Diverse Functions of Parkin in Midbrain Dopaminergic Neurons.

Parkinson's disease (PD) is characterized by preferential degeneration of midbrain dopaminergic neurons that contributes to its typical clinical manifestation. Mutations in the parkin gene (PARK2) represent a relatively common genetic cause of early onset PD. Parkin has been implicated in PINK1-dependent mitochondrial quantity control by targeting dysfunctional mitochondria to lysosomes via mitophagy. Recent evidence suggests that parkin can be activated in PINK1-independent manner to regulate synaptic function in human dopaminergic neurons. Neuronal activity triggers CaMKII-mediated activation of parkin and its recruitment to synaptic vesicles where parkin promotes binding of synaptojanin-1 to endophilin A1 and facilitates vesicle endocytosis. In PD patient neurons, disruption of this pathway on loss of parkin leads to defective recycling of synaptic vesicles and accumulation of toxic oxidized dopamine that at least in part explains preferential vulnerability of midbrain dopaminergic neurons. These findings suggest a convergent mechanism for PD-linked mutations in parkin, synaptojanin-1, and endophilin A1 and highlight synaptic dysfunction as an early pathogenic event in PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Fundamental Electrophysiology Principles Related to Perioperative Management of Cardiovascular Implantable Electronic Devices.

An increasing number of patients undergoing elective or emergency surgery in the United States have a cardiovascular implantable electronic device. Practice advisories and consensus statements have been issued by the American Society of Anesthesiologists and the Heart Rhythm Society, advocating a multidisciplinary approach. Unfortunately, anesthesia providers often find themselves in a situation in which they are left to manage these devices independently. At the University of Washington Medical Center, an anesthesiology-based service to manage these devices has existed for more than a decade. Many problems with devices have been observed, including confusing rhythms, failure of magnets to provide the desired change in device function, and actual device malfunction. With these clinical case examples taken from the authors' collective experience, this article provides an in-depth understanding of some key electrophysiology principles relevant to cardiovascular implantable electronic device function and appropriate perioperative management.

The effect of Ca2+-calcineurin signaling pathway on the antifungal activity of Pd-D-V against Botrytis cinerea.

Gray mold, caused by Botrytis cinerea is an intractable fungal disease that causes extensive damage to agricultural products. In the search for novel antifungal active ingredients, we discovered a linear pyranocoumarin Pd-D-V was effective against B. cinerea in both in vitro and in vivo assays. Furthermore, this study investigated the effects of Ca2+ and the Ca2+-calcineurin signaling pathway on its antifungal activity against B. cinerea. The results indicated that Pd-D-V reduced the concentration of Ca2+ in the mycelia of B. cinerea; CaCl2, the Ca2+ channel blocker verapamil, or the calcineurin inhibitor cyclosporin A could affect the sensitivity of Pd-D-V against B. cinerea; the expression of genes (Bccch1, Bcmid1, BccnA, Bccnb1, Bcpmc1, and Bcpmr1) of the Ca2+-calcineurin signaling pathway decreased after Pd-D-V treatment. In summary, Pd-D-V is compound for developing fungicides against B. cinerea. Pd-D-V can reduce intracellular Ca2+ concentration and disturb Ca2+ homeostasis. The Ca2+-calcineurin signaling pathway is important in the antifungal activity of Pd-D-V against B. cinerea.

Cooperative effects of three preservatives on physiological quality, endophytic bacterial community and volatile organic compounds of postharvest Codonopsis pilosula var. modesta roots.

BACKGROUND: Codonopsis pilosula var. modesta (CPVM) is a famous medicinal and edible plant of Campanulaceae. However, fresh CPVM roots (FCPVR) are prone to softening, browning and spoilage after concentrated harvesting in the main production area of Gansu Province, China in autumn, which poses great challenges to their large-scale storage and modern processing. In this study, effects of chitosan (CS), natamycin (NA) and modified atmosphere agent (MA) on the postharvest quality of FCPVR were first investigated. The roots after different treatments were stored at 4 °C and relative humidity of 75 ± 5% for 100 days. Their overall quality changes were evaluated from three perspectives: physiological quality, endophytic bacterial community and volatile organic compounds. RESULTS: The clustering heatmap and principal component analysis results indicated that CS (2 g kg-1), NA (0.5 g kg-1) and MA (5 g) had a synergistic effect on physiological quality. The roots in the CS + NA + MA group maintained better physiological state, effective components and antioxidant capacity throughout the storage process. On this basis, compared with room temperature storage, the relative abundance of the main spoilage bacterium Pseudomonas in the CS + NA + MA group roots decreased by 44% on the 100th day of storage. Furthermore, after CS + NA + MA composite treatment, the roots produced richer esters with fruit aroma during low-temperature storage. CONCLUSIONS: The CS + NA + MA composite treatment could maintain the physiological quality and flavor of FCPVR, inhibit spoilage by microbial contamination and maintain the optimal quality during low-temperature storage for up to 100 days. © 2024 Society of Chemical Industry.

Application of PBL combined with traditional teaching in the Immunochemistry course.

BACKGROUND: The problem-based learning (PBL) model has been widely carried out in many fields of medical colleges and universities. Immunochemistry as a cross-disciplinary science plays a vital role in preventing the occurrence of diseases and bridging the development of Life Science and Medicine. But now the Immunochemistry course still lacks the teaching practice in PBL. To explore the significance of PBL applied in the Immunochemistry course, the effect of the PBL model on the learning of undergraduates majoring in Chemicobiology was systematically evaluated. METHODS: The teaching objects were the undergraduates majoring in Chemicobiology from Guizhou Medical University. The PBL model was applied in the Immunochemistry course. 62 undergraduates in Grade 2018 were set as the control group and adopted the traditional expository model. 93 undergraduates in Grades 2019-2020 were separately set as the experimental groups, which adopted the PBL model based on traditional lecture-based learning. In the PBL model, six cases related to course contents were designed for the students to complete. The final exams of the undergraduates in Grades 2018-2020 were analyzed by the score ranges (< 60 points, 60-69 points, 70-79 points, and ≥ 80 points) and nonparametric test. Finally, the questionnaire survey about the teaching evaluation was performed in Grades 2019-2020. RESULTS: In Grades 2019 and 2020, the excellent rates (≥ 80 points), pass rates (≥ 60 points), fail rates (< 60 points), and average scores of the undergraduates were separately about 29%, 91.11% and 93.75%, 6.25%, and 8.89%, and 72.55 and 74.45 points. But in Grade 2018, the excellent rate, pass rate, failure rate, and average score of the undergraduates were separately 9.68%, 59.68%, 40.32%, and 62.55 points. By the statistical analysis, it was found that the excellent rates (χ2 = 8.317, P < 0.005) and pass rates (χ2 = 24.52, P < 0.0001) in Grades 2018-2020 were different, of which Grade 2020were the highest (29.17%, 93.75%) and Grade 2018 was the lowest (9.68%, 59.68%). The average score, excellent rate, and pass rate in Grade 2018 had significant differences with Grade 2019 (P < 0.0001, P < 0.0167) and Grade 2020 (P < 0.001, P < 0.0167). The questionnaire survey also showed that the student's learning interests, independent problem-solving ability, knowledge structure system, and scientific thought and teamwork awareness were enhanced. In Grades 2019 and 2020, the ICC (95% CI) of criterion validity and inter-rater reliability were separately 0.42/0.34 and 0.81/0.80 (P < 0.0001). CONCLUSION: The combination of PBL and traditional expository models played positive roles in the student's learning in the Immunochemistry course.

[Research status of insect infestation of Chinese medicinal materials during storage].

During the storage process, Chinese medicinal materials are susceptible to insect infestation due to their own nature and external storage factors. Infestation by insects can have varying impacts on the materials. In mild cases, it affects the appearance and reduces consumer purchasing power, while in severe cases, it affects the quality, reduces medicinal value, and introduces impurities such as insect bodies, excrement, and secretions, resulting in significant contamination of the medicinal materials. This study reviewed the rele-vant factors influencing insect infestation in Chinese medicinal materials and the compositional changes that occur after infestation and summarized maintenance measures for preventing insect infestation. Additionally, it provided an overview of detection techniques applicable to identifying insect infestation during the storage of Chinese medicinal materials. During the storage process, insect infestation is the result of the combined effects of biological factors(source, species, and population density of insects), intrinsic factors(moisture, chemical composition, and metabolism), and environmental factors(temperature, relative humidity, and oxygen content). After infestation, there are significant changes in the content of constituents in the medicinal materials. By implementing strict pre-storage inspections, regular maintenance after storage, and appropriate storage and maintenance methods, the occurrence of insect infestation can be reduced, and the preservation rate of Chinese medicinal materials can be improved. The storage and maintenance of Chinese medicinal materials are critical for ensuring their quality. Through scientifically standardized storage and strict adherence to operational management standards, the risk of insect infestation can be minimized, thus guaranteeing the quality of Chinese medicinal materials.

Saponins and their derivatives: Potential candidates to alleviate anthracycline-induced cardiotoxicity and multidrug resistance.

Anthracyclines (ANTs) continue to play an irreplaceable role in oncology treatment. However, the clinical application of ANTs has been limited. In the first place, ANTs can cause dose-dependent cardiotoxicity such as arrhythmia, cardiomyopathy, and congestive heart failure. In the second place, the development of multidrug resistance (MDR) leads to their chemotherapeutic failure. Oncology cardiologists are urgently searching for agents that can both protect the heart and reverse MDR without compromising the antitumor effects of ANTs. Based on in vivo and in vitro data, we found that natural compounds, including saponins, may be active agents for other both natural and chemical compounds in the inhibition of anthracycline-induced cardiotoxicity (AIC) and the reversal of MDR. In this review, we summarize the work of previous researchers, describe the mechanisms of AIC and MDR, and focus on revealing the pharmacological effects and potential molecular targets of saponins and their derivatives in the inhibition of AIC and the reversal of MDR, aiming to encourage future research and clinical trials.

Characterization of chemical composition variations in raw and processed Codonopsis Radix by integrating metabolomics and glycomics based on multiple chromatography-mass spectrometry technology.

Codonopsis Radix, a popular food homology medicine, is widely used in clinical traditional Chinese medicine and food supplement, raw products and three types of processed products are the main forms of decoction pieces in China. However, there is no scientific basis for comprehensive chemical characterization of raw and three types of processed products. Herein, we investigated qualitatively and quantificationally secondary and primary metabolites in raw Codonopsis Radix and three types of processed products by metabolomics and glycomics employing multiple chromatography-mass spectrometry technology combined with chemometric analysis further to look for differential compounds and propose the processing-induced chemical mechanisms. The results indicated that Codonopsis Radix became dark-colored and the smell of burnt incense odor was observed after processing. The principal component analysis demonstrated that secondary metabolome and glycome were significantly altered between raw and processed products, and 36 differential secondary metabolites and 11 differential primary metabolites were finally screened through orthogonal partial least-squares-discriminant analysis. The main types of compounds are alkaloids, terpenoids, glycosides, amino acids, monosaccharides, oligosaccharides, and furfural derivatives. Meanwhile, Chemical mechanisms could be involved, including oxidation, glycosidic hydrolysis, esterification, dehydration, and Maillard reaction. This work supplies a chemical basis for the application of various types of Codonopsis Radix decoction pieces.

Frameshift mutation of Timm8a1 gene in mouse leads to an abnormal mitochondrial structure in the brain, correlating with hearing and memory impairment.

BACKGROUND: Deafness-dystonia-optic neuronopathy (DDON) syndrome is a progressive X-linked recessive disorder characterised by deafness, dystonia, ataxia and reduced visual acuity. The causative gene deafness/dystonia protein 1 (DDP1)/translocase of the inner membrane 8A (TIMM8A) encodes a mitochondrial intermembrane space chaperon. The molecular mechanism of DDON remains unclear, and detailed information on animal models has not been reported yet. METHODS AND RESULTS: We characterized a family with DDON syndrome, in which the affected members carried a novel hemizygous variation in the DDP1 gene (NM_004085.3, c.82C>T, p.Q28X). We then generated a mouse line with the hemizygous mutation (p.I23fs49X) in the Timm8a1 gene using the clustered regularly interspaced short palindromic repeats /Cas9 technology. The deficient DDP1 protein was confirmed by western blot assay. Electron microscopic analysis of brain samples from the mutant mice indicated abnormal mitochondrial structure in several brain areas. However, Timm8a1I23fs49X/y mutation did not affect the import of mitochondria inner member protein Tim23 and outer member protein Tom40 as well as the biogenesis of the proteins in the mitochondrial oxidative phosphorylation system and the manganese superoxide dismutase (MnSOD / SOD-2). The male mice with Timm8a1I23fs49X/y mutant exhibited less weight gain, hearing impairment and cognitive deficit. CONCLUSION: Our study suggests that frameshift mutation of the Timm8a1 gene in mice leads to an abnormal mitochondrial structure in the brain, correlating with hearing and memory impairment. Taken together, we have successfully generated a mouse model bearing loss-of-function mutation in Timm8a1.

Late Diagnosis of a Large Extrapleural Hematoma in a Patient With Stanford Type B Aortic Dissection: A Case Report and Review of Literature.

Acute aortic dissection is a rare but catastrophic condition. When the dissection extends through the adventitia, blood can extravasate into the extrapleural or intrapleural spaces, causing an extrapleural hematoma or hemothorax. The early recognition of extrapleural hematoma and distinguishing it from hemothorax is critical because the management of those two entities is different. The authors present a case of a late diagnosis of a large extrapleural hematoma in a patient with Stanford type B acute aortic dissection that required thoracotomy for hematoma evacuation. The patient underwent successful thoracic endovascular aortic repair (TEVAR). Postoperatively, the patient had worsening pulmonary function, with a large fluid collection on imaging that was not drained by the thoracostomy tubes. Surgical exploration revealed a large extrapleural hematoma. Timely recognition of the extrapleural hematoma was key in the patient's clinical management. Without clear radiographic diagnostic features of extrapleural hematoma, unsuccessful drainage of hematoma after insertion of a chest tube may suggest an extrapleural hematoma or a clotted hemothorax. If patients continue to have circulatory or respiratory compromises, prompt surgical exploration should be considered. It is important for clinicians to be aware of extrapleural hematoma in complicated acute aortic dissection, especially when chest tube drainage of an apparent hemothorax is unsuccessful.

The Difference of Volatile Compounds in Female and Male Buds of Trichosanthes anguina L. Based on HS-SPME-GC-MS and Multivariate Statistical Analysis.

Trichosanthes anguina L. (family Cucurbitaceae) is a monoecious and diclinous plant that can be consumed as a vegetable and has anti-inflammatory and antioxidant effects. The chemical composition and content of volatile compounds in female and male buds of T. anguina were explored by headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) technology combined with multivariate statistical analysis. The results showed that the content of the volatile compounds was different between female and male buds. 2,2,6-trimethyl-6-vinyltetrahydro-2H-pyran-3-ol and 2,2,6-trimethyl-6-vinyldihydro-2H-pyran-3(4H)-one were the main volatile compounds in both female and male buds. Based on the multivariate statistical analysis of orthogonal projections to latent structures discriminant analysis (OPLS-DA) and t-test, the content of seven compounds was significantly different between female and male buds. The content of three compounds in male buds was higher than that in female, i.e., (E)-4,8-dimethyl-1,3,7-nonatriene, 1,5,9,9-tetramethyl-1,4,7-cycloundecatriene, and (E)-caryophyllene. Conversely, the content of (Z)-4-hexen-1-ol, (Z)-3-hexenyl benzoate, (Z)-3-hexenyl salicylate, and 2-hexen-1-ol in female buds was higher than that in male buds. This is the first report on the difference in the volatile compounds between female and male buds of T. anguina, which enriches the basic research on the monoecious and diclinous plant and provides a reference for the study of plant sex differentiation.

The Difference of Volatile Compounds in Female and Male Buds of Herpetospermum pedunculosum Based on HS-SPME-GC-MS and Multivariate Statistical Analysis.

Herpetospermum pedunculosum (Ser.) C. B. Clarke (Family Cucurbitaceae) is a dioecious plant and has been used as a traditional Tibetan medicine for the treatment of hepatobiliary diseases. The component, content, and difference in volatile compounds in the female and male buds of H. pedunculosum were explored by using headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) technology and multivariate statistical analysis. The results showed that isoamyl alcohol was the main compound in both female and male buds and its content in males was higher than that in females; 18 compounds were identified in female buds including 6 unique compounds such as (E)-4-hexenol and isoamyl acetate, and 32 compounds were identified in male buds, including 20 unique compounds such as (Z)-3-methylbutyraldehyde oxime and benzyl alcohol. (Z)-3-methylbutyraldehyde oxime and (E)-3-methylbutyraldehyde oxime were found in male buds, which only occurred in night-flowering plants. In total, 9 differential volatile compounds between female and male buds were screened out, including isoamyl alcohol, (Z)-3-methylbutanal oxime, and 1-nitropentane based on multivariate statistical analysis such as principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA). This is the first time to report the volatile components of H. pedunculosum, which not only find characteristic difference between female and male buds, but also point out the correlation between volatile compounds, floral odor, and plant physiology. This study enriches the basic theory of dioecious plants and has guiding significance for the production and development of H. pedunculosum germplasm resources.

Successful treatment of a 3-year-old girl with generalized pustular psoriasis using secukinumab monotherapy.

We report a case of a 3-year-old girl with generalized pustular psoriasis (GPP) and a compound heterozygous mutation within the IL36 receptor antagonist (IL36RN) gene at c.28C>T and c.115+6T>C, who was successfully treated using secukinumab monotherapy. The first dose of secukinumab (150 mg) was administered subcutaneously, followed by 75 mg of secukinumab subcutaneously once weekly for 4 weeks and then 75 mg every 4 weeks. The total course of treatment was 4 months, with a total of 8 doses. A PASI score of 75 and 100 was achieved at weeks 1 and 2, respectively, and maintained for 11 months of follow-up, without disease recurrence or adverse events.

1H NMR Combined with Multivariate Statistics for Discrimination of Female and Male Flower Buds of Populus tomentosa.

1H Nuclear Magnetic Resonance (1H NMR) combined with multivariate statistics was adopted to discriminate female and male flower buds of Populus tomentosa in the study. Samples of 11 female and 16 male flower buds of P. tomentosa were collected in Beijing, China. 1H NMR spectra were acquired on a 400 MHz spectrometer. In total, 30 chemical compounds were identified with standards and literature according to chemical shifts, peak areas, and multiplicity. Principal component analysis (PCA), hierarchical clustering analysis (HCA), and supervised orthogonal partial least squares-discriminant analysis (OPLS-DA) were applied to discriminate female and male flower buds. An apparent grouping trend (R2X, 0.809; Q2, 0.903) between female and male groups was exhibited with PCA and HCA. The two groups were also well discriminated with OPLS-DA (R2X, 0.808; R2Y, 0.976; Q2, 0.960). Combined with variable importance in projection (VIP) > 1.0 and p < 0.05 of OPLS-DA, it was found that the content of daucosterol, ß-sitosterol, ursolic acid, and betulonic acid in male group was higher than that in female, which should be the key differences of chemical constituents in female and male flower buds of P. tomentosa. The study demonstrated that 1H NMR combined with multivariate statistics could be used to discriminate female and male plants and clarify differences, which provided a novel method to identify the gender of dioecious plants.

Mild Acetylation and Solubilization of Ground Whole Plant Cell Walls in EmimAc: A Method for Solution-State NMR in DMSO-d6.

Lignocellulosic biomass is mainly composed of polysaccharides and lignin. The complexity and diversity of the plant cell wall polymers makes it difficult to isolate the components in pure form for characterization. Many current approaches to analyzing the structure of lignocellulose, which involve sequential extraction and characterization of the resulting fractions, are time-consuming and labor-intensive. The present study describes a new and facile system for rationally derivatizing and dissolving coarsely ground plant cell wall materials. Using ionic liquids (EmimAc) and dichloroacetyl chloride as a solvent/reagent produced mildly acetylated whole cell walls without significant degradation. The acetylated products were soluble in DMSO-d6 from which they can be characterized by solution-state two-dimensional nuclear magnetic resonance (2D NMR) spectrometry. A distinct advantage of the procedure is that it realizes the dissolution of whole lignocellulosic materials without requiring harsh ball milling, thereby allowing the acquisition of high-resolution 2D NMR spectra to revealing structural details of the main components (lignin and polysaccharides). The method is therefore beneficial to understanding the composition and structure of biomass aimed at its improved utilization.

TREM-1-targeting LP17 attenuates cerebral ischemia-induced neuronal injury by inhibiting oxidative stress and pyroptosis.

Stroke ranks as the second leading cause of disability and death globally. Trigger receptors expressed on myeloid cells (TREM) -1 are responsible for the activation of the innate immune response and also play a critical role in inflammation. In this study, we reported the contribution of TREM-1 after ischemic damage in a rat middle cerebral artery occlusion (MCAO) model. This study also demonstrated that TREM-1 expression was upregulated following cerebral infarction in rats. TREM-1 inhibition was determined using its selective inhibitor, LP17, which indicated a neuroprotective effect on cerebral infarction damage. The findings revealed that inhibition of TREM-1 by administering LP17 improved cerebral damage and decreased ischemic areas and brain water contents. Moreover, LP17 decreased MCAO-induced microglial activation and neurodegeneration, evidenced by a reduction in the expression of microglial Iba-1 and FJ-B positive cells, and reversed neuronal loss. Besides, the contribution of LP17 to ischemic neuronal damage may be associated with a decrease in the production of pro-inflammatory cytokines, and enhanced production of anti-inflammatory cytokine IL-10. Both in vivo and in vitro studies showed that inhibiting TREM-1 attenuated ROS accumulation, lipid per-oxidation (LPO) contents such as malondialdehyde (MDA) and enhanced the superoxide dismutase (SOD) activity after ischemia. Inhibiting TREM-1 alleviated inflammation and pyroptosis found in MCAO rats. This was achieved through the inhibition of the levels of NLRP3, caspase-1, ASC (an apoptosis-associated speck-like protein containing a CARD) and gasdermin D. These results confirmed that inhibiting TREM-1 protects against ischemia-induced neuronal damage and alleviates microglial mediated neuro-inflammation by reducing oxidative stress and pyroptosis. Therefore, blocking TREM-1 expression provides an effective intervention for improving ischemic stroke.

Focused ultrasonography for septic shock resuscitation.

PURPOSE OF REVIEW: Severe sepsis with septic shock is the most common cause of death among critically ill patients. Mortality has decreased substantially over the last decade but recent data has shown that opportunities remain for the improvement of early and targeted therapy. This review discusses published data regarding the role of focused ultrasonography in septic shock resuscitation. RECENT FINDINGS: Early categorization of the cardiovascular phenotypes with echocardiography can be crucial for timely diagnosis and targeted therapy of patients with septic shock. In the last few years, markers of volume status and volume responsiveness have been investigated, serving as valuable tools for targeting volume therapy in the care of both spontaneously breathing and mechanically ventilated patients. In tandem, investigators have highlighted findings of extravascular volume with ultrasonographic evaluation to compliment de-escalation of resuscitation efforts when appropriate. Furthermore, special attention has been given to resuscitation efforts of patients in septic shock with right ventricular failure. SUMMARY: Severe sepsis with septic shock is an insidious disease process that continues to take lives. In more recent years, data have emerged suggesting the utility of bedside ultrasonography for early cardiovascular categorization, goal directed resuscitation, and appropriate cardiovascular support based on its changing phenotypes.

A successfully treated malignant melanoma arising in a large congenital vulvar blue nevus.

An atypical cellular blue nevus, a benign mass, may sometimes transform into a malignant melanoma. Here, we report a rare case of melanoma arising in a large congenital vulvar blue nevus. A 28-year-old Chinese woman presented to our hospital with a chief complaint of a vulvar mass that had persisted for 8 years. The patient underwent extensive local excision, followed by reconstructive surgery of the female reproductive tract. The mass was diagnosed as being a vulvar malignant melanoma. Postoperatively, the patient received interferon immunotherapy and recovered without complications. No evidence of recurrence was observed after 32 months of follow-up. Our case thus shows that comprehensive treatment with surgery supplemented by immunotherapy can be effective against a malignant melanoma arising in a vulvar blue nevus.

Optical homogeneity measurement of parallel plates by wavelength-tuning interferometry using nonuniform fast Fourier transform.

Wavelength-tuning interferometry is commonly employed to measure the optical homogeneity of parallel plates. However, the nonlinearity of phase shifts caused by wavelength tuning errors and environmental vibration leads to a spatially uniform error in the calculated phase distribution. Herein, a wavelength-tuning interferometry method based on nonuniform fast Fourier transform (WTI-NUFFT) was developed, which solves the spectral aliasing resulting from the spatially uniform error. The characteristics of the WTI-NUFFT method were estimated through comparison with the FFT method. Both the simulated and experimental results showed that the WTI-NUFFT method can improve the accuracy of the optical homogeneity measurement of parallel plates.

Knockdown of NRAGE induces odontogenic differentiation by activating NF-κB signaling in mouse odontoblast-like cells.

PURPOSE: Neurotrophin receptor-interacting MAGE homologue (Nrage) plays an important role in bone development and the metabolism of normal skeletal structures. Our previous study showed that Nrage inhibited the odontogenic differentiation of mouse dental pulp cells. However, the potential roles and mechanism of Nrage in regulating odontogenic differentiation are unknown. The aim of this study was to investigate the molecular mechanism of Nrage in odontogenic differentiation of mouse odontoblast-like cells. MATERIALS AND METHODS: Endogenous expression of Nrage was stably downregulated by lentivirus-mediated shRNA. Mineralized nodules formation was detected by alizarin red S staining. Dmp-1, Dspp, and ALP mRNA and protein levels were detected by qRT-PCR and western blotting, respectively. In addition, ALPase activity was detected. Confocal microscopy and co-immunoprecipitation (co-IP) were used to analyze the interactions between NRAGE and NF-κB signaling molecules. An IKK inhibitor was also used in the study. RESULTS: NRAGE expression in odontoblasts was downregulated during mouse first maxillary molar development. Moreover, NRAGE expression was downregulated during odontogenic differentiation of odontoblast-like cells. NRAGE knockdown significantly upregulated DMP1 and DSP expression, increased ALPase activity, and promoted mineralized nodule formation. In addition, NRAGE knockdown increased the translocation of NF-κB1 to the nucleus and phosphorylation levels of p65. Co-IP results showed that NRAGE bound to IKKß. Most importantly, the promoting effect of Nrage knockdown on odontoblastic differentiation was reduced after treatment with an IKK inhibitor. CONCLUSIONS: Our data confirmed that NRAGE is an important regulator of odontogenic differentiation of odontoblasts by inhibiting the NF-κB signaling pathway through binding to IKKß. ABBREVIATIONS: Nrage: neurotrophin receptor-interacting MAGE homologue; DSP: dentin sialophospho protein; DMP-1: dentin matrix protein-1; BMP: bone morphogenetic protein; Wnt: wingless; NF-κB: nuclear factor of activated B cells; DAPI: 4',6-diamidino-2-phenylindole; KO: knockout; DPCs: dental pulp cells; AA: ascorbic acid; ß-Gly: ß-glycerophosphate; Dex: dexamethasone; co-IP: co-immunoprecipitation; IκB: inhibitor of NF-κB; IKK: IκB kinase.