Hexagon AgNCs/PVP Crystallization Induced Cathode Electrochemiluminescence Enhancement for miRNA221 Biosensing.

Aggredation-induced electrochemiluminescence (AIECL) promises an efficient strategy for synthesize highly luminescent emitter and co-reactant for ECL analysis, however, rational control of electrogenerated emission intensity is still challenging. The low electroconductivity and amorphous molecular configuration are intrinsic bottleneck. This work reveals the impact of polyvinyl pyrrolidone backbone regulated silver nanocrystallines (AgNCs/PVP) on the cathode AIECL properties in near infrared region, by employing the Box-Behnken designed response surface computation model to modulate crystal aggregates. Electron paramagnetic resonance spectroscopy discovered hydrogen radical (HO• ) dominant reductive-oxidative (R-O) ECL mechanism with AgNCs acting as the co-reaction accelerator in graphene oxide/persulfate system (GO/S2 O8 2- ). Both theoretical calculation and experimental measurement testified that the ECL of AgNCs in GO/S2 O8 2- dependent on the concentration of in situ electrochemical oxidized Ag+ . The high efficiency of crystallization-induced enhanced ECL (CIECL) originates from 1) the effective electron transfer of Ag+ accelerated HO• produce to notable promote radioactive transition, and 2) twisted intramolecular charge transfer from the electron-rich donor of PVP to electron-deficient receptor of Ag0 to restrict nonradioactive transition. The AgNCs/PVP with CIECL effect are applied to construct an ultrasensitive platform for miR-221 assay with a lower detection limit of 7.47 × 103  copies mL-1 than typical qPCR method.

Enhanced Hydrosaturation Selectivity and Electron Transfer for Electrocatalytic Chlorophenols Hydrogenation on Ru Sites.

Electrocatalytic hydrogenation is acknowledged as a promising strategy for chlorophenol dechlorination. However, the widely used Pd catalysts exhibit drawbacks, such as high costs and low selectivity for phenol hydrosaturation. Herein, we demonstrate the potential and mechanism of Ru in serving as a Pd substitute using 2,4,6-trichlorophenol (TCP) as a model pollutant. Up to 99.8% TCP removal efficiency and 99% selectivity to cyclohexanol, a value-added compound with an extremely low toxicity, were achieved on the Ru electrode. In contrast, only 66% of TCP was removed on the Pd electrode, with almost no hydrosaturation selectivity. The superiority of Ru over Pd was especially noteworthy in alkaline conditions or the presence of interfering species such as S2-. The theoretical simulation demonstrates that Ru possesses a hydrodechlorination energy barrier of 0.72 eV, which is comparable to that on Pd. Meanwhile, hydrosaturation requires an activation energy of 0.69 eV on Ru, which is much lower than that on Pd (0.92 eV). The main reaction mechanism on Ru is direct electron transfer, which is distinct from that on Pd (indirect pathway via atomic hydrogen, H*). This work thereby provides new insights into designing cost-effective electrocatalysts for halogenated phenol detoxification and resource recovery.

hsa_circ_0000264 promotes tumor progression via the hsa-let-7b-5p/HMGA2 axis in head and neck squamous cell carcinoma.

OBJECTIVE: Circular RNAs (CircRNAs) are involved in various tumors. However, their role in head and neck squamous cell carcinoma (HNSCC) is unknown. CircRNA sequencing data showed that hsa_circ_0000264 is significantly upregulated in HNSCC tissues. In this study, we aimed to investigate the role of hsa_circ_0000264 in HNSCC and elucidate its underlying regulation mechanism. MATERIALS AND METHODS: RNase R treatment was performed to confirm the loop structure of hsa_circ_0000264. Fluorescence in situ hybridization was performed to show the subcellular localization of hsa_circ_0000264. We then performed wound healing assay, Transwell assay, Western blot, and in vivo experiments to determine the effect of alterations in hsa_circ_0000264 expression. We performed RNA pull-down and dual luciferase reporter assay to identify and confirm the binding sites in RNAs. RESULTS: hsa_circ_0000264 was upregulated in HNSCC tissues and cells, and its loop structure was confirmed. Knockdown of hsa_circ_0000264 inhibited the migration, invasion, and epithelial-to-mesenchymal transition of HNSCC cells in vivo and in vitro. Mechanistically, hsa_circ_000026 upregulation can upregulate the expression of high mobility group AT-hook 2 (HMGA2) by sponging hsa-let-7b-5p, which in turn promotes HNSCC progression. CONCLUSION: Our results showed that hsa_circ_0000264 promotes HNSCC progression via the hsa-let-7b-5p/HMGA2 axis, and hsa_circ_0000264 can serve as a potential target for HNSCC treatment.

Asymmetric negative transfer effects of working memory training.

Gathercole et al. (Journal of Memory and Language, 105, 19-42, 2019) presented a cognitive routine framework for explaining the underlying mechanisms of working memory (WM) training and transfer. This framework conceptualizes training-induced changes as the acquisition of novel cognitive routines similar to learning a new skill. We further infer that WM training might not always generate positive outcomes because previously acquired routines may affect subsequent task performance in various ways. Thus, the present study aimed to demonstrate the negative effects of WM training via two experiments. We conducted Experiment 1 online using a two-phase training paradigm with only three training sessions per phase and replicated the key findings of Gathercole and Norris (in prep.) that training on a backward circle span task (a spatial task) transferred negatively to subsequent training on a backward letter span task (a verbal task). We conducted Experiment 2 using a reversed task order design corresponding to Experiment 1. The results indicated that the transfer from backward letter training to backward circle training was not negative, but rather weakly positive, suggesting that the direction of the negative transfer effect is asymmetric. The present study therefore found that a negative transfer effect can indeed occur under certain WM training designs. The presence of this asymmetric effect indicates that backward circle and backward letter tasks require different optimal routines and that the locus of negative transfer might be the acquisition process of such optimal routines. Hence, the routines already established for backward circle might hinder the development of optimal routines for backward letter, but not vice versa.

Zn-Induced Synthesis of Porous Fe-N,S-C Electrocatalyst with Iron-Based Active Sites Containing Sulfides, Oxides and Nitrides for Efficient Oxygen Reduction and Zinc-Air Batteries.

There is an urgent need to design and synthesize non-noble metal electrocatalysts (NNMEs) for the replacement of platinum-based electrocatalysts to enhance the sluggish oxygen reduction reaction (ORR) for Zn-air batteries and fuel cells. Herein, Fe-N,S-C materials were fabricated through two steps: first, reprecipitating hemin by adjusting the pH and, then, decorating it with melamine and cysteine in the presence of Zn2+. The resulting Fe-N,S-C-950 (Zn) was prepared after pyrolysis at 950 °C. Using this method, abundant iron-based active species with good dispersion were obtained. The fabrication of more micropores in Fe-N,S-C-950 (Zn) plays a positive role in the improvement of ORR activity. On comparison, Fe-N,S-C-950 (Zn) outperforms Fe-N,S-C-950 and Fe-N-C-950 (Zn) with respect to the ORR due to its larger specific surface area, porous structure, multiple iron-based active sites and N- and S-doped C. Fe-N,S-C-950 (Zn) achieves outstanding ORR performances, including a half-wave potential (E1/2) of 0.844 V and 0.715 V versus a reversible hydrogen electrode (RHE) in 0.1 M KOH and 0.1 M HClO4 solution, respectively. In addition, Fe-N,S-C-950 (Zn) shows an outstanding Zn-air battery performance with an open-circuit voltage (OCV) of 1.450 V and a peak power density of 121.9 mW cm-2, which is higher than that of 20 wt% Pt/C. As a result, the as-prepared electrocatalyst in this work shows the development of the Zn-assisted strategy combined with the assembly of porphyrins as NNMEs for the enhancement of the ORR in both alkaline and acidic solutions.

Simultaneous Phenol Removal and Resource Recovery from Phenolic Wastewater by Electrocatalytic Hydrogenation.

Efficient pollutants removal and simultaneous resource recovery from wastewater are of great significance for sustainable development. In this study, an electrocatalytic hydrogenation (ECH) approach was developed to selectively and rapidly transform phenol to cyclohexanol, which possesses high economic value and low toxicity and can be easily recovered from the aqueous solution. A three-dimensional Ru/TiO2 electrode with abundant active sites and massive microflow channels was prepared for efficient phenol transformation. A pseudo-first-order rate constant of 0.135 min-1 was observed for ECH of phenol (1 mM), which was 34-fold higher than that of traditional electrochemical oxidation (EO). Both direct electron transfer and indirect reduction by atomic hydrogen (H*) played pivotal roles in the hydrogenation of phenol ring. The ECH technique also showed excellent performance in a wide pH range of 3-11 and with a high concentration of phenol (10 mM). Moreover, the functional groups (e.g., chloro- and methyl-) on phenol showed little influence on the superiority of the ECH system. This work provides a novel and practical solution for remediation of phenolic wastewater as well as recovery of valuable organic compounds.

Role of EZH2 in Uterine Gland Development.

Enhancer of zeste homolog 2 (EZH2) is a core component of polycomb repressive complex 2 that plays a vital role in transcriptional repression of gene expression. Conditional ablation of EZH2 using progesterone receptor (Pgr)-Cre in the mouse uterus has uncovered its roles in regulating uterine epithelial cell growth and stratification, suppressing decidual myofibroblast activation, and maintaining normal female fertility. However, it is unclear whether EZH2 plays a role in the development of uterine glands, which are required for pregnancy success. Herein, we created mice with conditional deletion of Ezh2 using anti-Mullerian hormone receptor type 2 (Amhr2)-Cre recombinase that is expressed in mesenchyme-derived cells of the female reproductive tract. Strikingly, these mice showed marked defects in uterine adenogenesis. Unlike Ezh2 Pgr-Cre conditional knockout mice, deletion of Ezh2 using Amhr2-Cre did not lead to the differentiation of basal-like cells in the uterus. The deficient uterine adenogenesis was accompanied by impaired uterine function and pregnancy loss. Transcriptomic profiling using next generation sequencing revealed dysregulation of genes associated with signaling pathways that play fundamental roles in development and disease. In summary, this study has identified an unrecognized role of EZH2 in uterine gland development, a postnatal event critical for pregnancy success and female fertility.

An insight into volatile and non-volatile compounds of Chinese horsebean-chili-paste meju produced by natural brewing and temperature-controlled brewing methods.

BACKGROUND: Chinese horsebean-chili-paste (CHCP) is a traditional fermented condiment in China, known as 'the soul of Sichuan cuisine'. The horsebean-to-meju phase in its preparation is important for CHCP production and contributes significantly to its taste and odor. In this study, a comprehensive flavor compound profiling analysis of the naturally brewed horsebean meju (NBHM) and the temperature-controlled brewed horsebean meju (TCBHM) was performed with two-dimensional gas chromatography time-of-flight mass spectrometry (GC × GC-TOFMS), and the analysis of physicochemical characteristics and free amino acids. Their aroma-active components and characteristic flavor compounds were evaluated. The flavor compounds responsible for differentiating NBHM and TCBHM were also determined based on the Fisher ratio and principal component analysis. RESULTS: The pH and the reducing sugar and amino-acid nitrogen content of NBHM were 5.38, 64.43, and 5.76 g kg-1 , respectively, whereas those of TCBHM were 5.13, 29.20, and 7.43 g kg-1 . A total of 356 volatiles were identified from 2571 compounds, and 257 volatile compounds were identified in NBHM compared to 322 volatiles in TCBHM. These two horsebean mejus (HMs) exhibited a similar proportion profile for 30 aroma-active compounds. Benzoic acid ethyl ester, 4-ethyl-2-methoxy-phenol and argnine were determined to be characteristic flavor components for NBHM, while 1-(2-furanyl)-ethanone, 2,6-dimethyl-pyrazine, threonine, valine and tyrosine were specific to TCBHM. CONCLUSION: Temperature-controlled brewed horsebean meju possessed better physicochemical and flavor characteristics than NBHM. The temperature-controlled brewing technique in CHCP production can be used as a promising alternative to the traditional natural brewing method. © 2020 Society of Chemical Industry.

WITHDRAWN: Effects of cancer-associated point mutations on the structure, function, and stability of succinate dehydrogenase A.

This article has been withdrawn by the authors. Some of the SDHA enzyme activity data were flawed and were not performed and analyzed correctly. The withdrawing authors are in the process of correcting the data and re-evaluating them for resubmission.

Transforming growth factor beta signaling and decidual integrity in mice†.

Transforming growth factor beta (TGFß) signaling regulates multifaceted reproductive processes. It has been shown that the type 1 receptor of TGFß (TGFBR1) is indispensable for female reproductive tract development, implantation, placental development, and fertility. However, the role of TGFß signaling in decidual development and function remains poorly defined. Our objective is to determine the impact of uterine-specific deletion of Tgfbr1 on decidual integrity, with a focus on the cellular and molecular properties of the decidua during development. Our results show that the developmental dynamics of the decidua is altered in TGFBR1 conditionally depleted uteri from embryonic day (E) 5.5 to E8.5, substantiated by downregulation of genes associated with inflammatory responses and uterine natural killer cell abundance, reduced presence of nondecidualized fibroblasts in the antimesometrial region, and altered decidual cell development. Notably, conditional ablation of TGFBR1 results in the formation of decidua containing more abundant alpha smooth muscle actin (ACTA2)-positive cells at the peripheral region of the antimesometrial side versus controls at E6.5-E8.5. This finding is corroborated by upregulation of a subset of smooth muscle marker genes in Tgfbr1 conditionally deleted decidua at E6.5 and E8.5. Moreover, increased cell proliferation and enhanced decidual ERK1/2 signaling were found in Tgfbr1 conditional knockout mice upon decidual regression. In summary, conditional ablation of TGFBR1 in the uterus profoundly impacts the cellular and molecular properties of the decidua. Our results suggest that TGFBR1 in uterine epithelial and stromal compartments is important for the integrity of the decidua, a transient but crucial structure that supports embryo development.

Enhancer of Zeste 2 Polycomb Repressive Complex 2 Subunit Is Required for Uterine Epithelial Integrity.

Normal proliferation and differentiation of uterine epithelial cells are critical for uterine development and function. Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), a core component of polycomb repressive complexes 2, possesses histone methyltransferase activity that catalyzes the trimethylation of lysine 27 of histone H3. EZH2 has been involved in epithelial-mesenchymal transition, a key event in development and carcinogenesis. However, its role in uterine epithelial cell function remains unknown. To determine the role of uterine EZH2, Ezh2 was conditionally deleted using progesterone receptor Cre recombinase, which is expressed in both epithelial and mesenchymal compartments of the uterus. Loss of EZH2 promoted stratification of uterine epithelium, an uncommon and detrimental event in the uterus. The abnormal epithelium expressed basal cell markers, including tumor protein 63, cytokeratin 5 (KRT5), KRT6A, and KRT14. These results suggest that EZH2 serves as a guardian of uterine epithelial integrity, partially via inhibiting the differentiation of basal-like cells and preventing epithelial stratification. The observed epithelial abnormality was accompanied by fertility defects, altered uterine growth and function, and the development of endometrial hyperplasia. Thus, the Ezh2 conditional knockout mouse model may be useful to explore mechanisms that regulate endometrial homeostasis and uterine function.

A novel mouse model of testicular granulosa cell tumors.

STUDY QUESTION: What is the role of dysregulated transforming growth factor beta (TGFB) signaling in the development of sex cord-stromal tumors in the testis? SUMMARY ANSWER: Overactivation of TGFB signaling results in the development of testicular tumors resembling granulosa cell tumors (GrCTs). WHAT IS KNOWN ALREADY: In an earlier study, we demonstrated that constitutively active TGFB receptor 1 (TGFBR1) in ovarian somatic cells promotes the development of ovarian GrCTs. However, the consequence of dysregulation of TGFB signaling in the pathobiology of the testis, remains poorly defined. STUDY DESIGN, SIZE, DURATION: To identify the impact of dysregulation of TGFB signaling on the testis, we generated mice with constitutive activation of TGFBR1 using anti-Mullerian hormone receptor type 2 (Amhr2)-Cre recombinase. The effect of constitutively active TGFBR1 on testis development and the timeline of testicular tumor formation were examined. We further investigated the molecular features of testicular tumors and determined the expression of beta-catenin (CTNNB1) known to be involved in testicular GrCT development. PARTICIPANTS/MATERIALS, SETTING, METHODS: Male mice with constitutive activation of TGFBR1 were examined at various developmental stages (i.e. from 1 week up to 6 months) along with controls. Testis samples were collected and processed for histological and molecular analyses, including haematoxylin and eosin (H and E) staining, real-time PCR, immunohistochemistry, immunofluorescence and western blotting. Immunostaining/immunoblotting and real-time PCR experiments were performed using at least three animals per genotype. Data are presented as mean ± SEM. Statistical significance was determined using unpaired two-tail t-test and reported when P value is <0.05. MAIN RESULTS AND THE ROLE OF CHANCE: Mice harboring constitutively active TGFBR1 in the testes developed tumors resembling testicular GrCTs, a rare type of tumors in the testis. The formation of testicular tumors led to altered cell proliferation, loss of germ cells and defective spermatogenesis. Immunohistochemically, these tumors were positive for inhibin alpha (INHA), forkhead box O1 (FOXO1), and more importantly, forkhead box L2 (FOXL2), a protein specifically expressed in the ovary and required for normal granulosa cell differentiation and function. Consistent with the immunohistochemical findings, FOXL2 proteins were only detectable in testes of TGFBR1-CAAcre mice but not those of controls by western blotting, suggesting potential alteration of Sertoli cell fate. To explore mechanisms underlying the tumor-promoting effect of TGFBR1 overactivation, we examined the expression of CTNNB1. The results revealed increased expression of CTNNB1 in testicular tumors in TGFBR1-CAAcre mice. Collectively, this study uncovered tumorigenic function of enhanced TGFB signaling in the testis. LARGE-SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This study was performed using mice, and the direct relevance of the experimental paradigm and findings to human testicular GrCTs awaits further investigation. Of note, constitutive activation of TGFBR1 was employed to enhance TGFB/SMAD signaling activity and may not be interpreted as the genetic cause of the disease. WIDER IMPLICATIONS OF THE FINDINGS: This mouse model may prove to be a useful addition to the mouse genetics toolkit for GrCT research. Our finding that dysregulation of TGFB signaling results in the development of testicular GrCTs supports a common origin between Sertoli cells and granulosa cells, and highlights the paramount importance of balanced TGFB signaling in reproduction and development. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the National Institutes of Health grant R03HD082416 from the Eunice Kennedy Shriver National Institute of Child Health & Human Development and the New Faculty Start-up Funds from Texas A&M University awarded to Q.L. The authors declare no competing interest.

TGFß superfamily signaling and uterine decidualization.

Decidualization is an intricate biological process where extensive morphological, functional, and genetic changes take place in endometrial stromal cells to support the development of an implanting blastocyst. Deficiencies in decidualization are associated with pregnancy complications and reproductive diseases. Decidualization is coordinately regulated by steroid hormones, growth factors, and molecular and epigenetic mechanisms. Transforming growth factor ß (TGFß) superfamily signaling regulates multifaceted reproductive processes. However, the role of TGFß signaling in uterine decidualization is poorly understood. Recent studies using the Cre-LoxP strategy have shed new light on the critical role of TGFß signaling machinery in uterine decidualization. Herein, we focus on reviewing exciting findings from studies using both mouse genetics and in vitro cultured human endometrial stromal cells. We also delve into emerging mechanisms that underlie decidualization, such as non-coding RNAs and epigenetic modifications. We envision that future studies aimed at defining the interrelationship among TGFß signaling circuitries and their potential interactions with epigenetic modifications/non-coding RNAs during uterine decidualization will open new avenues to treat pregnancy complications associated with decidualization deficiencies.

Exogenous IFN-beta regulates the RANKL-c-Fos-IFN-beta signaling pathway in the collagen antibody-induced arthritis model.

BACKGROUND: Although a variety of drugs have been used to treat the symptoms of rheumatoid arthritis (RA), none of them are able to cure the disease. Interferon ß (IFN-ß) has pleiotropic effects on RA, but whether it can be used to treat RA remains globally controversial. Thus, in this study we tested the effects of IFN-ß on RA patients and on collagen antibody-induced arthritis (CAIA) model mice. METHODS: The cytokine and auto-antibody expression profiles in the serum and synovial fluid (SF) from RA patients were assessed using enzyme-linked immunosorbent assay (ELISA) and compared with the results from osteoarthritis (OA) patients. Exogenous IFN-ß was administered to RA patients and CAIA model mice, and the therapeutic effects were evaluated. Endogenous IFN-ß expression in the joint bones of CAIA model mice was evaluated by quantitative real-time PCR (qRT-PCR). The effects of exogenous IFN-ß on CAIA model mice were assessed using a clinical scoring system, hematoxylin eosin and safranin-O with fast green counterstain histology, molybdenum target X-ray, and tartrate-resistant acid phosphatase (TRAP) staining. The RANKL-RANK signaling pathway was analyzed using qRT-PCR. The RAW 264.7 cell line was differentiated into osteoclasts with RANKL stimulation and then treated with exogenous IFN-ß. RESULTS: The expression of inflammatory cytokines (IFN-γ, IL-17, MMP-3, and RANKL) and auto-antibodies (CII antibodies, RF-IgM, and anti-CCP/GPI) were significantly higher in RA compared with OA patients. After IFN-ß intervention, some clinical symptoms in RA patients were partially alleviated, and the expression of IFN-γ, IL-17, MMP-3, and OPG) returned to normal levels. In the CAIA model, the expression of endogenous IFN-ß in the joint bones was decreased. After IFN-ß administration, the arthritis scores were decreased; synovial inflammation, cartilage, and bone destruction were clearly attenuated; and the expression of c-Fos and NFATc1 were reduced, while RANKL and TRAF6 expression was unchanged. In addition, exogenous IFN-ß directly inhibited RANKL-induced osteoclastogenesis. CONCLUSIONS: Exogenous IFN-ß administration immunomodulates CAIA, may reduce joint inflammation and, perhaps more importantly, bone destruction by inhibiting the RANKL-c-Fos signaling pathway. Exogenous IFN-ß intervention should be selectively used on RA patients because it may only be useful for RA patients with low endogenous IFN-ß expression.

Monoamine oxidase B inhibits epithelial-mesenchymal transition and trigger apoptosis via targeting ERK1/2 signaling pathway in head and neck squamous cell carcinoma.

BACKGROUND: Monoamine oxidase B (MAOB), a flavin monoamine oxidase, regulates biogenic and xenobiotic amine oxidative deaminization. We demonstrate MAOB expression in head and neck epithelium and its biological importance in head and neck squamous cell carcinoma (HNSCC) development. METHODS: First, we found a possible MAOB downregulation in HNSCC using bioinformatic analysis. Second, we validated MAOB expression changes in vitro and assessed its tumorigenicity in HNSCC. Finally, preclinical xenograft models further confirmed our findings. RESULTS: Results proved that MAOB was significantly reduced in HNSCC tissues and cell lines. By comparing MAOB localization in patient specimens, we found that epithelial basal cells express MAOB and that it changes throughout HNSCC development. We observed that MAOB overexpression inhibited HNSCC cell malignancy via lentiviral transfection. We additionally discovered that selegiline partly counter-regulated MAOB overexpression-induced phenotypes in HNSCC cells. CONCLUSIONS: We found that MAOB is a potent biomarker and a unique and essential indication of HNSCC carcinogenesis.

Serum HMGB-1 released by ferroptosis and necroptosis as a novel potential biomarker for systemic lupus erythematosus.

High mobility group box proterin-1 (HMGB-1) is a multifunctional protein that can be released by various programmed cell deaths (PCDs), such as necroptosis and ferroptosis. PCDs play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). However, the role of HMGB-1 in the process of SLE remains unclear. This study aims to demonstrate the potential diagnosing role of serum HMGB-1 in SLE that released by necroptosis and ferroptosis. We found that the serum levels of HMGB-1, receptor-interacting protein kinase 3 (RIPK3) /mixed lineage kinase domain-like protein (MLKL) related with necroptosis, and metabolites associated with ferroptosis were significantly upregulated in SLE patients compared to HC individuals. These serum levels were positively correlated with SLE disease activity. Additionally, the serum level of HMGB-1 showed a strong positive correlated with the levels of RIPK3/MLKL and ferroptosis metabolites. Moreover, the serum level of HMGB-1 was correlated with renal involvement and high-antinuclear antibodies (ANA) titer. After SLE serum and interferon γ (IFN-γ) treatment in vitro, the level of necroptosis and ferroptosis markers were activated and HMGB1 was released both in HEK293 and HK2 cells. Clinically, HMGB-1 was considered as a significant independent risk factor in SLE serum by binary logistic assay. Notably, HMGB-1 exhibited outstanding diagnostic ability for SLE by the area under the curve (AUC) in receiver operating characteristic (ROC) curve analysis. Taken together, our study indicates that the serum level of HMGB-1 is a promising biomarker for the diagnosis and monitoring of SLE.

Electroacupuncture at different intensities inhibits nociceptive discharges of wide dynamic range neurons in spinal dorsal horn of rats. / ä¸åŒå¼ºåº¦ç”µé’ˆå¯¹å¤§é¼ è„Šé«“èƒŒè§’å¹¿åŠ¨åŠ›ç¥žç»å ƒä¼¤å®³æ€§æ”¾ç”µçš„æŠ‘åˆ¶ä½œç”¨.

OBJECTIVES: To observe the effect of electroacupuncture (EA) at different intensities on nociceptive discharges of wide dynamic range (WDR) neurons in the spinal dorsal horns (DHs) of rats, so as to explore its regulatory characteristics on nociceptive signals at the spinal level. METHODS: A total of 25 male SD rats were used in the present study. A microelectrode array was used to record the discharge activity of WDR neurons in the lumbar spinal DHs of normal rats. After finding the WDR neuron, electrical stimulation (pulse width of 2 ms) was administered to the plantar receptive field (RF) for determining its response component of discharges according to the latency of action potential generation (Aß ï¼»0 to 20 msï¼½, Aδ ï¼»20 to 90 msï¼½, C ï¼»90 to 500 msï¼½ and post-discharge ï¼»500 to 800 msï¼½). High-intensity electrical stimulation was continuously applied to the RF at the paw's plantar surface to induce DHs neuronal windup response. Subsequently, EA stimulation at different intensities (1 mA and 2 mA) was applied to the left "Zusanli"(ST36) at a frequency of 2 Hz/15 Hz for 10 min. The induction of WDR neuronal windup was then repeated under the same conditions. The quantity of nociceptive discharge components and the windup response of WDR neurons before and after EA stimulations at different intensities were compared. RESULTS: Compared to pre-EA, both EA1 mA and EA2 mA significantly reduced the number of Aδ and C component discharges of WDR neurons during stimulation, as well as post-discharge (P<0.01, P<0.001). The inhibitory rate of C component by EA2 mA was significantly higher than that by EA1 mA (P<0.05). Meanwhile, both EA1 mA and EA2 mA attenuated the windup response of WDR neurons (P<0.05, P<0.01), and the effect of EA2 mA was stronger than that of EA1 mA (P<0.05). Further analysis showed that when EA1 mA and EA2 mA respectively applied to both non-receptive field (non-RF) and RF, a significant reduction in the number of Aδ component, C component and post-discharge was observed (P<0.05, P<0.01). EA2 mA at the non-RF and RF demonstrated a significant inhibitory effect on the windup response of WDR neurons (P<0.01, P<0.05), but EA1 mA only at the non-RF showed a significant inhibitory effect on the windup response (P<0.01). CONCLUSIONS: EA can suppress nociceptive discharges of spinal DHs WDR neurons in rats. The inhibitory impact of EA is strongly correlated with the location and intensity of EA stimulation, and EA2 mA has a stronger inhibitory effect than EA1 mA.

Wedelolactone inhibits ferroptosis and alleviates hyperoxia-induced acute lung injury via the Nrf2/HO-1 signaling pathway.

Hyperoxia-induced acute lung injury (HALI) is a complication of oxygen therapy. Ferroptosis is a vital factor in HALI. This paper was anticipated to investigate the underlying mechanism of Wedelolactone (WED) on ferroptosis in HALI. The current study used hyperoxia to injure two models, one HALI mouse model and one MLE-12 cell injury model. We found that WED treatment attenuated HALI by decreasing the lung injury score and lung wet/dry weight ratio and alleviating pathomorphological changes. Then, the inflammatory reaction and apoptosis in HALI mice and hyperoxia-mediated MLE-12 cells were inhibited by WED treatment. Moreover, WED alleviated ferroptosis with less iron accumulation and reversed expression alterations of ferroptosis markers, including MDA, GSH, GPX4, SLC7A11, FTH1, and TFR1 in hyperoxia-induced MLE-12 cells in vitro and in vivo. Nrf2-KO mice and Nrf2 inhibitor (ML385) decreased WED's ability to protect against apoptosis, inflammatory response, and ferroptosis in hyperoxia-induced MLE-12 cells. Collectively, our data highlighted the alleviatory role of WED in HALI by activating the Nrf2/HO-1 pathway.

Sertoli Cell-Specific Activation of Transforming Growth Factor Beta Receptor 1 Leads to Testicular Granulosa Cell Tumor Formation.

The transforming growth factor ß (TGFß) superfamily, consisting of protein ligands, receptors, and intracellular SMAD transducers, regulates fundamental biological processes and cancer development. Our previous study has shown that sustained activation of TGFß receptor 1 (TGFBR1) driven by anti-Mullerian hormone receptor type 2 (Amhr2)-Cre in the mouse testis induces the formation of testicular granulosa cell tumors (TGCTs). As Amhr2-Cre is expressed in both Sertoli cells and Leydig cells, it remains unclear whether the activation of TGFBR1 in Sertoli cells alone is sufficient to induce TGCT formation. Therefore, the objective of this study was to determine whether Sertoli cell-activation of TGFBR1 drives oncogenesis in the testis. Our hypothesis was that overactivation of TGFBR1 in Sertoli cells would promote their transdifferentiation into granulosa-like cells and the formation of TGCTs. To test this hypothesis, we generated mice harboring constitutive activation of TGFBR1 in Sertoli cells using anti-Mullerian hormone (Amh)-Cre. Disorganized seminiferous tubules and tumor nodules were found in TGFBR1CA; Amh-Cre mice. A histological analysis showed that Sertoli cell-specific activation of TGFBR1 led to the development of neoplasms resembling granulosa cell tumors, which derailed spermatogenesis. Moreover, TGCTs expressed granulosa cell markers including FOXL2, FOXO1, and INHA. Using a dual fluorescence reporter line, the membrane-targeted tdTomato (mT)/membrane-targeted EGFP (mG) mouse, we provided evidence that Sertoli cells transdifferentiated toward a granulosa cell fate during tumorigenesis. Thus, our findings indicate that Sertoli cell-specific activation of TGFBR1 leads to the formation of TGCTs, supporting a key contribution of Sertoli cell reprogramming to the development of this testicular malignancy in our model.

How volatile composition facilitates olfactory discrimination of fat content in beef and pork.

Foods differing in fat content can be distinguished through olfaction alone. The mechanisms underlying the ability of humans to discriminate between foods differing in fat content through olfaction are underexplored. In this study, beef and pork samples were prepared (raw and roasted) with low (muscle tissue; raw: 2-5%; roasted: 5%), medium (muscle tissue with lard; raw: 25-30%; roasted: 36-44%), and high (lard; raw: 40-42%; roasted: 69-70%) fat content. Olfactory triangle discrimination tests and ranking tests were performed to explore whether humans can discriminate and rank fat content of the samples through orthonasal olfaction. Headspace-Solid Phase Micro Extraction-Gas Chromatography-Mass Spectrometry (SPME-GC-MS) was used to characterize the volatile compound composition of the headspace of samples differing in fat content. Partial least-squares regression and partial least squares-discriminant analysis were performed to determine the volatile compounds that were responsible for olfactory fat content discrimination. We found that fat content in both raw and roasted samples can be distinguished through orthonasal olfaction. Perceived odor differences did not always contribute to olfactory identification of fat content. Roasted beef and pork meats with higher fat content had more abundant fatty acids, aldehydes, and ketones. Phthalic acid, isobutyl 2-ropylpentyl ester, and carbon disulfide facilitated the olfactory discrimination of fat content in raw pork and beef samples. 2-Methyl-propanal, benzaldehyde, 1-hydroxy-2-propanone, 2,3-pentanedione, 2,5-octanedione, and 2-butanone contributed to odor differences of roasted beef samples differing in fat content. We conclude that beef and pork samples differing in fat content differ in volatile compound composition of the headspace, and that these differences facilitate discrimination between samples differing in fat content based on olfaction alone.