Exploiting Dual-Wavelength Depolarization of Skin-tissues for Camera-based Perfusion Monitoring.

Perfusion index (PI), the ratio between variable pulsatile (AC) and non-pulsatile (DC) components in a photoplethysmographic (PPG) signal, is an indirect and non-invasive measure of peripheral perfusion. PI has been widely used in assessing sympathetic block success, and monitoring hemodynamics in anesthesia and intensive care. Based on the principle of dual-wavelength depolarization (DWD) of skin tissues, we propose to investigate its opportunity in quantifying the skin perfusion contactlessly. The proposed method exploits the characteristic changes in chromaticity caused by skin depolarization and chromophore absorption. The experimental results of DWD, obtained with the post occlusive reactive hyperemia test and the local cooling and heating test, were compared to the PI values obtained from the patient monitor and photoplethysmography imaging (PPGI). The comparison demonstrated the feasibility of using DWD for PI measurement. Clinical trials conducted in the anesthesia recovery room and operating theatre further showed that DWD is potentially a new metric for camera-based non-contact skin perfusion monitoring during clinical operations, such as the guidance in anesthetic surgery.

Genome-wide identified VvOFP genes family and VvOFP4 functional characterization provide insight into fruit shape in grape.

Ovate Family Proteins (OFPs) are emerging as novel transcriptional regulators of fruit shape. Despite their established role in various species, their involvement in regulating grape fruit shape remains understudied. This study encompassed a comprehensive evaluation of 16 grape OFP genes in total at the whole genome level. Phylogenetic and synteny analyses established a close relationship between grape VvOFP genes and their tomato counterparts. Expression profiling post-treatment with gibberellic acid (GA3) and thidiazuron (TDZ) revealed that certain OFP genes responded to these regulators, with VvOFP4 showing peak expression three days post-anthesis. Functional assays via overexpression of VvOFP4 in tobacco and tomato altered the morphology of both vegetative and reproductive organs, including leaves, stamens, and fruits/pods. Paraffin sections of transgenic tobacco stems and tomato fruits demonstrated that VvOFP4 overexpression modifies cell dimensions, leading to changes in organ morphology. Additionally, treatments with GA3 and TDZ similarly influenced the shape of grape pulp cells and thereby the overall fruit morphology. These findings suggest that the VvOFP4 gene plays a crucial role in fruit shape determination by modulating cell shape and presents a potential target for future grape breeding programs aimed at diversifying fruit shapes.

Effects of acetylcysteine on micro-inflammation and pulmonary ventilation in chronic obstructive pulmonary disease exacerbation.

BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a serious complication of chronic obstructive pulmonary disease, often characterized by increased morbidity and mortality. In traditional Chinese medicine, AECOPD is linked to phlegm-heat and blood-stasis, presenting symptoms like thick sputum, fever, and chest pain. It has been shown that acetylcysteine inhalation in conjunction with conventional therapy significantly reduced inflammatory markers and improved lung function parameters in patients with AECOPD, suggesting that acetylcysteine may be an important adjunctive therapy for patients with phlegm-heat-blood stasis type AECOPD. AIM: To investigate the effect of acetylcysteine on microinflammation and lung ventilation in patients with phlegm-heat and blood-stasis-type AECOPD. METHODS: One hundred patients with phlegm-heat and blood-stasis-type AECOPD were randomly assigned to two groups. The treatment group received acetylcysteine inhalation (10% solution, 5 mL, twice daily) along with conventional therapy, whereas the control group received only conventional therapy. The treatment duration was 14 d. Inflammatory markers (C-reactive protein, interleukin-6, and tumor necrosis factor-alpha) in the serum and sputum as well as lung function parameters (forced expiratory volume in one second, forced vital capacity, and peak expiratory flow) were assessed pre- and post-treatment. Acetylcysteine inhalation led to significant reductions in inflammatory markers and improvements in lung function parameters compared to those in the control group (P < 0.05). This suggests that acetylcysteine could serve as an effective adjunct therapy for patients with phlegm-heat and blood-stasis-type AECOPD. RESULTS: Acetylcysteine inhalation significantly reduced inflammatory markers in the serum and sputum and improved lung ventilation function parameters in patients with phlegm-heat and blood-stasis type AECOPD compared with the control group. These differences were statistically significant (P < 0.05). The study concluded that acetylcysteine inhalation had a positive effect on microinflammation and lung ventilation function in patients with this type of AECOPD, suggesting its potential as an adjuvant therapy for such cases. CONCLUSION: Acetylcysteine inhalation demonstrated significant improvements in reducing inflammatory markers in the serum and sputum, as well as enhancing lung ventilation function parameters in patients with phlegm-heat and blood-stasis type AECOPD. These findings suggest that acetylcysteine could serve as a valuable adjuvant therapy for individuals with this specific type of AECOPD, offering benefits for managing microinflammation and optimizing lung function.

Nicotinamide N-Methyltransferase (NNMT) is Involved in Gastric Adenocarcinoma Immune Infiltration by Driving Amino Acid Metabolism.

Objectives: This study investigates the role of Nicotinamide N-methyltransferase (NNMT) in immune infiltration modulation through amino acid metabolism in gastric adenocarcinoma (STAD). Methods: Utilizing data from The Cancer Genome Atlas (TCGA) and validated with clinical samples, we analyzed NNMT expression and its prognostic implications in STAD. Differential amino acid profiles between cancerous and adjacent normal tissues were assessed, along with their associations with NNMT. Results: NNMT exhibits heightened expression in STAD cancer tissues, positively correlating with tumor immune infiltration. Additionally, twenty-eight amino acids display differential expression in gastric tissue, with their metabolic enzymes showing connections to NNMT. Conclusions: Elevated NNMT expression in STAD tissues potentially influences amino acid metabolism, thereby affecting immune infiltration dynamics and tumorigenesis in gastric adenocarcinoma.

A preoperative prediction of lymph node metastasis in early cervical squamous cell cancer with hematologica - based model.

Background: This study aimed to construct a preoperative model predicting lymph node metastasis (LNM) in IB1-IIA2 stage cervical squamous cell cancer (CSCC) based on hematological indexes. Merhods: Between February 2011 and February 2022, 463 patients with IB1-IIA2 stage CSCC underwent radical resection. Patients were allocated to either a model-development cohort (n=337) or a validation cohort (n=126). The final model was determined by comparing different methods of variable selection, and then its discrimination and calibration metrics were evaluated. A predicted probability of LNM < 5% was defined as low risk. ROC curves were used to define high risk. Results: Age, lactate dehydrogenase level, FIGO stage, squamous cell carcinoma antigen, cancer antigen 125, and cancer antigen 199 were identified as critical factors for the construction of the model. The model demonstrated good discrimination and calibration (concordance index, 0.761; 95% confidence interval, 0.666-0.884). In the validation cohort the discrimination accuracy was 0.821 (95% confidence interval, 0.714 - 0.927). In the model-development cohort, 11.9% were classified as low risk with a negative predictive value of 95.0%, and 24.9% were classified as high risk with a positive predictive value of 39.3%. Conclusion: A predictive model was developed and validated for LNM in IB1-IIA2 stage CSCC. The model will assist physicians in appraising the risk of LNM in preoperative patients and could aid in patient counseling and individualized clinical decision-making.

RNA m5C methylation orchestrates BLCA progression via macrophage reprogramming.

Recently, epigenetics showed essential roles in tumour microenvironment (TME) and immunotherapy response, however, the functions of RNA 5-methylcytosine (m5C) modification in TME remains unknown. According to 13 m5C regulators, we evaluated 412 BLCA patients from The Cancer Genome Atlas (TCGA) database. The m5C score was constructed by unsupervised clustering analysis and principal component analysis (PCA) algorithms. Gene set variation analysis (GSVA), ESTIMATE algorithm, and immunohistochemical (IHC) staining were performed. Macrophage chemotaxis assay was used to assess the M2 macrophages. Among the 412 patients, the frequency of mutation was 13%. m5C regulators was expressed significantly in BLCA tissue compared with normal tissue. Then, two m5C methylation modification patterns were identified with dissimilar TME cell infiltration patterns. The C1 alteration pattern in the m5C cluster was connected with better survival. In addition, we found that NSUN6 was highly correlated with recruitment of macrophages via bioinformatics and IHC. Further experiment validated that NSUN6 promoted HDAC10 expression by mediating m5C methylation, inhibited the transcription of macrophage-associated chemokines and thus inhibited the recruitment of M2 macrophages. The m5C score constructed by m5C modification pattern showed that high m5C score group had a better prognosis. This study uncovered the significant roles of m5C modifications in modulating the TME and indicated that NSUN6 could inhibit the recruitment of M2 macrophages via m5C methylation, which provided novel insight into epigenetic regulation of TME and clinical suggestions for immunotherapeutic strategies.

Adipose-derived mesenchymal stem cells secrete extracellular vesicles: A potential cell-free therapy for canine renal ischaemia-reperfusion injury.

BACKGROUND: Adipose-derived mesenchymal stem cells (ADMSCs) and their extracellular vesicles (EVs) are a promising source of therapies for ischaemia-reperfusion (IR) because of their potent anti-inflammatory and immunomodulatory properties. OBJECTIVES: The aims of this study were to explore the therapeutic efficacy and potential mechanism of ADMSC-EVs in canine renal IR injury. METHODS: Mesenchymal stem cells (MSCs) and EVs were isolated and characterised for surface markers. A canine IR model administered with ADMSC-EVs was used to evaluate therapeutic effects on inflammation, oxidative stress, mitochondrial damage and apoptosis. RESULTS: CD105, CD90 and beta integrin ITGB were positively expressed in MSCs, while CD63, CD9 and intramembrane marker TSG101 were positively expressed in EVs. Compared with the IR model group, there was less mitochondrial damage and reduction in quantity of mitochondria in the EV treatment group. Renal IR injury led to severe histopathological lesions and significant increases in biomarkers of renal function, inflammation and apoptosis, which were attenuated by the administration of ADMSC-EVs. CONCLUSIONS: Secretion of EVs by ADMSCs exhibited therapeutic potential in renal IR injury and may lead to a cell-free therapy for canine renal IR injury. These findings revealed that canine ADMSC-EVs potently attenuate renal IR injury-induced renal dysfunction, inflammation and apoptosis, possibly by reducing mitochondrial damage.

VvSUN may act in the auxin pathway to regulate fruit shape in grape.

Fruit shape is an essential agronomic feature in many crops. We identified and functionally characterized an auxin pathway-related gene, VvSUN. VvSUN, which belongs to the SUN/IQ67-DOMAIN (IQD) family, localizes to the plasma membrane and chloroplast and may be involved in controlling fruit shape through auxin. It is highly expressed in the ovary, and the expression level 1 week before the anthesis stage is positively correlated with the fruit shape index. Functional analyses illustrated that VvSUN gene overexpression in tomato and tobacco plants changed fruit/pod shape. The VvSUN promoter directly bound to VvARF6 in yeast and activated ß-glucuronidase (GUS) activity by indole-3-acetic acid (IAA) treatments in grapevine leaves, indicating that VvSUN functions are in coordination with auxin. Further analysis of 35S::VvSUN transgenic tomato ovaries showed that the fruit shape changes caused by VvSUN were predominantly caused by variations in cell number in longitudinal directions by regulating endogenous auxin levels via polar transport and/or auxin signal transduction process variations. Moreover, enrichment of the 35S::VvSUN transgenic tomato differentially expressed genes was found in a variety of biological processes, including primary metabolic process, transmembrane transport, calcium ion binding, cytoskeletal protein binding, tubulin binding, and microtubule-based movement. Using weighted gene co-expression network analysis (WGCNA), we confirmed that this plant hormone signal transduction may play a crucial role in controlling fruit shape. As a consequence, it is possible that VvSUN acts as a hub gene, altering cellular auxin levels and the plant hormone signal transduction pathway, which plays a role in cell division patterns, leading to anisotropic growth of the ovary and, ultimately, an elongated fruit shape.

Impact of Extracapsular Lymph Node Involving the Esophagus in Esophageal Perforation During and After Radiotherapy: A Propensity Score-Matched Analysis.

BACKGROUND: This study aimed to analyze the risk factors for esophageal squamous cell carcinoma (ESCC), especially extracapsular lymph node involving the esophagus (ECLNIE), occurring during or after radiotherapy (RT) in patients with esophageal perforation (EP). METHODS: In total, 306 patients with ESCC who received RT and/or chemotherapy between January 2016 and December 2017 in our hospital and who met the inclusion criteria of the study were recruited. The continuous variables were converted into classification variables using the receiver operating characteristic curve or common clinical parameters. Risk factors for EP were examined by univariable analysis using the chi-square test or Fisher's exact and by multivariable analysis using logistic regression model. Propensity score matching (PSM) was used to compensate for the differences in baseline characteristics, and the incidence of EP was compared after matching. RESULTS: EP was observed in 26 patients (incidence rate, 8.5%). Univariable analysis revealed that age, BMI, T4 stage, tumor length, esophageal wall thickness, ECLNIE, necrotic areas, niche sign by esophagogram before RT, neutrophil-to-lymphocyte ratio, and prognostic nutritional index were significantly associated with EP among patients with ESCC who received radiotherapy. Multivariable analysis demonstrated that age, ECLNIE, esophageal wall thickness, and niche sign by esophagogram before RT were independent risk factors for EP. After PSM, compared with patients without ECLNIE, patients with ESCC and ECLNIE had a significantly higher risk of EP. CONCLUSION: The presence of ECLNIE could be a strong risk factor of EP during and after RT.

Yes-associated protein promotes tumour necrosis factor α-treated cementoblast mineralization partly by inactivating NF-κB pathway.

Cementum regeneration, as one of the most difficult challenges of periodontal regeneration, is influenced by inflammatory factors. Inflammation may hamper or promote periodontal tissue repair under different circumstances, as it is found to do in dentin-pulp complex and bone tissue. Our team demonstrated that YAP promotes mineralization of OCCM, a cementoblast cell line. However, the effect of YAP on its mineralization under inflammatory microenvironment is unclear. In this study, cementogenesis in vitro was up-regulated after transient TNF-α treatment for 30 minutes. YAP expression also was increased by TNF-α treatment. YAP overexpression promoted OCCM mineralization after the cells were transiently treated with TNF-α because YAP overexpression inhibited NF-κB pathway activity, while YAP knockdown elevated it. The inhibited mineralization potential and activated NF-κB pathway activity by YAP knockdown also were partly rescued by the application of the NF-κB inhibitor Bay 11-7082. These results demonstrated that YAP plays a positive role in the mineralization of TNF-α transiently treated cementoblast, partly by inhibiting the NF-κB pathway activity.

Understanding the pattern of lymph node metastasis for trans-segmental thoracic esophageal cancer to develop precise delineation of clinical target volume for radiotherapy.

BACKGROUND: This study was conducted to explore the lymph node metastasis (LNM) pattern of thoracic esophageal cancer (TEC) depending upon the location of the primary tumor and provide a reference for the design of clinical target volume (CTV). METHODS: The data of patients who underwent radical esophagectomy and three-field lymph node dissection at Fujian Cancer Hospital from 2006 to 2010 were retrospectively analyzed. We segmented the esophagus according to the anatomical landmarks on computed tomography (CT) and defined the transsegmental and mono-segmental esophageal carcinoma. The LNM pattern in trans-segmental and monosegmental esophageal cancer was explored and the CTV delineation was determined based on LNM pattern. RESULTS: A total of 852 patients were included in this study. The top five sites of LNM for upper-middle TEC were cervical, upper and middle paraesophageal, and zone 1, 2, 4 regions. The most common sites of LNM for lower-middle TEC were cervical and middle paraesophageal, group 3, 7, and zone 7 regions. The top five sites of LNM for middle-upper TEC were cervical, middle paraesophageal, zone 1, 7, and group 7 regions. The most common sites of LNM for middle-lower TEC were cervical, middle paraesophageal, zone 7, and group 2, 7 regions. The top five sites of LNM for TEC involving all the segments were cervical, middle paraesophageal, zone 7, group 2 and 7 regions. CONCLUSIONS: LNM pattern of trans-segmental and mono-segmental TEC varies depending upon the primary tumor location. The irradiation field must be designed according to the primary tumor location.

Identification and characterization of antioxidant peptides from Chinese dry-cured mutton ham.

BACKGROUND: Chinese mutton ham is a dry-cured meat product with a long ripening time. The aim of this study was to identify and characterize antioxidant peptides from Chinese mutton ham. RESULTS: Mutton ham peptides (MHPs) were purified by gel filtration, anion exchange and reversed-phase high-performance liquid chromatography steps. The 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) free radical scavenging capacity was used to guide the purification of MHPs. Three antioxidant peptides were identified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) as Met-Trp-Thr-Asp (MWTD), Ala-Pro-Tyr-Met-Met (APYMM) and Phe-Trp-Ile-Ile-Glu (FWIIE), with molecular weights 551.61, 611.76, and 706.84 Da, respectively. Among them, APYMM exhibited the highest ABTS radical scavenging activity. The three peptides had the ability to inhibit lipid oxidation and Fenton's reagent-induced protein oxidation and DNA damage. After simulated gastrointestinal digestion, FWIIE and APYMM showed increased antioxidant activity, while MWTD showed decreased activity. CONCLUSION: Three novel peptides isolated from Chinese mutton ham had strong biological activity. Chinese mutton ham is potentially a functional food and an excellent source of natural antioxidants. © 2019 Society of Chemical Industry.

NAC-loaded electrospun scaffolding system with dual compartments for the osteogenesis of rBMSCs in vitro.

PURPOSE: In this study, we aimed to develop a unique N-acetyl cysteine (NAC)-loaded polylactic-co-glycolic acid (PLGA) electrospun system with separate compartments for the promotion of osteogenesis. MATERIALS AND METHODS: We first prepared solutions of NAC-loaded mesoporous silica nanoparticles (MSNs), PLGA, and NAC in N, N-dimethylformamide and tetrahydrofuran for the construction of the electrospun system. We then fed solutions to a specific injector for electrospinning. The physical and chemical properties of the scaffold were characterized through scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy. The release of NAC and Si from different PLGA scaffolds was estimated. The cell viability, cell growth, and osteogenic potential of rat bone marrow-derived stroma cell (rBMSCs) on different PLGA scaffolds were evaluated through MTT assay, live/dead staining, phalloidin staining, and Alizarin red staining. The expression levels of osteogenic-related markers were analyzed through real-time PCR (qRT-PCR). RESULTS: NAC was successfully loaded into MSNs. The addition of MSNs and NAC decreased the diameters of the electrospun fibers, increased the hydrophilicity and mechanical property of the PLGA scaffold. The release kinetic curve indicated that NAC was released from (PLGA + NAC)/(NAC@MSN) in a biphasic pattern, that featured an initial burst release stage and a later sustained release stage. This release pattern of NAC encapsulated on the (PLGA + NAC)/(NAC@MSN) scaffolds enabled to prolong the high concentrations of release of NAC, thus drastically affecting the osteogenic differentiation of rBMSCs. CONCLUSION: A PLGA electrospun scaffold was developed, and MSNs were used as separate nanocarriers for recharging NAC concentration, demonstrating the promising use of (PLGA + NAC)/(NAC@MSN) for bone tissue engineering.

[Effectiveness of an Interdisciplinary Health Education Intervention on Metabolic Syndrome in Community Residents: A Study of Four Towns in Northern Taiwan].

BACKGROUND: Metabolic syndrome, a widespread condition in Taiwan, increases the risks of cardiovascular diseases. Cardiovascular disease is the second leading cause of death in Taiwan after cancer. Thus, this health problem is a priority issue of concern. PURPOSE: To study the effects of active intervention of interdisciplinary health education on the prevalence of metabolic syndrome in community residents. METHODS: This longitudinal study was conducted from 2014 to 2015 on 661 participants who were all over 30 years old and living in four towns in northern Taiwan. The data were collected into two steps. In the first step, participants completed a blood study, body measurement, and pretest questionnaires and participated in the entire course of metabolic syndrome health education. The results of the blood test and body measurement were blinded to the experienced metabolic physicians before and after the education courses. In the second step, one year after administering the interdisciplinary health education course, the participants repeated the blood study, body measurement, and posttest questionnaires. RESULTS: 1. The participants had a higher incidence of metabolic syndrome. However, gender and marital status had no significant correlation with metabolic syndrome. Higher education levels were associated with a lower prevalence of metabolic syndrome. 2. The average scores for literacy rose from 2.30 pretest to 5.65 posttest. There were significant correlations (p < .05) between pretest and posttest health education. 3. The diagnosis of metabolic syndrome in this study changed from 215 participants (32.5%) to 170 participants (25.7%) between pretest and posttest (p < .05). 4. active health education had significant and positive effects on the cessation of smoking and chewing betel nut (p <.05). CONCLUSIONS: The active interdisciplinary health education intervention used in this study significantly decreased the smoking and betel-nut chewing habits and decreased the overall risk of metabolic syndrome in participants. Therefore, providing active health education on metabolic syndrome holds the potential to significantly decrease the prevalence of metabolic syndrome in at-risk populations. In addition, healthcare providers should make appropriately targeted health education more accessible to elderly patients who are prone to metabolic syndrome. Finally, the cessation of chewing betel nut should be seen as a major factor in the prevention and alleviation of metabolic syndrome.

IRX5 promotes NF-κB signalling to increase proliferation, migration and invasion via OPN in tongue squamous cell carcinoma.

Iroquois homeobox gene 5 (Irx5) is a highly conserved member of the Iroquois homeobox gene family. Members of this family play distinct and overlapping roles in normal embryonic cell patterning and development of malignancies. In this study, we observed that IRX5 was abnormally abundant in tongue squamous cell carcinoma (TSCC) tissues and cell lines. We used gain- and loss-of-function methods to overexpress and knockdown IRX5 expression in the TSCC cell line CAL27. Our results elucidated that elevated levels of IRX5 promoted proliferation, migration and invasion of TSCC cells, whereas stable or transient knockdown of IRX5 expression suppressed TSCC cell proliferation, migration and invasion. As a transcription factor, IRX5 performed this function by targeting osteopontin (OPN) promoter and activating the NF-κB pathway. Finally, studies in xenograft tumour model showed that IRX5 significantly enhanced OPN expression and promoted tumour growth. Taken together, our study elucidates a promotive effect of IRX5 in TSCC through the connection with OPN. These findings reveal the new molecular mechanism of TSCC, which may potentiate its use as a novel molecular therapy target for TSCC.

A fluorescent calixarene-based dimeric capsule constructed via a MII-terpyridine interaction: cage structure, inclusion properties and drug release.

Two analogues of capsule-like fluorescent cages have been constructed by dimerization of terpyridine-containing calixarene derivatives utilizing a MII-terpyridine (M = Zn and Cd) interaction. 1H NMR spectral studies show that the self-assembled molecular capsules Zn4L12 and Cd4L12 have a highly symmetrical D 4h-structure. The encapsulation of the anticancer drug mercaptopurine in their cavities has been documented by NMR, ESI-TOF-MS, fluorescence switching, and molecular simulation, indicating that strong S-π and π-π interactions between drug and cage are of importance for the host-guest binding. The nanoscale cages exhibit excellent behaviors to control the release of mercaptopurine in phosphate buffered saline solution (pH = 7.4). These results further highlight the potential of self-assembled Zn4L12 cages for drug-carrier applications.

The Role of Pannexin3-Modified Human Dental Pulp-Derived Mesenchymal Stromal Cells in Repairing Rat Cranial Critical-Sized Bone Defects.

BACKGROUND/AIMS: Human dental pulp-derived mesenchymal stromal cells (hDPSCs) are promising seed cells for tissue engineering due to their easy accessibility and multi-lineage differentiation. Pannexin3 (Panx3) plays crucial roles during bone development and differentiation. The aim of the present study was to investigate the effect of Panx3 on osteogenesis of hDPSCs and the underlying mechanism. METHODS: Utilizing qRT-PCR, Western blot, and immunohistochemistry, we explored the change of Panx3 during osteogenic differentiation of hDPSCs. Next, hDPSCs with loss (Panx3 knockdown) and gain (Panx3 overexpression) of Panx3 function were developed to investigate the effects of Panx3 on osteogenic differentiation of hDPSC and the underlying mechanism. Finally, a commercial ß-TCP scaffold carrying Panx3-modified hDPSCs was utilized to evaluate bone defect repair. RESULTS: Panx3 was upregulated during osteogenic differentiation in a time-dependent manner. Panx3 overexpression promoted osteogenic differentiation of hDPSCs, whereas depletion of Panx3 resulted in a decline of differentiation, evidenced by upregulated expression of mineralization-related markers, increased alkaline phosphatase (ALP) activity, and enhanced ALP and Alizarin red staining. Panx3 was found to interact with the Wnt/ß-catenin signaling pathway, forming a negative feedback loop. However, Wnt/ß-catenin did not contribute to enhancement of osteogenic differentiation as observed in Panx3 overexpression. Moreover, Panx3 promoted osteogenic differentiation of hDPSCs via increasing ERK signaling pathway. Micro-CT and histological staining results showed that Panx3-modified hDPSCs significantly improved ossification of critical-sized bone defects. CONCLUSION: These findings suggest that Panx3 is a crucial modulator of hDPSCs differentiation.

The epidemiological and clinical characteristics study on epilepsy in 8 ethnic groups of China.

To survey the epidemiological characteristics and clinical features on epilepsy in eight ethnic groups in Yunnan province of China. METHODES: The investigation was based on the WHO questionnaire and ICBERG screening questionnaire. This study was performed through random cluster sampling and door-to-door survey. RESULTS: A total of 76,302 individuals from eight ethnic groups were surveyed. The crude prevalence of epilepsy ranged from 1.2/1000 to 6.5/1000 in the eight ethnic groups, and the age-adjusted prevalence of epilepsy was from 2.1/1000 to 7.3/1000. The prevalence of active epilepsy varied from 1.0/1000 to 5.2/1000 in the eight ethnic groups, and the age-adjusted prevalence of active epilepsy was from 1.8/1000 to 6.7/1000. The age peak for seizures was below twenty, the patients of 61.1%-95.0% suffered from generalized seizures and 5%-21.2% had partial seizures. More than 60% of the cases in five ethnic groups, and the frequency of seizures were more than 10 events per year. More than 50% in other three ethnic groups, and the seizures had occurred less than 10 events per year. The treatment gap for active epilepsy ranged from 43.7% to 100.0% among the eight ethnic groups, while the natural remission rate varied from 5.6% to 21.0%. CONCLUSION: There were both disparity and similarity in the epidemiological and clinical features of epilepsy in different ethnic group communities.

Pyruvate kinase M2 interacts with mammalian sterile 20-like kinase 1 and inhibits tamoxifen-induced apoptosis in human breast cancer cells.

Tamoxifen has been reported to be associated with antagonism of estrogen-mediated cell growth signaling and activation of estrogen receptor-independent apoptosis events. It has been demonstrated that mammalian sterile 20-like kinase 1 is a direct target of Caspases to amplify the apoptotic signaling pathway. Here, we presented that breast cancer MCF-7 and SKBR3 cells under treatment with 4-hydroxytamoxifen displayed decreased level of pyruvate kinase M2. Western blot results also showed that 4-hydroxytamoxifen induced the activity of pro-apoptotic protein Caspase-3 in MCF-7 and SKBR3 cells, as evidenced by the cleavage of mammalian sterile 20-like kinase 1 substrate in a dose-dependent manner. Co-immunoprecipitation and immunofluorescence experiments were performed to clarify the relationship between pyruvate kinase M2 and mammalian sterile 20-like kinase 1. The results indicated that mammalian sterile 20-like kinase 1 was associated with pyruvate kinase M2 in cultured mammalian cells, and the interaction between mammalian sterile 20-like kinase 1 and pyruvate kinase M2 was decreased in response to 4-hydroxytamoxifen treatment. In addition, knockdown of pyruvate kinase M2 upregulated the level of cleaved Caspase-3 and subsequently facilitated the nuclear translocation of mammalian sterile 20-like kinase 1. Our data further supplemented the extensive functions of pyruvate kinase M2 in mediating breast cancer cell viability by substantially abating the mammalian sterile 20-like kinase 1-mediated apoptosis. In summary, our results identified that mammalian sterile 20-like kinase 1 is a novel downstream target of pyruvate kinase M2, and knockdown of pyruvate kinase M2 contributes apoptosis via promoting nuclear translocation of mammalian sterile 20-like kinase 1 by enhancing Caspase-3-dependent cleavage.

TßRII Regulates the Proliferation of Metanephric Mesenchyme Cells through Six2 In Vitro.

The transforming growth factor-ß (TGFß) family signaling pathways play an important role in regulatory cellular networks and exert specific effects on developmental programs during embryo development. However, the function of TGFß signaling pathways on the early kidney development remains unclear. In this work, we aim to detect the underlying role of TGFß type II receptor (TßRII) in vitro, which has a similar expression pattern as the crucial regulator Six2 during early kidney development. Firstly, the 5-ethynyl-2'-deoxyuridine (EdU) assay showed knock down of TßRII significantly decreased the proliferation ratio of metanephric mesenchyme (MM) cells. Additionally, real-time Polymerase Chain Reaction (PCR) and Western blot together with immunofluorescence determined that the mRNA and protein levels of Six2 declined after TßRII knock down. Also, Six2 was observed to be able to partially rescue the proliferation phenotype caused by the depletion of TßRII. Moreover, bioinformatics analysis and luciferase assay indicated Smad3 could transcriptionally target Six2. Further, the EdU assay showed that Smad3 could also rescue the inhibition of proliferation caused by the knock down of TßRII. Taken together, these findings delineate the important function of the TGFß signaling pathway in the early development of kidney and TßRII was shown to be able to promote the expression of Six2 through Smad3 mediating transcriptional regulation and in turn activate the proliferation of MM cells.