PAX3 mutation suppress otic progenitors proliferation and induce apoptosis by inhibiting WNT1/ß-catenin signaling pathway in WS1 patient iPSC-derived inner ear organoids.

Waardenburg syndrome type 1 (WS1) is a hereditary disease mainly characterized by sensorineural hearing loss, dystopia canthorum, and pigmentary defects. To elucidate molecular mechanisms underlying PAX3-associated hearing loss, we developed inner ear organoids model using induced pluripotent stem cells (iPSCs) derived from WS1 patient and healthy individual. Our results revealed a significant reduction in the size of inner ear organoids, accompanied by an increased level of apoptosis in organoids derived from WS1 patient-iPSCs carrying PAX3 c.214A > G. Transcriptome profiling analysis by RNA-seq indicated that inner ear organoids from WS1 patients were associated with suppression of inner ear development and WNT signaling pathway. Furthermore, the upregulation of the WNT1/ß-catenin pathway which was achieved through the correction of PAX3 isogenic mutant iPSCs using CRISPR/Cas9, contributed to an increased size of inner ear organoids and a reduction in apoptosis. Together, our results provide insight into the underlying mechanisms of hearing loss in WS.

Protoilludane-Type and Related Nor-Sesquiterpenes from Phellinus hartigii and Their Anti-Hypertrophic Activities in Rat Cardiomyocytes.

Three nor-sesquiterpenes, phellinharts A-C (1-3), isolated from Phellinus hartigii, exhibited unprecedented protoilludane and cerapicane-type structures. The structures of compounds 1-3 were elucidated via spectroscopic analysis, quantum chemical calculations, and X-ray diffraction. Potential biogenic pathways involving demethylation, ring cleavage, and rearrangement were proposed. Compounds 1-3 displayed potent anti-hypertrophic activities with low cytotoxicity (CC50 > 50 µM) in rat cardiomyocytes, underscoring their therapeutic potential.

Two new oleanane triterpenes from Maytenus hookeri.

Two new triterpenes mayteneri A (1), mayteneri B (2), and seven known compounds (3-9) were isolated from stems of Maytenus hookeri Loes. The chemical structures of compounds 1 and 2 were established by 1D, 2D NMR, HRESIMS analysis, and calculating electronic circular dichroism (ECD). The structures of known compounds 3-9 were determined by comparison of their spectral with those reported. Compounds 4-7 showed significant inhibitory activity for NLRP3 inflammasome, with the IC50 values of 2.36-3.44 µM.

Investigating the distribution of microplastics in soils from e-waste dismantling sites and their adsorption of heavy metals.

Microplastics are characterized by strong hydrophobicity, large specific surface area. In addition to the pollutant they contain, the heavy metals adsorbed on the surface of microplastics can migrate or be transformed with them into the environmental medium, which is potentially harmful to humans. The distribution characteristics of microplastics in contaminated soil at the e-waste dismantling site were studied. The study investigated the adsorption characteristics of polyvinyl chloride (PVC), polypropylene (PP) and acrylonitrile-butadiene-styrene (ABS) on copper (Cu), zinc (Zn) and lead (Pb). It analysed the influence of various factors on the adsorption process of heavy metals, the adsorption law of microplastics on some of the heavy metals in the environment, and the risk of heavy metal release from microplastics to soil. The results showed that ABS and PP were the main microplastics in the contaminated soil. Among them, black, white and transparent microplastics accounted for 89.91%. The shape of microplastics is mainly granular, and microplastics with a particle size of 1-2 mm accounted for the largest proportion. Further studies showed that plastic particles made of ABS, PP and PVC also have the adsorption capacity for different types of heavy metals in soil, and the trends of adsorption capacity are: PP>PVC>ABS. When PP does not reach adsorption equilibrium in the adsorption process, the smaller the particle size and the more added amount, the greater the adsorption capacity. This is because the smaller the particle size of the microplastic is, the more adsorption points it can provide, increasing its ability to adsorb heavy metal ions.

Highly Oxygenated Labdane Diterpenoids from Stevia rebaudiana and Their Anti-Atherosclerosis Activities.

Five unknown labdane diterpenoids Stevelins A-E (1-5), three known labdane diterpenoids (6-8) and three labdane norditerpenoids (9-11) were isolated from the Stevia rebaudiana. The structures were determined primarily via NMR spectroscopic data and HR-ESI-MS experiments. X-ray crystallography using CuKα radiation was used to determine the absolute configurations of 1, and the absolute configurations of 2-5 were deduced by electronic circular dichroism (ECD) calculations. The potential anti-atherosclerosis activities of all compounds were evaluated by measuring their inhibitory effects on the macrophage foam cell formation. As a result, most isolated compounds could significantly inhibit oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation, which suggests that these compounds may be promising candidates in the treatment for atherosclerosis.

Research and application progress in deep learning in otology. / æ·±åº¦å­¦ä¹ åœ¨è€³ç§‘å­¦ä¸­çš„ç ”ç©¶ä¸Žåº”ç”¨è¿›å±•.

With the optimization of deep learning algorithms and the accumulation of medical big data, deep learning technology has been widely applied in research in various fields of otology in recent years. At present, research on deep learning in otology is combined with a variety of data such as endoscopy, temporal bone images, audiograms, and intraoperative images, which involves diagnosis of otologic diseases (including auricular malformations, external auditory canal diseases, middle ear diseases, and inner ear diseases), treatment (guiding medication and surgical planning), and prognosis prediction (involving hearing regression and speech learning). According to the type of data and the purpose of the study (disease diagnosis, treatment and prognosis), the different neural network models can be used to take advantage of their algorithms, and the deep learning can be a good aid in treating otologic diseases. The deep learning has a good applicable prospect in the clinical diagnosis and treatment of otologic diseases, which can play a certain role in promoting the development of deep learning combined with intelligent medicine.

Clinical characteristics and surgical strategy of glomus tympanicum tumors. / 鼓室体瘤的临床特征及手术策略.

OBJECTIVES: To summarize the clinical characteristics of glomus tympanicum tumors, and to explore the surgical methods and the strategy for auditory protection. METHODS: Ten cases (ears) of glomus tympanicum tumors were collected from the Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University from August 2014 to February 2022. All patients underwent endoscopic or microscopic surgery to achieve total removal of the tumor, followed up for 3 months to 8 years. We summarized and analyzed its clinical characteristics, compared the preoperative and postoperative hearing levels of patients, and made a retrospective summary of the surgical methods and the strategy for auditory protection. RESULTS: Ten patients were all female at (49.50±8.00) years old. Their medical history ranged from 15 days to 6 years. Seven patients complained of pulsatile tinnitus, and 80% (8/10) of the affected ears suffered different degrees of hearing loss. According to the modified Fisch & Mattox classification of glomus tympanicum tumors, 3 ears (30%) of 10 ears were A1, 2 ears (20%) were A2 and 5 ears (50%) were B1. In all 10 cases (ears), hearing was improved in 3 cases, bone gas conductance was maintained in 6 cases, and hearing was slightly decreased in 1 case. The difference of bone gas conductance was 0-10 dB in 7 cases (ears) after operation, and 10-20 dB in 3 cases (ears). There was no significant difference in the average air conduction hearing threshold, bone conduction hearing threshold and air-bone conduction difference between before and after operation (all P>0.05). All cases had no postoperative complications, and the external auditory canal and the incision behind the ear healed well. There was no recurrence after follow-up. CONCLUSIONS: Glomus tympanicum tumor is easy to bleed, so it is a challenge for total tumor resection and hearing function protection during operation. For type A and type B1 tumors, they can be completely removed under the condition of keeping the tympanic membrane and the ossicular chain. At the same time, the postoperative hearing function can be preserved, and even the hearing can be improved.

Callicarpnoids A-C, structurally intriguing ent-Clerodane diterpenoid dimers with cytotoxicity against MCF-7 and HCT-116 cell lines from Callicarpa arborea Roxb.

Callicarpnoids A-C (1-3), three new ent-clerodane diterpenoid dimers formed via a [4 + 2] hetero Diels-Alder cycloaddition, appeared as a third example of this type of dimers, were isolated from the stems of Callicarpa arborea Roxb.. Their structures were elucidated by comprehensive spectroscopic analysis, and the absolute configurations were confirmed by single-crystal X-ray diffraction and electronic circular dichroism (ECD) calculations, as well as DP4 + analysis. Cytotoxicity test in two cell lines indicated that compounds 2 and 3 had significant cytotoxic effect against breast cancer cell (MCF-7) and colorectal cancer cell (HCT-116) with IC50 ranging from 5.2 to 7.2 µM, comparable to those of the positive control. Furthermore, the western blot analysis revealed that the protein expression levels of Bax were increased following compounds 2 and 3 treatment, whereas the expression levels of caspase 8, caspase 3, caspase 9 and Bcl2 were decreased in a dose-dependent manner, indicating that compounds 2 and 3 may induce apoptosis via both intrinsic and extrinsic pathways in MCF-7 and HCT-116 cells.

Establishment of a risk index for early complications after trans-canal endoscopic ear surgery.

PURPOSE: This study aimed to determine the risk factors associated with early postoperative complications of trans-canal endoscopic ear surgery (TEES), then to develop a risk index. MATERIALS AND METHODS: This single-institution retrospective study reviewed TEESs from January 1, 2017, to December 31, 2019 in a tertiary hospital. In the derivation cohort, univariable and multivariable logistic regression were performed to identify factors significantly associated with early postoperative complications of TEES. Then these parameters were integrated into a trans-canal endoscopic ear surgery risk index (TEESRI). The performance of TEESRI was compared with that of the American Society of Anesthesiologists (ASA) classification using the validation cohort. RESULTS: 932 TEESs were enrolled in total and 151 (16.2%) developed early postoperative complications. In the derivation set, 8 factors including state of the opposite ear and presence of nasal or pharyngeal diseases were found to be independently associated with the occurrence of early postoperative complications on multivariable regression analysis [area under the curve (AUC), 0.806; 95% confidence interval (CI), 0.765-0.848]. Using the validation cohort, the AUC of the TEESRI was 0.776 [95%CI, 0.711-0.842], with a sensitivity of 82.2% and specificity of 65.5%, while the AUC of the ASA classification was 0.512 (95%CI, 0.421-0.603). The TEESRI outperformed the ASA classification when evaluating the risk for early postoperative complications of TEES. CONCLUSIONS: Based on the 8 risk factors, the TEESRI was established with satisfactory predicting capacity. Surgeons should pay extra attention to the risk factors in the TEESRI, when treating patients.

Ainslides A-F, Six Sesquiterpenoids Isolated from Ainsliaea pertyoides and Their NLRP3-Inflammasome Inhibitory Activity.

Six new sesquiterpenoids, named as ainslides A-F (1-6), including one carotene-type sesquiterpene (1), one eudesmane (2), four guaianolides (3-6), together with eight known sesquiterpenoids (7-14), were purified from the whole plants of Ainsliaea pertyoides. The structures of these sesquiterpenoids were characterized based on spectroscopic methods including 1D and 2D NMR, HR-ESI-MS, UV, and IR spectra, together with ECD calculations and X-ray diffraction experiments. The anti-inflammatory activity of all the isolated compounds was screened and compounds 3 and 7-13 exhibited NLRP3-inflammasome inhibitory activity with IC50 values of 1.80-4.33 µM.

Work Efficiency and Economic Efficiency of Actual Driving Test of Proton Exchange Membrane Fuel Cell Forklift.

A 3.5 tonne forklift containing proton exchange membrane fuel cells (PEMFCs) and lithium-ion batteries was manufactured and tested in a real factory. The work efficiency and economic applicability of the PEMFC forklift were compared with that of a lithium-ion battery-powered forklift. The results showed that the back-pressure of air was closely related to the power density of the stack, whose stability could be improved by a reasonable control strategy and membrane electrode assemblies (MEAs) with high consistency. The PEMFC powered forklift displayed 40.6% higher work efficiency than the lithium-ion battery-powered forklift. Its lower use-cost compared to internal engine-powered forklifts, is beneficial to the commercialization of this product.

Application of high resolution computed tomography image assisted classification model of middle ear diseases based on 3D-convolutional neural network. / 基于3Då·ç§¯ç¥žç»ç½‘ç»œçš„ä¸­è€³ç–¾ç— é«˜åˆ†è¾¨çŽ‡CTå›¾åƒè¾ åŠ©åˆ†ç±»è¯Šæ–­æ¨¡åž‹çš„åº”ç”¨.

OBJECTIVES: Chronic suppurative otitis media (CSOM) and middle ear cholesteatoma (MEC) are the 2 most common chronic middle ear diseases. In the process of diagnosis and treatment, the 2 diseases are prone to misdiagnosis and missed diagnosis due to their similar clinical manifestations. High resolution computed tomography (HRCT) can clearly display the fine anatomical structure of the temporal bone, accurately reflect the middle ear lesions and the extent of the lesions, and has advantages in the differential diagnosis of chronic middle ear diseases. This study aims to develop a deep learning model for automatic information extraction and classification diagnosis of chronic middle ear diseases based on temporal bone HRCT image data to improve the classification and diagnosis efficiency of chronic middle ear diseases in clinical practice and reduce the occurrence of missed diagnosis and misdiagnosis. METHODS: The clinical records and temporal bone HRCT imaging data for patients with chronic middle ear diseases hospitalized in the Department of Otorhinolaryngology, Xiangya Hospital from January 2018 to October 2020 were retrospectively collected. The patient's medical records were independently reviewed by 2 experienced otorhinolaryngologist and the final diagnosis was reached a consensus. A total of 499 patients (998 ears) were enrolled in this study. The 998 ears were divided into 3 groups: an MEC group (108 ears), a CSOM group (622 ears), and a normal group (268 ears). The Gaussian noise with different variances was used to amplify the samples of the dataset to offset the imbalance in the number of samples between groups. The sample size of the amplified experimental dataset was 1 806 ears. In the study, 75% (1 355) samples were randomly selected for training, 10% (180) samples for validation, and the remaining 15% (271) samples for testing and evaluating the model performance. The overall design for the model was a serial structure, and the deep learning model with 3 different functions was set up. The first model was the regional recommendation network algorithm, which searched the middle ear image from the whole HRCT image, and then cut and saved the image. The second model was image contrast convolutional neural network (CNN) based on twin network structure, which searched the images matching the key layers of HRCT images from the cut images, and constructed 3D data blocks. The third model was based on 3D-CNN operation, which was used for the final classification and diagnosis of the 3D data block construction, and gave the final prediction probability. RESULTS: The special level search network based on twin network structure showed an average AUC of 0.939 on 10 special levels. The overall accuracy of the classification network based on 3D-CNN was 96.5%, the overall recall rate was 96.4%, and the average AUC under the 3 classifications was 0.983. The recall rates of CSOM cases and MEC cases were 93.7% and 97.4%, respectively. In the subsequent comparison experiments, the average accuracy of some classical CNN was 79.3%, and the average recall rate was 87.6%. The precision rate and the recall rate of the deep learning network constructed in this study were about 17.2% and 8.8% higher than those of the common CNN. CONCLUSIONS: The deep learning network model proposed in this study can automatically extract 3D data blocks containing middle ear features from the HRCT image data of patients' temporal bone, which can reduce the overall size of the data while preserve the relationship between corresponding images, and further use 3D-CNN for classification and diagnosis of CSOM and MEC. The design of this model is well fitting to the continuous characteristics of HRCT data, and the experimental results show high precision and adaptability, which is better than the current common CNN methods.

NLRP6 suppresses gastric cancer growth via GRP78 ubiquitination.

Nod-like receptor pyrin domain-containing protein 6 (NLRP6) plays a key role in innate immunity, host defense and tumorigenesis. Our previous study has demonstrated the tumor suppressor role of NLRP6 in gastric cancer. In the present study, we explored the interaction protein of NLRP6 by Flag-tagged immunoprecipitation assay and liquid chromatography/mass spectrometry-based proteomics analysis. The 78 kDa glucose-regulated protein (GRP78), a heat shock protein, was identified as an interaction protein of NLRP6. The binding of NLRP6 to GRP78 was through the Pyrin domain, and the substrate binding domain (SBD) domain of GRP78 was responsible for the interaction with NLRP6. NLRP6 overexpression enhanced the polyubiquitination of GRP78 in gastric cancer cells. Overexpression of GRP78 abolished the effects of NLRP6 overexpression in gastric cancer cell proliferation, cell cycle progression, cell apoptosis, migration and Cyclin D1 expression. GRP78 knockdown reversed the effects of NLRP6 knockdown on cell proliferation and cell cycle progression. NLRP6 expression was negatively correlated with GRP78 expression in human gastric tissues. Tumorigenicity assay indicated that GRP78 mediated the functions of NLRP6 on gastric cancer cell growth in vivo. ON-013100, which could inhibit Cyclin D1 expression, was less effective in treating xenografts of gastric cancer cells with higher level of NLRP6 than in those with lower level of NLRP6. In conclusion, our study suggested that NLRP6 exerted inhibitory effects on gastric cancer cell growth by promoting the ubiquitination of GRP78.

Can auditory brain stem response accurately reflect the cochlear function?

Auditory brain stem response (ABR) and compound action potential (CAP) recordings have been used in animal research to determine hearing sensitivity. Because of the relative ease of testing, the ABR test has been more commonly used in assessing cochlear lesions than the CAP test. The purpose of this experiment is to examine the difference between these two methods in monitoring the dynamic changes in auditory function after cochlear damage and in detecting asymmetric hearing loss due to unilateral cochlear damage. ABR and CAP were measured in two models of cochlear damage: acoustic trauma induced by exposure to a narrowband noise centered at 4 kHz (2,800-5,600 Hz) at 105 dB sound pressure level for 5 h in chinchillas and unilateral cochlear damage induced by surgical destruction of one cochlea in guinea pigs. Cochlear hair cells were quantified after completing the evoked potential testing. In the noise-damaged model, we found different recovery patterns between ABR and CAP. At 1 day after noise exposure, the ABR and CAP assessment revealed a similar level of threshold shifts. However, at 30 days after noise exposure, ABR thresholds displayed an average of 20-dB recovery, whereas CAP thresholds showed no recovery. Notably, the CAP threshold signifies the actual condition of sensory cell pathogenesis in the cochlea because sensory cell death is known to be irreversible in mammals. After unilateral cochlear damage, we found that both CAP and ABR were affected by cross-hearing when testing the damaged ear with the testing stimuli delivered directly into the canal of the damaged ear. When cross-hearing occurred, ABR testing was not able to reveal the presence of cross-hearing because the ABR waveform generated by cross-stimulation was indistinguishable from that generated by the test ear (damaged ear), should the test ear be intact. However, CAP testing can provide a warning sign, since the typical CAP waveform became an ABR-like waveform when cross-hearing occurred. Our study demonstrates two advantages of the CAP test over the ABR test in assessing cochlear lesions: contributing evidence for the occurrence of cross-hearing when subjects have asymmetric hearing loss and providing a better assessment of the progression of cochlear pathogenesis.NEW & NOTEWORTHY Auditory brain stem response (ABR) is more commonly used to evaluate cochlear lesions than cochlear compound action potential (CAP). In a noise-induced cochlear damage model, we found that the reduced CAP and enhanced ABR caused the threshold difference. In a unilateral cochlear destruction model, a shadow curve of the ABR from the contralateral healthy ear masked the hearing loss in the destroyed ear.

A RuII Polypyridyl Alkyne Complex Based Metal-Organic Frameworks for Combined Photodynamic/Photothermal/Chemotherapy.

Despite drug delivery nanoplatforms receiving extensive attention, development of a simple, effective, and multifunctional theranostics nanoplatform still remains a challenge. Herein, a versatile nanoplatform based on a zirconium framework (UiO-66-N3 ) was synthesized, which demonstrated a combined photodynamic therapy (PDT), photothermal therapy (PTT), and chemotherapy (CT) for cancer treatment. A RuII polypyridyl alkyne complex (Ra) as a photosensitizer was modified into a nanoplatform by click reactions for the first time. When exposed to suitable light irradiation, the as-prepared multifunctional nanoplatform (UiO-Ra-DOX-CuS) not only demonstrated efficient 1 O2 generation, but also exhibited excellent photothermal conversion ability. In particular, the nanotherapeutic agent presented a dual-stimuli response; either acidic environment or NIR laser irradiation would trigger the drug release. The synergetic efficacy of UiO-Ra-DOX-CuS combined PDT, PTT, and CT, which was evaluated by cell experiments. Moreover, the design could promote the development of RuII polypyridyl alkyne complexes based multifunctional nanoparticles and multimodal cancer treatment.

Genomic insights into a novel species Rhodoferax aquaticus sp. nov., isolated from freshwater.

A novel non-phototrophic member of the genus Rhodoferax was obtained from freshwater. The purpose of this study was to analyse the genome of a nonphototrophic strain and propose a new species based on its phylogenetic, genomic, physiological and chemotaxonomic characteristics. The results of phylogenetic analysis based on 16S rRNA gene sequences supports that the strain, designated Gr-4T, has a close relationship to the genus Rhodoferax. The observed average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain Gr-4T and its closest related strains were 72.3-74.6 % and 21.9-22.8 %, respectively. These values were much lower than the species separation thresholds for ANI or dDDH of 95-96 and 70 %, respectively, and in fact fall in the intergeneric range. Strain Gr-4T does not contain RuBisCO-related genes, but does contain GS/GOGAT pathway-related genes enabling nitrate ammonification. A polyphasic study and a genomic-level investigation were done to establish the taxonomic status of strain Gr-4T. Based on the phylogenetic, genomic and physiological differences, it is proposed that the isolate be classified to the genus Rhodoferax as Rhodoferax aquaticus sp. nov. with isolate Gr-4T (=KCTC 32394T=JCM 19166T) as the type strain.

Toonaolides A-X, limonoids from Toona ciliata: Isolation, structural elucidation, and bioactivity against NLRP3 inflammasome.

Twenty-four new limonoids, toonaolides A-X (1-24), characterized with an α,ß-unsaturated-γ-lactone A-ring were isolated from the twigs of Toona ciliata. Their structures and absolute configurations were elucidated by spectroscopic data, X-ray diffraction crystallography, and quantum chemistry calculations. Most of the isolated compounds (except 9, 18, and 24 which possessed the maleimide ring) featured the rare 21-hydroxybutenolide or 23-hydroxybutenolide moieties. In particular, compound 1 has an unprecedented limonoid architecture with 6/6 cis-fused A/B ring system and 2 has an unusual tetrahydrofuran ring B skeleton, featuring a 7/5/6/5 ring system. The biological evaluation showed that compounds 9, 11, 12, 14, and 18 exhibited significantly anti-NLRP3 inflammasome activity with IC50 values ranging from 3.2 to 9.7 µM. Analysis of IL-1ß and caspase-1 expression revealed that compounds 11 and 12 are selective inhibitors of NLRP3 inflammasome, which could ameliorate cell pyroptosis by blocking NLRP3 inflammasome activation.

Lacisediminimonas profundi gen. nov., sp. nov., a member of the family Oxalobacteraceae isolated from freshwater sediment.

A novel Gram-stain-negative bacterial strain, CHu64-6-4T, was isolated from a 67-cm-long sediment core collected from the Daechung Reservoir at a water depth of 17 m, Daejeon, Republic of Korea. The cells of strain CHu64-6-4T were aerobic nonmotile and formed colorless colonies on R2A agar. The phylogenetic analysis based on 16S rRNA gene sequencing indicated that the strain formed a separate lineage within the family Oxalobacteraceae, exhibiting 97.2% and 97.1% 16S rRNA gene sequence similarities to Glaciimonas singularis and Paraherbaspirillum soli, respectively. Strain CHu64-6-4T showed less than 74.4% average nucleotide identity compared to the type strains of related genera within the family Oxalobacteraceae. In the UPGMA dendrogram based on the ANI values of genomic sequences, strain CHu64-6-4T formed an evolutionary lineage independent of the genera Glaciimonas and some other taxa. The chemotaxonomic results showed Q-8 as the predominant respiratory ubiquinone, phosphatidylglycerol, diphosphatidylglycerol, and phosphatidylethnolamine as the major polar lipids, Summed Feature 3 (C16:1ω7c and/or iso-C15:0 2-OH), C16:0, and C18:1ω7c as the major fatty acids, and a DNA G+C content of 62.1 mol%. The combined genotypic and phenotypic data showed that strain CHu64-6-4T could be distinguished from all genera within the family Oxalobacteraceae and represents a novel genus, Lacisediminimonas profundi gen. nov., with the name Lacisediminimonas profundi sp. nov., in the family Oxalobacteraceae. The type strain is CHu64-6-4T (=KCTC 62287T=JCM 32676T).

Rubellawus A-D, Four New Diterpenoids Isolated from Callicarpa rubella and Their Anti-NLRP3 Inflammasome Effects.

Four new diterpenoids, rubellawus A-D (1-4), along with three known compounds, were isolated and identified from the flowers of Callicarpa rubella. Their structures were elucidated by various spectroscopic analysis. All the compounds were screened for their anti-inflammatory activity and 14α-hydroxyisopimaric acid and isopimaric acid showed significant NLRP3 inflammasome inhibitory activity with IC50 values of 7.02 and 3.99 µM.

Expression pattern of Connexin 26 and Connexin 30 in mature cochlea of the monkey.

Connexin26 (Cx26) and Cx30 are the predominant connexin subtypes found in the cochlea. They play an essential role in the cochlear functions. However, most studies use mice and the data on the cochlear expression profiles of the two Cxs in higher animals (e.g., humans) are scarce. Studies using the cochleae from non-human primate other than mice may provide information needed to narrow this gap. Here we studied cellular distributions of Cx26 and Cx30 in the adult monkey and guinea pig cochleae by immunofluorescent labeling and confocal microscopy observations. We detected Cx26 and Cx30 expressions in the type I, II& V fibrocytes in the spiral ligament, fibrocytes of the spiral limbus, in the supporting cells of organ of Corti, inner and outer sulcus cells, and in the basal cells of the stria vascularis. Both Cx26 and Cx30 were not detected in hair cells, in mesenchymal cells under the basilar membrane and cells lining the scala vestibule. Cells of the Reissner's membrane and spiral ganglion neurons are also negative. These findings demonstrate that cochlear expressions of Cx26 and Cx30 in the adult mouse, guinea pig and non-human primate have a common cellular pattern.