Mutation Ter462GlnextTer17 introduces a tail to C-terminus of protein C and causes venous thrombosis.

Protein C (PC), a vitamin K-dependent serine protease zymogen in plasma, can be activated by thrombin-thrombomodulin(TM) complex, resulting in the formation of activated protein C (APC). APC functions to downregulate thrombin generation by inactivating active coagulation factors V(FVa) and VIII(FVIIIa). Deficiency in PC increases the risk of venous thromboembolism (VTE). We have identified two unrelated VTE patients with the same heterozygous mutation (c.1384 T > C, p.Ter462GlnextTer17) in PROC. To comprehend the role of this mutation in VTE development, we expressed recombinant PC-Ter462GlnextTer17 in mammalian cells and evaluated its characteristics using established coagulation assay systems. Functional studies revealed a significant impairment in the activation of the mutant by thrombin or thrombin-TM complex. Furthermore, APC-Ter462GlnextTer17 demonstrated diminished hydrolytic activity towards the chromogenic substrate S2366. APTT and FVa degradation assays showed that both the anticoagulant activity of the mutant protein was markedly impaired, regardless of whether protein S was present or absent. These results were further supported by a thrombin generation assay conducted using purified and plasma-based systems. In conclusion, the Ter462GlnextTer17 mutation introduces a novel tail at the C-terminus of PC, leading to impaired activity in both PC zymogen activation and APC's anticoagulant function. This impairment contributes to thrombosis in individuals carrying this heterozygous mutation and represents a genetic risk factor for VTE.

Met343Val mutation disrupts the shuttling of Trp380 leading to a low-activity conformer of activated protein C and causes thrombosis.

BACKGROUND: Protein C (PC) pathway serves as a major defense mechanism against thrombosis by the activation of PC through the thrombin-thrombomodulin complex and subsequent inactivation of the activated factor (F)V (FVa) and FVIII (FVIIIa) with the assistance of protein S, thereby contributing to hemostatic balance. We identified 2 unrelated patients who suffered from recurrent thrombosis and carried the same heterozygous mutation c.1153A>G, p.Met343Val (M343V), in PROC gene. This mutation had not been previously reported. OBJECTIVES: To explore the molecular basis underlying the anticoagulant defect in patients carrying the M343V mutation in PROC. METHODS: We expressed PC-M343V variant in mammalian cells and characterized its properties through coagulation assays. RESULTS: Our findings demonstrated that while activation of mutant zymogen by thrombin-thrombomodulin complex was slightly affected, cleavage of chromogenic substrate by APC-M343V was significantly impaired. However, Ca2+ increased the cleavage efficiency by approximately 50%. Additionally, there was a severe reduction in affinity between APC-M343V and Na+. Furthermore, the inhibitory ability of APC-M343V toward FVa was markedly impaired. Structural and simulation analyses suggested that Val343 might disrupt the potential hydrogen bonds with Trp380 and cause Trp380 to orient closer to His211, potentially interfering with substrate binding and destabilizing the catalytic triad of APC. CONCLUSION: The M343V mutation in patients adversely affects the reactivity and/or folding of the active site as well as the binding of the physiological substrate to the protease, resulting in impaired protein C anticoagulant activity and ultimately leading to thrombosis.

Organic iontronic memristors for artificial synapses and bionic neuromorphic computing.

To tackle the current crisis of Moore's law, a sophisticated strategy entails the development of multistable memristors, bionic artificial synapses, logic circuits and brain-inspired neuromorphic computing. In comparison with conventional electronic systems, iontronic memristors offer greater potential for the manifestation of artificial intelligence and brain-machine interaction. Organic iontronic memristive materials (OIMs), which possess an organic backbone and exhibit stoichiometric ionic states, have emerged as pivotal contenders for the realization of high-performance bionic iontronic memristors. In this review, a comprehensive analysis of the progress and prospects of OIMs is presented, encompassing their inherent advantages, diverse types, synthesis methodologies, and wide-ranging applications in memristive devices. Predictably, the field of OIMs, as a rapidly developing research subject, presents an exciting opportunity for the development of highly efficient neuro-iontronic systems in areas such as in-sensor computing devices, artificial synapses, and human perception.

Comparative Experimental Study on the Cracking Effect of Liquid Nitrogen Freeze-Thaw Cycles between Anthracite and Long-Flame Coal.

In order to explore the differences in the cracking effect of freeze-thaw cycles on coal of different coal grades, this study used liquid nitrogen to carry out freeze-thaw cycle cracking experiments on coal samples of anthracite and long-flame coal with two degrees of metamorphism. By combining a low-temperature nitrogen adsorption experiment and scanning electron microscopy, the surface cracks and pore structure development of water-saturated coal samples before and after freeze-thaw cycles were tested. Scanning electron microscope (SEM) test results show that the freeze-thaw cycle has an obvious destructive effect on the coal matrix. After three freeze-thaw cycles, the anthracite coal sample is obviously damaged, the coal sample is damaged, and the coal chips are peeled off. The surface of a long-flame coal sample is rough, the structure is loose, and the damage of the coal body is more serious by a freeze-thaw cycle. The results of the low-temperature nitrogen adsorption experiment show that the freeze-thaw cycle can effectively promote the development of the pore structure of the coal body. After three freeze-thaw cycles, the specific surface area growth rates of anthracite and long-flame coal samples are 69.57 and 49.13%, respectively. The pore volume growth rates were 73.01 and 35.54%, respectively. The increment of specific surface area and pore volume of the anthracite coal sample is lower than that of the long-flame coal sample, but the growth rate of specific surface area and pore volume of the anthracite coal sample is higher than that of the long-flame coal sample.

Functional identification of PhMATE1 in flower color formation in petunia.

Multidrug and toxic compound extrusion (MATE) transporter proteins are a class of secondary transporter proteins that can transport flavonoids. Anthocyanins, a kind of flavonoid, are important secondary metabolites widely found in higher plants; they determine the flower color of most angiosperms. TT12 in Arabidopsis was the first MATE protein identified to be involved in flavonoid transport. Petunia (Petunia hybrida) is an important ornamental plant and is one of the ideal plants for studying plant flower color. However, there are few reports on anthocyanin transport in petunia. In this study, we characterized a homolog of Arabidopsis TT12 in the petunia genome, PhMATE1, that shares the highest amino acid sequence identity with Arabidopsis TT12. PhMATE1 protein contained 11 transmembrane helices. PhMATE1 showed a high transcription level in corollas. The silencing of PhMATE1 mediated by both virus-induced gene silence and RNA interference changed flower color and reduced anthocyanin content in petunia, suggesting that PhMATE1 is involved in anthocyanin transport in petunia. Furthermore, PhMATE1 silencing downregulated the expression of the structural genes of the anthocyanin synthesis pathway. The results of this study supported the hypothesis that MATEs are involved in the sequestration of anthocyanins during flower color formation.

Isothermal Storage Delays the Senescence of Post-Harvest Apple Fruit through the Regulation of Antioxidant Activity and Energy Metabolism.

The purpose of this work was to elucidate the influence of TF (5 ± 5 °C, and 5 ± 1 °C) and CT (5 ± 0.1 °C served as an isothermal state) storage environment on the antioxidant ability and energy metabolism in post-harvest apple fruit during storage. Specifically, compared with fruit in TFs groups, the quality attributes of apples in the CT group, including firmness, fresh weight, contents of SSC, and TA were maintained at a higher level. In addition, fruit stored in the CT environment revealed a suppressed respiration rate and EL, lower MDA, O2·-, and H2O2 accumulation but increased the activities of SOD, CAT, APX, and GR. At the end of storage, the SOD, CAT, APX, and GR activities of fruit in the CT group were 38.14%,48.04%, 115.29%, and 34.85% higher than that of the TF5 group, respectively. Fruit in the CT environment also revealed higher AsA, GSH, total phenols, and total flavonoid content. In addition, fruit stored in the CT environment maintained higher ATP content, EC, and more active H+-ATPase, Ca2+-ATPase, CCO, and SDH. At the end of storage, the SDH and CCO activities of fruit in the TF0.1 group were 1.74, and 2.59 times higher than that in the TF5 group, respectively. Taken together, we attributed the fact that a constant temperature storage environment can retard the fruit senescence to the enhancement of antioxidant capacities and maintaining of higher energy status in apple fruit.

Carbon Nanodots Memristor: An Emerging Candidate toward Artificial Biosynapse and Human Sensory Perception System.

In the era of big data and artificial intelligence (AI), advanced data storage and processing technologies are in urgent demand. The innovative neuromorphic algorithm and hardware based on memristor devices hold a promise to break the von Neumann bottleneck. In recent years, carbon nanodots (CDs) have emerged as a new class of nano-carbon materials, which have attracted widespread attention in the applications of chemical sensors, bioimaging, and memristors. The focus of this review is to summarize the main advances of CDs-based memristors, and their state-of-the-art applications in artificial synapses, neuromorphic computing, and human sensory perception systems. The first step is to systematically introduce the synthetic methods of CDs and their derivatives, providing instructive guidance to prepare high-quality CDs with desired properties. Then, the structure-property relationship and resistive switching mechanism of CDs-based memristors are discussed in depth. The current challenges and prospects of memristor-based artificial synapses and neuromorphic computing are also presented. Moreover, this review outlines some promising application scenarios of CDs-based memristors, including neuromorphic sensors and vision, low-energy quantum computation, and human-machine collaboration.

PhAAT1, encoding an anthocyanin acyltransferase, is transcriptionally regulated by PhAN2 in petunia.

Anthocyanins widely exist in plants and they are important pigments for color of petals and fruits. They are produced through a multi-step pathway controlled by transcription factor complexes. The anthocyanin skeleton modification is the last reaction in the anthocyanin synthesis pathway, which improves the stability of anthocyanins. Acylation modification is an important modification of anthocyanins. However, the identification and function of anthocyanin acyltransferase genes and their expression regulation are rarely reported. In this study, we identified the petunia anthocyanin acyltransferase gene, PhAAT1. PhAAT1 is located in the cytoplasm and PhAAT1 silencing changed flower color and reduced the stability of anthocyanin. Metabolomics analysis showed that PhAAT1 silencing led to the reduction of p-coumaroylated and caffeoylated anthocyanins. In addition, PhAAT1 was positively regulated by the MYB transcription factor, PhAN2, which directly interacts with the promoter of PhAAT1.

Shikimate Kinase Plays Important Roles in Anthocyanin Synthesis in Petunia.

In plants, the shikimate pathway is responsible for the production of aromatic amino acids L-tryptophan, L-phenylalanine, and L-tyrosine. L-Phenylalanine is the upstream substrate of flavonoid and anthocyanin synthesis. Shikimate kinase (SK) catalyzes the phosphorylation of the C3 hydroxyl group of shikimate to produce 3-phosphate shikimate (S3P), the fifth step of the shikimate pathway. However, whether SK participates in flavonoid and anthocyanin synthesis is unknown. This study characterized the single-copy PhSK gene in the petunia (Petunia hybrida) genome. PhSK was localized in chloroplasts. PhSK showed a high transcription level in corollas, especially in the coloring stage of flower buds. Suppression of PhSK changed flower color and shape, reduced the content of anthocyanins, and changed the flavonoid metabolome profile in petunia. Surprisingly, PhSK silencing caused a reduction in the shikimate, a substrate of PhSK. Further qPCR analysis showed that PhSK silencing resulted in a reduction in the mRNA level of PhDHQ/SDH, which encodes the protein catalyzing the third and fourth steps of the shikimate pathway, showing a feedback regulation mechanism of gene expression in the shikimate pathway.

Effects of Fruit Storage Temperature and Time on Cloud Stability of Not from Concentrated Apple Juice.

Apple juice that is designated 'Not from concentrated' (NFC) is now increasingly popular with consumers due to its unique taste and rich nutritional value. However, layered precipitation and instability have emerged as serious technical problems that restrict the viability of the NFC apple juice industry. This study researched the influence of water-cored 'Fuji' apple fruit storage under different temperatures (0, 20 °C) and times (0, 9, 18, 30, 60 days) on the turbidity stability of NFC apple juice. Changes in the physicochemical properties (juice yield, pH, total soluble solids and titratable acid), turbidity stability (turbidity and particle size) and precipitation sensitive substances (insoluble starch, total phenolics, soluble protein and pectin) of NFC apple juice were determined, combined with the respiratory rates and ethylene release of apples, in order to study post-harvest regulation and control of processed fruit. Results indicated that fruit storage temperature and time significantly guided the turbidity stability of NFC apple juice. As a typical respiratory climacteric fruit, apple fruit stored 45 days at 0 °C and 15 days at 20 °C gained the best juice stability, respectively. This is basically consistent with the respiratory peak of fruit when processing raw materials. During the post-ripening process, the insoluble starch in apple gradually hydrolyzed into fructose and glucose, while total phenolics diminished and water-soluble pectin content increased. On the other hand, the amounts of pectin, soluble protein and phenolics in fruit juice declined as the fruit aged in the late storage period (stored 75 days at 0 °C and 40 days at 20 °C). Meanwhile particle size became larger and the turbidity stability of cloudy juices also decreased. This study's results will provide a sound theoretical basis for improving the turbidity stability of NFC apple juice by regulating the physiological state of processed raw materials.

Research on the Effect of Freeze-Thaw Cycles at Different Temperatures on the Pore Structure of Water-Saturated Coal Samples.

To study the pore structure transformation of coal at different temperatures, freeze-thaw cycle experiments at different temperature intervals (20 to -20 °C, 20 to -40 °C, 20 to -196 °C) were carried out. The low-field nuclear magnetic resonance equipment was used to characterize the peak area, pore size distribution, and pore number of each group of coal samples. The pore transformation effect of coal samples at different temperature intervals was compared, and the change characteristics of the pore structure of coal samples under the freeze-thaw action were explored. The research shows that the freeze-thaw cycles at different freezing temperature intervals have obvious differences in the effect of coal pore transformation. The area of each peak spectrum in the T 2 distribution curve of coal samples increased significantly under the action of freeze-thaw cycles in different freezing temperature intervals. The increased value of the number of mesopores and macropores shows the phenomenon of "first increase and then decrease" with the increase of the temperature difference. There is a quadratic function relationship between the temperature difference in the freezing temperature interval and the proportion change rate of the adsorption pore or seepage pore. The continuous increase of the temperature difference has a certain marginal effect on the proportion change rate of seepage pores and adsorption pores in coal.

Nanomicelles Array for Ultrahigh-Density Data Storage.

High-density data storage devices based on organic and polymer materials are currently restricted by two key issues, size limitations and uniformity of memory cells. Herein, one triblock polymer is synthesized by ring-opening metathesis polymerization, where the polymer contains an electron-donor-acceptor (A1 D) segment, an electron-acceptor (A2 ) segment, and a hydrophilic segment, that shows ternary memory behavior in a conventional sandwich-type device. The polymers that have monodisperse molecular weight dispersity self-assemble into nanomicelles with a uniform size of 80 nm. Each nanomicelle is composed of an A1 DA2 -type hydrophobic core stabilized with a hydrophilic shell. Nanobowls based on conductive oxide are prepared via the template method, wherein the nanomicelles are present as independent nanoscale memory units to produce an array of micelle matrices. Investigations of the resulting nanomemory device using conductive atomic force microscopy show that the micelles exhibit a predominant semiconductor memory behavior. Compared to traditional ternary devices with a memory unit size of ≈1 mm, this innovative fabrication method based on arrayed uniform nanomicelles downscales the size of storage cells to 80 nm. Furthermore, the described system leads to a greatly enhanced storage density (>108 times over the same area), which opens up new paths for further development of ultrahigh-density data storage devices.

Effect of Freeze-Thaw Cycles on Coal Pore Structure and Gas Emission Characteristics.

Here, we aim to clarify the influence of freeze-thaw cycle on pore structure and gas emission characteristics of coal body and to improve the application level of antipermeability and pumping technology based on freezing-induced cracking in a low-permeability coal seam. Freeze-thaw cycles of anthracite and coking coal were carried out in a freezer (-20 °C). Nuclear magnetic resonance was used to test the transformation characteristics of the freeze-thaw cycles on the pore structure of coal samples. The effect of freeze-thaw cycles on the gas emission characteristics of coal particles (1-3 mm) was studied using a self-built gas emission experimental platform (adsorption equilibrium gas pressure was 1.5 MPa). The results show that the pore structure of coal samples changes after the freeze-thaw cycle and the number of large pores and medium pores increases. The amount of gas emission, emission velocity, and gas diffusion coefficient of anthracite and coking coal all increase to different degrees after freeze-thaw cycles. The freeze-thaw damage of coking coal is greater than that of anthracite. In the third freeze-thaw cycle, the increase of each parameter is the largest, and the third freeze-thaw cycle is considered the optimal number of freezing-thawing cycles. The research results provide a theoretical basis for the production of low-permeability coal seam.

Study on the Evolution of Pore Structure of Anthracite Coal under Liquid-Nitrogen Freeze-Thaw Cycles.

To analyze the evolution characteristics of the internal pore structure of anthracite by liquid-nitrogen (LN2) freeze-thaw cycles, nuclear magnetic resonance was used to test the water-saturated samples, which were frozen-thawed with LN2 for 0-9 exposure. The pore size distribution, development degree, and variation characteristics of different pores were examined from the changes of parameters related to T 2 spectra, which increased the macropore frequency: First, LN2 freeze-thaw cycles are beneficial to the development of cracks and have the greatest promoting effect on macropores. Second, the crack development rate of coal samples decreased with the increase of the number of freeze-thaw cycles. The crack development rate was the fastest in the first freeze-thaw cycle, and the crack development did not increase significantly after the third freeze-thaw cycle. Third, the pore structure of anthracite is under the influences of thermal stress and frost heaving force (the force caused by the expansion of water as it freezes). Therefore, it can be determined that three times of LN2 freeze-thaw cycles has the best effect in the LN2 injection to increase coal permeability and recover coalbed methane. The results provide theoretical support for the field application of coal freezing cracking and antireflection promotion pumping.

Layer-by-Layer Assembly of Monolayer Films Precisely Controlled by LB Technology to Realize Low-Energy Consumption and High-Stability Ternary Data-Storage Devices.

Organic semiconductor devices with low energy consumption and excellent stability are highly desirable. Controlling the intermolecular alignment orientation by designing the molecular structure or optimization of the film preparation process is an alternative way to achieve this goal. In this paper, a new idea was proposed to realize the formation of an aligned monomolecular layer and multimolecular layer thin films on the electrode substrate by controlling the surface pressure of molecular layer on the liquid surface by LB technology. An amphiphilic π-conjugated D-A molecule was synthesized, and the influence of spin coating and LB technology on intermolecular ordered stacking in the film and the electrical memory performance were investigated. The results demonstrated that the film fabricated by LB technology has some advantages compared with that fabricated by spin-coating method, such as higher crystallinity, lower surface roughness and better-organized monomolecular and multimolecular layer, which significantly promoted the performance of the electrical memory device with lower power consumption and longer stability.

Study on Eliminating the Water Blocking Effect in Coal Seams Using Gas-Wetting Reversal Technology.

To eliminate or alleviate the water blocking effect (WBE) encountered while hydraulic fracturing of coal seams, the wettability of the coal body was changed, using gas-wetting reversal technology, thus improving gas drainage. After initial measurements of contact angles, surface tension, surface free energies, erosion resistance, self-absorption capacities, and self-absorption rates of coal samples, a hydrophobic and low-surface-tension gas surfactant was selected. After comparing the results of four candidate surfactants, two surfactants were selected, FC117 and FC134, which were both hydrophobic and exhibited low surface tension, to achieve the desired effect. Testing showed that with increased surfactant concentration contact angles increased and surface tension gradually decreased. After surfactant treatment, the coal surface energy decreased, self-absorption capacities and rates of coal samples decreased significantly, and their erosion resistance was good. After determination and verification of several evaluation parameters, the results showed that the two surfactants performed well and achieved the expected effect. By optimizing and evaluating gas-wetting reversal agents, our work has provided a theoretical basis and scientific guidelines for eliminating the WBE from coal seams, thereby facilitating gas drainage.

[Effects of rootstocks on the growth and berry quality of Vitis vinifera cv. Cabernet Sauvignon grapevine in Changli zone, Hebei Province, China].

Cabernet Sauvignon grafted onto seven rootstocks 188-08, 5BB, SO4, 3309C, 110R, 5C and 101-14M, with the own-rooted vines as control, were investigated to study the effects of different rootstocks on the growth, fruit quality and yield of Cabernet Sauvignon in Changli zone, Hebei Province, China. The results showed that Cabernet Sauvignon grafted on 5BB and 5C significantly increased the trunk diameter, and 5C significantly increased one-year-old shoot diameter. 188-08, 5BB and 5C as rootstock obviously improved berry soluble solid content, in addition 188- 08 and 5BB significantly increased berry reducing sugar content. The vines on 101-14M and 3309C significantly decreased berry titratable acid content. The rootstock 5C and 101-14M significantly raised grape skin phenol and anthocyanin contents, and rootstock 101-14M significantly increased tannin content in grape skin. Cabernet Sauvignon grafted onto 3309C, 110R, 5C and 101-14M obviously got higher yield per vine than own-rooted vines. Growing parameter, grape quality index and yield per vine grafted on seven rootstocks and own-rooted vine were synthetically evaluated by fuzzy evaluation method, and the synthetical effects of vine grafted on seven rootstocks were better than own-rooted vine, with the order of scores from high to low as 5C, 101-14M, 3309C, 5BB, 188-08, 110R and SO4 under Changli unique climate and environment conditions.

Translation and psychometric properties of the Chinese (Mandarin) version of the Child Oral Health Impact Profile-Short Form 19 (COHIP-SF 19) for school-age children.

BACKGROUND: Although caries and malocclusion occur with a high prevalence in Chinese school-age children, there were no appropriate instrument to assess the oral health-related quality of life (OHRQoL) for this population. The aim of our study was to develop a Chinese (Mandarin) version of the Child Oral Health Impact Profile-Short Form 19 (COHIP-SF 19) and provide a preliminary test of its psychometric properties. METHODS: The Chinese version of COHIP-SF 19 was developed through a standard translation and back translation procedure. The psychometric properties of the instrument were tested among 644 school-age children in Beijing, China, including the internal consistency, test-retest reliability, discriminant and convergent validity. A Mann-Whitney U test was used to determine the capability of the instrument to differentiate children with different caries and malocclusion outcomes. And partial Spearman correlations were used to determine the relationships between the OHRQoL scores and clinical-severity indicators and self-perceived health ratings, respectively. RESULTS: Chinese school-age children had relatively high OHRQoL scores, in spite of the fact that oral impacts were quite common (56.3%). The internal consistency and retest reliability were good to excellent with a Chronbach's alpha of 0.81 and an intra-class correlation coefficient (ICC) of 0.77. Children who had active tooth decay or severe malocclusion had significantly lower COHIP-SF 19 scores (P ≤0.001). Girls had somewhat higher scores in the oral health and functional well-being subscales (P <0.05), while children from rural districts had lower scores than children from urban areas (P <0.05). We observed a low to moderate correlation between the overall COHIP-SF 19, subscale scores and clinical severity indicators as well as self-perceived health ratings, after adjustment for children's age, gender, and school district (│r s │ =0.11 - 0.51, P <0.05). CONCLUSION: We confirmed satisfactory psychometric properties for the Chinese version of COHIP-SF 19 in a community sample of Chinese school-age children. The OHRQoL instrument should play a more important role in future clinical studies, epidemiological surveys and potential public health policy in China.

[Studies on keratocystic odontogenic tumors].

Keratocystic odontogenic tumors (KCOTs, previously known as odontogenic keratocysts) are aggressive, noninflammatory jaw lesions with a putative high growth potential and a propensity for recurrence. This article puts together a summary of the serial studies related to KCOTs undertaken by the author's research group in recent years. Intraosseous jaw cysts with a solely orthokeratinized lining epithelium have been suggested to differ from the typical KCOTs. We report 20 cases of such cyst type under the term of 'orthokeratinized odontogenic cyst (OOC)'. Apart from the presence of a keratinizing epithelial lining, the OOC lacks the other histological features of KCOT, exhibits little if any tendency to recur, has no apparent association with NBCCS, may be cured by simple enucleation, and may thus constitute its own clinical entity. Mutations in PTCH1 gene are responsible for NBCCS and are related in tumors associated with this syndrome. We have so far detected 26 PTCH1 mutations (2 mutations occurred twice) in 10 out of 34 (29.4%) sporadic and 14 out of 16 (87.5%) NBCCS-associated KCOTs. The 26 mutations consisted of 10 frameshift, 2 nonsense, 3 aberrant splicing, 4 in-frame insertion/deletion/ duplication and 7 missense mutations. Two missense mutations in PTCH2 were also detected in 2 out of 15 NBCCS related KCOT patients. By contrast, no pathogenic mutation was detected in SMO. Thus, our data, together with reports from other groups, indicate that defects of PTCH1 are involved in the pathogenesis of syndromic as well as sporadic KCOTs. The pathogenic role of PTCH2 requires further investigation. A series of in vitro studies on bone resorption of KCOTs and ameloblastomas were undertaken by this group. The results indicate that odontogenic lesions could promote bone resorption in vitro and it is likely to be related to some of the cytokines secreted by the lesions.

[PTCH gene mutations in odontogenic keratocysts].

OBJECTIVE: To investigate the frequency, type and distribution of PTCH mutations in odontogenic keratocysts (OKC) and to analyze the molecular pathological relationship between sporadic OKC and OKC associated with nevoid basal cell carcinoma syndrome (NBCCS). METHODS: Genomic DNA was extracted from 8 cases of OKC lesions (4 sporadic OKCs and 4 NBCCS-related OKCs). PTCH gene mutations were detected by PCR-direct sequencing. RESULTS: Six novel PTCH mutations were identified in 6 out of 8 cases (2 sporadic and 4 NBCCS-related OKCs). Two of these were missense mutations leading to substitution of an amino acid residue respectively. The other 4 mutations were identified as insertion or deletion ranging from one single base to 7 bases, three of which caused frame-shift leading to premature truncation of PTCH protein and one resulted in an insertion of 2 amino acid residues. All these identified mutations were novel and have not been previously described. CONCLUSIONS: PTCH gene mutation is a common event in NBCCS-related OKCs and could also be detected in some sporadic OKCs. Abnormalities of PTCH gene may be involved in the pathogenesis of OKC.