IL-33 regulates adipogenesis via Wnt/ß-catenin/PPAR-γ signaling pathway in preadipocytes.

Interleukin-33 (IL-33), an emerging cytokine within the IL-1 family, assumes a pivotal function in the control of obesity. However, the specific mechanism of its regulation of obesity formation remains unclear. In this study, we found that the expression level of IL-33 increased in visceral adipose tissue in mice fed with a high-fat diet (HFD) compared with that in mice fed with a normal diet (ND). In vitro, we also found the expression level of IL-33 was upregulated during the adipogenesis of 3T3-L1 cells. Functional test results showed that knockdown of IL-33 in 3T3-L1 cells differentiation could promote the accumulation of lipid droplets, the content of triglyceride and the expression of adipogenic-related genes (i.e. PPAR-γ, C/EBPα, FABP4, LPL, Adipoq and CD36). In contrast, overexpression of IL-33 inhibits adipogenic differentiation. Meanwhile, the above tests were repeated after over-differentiation of 3T3-L1 cells induced by oleic acid, and the results showed that IL-33 played a more significant role in the regulation of adipogenesis. To explore the mechanism, transcriptome sequencing was performed and results showed that IL-33 regulated the PPAR signaling pathway in 3T3-L1 cells. Further, Western blot and confocal microscopy showed that the inhibition of IL-33 could promote PPAR-γ expression by inhibiting the Wnt/ß-catenin signal in 3T3-L1 cells. This study demonstrated that IL-33 was an important regulator of preadipocyte differentiation and inhibited adipogenesis by regulating the Wnt/ß-catenin/PPAR-γ signaling pathway, which provided a new insight for further research on IL-33 as a new intervention target for metabolic disorders.

Response of photosynthetic characteristics and antioxidant system in the leaves of safflower to NaCl and NaHCO3.

KEY MESSAGE: Compared with NaCl, NaHCO3 caused more serious oxidative damage and photosynthesis inhibition in safflower by down-regulating the expression of related genes. Salt-alkali stress is one of the important factors that limit plant growth. NaCl and sodium bicarbonate (NaHCO3) are neutral and alkaline salts, respectively. This study investigated the physiological characteristics and molecular responses of safflower (Carthamus tinctorius L.) leaves treated with 200 mmol L-1 of NaCl or NaHCO3. The plants treated with NaCl treatment were less effective at inhibiting the growth of safflower, but increased the content of malondialdehyde (MDA) in leaves. Meanwhile, safflower alleviated stress damage by increasing proline (Pro), soluble protein (SP), and soluble sugar (SS). Both fresh weight and dry weight of safflower was severely decreased when it was subjected to NaHCO3 stress, and there was a significant increase in the permeability of cell membranes and the contents of osmotic regulatory substances. An enrichment analysis of the differentially expressed genes (DEGs) using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes identified significant enrichment of photosynthesis and pathways related to oxidative stress. Furthermore, a weighted gene co-expression network analysis (WGCNA) showed that the darkgreen module had the highest correlation with photosynthesis and oxidative stress traits. Large numbers of transcription factors, primarily from the MYB, GRAS, WRKY, and C2H2 families, were predicted from the genes within the darkgreen module. An analysis of physiological indicators and DEGs, it was found that under saline-alkali stress, genes related to chlorophyll synthesis enzymes were downregulated, while those related to degradation were upregulated, resulting in inhibited chlorophyll biosynthesis and decreased chlorophyll content. Additionally, NaCl and NaHCO3 stress downregulated the expression of genes related to the Calvin cycle, photosynthetic antenna proteins, and the activity of photosynthetic reaction centers to varying degrees, hindering the photosynthetic electron transfer process, suppressing photosynthesis, with NaHCO3 stress causing more pronounced adverse effects. In terms of oxidative stress, the level of reactive oxygen species (ROS) did not change significantly under the NaCl treatment, but the contents of hydrogen peroxide and the rate of production of superoxide anions increased significantly under NaHCO3 stress. In addition, treatment with NaCl upregulated the levels of expression of the key genes for superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), the ascorbate-glutathione cycle, and the thioredoxin-peroxiredoxin pathway, and increased the activity of these enzymes, thus, reducing oxidative damage. Similarly, NaHCO3 stress increased the activities of SOD, CAT, and POD and the content of ascorbic acid and initiated the glutathione-S-transferase pathway to remove excess ROS but suppressed the regeneration of glutathione and the activity of peroxiredoxin. Overall, both neutral and alkaline salts inhibited the photosynthetic process of safflower, although alkaline salt caused a higher level of stress than neutral salt. Safflower alleviated the oxidative damage induced by stress by regulating its antioxidant system.

Electrical Interference Simulation and Prediction Model for Acoustoelectric Logging Detector.

Acoustic logging instruments generate high voltages in the order of thousands of volts. Electrical interferences are thus induced by high-voltage pulses that affect the logging tool and make it inoperable owing to damaged components in severe cases. High-voltage pulses from the acoustoelectric logging detector interfere with the electrode measurement loop through capacitive coupling, which has seriously affected the acoustoelectric signal measurements. In this paper, we simulate high voltage pulses, capacitive coupling and electrode measurement loops based on qualitative analysis of the causes of electrical interference. Based on the structure of the acoustoelectric logging detector and the logging environment, an electrical interference simulation and prediction model was developed to quantify the characteristics of the electrical interference signal.

DsbA-L prevents obesity-induced inflammation and insulin resistance by suppressing the mtDNA release-activated cGAS-cGAMP-STING pathway.

Chronic inflammation in adipose tissue plays a key role in obesity-induced insulin resistance. However, the mechanisms underlying obesity-induced inflammation remain elusive. Here we show that obesity promotes mtDNA release into the cytosol, where it triggers inflammatory responses by activating the DNA-sensing cGAS-cGAMP-STING pathway. Fat-specific knockout of disulfide-bond A oxidoreductase-like protein (DsbA-L), a chaperone-like protein originally identified in the mitochondrial matrix, impaired mitochondrial function and promoted mtDNA release, leading to activation of the cGAS-cGAMP-STING pathway and inflammatory responses. Conversely, fat-specific overexpression of DsbA-L protected mice against high-fat diet-induced activation of the cGAS-cGAMP-STING pathway and inflammation. Taken together, we identify DsbA-L as a key molecule that maintains mitochondrial integrity. DsbA-L deficiency promotes inflammation and insulin resistance by activating the cGAS-cGAMP-STING pathway. Our study also reveals that, in addition to its well-characterized roles in innate immune surveillance, the cGAS-cGAMP-STING pathway plays an important role in mediating obesity-induced metabolic dysfunction.

Multi-targeting chemoprevention of Chinese herb formula Yanghe Huayan decoction on experimentally induced mammary tumorigenesis.

BACKGROUND: Development of safe and effective chemopreventive agents is a winning strategy in reducing the morbidity and mortality of breast cancer. The current study was to investigate the mechanism-based chemopreventive potential of a Chinese herb formula Yanghe Huayan (YHHY) Decoction on the classical 7,12-dimethylbenz(a)anthracene (DMBA) induced rat mammary carcinogenesis model. METHODS: Female Sprague-Dawley rats at 42 days of age were orally administered with a human equivalent dose of YHHY Decoction at 0.02 ml/g (10 mg/ml) once daily, starting 1 wk. before and 4 wks following DMBA treatment. Mammary tumor occurrence was monitored every day. The length of time before palpable tumor is examined is defined as tumor-free survival time. High performance liquid chromatography (HPLC) analyses were adopted to identify major chemical compositions of the decoction. Following bioinformatics data mining and experimental analyses were performed to demonstrate the underlying mechanism of action. RESULTS: DMBA animals receiving YHHY Decoction exhibited a significant delay (P = 0.014) and in some animals prevention (P = 0.046) of tumor occurrence without obvious toxicity. Oncogenic myc activation was significantly suppressed in the DMBA-induced rats by the YHHY treatment. Eight major chemical compositions of the decoction were identified and were shown to interfere with multiple tumorigenic pathways simultaneously in the mammary tumors, including inducing tumor apoptosis and up-regulating pro-apoptotic protein Bax and down-regulating anti-apoptotic protein Bcl-2; suppressing abnormal cell proliferation and the MAPK/ERK, PI3K/AKT signalings; blocking neo-angiogenesis and the VEGF/KDR signaling, and inhibiting oxidative stress in the mammary tumors. CONCLUSION: The multi-components and multi-targeting properties of the YHHY Decoction support its use as a potent chemopreventive drug in breast cancer.

Deformation Monitoring of Earth Fissure Hazards Using Terrestrial Laser Scanning.

Deformation monitoring is a powerful tool to understand the formation mechanism of earth fissure hazards, enabling the engineering and planning efforts to be more effective. To assess the evolution characteristics of the Yangshuli earth fissure hazard more completely, terrestrial laser scanning (TLS), a remote sensing technique which is regarded as one of the most promising surveying technologies in geohazard monitoring, was employed to detect the changes to ground surfaces and buildings in small- and large-scales, respectively. Time-series of high-density point clouds were collected through 5 sequential scans from 2014 to 2017 and then pre-processing was performed to filter the noise data of point clouds. A tiny deformation was observed on both the scarp and the walls, based on the local displacement analysis. The relative height differences between the two sides of the scarp increase slowly from 0.169 m to 0.178 m, while no obvious inclining (the maximum tilt reaches just to 0.0023) happens on the two walls, based on tilt measurement. Meanwhile, global displacement analysis indicates that the overall settlement slowly increases for the ground surface, but the regions in the left side of scarp are characterized by a relatively larger vertical displacement than the right. Furthermore, the comparisons of monitoring results on the same measuring line are discussed in this study and TLS monitoring results have an acceptable consistency with the global positioning system (GPS) measurements. The case study shows that the TLS technique can provide an adequate solution in deformation monitoring of earth fissure hazards, with high effectiveness and applicability.

Hepatic DsbA-L protects mice from diet-induced hepatosteatosis and insulin resistance.

Hepatic insulin resistance and hepatosteatosis in diet-induced obesity are associated with various metabolic diseases, yet the underlying mechanisms remain to be fully elucidated. Here we show that the expression levels of the disulfide-bond A oxidoreductase-like protein (DsbA-L) are significantly reduced in the liver of obese mice and humans. Liver-specific knockout or adenovirus-mediated overexpression of DsbA-L exacerbates or alleviates, respectively, high-fat diet-induced mitochondrial dysfunction, hepatosteatosis, and insulin resistance in mice. Mechanistically, we found that DsbA-L is localized in mitochondria and that its deficiency is associated with impairment of maximum respiratory capacity, elevated cellular oxidative stress, and increased JNK activity. Our results identify DsbA-L as a critical regulator of mitochondrial function, and its down-regulation in the liver may contribute to obesity-induced hepatosteatosis and whole body insulin resistance.-Chen, H., Bai, J., Dong, F., Fang, H., Zhang, Y., Meng, W., Liu, B., Luo, Y., Liu, M., Bai, Y., Abdul-Ghani, M. A., Li, R., Wu, J., Zeng, R., Zhou, Z., Dong, L. Q., Liu, F. Hepatic DsbA-L protects mice from diet-induced hepatosteatosis and insulin resistance.

The expression profile and clinicopathological significance of Notch1 in patients with colorectal cancer: a meta-analysis.

AIM: This meta-analysis was conducted to evaluate the clinicopathological significance of Notch1 expression in patients with colorectal cancer (CRC). METHODS: Available articles were searched from diverse databases, and the meta-analysis was done by using Stata 12.0 software. RESULTS: Thirteen studies were included in this analysis (3401 samples). The Notch1 expression in CRC tissues was significantly higher than that in normal tissues statistically (OR: 15.46; 95% CI: 8.11-29.45; p = 0.003), and were associated with lymph node metastasis, tumor stage, depth of infiltration and histological differentiation. DISCUSSION:  There is a close relationship between higher Notch1 expression in CRC. Notch1 may be involved in tumor progression, invasion and metastasis with CRC. CONCLUSION: Notch1 overexpression in CRC suggested aggressive biological behaviors and thus implying that Notch1 may be a useful biomarker in CRCs.

Endoplasmic reticulum (ER) localization is critical for DsbA-L protein to suppress ER stress and adiponectin down-regulation in adipocytes.

Adiponectin is an adipokine with insulin-sensitizing and anti-inflammatory functions. We previously reported that adiponectin multimerization and stability are promoted by the disulfide bond A oxidoreductase-like protein (DsbA-L) in cells and in vivo. However, the precise mechanism by which DsbA-L regulates adiponectin biosynthesis remains elusive. Here we show that DsbA-L is co-localized with the endoplasmic reticulum (ER) marker protein disulfide isomerase and the mitochondrial marker MitoTracker. In addition, DsbA-L interacts with the ER chaperone protein Ero1-Lα in 3T3-L1 adipocytes. In silico analysis and truncation mapping studies revealed that DsbA-L contains an ER targeting signal at its N terminus. Deletion of the first 6 residues at the N terminus greatly impaired DsbA-L localization in the ER. Overexpression of the wild type but not the ER localization-defective mutant of DsbA-L protects against thapsigargin-induced ER stress and adiponectin down-regulation in 3T3-L1 adipocytes. In addition, overexpression of the wild type but not the ER localization-defective mutant of DsbA-L promotes adiponectin multimerization. Together, our results reveal that DsbA-L is localized in both the mitochondria and the ER in adipocytes and that its ER localization plays a critical role in suppressing ER stress and promoting adiponectin biosynthesis and secretion.

Virulence determinants in the PB2 gene of a mouse-adapted H9N2 virus.

The molecular bases of adaptation and pathogenicity of H9N2 influenza virus in mammals are largely unknown. Here, we show that a mouse-adapted PB2 gene with a phenylalanine-to-leucine mutation (F404L) mainly contributes to enhanced polymerase activity, replication, and pathogenicity of H9N2 in mice and also increases the virulence of the H5N1 and 2009 pandemic H1N1 influenza viruses. Therefore, we defined a novel pathogenic determinant, providing further insights into the pathogenesis of influenza viruses in mammals.

Terahertz polarization splitter based on a dual-elliptical-core polymer fiber.

A terahertz polarization splitter based on a dual-elliptical-core polymer fiber is proposed and theoretically optimized. Dual-elliptical cores with subwavelength-scale diameters are independently suspended within a fiber, which not only support two orthogonal polarization modes, being single-mode guided with low absorption losses, but also allow them to switch from one core to the other, with different coupling lengths. As a consequence, the two polarizations can be easily separated by choosing a suitable transmission length at a desired operation frequency. The transmission modes, coupling lengths for x- and y-polarizations, as well as the performance of the proposed polarization splitter at a center-frequency of 0.6 THz are investigated and numerically analyzed. A 1.43 cm long splitter with an ultralow loss of 0.4 dB, a high extinction ratio better than -10 dB and a bandwidth of 0.02 THz is achieved.

Molecular mechanism of the airborne transmissibility of H9N2 avian influenza A viruses in chickens.

UNLABELLED: H9N2 avian influenza virus has been prevalent in poultry in many parts of the world since the 1990s and occasionally crosses the host barrier, transmitting to mammals, including humans. In recent years, these viruses have contributed genes to H5N1 and H7N9 influenza viruses, threatening public health. To explore the molecular mechanism for the airborne transmission of H9N2 virus, we compared two genetically close strains isolated from chickens in 2001, A/chicken/Shanghai/7/2001(SH7) and A/chicken/Shanghai/14/2001 (SH14). SH7 is airborne transmissible between chickens, whereas SH14 is not. We used reverse genetics and gene swapping to derive recombinant SH7 (rSH7), rSH14, and a panel of reassortant viruses. Among the reassortant viruses, we identified segments HA and PA as governing the airborne transmission among chickens. In addition, the NP and NS genes also contributed to a lesser extent. Furthermore, the mutational analyses showed the transmissibility phenotype predominantly mapped to the HA and PA genes, with HA-K363 and PA-L672 being important for airborne transmissibility among chickens. In addition, the viral infectivity and acid stability are related to the airborne transmissibility. Importantly, airborne transmission studies of 18 arbitrarily chosen H9N2 viruses from our collections confirmed the importance of both 363K in HA and 672L in PA in determining their levels of transmissibility. Our finding elucidates the genetic contributions to H9N2 transmissibility in chickens and highlights the importance of their prevalence in poultry. IMPORTANCE: Our study investigates the airborne transmissibility of H9N2 viruses in chickens and the subsequent epidemic. H9N2 virus is the donor for several prevalent reassortant influenza viruses, such as H7N9/2013 and the H5N1 viruses. Poultry as the reservoir hosts of influenza virus is closely associated with human society. Airborne transmission is an efficient pathway for influenza virus transmission among flocks and individuals. Exploring the mechanism of the airborne transmission of the H9N2 virus in chickens could provide essential data regarding prevention and control of influenza endemics and pandemics.

The PA and HA gene-mediated high viral load and intense innate immune response in the brain contribute to the high pathogenicity of H5N1 avian influenza virus in mallard ducks.

Most highly pathogenic avian influenza A viruses cause only mild clinical signs in ducks, serving as an important natural reservoir of influenza A viruses. However, we isolated two H5N1 viruses that are genetically similar but differ greatly in virulence in ducks. A/Chicken/Jiangsu/k0402/2010 (CK10) is highly pathogenic, whereas A/Goose/Jiangsu/k0403/2010 (GS10) is low pathogenic. To determine the genetic basis for the high virulence of CK10 in ducks, we generated a series of single-gene reassortants between CK10 and GS10 and tested their virulence in ducks. Expression of the CK10 PA or hemagglutinin (HA) gene in the GS10 context resulted in increased virulence and virus replication. Conversely, inclusion of the GS10 PA or HA gene in the CK10 background attenuated the virulence and virus replication. Moreover, the PA gene had a greater contribution. We further determined that residues 101G and 237E in the PA gene contribute to the high virulence of CK10. Mutations at these two positions produced changes in virulence, virus replication, and polymerase activity of CK10 or GS10. Position 237 plays a greater role in determining these phenotypes. Moreover, the K237E mutation in the GS10 PA gene increased PA nuclear accumulation. Mutant GS10 viruses carrying the CK10 HA gene or the PA101G or PA237E mutation induced an enhanced innate immune response. A sustained innate response was detected in the brain rather than in the lung and spleen. Our results suggest that the PA and HA gene-mediated high virus replication and the intense innate immune response in the brain contribute to the high virulence of H5N1 virus in ducks.

A nonpathogenic duck-origin H9N2 influenza A virus adapts to high pathogenicity in mice.

H9N2 influenza viruses continue to circulate in wild birds and poultry in Eurasian countries and have repeatedly infected mammals, including pigs and humans, posing a significant threat to public health. To understand the adaptation of H9N2 influenza viruses to mammals, we serially passaged a nonpathogenic duck-origin H9N2 influenza virus, A/duck/Jiangsu/1/2008 (DK1), in mouse lungs. Increased virulence was detectable after five sequential passages, and a highly pathogenic mouse-adapted strain (DK1-MA) with a 50% mouse lethal dose of 10(2.37) 50% egg infectious dose was obtained after 18 passages. DK1-MA grew faster and reached significantly higher titers than DK1 in mouse lungs and could sporadically spread to other organs. Moreover, DK1-MA induced a greater magnitude of pulmonary edema and higher levels of inflammatory cellular infiltration in bronchoalveolar lavage fluids than DK1 did. Genomic sequence alignment revealed eight amino acid substitutions (HA-L80F, HA-N193D, NA-A27T, PB2-F404L, PA-D3V, PA-S225R, NP-V105M, M1-A166V) in six viral proteins of DK1-MA compared with DK1 virus. Except for HA-L80F, the other seven substitutions were all located in known functional regions involved in interaction of viral proteins or interaction between the virus and host factors. Taken together, our results suggest that multiple amino acid substitutions may be involved in the adaptation of H9N2 avian influenza virus to mice, resulting in lethal infection, enhanced viral replication, severe pulmonary edema, and excessive inflammatory cellular infiltration in lungs. These observations provide helpful insights into the pathogenic potential of H9N2 avian influenza viruses that could pose threats to human health in the future.

[Effect of yanghe huayan decoction on precancerosis of breast cancer, protein and mRNA expression of ki67: an experimental research].

OBJECTIVE: To explore the effect of Yanghe Huayan Decoction (YHD, a representative recipe for warming yang mass dissipating) in inhibiting precancerosis of breast cancer (PBC) and on the protein and mRNA expression of ki67. METHODS: The PBC rat model was established by dimethylbenzanthracene (DMBA), and 9 weeks later rats were randomly divided into the blank control group, the model group, the YHD group, the Sanjie Huatan Decoction group (SHD), the Pingxiao Tablet group (PT), and the tamoxifen group. Rats in the model group were administered with water by gastrogavage. Rats in the YHD group received YHD (deglued antler powder 12 g, prepared rhizome of rehmannia 9 g, cassia bark 6 g, white mustard seed 3 g, zedoary root 12 g, appendiculate cremastra pseudobulb 15 g, chekiang fritillary bulb 9 g, licorice root 6 g) at the daily dose of 7.2 g/kg by gastrogavage. Rats in the SHD group received SHD (oldenlandia diffusa 15 g, Scutellaria Barbata 15 g, Trichosanthes Kirilowii 15 g, pinellia 9 g) at the daily dose of 5.4 g/kg by gastrogavage. Rats in the PT group received PT at the daily dose of 144 mg/kg by gastrogavage. Those in the tamoxifen group received tamoxifen at the daily dose of 4 mg/kg by gastrogavage. Pathomorphological changes of the breast tissue were observed by HE staining. The positive rate and the gray value of ki67 expression were detected by immunohistochemical assay. And the expression of ki67 mRNA was detected by q-PCR. RESULTS: Compared with the model group, the general hyperplasia and the occurrence rate of precancerous lesion were higher and the occurrence rate of invasive carcinoma was lower in each treatment group (P < 0.05). Except the SHD group, the intensity of ki67 grey value increased in each treatment group (P < 0.05, P < 0.01). Except the PT group, the positive rate of ki67 and mRNA expression of ki67 increased in the rest treatment groups (P < 0.05, P < 0.01). Compared with the YHD group, there was no statistical difference in the occurrence rate of infiltration or the occurrence rate of precancerous lesion (P > 0.05). The positive rate of ki67 expression and mRNA expression of ki67 increased in the PT group, showing statistical difference (P < 0.05). CONCLUSIONS: YHD could partially inhibit and reverse canceration of breast cancer. It also could inhibit ki67 protein and mRNA expression. Its effect was similar to tamoxifen and superior to PT. So it was suitable for prevention and treatment of precancerous lesion of breast cancer.

An Accurate and Transferable Coarse-Graining Method for the Investigation of Microscopic Fracture Behaviors of Epoxy Thermosets.

Coarse-grained modeling shows potential in exploring the thermo-mechanical behaviors of polymers applied in harsh conditions such as cryogenic environment, but its accuracy in simulating fracture behaviors of highly cross-linked epoxy thermosets is largely limited due to the complex molecular structures of the cross-linked networks. We address this fundamental problem by developing a CG modeling method where the backbones and electrostatic interaction (EI) contributions in the cross-linked networks are retained, and thus the potentials of the CG model can be directly extracted, or parametrized on the basis of, existing all-atomistic (AA) force fields. A multilevel parametrization procedure was adopted, where the bond potentials were parametrized relying on the results of density functional theory (DFT) simulation, whereas the nonbond potentials were parametrized by renormalizing the cohesive interaction strength. Remarkably, the CG model can reproduce stress-strain responses highly consistent with the AA simulation results at multiple stages, including elastic deformation, yielding, plastic flow, strain hardening, etc., and the straightforward parametrization procedure can be easily transferred to different materials and thermodynamic conditions. The CG modeling method was then used to build a large-scale representative volume element (RVE) to investigate the microscopic fracture behavior of an epoxy thermoset. It has been discovered that EI contributions play a significant role in generating correct mechanical responses and fracture morphologies. The influences of temperature (i.e., from room to cryogenic temperatures) and strain rates were discussed, and the fracture morphology in the RVE was unveiled and analyzed in a quantitative manner.

Effects of Seipin on Mouse Mesenchymal Stem Cell Osteo-Adipogenic Balance.

Seipin deficiency is an important cause of type 2 Berardinelli-Seip congenital dyslipidemia (BSCL2). BSCL2 is a severe lipodystrophy syndrome with lack of adipose tissue, hepatic steatosis, insulin resistance, and normal or higher bone mineral density. Bone marrow mesenchymal stem cells (BMSCs) are believed to maintain bone and fat homeostasis by differentiating into osteoblasts and adipocytes. We aimed to explore the role of seipin in the osteogenic/adipogenic differentiation balance of BMSCs. Seipin loxP/loxP mice are used to explore metabolic disorders caused by seipin gene mutations. Compared with wild-type mice, subcutaneous fat deficiency and ectopic fat accumulation were higher in seipin knockout mice. Microcomputed tomography of the tibia revealed the increased bone content in seipin knockout mice. We generated seipin-deficient BMSCs in vitro and revealed that lipogenic genes are downregulated and osteogenic genes are upregulated in seipin-deficient BMSCs. In addition, peroxisome proliferator-activated receptor gamma (PPARγ) signaling is reduced in seipin-deficient BMSCs, while using the PPARγ activator increased the lipogenic differentiation and decreased osteogenic differentiation of seipin-deficient BMSCs. Our findings indicated that bone and lipid metabolism can be regulated by seipin through modulating the differentiation of mesenchymal stem cells. Thus, a new insight of seipin mutations in lipid metabolism disorders was revealed, providing a prospective strategy for MSC transplantation-based treatment of BSCL2.

[Acupoint application for Hashimoto's thyroiditis with liver-qi stagnation: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy and safety of acupoint application for Hashimoto's thyroiditis (HT) with liver-qi stagnation. METHODS: One hundred and fifty patients of HT with liver-qi stagnation were randomly divided into an acupoint application group (75 cases, 11 cases were excluded, 5 cases dropped out) and a control group (75 cases, 12 cases excluded, 3 cases dropped out). Based on the health education combined with conventional western medicine treatment, the patients in the acupoint application group were treated with acupoint application, while the patients in the control group were treated with placebo acupoint application. Shenque (CV 8), bilateral Yongquan (KI 1), Yeshi, and ashi point were selected in both groups, with Yeshi treated once a week and the remaining acupoints treated every other day, for a total of 4 weeks. The serum levels of thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH), as well as the thickness of thyroid left lobe, right lobe, and isthmus, TCM symptom score, hospital anxiety and depression scale (HADS) score, and MOS 36-item short form health survey (SF-36) score were compared between the two groups before and after treatment. Adverse reactions in both groups were observed. RESULTS: Compared with before treatment, in the acupoint application group, the serum levels of TgAb and TPOAb were reduced after treatment (P<0.05), and the scores of role physical (RP), body pain (BP), vitality (VT), role emotional (RE), and mental health (MH) in SF-36 were increased after treatment (P<0.01, P<0.001). The thickness of the thyroid isthmus after treatment was smaller than that before treatment (P<0.05), and the TCM symptom scores and HADS anxiety (HADS-A) scores after treatment were lower than those before treatment (P<0.001, P<0.01) in both groups. In the control group, the scores of physical function (PF), RP, BP, VT, and RE in SF-36 after treatment were higher than those before treatment (P<0.05, P<0.01, P<0.001). There was no statistically significant difference in serum FT3, FT4, and TSH levels within the groups (P>0.05). There was no statistically significant difference in the above indexes between the two groups (P>0.05). The incidence of adverse reactions in the acupoint application group and the control group was 20.0% (15/75) and 10.7% (8/75) respectively, with skin allergy being the main adverse reaction. CONCLUSION: Acupoint application could reduce the serum levels of TgAb and TPOAb in patients of HT with liver-qi stagnation, alleviate thyroid enlargement, improve TCM symptoms and anxiety, and improve quality of life, with safe and reliable clinical efficacy.

Hsa_circRNA_405498 and hsa_circRNA_100033 Serve as Potential Biomarkers for Differential Diagnosis of Type 1 Diabetes.

CONTEXT: The role of circular RNAs (circRNAs) in type 1 diabetes (T1D) is largely unknown. OBJECTIVE: We aimed to identify some circRNAs as differential diagnostic biomarkers for T1D to distinguish between patients with latent autoimmune diabetes in adults (LADA) and type 2 diabetes (T2D). METHODS: The circRNA expression profiles were determined by Arraystar human circRNA microarray in T1D compared to controls (n = 6 each). The differentially expressed circRNAs were validated by real-time quantitative polymerase chain reaction using a validation cohort with 20 T1D and 20 controls. The diagnostic performances of the candidate circRNAs and the clinical parameters were assessed using the logistic least absolute shrinkage and selection operator (LASSO) regression model in a larger cohort with 457 individuals, including patients with T1D, T2D, and LADA, and controls. RESULTS: We identified 110 differentially expressed circular transcripts (53 upregulated and 57 downregulated) in T1D patients compared with controls. Further analysis showed that the levels of hsa_circRNA_405498 and hsa_circRNA_100033 were significantly downregulated in T1D compared to controls (both P < .05). Moreover, the expression levels of these 2 circRNAs showed sequential downregulation from controls, patients with T2D, LADA, to T1D (P < .05). The area under the curve (AUC) of receiver operating characteristic plots in logistic LASSO regression model showed high diagnostic accuracy for combination model with the 2 circRNAs and some clinical parameters in distinguishing T1D from LADA (AUC = 0.915), T2D (AUC = 0.993), and controls (AUC = 0.992). CONCLUSION: Our study demonstrated that hsa_circRNA_405498 and hsa_circRNA_100033 are promising novel differential diagnostic biomarkers for T1D.