[Application of interventional respiratory techniques in the treatment of pulmonary bullae:an update].

Pulmonary bullae is a common complication of chronic obstructive pulmonary disease(COPD), causing the deterioration in lung function, leading to aggravated dyspnea and poor quality of life for patients. The traditional therapeutic approach for pulmonary bullae is bullectomy using surgical thoracoscopy. The disadvantage of this approach is the postoperative complications and high risk of recurrence in many patients. In addition, for some patients, due to the patient's physical conditions, such as poor lung function and other diseases, bullectomy could not be used. Therefore, new alternative approaches were urgently needed. In recent years, interventional respiratory technology has been trialed to treat pulmonary bulla all around the world and has achieved great success. In this paper, we reviewed the relevant clinical research progress of interventional respiratory medicine techniques in the treatment of pulmonary bullae.

[Constructions of the scale of difficulty in the extraction of impacted mandibular third molars by using Delphi method].

OBJECTIVE: To evaluate the relevant indicators affecting difficulty in the extraction of impacted mandibular third molars and score difficulty of different operation and risk indicators, so as to build an intuitive and accurate scale to help operators make more accurate analysis and prediction of difficulty before the operation. METHODS: Based on literature and the clinical review, the difficulty indicators of tooth extraction were summarized. Firstly, 10 doctors from Peking University School and Hospital of Stomatology who had been engaged in alveolar surgery for a long time established an expert nominal group, and then rated whether the summarized indicators needed to be retained in the form of face-to-face questionnaires. A level 1 and 2 item frame for evaluating difficulty in the tooth extraction was formed after discussion; Then Delphi method was used to send a questionnaire to 30 experts by e-mail. After two rounds of scoring and modification, the scale of difficulty in the extraction of impacted mandibular third molars was formed. RESULTS: The recycling rate of two rounds of questionnaires was 100.0%, which showed that the experts were very enthusiastic about the study; The authority coefficients (Cr) of the two rounds of Delphi expert consultation were both 0.92, which showed that the results were representative and authoritative. After two rounds of grading and revision, the variable coefficient (CV) decreased and the Kendall's concordance coefficient (W) increased, which were statistically significant: In the first round, the CV was 0.24 and W was 0.56 (P < 0.001), and in the second, the CV was 0.19 and W was 0.72 (P < 0.001), which indicated that there was a good convergence among the expert opinions. Finally, a scale of difficulty in the tooth extraction containing 12 items at level A and 37 items at level B was formed, including operation difficulty indicators, risk difficulty indicators and common difficulty indicators. CONCLUSION: Based on comprehensive literature retrieval, the study has put forward the concept that difficulty in the extraction of impacted mandibular third molars is composed of operation difficulty and risk difficulty. Using Delphi method, the long-term clinical experience and professional knowledge of experts are transformed into quantitative indicators as a scoring scale. The scale has certain representativeness and authority.

[Risk factors and risk model of lymph node metastasis in early gastric cancer].

To investigate the risk factors of lymph node metastasis in early gastric cancer (EGC) and to develop a risk model for the presence of lymph node metastasis. A total of 172 EGC patients, with a median age of 62(52, 68) years, who underwent gastric cancer resection in the First Affiliated Hospital of Nanjing Medical University from January 2017 to June 2019 were selected. Clinical data of the patients were collected through the case system. Logistic regression analysis was used to determine the variables significantly related to lymph node metastasis. ROC curve and calibration curve were used to evaluate the risk model. The results showed that the lymph node metastasis rate of 172 EGC patients was 19.19% (33/172). Tumor size, depth of invasion, degree of differentiation and vascular tumor thrombus were associated with lymph node metastasis (P<0.05), but age ≥ 60 years (OR=5.556, 95%CI: 1.757-17.569, P=0.004), invasion depth (OR=4.218,95%CI:1.418-12.548, P=0.010) and vascular cancer embolus (OR=13.878,95%CI:4.081-47.196,P<0.001) were independent risk factors for lymph node metastasis of EGC. The consistency index of the risk model based on the above risk factors was 0.8835 (95%CI: 0.818 8-0.948 2). The calibration curve shows that the risk assessment model is in good agreement with the actual results, indicating that the model has high accuracy and discrimination.The most common site of metastasis was group 3, followed by group 4. Therefore, patients over 60 years old with submucosal invasion and vascular tumor thrombus may have a higher risk of lymph node metastasis.

[Association between serum lipid level and depression in patients with chronic heart failure].

Objective: To investigate the association between serum lipid level and depression in patients with chronic heart failure (CHF). Methods: A total of 348 patients with CHF from the First department of Cardiology of the people's hospital of Shaanxi province from September 2016 to June 2017 were included.The Hamilton Depression Scale (HAMD) was used to evaluate the degree of depression and some related clinical data were tested.The serum lipid level and depression scores in the patients were analyzed using Pearson correlation analysis, and Logistic regression analysis was used to analyze the confounding factors of depression. Results: There was significant difference in the proportion of depression between normal serum lipid group and dyslipidemia group (P=0.044). Pearson correlation analysis showed that depression score was linearly related to total cholesterol (r=0.326, P<0.001) and low density lipoprotein cholesterol (r=0.354, P<0.001), and Logistic regression analysis showed that after adjusting for age, BMI, triglyceride, low density lipoprotein cholesterol, creatinine, total bilirubin, albumin, B type natriuretic peptide, total cholesterol (OR=3.523, P=0.007) and high density lipoprotein cholesterol (OR=0.205, P=0.041) were associated with depression in CHF patients. Conclusion: Total cholesterol can increase the risk of depression, and high density lipoprotein cholesterol can reduce the risk of depression in CHF patients.

The cardiovascular macrophage: a missing link between gut microbiota and cardiovascular diseases?

The prevalence of cardiovascular diseases is on the rise. Interventions that would aid prevention or treatment of these diseases are essential. The microbes residing in the gut, collectively called "gut microbiota", produce a plethora of compounds that enter the bloodstream and affect the cardiovascular system. Signals ascending from gut microbiome are believed to modulate differentiation and functional activity of macrophages residing in perivascular tissue, atherosclerotic plaques, and perivascular areas of the brain. Cardiovascular macrophages may be the key players that transform the signals ascending from gut microbiome into increased predisposition to cardiovascular diseases. The present review summarizes the knowledge to date on potential relationships between gut microbiota, cardiovascular macrophages, and cardiovascular diseases.

High-level expression and characterization of a new κ-carrageenase from marine bacterium Pedobacter hainanensis NJ-02.

A novel κ-carrageenase gene (CgkB) has been cloned from Pedobacter hainanensis NJ-02 and expressed heterologously in Escherichia coli BL21 (DE3). It consisted of 1935 bp and encoded 644 amino acid residues with a molecular weight of 71·61 kDa. The recombinant enzyme showed maximal activity of 2458 U mg-1 at 40°C and pH 8·0. Additionally, it could retain more than 70% of its maximal activity after being incubated at pH of 5·5-10·0 below 40°C. K+ and a broad range of NaCl can activate the enzyme. The Km and Vmax of CgkB was 2·4 mg ml-1 and 126 mmol mg-1  min-1 . The ESI-MS analysis of hydrolysates indicated that the enzyme can endolytically depolymerize the carrageenan into tetrasaccharides and hexasaccharides. The results indicated that the enzyme with high activity could be a valuable enzyme tool to produce carrageenan oligosaccharides with various activities. SIGNIFICANCE AND IMPACT OF THE STUDY: Enzymatic preparation of carrageenan oligosaccharides has drawn increased attention due to their various physiological activities. It is urgent to explore enzyme tools with higher activity and better stability. In this work, a novel κ-carrageenase was identified and characterized from marine bacterium Pedobacter hainanensis NJ-02. The enzyme with high activity could be a valuable tool to produce carrageenan oligosaccharides with various activities.

Regulatory T cell microRNA expression changes in children with acute Kawasaki disease.

Kawasaki disease (KD) is a type of systemic vasculitis syndrome related to immune dysfunction. Previous studies have implicated that dysfunctional regulatory T cells (Treg ) may be associated with the immune dysfunction in KD. In the absence of microRNAs (miRNAs), forkhead box protein 3 (FoxP3)(+) Treg develop but fail to maintain immune homeostasis. This study was designed to investigate the effects of miR-155, miR-21 and miR-31 on Treg in children with KD. The proportions of CD4(+) CD25(+) FoxP3(+) Treg and the mean fluorescence intensity (MFI) of phosphorylated-signal transducer and activator of transcription (pSTAT)-5 and pSTAT-3 protein in CD4(+) CD25(+) Treg were analysed by flow cytometry. The concentration of interleukin (IL)-6 in plasma was measured by cytometric bead array. Real-time polymerase chain reaction was performed to detect the levels of microRNAs and associated factors in CD4(+) CD25(+) Treg . The proportion of Treg and the mRNA levels of the associated factors [FoxP3, glucocorticoid-induced tumour necrosis factor-receptor (GITR), cytotoxic T lymphocyte antigen (CTLA)-4)] were significantly lower in KD patients (P < 0·05). MiR-155 and miR-21 levels were significantly down-regulated and miR-31 expression was higher in KD patients (P < 0·05). Plasma interleukin (IL)-6 concentrations, pSTAT-3 protein levels and suppressors of cytokine signalling (SOCS)-1 mRNA expression were remarkably elevated in acute KD (P < 0·05), while pSTAT-5 protein levels were remarkably decreased in acute KD (P < 0·05). These findings were reversed after intravenous immunoglobulin treatment (P < 0·05). Our results demonstrate that FoxP3 mRNA levels were primarily affected by the miR-155/SOCS1 and the miR-31 signalling pathways. These results suggest that the decrease in FoxP3(+) Treg might be associated with decreased expression of miR-155, leading to aberrant SOCS1/STAT-5 signalling and overexpression of miR-31 in patients with acute KD.

Nanofiltration process of glyphosate simulated wastewater.

Nanofiltration separation of glyphosate simulated wastewater was investigated using a DK membrane. The effects of operating parameters and the addition of impurities on membrane performance were studied in detail. It was found that at 20 °C, with a glyphosate concentration of 500 mg/L and pH of 2.96, the glyphosate retention rate and the membrane permeate flux increased slightly with increasing transmembrane pressure. With an increase in operating temperature, the permeate flux increased linearly while the retention rate decreased. The permeate flux and glyphosate retention rate decreased with increasing feed concentration. Within the pH range of 3-5, the glyphosate retention rate decreases with increasing pH and reaches a minimum at the isoelectric point of the membrane, while the permeate flux reaches a maximum level at this point. In the pH range of 5-11, with the increases of pH, the glyphosate retention rate increases and the permeate flux decreases. Glyphosate retention decreases slightly with increasing NaCl and phosphite concentrations. This can be explained in terms of the shielding phenomenon.

Magnetic resonance molecular imaging of post-stroke neuroinflammation with a P-selectin targeted iron oxide nanoparticle.

We have developed a magnetic resonance molecular imaging method using a novel iron-oxide contrast agent targeted towards P-selectin - MNP-PBP (magnetic nanoparticle-P-selectin binding peptide) - to image endothelial activation following cerebral ischemia/reperfusion. MNP-PBP consists of approximately 1000 PBP ligands (primary sequence: GSIQPRPQIHNDGDFEEIPEEYLQ GGSSLVSVLDLEPLDAAWL) conjugated to a 50 nm diameter aminated dextran iron oxide particle. In vitro P- and E-selectin binding was assessed by competition ELISA. Transient focal cerebral ischemia was induced in male C57/BL 6 mice followed by contrast injection (MNP-PBP; MNP-NH2; Feridex; MNP-PBP-FITC) at 24 h after reperfusion and T(2) magnetic resonance imaging at 9.4 T was performed. Infarction and microvasculature accumulation of contrast agent was assessed in coronal brain sections. MNP-PBP attenuated antibody binding to P-selectin by 34.8 +/- 1.7%. P-selectin was preferentially increased in the infarct hemisphere and MNP-PBP-FITC accumulation in the infarct hemisphere microvasculature was observed. Compared with the nontargeted iron oxide agents MNP-NH2 and Feridex, MNP-PBP showed a significantly greater T(2) effect within the infarction. MR imaging of P-selectin expression with a targeted iron oxide nanoparticle contrast agent may reveal early endothelial activation in stroke and other neuroinflammatory states.

[Regulation of geochemical activity of microorganisms in a petroleum reservoir by injection of H2O2 or water-air mixture].

In the course of pilot trials of biotechnologies for the enhancement of oil recovery in the Gangxi bed of the Dagang oil field (China), microbiological processes were investigated. The biotechnologies were based on injection into the petroleum reservoir of different oxygen sources (H2O2 solution or a water-air mixture) with nitrogen and phosphorus salts. The injection of water-air mixture with nitrogen and phosphorus salts resulted in an increase in the number of aerobic and anaerobic organotrophic bacteria, rates of sulfate reduction and methanogenesis in formation water and also the content of CO2 (from 4.8-12 to 15-23.2%) and methane (from 86-88 to 91.8%) in the gas. The preferential consumption of isotopically light bicarbonate by methanogens resulted in a higher content of the light 12C in methane; the delta13C/CH4 value changed from -45.1...-48.3 to -50.7...-59.3 per thousand). At the same time, mineral carbonates of the formation water became isotopically heavier; the delta13C/Sigmacarbonates value increased from 3.4...4.0 to 5.4...9.6 per thousand. Growth of hydrocarbon-oxidizing bacteria was accompanied by production of biosurfactants and decreased interfacial tension of formation water. Injection of H2O2 solution resulted in the activation of aerobic processes and in suppression of both sulfate reduction and methanogenesis. Methane content in the gas decreased from 86-88 to 75.4-79.8%, probably due to its consumption by methanotrophs. Due to consumption of isotopically light methane, the residual methane carbon became heavier, with the delta13C/CH4 values from -39.0 to -44.3 per thousand. At the same time, mineral carbonates of the formation water became isotopically considerably lighter; the delta13C/Sigmacarbonates value decreased from 5.4... 9.6 to -1.4...2.7 per thousand). The additional amount of oil recovered during the trial of both variants of biotechnological treatment was 3819 t.

[Microbiological and production characteristics of the high-temperature Kongdian bed revealed during field trial of biotechnology for the enhancement of oil recovery].

Microbiological technology for the enhancement of oil recovery based on the activation of the stratal microflora was tested in the high-temperature horizons of the Kongdian bed (60 degrees C) of the Dagang oil field (China). This biotechnology consists in the pumping of a water-air mixture and nitrogen and phosphorus mineral salts into the oil stratum through injection wells in order to stimulate the activity of the stratal microflora which produce oil-releasing metabolites. Monitoring of the physicochemical, microbiological, and production characteristics of the test site has revealed large changes in the ecosystem as a result of the application of biotechnology. The cell numbers of thermophilic hydrocarbon-oxidizing, fermentative, sulfate-reducing, and methanogenic microorganisms increased 10-10 000-fold. The rates of methanogenesis and sulfate reduction increased in the near-bottom zone of the injection wells and of some production wells. The microbial oil transformation was accompanied by the accumulation of bicarbonate ions, volatile fatty acids, and biosurfactants in the formation waters, as well as of CH4 and CO2 both in the gas phase and in the oil. Microbial metabolites promoted the additional recovery of oil. As a result of the application of biotechnology, the water content in the production liquid from the test site decreased, and the oil content increased. This allowed the recovery of more than 14000 tons of additional oil over 3.5 years.

[Microbiological investigations of high-temperature horizons of the Kongdian petroleum reservoir in connection with field trial of a biotechnology for enhancement of oil recovery].

The physicochemical conditions and microbiological characteristics of the formation waters of the Kongdian bed of the Dagang oil field (China) were studied. It was demonstrated that this bed is a high-temperature ecosystem with formation waters characterized by low mineralization. The concentrations of nitrogen and phosphorus compounds, as well as of electron acceptors, are low. Oil and oil gas are the main organic matter sources. The bed is exploited with water-flooding. The oil stratum was inhabited mostly by anaerobic thermophilic microorganisms, including fermentative (10(2)-10(5) cells/ml), sulfate-reducing (0-10(2) cells/ml), and methanogenic (0-10(3) cells/ml) microorganisms. Aerobic bacteria were detected mainly in the near-bottom zone of injection wells. The rate of sulfate reduction varied from 0.002 to 18.940 microg S(2-) l(-1) day(-1) and the rate of methanogenesis from 0.012 to 16.235 microg CH4 l(-1) day(-1). Microorganisms with great biotechnological potential inhabited the bed. Aerobic thermophilic bacteria were capable of oxidizing oil with the formation of biomass, the products of partial oxidation of oil (volatile acids), and surfactants. During growth on the culture liquid of oiloxidizing bacteria, methanogenic communities produced methane and carbon dioxide, which also had oil-releasing capabilities. Using various labeled tracers, the primary filtration flows of injected solutions at the testing site were studied. Our comprehensive investigations allowed us to conclude that the tested method for microbial enhancement of oil recovery based on the activation of the stratal microflora can be applied in the Kongdian bed horizons.

[Phylogenetic diversity and activity of anaerobic microorganisms of high-temperature horizons of the Dagang Oilfield (China)].

The number of microorganisms of major metabolic groups and the rates of sulfate-reducing and methanogenic processes in the formation waters of the high-temperature horizons of Dagang oilfield have been determined. Using cultural methods, it was shown that the microbial community contained aerobic bacteria oxidizing crude oil, anaerobic fermentative bacteria, sulfate-reducing bacteria, and methanogenic bacteria. Using cultural methods, the possibility of methane production from a mixture of hydrogen and carbon dioxide (H2 + CO2) and from acetate was established, and this result was confirmed by radioassays involving NaH14CO3 and 14CH3COONa. Analysis of 16S rDNA of enrichment cultures of methanogens demonstrated that these microorganisms belong to Methanothermobacter sp. (M. thermoautotrophicus), which consumes hydrogen and carbon dioxide as basic substrates. The genes of acetate-utilizing bacteria were not identified. Phylotypes of the representatives of Thermococcus spp. were found among 16S rDNAs of archaea. 16S rRNA genes of bacterial clones belong to the orders Thermoanaerobacteriales (Thermoanaerobacter, Thermovenabulum, Thermacetogenium, and Coprothermobacter spp.), Thermotogales, Nitrospirales (Thermodesulfovibrio sp.) and Planctomycetales. 16S rDNA of a bacterium capable of oxidizing acetate in the course of syntrophic growth with H2-utilizing methanogens was found at high-temperature petroleum reservoirs for the first time. These results provide further insight into the composition of microbial communities of high-temperature petroleum reservoirs, indicating that syntrophic processes play an important part in acetate degradation accompanied by methane production.

Cloning and expression of pinB gene from Triticum monococum seeds.

Puroindolines (PIN) are low molecular weight, cysteine-rich, endosperm-specific, basic proteins with a unique tryptophan-rich domain found in wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.) as well as other members of Triticaceae. PINs appear to be involved in both flour softness as well as resistance against fungal diseases. These proteins are known to be the major components of 'friabilin' associated with the surface of water washed starch grains and possess lipid binding properties. Structural characterization of puroindolines from Triticum monococum was initiated by amplifying and subsequently cloning the corresponding pin gene into an expression vector, known as pET-32a(+). The protein contains five tryptophanin domains and ten cysteine residues. The pinB gene was fused with the 109aa Trx.Tag thioredoxin for a high-level expression. The cloning sites used for producing fusion proteins also contained cleavable His.Tag and S.tag sequences for detection and purification. After transformation of competent Origami cells, fusion protein expression was detected by growing a transformant in LB medium in the presence of 0.1 mM IPTG at room temperature for 6 hrs on a shaker. Both soluble and insoluble fusion proteins were extracted from Origami cells after sonication. Ni-NTA column (Qiagen) was used to extract and purify these fractions. Following an overnight digestion of the recombinant protein with enterokinase at room temperature, the corresponding fractions were electrophoresed in polyacrylamide gel, electroblotted onto a nitrocellulose membrane and cross-reacted with the anti-friabilin monoclonal antibody. We found that the recombinant PINB protein had a molecular weight of 16 kDa whereas TrxB was 21 kDa. Fusion protein ran at 34 kDa. PINB protein from wheat was shown to be immunologically related to a homologue, tryptophanin, in oat seed. Further study is currently underway to characterize these proteins structurally using NMR.

Partial purification and characterization of proteins with growth promoting activities from ovine mammary gland secretions.

Developmental regulation of growth promoting activities in mammary secretions of pregnant Awassi ewes was defined, and growth factors contained in these secretions were partially purified and characterised. Mammary secretions from pregnant ewes enhanced fibroblast cell (AKR-2B) and mammary cell (CID-9 cell strain) proliferation to levels comparable to that induced by 10% Foetal calf serum. Major milk proteins in mammary secretions collected from pregnant ewes one month prior to lambing up to one week after lambing, were resolved by SDS-PAGE, while gelatinases were resolved by zymography. Gelatinase activity was noted prior to P134 and decreased thereafter to reach a minimum during lactation. This decrease was concomitant with the onset of casein production. It is during this critical developmental period that highest growth promoting activity in mammary secretions was detected. Secretions with highest growth promoting activity were fractionated by ion exchange and gel filtration chromatography. Two heat-resistant, trypsin/chymotrypsin sensitive, growth-promoting activities were characterised. The first, designated ovine mammary derived growth factor-1 (oMDGF-1), had around a 30 kDa molecular weight and eluted at 0.65 M NaCl gradient on cation ion exchange chromatography. The second, oMDGF-2, eluted under gel filtration conditions at a molecular weight of 50 kDa and 150 kDa. oMDGF-1 induced changes in Connexin 43, but not in beta-casein mRNA expression by CID-9 mammary cells. In conclusion, growth factor activities in ewe mammary secretions peak during gestation at a period that overlaps maximal gelatinase expression and precedes milk protein synthesis. The factors modulate mammary cell function and may play a role in mammary gland development.

Molecular interactions of the Gbeta binding domain of the Ste20p/PAK family of protein kinases. An isolated but fully functional Gbeta binding domain from Ste20p is only partially folded as shown by heteronuclear NMR spectroscopy.

The transmission of the mating signal of the budding yeast Saccharomyces cerevisiae requires Ste20p, a member of the serine/threonine protein kinases of the Ste20p/PAK family, to link the Gbeta subunit of the heterotrimeric G protein to the mitogen-activated protein kinase cascades. The binding site of Ste20p to the Gbeta subunit was mapped to a consensus sequence of SSLphiPLI/VXphiphibeta (X for any residue; phi for A, I, L, S or T; beta for basic residues), which was shown to be a novel Gbeta binding (GBB) motif present only in the noncatalytic C-terminal domains of the Ste20p/PAK family of protein kinases (Leeuw, T., Wu, C., Schrag, J. D., Whiteway, M., Thomas, D. Y., and Leberer, E. (1998) Nature 391, 191-195; Leberer, E., Dignard, D., Thomas, D. Y., and Leeuw, T. (2000) Biol. Chem. 381, 427-431). Here, we report the results of an NMR study on two GBB motif peptides and the entire C-terminal domain derived from Ste20p. The NMR data show that the two peptide fragments are not uniquely structured in aqueous solution, but in the presence of 40% trifluoroethanol, the longer 37-residue peptide exhibited two well defined, but flexibly linked helical structure elements. Heteronuclear NMR data indicate that the fully functional 86-residue C-terminal domain of Ste20p is again unfolded in aqueous solution but has helical secondary structure preferences similar to those of the two peptide fragments. The NMR results on the two GBB peptides and the entire GBB domain all indicate that the two important binding residues, Ser(879) and Ser(880), are located at the junction between two helical segments. These experimental observations with the prototype GBB domain of a novel family of Gbeta-controlled effectors may have important implications in understanding the molecular mechanisms of the signal transduction from the heterotrimeric G protein to the mitogen-activated protein kinase cascade.

Optimal design features of camelized human single-domain antibody libraries.

We have constructed a human V(H) library based on a camelized V(H) sequence. The library was constructed with complete randomization of 19 of the 23 CDR3 residues and was panned against two monoclonal antibody targets to generate V(H) sequences for determination of the antigen contact residue positions. Furthermore, the feasibility and desirability of introducing a disulfide bridge between CDR1 and CDR3 was investigated. Sequences derived from the library showed a bias toward the use of C-terminal CDR3 residues as antigen contact residues. Mass spectrometric analyses indicated that CDR1-CDR3 disulfide formation was universal. However, surface plasmon resonance and NMR data showed that the CDR3 constraint imposed by the disulfide bridge was not always desirable. Very high yields of soluble protein products and lack of protein aggregation, as demonstrated by the quality of the (1)H-(15)N HSQC spectra, indicated that the V(H) sequence for library construction was a good choice. These results should be useful in the design of V(H) libraries with optimal features.

pH-induced conformational transitions of a molten-globule-like state of the inhibitory prodomain of furin: implications for zymogen activation.

The endoprotease furin, which belongs to the family of mammalian proprotein convertase (PC), is synthesized as a zymogen with an N-terminal, 81-residue inhibitory prodomain. It has been shown that the proenzyme form of furin undergoes a multistep 'autocatalytic' removal of the prodomain at the C-terminal side of the two consensus sites, R(78)-T-K-R(81) approximately and R(44)-G-V-T-K-R(49) approximately. The furin-mediated cleavage at R(44)-G-V-T-K-R(49) approximately, in particular, is significantly accelerated in an 'acidic' environment. Here, we show that under neutral pH conditions, the inhibitory prodomain of furin is partially folded and undergoes conformational exchanges as indicated by extensive broadening of the NMR spectra. Presence of many ring-current shifted methyl resonances suggests that the partially folded state of the prodomain may still possess a 'semirigid' protein core with specific packing interactions among amino acid side chains. Measurements of the hydrodynamic radii and compaction factors indicate that this partially folded state is significantly more compact than a random chain. The conformational stability of the prodomain appears to be pH sensitive, in that the prodomain undergoes an unfolding transition towards acidic conditions. Our NMR analyses establish that the acid-induced unfolding is mainly experienced by the residues from the C-terminal half of the prodomain (residues R(44)-R(81)) that contains the two furin cleavage sites. A 38-residue peptide fragment derived from the entire pH-sensitive C-terminal region (residues R(44)-R(81)) does not exhibit any exchange-induced line broadening and adopts flexible conformations. We propose that at neutral pH, the cleavage site R(44)-G-V-T-K-R(49) approximately is buried within the protein core that is formed in part by residues from the N-terminal region, and that the cleavage site becomes exposed under acidic conditions, leading to a facile cleavage by the furin enzyme.