on the APR and stage.

Protein tyrosine phosphatase non-receptor type 2 andinflammatory bowel disease

Genome wide association studies have associated single nucleotide polymorphisms within the gene locus encoding protein tyrosine phosphatase non-receptor type 2(PTPN2) with the onset of inflammatory bowel disease(IBD) and other inflammatory disorders. Expression of PTPN2 is enhanced in actively inflamed intestinal tissue featuring a marked up-regulation in intestinal epithelial cells. PTPN2 deficient mice suffer from severe intestinal and systemic inflammation and display aberrant innate and adaptive immune responses. In particular, PTPN2 is involved in the regulation of inflammatory signalling cascades, and critical for protecting intestinal epithelial barrier function, regulating innate and adaptive immune responses, and finally for maintaining intestinal homeostasis. On one hand, dysfunction of PTPN2 has drastic effects on innate host defence mechanisms, including increased secretion of pro-inflammatory cytokines, limited autophagosome formation in response to invading pathogens, and disruption of the intestinal epithelial barrier. On the other hand, PTPN2 function is crucial for controlling adaptive immune functions, by regulating T cell proliferation and differentiation as well as maintaining T cell tolerance. In this way, dysfunction of PTPN2 contributes to the manifestation of IBD. The aim of this review is to present an overview of recent findings on the role of PTPN2 in intestinal homeostasis and the impact of dysfunctional PTPN2 on intestinal inflammation.

Albumin-to-alkaline phosphatase ratio: A novel prognostic index of overall survival in cholangiocarcinoma patients after surgery

AIM To clarify the prognostic significance of preoperative albumin-to-alkaline phosphatase ratio(AAPR) in cholangiocarcinoma(CCA) subjects receiving surgery.METHODS In this retrospective study, we included 303 CCA patients receiving surgery without preoperative therapy between 2002 and 2014. Clinicopathological characteristics(including AAPR) were analyzed to determine predictors of postoperative overall survival and recurrence-free survival(RFS). In addition,univariate and multivariate Cox proportional hazards models were conducted,followed by application of time-dependent receiver operating curves to identify the optimal cut-off.RESULTS Univariate and multivariate analyses revealed both decreased overall survival[hazard ratio(HR): 2.88, 95%CI: 1.19-5.78] and recurrence-free survival(HR: 2.31,95%CI: 1.40–3.29) in patients with AAPR < 0.41 compared to those with AAPR ≥0.41. The optimal cut-off of AAPR was 0.41. Of the 303 subjects, 253(83.5%) had an AAPR over 0.41. The overall 1-, 3- and 5-year survival rates were 70.2%, 38.0% and 16.5%, respectively in the low(< 0.41) AAPR group, which were significantly lower than those in the high(≥ 0.41) AAPR group(81.7%, 53.9%, and 33.4%,respectively)(P < 0.0001). Large tumor size, multiple tumors, and advanced clinical stage were also identified as significant predictors of poor prognosis.CONCLUSION Our outcomes showed that AAPR was a potential valuable prognostic indicator in CCA patients undergoing surgery, which should be further confirmed by prospective studies. Moreover, it is necessary to investigate the mechanisms concerning the correlation of low AAPR with poor post-operative survival in CCA patients.

Effects of a decade of organic fertilizer substitution on vegetable yield and soil phosphorus pools, phosphatase activities, and the microbial community in a greenhouse vegetable production system

Partial substitution of chemical fertilizers by organic amendments is adopted widely for promoting the availability of soil phosphorus(P)in agricultural production.However,few studies have comprehensively evaluated the effects of longterm organic substitution on soil P availability and microbial activity in greenhouse vegetable fields.A 10-year(2009–2019)field experiment was carried out to investigate the impacts of organic fertilizer substitution on soil P pools,phosphatase activities and the microbial community,and identify factors that regulate these soil P transformation characteristics.Four treatments included 100%chemical N fertilizer(4 CN),50%substitution of chemical N by manure(2 CN+2 MN),straw(2 CN+2 SN),and combined manure with straw(2 CN+1 MN+1 SN).Compared with the 4 CN treatment,organic substitution treatments increased celery and tomato yields by 6.9-13.8%and 8.6-18.1%,respectively,with the highest yields being in the 2 CN+1 MN+1 SN treatment.After 10 years of fertilization,organic substitution treatments reduced total P and inorganic P accumulation,increased the concentrations of available P,organic P,and microbial biomass P,and promoted phosphatase activities(alkaline and acid phosphomonoesterase,phosphodiesterase,and phytase)and microbial growth in comparison with the 4 CN treatment.Further,organic substitution treatments significantly increased soil C/P,and the partial least squares path model(PLS-PM)revealed that the soil C/P ratio directly and significantly affected phosphatase activities and the microbial biomass and positively influenced soil P pools and vegetable yield.Partial least squares(PLS)regression demonstrated that arbuscular mycorrhizal fungi positively affected phosphatase activities.Our results suggest that organic fertilizer substitution can promote soil P transformation and availability.Combining manure with straw was more effective than applying these materials separately for developing sustainable P management practices.