TRPV3 promotes sebocyte inflammation via transcriptional modulating TLR2 in acne.

Acne is a common chronic inflammatory disease of the pilosebaceous unit. Transient receptor potential vanilloid 3 (TRPV3) is an ion channel that is involved in inflammatory dermatosis development. However, the involvement of TRPV3 in acne-related inflammation remains unclear. Here, we used acne-like mice and human sebocytes to examine the role of TRPV3 in the development of acne. We found that TRPV3 expression increased in the skin lesions of Propionibacterium acnes (P. acnes)-injected acne-like mice and the facial sebaceous glands (SGs) of acne patients. TRPV3 promoted inflammatory cytokines and chemokines secretion in human sebocytes and led to neutrophil infiltration surrounding the SGs in acne lesions, further exacerbating sebaceous inflammation and participating in acne development. Mechanistically, TRPV3 enhanced TLR2 level by promoting transcriptional factor phosphorylated-FOS-like antigen-1 (p-FOSL1) expression and its binding to the TLR2 promoter, leading to TLR2 upregulation and downstream NF-κB signaling activation. Genetic or pharmacological inhibition of TRPV3 both alleviated acne-like skin inflammation in mice via the TLR2-NF-κB axis. Thus, our study revealed the critical role of TRPV3 in sebaceous inflammation and indicated its potential as an acne therapeutic target.

NK-cell-elicited gasdermin-D-dependent hepatocyte pyroptosis induces neutrophil extracellular traps that facilitate HBV-related acute-on-chronic liver failure.

BACKGROUND AND AIMS: HBV infection is a major etiology of acute-on-chronic liver failure (ACLF). At present, the pattern and regulation of hepatocyte death during HBV-ACLF progression are still undefined. Evaluating the mode of cell death and its inducers will provide new insights for developing therapeutic strategies targeting cell death. In this study, we aimed to elucidate whether and how immune landscapes trigger hepatocyte death and lead to the progression of HBV-related ACLF. APPROACH AND RESULTS: We identified that pyroptosis represented the main cell death pattern in the liver of patients with HBV-related ACLF. Deficiency of MHC-I in HBV-reactivated hepatocytes activated cytotoxic NK cells, which in turn operated in a perforin/granzyme-dependent manner to trigger GSDMD/caspase-8-dependent pyroptosis of hepatocytes. Neutrophils selectively accumulated in the pyroptotic liver, and HMGB1 derived from the pyroptotic liver constituted an important factor triggering the generation of pathogenic extracellular traps in neutrophils (NETs). Clinically, elevated plasma levels of myeloperoxidase-DNA complexes were a promising prognostic biomarker for HBV-related ACLF. More importantly, targeting GSDMD pyroptosis-HMGB1 release in the liver abrogates NETs that intercept the development of HBV-related ACLF. CONCLUSIONS: Studying the mechanisms that selectively modulate GSDMD-dependent pyroptosis, as well as its immune landscapes, will provide a novel strategy for restoring the liver function of patients with HBV-related ACLF.

Lysosome-targeting and legumain-triggered 68Ga-labeled probe for enhanced tumor PET imaging.

Legumain is overexpressed in diverse tumors, serving as a significant tumor biomarker. Our study aimed to develop a new positron emission tomography (PET) probe [68Ga]Ga-NOTA-SF-AANM for imaging the expression level of legumain in vivo. The radio-labeling of [68Ga]Ga-NOTA-SF-AANM was accomplished within 15 min. The probe has good stability in vitro. NOTA-SF-AANM exhibited rapid response to recombinant human legumain enzyme, enabling intramolecular condensation cyclization. Cellular uptake and lysosomal co-localization experiments demonstrated that the probe was able to differentiate specifically between MDA-MB-468 and PC-3 cancer cells with varying degrees of legumain expression. PET imaging displayed a significant and persistent signal (3.59 ± 0.30 %ID/mL at 60 min) in MDA-MB-468 tumors, while PC-3 tumors exhibited lower radioactivity (1.08 ± 0.35 %ID/mL at 60 min), further validating the specific targeting of [68Ga]Ga-NOTA-SF-AANM towards legumain. [68Ga]Ga-NOTA-SF-AANM is a promising tool for precise diagnosis of legumain-related diseases due to its advantages in radio-labeling and accurate monitoring of legumain expression levels.

Validation and performance of three scoring systems for predicting primary non-function and early allograft failure after liver transplantation.

BACKGROUND: Primary non-function (PNF) and early allograft failure (EAF) after liver transplantation (LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function (MEAF), PNF score by King's College (King-PNF) and Balance-and-Risk-Lactate (BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. METHODS: A retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic (ROC) and the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) analyses. RESULTS: Of all 720 patients, 28 (3.9%) developed PNF and 67 (9.3%) developed EAF in 3 months. The overall early allograft dysfunction (EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0 (3.5-6.3), -2.1 (-2.6 to -1.2), and 5.0 (2.0-11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves (AUCs) of 0.871 and 0.891, superior to BAR-Lac (AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. CONCLUSIONS: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use of these scores will help early identify PNF, standardize grading of EAF and reasonably select clinical endpoints in relative studies.

Dual-Targeting PET Tracers Enable Enzyme-Mediated Self-Assembly for the PET Imaging of Legumain Activity.

Legumain, a lysosomal cysteine protease overexpressed in a variety of tumors, has been considered a promising biomarker for various cancers. Precise detection of legumain activity in the lysosome represents an important strategy for early diagnosis and prognosis of tumors. Small-molecule probes with the property of target-enabled self-assembly hold great potential for molecular imaging. In this study, we reported two dual-targeting radiotracers ([18F]SF-AAN-M and [18F]SF-AAN-HEM) with a property of legumain-mediated self-assembly for positron emission tomography (PET) imaging. Both the radiotracers were synthesized with high labeling yield (>50%) and the radiochemical purity was over 99% via one-step straightforward 18F-labeling. Both tracers were efficiently activated by the reducing agent and legumain to self-assemble into aggregates and showed enhanced retention in legumain-overexpressed MDA-MB-468 cells and tumors, indicating that the introduction of lysosome-targeting morpholine increased the tumor uptake and extended the retention of radiotracers in legumain-overexpressed tumors. In addition, [18F]SF-AAN-HEM with a hydrophilic (histidine-glutamate)3 tag displayed significantly reduced liver uptake with no conspicuous reduction in tumor uptake, affording high signal-to-noise ratios (tumor/liver and tumor/muscle). All of these results suggest that dual-targeting tracer [18F]SF-AAN-HEM could provide a promising tool for in vivo monitoring legumain activity in tumors.

Preparation and Bioevaluation of 18F-Labeled Small-Molecular Radiotracers via Sulfur(VI) Fluoride Exchange Chemistry for Imaging of Programmed Cell Death Protein Ligand 1 Expression in Tumors.

Nowadays, one of the most effective methods of tumor immunotherapy is blocking programmed cell death protein 1/programmed cell death protein ligand 1 (PD-1/PD-L1) immune checkpoints. However, there is still a significant challenge in selecting patients to benefit from immune checkpoint therapies. Positron emission tomography (PET), a noninvasive molecular imaging technique, offers a new approach to accurately detect PD-L1 expression and allows for a better prediction of response to PD-1/PD-L1 target immunotherapy. Here, we designed and synthesized a novel group of aryl fluorosulfate-containing small-molecule compounds (LGSu-1, LGSu-2, LGSu-3, and LGSu-4) based on the phenoxymethyl-biphenyl scaffold. After screening by the time-resolved fluorescence resonance energy transfer (TR-FRET) assay, the most potent compound LGSu-1 (half maximal inhibitory concentration (IC50): 15.53 nM) and the low-affinity compound LGSu-2 (IC50: 189.70 nM) as a control were selected for 18F-radiolabeling by sulfur(VI) fluoride exchange chemistry (SuFEx) to use for PET imaging. [18F]LGSu-1 and [18F]LGSu-2 were prepared by a one-step radiofluorination reaction in over 85% radioconversion and nearly 30% radiochemical yield. In B16-F10 melanoma cell assays, [18F]LGSu-1 (5.00 ± 0.06%AD) showed higher cellular uptake than [18F]LGSu-2 (2.55 ± 0.04%AD), in which cell uptake could be significantly blocked by the nonradioactivity LGSu-1. In vivo experiments, micro-PET imaging of B16-F10 tumor-bearing mice and radiographic autoradiography of tumor sections showed that [18F]LGSu-1 was more effectively accumulated in the tumor due to the higher binding affinity with PD-L1. The above experimental results confirmed the potential of the small-molecule probe LGSu-1 as a targeting PD-L1 imaging tracer in tumor tissues.

Novel dry pericardiocentesis: Transvenous puncture of the right ventricle with the back end of a 0.014-inch PTCA guidewire and a 1.8 Fr microcatheter.

Background: Dry transthoracic pericardiocentesis is challenging and carries the risk of right ventricle (RV) or coronary artery injury. The RV can usually control bleeding automatically. For example, most perforations of the RV caused by pacemaker leads are treated without open surgery. Thus, we performed a transvenous puncture of the RV for dry pericardiocentesis with the back end of a 0.014-inch percutaneous transluminal coronary angioplasty (PTCA) guidewire and a 1.8 Fr microcatheter. Methods: The back end of a 0.014-inch PTCA guidewire within a 1.8 Fr microcatheter was used to transvenously punctured through the middle of the acute margin of the RV into the pericardial space in 12 Yorkshire swine and 5 beagles. PTCA balloons of different diameters were used to dilate the puncture holes for 15 min under anticoagulation in all the animals to assess the ability of the RV to control the bleeding. Then, for 3 days, the puncture hole was dilated by a 6 Fr catheter in 9 swine and 5 dogs. Results: The puncture was successful in all the animals. After withdrawal of the 2.5-mm balloon or the 6 Fr catheter, none of the animals exhibited pericardial effusion, as observed by echocardiography. There was no sustained ventricular arrhythmia or other complications. All the animals survived. Conclusion: Transvenous puncture of the right ventricle with the back end of a 0.014-inch PTCA guidewire and 1.8 Fr microcatheter may be feasible and have a good safety margin.

Effect of Neiyi Prescription of QIU on autophagy and angiogenic ability of endometriosis via the PPARγ/NF-κB signaling pathway.

OBJECTIVES: Neiyi Prescription of QIU (NYPQ) is a traditional Chinese medicine prescription for the treatment of endometriosis (EMS). Here, we aimed to examine the effects and mechanisms of NYPQ on angiogenic ability in EMS. STUDY DESIGN: EMS rats were established with estradiol valerate and autologous transplantation. EMS rats were intraperitoneally injected with chloroquine (CQ, 40 mg/kg), rapamycin (RAPA, 1 mg/kg), and monoclonal antibody VEGF (anti-VEGF, 3 mg/g/d) or administered 5, 10, 20 mg/g/d NYPQ decoction through oral gavage for 4 weeks, respectively. By the before and end of the treatment period, the volume of the endometriotic lesions was measured. The pathological morphology, angiogenesis, and the number of autophagosomes of the endometriotic lesion were observed by hematoxylin and eosin staining, immunohistochemistry, and transmission electron microscope, respectively. The cell viability, apoptosis, and angiogenesis of HUVECs were detected by MTT, flow cytometry, and lumen formation experiment, respectively. The expression levels of VEGF, autophagy-/apoptosis-/PPARγ/NF-κB- pathway-related proteins in endometrium tissues or HUVECs were detected by western blot assays. RESULTS: The autophagy agonist rapamycin reduced the lesion size, the microvessel density, and VEGF expression, and promoted the production of autophagosomes and the expression of autophagy-related proteins, while the autophagy inhibitor chloroquine had the opposite effects. In vivo, NYPQ could dose-dependently reduce lesion volume and microvessel density, ameliorate histopathological features and promote autophagosome production of ectopic endometrium. Moreover, serum-containing NYPQ could significantly inhibit the cell viability and tube formation of HUVECs and elevate HUVECs apoptosis. Besides, NYPQ significantly reduced VEGF and promoted autophagy-/apoptosis-related protein expressions. Also, NYPQ might promote autophagy and inhibit angiogenesis by activating the PPARγ/NF-κB pathway. CONCLUSIONS: Collectively, these findings indicate that NYPQ has therapeutic potential in experimentally induced peritoneal endometriosis, and its mechanism may be related to the activation of the PPARγ/NF-κB signaling pathway.

Ginseng-derived nanoparticles potentiate immune checkpoint antibody efficacy by reprogramming the cold tumor microenvironment.

Cold tumor microenvironment (TME) marked with low effector T cell infiltration leads to weak response to immune checkpoint inhibitor (ICI) treatment. Thus, switching cold to hot TME is critical to improve potent ICI therapy. Previously, we reported extracellular vesicle (EV)-like ginseng-derived nanoparticles (GDNPs) that were isolated from Panax ginseng C.A. Mey and can alter M2 polarization to delay the hot tumor B16F10 progression. However, the cold tumor is more common and challenging in the real world. Here, we explored a combinatorial strategy with both GDNPs and PD-1 (programmed cell death protein-1) monoclonal antibody (mAb), which exhibited the ability to alter cold TME and subsequently induce a durable systemic anti-tumor immunity in multiple murine tumor models. GDNPs enhanced PD-1 mAb anti-tumor efficacy in activating tumor-infiltrated T lymphocytes. Our results demonstrated that GDNPs could reprogram tumor-associated macrophages (TAMs) to increase CCL5 and CXCL9 secretion for recruiting CD8+ T cells into the tumor bed, which have the synergism to PD-1 mAb therapy with no detected systemic toxicity. In situ activation of TAMs by GDNPs may broadly serve as a facile platform to modulate the suppressive cold TME and optimize the PD-1 mAb immunotherapy in future clinical application.

Application of TPGS as an efflux inhibitor and a plasticizer in baicalein solid dispersion.

The oral bioavailability and efficacy of baicalein is dramatically limited by its low solubility and effect of efflux. In our study, we chose PVP-VA64 as a carrier and TPGS as a plasticizer and efflux inhibitor to prepare a solid dispersion of baicalein using hot-melt extrusion technology to improve its solubility and bioavailability. The hot-melt process and formulation were optimized, and a BAC-PVP VA64-TPGS solid dispersion (BPT-SD) was prepared. BAC exists in an amorphous or molecular state in BPT-SD. BPT-SD comprised irregular lumps and small particles without BAC or carrier characteristics. The dissolution efficiency of BPT-SD improved under sink conditions. FTIR showed a strong hydrogen bond between BAC and PVP-VA64 in BPT-SD. BPT-SD maintained good physical stability for 6 months. The apparent permeability coefficient of BAC in the Caco-2 cell model confirmed that BPT-SD had higher gastrointestinal membrane permeability. A rat pharmacokinetic study showed that BPT-SD had higher Cmax and AUC0-24h, shorter Tmax, and 2.88-fold higher bioavailability than BAC. A behavioral experiment in chronic unpredictable mild stress (CUMS) mice confirmed the antidepressant efficacy of BAC. BPT-SD reversed depression-like behavior in CUMS mice and improved BAC bioavailability. BAC preparation into a solid dispersion significantly enhanced dissolution performance and bioavailability.

Biodegradable microplastics (BMPs): a new cause for concern?

With the increasingly serious pollution of plastics, biodegradable plastics (BDPs) have attracted attention as a new material that can replace conventional plastics in certain applications. The global production of BDPs also gradually increases in recent years. However, unfortunately, with the application of BDPs, some potential problems are gradually exposed. The biodegradability of BDPs needs suitable conditions, which is difficult for the natural environment to reach the necessary conditions. If the degradation conditions are not met, BDPs and conventional plastics are basically the same in terms of the longevity. The biodegradable microplastics (BMPs) can also be formed by BDPs entering the environment. Up to now, the research on the degradation and application of BDPs is relatively common. The environmental and ecological effects of the BMPs, the adsorption and release of toxic substances, and the role of BMPs as vectors of microorganisms, epiphytes, and plants still need to be studied. This paper focuses on the formation mechanism and the environmental behavior of BMPs. The role of BMPs as multiple stronger vectors of microorganisms and pollutants compared to conventional microplastics is also discussed. Systematic research on environmental pollution and ecotoxicology of BMPs should be carried out as soon as possible.

ZhiJingSan Inhibits Osteoclastogenesis via Regulating RANKL/NF-κB Signaling Pathway and Ameliorates Bone Erosion in Collagen-Induced Mouse Arthritis.

Bone erosion is the most evident pathological condition of rheumatoid arthritis (RA), which is the main cause of joint deformities and disability in RA patients. At present, the conventional RA drugs have not achieved satisfactory effect in improving bone erosion. ZhiJingSan (ZJS), which is a traditional Chinese prescription composed of scolopendra (dried body of Scolopendra subspinipes mutilans L. Koch, scolopendridae) and scorpion (dried body of Buthus martensii Karsch, Buthus), exhibits anti-rheumatism, analgesic and joint deformities improvement effects. This study aimed to assess the therapeutic effect of ZJS on RA bone erosion and to elucidate the underlying mechanism. The effect of ZJS on RA bone erosion was investigated in a murine model of bovine collagen-induced arthritis (CIA), and the underlying mechanism was investigated in vitro in an osteoclast differentiation cell model. Administration of ZJS delayed the onset of arthritis, alleviated joint inflammation, and attenuated bone erosion in the CIA mice. Meanwhile, ZJS decreased the serum levels of TNF-α, IL-6, and anti-bovine collagen II-specific antibodies. Furthermore, ZJS treatment reduced the number of osteoclasts and the expression of cathepsin K in the ankle joints of CIA mice. ZJS also inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation and the expression of MMP9 and cathepsin K in vitro. Mechanistically, ZJS blocked RANKL-induced p65 phosphorylation, nucleation, and inhibited the expression of downstream NFATc1 and c-Fos in bone marrow-derived macrophages (BMMs). Taken together, ZJS exerts a therapeutic effect on bone erosion in CIA mice by inhibiting RANKL/NF-κB-mediated osteoclast differentiation, which suggested that ZJS is a promising prescription for treating RA bone erosion.

Soufeng sanjie formula alleviates collagen-induced arthritis in mice by inhibiting Th17 cell differentiation.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease. Soufeng sanjie formula (SF), which is composed of scolopendra (dried body of Scolopendra subspinipes mutilans L. Koch), scorpion (dried body of Buthus martensii Karsch), astragali radix (dried root of Astragalus membranaceus (Fisch.) Bge), and black soybean seed coats (seed coats of Glycine max (L.) Merr), is a traditional Chinese prescription for treating RA. However, the mechanism of SF in treating RA remains unclear. This study was aim to investigate the anti-arthritic effects of SF in a collagen-induced arthritis (CIA) mouse model and explore the mechanism by which SF alleviates arthritis in CIA mice. METHODS: For in vivo studies, female DBA/1J mice were used to establish the CIA model, and either SF (183 or 550 mg/kg/day) or methotrexate (MTX, 920 mg/kg, twice/week) was orally administered to the mice from the day of arthritis onset. After administration for 30 days, degree of ankle joint destruction and serum levels of IgG and inflammatory cytokines were determined. The balance of Th17/Treg cells in the spleen and lymph nodes was analyzed using flow cytometry. Moreover, the expression levels of retinoic acid receptor-related orphan nuclear receptor (ROR) γt and phosphorylated STAT3 (pSTAT3, Tyr705) in the spleen were detected by immunohistochemistry. Furthermore, the effect of SF on Th17 cells differentiation in vitro was investigated in CD4+ T cells under Th17 polarization conditions. RESULTS: SF decreased the arthritis score, ameliorated paw swelling, and reduced cartilage loss in the joint of CIA mice. In addition, SF decreased the levels of bovine collagen-specific IgG in sera of CIA mice. SF decreased the levels of inflammatory cytokines (TNF-α, IL-6, and IL-17A) and increased the level of IL-10 both in the sera and the joint of CIA mice. Moreover, SF treatment rebalanced the Th17/Treg ratio in the spleen and lymph nodes of CIA mice. SF also reduced the expression levels of ROR γt and pSTAT3 (Tyr705) in the spleen of CIA mice. In vitro, SF treatment reduced Th17 cell generation and IL-17A production and inhibited the expression of RORγt, IRF4, IL-17A, and pSTAT3 (Tyr705) under Th17 polarization conditions. CONCLUSIONS: Our results suggest that SF exhibits anti-arthritic effects and restores Th17/Treg homeostasis in CIA mice by inhibiting Th17 cell differentiation.

Effects of slight structural distortion on the luminescence performance in (Ca1-x Eux )WO4 luminescent materials.

(Ca1-x Eux )WO4 (x = 0-21 mol%) phosphors were prepared using the classical solid-state reaction method. The influence of Eu3+ ion doping on lattice structure was observed using powder X-ray diffraction and Fourier transform infrared spectroscopy. Furthermore, under this influence, the luminescence properties of all samples were analyzed. The results clearly illustrated that the element europium was successfully incorporated into the CaWO4 lattice with a scheelite structure in the form of a Eu3+ ion, which introduced a slight lattice distortion into the CaWO4 matrix. These lattice distortions had no effect on phase purity, but had regular effects on the intrinsic luminescence of the matrix and the f-f excitation transitions of Eu3+ activators. When the Eu3+ concentration was increased to 21 mol%, a local luminescence centre of [WO4 ]2- groups was detected in the matrix and manifested as the decay curves of [WO4 ]2- groups and luminescence changed from single exponential to double exponential fitting. Furthermore, the excitation transitions of Eu3+ between different energy levels (such as 7 F0 →5 L6 , 7 F0 →5 D2 ) also produced interesting changes. Based on analysis of photoluminescence spectra and the chromaticity coordinates in this study, it could be verified that the nonreversing energy transfer of [WO4 ]2- →Eu3+ was efficient and incomplete.

Molten salt synthesis and luminescence of Dy3+ -doped Y3 Al5 O12 phosphors.

Dy3+ -doped Y3 Al5 O12 phosphors were prepared at a relatively low temperature using molten salt synthesis. The phase of the prepared Dy3+ -doped Y3 Al5 O12 phosphors was confirmed using X-ray powder diffraction. Results indicated that Dy3+ doping did not change the Y3 Al5 O12 phase. Following excitation at 352 nm, emission spectra of the Dy3+ -doped Y3 Al5 O12 phosphors consisted of blue, yellow, and red emission bands. The influence of Dy3+ concentration and excitation wavelength on emission was investigated. The ratio of yellow light to blue light varied with change in Dy3+ doping concentration, due to changes in the structure around Dy3+ . Emission intensities also changed when the excitation wavelength was changed. This variation is luminescence generated a system for tunable white light for Dy3+ -doped Y3 Al5 O12 phosphors.

Advanced uterine adenosarcoma with sarcomatous overgrowth in a young woman: A case report.

RATIONALE: Uterine adenosarcoma (UA) with sarcomatous overgrowth (ASSO) is a rare and aggressive disease. Herein, wereported the case of a young patient with advanced uterine ASSO. PATIENTS CONCERNS: A 29-year-old woman with the diagnoses of endometrial polyp and adenomyosis underwent hysteroscopic endometrial polypectomy for the giant endometrial polyp. Postoperative regular ultrasound scan indicated thickened endometriumand an ill-defined mass with continuous enlargement in the myometrium of the posterior wall of the uterus, which was considered as an adenomyoma. Two years after hysteroscopy, she was re-admitted due to lower abdominal distension and large pelvic mass. At that time, she had taken oral short-acting contraceptives for 2.5 years. DIAGNOSES: Magnetic resonance imaging (MRI) of the pelvis revealed an irregular mass with the size of 12*56*107 mm in the right annex area, without distinct border with the rectum, moreover, an uneven intrauterine echo that has no obvious boundary with uterine wall. Right ovarian cancer and adenomyoma were initially considered. INTERVENTIONS: The patient received transperitoneal retroperitoneal pelvic combined with total viscera resection, including uterus, bilateral appendages and rectum, omentectomy, appendectomy, lymphadenectomy, and ileostomy. Postoperative pathology confirmed ASSO in the uterine cavity and muscular layer, the whole cervical duct and the right adnexal. She underwent 2 systemic chemotherapy sessions after the surgery. The chemotherapy regimen was ifosfamide 2.5 g day 1 to 3, with liposomal doxorubicin 40 mg day 1. OUTCOMES: The final diagnosis was uterine ASSO, International Federation of Gynecology and Obstetrics stage IVa. The patient has been following-up so far, with no progression. LESSONS: Review of the case indicated that history of long-term oral short-acting contraceptives and giant endometrial polyps may be the high-risk factors for UA. For patients with high-risk factors, the follow-up ultrasound scan should be more frequently conducted. Moreover, 3D-ultrasound, MRI and outpatient hysteroscopy are recommended for routine screening. Placement of levonorgestrel-releasing intra-uterine system after hysteroscopy may be an effective intervention for patients with a high risk of giant polyps. Cluster of Differentiation 10, Estrogen receptor, Progesterone receptor, and nuclear antigen may be predictors for prognosis and selection of individualized treatment program.

Luminescence of Tb3Al5O12 phosphors co-doped with Ce3+/Gd3+ for white light-emitting diodes.

Tb2.96- x Ce0.04GdxAl5O12 phosphors were synthesized through solid-state reactions. The influence of Gd3+ on the luminescence was investigated. Under the excitation at 460 nm, Tb2.96Ce0.04Al5O12 shows the characteristic emission band of Ce3+ with a peak wavelength at about 554 nm. After co-doping Gd3+ into Tb2.96Ce0.04Al5O12, the peak wavelength of the Ce3+ emission band shifts to longer wavelengths, which is induced by the increasing crystal field splitting. However, the Ce3+ emission intensity also decreases because the substitution of Tb3+ with Gd3+ causes lattice deformation and generates numerous structural and chemical defects. By comparing the light parameters of white light-emitting diodes (WLEDs) containing Y2.96Ce0.04Al5O12, Tb2.96Ce0.04Al5O12 and Tb2.81Ce0.04Gd0.15Al5O12 phosphors, we can find that the WLED containing the Tb2.81Ce0.04Gd0.15Al5O12 phosphor generates warmer light than the WLEDs containing Y2.96Ce0.04Al5O12 and Tb2.96Ce0.04Al5O12 phosphors. Moreover, the WLEDs fabricated by integrating a blue LED chip and Ce3+/Gd3+-co-doped Tb3Al5O12 phosphors show outstanding colour stability when driven under different currents.

Vagal Nerve Stimulation Attenuates Ischemia-Reperfusion Induced Retina Dysfunction in Acute Ocular Hypertension.

Purpose: The present study aimed to investigate whether cervical vagal nerve stimulation (VNS) could prevent retinal ganglion cell (RGC) loss and retinal dysfunction after ischemia/reperfusion (I/R) injury. Methods: First, rats were randomly divided into sham group (n = 4) and VNS group (n = 12). Activation of the nodose ganglia (NOG), nucleus of the solitary tract (NTS), superior salivatory nucleus (SSN), and pterygopalatine ganglion (PPG) neural circuit were evaluated by c-fos expression at 0 h after sham VNS and at 0 h (n = 4), 6 h (n = 4), 72 h (n = 4) after VNS. Secondly, rats were randomly assigned to I/R group (pressure-induced retinal ischemia for 1 h and reperfusion for 1 h in the right eye, n = 16) and I/R+VNS group (right cervical VNS for 2 h during the I/R period, n = 16). The left eye of each rat served as a control. Electroretinogram (ERG), RGC numbers, tumor necrosis factor-α (TNF-α) and vasoactive intestinal polypeptide (VIP) levels in retina were determined. Additionally, the level of VIP in PPG was evaluated. Results: In the first part of the study, compared with the sham group, the VNS group exhibited significantly increased expression of c-fos in NOG, NTS, SSN, and PPG tissues at 0, 6, and 72 h. In the second part of the study, compared with left eyes, retinal function in right eyes (as assessed by the a-wave, b-wave and the oscillatory potential amplitudes of ERG and RGC data) was significantly decreased by I/R. The decreased retinal function was attenuated by VNS. In addition, I/R induced an increase in inflammation, which was reflected by elevated TNF-α expression in the retina. VNS significantly attenuated the increase in I/R-induced inflammation. Moreover, VIP expression in the retina and PPG, which may contribute to the inhibition of the inflammatory response, was significantly increased after VNS. Conclusion: VNS could protect against retinal I/R injury by downregulating TNF-α. Upregulation of VIP expression due to activation of the NOG-NTS-SSN-PPG neural circuit may underlie to the protective effects of VNS.

Piezoresistive temperature sensors fabricated by a surface micromachining CMOS MEMS process.

This paper presents a micromachined monocrystalline silicon piezoresistive temperature sensor fabricated by a surface micromachining CMOS (Complementary Metal Oxide Semiconductor) MEMS (Micro-Electro-Mechanical System) process. The design of the temperature sensor is based on the structure of the multi-layer cantilever beam and the bimetallic effect. The temperature change of the cantilever beam is translated into the change of the piezoresistance's value. The test results show that the sensitivities of the sensors are 27.9 mV/°C with 100 Ω/▯ piezoresistance between -40 °C to 60 °C and 7.4 mV/°C with 400 Ω/▯ piezoresistance between -90 °C to 60 °C. The temperature sensor proposed in this paper can be used in radiosondes for its low operating temperature (as low as -90 °C), small size (below 1 mm2) and low heat capacity.