Environmentally relevant concentrations of microplastics modulated the immune response and swimming activity, and impaired the development of marine medaka Oryzias melastigma larvae.

Microplastics (MPs), due to their impacts on the ecosystem and their integration into the food web either through trophic transfer or ingestion directly from the ambient environment, are an emerging class of environmental contaminants posing a great threat to marine organisms. Most reports on the toxic effects of MPs exclusively focus on bioaccumulation, oxidative stress, pathological damage, and metabolic disturbance in fish. However, the collected information on fish immunity in response to MPs is poorly defined. In particular, little is known regarding mucosal immunity and the role of mucins. In this study, marine medaka (Oryzias melastigma) larvae were exposed to 6.0 µm beads of polystyrene microplastics (PS-MPs) at three environmentally relevant concentrations (102 particles/L, 104 particles/L, and 106 particles/L) for 14 days. The experiment was carried out to explore the developmental and behavioural indices, the transcriptional profiles of mucins, pro-inflammatory, immune, metabolism and antioxidant responses related genes, as well as the accumulation of PS-MPs in larvae. The results revealed that PS-MPs were observed in the gastrointestinal tract, with a concentration- and exposure time-dependent manner. No significant difference in the larval mortality was found between the treatment groups and the control, whereas the body length of larvae demonstrated a significant reduction at 106 particles/L on 14 days post-hatching. The swimming behaviour of the larvae became hyperactive under exposure to 104 and 106 particles/L PS-MPs. In addition, PS-MP exposure significantly up-regulated the mucin gene transcriptional levels of muc7-like and muc13-like, however down-regulated the mucin gene expression levels of heg1, muc2, muc5AC-like and muc13. The immune- and inflammation and metabolism-relevant genes (jak, stat-3, il-6, il-1ß, tnf-а, ccl-11, nf-κb, and sod) were significantly induced by PS-MPs at 104 and 106 particles/L compared to the control. Taken together, this study suggests that PS-MPs induced inflammation response and might obstruct the immune functions and retarded the growth of the marine medaka larvae even at environmentally relevant concentrations.

The Application of Deep Learning in the Risk Grading of Skin Tumors for Patients Using Clinical Images.

According to diagnostic criteria, skin tumors can be divided into three categories: benign, low degree and high degree malignancy. For high degree malignant skin tumors, if not detected in time, they can do serious harm to patients' health. However, in clinical practice, identifying malignant degree requires biopsy and pathological examination which is time costly. Furthermore, in many areas, due to the severe shortage of dermatologists, it's inconvenient for patients to go to hospital for examination. Therefore, an easy to access screening method of malignant skin tumors is needed urgently. Firstly, we spend 5 years to build a dataset which includes 4,500 images of 10 kinds of skin tumors. All instances are verified pathologically thus trustworthy; Secondly, we label each instance to be either low-risk, high-risk or dangerous in which Junctional nevus, Intradermal nevus, Dermatofibroma, Lipoma and Seborrheic keratosis are low-risk, Basal cell carcinoma, Bowen's disease and Actinic keratosis are high-risk, Squamous cell carcinoma and Malignant melanoma are dangerous; Thirdly, we apply the Xception architecture to build the risk degree classifier. The area under the curve (AUC) for three risk degrees reach 0.959, 0.919 and 0.947 respectively. To further evaluate the validity of the proposed risk degree classifier, we conduct a competition with 20 professional dermatologists. The results showed the proposed classifier outperforms dermatologists. Our system is helpful to patients in preliminary screening. It can identify the patients who are at risk and alert them to go to hospital for further examination.

Dual functional photo-response for p-Si/SiO2/n-InGaZnO graphene nanocomposites photodiodes.

This study demonstrates dual functional hybrid heterojunction photodiodes (PDs) that comprise an amorphous indium gallium zinc oxide (a-IGZO) thin film blended with graphene nanoflakes and a SiO2 (5 nm)/Si substrate. The PDs exhibit a photo-responsivity of approximately 0.15-0.27 A W-1 under 633 nm illumination, which is much higher than that for a-IGZO based phototransistor in the visible region. The device also gives a long-lasting persistent photocurrent (PPC) when the UV light is extinguished. This results show that the hybrid heterojunction acts as a high performance photodetector for the detection of visible light and provides a universal scenario for development of PPC.

The role of CGRP and CALCA T-692C single-nucleotide polymorphism in psoriasis vulgaris.

Calcitonin gene related protein (CGRP) is increased in both lesional and non-lesional psoriasis. The role of CGRP in the pathogenesis of psoriasis vulgaris is still not clear. We designed to determine the CGRP-I (or CALCA), II (or CALCB) gene expression and morbidity and CALCA T-692C single-nucleotide polymorphism (SNP). Peripheral blood mononuclear cells (PBMCs) and plasma samples were collected, and CGRP level and CGRP-I, II mRNA expression were measured in psoriasis patients and healthy controls. The CALCA T-692C genetic polymorphism in psoriasis and control subjects was also compared. A higher expression of CGRP-I, II mRNA in PBMCs in psoriasis patients. The plasma CGRP level in psoriasis patients was also higher than that in healthy subjects. SNP analysis showed carriers of the T-692C allele were over-represented in non-drinking Patients. The plasma CGRP level was higher in alcohol-drinking patients with TT genotype than that with TC genotype. The plasma CGRP level is increased in psoriasis patients and CALCA T-692C polymorphism TT genotype is a factor for the affectability in alcohol-drinking Psoriasis vulgaris patients.

[Role and mechanism of all-trans retinoic acid in up-regulating apelin expression in vascular smooth muscle cells].

This study was aimed to investigate the mechanism of all-trans retinoic acid (ATRA) up-regulating apelin expression in vascular smooth muscle cells (VSMCs). The effect of ATRA on apelin expression in the VSMCs was investigated by RT-PCR, real-time PCR and Western blot analysis. To further define whether retinoic acid receptor α (RARα) mediated the induction of apelin by ATRA, endogenous RARα was down regulated by transfection of siRNA against RARα (si-RARα) or RARα was over-expressed by infection of the adenovirus vector pAd-GFP-RARα in the VSMCs. The results showed that ATRA significantly induced apelin expression in a time- and dose-dependent manner in the VSMCs. Although RARα expression was increased in a time-dependent manner, the expressions of RARß and RARγ were little changed by the ATRA treatment. When VSMCs were treated with a RARα antagonist Ro 41-5253 prior to the addition of ATRA, or si-RARα was used to down regulate endogenous RARα expression, the blockade of RARα signaling partially reduced the response of apelin to ATRA. Moreover, RARα over-expression, induced by infection of pAd-GFP-RARα, further increased the induction of apelin by ATRA. In conclusion, ATRA may up-regulate apelin expression in VSMCs, and the mechanism may be RARα dependent.

Comparison of three problem-based learning conditions (real patients, digital and paper) with lecture-based learning in a dermatology course: a prospective randomized study from China.

BACKGROUND: The precise effect and the quality of different cases used in dermatology problem-based learning (PBL) curricula are yet unclear. AIM: To prospectively compare the impact of real patients, digital, paper PBL (PPBL) and traditional lecture-based learning (LBL) on academic results and student perceptions. METHODS: A total of 120 students were randomly allocated into either real-patients PBL (RPBL) group studied via real-patient cases, digital PBL (DPBL) group studied via digital-form cases, PPBL group studied via paper-form cases, or conventional group who received didactic lectures. Academic results were assessed through review of written examination, objective structured clinical examination and student performance scores. A five-point Likert scale questionnaire was used to evaluate student perceptions. RESULTS: Compared to those receiving lectures only, all PBL participants had better results for written examination, clinical examination and overall performance. Students in RPBL group exhibited better overall performance than those in the other two PBL groups. Real-patient cases were more effective in helping develop students' self-directed learning skills, improving their confidence in future patient encounters and encouraging them to learn more about the discussed condition, compared to digital and paper cases. CONCLUSION: Both real patient and digital triggers are helpful in improving students' clinical problem-handling skills. However, real patients provide greater benefits to students.

[Analysis of the curative effect of triple surgery under endoscope in the treatment of intractable heel pain].

OBJECTIVE: To investigate the clinical effect the treatment of arthroscopy-assisted calcaneal spur resection combined with plantar fascia release and calcaneal decompression in the treatment of the patients with intractable calcaneal pain. METHODS: The clinical data of 50 patients with intractable heel pain from January 2016 to January 2019 were retrospectively analyzed, including 20 males and 30 females;aged from 40 to 68 years old with an average of (50.12±7.35)years old, the medical history ranged from 1 to 4 years. All patients underwent arthroscopy-assisted calcaneal spur resection combined with plantar fascia release and calcaneal decompression, and were followed up, the duration ranged from 24 to 60 months with an average of(42.00±3.28) months. All patients had obvious heel pain before surgery, and X-ray examinations often showed the presence of calcaneal spurs. In addition to the routine foot examination, the changes in the height and angle of the arch of the foot were also measured pre and post-operatively by X-ray, for the evaluation of clinical effect. The VAS system was used to evaluate the degree of foot pain;the AOFAS scoring system was used to comprehensively evaluate the foot pain, voluntary movement, gait and stability. RESULTS: The VAS decreased from (8.75±1.24) before surgery to (5.15±2.35) at 3 months after surgery, (4.07±2.53) at 6 months after surgery, and (3.95±2.44) at the last fllow-up(P<0.05). The AOFAS score increased from (53.46±4.17) before surgery to(92.46±2.53) at 3 months after surgery, (96.33±2.46) at 6 months after surgery, and (97.05±2.37) at the last follow-up(P<0.05). The arch height was (41.54±1.15) mm before operation and (41.49±1.09) mm after the operation, the difference was not statistically significant(P>0.05). The internal arch angle of the foot arch was (121±6)° before operation and (122±7)° after operation. The difference was not statistically significant(P>0.05). CONCLUSION: Arthroscopy-assisted calcaneal bone spurs resection combined with plantar fascia release and calcaneal decompression exhibited great clinical effect for treating intractable heel.

Avoiding misdiagnosis of duodenal papilla adenocarcinoma in a situs inversus totalis patient via laparoscopic pancreaticoduodenectomy: A rare case report.

Situs inversus totalis is a rare congenital anatomical anomaly that causes some difficult problems for surgeons when performing an operation. However, without histopathology specimens from surgery, a misdiagnosis of cancer may be unavoidable, in addition to affecting the improvement of prognosis. This study reports a rare patient with situs inversus totalis who presented with the main complaints of pruritus and vague abdominal pain. She was first misdiagnosed with cholangiocarcinoma and was finally diagnosed with duodenal papilla adenocarcinoma via laparoscopic pancreaticoduodenectomy. Situs inversus totalis was not a contraindication for surgery. Skilled surgeons and complete preparation during the perioperative period are two important keys to successful surgeries. Performing laparoscopic pancreaticoduodenectomy for patients with situs inversus totalis to avoid misdiagnosis of cancer and tailor appropriate therapy plans is cost-effective.

[Research progress of lower limb alignment correction and prosthesis position angle in unicompartmental knee arthroplasty].

The angle between the lower extremity force line and the position of the unicondylar prosthesis is an important factor affecting the long-term survival and rate clinical outcome of the unicondylar replacement prostheses. Insufficient lower limb alignment will accelerate the wear of prosthesis and reduce the survival rate of prosthesis. Excessive lower limb alignment will accelerate the progress of contralateral interventricular arthritis. It is generally believed that the lower limb force line should be corrected in mild varus after unicompartmental knee arthroplasty. However, some scholars believe that the lower limb alignment has no effect on the functional score and prosthesis survival rate after unicompartmental knee arthroplasty. The poor position of femoral and tibial prosthesis will cause unexplained pain and even prosthesis wear, but the optimal position of femoral and tibial prosthesis is controversial. It is generally believed that the posterior tibial slope should be corrected in the range of 3° to 7° in unicompartmental knee arthroplasty, but some scholars believe that excessive change of posterior tibial slope will also affect the balance of knee joint space and knee joint range of motion. This study shows that the correction of lower limb alignment to mild varus is still the best lower limb alignment for unicompartmental knee arthroplasty. The best position of femoral and tibial prosthesis needs to be confirmed by further biomechanical research. The correction of tposterior tibial slope should be changed according to the specific original dissection angle of patients before operation.

Ultrasound-triggered microbubble destruction enhances the radiosensitivity of glioblastoma by inhibiting PGRMC1-mediated autophagy in vitro and in vivo.

BACKGROUND: Ultrasound-triggered microbubble destruction (UTMD) is a widely used noninvasive technology in both military and civilian medicine, which could enhance radiosensitivity of various tumors. However, little information is available regarding the effects of UTMD on radiotherapy for glioblastoma or the underlying mechanism. This study aimed to delineate the effect of UTMD on the radiosensitivity of glioblastoma and the potential involvement of autophagy. METHODS: GL261, U251 cells and orthotopic glioblastoma-bearing mice were treated with ionizing radiation (IR) or IR plus UTMD. Autophagy was observed by confocal microscopy and transmission electron microscopy. Western blotting and immunofluorescence analysis were used to detect progesterone receptor membrane component 1 (PGRMC1), light chain 3 beta 2 (LC3B2) and sequestosome 1 (SQSTM1/p62) levels. Lentiviral vectors or siRNAs transfection, and fluorescent probes staining were used to explore the underlying mechanism. RESULTS: UTMD enhanced the radiosensitivity of glioblastoma in vitro and in vivo (P < 0.01). UTMD inhibited autophagic flux by disrupting autophagosome-lysosome fusion without impairing lysosomal function or autophagosome synthesis in IR-treated glioblastoma cells. Suppression of autophagy by 3-methyladenine, bafilomycin A1 or ATG5 siRNA had no significant effect on UTMD-induced radiosensitization in glioblastoma cells (P < 0.05). Similar results were found when autophagy was induced by rapamycin or ATG5 overexpression (P > 0.05). Furthermore, UTMD inhibited PGRMC1 expression and binding with LC3B2 in IR-exposed glioblastoma cells (P < 0.01). PGRMC1 inhibitor AG-205 or PGRMC1 siRNA pretreatment enhanced UTMD-induced LC3B2 and p62 accumulation in IR-exposed glioblastoma cells, thereby promoting UTMD-mediated radiosensitization (P < 0.05). Moreover, PGRMC1 overexpression abolished UTMD-caused blockade of autophagic degradation, subsequently inhibiting UTMD-induced radiosensitization of glioblastoma cells. Finally, compared with IR plus UTMD group, PGRMC1 overexpression significantly increased tumor size [(3.8 ± 1.1) mm2 vs. (8.0 ± 1.9) mm2, P < 0.05] and decreased survival time [(67.2 ± 2.6) d vs. (40.0 ± 1.2) d, P = 0.0026] in glioblastoma-bearing mice. CONCLUSION: UTMD enhanced the radiosensitivity of glioblastoma partially by disrupting PGRMC1-mediated autophagy.

[Sphingomyelin synthase 2 deficiency decreases atherosclerosis and inhibits inflammation in mice].

Plasma sphingomyelin (SM) has been shown to be an independent risk factor for coronary heart disease, and sphingomyelin synthase 2 (SMS2) contributes to de novo SM biosynthesis and plasma membrane SM levels. The aim of the present study is to evaluate the in vivo role of SMS2 deficiency in serum SM metabolism and atherosclerosis (AS) development. We used male SMS2 knockout (SMS2(-/-)) and C57BL/6J (wild-type, WT) mice as experimental and control groups, respectively. Each group was fed high-fat diet (1% cholesterol, 20% leaf fat), as well as bile salt for accelerating the atherosclerotic formation. After three months of feeding, the mice were killed to observe aortic arches and oil red-stained longitudinal sections of thoracoabdominal aortae. Fasting blood samples were taken from the tail vein before and after high-fat diet, and the serum lipid and SM levels were measured by using kits and enzymatic method respectively. Western blot was used to analyze the contents of nuclear factor-kappaB (NFkappaB) p65 subunit in peritoneal macrophages stimulated with lipopolysaccharide (LPS) after high-fat diet. The results showed that after high-fat diet, SMS2(-/-) mice presented decreased atherosclerotic lesions in aortic arch and thoracoabdominal aorta compared with WT mice. Regardless of whether high-fat diet were given or not, SMS2(-/-) mice showed a significant decrease in serum SM level (P<0.05), but no significant changes in serum lipid levels, compared with WT mice. The expressions of NFkappaB p65 were attenuated in macrophages from SMS2(-/-) mice in response to LPS stimulation compared with those of the WT mice. These results suggest that SMS2 deficiency decreases AS and inhibits inflammation in mice. Thus, SMS2 deficiency may be a potential therapeutic strategy.

Postoperative local incision analgesia for acute pain treatment in patients with hepatocellular carcinoma.

OBJECTIVE: The present study aimed to investigate the analgesic effect and safety of using local incision analgesia to treat acute postoperative pain in patients with hepatocellular carcinoma (HCC). METHOD: A cohort of 60 patients undergoing liver cancer resection was randomly divided into three groups (n=20 per group): local incision analgesia (LIA) group, which received local infiltration with ropivacaine combined with a postoperative analgesia pump; intravenous patient-controlled analgesia (PCA) group, which received fentanyl intravenous analgesia postoperatively; and the control group, which received tramadol hydrochloride injection postoperatively according to the NRS scoring system. The postoperative analgesic effect in each group was compared and tumor recurrence (survival) was analyzed using the Kaplan-Meier method. RESULTS: NRS scores, rate of analgesic usage, ambulation time (h) and intestinal function recovery time (h) were significantly reduced in LIA group compared with the control group at each postoperative time point (6, 12, 24 and 48 hours; p<0.05). Additionally, the NRS scores of LIA patients at 12 hours post-surgery was significantly reduced compared with PCA group (p<0.05), and the occurrence of postoperative adverse events in LIA group was significantly lower than that in PCA group (p<0.05). Survival analysis demonstrated that the mean survival time (tumor recurrence) was significantly increased in LIA group compared with the control group (χ2=4.749; p=0.029). CONCLUSION: Local incision analgesia improves the analgesic effect, causes fewer adverse reactions and increases postoperative survival time. Our study demonstrated that local incision analgesia is a safe and effective method of postoperative pain management following hepatectomy.

Trimethylamine-N-Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3-SOD2-mtROS Signaling Pathway.

BACKGROUND: Trimethylamine-N-oxide (TMAO) has recently been identified as a novel and independent risk factor for promoting atherosclerosis through inducing vascular inflammation. However, the exact mechanism is currently unclear. Studies have established a central role of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in the pathogenesis of vascular inflammation. Here, we examined the potential role of the NLRP3 inflammasome in TMAO-induced vascular inflammation in vitro and in vivo and the underlying mechanisms. METHODS AND RESULTS: Experiments using liquid chromatography-tandem mass spectrometry, Western blot, and fluorescent probes showed that TMAO-induced inflammation in human umbilical vein endothelial cells (HUVECs) and aortas from ApoE-/- mice. Moreover, TMAO promoted NLRP3 and activated caspase-1 p20 expression and caspase-1 activity in vitro and in vivo. Notably, a caspase-1 inhibitor (YVAD), an NLRP3 inhibitor (MCC950), as well as NLRP3 short interfering RNA attenuated TMAO-induced activation of the NLRP3 inflammasome, subsequently leading to suppression of inflammation in HUVECs. TMAO additionally stimulated reactive oxygen species (ROS) generation, in particular, mitochondrial ROS, while inhibiting manganese superoxide dismutase 2 (SOD2) activation and sirtuin 3 (SIRT3) expression in HUVECs and aortas from ApoE-/- mice. TMAO-induced endothelial NLRP3 inflammasome activation was ameliorated by the mitochondrial ROS scavenger Mito-TEMPO, or SIRT3 overexpression in HUVECs. Conversely, TMAO failed to further inhibit SOD2 and activate the NLRP3 inflammasome or induce inflammation in SIRT3 short interfering RNA-treated HUVECs and aortas from SIRT3-/- mice. CONCLUSIONS: TMAO promoted vascular inflammation by activating the NLRP3 inflammasome, and the NLRP3 inflammasome activation in part was mediated through inhibition of the SIRT3-SOD2-mitochondrial ROS signaling pathway.

[Hepatitis C virus infection combined with systemic lupus erythematosus].

OBJECTIVE: To examine the hepatitis C virus (HCV) infection in systemic lupus erythematosus (SLE) patients, to investigate the influence of HCV infection, and to analyze the clinical appearances and experimental immunological characters of SLE. METHODS: Serum of 92 SLE patients and 58 normal control people was taken, and the HCV infection and experimental immunological characters were detected. SLE patients were divided into HCV infection group and non-HCV infection group according to the detective results. The immunological characters and clinical appearances were analyzed in the two groups. RESULTS: Thirteen of the 92 SLE patients were HCV positive, while only 2 of the 58 normal controls were positive. There were no significant differences in the clinical features including oral ulcer, arthritis, serositis, nephropathy, neural disorder, fever, as well as in the laboratory results including ANA, Anti-Ro/SSA, Anti-La/SSB, Anti-Sm, IgG and IgM in the two groups. HCV positive patients showed a lower frequency of butterfly erythema and positivity for Anti-dsDNA, and a higher frequency of cutaneous vasculitis, liver damage, positivity for RF and low C3, C4 levels. CONCLUSION: Patients with SLE showed a high prevalence of HCV infection, and HCV may cause some clinical and immunological changes in SLE.

Protective effect of resveratrol against oxidative damage of UVA irradiated HaCaT cells.

OBJECTIVE: To observe the photoprotective effect and possible mechanisms of resveratrol for ultraviolet A (UVA) irradiated HaCaT cells. METHODS: HaCaT cells under UVA irradiation with 5J/cm(2) were interfered with 0.01 mmol/L and 0.1 mmol/L resveratrol. The testing objects were divided into a control and a UVA irradiation group, and then we detected the proliferation capacity with methylthiazdyl tetrazolium (MTT) and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activity, content of maleic dialdehyde (MDA) with hydroxylamine, colorimetric, thiobarbituric acid (TBA) methods. The ultrastructure was observed under electron microscope. RESULTS: Resveratrol could enhance the proliferation activity, SOD, GSH-Px activity of HaCaT cells under UVA irradiation, decrease the content of MDA in dose-dependent manner (P<0.05). The electron microscope revealed that resveratrol could relieve the injury of HaCaT cells' ultrastructure. CONCLUSION: Resveratrol can relieve the inhibition to HaCaT cell proliferation,injury of their ultrastructure and oxidation by UVA irradiation. The protection is dose-dependent. That resveratrol raises the oxidase activity and clears the oxyradical may account for these results.

Resveratrol Attenuates Trimethylamine-N-Oxide (TMAO)-Induced Atherosclerosis by Regulating TMAO Synthesis and Bile Acid Metabolism via Remodeling of the Gut Microbiota.

UNLABELLED: The gut microbiota is found to be strongly associated with atherosclerosis (AS). Resveratrol (RSV) is a natural phytoalexin with anti-AS effects; however, its mechanisms of action remain unclear. Therefore, we sought to determine whether the anti-AS effects of RSV were related to changes in the gut microbiota. We found that RSV attenuated trimethylamine-N-oxide (TMAO)-induced AS in ApoE(-/-) mice. Meanwhile, RSV decreased TMAO levels by inhibiting commensal microbial trimethylamine (TMA) production via gut microbiota remodeling in mice. Moreover, RSV increased levels of the genera Lactobacillus and Bifidobacterium, which increased the bile salt hydrolase activity, thereby enhancing bile acid (BA) deconjugation and fecal excretion in C57BL/6J and ApoE(-/-) mice. This was associated with a decrease in ileal BA content, repression of the enterohepatic farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) axis, and increased cholesterol 7a-hydroxylase (CYP7A1) expression and hepatic BA neosynthesis. An FXR antagonist had the same effect on FGF15 and CYP7A1 expression as RSV, while an FXR agonist abolished RSV-induced alterations in FGF15 and CYP7A1 expression. In mice treated with antibiotics, RSV neither decreased TMAO levels nor increased hepatic BA synthesis. Additionally, RSV-induced inhibition of TMAO-caused AS was also markedly abolished by antibiotics. In conclusion, RSV attenuated TMAO-induced AS by decreasing TMAO levels and increasing hepatic BA neosynthesis via gut microbiota remodeling, and the BA neosynthesis was partially mediated through the enterohepatic FXR-FGF15 axis. IMPORTANCE: Recently, trimethylamine-N-oxide (TMAO) has been identified as a novel and independent risk factor for promoting atherosclerosis (AS) partially through inhibiting hepatic bile acid (BA) synthesis. The gut microbiota plays a key role in the pathophysiology of TMAO-induced AS. Resveratrol (RSV) is a natural phytoalexin with prebiotic benefits. A growing body of evidence supports the hypothesis that phenolic phytochemicals with poor bioavailability are possibly acting primarily through remodeling of the gut microbiota. The current study showed that RSV attenuated TMAO-induced AS by decreasing TMAO levels and increasing hepatic BA neosynthesis via gut microbiota remodeling. And RSV-induced hepatic BA neosynthesis was partially mediated through downregulating the enterohepatic farnesoid X receptor-fibroblast growth factor 15 axis. These results offer new insights into the mechanisms responsible for RSV's anti-AS effects and indicate that the gut microbiota may become an interesting target for pharmacological or dietary interventions to decrease the risk of developing cardiovascular diseases.

Current harmonics elimination control method for six-phase PM synchronous motor drives.

To reduce the undesired 5th and 7th stator harmonic current in the six-phase permanent magnet synchronous motor (PMSM), an improved vector control algorithm was proposed based on vector space decomposition (VSD) transformation method, which can control the fundamental and harmonic subspace separately. To improve the traditional VSD technology, a novel synchronous rotating coordinate transformation matrix was presented in this paper, and only using the traditional PI controller in d-q subspace can meet the non-static difference adjustment, the controller parameter design method is given by employing internal model principle. Moreover, the current PI controller parallel with resonant controller is employed in x-y subspace to realize the specific 5th and 7th harmonic component compensation. In addition, a new six-phase SVPWM algorithm based on VSD transformation theory is also proposed. Simulation and experimental results verify the effectiveness of current decoupling vector controller.

Cortistatin is dysregulated in skin tissue of patients with psoriasis vulgaris and suppresses keratinocyte proliferation in vitro.

BACKGROUND: Psoriasis is characterized by the unregulated proliferation of epidermal keratinocytes and increased expression of proinflammatory mediators in the skin. Cortistatin, an endogenous cyclic neuropeptide, inhibits the proliferation of inflammatory cells. We investigated the expression of cortistatin in patients with psoriasis vulgaris and examined its effects on keratinocyte growth in vitro. METHODS: Serum levels of cortistatin were determined by enzyme-linked immunosorbent assay (ELISA) in 72 patients with psoriasis vulgaris and 76 age-matched healthy volunteers. Cortistatin expression was also examined by immunohistochemistry of skin biopsies from 14 patients and 14 healthy subjects. The effects of cortistatin on the proliferation of primary keratinocytes were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and BrdU incorporation assay. Intracellular levels of cAMP in keratinocytes in the presence or absence of cortistatin were determined by ELISA. RESULTS: Serum levels of cortistatin and expression levels in skin were significantly lower in patients with psoriasis than in healthy subjects. Cortistatin inhibited keratinocyte proliferation in vitro in a dose-dependent manner and substantially reduced intracellular cAMP levels in keratinocytes. CONCLUSIONS: Cortistatin is downregulated in the skin of patients with psoriasis vulgaris and suppresses keratinocyte growth in vitro.

Co-expression of CXCL8 and HIF-1α is associated with metastasis and poor prognosis in hepatocellular carcinoma.

Hypoxia inducible factor-1α (HIF-1α), induces cytokines such as CXCL8 and tumor dissemination, chemo- and radio-resistance. We analyzed correlation between HIF-1α and CXCL8 levels, tumor characteristics and overall survival in 102 hepatocellular carcinoma (HCC) patients. Levels of HIF-1α and CXCL8 were increased in HCC tissues and cell lines. Patients with high levels of HIF-1α and CXCL8 had worse outcome and poorer prognosis than those with lower levels. Co-overexpression of HIF-1α and CXCL8 was an independent negative prognostic factor for overall and disease-free survival. HIF-1α silencing and CXCL8 siRNA decreased migration under hypoxic conditions in vitro. Hypoxia-induced activation of AKT/mTOR/STAT3 pathways was reversed by depletion of CXCL8. We conclude that HIF-1α and CXCL8 induce HCC progression and metastasis, associated with activation of AKT/mTOR/STAT3. Co-expression of HIF-1α and CXCL8 is a prognostic marker and a potential therapeutic target in HCC.